Cutaneous diseases and their laboratory findings

Cutaneous diseases and their laboratory findings

1 Cutaneous Diseases and Their Laboratory Findings Thomas Butterworth. MD, MED SCM Emeritus Associate Professor of Dermatology, University of Penns...

7MB Sizes 0 Downloads 10 Views

1

Cutaneous Diseases and Their Laboratory Findings

Thomas Butterworth. MD, MED SCM

Emeritus Associate Professor of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

A Abscess Staphylococcus aureus is frequently the offender. In addition, Echerichia coli, as well as other enteric organisms, may be found in

perirectal abscesses. Chronic subcutaneous abscesses, particularly following injections, may be due to Mycobacterium chelonei (M. abscessus). A rare cause of abscesses in patients with immune defects is M. haemophilum. Acatalasia SYN: Takahara’s disease The absence of catalase may be demonstrated in the erythrocytes. Anaerobic organisms commonly are found in the gingiva and other oral structures. Acne Staphylococcus epidermidis and Propionibacterium (Corynebacterium) awes are the predominant organisms associated with acne. Malassezia furfur (Pityrosporon orbicularis) is also found frequently in the lesions. P. acnes is ascribed the greatest clinical

significance. Sera from patients with pustular forms of acne have significantly elevated levels of antibodies to P. awes, indicated by bacterial agglutination, agar gel immunodiffusion, immunofluorescence, and complement fixation tests. Patients also exhibit cell-mediated immunity to P. acnes. Some patients have mild or moderate anemia. Elevated values of serum cyanocobalamin (vitamin Blz) have been reported in acne, especially among those with the severest types of the disease. Low y-globulin titers have been found in acne conglobata. Zinc insufficiency is more apparent in patients with advanced grades of acne. In any group of acne patients, a minority, particularly women, shows endocrine alterations. 1

Clmics

2

Butterworth and Cawley

After long-term systemic or topical antibiotics, a gram-negative folliculitis may occur owing to Pseudomonas aeruginosa. Proteus organisms, and others. In acne fulminans. there is a polymorphonuclear leukocytosis averaging 16,000 white blood cells. The erythrocyte sedimentation rate has a median elevation of 84 mm/hr.

Acrodermatitis

Acne Urticata Polycythemica

Acrodermatitis

There is a striking increase in the erythrocyte count and total blood volume. Leukocytosis or thrombocytosis or both are frequently present. There is increased viscosity of the blood. Defects in either plasma or platelet coagulation factors may be present. Signs of bone marrow activity are found. Hyperuricemia is common. Urate clearance is impaired in about half the patients. Increased histamine levels in the blood and urine correlate with the pruritus.

SYN: Danbolt-Closs

Acne Varioliformis SYN: acne necrotica

Staphylococcus aureus is usually able from lesions of this disease.

recover-

Acrodermatitis Acrodermatitis

Chronica Atrophicans

Serum electrophoresis shows an increase in al,- a~,- and y-globulins and a decrease in albumins in most patients. Cryoglobulins are found in the blood of about 75% of cases. Creactive protein is positive in a quarter of the cases, while the rheumatoid factor (latex reagent) is positive half as frequently. High ceruloplasmin, low transferrin, and increased IgG and IgM have been found. Eosinophilia occurs in one quarter of the patients. The erythrocyte sedimentation rate is generally increased. Bone marrow studies reveal a moderate to marked increase in plasma cells, mast cells, and eosinophils. There is some evidence that this disorder is an infection spread by the tick Ixodes ricinus. A group B arbovirus has been implicated.

Continua

SYN: acrodermatitis repens

perstans.

dermatitis

The causative organism is Staphylococcus CIL(WU,S, often with superimposed Pseudomo~(1,saeruyinosa. During exacerbations, there are increases in the erythrocyte sedimentation rate and leukocytosis. Enteropathica disease

Many aberrant laboratory findings have been recorded, but the most significant are the low serum zinc levels ranging from lo-35 pg/dl (normal 80-165 pg/dl). There is no hyperzincuria. Many serum protein abnormalities have been recorded including fi-lipoproteinemia, decreased levels of low-density lipoprotein, and agammaglobulinemia. IgA deficiency has been found alone, with diminished IgM, and with a decrease in IgG. On the other hand, an increase in IgA has been noted. A zinc-responsive defect in chemotaxis of neutrophils and monocytes has been reported several times. Abnormalities in fat metabolism have also been described, and serum vitamin A levels may be decreased. Variants have exhibited lactose and fructose intolerance. Candida albicans may be recovered often from the stool, scrapings, draining ear, paronychia, mouth, sinuses, etc. Giardia lamblia has been found in the intestinal tract in a few cases. Most patients have a mild to moderate anemia and a normal or slightly increased white blood cell count. Eosinophilia may occur. Indicanuria, hematuria. and pyuria have been reported. Acrodermatitis

of Childhood,

SYN: papulovesicular

Papular

acrodermatitisof

child-

hood Called Gianotti’s disease by some, the Gianotti-Crosti syndrome by others, this entity is a primary infection with hepatitis B virus. It is characterized by hepatitis B surface antigenemia (HBsAg/ayw), antibody to

July-September Volume 4 Number 3

1986

3

Cutaneous Diseases

HBsAg, and antibody to core antigen (antiHBc). Enzymatic findings include elevated levels of lactic dehydrogenase (LDH), serum aspartate aminotransferase (AST = SGOT), serum alanine aminotransferase (ALT = SGPT), and alkaline phosphatase. Gradual disappearance of the antigenemia occurs within a few months; but in approximately one third of patients, it may persist for many months or years, usually in association with elevated AST (SGOT) and ALT (SGPT) levels. Hematologic studies show a mild hypochromic anemia with Turk cells and 5-20% histiocytic monocytes and, sometimes, a moderate eosinophilia (maximally 12%). Capillary fragility is increased. Increased CYand P-globulin in the serum and increase of histiocytic elements in the bone marrow have been reported. The antistreptolysin titer is normal or slightly elevated, and cold agglutination may be increased. A smaller group of clinically related patients is probably best designated as having “papulovesicular acrolocalized syndrome,” but it shares the same eponymic confusion enjoyed by the type described above. There is neither hepatitis B viral infection nor altered hepatic enzyme levels. Although the majority of cases are idiopathic, virus infectionEpstein-Barr, parainfluenza, and coxsackie virus A16; Schonlein-Henoch purpura; infectious mononucleosis; and smallpox vaccinations have been suspected as having a role in causing some cases. Streptococcus Acrodermatitis The streptococci may be demonstrated in stained smears and cultures of the clear thick serum from an unruptured vesicle. Acrodynia SYN: pink disease

Presence of mercury in the urine is the most reliable diagnostic aid. Albuminuria and hematuria frequently are present. Usually, urine also shows increased excretion of cortisone and 17-ketosteriods.

Acrokeratosis Paraneoplastica The finding of immunoglobulins in the basal layer-reported by some, has been denied by others. Low serum vitamin A levels, hyperglycemia, and increased catecholamine levels have been reported. Acropustulosis, Infantile The pustules are filled with neutrophils; no eosinophils are present. Cultures are negative for bacteria, yeasts, and fungi. Actinomycosis Actinomyces israelii may be demonstrated in sputum or in pus, particularly in the “sulfur” granules, in the majority of human disease.A. naeslundi, A. viscosus, A. odontolyticus, and Arachnia propionica may produce an identical clinical picture. The causative organism must be cultured anaerobically. Smears from colonies or tissue can be stained by fluorescent antibody technique. Slight to moderate anemia, moderate leukocytosis, and an elevated erythrocyte sedimentation rate are common findings.

Addison’s Disease There may be a normocytic-normochromic mild anemia and relative lymphocytosis with a decreased neutrophil count. Total circulating eosinophils are usually close to normal. There are low serum sodium and chloride levels with an elevated potassium reading. Increased sodium and chloride levels are found in the urine despite low serum findings. The diagnosis is made by stimulating the adrenal glands with ACTH and measuring cortisol secretion (decreased). AIDS (Acquired lmmunodeficiency Syndrome) Most of the patients have shown cutaneous anergy, anemia, lymphopenia, decreased number of T lymphocytes, reversal of normal T helper (OKT4) to T suppressor (OKT8) lymphocyte ratios, and decreased mitogenic and

4

Butterworth and

antigenic response of T lymphocytes. Pancytopenia has been reported. Patients with AIDS also have been shown to have significant reduction in their primary antibody response to polysaccharide and protein antigens, indicating that they have acquired B-cell as well as T-cell immunodeficiency. Elevated levels of total immunoglobulin. predominantly IgG and IgA, and immune complexes have been shown in the sera of most patients. Elevated levels of pz microglobulin (@M) characterize patients with confirmed and suspected AIDS. Data suggest that quantitation of flzM serves as a valuable component in a screen for persons in groups at high risk for AIDS. The human T cell leukemia-lymphoma virus Type III (HTLV-III) is suspected to be the cause of AIDS. The HTLV-III enzymelinked immunosorbent assay (ELISA) is a specific and sensitive screening test for the presence of antibodies and, hence, exposure to HTLV-III. The virus has been isolated from saliva and T cells in the seminal fluid of AIDS patients. Mycobacterium avium-intraceLlulare is typically shown in and cultured from bone marrow, lymph node, and liver biopsy. EpsteinBarr virus has been isolated from the throat washings and peripheral blood lymphocytes of many patients. Bowel problems due to various enteric organisms are common. Diseases complicating AIDS include severe recurrent herpes simplex, herpes zoster, Kaposi’s sarcoma, malignant lymphoma, Pneumocystis carinii pneumonia, candidiasis, aspergillosis, strongyloidosis, nocardiosis, necrotizing toxoplasmosis of the CNS, cryptococcal meningitis, and cytomegalovirus infections. Few or isolated reports have mentioned pancytopenia, hyperalbuminemia, and elevated aminotransferases.

Albinism, Oculocutaneous Albinism may be divided into tyrosinasepositive and tyrosine-negative forms on the basis of whether or not separated epidermis

Clrics In

Dermotoloav

Cawlev

and plucked depigmented anagen hair bulbs become pigmented when incubated with tyrosine.

Albright’s Hereditary Osteodystrophy Pseudohypoparathyroidism and pseudopseudohypoparathyroidism are variants of the same abnormality and are jointly referred to as Albright’s hereditary osteodystrophy. Serum calcium is decreased and serum phosphorus is increased in the former; they are normal in the latter.

Albright’s Syndrome SYN: polyostotic

fibrous

dysplasia

Serum alkaline phosphatase levels are elevated in about one third of the cases. Mild hyperthyroidism is common. Diabetes mellitus is an infrequent finding.

Alkaptonuria There is absence of the enzyme homogentisic acid oxidase, which leads to an accumulation of homogentisic acid in the blood and urine. The urine is dark and gives a positive result to Benedict’s test but a negative result to the glucose oxidase reagent strip test. Homogentisic acid may be identified by chromatography.

Alopecia Alopecia Are&a Demonstrated defects in cell-mediated immunity have included diminished numbers of circulating T cells and depressed in vitro lymphocyte transformation secondary to mitogen stimulation. Alopecia: Biotin-Responsive Carboxylase Deficiency

Multiple

Acidosis is commonly present and is apparent in routine blood electrolyte studies. Blood lactic acid is significantly increased. Chromatographic studies of the urine demonstrate increased levels of 3-hydroxyisovalerate, 3methylcrotanyl-glycine, 3-hydroxypropionate, and methyl citrate.

July-September 1986 Volume 4 Number 3

Cutaneous

Alopecia Mucinosa

Clinical pathology offers very little in the diagnosis of this disease. Decreased y-globulin and slightly increased serum cholesterol have been reported. Alopecia: Vitamin D-Dependent

Rickets

Serum calcium is low and serum phosphorus is normal or low. Serum alkaline phosphatase and immunoreactive parathyroid hormone are increased. 1,25-Dihydroxy-vitamin D levels are usually high.

Diseases

5

urea nitrogen, creatinine, and uric acid. Anemia may be present and the sedimentation rate may be elevated. Albumin and various clotting factors may be decreased. Calcium is frequently elevated in myeloma-associated cases. Serum or urine or both frequently show abnormalities in the gamma region on electrophoresis and immunoelectrophoresis. Bone marrow examination reveals increased plasma cells. Anemias, Congenital Hemolytic

Altemariosis A culture from scrapings of the involved area will show Alternaria sp. Other laboratory study results are usually within normal limits. Amebiasis Cutis Hanging slides prepared with material from the edge of an ulcer contain motile Entamoeba histolytica. Stools should also be examined for amebae. Immunologic studies include complement fixation, hemagglutination, gel-diffusion and precipitin, and indirect fluorescent antibody tests. Anemia may be moderate to severe. Leukocytosis occurs with neutrophilia. The erythrocyte sedimentation rate is increased. Amyloidosis, Localized Cutaneous Clq has been detected in amyloid islands in a high percentage of cases of localized cutaneous amyloidosis. Amyloidosis,

Systemic

The features of amyloidosis and the laboratory findings associated with them vary with the type of amyloidosis and the affected organs. Secondary amyloidosis is associated with long-standing inflammatory conditions. Primary amyloidosis and that associated with myeloma have similar organ distributions and proteins. Common findings due to organ distribution (or distribution in neoplasmassociated cases) are proteinuria accompanied by red cells and casts and elevated blood

The familial diseases in this group usually present themselves as nondermatologic complaints; but, occasionally, the presenting symptom is an intractable ulcer of the leg. For practical purposes, since these lesions are clinically indistinguishable, the several hemolytic anemias are presented here as a group. They share many laboratory features common to hemolysis regardless of their pathologic bases. The peripheral smear may show polychromatophilia, basophilic stippling, and nucleated red cells. Serum haptoglobin, lactic dehydrogenase, and indirect bilirubin are frequently elevated. Hereditary Spherocytosis

SYN:familial hemolytic anemia The anemia is usually mild but may be severe during aplastic crises. The peripheral smear shows a variable number of spherocytes, and the mean corpuscular hemoglobin concentration is usually elevated. Osmotic fragility of red blood cells is increased. White blood cells may be increased during crises. The marrow shows erythroid hyperplasia. During crises it may be hypoplastic. An occasional false-positive result of the serologic test for syphilis has been noted. Hereditary Elliptocytosis

SYN:Ovalocytosis There is mild or no anemia, but more than 75% of erythrocytes have elongated shapes. Osmotic fragility is usually normal, rarely increased.

Butterwoldh

6

and Cawiey

Hereditary Nonspherocytic Hemolytic Anemia Anemia and jaundice are usually present at birth. The red cells tend to be macrocytic. and spherocytes are either absent or present in small numbers. The osmotic fragility is usually normal. This heterogeneous group of hemolytic anemias is related to various enzyme deficiencies, notably pyruvate kinase and erythrocyte glucose-&phosphate dehydrogenase. The heterozygous parents have intermediate levels of the involved enzymes. Thalassemia

Clinics in Dermatology

Major

SYN: Mediterranean anemia, Cooley’s anemia, hereditary leptocytosis, p-thalassemia

There is pronounced anemia of a hypochromic, microcytic type. The hemoglobin range is 5-9 g/d1 and the red cell count, 2,500,0003,500,000/~1. The erythrocytes, often fragmented, show polychromatophilia, marked hypochromia. anisocytosis, and poikilocytosis. Although microcytes predominate, other abnormalities noted include reticulocytes, target cells, ovalocytes, Cabot rings. Howell-Jolly bodies, nuclear fragments, siderocytes, anisochromia, normoblasts, and basophilic stippling. Of the circulating hemoglobin, 40-100?0 is of the alkaline-resistant or fetal type. The red blood cells show markedly decreased osmotic fragility. The white blood cells range from normal to 30,000/~1. Granulocytes predominate, and myelocytes are common. The platelet count is generally normal. Moderate leukopenia and, to a lesser extent, thrombocytopenia are occasionally observed. The serum level of iron is increased, and the serum iron-binding capacity is less than normal. Plasma copper is increcsed, but plasma zinc is decreased. Serum bilirubin values are raised mildly. Free protoporphyrin of the red blood cells and serum lactic dehydrogenase levels are significantly elevated. The bone marrow is hypercellular, erythrocyte precursors being predominant. Prenatal diagnosis may be carried out

through bin-gene

endonuclease mapping deletion in some cases.

Thalassemia

of the glo-

Minor

.\nemia may be slight or absent. Hemoglobin range is lo-12 g/dl. The essential features include hypochromic microcytes, basophilic stippling, polychromatophilia, and oval and target cells. The mean corpuscular volume is decreased. Varying degrees of poikilocytosis and anisocytosis are seen. Oval cells and cylindrical or cigarette-shaped forms are common. Reticulocytosis is slight (3-W). Osmotic fragility is greatly decreased even in the absence of anemia. Serum iron is normal or high. Fetal hemoglobin is slightly elevated in one half of the cases. The white blood cells and platelets are within normal limits. Sickle Cell Disease and Trait In sickle cell disease, the usual erythrocyte count range is 2.0-3.5 million, although at times it may fall to 1 million cells. The stained film shows moderate anisocytosis, hypochromia, polychromasia, sickle cells, nucleated red blood cells, sometimes target cells, Howell-Jolly bodies, and 5-20% reticulocytes. Sickling may be noted readily when sealed preparations of blood are allowed to stand at room temperature for several days. The same phenomenon can be demonstrated within a few hours by the bisulfite method. Erythrocyte osmotic fragility is generally decreased, but there may be a small number of unusually fragile cells. Mechanical fragility is increased. The survival time of erythrocytes is shortened. The hemoglobin usually remains in the range of 5-9 g/dl. The plasma volume is increased, and there are hemoglobinemia and methemalbuminemia. There is commonly defective generation of thromboplastin. Zinc and immunoglobulin are increased. As a rule, there are associatsd leukocytosis, often with a “shift to the left,“and thrombocytosis. Moderate bilirubinemia occurs, and urobitinogen is increased in urine and

July-September Volume 4 Number 3

1986

Cutaneous Diseases

feces. The bone marrow shows marked erythroid hyperplasia except during periods of aplastic crises. At such times there are significant decreases in the bicarbonate and pH of the blood. Hematuria may be present in some patients. The diagnosis is confirmed by the electrophoretic demonstration of hemoglobin S (HbS). In sickle cell disease there is 80-100% HbS, with a varying but usually small proportion of HbF. The normal HbA is absent. In the sickle cell trait, there is 30-45% HbS and the remainder HbA. In the sickle-thalassemia variation, one finds 60-80% HbS and HbF usually increased. Prenatal diagnosis may be achieved by direct testing of fetal blood or by specific gene fragments obtained from amniotic fluid cells’ nuclear DNA subjected to restriction endonuclease treatment. Some laboratories are now testing chorionic biopsy specimens. In patients with sickle cell trait, there may be no anemia as a rule and the blood film appears normal except for the presence of a few target cells.

Anemia, Pernicious Macrocytic anemia, histamine-fast achlorhydria, megaloblastic marrow, decreased level of serum vitamin Blz, and reduced excretion of orally administered radioactive vitamin BU characterize this entity. Almost 75% of the patients have anti-intrinsic factor antibodies.

cocci may be found in a bacteriologic smear. An underlying blood dyscrasia, such as granulocytopenia or leukemia, must be sought.

Angioedema Angioeaema, Acquired Eosinophilia is usually found. Cryoglobulins may be present. Normal values for complement components are found.

Angioedema, Hereditary There is a deficiency of Cl esterase inhibitor, with a secondary depletion of C4 and C2. Normal amounts of C3 and Clq are present. In contrast, with acquired Cl esterase inhibitor deficiency secondary to malignant disease, Clq levels are decreased. The finding of low serum values for either C4 or C2 serves as a useful screen for a deficit in Cl esterase inhibitor activity. C4 assay is recommended because of its simplicity and the commercial availability of the reagents used. About 85% of patients have low levels of Cl esterase inhibitor (Type I) described above. The remainder (patients with Types II and III) have normal or increased levels of functionally deficient Cl esterase inhibitor.

Angioedema, Hereditary Vibratory Peak levels of plasma histamine are reached within a minute after provocation and subside quickly.

Angiokeratoma Corporis Diff usum

Angiitis, Cutaneous/Systemic The erythrocyte sedimentation rate is elevated. The leukocyte count is not changed, but lo-20% of patients have eosinophilia. The platelet count may be depressed during exacerbations. Hyperglobulinemia may also be present.

Angina, Vincent’s SYN: acute necrotizing gingivostomatitis

ulcerative

Bacteroides and Fusobacterium Borrelia vincentii, and anaerobic

species, strepto-

7

SYN: Fabry’s

disease

The basic biochemical defect is the absence or deficiency of ceramide trihexosidase (ugalactosidase), which results in an accumulation of ceramide trihexoside in widespread tissues. The enzymatic deficiency may be demonstrated in the leukocytes and serum of males with Fabry’s disease. Heterozygotes may be detected by finding a diminished (Ygalactosidase-fi-hexosaminidase ratio upon hair root analysis. The enzyme is decreased in female carriers by about one half. Antenatal diagnosis is possible.

a

Clinics in

Butterworth and Cawley

Affected men show a marked increase of urinary ceramide trihexoside and a slightly elevated output of ceramide trihexoside. The urine of female carriers shows a slight increase of these two substances. Urinalysis regularly reveals albumin. red and white blood cells, occasional hyaline and granular casts, and a low or fixed specific gravity. The most distinctive finding, however, is the presence of doubly refractile fatladen epithelial cells (mulberry cells) and free-lying fat bodies in centrifuged urinary sediment. The bone marrow also reveals lipid-filled cells, and a moderate and usually hypochromic anemia is fairly common. Eosinophilia and an elevated erythrocyte sedimentation rate may be found. The blood urea nitrogen and creatinine are increased. In some cases, electrophoresis has shown an increased p-lipoprotein. Fractionation of red blood cell stroma reveals an increase in cholesterol-phospholipid ratio, a decrease in the phospolipid content, and a marked reduction in phosphatidylserine of the cephalin factor.

Angioma Serpiginosum No helpful reported.

laboratory

findings

have been

Dermatology

L’O,OOO.Likewise, the differential cell count is ordinarily not affected, but there may be a slight to moderate increase in the percentage of polymorphonuclear leukocytes. The erythrocyte sedimentation rate may be increased. An indirect hemagglutination test for detecting antibodies has been developed.

Aphfhae, Recurrent L-forms of Streptococcus sanguis have been isolated from aphthae. Patients with aphthae have enhanced delayed hypersensitivity responses to streptococcal extracts.

Arachnidism In North America, this condition is caused by the bite of the black widow spider, Latrodwtus mactans, or the brown recluse spider, 1,o~~~~elr.s reclusa. A hemolytic anemia may develop after the bite of the latter, with hematuria and thrombocytopenia.

Argininosuccinicaciduria Chromatography of urine reveals the abnormal excretion of argininosuccinic acid as well as citrulline. An increased blood ammonia level is suggestive. There is absence or deficiency of argininosuccinate lyase. Prenatal diagnosis is possible.

Anterior Tibia1 Syndrome

Arsenism

Leukocytosis and an increased blood sedimentation rate are noted. If muscle necrosis occurs, creatine phosphokinase, aldolase, lactic dehydrogenase, and serum aspartate aminotransferase may be elevated.

In acute or subacute poisoning, arsenic is eliminated in the urine in excess of 0.1 mg/day (normal 0.005-0.04 mg/day). In chronic arsenism, 0.01 mg/lOO g is found in the hair (normal 0.008-0.025 mg/lOO g).

Anthrax

Takayasu’s Arteriopathy

Bacillus anthracis may be demonstrated in smears taken from vesicles or beneath the edge of the crust. Immunofluorescent stains, especially, provide rapid and specific identification. Cultures from the same sources and of the blood are indicated. Virulence tests are performed by animal inoculation. White blood cell counts are often within the normal range and are seldom above

This variety of aortic arch syndrome manifests a persistently elevated erythrocyte sedimentation rate, moderate anemia, and plasma protein abnormalities.

Arteriosclerosis Obliterans Search for diabetes mellitus, mia, and hyperlipidemia.

polycythe-

July-September 1986 Volume 4 Number 3

9

Cutaneous Diseases

Aspergillosis

Arteritis, Giant Cell SYN:temporal arteritis The most significant finding is a moderate to marked increase in the erythrocyte sedimentation rate, sometimes exceeding 100 mm/hr (Westergren). Hypochromic or normochromic anemia is also common. Mild to moderate leukocytosis and mild thrombocytosis are found frequently. Decreased serum albumin with an occasional reversal of the albumin-globulin ratio and increased r-globulins, complement, and blood fibrinogens are noted. Alkaline phosphatase may be elevated. Arthritis, Rheumatoid Serum electrophoresis may show a low albumin peak, and a broad increase in yglobulin may be seen. Most of the increase can be attributed to the rheumatoid factor, which is usually IgM and, rarely, IgG. Some patients have elevation of all three major classes of immunoglobulins to a significant degree. Deposits of immunoglobulin are seen frequently in vessel walls. The rheumatoid factor may be detected in 80% of patients by direct tests such as latex fixation and bentonite flocculation. High titers are associated with subcutaneous nodules and vasculitis. With the latter, there are usually high hemagglutinin titers. Serum complement is usually normal or elevated: in vasculitis, levels may be sharply depressed. Antinuclear antibodies occur in 14-18%, whereas the LE cell test result is positive in the more active 5% of cases. A few patients have cryoglobulins. False-positive results of serologic tests for syphilis are noted. Mild or moderate normocytic and hypochromic anemia is common. White blood cell counts are most often normal or only minimally elevated. A number of studies have demonstrated abnormalities of lymphocyte function. Accompanying the inflammation, one finds an elevated erythrocyte sedimentation rate, C-reactive protein, and increased a-globulin and fibrinogen. Serum iron level and iron-binding capacity are low normal or decreased.

Recovery of Aspergillus dulans,

fumigatus, A. niA. flawus, A. terreus, or A. niger on

culture of a rare cutaneous lesion is of little value since the fungus is so often found as a laboratory contaminant. The recommended procedure is the gel-precipitin test with species-specific antigens. Eosinophilia is not uncommon, and the serum IgE level may be elevated.

Ataxia-Telangiectasia SYN:Louis-Bar syndrome Significant lymphopenia is found in all cases, with the major reduction in the small lymphocyte. The lymphoblastic transformation index is decreased. There is depressed, but not absent, in vitro lymphocyte responsiveness. The ratio of helper to suppressor T cells is also reduced. Granulocytopenia and eosinophilia are often noted. An elevated erythrocyte sedimentation rate is the rule. Results of bone marrow studies have been normal. One of the most consistent laboratory findings is elevation of the serum a-fetoprotein level (above 30 ng/ml). Hypogammaglobulinemia is a regular feature. About 70% lack serum and secretory IgA, and a similar number has been reported to have IgE deficits as well. Evidence of specific IgG2 deficiency has been reported recently. Many patients may frequently produce lowmolecular weight IgM; 50% have autoantibodies. The patients show a sluggish circulating antibody response, particularly to weak antigens, and almost complete failures of the function of delayed hypersensitivity associated with a decrease in T-cell population. Chromosome breaks and rearrangements occur in 80%. Many die from lymphoreticular or other malignancies. Aminoaciduria has been noted and abnormal collagen reported. An unusual form of diabetes occurs, characterized by hyperglycemia with only rare glycosuria, absence of ketosis, marked hyper-

Clinics

Buttenvorth and Cawley

10

secretion of insulin, and peripheral resistance to the action of insulin. Associated endocrinologic abnormalities include decreased urinary excretion of 1’7 ketosteroids and increased urinary excretion of FSH.

phytohemagglutinin is reduced. The chemotactic activity of the polymorphonuclear leukocytes is slightly, but significantly, lowered. Results of skin tests with staphylococcus and streptococcus toxins are generally strongly positive.

Atrophie Blanche, Idiopathic

Balanoposthitis

Results of laboratory studies normal in these patients.

are usually

Atrophy, Macular Serologic

tests for syphilis

are indicated.

Autoerythrocyte Sensitization Syndrome SE’N:

Gardner-Diamond

;2licroscopic examination and culture reveal the presence of Cnndidu albicans. fusiform bacilli, Borrelia llincentii, cryptococci, or other organisms. Cases under treatment with topical steroid, antibacterial, and anticandidal agents may be colonized by Pseu(/o~o~/o.s trfruginosa, giving rise to severe erosive balanitis.

syndrome

Extensive studies of hematologic and coagulation factors have failed to reveal any characteristic abnormalities. Patients develop lesions upon injection of autologous red blood cells. Hematuria and gastrointestinal bleeding may occur.

Autoimmune Progesterone Dermatitis of Pregnancy One finds eosinophilia and elevated serum IgG and IgM. Intradermal skin tests produce a painful abscess at the test site injected with progesterone but not with estrogen.

B Bacterid, Pustular Cultures of the vesicopustules are consistently sterile. Cytologic studies of the contents of the pustules reveal 85% neutrophil leukocytes and 12% lymphocytes. During fresh outbreaks, the white cell count may show a leukocytosis that ranges from 12,000 to 19,000 cells with 6580% polymorphonuclears. About half of the patients have a slightly increased erythrocyte sedimentation rate. The rate of lymphocyte transformation by

Beckwith-Wiedemann Syndrome Chemical or clinical hypoglycemia occurs in 50’)1,or more of the infants within 2 days after birth. Polycythemia, hyperlipemia, hypercholesterolemia, and hypocalcemia have been noted in a few instances.

Beh$et’s Syndrome Dysproteinemia is the outstanding finding in this disease. Serum albumin is decreased, but elevated values are found for globulin (especially the y fraction), mucoprotein, and serum protein-bound hexoses. Values of IgG, IgM. and IgD are high in sera and cerebrospinal fluids. Immunofluorescenceshows the disposition of IgM and IgG in vascular walls, especially in the venules. IgA is markedly decreased in the saliva. Also found are high levels of total hemolytic complement titer and concentrations of C9, although there is a significant reduction of C2, C3, and C4 just before an attack of uveitis. A biopsy specimen of an oral ulcer shows deposition of C3 and C9 in blood vessel walls and of C9 in the basement membrane. Many patients show elevated levels of circulating immune complexes. C-reactive protein is positive in almost half the cases. Fibrinogen levels have been elevated in some individuals, normal in others. Sometimes there is a moderate increase of the antistreptolysin titer. Parapro-

July-September 1986 Volume 4 Number 3

Cutaneous

teinemia and cryoglobulinemia have been reported. Leukocytosis occurs in more than half the patients, while eosinophilia is noted in a few. Increased leukocyte chemotaxis has been reported. The mean percentage of T cells is decreased, with the loss notably in the helper cells. Suppressor cells are increased. An elevated erythrocyte sedimentation rate is the rule. Hypercholesterolemia is found in about 25% of the cases. In addition to increased protein, the cerebrospinal fluid shows pleocytosis with polymorphonuclear leukocytes and lymphocytes in equal frequency. Autoantibodies against human oral mucous membranes have been reported in almost half of the patients studied.

11

Diseases

tion (CF) and immunodiffusion (ID) tests are available. The latter is positive and specific in about 80% of patients. Complement fixation is less sensitive (about 50%) and shows cross-reactivity with other fungal diseases.

Bloom’s Syndrome Chromosome breakage and sister chromatid exchanges occur with a very high frequency. Laboratory evidence of immune deficiency, when present, has been inconsistentpartial or complete deficiencies of one or more immunoglobulins (IgA and IgM) in some. Patients may have impaired humoral or cellular response to antigenic challenges, and some may have partial dysfunction of T lymphocytes. A number of patients have died of leukemia.

Bejel

Botryomycosis

Serologic tests for syphilis are reactive. Darkfield examination of scrapings shows spirochetes.

Bites, Animal Cultures of bites of cats and dogs have yielded Pasteurella multocida with increasing frequency. Many other organisms may be found.

Blastomycosis, Lobe’s Keloldal Type The causative organism be classified as a fungus.

(Loboa [oboi) may

Blastomycosis, North American Blastomyces dermatitidis may be demonstrated by a KOH mount, McManus stained smear, fluorescent antibody technique, and culture of pus from cutaneous lesions, draining sinuses, abscesses, sputum, urine, biopsy specimens, prostatic secretion, gastric contents, blood, bone marrow, and abdominal fluid. Guinea pigs and mice may be inoculated successfully. Intradermal tests may be done with blastomycin and B. dermatitidis vaccine, the latter giving a higher percentage of positive readings than the former. Complement fixa-

Reported cases have been due to Staphylococcus aureus most frequently, but the disorder may also be produced by Pseudomonas aeruginosa, Escherichia coli, Bacteroides species, Proteus species, and streptococci.

Brachmann-delcnge Syndrome SYN: Cornelia

delange

syndrome

Infants show an inability to concentrate urine. Aminoaciduria is present, and there is diminished excretion of l’i’-hydroxycorticoids in response to corticotropin. The babies also show hypogammaglobulinemia. A normochromic normocytic anemia and leukocytosis occur. These patients have an abnormal sensitivity to insulin. The consensus is that the condition is not associated with karyotype alteration.

Bromoderma A plasma bromide gestive of bromism.

level of 75 mg/dl

is sug-

Bwcellosis Several species of Brucella (B. melitensis, B. suis, B. abortus, and B. canis) are the etiologic agents of this disease. Cultures are usu-

Clinics in

Butterworth and Cawlev

12

ally taken from the blood, but the organisms may be recovered occasionally from the urine, joint fluid, spinal fluid, bone marrow, duodenal drainage, excised lymph nodes, or pus aspirated from foca! abscesses. Agglutination tests are of great value. Patients with titers of 1:160 to 1:320 are most likely to have brucellosis. An increasing titer is also important. Other serologic tests are of no particular value. In about 90% of patients, the white blood cell count is normal or reduced, and the lymphocytes are usually relatively increased in number. Macrocytic hyperchromic anemia may be present. The erythrocyte sedimentation rate is normal or slightly elevated. When the central nervous system is involved, the spinal fluid has a xanthochromic appearance, pleocytosissometimes with high percentage of polymorphonuclear neutrophils, low sugar concentration, and high protein values.

C Calcinosis Cutis In “metastatic” calcification (disturbed parathyroid function. bone destruction, renal disturbance, vitamin D intoxication, milkalkali syndrome, chronic fluorosis), there are elevated serum calcium or phosphorus levels. In “dystrophic”calcification, such as that seen in scleroderma or dermatomyositis or following panniculitis, these levels are normal. Serum calcium is decreased and serum phosphorus is increased in pseudohypoparathyroidism.

Dermotoloav

obic bacteria including Bacteroides and Fusobacterium species and Borrelia chcentii.

Candid&is SYN: Moniliasis Candida albicans and, less often, C. troyicalis, C. stellatoidea, C. krusei, and C. (Toru1opusis)glabratamay be found in KOH preparations and culturesof skin and nail scrapings. Sputum, mucus, vaginal discharge, and pus may show the organism when examined fresh or after Gram’s staining. In addition to the above sources of material, the stool often yields positive cultures on Sabouraud’s medium. Latex agglutination, immunodiffusion, and counterelectrophoresis are of value in the diagnosis of systemic disease. The complement fixation test is less reliable. Skin testing shows no difference between well and infected persons and is used as a test of cellmediated immunity. In disseminated moniliasis, Candida albiULIISmay be recovered in cultures of the blood, cerebrospinal fluid, and urine. In patients who are not immunosuppressed, the leukocyte count varies from 10,000 to 40,000, with mature polymorphonuclear and band forms rising to between 75 and 95%.

Carcinoid The blood level of serotonin is greatly increased. A screening test for its metabolite in the urine, 5-hydroxyindoleacetic acid, is available. Quantitation of urinary 5-hydroxyindoleacetic acid and blood serotonin may be done.

Cancer, Oral Cytologic examination of smears or aspirates of suspected lesion is often of diagnostic value.

Cancrum Oris SYN: Noma Noma is due to a symbiosis

of various anaer-

Carotenemia SYN: aurantiasis

cutis

Excessive amounts of carotene are demonstrable in the blood serum and in the urine. Diabetes mellitus or myxedema may be an associated finding. Serum lipids may be increased with high cholesterol.

July-September Volume 4 Number 3

1986

Cartilage-Hair Hypoplasia Laboratory studies reveal chronic neutropenia and lymphopenia and reduced delayed hypersensitivity skin reactions. Diminished responsiveness of lymphocytes in vitro and delayed rejection of a skin allograft have been reported. Serum immunoglobulin levels have been normal or elevated.

Cat-Scratch Disease SYN:benign

Cellulitis, Gangrenous, Compromised Host

Cellulitis Although a streptococcus is the common etiologic agent, in a small group of babies, cellulitis of the face has been caused by Hemophilus influenxae, type B. In a large percentage of these infants, this organism was also recovered in cultures of the nose, throat, and blood. In a few cases, the organism has been found in the cerebrospinal fluid. A blood count reveals leukocytosis often exceeding 20,000 cells. Pseudomonas aeruginosa, cryptococci, Serratia marcescens, and Aeromonas hydrophila have caused some cases of cellulitis especially in debilitated and immunosuppressed patients. A localized cellulitis following the bite or scratch of an animal may be due to Pasteurella multocida (P. septica). Crepitant

Clostridia, usually Clostridium perfringens, cause clostridial cellulitis. A variety of aerobic and facultative bacteria, including peptostreptococci, Bacteroides species, and Enterobacteriaceae, are responsible for nonclostridial crepitant cellulitis.

in the

Gram’s stain of an aspirate from the skin lesion usually shows Pseudomonas aeruginosa. Rarely, other gram-negative facultative bacilli may be involved. Necrotic ulcers have been described during aspergillus infection, phycomycosis, cryptococcosis, and Aeromonas hydrophila sepsis.

lymphoreticulosis

An as yet unclassified pleomorphic gramnegative bacillus has recently been described in this disease. It is best demonstrated in tissue by a Warthin-Starry stain. Positive complement fixation test results are obtained with lymphogranuloma venereum antigen. An elevated erythrocyte sedimentation rate is found during the acute lymphadenitis. Thrombocytopenic purpura may be a complication.

Cellulitis,

13

Cutaneous Diseases

Chancroid SYN:soft chancre The classic test for the laboratory diagnosis is the smear examination taken from the border of the ulcer or by aspiration from a bubo. Hemophilus ducreyi is seen in a Gramstain preparation as gram-negative bacilli occurring in clusters in the classic “school of fish” pattern. This is not specific, and other organisms may mimic this pattern. The Ito-Reenstierna skin test is no longer commercially available.

Chhdiak-Higashi Syndrome A constant and characteristic finding of this disease is the presence of anomalous granulation in the polymorphonuclear leukocytes and lymphocytes of the peripheral blood and abnormal “inclusion-like” bodies in the myeloid series as demonstrated in bone marrow preparations. Chemotactic and bactericidal functions of neutrophils are deficient. In the terminal stages, the process resembles leukemia with the development of pancytopenia. Widespread disturbances in lipid metabolism occur.

Cheilitis Scrapings and culture may reveal the presence of Candida albicans, probably as a secondary invader. If the cheilitis is a sign of Plummer-Vinson syndrome, an iron-deficiency anemia is present.

Chiggers This condition is due to various the Trombicula species.

members

of

14

Butterworth

and Cawlev

Coccidioidomycosis

Chikungunya Fever Common findings are a raised erythrocyte sedimentation rate and a high (‘-reactive protein level. In the acute stage, an arbovirus of the alphavirus subgroup can be isolated from the patient’s serum. A rise in the chikungunya antibody titer during convalescence can be demonstrated. Rheumatoid factors in low titers are found in about one quarter of the patients.

Chromomycosis SYK: chromoblastomycosis Curettings and cultures usually reveal the presence of one of the following organisms: F~~~SYCYIP~I prdrosc~i. Wangirilu dertttutitidis. (‘ltr-

Phiialoyhortr wrrucosu.

F. eompxfutr~. dosyorium pera.

carrioni,

or Rhinocladiella

aquas-

Chromonychia A host of fungi can cause discoloration of the nails. Frequently overlooked is the fact that Pseudomorzas aeruyinosu may cause green nails and Proteus mirnbilis black nails. KOH preparations and cultures are indicated.

Churg-Strauss Syndrome SYN:

allergic vasculitis

granulomatosis,

Clinics in Dermatoloov

granulomatous

There is leukocytosis, with eosinophils constituting20-90% of the white blood cell count at some point of the disease.

Citrullinemia Plasma citrulline range is 25-35 mg/ml (normal, less than 1 mg/ml), whereas urinary excretion is 450-2500 mg/day (normal, less than 10 mg/day). There is a deficiency of the enzyme argininosuccinic acid synthetase so that urea synthesis is compromised and hyperammonemia results. Arginine deficiency occurs.

SYN: San Joaquin

fever

organism is Coccidioides diagnosis is made by demonstrating the characteristic endosporulating spherules in KOH wet mounts of sputum. pus from draining sinuses, scrapings from skin lesions or biopsy specimens, or by culture of the fungus. A specific fluorescent stain is available. Of great diagnostic value is the delayed tuberculin type of reaction that occurs following the intradermal injection of coccidioidin. Latex agglutination and precipitin tests are useful in detecting IgM that appears early in the disease process. Latex agglutination results are positive l-2 weeks after primary infection, persist 2-4 weeks, and then become negative. Precipitins are demonstrable within 4 weeks in the serum of 90% of patients. The precipitin titer usually disappears within 4 or 5 months regardless of the course of the disease. The complement fixation test result becomes positive later and parallels the clinical course. Levels above 1:32 are indicative of dissemination. Complement fixation titer of 1:8 may persist for many years after the disease is apparently cured. A recent development, enzyme-linked immunosorbent assay (ELISA), has been used to detect circulating antigens in human sera in the early stages of the disease. About 20% of patients develop erythema nodosum, and this complication is frequently accompanied by eosinophilia. When meningeal involvement occurs, the cerebrospinal fluid shows elevated protein, depressed sugar, and pleocytosis with lymphocytes predominating. The causative

Lrrrttrifis. A definite

Cockayne’s Disease At present, laboratory procedures are of little value in the study of these cases. Electrophoresis and ultracentrifugation have shown slight abnormality of P-lipoproteins.

Cold Sensitivity Several

types occur. Cold urticaria

is due

July-September Volume 4 Number 3

1986

Cutaneous

to histamine

release from the mast cells of the skin and the basophilic granulocytes of blood (basophilic degranulation). In paroxysmal hemoglobinuria, the Donath-Landsteiner test demonstrates the presence of cold hemolysins that act upon red blood cells and lead to hemoglobinemia and anemia. Cold leukoagglutinins are also present and result in neutropenia. Thrombocytopenia is frequently observed. Increased platelet adhesiveness and platelet-associated clotting may occur. The urine is dark intermittently, and red blood cells, oxyhemoglobin, methemoglobin, hemosiderin, red blood cell “ghosts,” urobilinogen, and albumin are found. Two forms exist: an acute variety due to viral infection and a chronic type due to syphilis. Acute cases may show false-positive results of tests for syphilis. Constituting another type are cryoglobulins and cryofibrinogens, abnormal globulins that precipitate at cold temperature and redissolve on warming. Cryoglobulins may be a single immunoglobulin or mixtures of IgG-IgM, or IgG-IgA, or others. Cryofibrinogenemia exhibits the chronic paradox of intravascular clotting appearing simultaneously with a hemorrhagic diathesis. Anemia, leukopenia, thrombocytopenia, and an elevated erythrocyte sedimentation rate are found. The urine shows albumin and red and white blood cells. Three fourths of patients with essential mixed cryoglobulinemia have been exposed to hepatitis B as demonstrated by serum and cryoprecipitate evaluation for HBsAg and anti-HBs. A high cold agglutinin titer suggests the diagnosis of cold agglutinin syndrome. This is caused by hemagglutinins that are 19 S or a-M globulins and agglutinate erythrocytes of all groups at temperatures of 0” to 5’ C.

Collagen Disease Included in this category are systemic lupus erythematosus, scleroderma, dermatomyositis, periarteritis nodosa, Sj6gren’s syndrome, rheumatoid arthritis, and others. The group of diseases shares many labora-

Diseases

15

tory findings in common. Biologic false-positive serologic reactions for syphilis may precede other abnormalities by a number of years. The erythrocyte sedimentation rate is increased. Abnormal A/G ratios occur. Serum albumin is decreased, but globulin, fibrinogen, and glycoprotein are elevated in many collagen diseases. Positive results of lupus erythematosus and rheumatoid factor tests are recorded with great frequency. Antinuclear factors are found in high percentages of cases with systemic lupus erythematosus, scleroderma, dermatomyositis, and rheumatoid arthritis. Abnormalities of the complement system are common. It is interesting that some of the laboratory changes described above may exist in relatives of those affected with collagen disease.

Colorado Tick Fever In this viral disease, transmitted by Dermacentor andersoni, the laboratory findings include a leukopenia of 2,000-3,000 cells and a complement fixation titer that rises at least fourfold from acute to convalescent sera. There is positive fluorescent antibody stainingof patients’erythrocytes. The pathogen is a member of the group orbivirus.

Confluent and Reticulate Papillomatosis Pityrosporon orbiculare has been suspected of playing a role in a few cases.

Connective Tissue Disease (Mixed) A positive ANA test result occurs in over 95%, a positive LE prep in 2096, and elevated anti-nDNA antibody in about 25%. There is a high titer of autoantibody to ribonucleoprotein (RNP). One third show dermal-epiderma1 deposition of IgG indistinguishable from the lupus band. A few have hyperglobulinemia.

Conradi’s Disease Laboratory

studies

have shown consistent-

16

Butterworth

and Cawley

ly normal findings except in occasional cases with high or low cholesterol levels, low calcium values, or low results with thyroid screening tests.

Cowden’s Disease No characteristic been reported.

laboratory

findings

Clinics in Dermatology

have

screening test for hypothyroidism; T4 is low in most cases. Serum TSH levels are nearly always increased. Anemia is often present. Serum phosphatase is decreased, and the circulation time is slow. The cholesterol and carotene levels of the serum may be elevated, but these are not constant findings. Radioactive iodine uptake may be normal or high.

Crohn’s Disease

cowpox SYN: Vaccinia Keratoconjunctivitis or dermal lesions may be produced in rabbits by vesicle fluid. Good complement fixation and neutralization tests are available, also using for this purpose the contents of the vesicles. The virus produces large hemorrhagic plaques on chick embryo. A hemagglutination test is also employed. Biologic false-positive STS results may be as frequent as 20-30% of those with vaccination “takes.” The TPI (Treponema pallidunr immobilization) test is negative and the STS ordinarily becomes nonreactive within 2-4 months.

Creeping Eruption Most cases are due to Ancylosto,ma bruziliense; less commonly, A. caninum, A. duodenale, and Necator americanus are found. Rarely, Uncinaria stenoceph,ala, Bunostomum phlebotomum, Gnathostoma spinigerum, and Strongyloides stercoralis are the etiologic agents. Eosinophilia is the rule. Loffler’s syndrome, consisting of a patchy infiltrate of the lungs with eosinophilia as high as 51% in the blood and 90% in the sputum, may appear with some frequency in creeping eruption.

Cretinism, Metabolic goitrous

cretinism

Cronkhite-Canada Syndrome There is a relentless loss of albumin and electrolytes through the gut wall with concomitant steatorrhea. Many patients become hypoproteinemic and anemic. Hypocalcemia may be severe in the late stages and hypomagnesemia may also be present. D-Xylose absorption is impaired in most patients.

CRST Syndrome SYN: crest syndrome

SYN: larva migrans

SYN: familial Myxedema)

Many patients have anemia. Iron and vitamin BU are frequently decreased. About half of the patients with Crohn’s disease have a positive result of the Kveim test.

(see also

There is a defect in thyroid hormone synthesis with a compensatory increase in production of thyroid-stimulating hormone. Determination of serum T4 level is the major

In this variant of scleroderma, serum globulin abnormalities and elevated sedimentation rates are rather common. Anticentromere antibodies are frequently demonstrated.

Cryptococcosis SYN: torulosis,

European

blastomycosis

The yeastlike fungus, Cryptococcus neoformans, may be demonstrated in India ink smears of pus from abscesses and granulomas, sputum, urine, prostatic fluid, centrifuged spinal fluid, and aspirates from areas of cellulitis. Tzanck preparations from blisters may show characteristic organisms. Cultural isolation on Sabouraud’s medium is simple. When injected intracerebrally into mice, C. neoformans produces a rapidly progressive fatal disease that distinguishes it from other Cryptococcus species. The latex slide agglutination test for cryptococcal antigen is a simple, rapid, and accu-

July-September 1986 Volume 4 Number 3

17

Cutaneous Diseases

rate method for screening body fluids. It should be used in conjunction with the tube agglutination test for cryptococcal antibody since antibody may be found in cases in which the result of the test for antigen is negative. The indirect fluorescent antibody (IFA) test gives positive results more often than does the tube agglutination test (for antibodies), but these positive reactions often occur in the absence of any evidence of cryptococcal infection. A complement-fixation test has also been found to be sensitive. Cushing’s Syndrome Urinary 17-ketosteroids and plasma and urinary 17-hydroxycorticoids are elevated. Disturbed carbohydrate metabolism is manifested by hyperglycemia, glycosuria, or impaired glucose tolerance test. Most patients have mild leukocytosis. About 30% have mild lymphocytopenia and a low absolute eosinophi1 count. Polycythemia is found in about 10% of cases. One quarter have a mild hypokalemic alkalosis. Serum sodium level is usually normal, although it is slightly increased in about 5%. Before a diagnosis can be made with certainty, various stimulating or suppressive tests are necessary. Cutis Laxa A decreased level of circulating elastase inhibitor is found in the serum. Elevation of serum copper has also been reported. Cutis Verticis Gyrata Leukemia is one of the many causes of this abnormality. Syphilis has played acausative role in a few cases. Cysticercosis, Subcutaneous This is an infection with Cgsticercus cellulosae, the larval or bladder worm form of the pork tapeworm, Taenia solium. The latter, as well as ova, may be found in the stools. At present, the most useful diagnostic test is indirect hemagglutination. Anemia, intermittent eosinophilia in 15%, and elevated

erythrocyte findings.

sedimentation

rate are usual

Cytomegalic Inclusion Disease Diagnosis may be made by finding intracytoplasmic or intranuclear inclusions in epithelial cells in urine sediment. Cytomegaloviruses can be isolated from throat swabs and urine by tissue cultivation methods. Complement-fixing titers strongly suggest active and then resolving infection, Antibodies are demonstrated by the immunofluorescent technique. In the acute forms, there are thrombocytopenia, anemia, nucleated RBCs, and a shift to the left on the peripheral blood smear. The disease has been found in patients with acute leukemia in a number of instances and in others with depressed immune reactions, including AIDS patients.

D Defibrination Syndrome, Acute Hypofibrinogenemia or afibrinogenemia gives rise to a delayed clotting time or failure to clot. If the blood clots, it may undergo partial or complete dissolution within 30-60 minutes. Demodicidosis Demodexfolliculorum may be readily demonstrated by examining contents of a sebaceous gland on a slide with a drop of glycerin.

Dengue Fever Serologic diagnosis may be made by finding a fourfold or greater rise in hemagglutination-inhibition titers between acute and convalescent sera. Virus isolation is performed by using the mosquito inoculation technique. Viral antigen in these mosquitoes is determined by a direct flourescent antibody test. Virus identification is accomplished by the complement fixation test using antigen prepared in mosquitoes. A flavivirus is the causative agent.

Butterworth

18

and Cawiey

About half of the patients show leukopenia. Occasionally, thrombocytopenia is found.

Dermatitis Cruris Pustulosa et Atrophicans c:oagulase-positive staphylococci ally found in the cultures.

Dermatitis

Dermatitis,

Dermatitis, Atopic SYN: disseminated

neurodermatitis

Significant changes are noted in the cellular structures of the blood and in the circulating immunoglobulins during exacerbations of the dermatitis but with strong tendencies to return toward normal standards with clinical remission. There is a definite depression of T cells in number and function. On the other hand. the absolute number of B cells is significantly higher and correlates with clinical severity. They show depressed responses to phytohemagglutinin. Random mobility of leukocytes is normal, but there is serum inhibition of monocyte and neutrophil migration and impairment of chemotaxis of the latter two types of cells. Neutrophils exhibit decreased phagocytic capacity. Eosinophils are significantly increased in number in accordance with the severity of the dermatitis. Depressed delayed-type hypersensitivity responses to tuberculin, streptokinase-streptodornase. and candidin have been noted. IgE is significantly elevated in serum and skin and correlates with the clinical activity of the dermatitis in about 80% of patients. A high IgE concentration in the umbilical cord blood tends to predict the later development of atopic dermatitis, particularly in persons with a positive family history of the disease. A deficiency of IgA occurs in about 7%. Elevations of IgG and IgM may be related to secondary infection. A “flat” glucose tolerance test result is a common finding. About 70% of the patients exhibit a delayed blanch phenomenon to intradermal injection of acetylcholine. Dermatitis, Chronic Discoid and Lichenoid Moderate leukocytosis frequently observed.

and eosinophilia

Cltnlcs In Dermatology

are

are usu-

Diaper

(‘ultures show Staphylococcus uureus in Cundida a&cam in 500/o, and both 6O”+lO, organisms in 25% of patients. Coagulasenegative staphylococci, Escherichia coli, and Proteus mirabilis are also found frequently. Dermatitis,

Exfoliative

These patients show slight anemia, considerable leukocytosis, and eosinophilia. The erythrocyte sedimentation rate is elevated. Some cases are due to leukemia. Decreased serum albumin and a relative increase in serum globulin are noted. Staphylococcus CIL~WUS Group 2, phage type 71. is usually found in exfoliative dermatitis of the newborn (staphylococcal scalded skin syndrome Ritter’s disease). Dermatitis,

Gonococcal

Cultures of blood, joint aspirates, and smears from cervix may be positive for gonococci. Those from skin lesions may be positive only in early stages. The erythrocyte sedimentation rate is usually elevated. Leukocytosis with neutrophilia may be found. Dermatitis

Herpetiformis

SYN: Duhring’s

disease

Perhaps the best criterion for the diagnosis of dermatitis herpetiformis is the direct immunofluorescence finding of granular IgA deposits at the tips of the dermal papillae that surround the bullae and in a continuous band at the dermal-epidermal junction of involved skin. Although IgA is the predominant demonstrated immunoglobulin, IgG and IgM deposits may be found. In addition, fibrin, C3, and other immunoreactants may also be deposited. HLA-B8, HLA-Dw3, and a P-lymphocyte surface antigen DRw3 are encountered in a high percentage of patients. Circulating antibodies to reticulin, gluten, gliadin, thyroglobulin, microsome, gastric

July-September Volume 4 Number 3

1986

Cutaneous

parietal cells, nuclei, and immune complexes are also found. Reticulin and gluten antibodies decrease or disappear in patients on a gluten-free diet. Fluid in the bullae shows many eosinophils, which form 20-90% of the cellular elements. Although not a constant feature, the blood may present an eosinophilia as high as 40%. A few patients have a moderate polymorphonuclear leukocytosis. Others present with a hypochromic anemia. Pernicious anemia has been reported. Treatment with sulfones may produce a self-limited acute hemolytic anemia in persons with GGPD deficiency. Achlorhydria, altered disaccharidase activity, and increased fecal fat excretion are found in accordance with the histologic changes in the small intestines. Absorption dysfunction, shown by D-xylose absorption test, lactose tolerance test, or fecal fat excretion can be detected, however, in only 50% of patients. Sulfobromophthalein retention is a common feature. Decreased folate and iron have been noted in the serum and red blood cells. M globulins have been reported in the serum. The urine may show decreased chlorides and increased indican. Associated malignancies include leukemia among many others. An atypical form of dermatitis herpetiformis, or perhaps a distinct entity, known as linear IgA bullous dermatosis, is characterized by the presence of circulating IgA BMZ antibodies as well as homogeneous linear deposition of IgA along the basement membrane zone.

Dermatitis, Infectious Eczematoid Coagulase-positive staphylococci are the organisms most frequently isolated. Tests for antibotic sensitivities are indicated.

Dermatitis Medicamentosa Studies of serum proteins show increased (Al-and crz-globulin, ceruloplasmin, and haptoglobin. Albumin, IgM, and transferrin are found in decreased amounts. C-reactive protein is positive.

19

Diseases

Dermatitis, Papular, of Pregnancy Markedly elevated level of urinary chorionit gonadotropin ranging from 25,000 to 500,000 units in the last trimester characterizes this entity. Lowered plasma hydocortisone level and shortened hydrocortisone halflife are recorded. A significant number of mothers are Rh negative.

Autoimmune Progesterone Dermatitis of Pregnancy At 48 hours, a large painful abscess is found at the site of intradermal injection of progesterone. No reaction occurs to estrogen injected in similar fashion. Elevated levels of IgG and IgM are found. Eosinophilia parallels the course of the disease.

Dermatitis, Seaweed This process is due to the marine alga Lyngbya majuscula, which may be found in bathing garments.

Dermatitis, Seborrheic Malassexiafurfur is thought by many to be a factor in the production of the inflammatory phase of the disease. A pyogenic component due to staphylococci is undoubtedly important in many instances. A linkage of the seborrheic diseases with blood group B has been recorded. The pH of the skin is high.

Dermatitis Vegetans SYN: pyoderma vegetans

vegetans,

pyostomatitis

Cultures commonly show Staphylococcus aureus. Some authors believe that a viralbacterial symbiosis is the cause of the disease. More than half of the cases have an eosinophilia ranging from lo-20%. A smaller number show mild anemia.

Dermatitis Venenata About one third of the severe cases have leukocytosis between 10,000 and 16,000. An equal number have eosinophilia ranging from 5 to 10%.

20

Cltnlcs in Dermatology

Butterwotth and Cawley

Dermatitis, Whirlpool-Associated Pseudomonas aeruginosa dermatitis has been increasingly recognized among users of contaminated whirlpools.

Dermatofibrosis Lenticularis An increased incidenceof is found in these patients.

diabetes

mellitus

Dermatomyositis SYN: Polymyositis

Increase in muscle enzymes-including creatine phosphokinase, lactic dehydrogenase, aspartate aminotransferase (AST = SGOT), alanine aminotransferase (ALT = SGPT), and aldolase-is the best indicator of disease activity. Cholinesterase may be depressed in dermatomyositis. Serum CU-and y-globulin may be elevated. Results of tests for rheumatoid factor are positive in about lo-20%of cases, and the antinuclear factor is present in about a third of cases. Transferrin values are low, and the ceruloplasmin and haptoglobin levels are high. The blood shows a mild hypochromic anemia and leukocytosis that is sometimes marked. The eosinophil count in the peripheral blood is frequently increased. The erythrocyte sedimentation rate parallels the increase or decrease of the enzyme levels. A significant hypercreatinemia is noted. Albuminuria, hematuria, and creatinuriaare present. There is decreased excretion of creatinine in the urine. In severe cases, myoglobulinemia may occur. A number of case reports have suggested an association between toxoplasmosis and dermatomyositis.

Dermatophilosis Exudates stained with Giemsa stain show Dermatophilus congolensis. The organism may be cultured from lesions.

Dermatosis Acute Febrile Neutrophilic SYN: Sweet’s syndrome

Dermatosis

The significant laboratory abnormalities are neutrophilic leukocytosis and an elevated erythrocyte sedimentation rate. Increased serum proteins with reversal of A/G ratio are less common. Transient proteinuria occurs in a few, with or without hematuria. Marked leukocytosis, thrombocytopenia, or anemia should raise the suspicion of acute myelogenous leukemia, which occurs in nearly 10% of all cases. Benign Chronic Bullous Dermatosis of Childhood IgA anti-basement membrane antibodies are found in indirect immunofluorescence. A high association with HLA-B8 is the significant immunologic finding. Bullous Dermatosis

of Hemodialysis

Some patients present the laboratory ings of porphyria cutanea tarda. Dermatosis, Subcorneal SYN: Sneddon-Wilkinson

find-

Pustular disease

Leukocytosis is present at the time of eruption of pustules. The exudate of the lesions contains neutrophils, a few lymphocytes, and a few epidermal cells from the stratum granulosum. Cultures of the blood and exudate are negative. The erythrocyte sedimentation rate may be increaeed. Electrophoretic studies of sera show a prominence of the IgA fraction. Immunofluorescent studies are consistently negative.

Desert Sore STN: veldt sore Cultures show staphylococci, streptococci, and Cor:yxebacterium diphtheriae.

Diphtheria of the Skin Gram-positive corynebacteria are found in smears taken from the lesion. Definite diagnosis is made by cultural isolation of Corynebacterium diphtheriae. There is often a mixed infection with staphylococcus. The Schick test is a means of distinguishing between susceptible and resistant individuals.

July-September 1986 Volume 4 Number 3

Disease, Chronic Granulomatous SYN: fatal granulomatous chronic dysphagocytosis

disease,

In this X-linked disorder, the total white blood cell and differential cell count may be normal, or there may be a pronounced polymorphonuclear leukocytosis. The polymorphonuclear leukocytes appear normal morphologically but have a functional microbicidal defect. There is a decreased ability to destroy catalase-positive bacteria. The organisms usually associated with this disease are staphylococci and streptococci. All the serum immunoglobulins are markedly elevated. Prenatal diagnosis is possible.

Down’s Syndrome SYN: mongolism, genital drome

acromicria,

trisomy 21 syndrome, Langdon Down’s

consyn-

Regular trisomy 21 is found in 95% of cases, whereas a translocation involving a group D chromosome and chromosome 21 is found in 3-4% of those involved. Mosaic trisomy accounts for about 2% of affected individuals. Down’s syndrome may be readily diagnosed in utero. Amniotic cells are grown in culture and then subjected to chromosome studies. Acute lymphatic and myelogenous leukemias have about a 20-fold greater frequency in individuals with Down’s syndrome. Other forms of bone marrow dysfunction have been reported including polycythemia, leukocytosis, and thrombocytopenia. Diabetes mellitus, hypothyroidism, and hyperuricemia are also observed in trisomy 21.

Dracunculiasis The larvae of Dracunculus medinensis may be seen in the milky exudate that follows spraying of the affected area with cold water.

Drug Eruption, Fixed Following a challenge test with the appropriate drug, the peripheral blood leukocyte

21

Diseases

Cutaneous

count begins to rise within 6 hours. The basophil count declines substantially. The eosinophil count usually declines also, but eosinophilia has been reported. Serum IgG and IgA levels are elevated. IgG and C3 have been observed in the intercellular spaces of the affected epidermis and fibrin deposition noted at the dermoepidermal junction of the fixed drug eruption lesion.

Dysautonomia, Familial SYN: Riley-Day

syndrome

Urinary excretion of homovanillic acid is increased, and excretion of vanillylmandelic acid is decreased. Serum dopamine fi-hydroxylase is decreased. Intradermal injection of histamine phosphate, l:lOOO, is followed by development of a wheal, but the zone of erythema is missing. Instillation of subpharmacologic doses of methacholine in the conjunctival sac results in marked constriction of the pupil. A prolonged hypoglycemic response to insulin is present.

Dyshidrosis SYN: pompholyx The vesicles

and bullae

are sterile.

Dyskeratosis Congenita Many cases are anemic; some have aplastic anemia. There are associated leukopenia and thrombocytopenia. Alkali-resistant hemoglobin is increased. Low serum levels of vitamin BE and folate have been reported.

E Echinococcosis SYN: hydatid

disease

The causative tapeworm is Echinococcus granulosus. The intradermal test is useful but has a high percentage of false-positive results. The most reliable procedures are indirect hemagglutination and latex agglu-

Butterworth and Cawley

22

tination antibody tests. Eosinophilia is found in 20-25% of cases. IgE levels may be elevated.

Echovirus Exanthem Diagnosis is made by the isolation of the virus from the throat, stool, or cerebrospinal fluid and the demonstration of specific neutralizing antibodies in serum drawn during the first 4 days and then lo-14 days later.

Ecthyma p-Hemolytic streptococci initiate the process, but, later in its course. Stayhy(ococ~c.rcs aureus and Pseudomonas arr-uginosu frequently may be recovered from the ulcers. Rarely, the causative organism may be Nrisseria gonorrhoeae. Ecthyma Gangrenosum SYN: dermatitis

TABLE

l-l.

infantum

Subtypes of Ehlers-Danlos Biochemical

Type

I III IV

Gravis Mitis Benign hypermobile Ecchymotic

V

X-linked

VI

Ocular

VII

Arthrochalasis multiplex congenita Periodontitis Lysyloxidase deficiency Dysfibronectinemic

VIII IX X

Eczema, Nummular Hemolytic Staphylococcus ~ic,rmidis may be recovered of the lesions.

~MI‘~JUS or S. rpifrom the surface

Ehlers-Danlos Syndrome SYN: cutis hyperelastica At least 10 subtypes are recognized (Table l-1). and the molecular defect is known in about. half of them. The Ehlers-Danlos syndrome has been complicated by many abnormalities including polgcythemia Vera, sickle cell anemia, and anemia secondary to hematemesis and melena. Plasma thromboplastic component deficiency and defects in platelet functions with impaired clot reaction have been observed. Some types may be diagnosed prenatally.

Elastosis Perforans Serpiginosa

gangrenosa

Anemia and leukocytosis are the rule. Pancytopenia and hypoproteinemia are frequently observed laboratory findings. Tzanck preparation reveals gram-negative rods. Blood cultures are almost universally positive for Psrudomonas aemginosa. Staphylococci and streptococci have also been incriminated. Arromonas hydrophila may be a rare cause in debilitated patients.

II

Clinics in Dermatology

Syndrome Defect

Unknown Unknown Unknown Deficiency of type Ill collagen Lysyloxidase deficiency Lysyl hydroxylase deficiency N-peptidase deficiency Unknown Lysyloxidase deficiency Dysfibronectinemia

There ings.

are no significant

laboratory

find-

Elephantiasis Filariasis or elephantiasis arabicum or tropica is due to Wuchereria bancrofti, Brugia malayi, Onchocerca volw~lus, Dipetalonema perstans, and Loa loa, in various tropical and subtropical countries. Microfilaremia may be diurnal or nocturnal according to species. Complement-fixation and intradermal tests are available. The patients have leukocytosis and eosinophilia as high as 12%. IgG fraction of filarial serum immunoglobulins conjugated to penicillinase has been used to detect, by enzyme-linked immunosorbent assay (ELISA), filarial antigen in circulating immune complexes (CICs) in bancroftian filariasis. Elephantiasis nostras is due to streptococcal or tuberculous infiltration of lymph glands.

Enterobiasis SYK: pinworm Diagnosis

infestation,

oxyuriasis

is made by the finding

of eggs of

July-September 1986 Volume 4 Number 3

Cutaneous Diseases

Entefrobius vermicularis in the perianal region by means of Scotch tape or paraffin swabs. Best results are obtained when the examination is conducted early in the morning. The eosinophil count may be slightly increased but is of no diagnostic significance.

23

have circulating IgG autoantibodies against a basement membrane component of normal skin detected by indirect immunofluorescence.

Junctional Epidermolysis Bullosa SYN:epidermolysis

bullosa

hereditaria

leta-

lis

Epidermodysplasia Verruciformis Electron microscopy reveals the presence of a virus identical to or closely related to that of verruca vulgaris.

Epidermolysis Bullosa Biochemical defects have been recorded for the major types of the disease. Thus, recessive dystrophic epidermolysis bullosa (EB) has been associated with enhanced biosynthesis of skin collagenase. In such patients, both collagenase and neutral protease activities are considerably increased in blister fluid as well as in the skin. Dominant dystrophic EB has been linked with increased glycosaminoglycan synthesis. In some families, patients with EB simplex have shown a deficiency of galactosylhydroxylysyl glucosyltransferase. Many laboratory abnormalities have been reported in epidermolysis bullosa dystrophica. The patients usually have a hypochromic anemia. There may be mild or moderate leukocytosis with eosinophilia. Shortened coagulation times have been reported. Inversion of the A/G ratio is the rule. Serum albumin, prealbumin, and transferrinvalues are low, but the a2- and r-globulin levels are high. Urinary amino acid analysis shows a glytine value markedly higher than normal. Some cases have been described in which there was elevation of the urinary porphyrins. The result of the Rumpel-Leede test has been positive in many patients.

Epidermolysis Bullosa Acquisita Direct immunofluorescence shows IgG and C3 deposits within the basement membrane zone. One quarter to one half of the patients

Patients who survive the neonatal period usually are found to have a moderate to severe refractory anemia, low normal erythrocyte survivals, increased plasma iron clearance, increased plasma iron turnover, and slightly decreased erythrocyte iron utilization.

Erosio Interdigitalis Blastomycetica Candida albicans is found in scrapings and culture. The same yeast may be found in cultures of the stools. One or more gramnegative rods may be recovered with C. albicans. Blood and urine studies should be performed to rule out diabetes mellitus.

Erysipelas fi-Hemolytic streptococci, group A, are the common causative organisms. The classic antistreptolysin 0 (ASO) titer usually reaches high levels (600-800 Todd units) within l-2 weeks of the onset of infection. The white blood cells are increased to 20,000 or more, with the polymorphonuclear leukocytes in the range of 80-95%. The erythrocyte sedimentation rate is increased. Both staphylococci and streptococci are observed in many cases of erysipelas. Lesions resembling erysipelas can be produced by Pseudomonas aeruginosa. Streptococcus pneumoniae has been implicated in erysipelas in children with hypogammaglobulinemia. It is advisable to check these patients for the presence of diabetes mellitus.

Erysipeloid Ergsipelothrix rhusiopathiae may be grown from cultures of tissue specimens. The organism is rarely obtained by swabbing the unbroken skin. Infectious material

24

Butterworth

and Cawley

may also be inoculated into mice from which positive blood cultures are readily obtainable.

Erythema Etythema

Annulare

Centrifugum

This condition may be an “id” eruption. Seek dermatophytes and Candida in scrapings and cultures of cutaneous foci, nails, and stools. Positive skin reactions to Candida extract have been reported. Cases have been found due to the fungus in blue cheese, blood dyscrasias, tuberculosis, and infestation by the nematode Ascaris lumbrz’coides. Erythema

Chronicum

Migrans

The exact cause is not known but the disease usually follows a tick bite involving Ixodes dammini in the northeast and midwest or I. pacificus in the west. Increased serum IgM and cryoglobulins and decreased C3 and C4 have been noted. Some patients have had a positive Weil-Felix reaction indicative of rickettsial infection. Erythema chronicurn migrans may be an early or only sign of Lyme disease. The latter is thought to be a spirochetosis transmitted by the tick Ixodes. The organism has been classified as Borrelia burgdorferi. Indirect immunofluorescence assay may be used to measure antibodies against the spirochete. In patients, the specific IgM antibody titers usually reach a peak between the third and sixth week after the onset of the disease; specific IgG antibody titers increase slowly and are generally highest months later when arthritis is present. Circulating immune complexes are present at the time of the skin lesions. Ery-thema

Elevatum

Clinics I” Dermatology

Diutinum

Increased total serum protein with reversal of the A/G ratio is a common finding. Elevated IgG and IgA occur frequently. Cryoglobulinemiaand paraproteinemia have been recorded. Other laboratory abnormalities have been reported in a few isolated cases. Included in this group are an exaggerated response to

streptokinase-streptodornase, elevated leukocyte alkaline phosphatase, positive hepatitis B surface antigen test result, and aminoaciduria with normal plasma levels. Erythema

Gyratum

Repens

IgG and C3 have been found at the basement membrane zone on direct immunofluorescence of both lesional and nonlesional skin. Erythema

lnduratum

Historically accepted as due to tuberculosis. most cases are probably examples of necrotizing vasculitis, the etiology of which is usually undeterminable. Increased yglobulin has been reported. Hypergic reactions are obtained with tuberculin tests. Erythema

lnfectiosum

SYN: fifth disease The blood picture shows an early leukopenic trend followed by a mild to moderate leukocytosis. A moderate eosinophilia is a common finding. Some authors have recovered enterovirus types from stools, sputum, and throat swabs. Neutralizing and complement-fixing antibodies have been found in the patient’s sera. Others have failed to confirm such findings. Throat cultures have also revealed cY-hemolytic streptococci and Staphylococcus aureus. Erythema

Marginatum

,&Hemolytic streptococcal disease almost always precedes the appearanceof erythema marginatum. Erythema

Multiforme

This disease has many causes, associations, and grades of severity. Laboratory findings are varied and have no consistent pattern. Thus, patients may show eosinophilia, elevated y-globulin, albuminuria, hematuria, elevated blood urea nitrogen, and increased erythrocyte sedimentation rate. C-reactive protein may be positive. Leukocytosis, anemia, and thrombocytopenia haveoccurred in isolated instances.

July-September Volume A Number 3

1986

Cutaneous Diseases

An almost endless host of bacteria, viruses, fungi, and parasites has been found in the lesions, nasopharynx, stools, or genitourinary tract. Elevations in titers of specific antibodies to infectious agents have been documented in many patients. It isof interest to note that 15%of individuals with recurrent erythema multiforme have experienced preceding episodes of herpes simplex infection. In such cases, immunofluorescence microscopy demonstrates the deposition of C3 and fibrin along the dermoepidermal junction and the location of IgM, C3, and fibrin around dermal bloodvessels. Internal malignancies, including lymphoma, and polycythemia have been incriminated. Erythema Nodosum About half of the cases are due to hemolytic streptococcus infection of the upper respiratory tract, and these patients have a markedly elevated serum IgE. The remainder have diverse origins including tuberculosis, sarcoidosis, leprosy, syphilis, lymphogranuloma venereum, cat-scratch fever, coccidioidomycosis, histoplasmosis, blastomycosis, leishmaniasis, psittacosis, and ulcerative colitis; several types of leukemia and fungi; Staphglococc~s aureus, Yersinia bacilli, salmonella, pneumococcus, and meningococcus infections; and drugs. Laboratory studies, therefore, must vary from case to case. Throat cultures, antistreptolysin titers, sputum examinations, smears from nasal septum, serologic tests for syphilis, blood counts, urine and stool examinations, serum protein studies, and sedimentation rates have their indications. The Kveim, tuberculin, histoplasmin, and coccidioidin tests are likewise of great value in making an etiologic diagnosis. Increased a-globulin and complement disturbances have been reported. Ery-themaof the Palms Many of these cases are due to disturbed hepatic function, as in cirrhosis or metastatic carcinoma. Laboratory tests indicated include total serum cholesterol, total serum protein, albumin, globulin, serum bilirubin,

25

ALT, AST, and ALP determinations. gens may be elevated.

Estro-

Erythema Perstans About one third of these patients have elevated erythrocyte sedimentation rates. There is a high incidence of tineal infection in this group. Erythema Toxicum Neonatorum SYN: erythema

neonatorum allergicum

Eosinophilia is constant and proportional to the severity of the disease. The pustules are sterile, but Wright’s stain of their contents shows over 90%eosinophils. Large numbers of eosinophils can also be found in nasal and rectal smears. Erythrasma Scales exhibit a coral red fluorescence. Gram-stained preparations show rod-like organisms, filaments, and coccoid forms. Corynebacterium minutissimum may be isolated on appropriate cultural media. Among obese patients with extensive erythrasma, almost half have diabetes. Erythroderma, Congenital lchthyosiform SYN: lamellar ichthyosis Candida albicans may be found as a sec-

ondary invader. Erythrokeratoderma Variabilis Laboratory normal.

findings have been essentially

Erythromelalgia There are no distinctive laboratory findings in this disease. The patient should be checked for diabetes, nephritis, polycythemia, thrombocythemia, gout, and heavy metal poisoning, which may accompany this condition.

26

Butterworth

and Cawley

Clinics in Dermatology

PLATE 1. Erythemas

FIG. 1. (above, left) In erythema multiforme, vivid, more or less purpuric lesions appear suddenly, often in a symmetricdistribution. The clinical picture of varying types of lesions does not reflect cause. Laboratory findings are equally variable. FIG. 2. (above, right) Toxic epidermal necrolysis (Lyell’s or scalded skin syndrome) is often drug-induced. Leukocytosis and hypocalcemia are usual findings. FIG. 3. (left) Erythema gyratum repens, an almost artistic eruption, is often associated with internal malignancies. Direct immunofluorescence shows IgG and C3 at the basement membrane zone. FIG. 4. (below) Two examples of erythema annularecentrifugum show typical specific annular lesions with central clearing. These are accompanied by variable pruritus and may be “id” eruptions.

July-September 1986 Volume 4 Number 3

Cutaneous

Diseases

PLATE 2. Immunologic

27

Disorders

FIG. 1. Reiter’sdisease, a triad of nongonococcal urethritis (left), conjunctivitis (above), and arthritis, is seen primarily in men and may be considered a sexually transmitted disease. Chlamydia trachomatis is thought to be a major cause; antichlamydia complement-fixation antibodies are found in sera.

FIG. 2. In Behcet’s syndrome, which most often affects young men, there are severe uveitis, retinal vasculitis, and optic atrophy. Aphtha-like lesions of mouth and genitalia suggest diffuse vasculitis. Dysproteinemia is the outstanding finding

FIG. 3. In AIDS patients, complicating diseases include recurrent herpes simplex (left) and Kaposi’s sarcoma (below). Patients with confirmed or suspected AIDS characteristically have elevated levels of /3*-microglobulin.

Clinics

28

In Dermotoionv

Butterworth and Cawlev

F Familial Mediterranean Fever SYN: familial recurrent polyserositis, familial paroxysmal polyserositis, periodic disease, benign paroxysmal peritonitis Many patients show a moderate anemia with spherocytosis. The erythrocyte sedimentation rate is increased. During attacks, the white blood cells increase to lO,OOO-20,000, with neutrophilia and a drop in the eosinophi1 count. Benhamou’s triad includes increased serum fibrinogen, elevated titer of antistreptolysin 0, and haptoglobinemia. Serum bilirubin may be increased, often to the point of icterus. Positive results of indirect Coombs’ tests and Rumpel-Leede phenomena have been reported. A positive result of the Harrison spot test for bilirubinuria is found in the majority of attacks. Urinary urobilinogen is increased. Amyloidosis may accompany this disorder. Renal involvement is indicated by proteinuria, uremia, and elevation of serum cholesterol.

Fanconi’s Anemia SYN: congenital

familial

pancytopenia

The blood picture is characterized by leukopenia with granulocytopenia, macrocytic anemia, and thrombocytopenia. Occasional immature forms of red or white blood cells may be noted in blood smears, and reticulocytes have sometimes been increased. Osmotic and mechanical fragility are slightly and greatly increased, respectively. Alkaliresistant hemoglobin is elevated. Hematologic defects, such as mild neutropenia or pancytopenia, may be found in an otherwise normal parent or sibling. Bone marrow shows simultaneous disturbance of delayed maturation and hyperplasia of red-cell precursors, with megaloblastic changes in some cells, reduced myelopoiesis, and severe diminution of megakaryocytes. The number of chromosomes is normal, but a large percentage of cases exhibit an

increased frequency of chromatid breaks, endoreduplications. and chromatid changes. Affected individuals and relatives have a higher susceptibility to leukemia.

Fasciitis Fasciitis, Eosinophilic SYN: Shulman’s

syndrome

Eosinophilia, hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate are the consistent findings. Peripheral eosinophiliaof up to 50% is found in almost all patients. The total white blood cell count may be normal or elevated. About three quarters have hypergammaglobulinemia predominantly due to IgG, but sometimes due to IgM or to both. A somewhat smaller number has an elevated erythrocyte sedimentation rate. in the range of 40-60 mm/h. Other hematologic changes have included megakaryocyte aplasia, aplastic anemia, and thrombocytopenia. About one third of the patients have had rheumatoid factor. Antinuclear antibodies are found in about 20%, and these are low titers and homogeneous patterns as opposed to high-titer speckled antinuclear antibodies in scleroderma. About half of the patients have elevated levels of circulating immune complexes. Increased serum eosinophil chemotactic activity is usually found in all the patients early in the illness and shows progressive reduction later. An elevated serum creatinine phosphokinase has been reported. Fasciitis. Necrotizing SYN: hemolytic

streptococcal

gangrene

Some authors have described two forms of the disease: one caused by p-hemolytic streptococcus, and the other due to a synergistic infection of facultative (non-Group A streptococci or Enterobacteriaceae) and anaerobic bacteria. Evidence of streptococcal infection may be ascertained by finding high levels of serum antideoxyribonuclease B and antihyaluronidase. Measurement of antistreptolysin 0 (ASO) titer is less helpful. Recent reports have also implicated coagulase-posi-

July-September 1986 Volume 4 Number 3

Cutaneous

tive hemolytic staphylococci, Pseudomonas aeruginosa and Bacterioides sp. Bacteremia is usual and fatal septicemia sometimes results. Polymorphonuclear leukocytosis and elevated erythrocyte sedimentation rate are the rule. Patients often have anemia, thrombocytopenia, and hypocalcemia. IgA is slightly increased. Elevated serum complement levels have been reported. Feltyk Syndrome The characteristic hematologic finding is a severe and persistent neutropenia with cell counts less than lOOO/pL. In general, the total white blood cell count is also reduced, although sometimes to a lesser degree than the neutrophils. A mild to moderate normocytic and normochromic anemia is usual but not invariable. The platelet count is normal or there may be mild thrombocytopenia. There is increased cellularity of the bone marrow due primarily to granulocytic hyperplasia. As a rule, the erythrocyte sedimentation rate is increased. Additional studies show positive tests for rheumatoid factor, antinuclear antibodies, and increased concentration of all three major classes of immunoglobulins. Fibrosis, Submucous Investigations usually show neutropenia with a relative eosinophilia, microcytic anemia, raised erythrocyte sedimentation rate, and an increase in r-globulins. Fish Odor Syndrome SYN:trimethylaminuria Gas chromatographic examination of the urine reveals an excessive amount of trimethylamine. Folliculitis Coagulase-positive staphylococci are found most often in superficial folliculitis. Less commonly, cases have been due to Pseudomonas aeruginosa,

Candida, Propionibacte-

Diseases

29

rium acnes, and Malassezia furfur. Folliculitis following the use of whirlpool baths is usually due to Pseudomonas aeruginosa. Folliculitis Decalvans Coagulase-positive staphylococci are recovered in cultures. Folliculitis, Eosinophilic Pustular SYN:Ofuji’s disease The follicular papules and pustules contain numerous eosinophils. Leukocytosis with eosinophilia and high levels of IgG, IgA, and IgE in the blood are constant features. High circulating titers of IgG and IgM directed to basal cell cytoplasm have been reported. Folliculitis Keloidalis SYN: dermatitis keloidalis

papillaris

capillitii,

acne

Although staphylococci are found most frequently in cultures, a host of other organisms has been isolated. Foot Rot SYN:swamp rot Pseudomonas

cepacia

may be cultured

from the webs of the toes. Fucosidosis The marked deficiency or absence of a-~fucosidase may be demonstrated by assay of serum, leukocytes, urine, or cultured skin fibroblasts and, possibly, prenatally by assay of amniotic fluid cells. Carriers have abnormally low a-L-fucosidase activity in cells and serum. Furunculosis and Carbuncles Staphylococcus aureus is usually the offending organism. Antibiotic sensitivity tests are helpful in management of the disease. In chronic recurrent cases, a search should be made for evidence of diabetes mellitus, renal or hepatic disease, hypogammaglobulinemia, and blood dyscrasias including anemia. Cul-

Cllnlcs

30

in Dermatology

Butterworth and Cawley

ture of the nostrils state.

may reveal a nasal carrier

Gardner’s Syndrome The results of laboratory tially normal.

studies are essen-

Gaucher’s Disease

G Gangrene Gangrene,

Fournier’s, of the Scrotum

Bacteria such as Proteus, PselLdovlonoS, Escherichia coli, Staphylococcus aureus, and anaerobic streptococci have been cultured from the lesions, which may be produced by several organisms working synergistically. Gangrene, Gas SYN: clostridial

myonecrosis

Anaerobic gram-positive bacilli of the genus Clostridiwn are responsible for this condition. C. perfringens is found in more than half of the cases. Less often encountered are C. noryi, C. septicurn, C. histolyticum, C. hifermentans, and C. fallax. Several species occur in the majority of wounds. Stained smears of the infected tissues reveal many large gram-positive bacterial rods and small numbers of degenerated leukocytes. Cultures yield clostridia, and blood cultures may also be positive. Leukocytosis, with high polymorphonuclear cell count, is usually present. There may be a drop in the hemoglobin level within a few days of onset. The anaerobic streptococcus (peptostreptococcus) and, occasionally, a variety of bacteria other than clostridia cause myositis or myonecrosis, which usually acts like subacute gas gangrene. Gangrene, Meleney’s Postoperative Progressive Microaerophilic streptococci (peptostreptococcus) are found in the spreading periphery of the lesion. Staphylococcus aureus or Enterobacteriaceae is cultured from the gangrenous margin.

Diagnosis is usually made by finding Gaucher’s cells in smears of the bone marrow. Similar cells may often be found in normal relatives of patients with overt Gaucher’s disease. Elevation of serum acid phosphatase is almost invariably associated with this disorder. The blood lipids are normal. Anemia and thrombocytopenic purpura are not characteristic of the infantile form of Gaucher’s disease. In adults, there is frequently pancytopenia; anemia, leukopenia, and thrombocytopenia may be found in various combinations. The anemia is usually hypochromic and microcytic, but, occasionally, it is macrocytic. There is decreased activity of the enzyme glucocerebrosidase, which catalyzes the cleavage of glucose from glucocerebroside, a substance that accumulates in various tissues in these patients. Cultures of white blood cells and skin fibroblasts demonstrate deficient activity of glucocerebrosidase. These cultures are also deficient in p-glucosidase, which, in practice, is more rapidly assayed than glucocerebrosidase; this is used in the diagnosis of the abnormality. Prenatal diagnosis is possible by measuring glucocerebrosidase or p-glucosidase in cultured amniotic fluid cells.

Gingivostomatitis, Primary Herpetic The clinical manifestations are due to herpes simplex virus, type 1. Diagnosis is confirmed by the presence of characteristic multinucleated cells on exfoliative cytologic examination. A fluorescent stain is also available. Isolation of the virus provides a positive method of identification. A rise in complement fixing or neutralizing antibody in acute and convalescent sera provides conclusive evidence of a primary herpes simplex virus infection. Restriction enzyme analysis is ex-

July-September 1986 Volume 4 Number 3

Cutaneous

tremelyvaluable

in investigating herpes simplex virus isolates. Glanders SYN: equinia Pseudomonas mallei is recovered from the nasal discharge, pus of skin ulcers, and the blood. Isolation by animal inoculation is possible. Serologic test results show a rapidly rising agglutination titer. Complement fixation is less sensitive but more specific, and its result becomes positive in 3 weeks. The white blood cell count may be normal or even depressed.

Glomus Tumors Routine laboratory examinations are usually within normal limits. Cases with large numbers of tumors may be accompanied by thrombocytopenia. Glossitis, Atrophic SYN:Hunter’s glossitis In diffuse or patchy atrophy of the tongue, blood studies are indicated for the detection of pernicious anemia, sickle cell anemia, thalassemia, and sprue. Achlorhydria is found in some patients. Syphilis must also be eliminated as a possible cause. Glossitis, Median Rhomboid Some authors believe this is a manifestation of candidiasis and not a developmental anomaly. Glossopyrosis SYN:burning tongue A blood count is indicated to determine the presence of primary anemia. Glucagonoma Syndrome The laboratory studies feature hyperglucagonemia, diabetes or abnormal glucose tolerance test, normochromic normocytic anemia, elevated erythrocyte sedimentation rate,

31

Diseases

and, perhaps also, hypocholesterolemia. Low levels of amino acids have been reported. Gonococcal Infections In men, a Gram-stained smear of urethral discharge with the finding of the gramnegative intracellular diplococcus, Neisseria gonorrhoeae, is adequate for diagnosis. In women, smears of the endocervix and rectal area are of little value, and culture material must be taken. In gonococcemia, cultures are taken on Thayer-Martin or Transgrow media from endocervix, male urethra, prostatic fluid, rectum, oropharynx, blood, and skin lesions. Direct and indirect fluorescent tests may be used for the identification of gonococci in special cases. Gonozyme (Abbott, North Chicago, IL) enzyme immunoassay is highly sensitive and specific. Results can be available within 3 hours. Gout This is a disturbance of purine metabolism manifested by excessive uric acid in the blood. In the acute phases, leukocytosis is usually present, but the differential count is frequently normal. At this time, the erythrocyte sedimentation rate is always elevated. C-reactive protein is strongly positive during the acute attack. Microcrystals of uric acid may be demonstrated in synovial fluid in acute gouty arthritis, the majority of crystals lying within leukocytes. Crystals may be seen by ordinary light microscopy, but they are more readily detected when polarized light microscopy is employed. Primary gout is a specific hereditary metabolic or renal defect. Asymptomatic hyperuricemia is quite common among relatives of this group of patients. Secondary gout occurs in glycogen storage disease, polycythemia Vera, chronic leukemia, psoriasis, chronic hemolytic anemias, and certain other hematologic conditions. Tests to determine the type of gout include a 24-hour urine collection for uric acid after the patient has been on a low-purine diet for ‘72hours, evaluation of

Cllnlcs 32

Butterworth

glomerular filtration rate by creatinine or urea clearance, and adequate hematologic studies.

Graft-versus-Host Disease (GVHD) Immunofluorescence microscopy shows deposition of IgM and C3 at the dermoepiderma1 junction and around blood vessels in a high percentage of patients.

Granuloma Granuloma

Annulare

A number of inconstant laboratory findings have been recorded including serum antithyroid antibodies, defective neutrophilic migration, and elevated levels of heparinprecipitable fraction of plasma. HLA-Bw35 occurs in 95% of patients with the generalized form, but there is no increase in patients with the localized type of granuloma annulare. About one third of the patients have abnormal responses to the prednisone glycosuria tests. Granuloma

Faciale

Moderate eosinophilia has been reported in a few instances, and its presence may depend on the stage of the process at the time of examination. Immunofluorescent studies reveal consistent deposits of IgG, fibrin, and complement along the basement membrane and fibrin in the vascular walls. IgA and IgM deposits at the dermal-epidermal junction are less common. Granuloma

I” Dermatology

and Cawley

lnguinale

The causative organism is a gram-negative coccobacillus, Calymmatobacterium (Donomania) granulomatis. Wright’s_ or Giemsastained scrapings from the periphery of skin lesions or smears of granulation tissue obtained by punch biopsy show Donovan bodies in the cytoplasm of large mononuclear cells. At times, smaller numbers of the organism are extracellular. The bacterium can be demonstrated by electron microscopy. The result of the granuloma inguinale complement-fixation test is negative early in the disease but becomes positive later. Poly-

morphonuclear leukocytosis occurs in some patients, and anemia may become pronounced in generalized cases. “Pseudogranuloma inguinale,” a variety of chancroid clinically resembling granuloma inguinale, is caused by HewophGus ducreyi. Granuloma,

Swimming

Pool

Mycobucterium marinum (balnei) may be cultured from biopsy specimens and from the water in the pool or fish tank in most instances. Intradermal tests with tuberculin or l:l.OOO M. ma&urn are usually positive. Granuloma

Trichophyticum

Practically all cases are due to Trichophytorr rubwm. An occasional infection may be due to Microspo,rongypseum, M. audouini, Trichophyton mentagrophytes, or T. viola(‘Purri.

Granulomatous Vasculitides Included in this category are allergic, lethal midline, lymphomatoid, and Wegener’s granulomatoses, and malignant atrophic papulosis. Periarteritis nodosa and dermatitis nodularis necrotica share some features with these disorders. The erythrocyte sedimentation rate is invariably elevated and, in general, reflects disease activity. There is a microcytic hypochromic anemia in the late stages of the disease. The total white blood cell count rarely goes above 15,000, and eosinophilia is found in about half the cases, usually in those patients with an associated asthma. There is a tendency toward thrombocytosis. A constant finding is the reversal of the albumin-globulin ratio with a considerable rise in the r-globulins, particularly IgA. Some authors have reported elevated serum IgE, but this has not been confirmed by others. Cryoglobulinemia has been found in periarteritis nodosa. Albuminuria and hematuria are indicative of renal involvement. Melena has been noted.

Green Monkey Disease Laboratory

findings

show extremely

high

July-September Volume 4 Number 3

1986

33

Cutaneous Diseases

serum aspartate aminotransferase (AST = SGOT) values, thrombocytopenia, and oliguric renal failure. A rod-shaped virus suggestive of an arbovirus has been isolated. It produces neutralizing and complement-fixing antibodies during the course of the disease.

H Haber’s Syndrome The erythrocyte sedimentation rate may be slightly elevated, but otherwise laboratory findings are within normal limits. Half-and-Half Nail Syndrome The patients azotemia.

have kidney disease, often

Hand, Foot, and Mouth Disease In many cases, coxsackievirus Al6 may be isolated from throat or rectal swabs, feces, or vesicle fluid. Echovirus 9 and coxsackieviruses A5 and B5 have been found in a few sporadic cases. Acute and convalescent sera of patients can demonstrate a rising antibody titer. Hanot-Chauffard Syndrome Diabetes mellitus is present, and there is laboratory evidence for cirrhosis of the liver. Hartnup Disease There is a constant aminoaciduria involving the monamino-monocarboxylic aminoacids. It is accompanied by an abnormally large urinary output of idole-3-acetic acid and, less commonly, of indican. The feces often contain an excess of protoporphyrin, tryptophan, leucine, isoleucine, valine, and phenylalanine. Hemangioma-Thrombocytopenia Syndrome SYN: Kasabach-Merritt

syndrome

The platelet count may be as low as 10,000 or 12,000. The bone marrow shows an in-

crease in megakaryocytes, but there is little evidence of platelet formation. There are hypoprothrombinemia, defective clot retraction, increased bleeding and coagulation time, and anemia. Coagulation factors I (fibrinogen), II (prothrombin), V, and VIII are reduced. Platelet and fibrinogen survival times are shortened. The blood smear shows nucleated red cells, anisocytosis, and microcytosis. Serum bilirubin may be elevated. Hemochromatosis SYN:bronzed diabetes Of the many procedures employed to substantiate the diagnosis of iron-storage disease, the only definite test is liver biopsy. Presumptive tests include elevation of the plasma iron with saturation of the ironbinding protein, transferrin; excessive deposits of hemosiderin in the bone marrow, skin, gastric mucosa, prostatic secretion, and urinary sediment; increased liver density by x-ray; and failure to develop iron deficiency anemia despite repeated phlebotomies. Radioiron studies show prolonged plasma iron clearance. Serum ferritin is increased in more than 70% of patients. Other reported laboratory test results of interest include a decrease in transferrin concentration in the serum, absence in the gastric juice of the iron-binding protein gastroferrin, and abnormally low xanthine oxidase activity in the liver. Deferoxamine injections have been used to measure 24-hour urinary iron excretion and to assess the high values of total chelatable iron stores found in untreated patients. When xanthomatosis occurs, the total fatty acids are high due to elevated total cholesterol and phospholipids. Neutral fat remains low. Serum bilirubin is high, and hyperglycemia and glycosuria may occur. Diabetes mellitus occurs in about 80% of those with hemochromatosis. Porphyria cutanea tarda occurs infrequently, while hypoprothrombinemia is a rare finding. The hemochromatosis gene is inherited along with HLA determinants A3 and B14. The functional impairment of the involved

Clfnlcs In Dermatology

Butterworth and Cawley

34

organs may be judged by a glucose tolerance test, liver function tests, urinary l’i-ketosteroid determination, and an ACTH stimulation test.

Hepatitis Hepatitis 6 Virus Syndromes Serum sickness-like prodrome (SSLP). The patients manifest mild proteinuria and hematuria often associated with hypocomplementemia. Onset is usually l-6 weeks prior to the beginning of jaundice. Hepatitis B surface antigen (HBsAg) (Australian antigen) appears first, and the antibody to it (anti-HBs) develops as the antigen decreases. Patients often develop cryoprecipitates of the mixed type. The electron microscope demonstrates hepatitis B virus in the serum and cryoprecipitates. Periarteritis nodosa (PAN) (see also p. 60). Eosinophilia, hematuria, and azotemia are common. One third or more of the cases are associated with HBsAg positivity. The mild liver involvement is manifested only by an elevation of serum enzymes. HBV particles may be demonstrated in the serum by electron microscopy. Essential mixed cryoglobulinemia (EMC) (see also Cold Sensitivity, p. 14). Cryoglobulins show a mixed pattern, with IgG and IgM in near-equal amounts. The antigammaglobulin is most commonly the IgM fraction. Both the IgG and IgM fraction may exhibit anti-HBs activity. The serum complement is frequently depressed at times of active disease. HBV particles may be found on electron microscopy. Papular acrodermatitis of childhood (PAC) (see also p. 2). HBsAg, as well as HBV particles, is always found in the serum by electron microscopy. Subtyping of HBV has consistently revealed the ayw determinant, although two cases with subtype adr have been reported from Korea. Anti-HBs is not detected in the dermatitis phase but has its peak incidence 6-12 months later.

Hepatitis, Cholestatic When due to drugs, the process is characterized by peripheral eosinophilia and by increased transferases, serum bilirubin levels. and alkaline phosphatases.

Hermansky-Pudlak Syndrome There is prolongation of the bleeding time. The platelets show reduced dense bodies and deficient aggregation.

Herpangina A number of serologic types of coxsackievirus, groups A and B, and echovirus are associated with herpangina. The virus may be grown in cultures of the throat tissue or stool. Intraperitoneal or intracerebral inoculation of l-day-old suckling mice produces a characteristic myositis. Diagnosis is made by the demonstration of a relative increasing titer of homologous neutralizing antibody, complement fixation test with suckling mouse virus, or hemagglutination inhibition tests. The total white cell count varies from about 4,000 to 16,000, with more than half in the normal range. In most of the cases showing leukocytosis, there are approximately equal numbers of polymorphonuclear and lymphocytic cells.

Herpes Herpes Gestationis The linear deposition of C3, with or without IgG, along the basement membrane zone is characteristic of herpes gestationis, as is the presence in serum of the herpes gestationis (HG) factor and IgG antibody that fixes C3 along the basement membrane zone of normal human skin or esophagus in vitro. Also identified at times in the basement membrane zone have been IgM, IgA, C4, C5, Cl, and properdin. There may be mild to moderate leukocytosis. Although not constant, eosinophils may constitute as much as 50% of the white blood cell count. Numerous eosinophils are also

July-September 1986 Volume 4 Number 3

Cutaneous

found in the vesicular fluid. Albumin and red blood cells are common urinary findings. The albumin in the serum may be normal or slightly lowered. Blood levels of chorionic gonadotropin are increased in many patients. There is some evidence that herpes gestationis is related to Rh isosensitization in certain cases. Among these patients, 43-50% have the antigen combination HLA-DR3 and -DR4. Husbands of women with HG have an increase in the incidence of HLA-DR2.

Herpes Simplex In general, herpes simplex virus type 1 causes facial lesions; type 2, genital lesions. There are many exceptions. Cytologic tests include the Tzanck and Papanicolaou smears. Both preparations demonstrate the characteristic multinucleated giant cells in scrapings prepared with Giemsa or Wright’s stain; but, in addition, the Papanicolaou smear shows intranuclear inclusions. Cytology differentiates neither initial from recurrent infection nor between type 1 and type 2 infections. In addition, similar changes can be seen in varicella-zoster infections. Other new methods for detecting herpes simplex virus are electron microscopy and fluorescent antibody studies of infected squamous epithelial cells. Even more sensitive than the latter is the immunoperoxidase method, which does not require a fluorescent microscope for performance of the test. Electron microscopy does not distinguish herpes simplex from varicella-zoster, and none of the three tests distinguishes type 1 from type 2 herpes simplex virus. The most definite diagnostic method is virus isolation. Although this can be performed in eggs or mice, cell culture methods are more widely used today. The virus is usually cultured on HEp-2 cells but also grows well on rabbit kidney and human amnion cell cultures. Serologic tests are more significant in primary infections. Seroconversion from negative to positive with a fourfold increase in antibody titer between acute and convales-

Diseases

35

cent sera is indicative of an initial herpes simplex virus infection. Serologic tests can be performed on blood or cerebrospinal fluid and include complement fixation assay, radioimmunoassay, and enzyme-linked immunosorbent assay (ELISA) as well as the older serologic techniques such as precipitation, hemagglutination, and neutralization assays. The frequency of HLA-Al is consistently increased. In primary herpes simplex virus infections, there may be leukocytosis above 12,000, with 75-80% polymorphonuclear leukocytes. In recurrent cases, the white blood cell count is normal or decreased with an increase in lymphocytes and monocytic cells. IgA has been reported low in recurrent herpes simplex.

Herpes Zoster SYN: shingles Herpes zoster is caused by the same virus that produces varicella. Smears from the floors of bullae, prepared with Wright’s stain, demonstrate multinucleated giant cells. In contrast to herpes simplex, there is no growth of the virus on chick embryo or in laboratory animals. Thevirus, however, may be cultivated in the early days of the rash in primary cultures of human amnion cells. Demonstration of IgG, IgA, and IgM antibodies in serum may be made by complement fixing, agglutination, neutralizing, fluorescent antibody to membrane antigen (FAMA), immune adherence hemagglutination techniques, the ELISA test, and radioimmunoassay procedures. Circulating antigen-antibody complexes may occur. Leukopenia, high hemoglobin levels, and elevation of the erythrocyte sedimentation rate are sometimes found. There may be pleocytosis varying from 10 to 300 cells in the spinal fluid. Herpes zoster may be associated with lymphomas, chronic leukemia, myeloma, tabes dorsalis, tumors of the cerebrospinal system, and other conditions for the diagnosis of which appropriate laboratory studies are indicated.

36

Butterworth

Cilnlcs in Dermatology

and Cawley

Hidradenitis Suppurativa Cultures show a variety of bacteria, especially Staphylococcus aureus, but also other staphylococci, streptococci, and Escherichia cobi. Proteus and pseudomonas organisms are inevitably encountered in the chronic cases. Some cases may show anemia. An increased erythrocyte sedimentation rate, elevated serum y-globulin, or reversal of the albumin-globulin ratio may be seen.

Hirsutism Most patients show no endocrine abnormalities. Initial studies should include plasma levels of free and total testosterone and dehydroepiandrosterone. Urinary excretion of testosterone and 1’7-ketosteroids is elevated in some patients,

Histidinemia There is a deficiency of histidine deaminase (histidase), which can be demonstrated in the stratum corneum. Epidermal and sweat urocanic acid levels are reduced. A positive ferric chloride test result in the urine, in the absence of elevated blood phenylalanine, suggests the diagnosis.

Sinus Histiocytosis with Massive Lymphadenopathy There are usually leukocytosis with neutrophilia, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia.

Histiocytosis X SYN: reticuloendotheliosis

Included in this category as varying manifestations of the same basic process are Letterer-Siwedisease, Hand-Schiiller-Christian disease, and eosinophilic granuloma of the bone. Hematologic findings are normal in about half of the cases. Approximately one quarter of the patients have anemia of the nonregenerative type. Some of these present with leu-

kopenia and thrombocytopenia. About another 25% show mild leukocytosis, often with eosinophilia in the range of 513%. Blood chemical examination results are within normal limits. If liver involvement is extensive, bilirubin may be elevated. When diabetes insipidus is present. the urine is pale and of low specific gravity. Alkaline phosphatase activity is often increased in patients with diffuse skeletal involvement. Cytology shows abnormal reactive histiocytes on direct scrapings from an active oozing hemorrhagic skin lesion in LettererSiwe disease.

Histoplasmosis Stained smears (Wright’s or Giemsa) of blood, sputum, bone marrow, urine, skin scrapings, or exudates from ulcers reveal Histoplasma capsulatumas small oval yeastlike bodies within large mononuclear cells. In African histoplasmosis, due to H. capsulaturn var. duboisii, the ovoid bodies are large. The mycelial phase may be demonstrated by cultures on Sabouraud’s dextrose agar, Micosel (BBL Microbiology Systems, Cockeysville, MD) media, or brain-heart infusion agar. Histoplasma capsulatum and H. capsulatum var. duboisii have similar characteristics, and the latter is considered a variant of the former. A skin test is available, but it is more useful epidemiologically than in an individual patient. Complement fixation, the most sensitive test, iscomplex and time consuming. It is best to screen sera by using latex agglutination and immunodiffusion. Complement fixation is useful to follow antibody titers in the course of the disease. Clinical and cultured material can be positively identified with a specific fluorescent stain. Anemia, leukopenia, and thrombopenia are almost always present. The differential count is usually normal, but a marked neutropenia with relative or absolute lymphocytosis is sometimes seen.

Hodgkin’s Disease The hematologic picture is extremely able in this disease. Thus, the white

variblood

July-September 1986 Volume 4 Number 3

Cutaneous Diseases

cells may be elevated, normal, or decreased. One may find all or any combination of neutrophilia, lymphocytopenia, monocytosis, and eosinophilia. The platelet count may likewise be increased, normal, or decreased. A mild to severe normocytic anemia is seen in about 50% of cases. Decreased leukocyte chemotaxis has been reported. The bone marrow shows a shift to the left of the granulocytes, slight monocytosis, and eosinophilia. Diagnosis is made by finding Reed-Sternberg cells in the lymph nodes and bone marrow. Abnormalities vary according to the stage and distribution of the disease. Elevated plasma levels of hydroxyproline-containing protein are found. Cryoglobulinemia may also occur. There is slight deviation of the plasma proteins from normal in the latent stages of Hodgkin’s disease. The course of such patients may be prolonged. az-Globulin above 13% usually indicates a more or less generalized involvement with an unfavorable prognosis. When az-globulin is only slightly increased and y-globulin is over 25%, the disease has an intermediate course. It has long been recognized that anergy to intradermal skin test antigens may be an early finding in Hodgkin’s disease. Homocystinuria The metabolic fault is a deficiency of cystathionine synthase, as a result of which homocystine and methionine accumulate in the blood and cerebrospinal fluid. Reduced activity of this enzyme has been found in livers of parents of homocystinuria patients and in amniotic fluid cells. A positive result of the cyanide-nitroprusside test suggests the presence of homocystine in the urine. Chromatography is necessary for its final identification. Anemia occurs, folic acid levels tend to be decreased, and abnormal stickiness of the platelets has been described. Hookworm SYN:ground itch The ova of Ancylostoma duodenale or Neca-

37

tor americanus are found in the stool. Rarely, Ancylostoma braziliense or A. malaynum has

been involved. An iron deficiency anemia results from the continuous intestinal blood loss. The white blood cell count usually remains normal, but the eosinophils are increased up to about 15%. Hutchinson’s Triad Investigate for congenital syphilis. Hypereosinophilic Syndrome All laboratory findings are usually within normal limits except for an elevated eosinophilic count and serum IgE. Hyperimmunoglobulin E Syndrome SYN:hyper IgE-staphylococcal abscess syndrome, Buckley’s syndrome (see also Job’s Syndrome) Staphylococcus aureus is the usual cause of the recurrent skin infections, but streptococci, Pseudomonas aeruginosa, and Candida albicans have been found. There are extreme elevations of serum IgE and antistaphylococcal IgE antibody. Defective neutrophil chemotaxis and peripheral blood eosinophilia are usual.

Hypervitaminosis A Hypochromic anemia, depressed serum proteins, and elevated alkaline phosphatase may be present. Hypodermomycosis Pigmented fungus elements including hyphae are constantly present in the exudate and wall of the abscess. The species usually cultured from the lesions is Exophiliajeanselmei (formerly classified as Sporotrichum gougerotii) and, rarely, Phialophora richardsiae.

Hypoplasia, Focal Dermal There are no consistent laboratory findings, although increased alkaline phospha-

38

Clinics in Dermotoloav

Butterworth and Cawlev

tase, aminoaciduria, and low serum phorus have been reported.

phos-

I

Hypogammaglobulinemia, Congenital

lchthyosis lchthyosis Linearis Circumflexa This disease is probably a variety of congenital ichthyosiform erythroderma. Subnormal fasting serum vitamin A levels have been recorded.

lchthyosis Vulgaris SYN: ichthyosis

Impetigo laboratory

find-

These patients have a deficiency of the microsomal enzymes, arylsulfatase C and steroid sulfatase, in cultured fibroblasts and epidermal cells. Cholesterol sulfate concentration in plasma and stratum corneum is increased appreciably. The increased electrophoretic mobility of p-lipoprotein and preP-lipoprotein is a simple screening test to detect X-linked ichthyosis.

lmmunoglobulin Deficiency Agammaglobulinemia, Lymphopenic SYN: Swiss-type

agammaglobulinemia, aplasia

Impetigo of Bockhart SyN: superficial

Ichthyosis, X-linked

hered-

The infants are deficient in all immunoglobulin classes and have a marked lymphopeniaassociated withan inabilitytodevelop delayed hypersensitivity reactions. They are susceptible to yeast, bacterial, and viral infections.

Agammaglobulinema, X-linked SYN: Bruton’s

Both sexes are involved. There is a deficiency of the three major classes of immunoglobulins although their serum levels range higher than in the X-linked group. Circulating antibodies are absent, but delayed hypersensitivity is intact.

simplex

There are no distinctive ings in this disorder.

itary thymic

of T cells is either normal or elevated. Circulating B cells are absent. Isohemagglutinins and Clq are decreased. The patients are prone to bacterial infections such as pneumococcal, streptococcal, meningococcal, and echoviral.

agammaglobulinemia

The serum shows less than 1 mg/ml of IgG and marked depression of IgA and IgM. Delayed hypersensitivity is normal. Lymphopenia is uncommon, and the percentage

pustular

perifolliculitis

Staphylococcus aureus covered from the lesions.

can usually

be re-

Impetigo Contagiosa Staphylococcus aureus is the organism found most frequently. p-Hemolytic streptococcus occurs less often. Both organisms are sometimes present. Albuminuria may indicate involvement of the kidneys.

Impetigo Herpetiformis Leukocytosis and a high erythrocyte sedimentation rate are expected during exacerbations. Blood cultures and pus from the lesions are sterile except when there is secondary infection. Some cases have been associated with hypocalcemia and hyperphosphatasia as manifestations of hypoparathyroidism.

Impetigo Neonatorum SYN: pemphigus

neonatorum

This bullous form of impetigo is caused by coagulase-positive staphylococci.

lncontinentia Pigmenti SYN: Bloch-Sulzberger

Leukocytosis

as high

disease as 43,000

cells

is

July-September 1986 Volume 4 Number 3

present early in life in many patients. Blood eosinophilia may reach 50%, while smears from vesicular lesions may show up to 90% eosinophils. Thrombocytosis may occur. A few patients have shown immunologic deficiency manifested by defective neutrophil chemotaxis and lymphocytic dysfunction.

lnfundibulofolliculitis, Disseminated and Recurrent All of a group of four cases had elevated serum IgG; two had elevated IgE levels also.

lntertrigo Species of streptococci, staphylococci, and pseudomonas as well as Candida albicans are found singly or in combination. Diabetes and anemia are frequent predisposing factors.

Intestinal Bypass Syndrome SYN:

39

Cutaneous Diseases

bowel bypass

syndrome

Complete blood counts show no distinct pattern, but the erythrocyte sedimentation rate is elevated. Serum cholesterol and creatinine levels are depressed. Serum potassium may be normal or decreased in amount. Circulating immune complexes are almost a universal finding. Most of them are cryoproteins consisting of several types of immunoglobulins and complement. Some patients have Escherichia coli antigens and antibodies in their cryoprotein. Rheumatoid factor in low titer is found in half of the cases. Peripheral blood T and B lymphocytes occur in normal percentages.

Jaundice, Familial Hereditary defects in bilirubin metabolism may be divided into two groups of cases depending on whether the increased plasma bilirubin occurs only in the free or in both the free and conjugated forms. In the first group,

there is impairment of the hepatic conjugation of bilirubin. Patients in the second group are able to conjugate bilirubin, but their livers lack the ability to excrete bilirubin.

Severe Glucuronyl Transferase Deficiency SYN: Crigler-Najjar hemolytic jaundice

disease, familial with kernicterus

non-

Severe glucuronyl transferase deficiency is the enzymatic defect in this disorder. Serum bilirubin totals 15-40 mg/dl, of which never more than 2 mg/dl represent the direct fraction. With the exception of delayed excretion of bilirubin, results of studies of the blood and other liver function tests have been within normal limits.

Chronic Unconjugated Hyperbilirubinemia SYN: Gilbert’s disease, constitutional hepatic dysfunction, constitutional hyperbilirubinemia

There is a deficiency of the hepatic enzyme glucuronyl transferase. The elevated serum bilirubin in this disorder is entirely dependenton unconjugated bilirubin rarely exceeding 6 mg/dl and which may be intermittent or persistent. No increase in direct-reacting pigment is demonstrable. The bilirubin clearance test shows delayed excretion.

Chronic Idiopathic Jaundice Hyperbilirubinemia, SYN:

Dubin-Johnson

Type II syndrome

There is hyperbilirubinemia, about 60% of which is of the conjugated type. There are abnormal retention of sulfobromophthalein sodium dye and nonvisualization of the gallbladder. The stools may be acholic, and half the cases show bile and increased urobilinogen in the urine. There is a greenish black discoloration of the liver. Hyperbilirubinemia, SYN:

Rotor-type

Type I

hyperbilirubinemia

Type I hyperbilirubinemia,

the Rotor type,

40

Climes in

Butterworth and Cawley

has the same laboratory findings but milder symptoms, and the liver is not pigmented.

Job’s Syndrome (see also Hyper-lgE Syndrome) Large staphylococcal cold abscesses. elevated serum IgE, and impaired neutrophil granulocyte chemotaxis are the findings in this entity.

Dermatology

cinatum. In addition to a virus, Staphylococ(‘IIS nureus is frequently found in the vesicopustules. Coxsackievirus Al6 has been recovered from the throat and stools of some patients with Kaposi’s varicelliform eruption. Recently, a 26-year-old white man with Darier’s disease experienced eczema herpeticum due to herpesvirus type 2.

Kawasaki Disease SYN: mucocutaneous

K Kaposi’s Sarcoma Monocytosis is rather frequent; eosinophilia occurs less often. Patients may show anergy to tuberculin, trichophytin, streptokinase, streptodornase, and candidin. In homosexual men, cytomegalovirus has been cultured from the urine and semen. Kaposi’s sarcoma may be associated with malignant lymphoma, including leukemia.

Kaposi’s Varicelliform Eruption SYN: eczema

herpeticum,

eczema

vaccina-

turn Kaposi’s varicelliform eruption is designated as eczema herpeticum or eczema vaccinatum depending upon the etiologic agent involved. Multinucleate giant epithelial cells with intranuclear inclusions appear in stained Tzanck smears from cases due to herpes simplex but not in those due to vaccinia. The virus may be recovered from the contents of vesicopustules by culturing on human amnion cells or chorioallantoic membranes of 12-day-old chick embryos. From such cultures, viral neutralization tests may be conducted. An increase in antibody titer in the blood serum obtained during the acute phase of the disease from that obtained during the convalescence is indicative of a primary infection. The complement fixation test is probably of less value in this disease. A hemagglutination test is available in eczema vac-

lymphnode

syndrome

There is polymorphonuclear leukocytosis with a shift to the left, thrombocytosis, and slight anemia. The erythrocyte sedimentation rate is elevated. One finds high levels of C-reactive protein, an-globulin, and IgE. There is a negative antistreptolysin 0 titer. Increased serum aminotransferases, alkaline phosphatase, and bilirubin are other abnormalities that may beencountered. Minimal cerebrospinal fluid pleocytosis is seen occasionally. The urine often shows white blood cells and small amounts of protein. Japanese investigators have reported an association with house dust mites and have found elevated serum levels of anti-mitespecific IgG and IgE.

Keloids In white populations, individuals who carry HLA-B14 or HLA-Bwl6 have a greater risk of developing keloids.

Keratoacanthoma Several authors have reported virus-like intranuclear particles in some of the tumor cells. A positive result of the antinuclear factor test by the immunofluorescent tumor imprint technique was found in a case reported.

Keratolysis, Pitted The consensus favors a filamentous organism of the Corynebacterium species as the cause. In one case, Dermophilus congolensis was recovered.

July-September 1986 Volume 4 Number 3

Cutaneous

Keratosis Blennorrhagica (see Reiter’s disease) The view that gonorrhea causes keratosis blennorrhagica has been discredited, and this rash is now accepted as being peculiar to Reiter’s disease, which in the majority of cases, is not associated with gonorrhea. Nevertheless, gram-negative diplococci have been found in smears of skin lesions of some cases. Smears of urethral or cervical exudate are more likely to show gram-negative intracellular diplocci. Occasionally the organisms may be recovered from the blood. The disease favors young men with the HLA-B27 genotype. As a rule, there is a moderate leukocytosis with a preponderance of young neutrophils. The erythrocyte sedimentation rate is generally elevated. Keratosis Follicularis SYN:Darier’s disease, Darier-White

disease

Cytologic smears of vesicular lesions reveal many typical corps ronds. In vivo bound immunoglobulins G, A, and M and C3 are found in the epidermal intercellular areas of skin lesions with direct fluorescence. Low serum levels of vitamin A and carotene may be found in some patients. Darkfield adaptation tests may be beyond the normal range, although there is no close correlation with the clinical picture. Decreased delayed hypersensitivity has been noted. Keratosis Palmoplantaris Diffusa SYN:tylosis of the palms and soles Low serum vitamin A levels have been reported in some cases. Kerion The lesion is usually caused by a zoophilic organism, notably Trichophyton verrucosum, T. mentagrophytes, or Microsporon canis. Much less frequently anthropophilic fungi are recovered including M. audouini, M. gypseum, T. tonsurans, or T. rubrum. The boggy tumefaction should be examined under the Wood’s light and fluorescent

41

Diseases

hairs planted on Sabouraud’s dextrose medium. Immunologically, a trichophytin reaction usually changes from negative or weakly positive to strongly positive. Kimura’s Disease The peripheral blood has an eosinophilia of more than 20%. The bone marrow shows many mature eosinophils and the absence of leukemic cells. Many cases have a high level of IgE. Klinefelter’s Syndrome The classic genotype is XXY; variants include XXYY, XXXY, XXXXY, and probably others. Buccal smears of all cases are positive for Barr bodies, which number one fewer than the total of X chromosomes. Karyotyping is indicated to exclude mosaicism and to detect extra Y chromosomes. There are increased urinary gonadotropin excretion and low or normal 17-ketosteroid levels. Plasma testosterone is also found to be below normal. Klippel-Trenaunay-Weber Syndrome There are usually no significant tory findings.

labora-

Koilonychia SYN:spoon nails It has been most frequently mentioned with hypochromic or iron-deficiency anemias. Koilonychia has accompanied Plummer-Vinson syndrome, polycythemia, hyperthyroidism, hypothyroidism, syphilis, and others. The cystine content of spoon-shaped nails is lower than normal. Kwashiorkor Hypoproteinemia is the most constant laboratory finding, the reduction being chiefly and sometimes solely in the albumin fraction. Plasma-free amino acids and urea are markedly reduced. Blood glutathione and serum guanidinoacetic acid, arginine, crea-

Butterworth and Cawley

42

tine, and creatinine are low. All of the plasma lipids are reduced to low levels. Plasma zinc, copper, and magnesium are low. Also decreased are serum iron and total iron-binding capacity, calcium, potassium, and phosphorus. Serum levels of amylase, esterase, cholinesterase, aminotransferase, lipase, and alkaline phosphatase are diminished. Serum lactic dehydrogenase may be increased. Duodenal enzymes, too, show exceptionally low values. There is usually a mild anemia, which may be of the normocytic, microcytic, or macrocytic type. It is accompanied by low serum levels of vitamins A and E and a wide range of vitamin BIZ levels. Urinary excretion of amino acids is increased but the patients excrete low amounts of creatinine in theurine. Mild steatorrhea is usually present. Cell-mediated immunity is abnormal. Phagocytosis may be impaired. Abnormalities of the complement system have been reported.

Kyrle’s Disease SYN:hyperkeratosis cularis

Clinics in Dermatology

follicularis in cutem penetrans

Patients have shown evidence glucose metabolism, disturbed tion, and albuminuria.

et parafolliof abnormal liver func-

Lazy Leukocyte Syndrome There is severe peripheral neutropenia with decreased chemotaxis and random mobility of the polymorphonuclear cells. Neutrophils in the bone marrow are normal. Humoral and cellular immunities are unchanged.

Lead Poisoning Blood studies show normochromic, microcytic anemia, decreased red blood cell life span, and increased osmotic and mechanical

fragility. Basophilic stippling of the red blood cells is nonspecific, but may be an initial clue. Increased erythrocytic protoporphyrin occurs, but there is no photosensitivity. Kidney changes give rise to aminoaciduria and renal glycosuria. The diagnosis is made by determination of the content of lead in the blood and urine.

Leiner’s Disease SYX: erythema

desquamativum

Culture of the skin usually shows Staphylococcz~saureus or Candida albicans or both. Occasionally, a colony of ,&hemolytic streptococci is found. Anemia and leukocytosis with eosinophilia are common. A deficiency of the fifth component of complement has been demonstrated in these children. Biotin deficiency is implicated by some authors,

Leishmaniasis (see also Oriental Sore) Variable systemic and cutaneous manifestations are produced by Leishmania dono/-ani, L. tropica, L. braziliensis, and other strains. Diagnosis is established by demonstrating the organism by Wright’s_ or Giemsastained smear or culture of curettings from the edges of cutaneous or mucosal ulcers, blood, bone marrow, liver, or by splenic puncture. The organism is found in the leukocytes of the peripheral blood. Hamsters may be inoculated intraperitoneally or by intracardiac injection of exudate. Diagnostic laboratory studies include hemagglutination, complement fixation, agargel diffusion, and the indirect fluorescent antibody test. The latter has high sensitivity, high specificity, and few false-positive reactions. A less sensitive direct agglutination test is also available. A number of intraderma1 tests may be used: (1) Montenegro’s test (leishmanin), (2) Rotberg’s delayed reaction (leptomonads), (3) polysaccharide antigen (of L. tropica), and (4) soluble antigen (of L. braxiliensis j. Anemia and leukopenia are invariable in well-established cases. Reticulocytes are usu-

July-September 1986 Volume 4 Number 3

ally increased. There is a tendency toward agranulocytosis, monocytosis, and a relative lymphocytosis. Platelets are moderately decreased. Liver function test results are normal and there is high total serum protein, with reversal of the A/G ratio. Polyclonal gammopathy is a frequent finding. Leprechaunism The biochemical hallmark of the syndrome is disordered carbohydrate metabolism manifested by postprandial hyperglycemia, fasting hypoglycemia, insulin resistance, and notable hyperinsulinemia. The serum alkaline phosphatase level is usually low. There is increased urinary excretion of 17-ketosteroids. Aminoaciduria is sometimes present. No chromosomal abnormality has been described to this time. Leprosy SYN: Hansen’s disease The causative organism is Mycobacterium bacillus), which may be found in smears from deep scrapings of the skin or from the cut surface of incisions into the corium of an affected area. Large numbers of acid-fast organisms are found in the skin of patients with the lepromatous form, but few in other types. Demonstration of acid-fast bacilli in discharges from the nose, in any type of ulcer, or from the skin surface is not diagnostic because of the possible presence of saprophytes. The organism may be inoculated into the ears and testes of hamsters and the foot pads of the white mouse. M. leprae recently has been grown successfully in a culture of embryonic human lung cells and on an enriched Eagle’s medium. Most consistently, the intradermal injection of lepromin gives rise to Metsuda’s reaction, an edematous indurated papular reaction appearing approximately 4 weeks after inoculation. Less often, a delayed hypersensitivity-like Fernandez reaction is seen 48 hours after injection. The lepromin test result is positive in the tuberculoid type of leprosy, positive or negaleprae (Hansen’s

43

Cutaneous Diseases

tive in the indeterminate type, and negative in the dimorphous and lepromatous types. Altered immunologic reactivity occurs chiefly in lepromatous leprosy. There are defects in cell-mediated immunity, high titers of circulating antimycobacterial antibodies, and serum immune complexes of M. leprae antigen and its antibody. On the other hand, tuberculoid leprosy has a high degree of cell-mediated immunity and no circulating antimycobacterial antibodies. Accordingly, serum IgG, IgA, and sometimes IgM levels are increased in lepromatous leprosy, whereas levels of all the major immunoglobulins may be normal in tuberculoid leprosy. Precipitins are found in 75% of the lepromatous cases. Cryoglobulins appear in all forms of the disease after prolonged infection. Complement is elevated in those lepromatous patients with erythema nodosum or amyloidosis. C-reactive protein is found in the peripheral blood in almost half of the cases of lepromatous leprosy. az-Globulin may be increased, crl-globulin depressed. Various serologic tests for syphilis may be reactive in leprosy, but the TPI test is not influenced. In the intradermal histamine test, there is absence of reflex erythema. Anhidrosis may be demonstrated by injection of pilocarpine or methacholine into an area previously painted with iodine and later covered with starch. In lepromatous and dimorphous leprosy, the blood may show leukocytes, 12,00040,000/~1, often with a shift to the left. Some degree of anemia is usually present. The A/G ratio is reversed. Rheumatoid factor may be present. Leptospirosis Two varieties are of interest to dermatologists-Weil’s disease and pretibial fever. The former is caused by Leptospira icterohemorrhagica and manifests leukocytosis of 15,000/~1 with a shift to the left and increased lymphocytes in the cerebrospinal fluid. A mild normocytic-normochromic anemia usually develops. Renal involvement presents as proteinuria, hematuria, and azo-

44

Butterworth

and Cawley

temia. After jaundiceoccurs, abnormal liver function test results are found. Pretibial (Fort Bragg) fever is a milder disease caused by Leptospira autumnalis. Leukopenia occurs early, and the infection runs its course in about a week. Leptospira may be found in the blood by darkfield examination during the first week. It may be cultured from the blood and cerebrospinal fluid in the early stages of the disease and from urine later. Guinea pig inoculation may be helpful. Beginning in the second week, rising antibody titers may be demonstrated by agglutination.

Lesch-Nyhan Syndrome SYN: X-linked

primary

Clinics in Dermatology

hyperuricemia

These patients have all the clinical findings of gout, including hyperuricemia, hyperuricuria, hematuria, crystalluria, and urinary tract stones. The abnormality is caused by a deficiency of hypoxanthine guanine phosphoribosyltransferase. Carriers may be identified by measuring activity of the above enzyme in individual hair roots taken from the scalps of suspected heterozygotes.

Leukemia Cutis In addition to changes in the lymphocytic. granulocytic, or monocytic elements in the blood, hyperuricemia is common. Cryoglobulinemia and low levels of IgG may be found in chronic lymphatic leukemia. Most cases of the latter have a monoclonal increase in B lymphocytes; but a very small percentage have increased numbers of T lymphocytes, more often of the helper than of the suppressor subsets. T lymphocytosis is likely to be reactive rather than neoplastic in nature.

Leukoplakia Oris Serologic tests for syphilis are indicated. Cytologic studies may be helpful in detecting early malignancy or white sponge nevus.

Lichen Lichen Amyloidosus Usually there are no abnormalities in routine studies of the blood and urine, liver function tests. or protein electrophoresis. Lichen Myxedematosus SYN: papular

mucinosis,

scleromyxedema

Results of thyroid function studies are normal. There are decreased serum albumin and increased serum y-globulin. The sera of most patients contain a monoclonal immunoglobulin, usually IgG with A light chains. IgA may also be increased. Elevated erythrocyte sedimentation rates and albuminuria are frequent nonspecific findings. There may be leukocytosis and, very rarely, eosinophilia. Changes in the blood lipids, especially in the a-~ lipoprotein ratio, have been recorded. The bone marrow may show plasmacytosis. Lichen Planus Consistent laboratory findings are few. The white blood cell count may be lowered, with lymphopenia. Impaired glucose tolerance has been found in more than half of the cases in some reported series. A linkage with blood group A is stressed by some writers. A deficiency of circulating IgA and IgM has been noted in adult patients with lichen planus. Immunofluorescence studies characteristically show deposits at the dermoepidermal junction. These may be of any immunoglobulin class plus complement and fibrin. IgM being found most consistently. Recently, a lichen planus-specific antigen has been demonstrated, by indirect immunofluorescence, in the stratum granulosum and stratum spinosum. Lichen Sclerosus et Atrophicus Patients with vulvar lesions have shown decreased serum levels of dihydrotestosterone, free testosterone, and androstenedione. Lichen Striatus Elevated serum alkaline been found in a few cases.

phosphatase

has

July-September Volume 4 Number 3

1986

Cutaneous Diseases

Lichen Urticatus

cerebrospinal fluid. The prenatal diagnosis of this disease has been made from cultured amniotic fluid cells.

SYN: papular

urticaria

Skin testing itive reaction tients.

with flea antigen causes a posin a large percentage of pa-

Lipodystrophy, Lipodystrophy, Congenital Generalized SYN: lipoatrophic syndrome

diabetes,

Lawrence-Seip

Intense hyperlipemia usually precedes diabetes. The serum is intermittently turbid owing to increased triglycerides and lowdensity lipoproteins. The cholesterol levels are usually only slightly elevated. The patients present a nonketotic insulin-resistant diabetes. Glycosuria may precede hyperglycemia by a number of years. A high level of plasma insulin has been found in some patients. Many individuals have an elevated basal metabolic rate, but are euthyroid. Serum albumin has been elevated in some patients. Abnormal liver function test results have been found with elevated serum alanine aminotransferase and serum alkaline phosphatase. Plasma concentrations of pituitary growth hormone tend to be elevated. Urinary excretion of 17-ketosteroids and pregnanediol is also increased.

Lipodystrophy, Progressive SYN: partial lipodystrophy, atrophy, Barraquer-Simons

partial disease

lipo-

Most patients have hypocomplementemia. A high percentage of them have decreased serum C3, with normal C4 and C2 levels, and a serum C3 nephritic factor. Many exhibit albuminuria, hematuria, and other evidence of renal disease. A significant proportion of cases have glycosuria, most with typical blood sugar curves. Some patients show elevation of triglycerides with increase in prebetalipoproteins and chylomicrons.

Lipogranulomatosis

45

of Farber

The enzymatic fault is a deficiency of acid ceramidase. Excess protein is found in the

Listeriosis Listeria monocytogenes, a gram-positive rod, may be found in smears of meconium. The pathogen is recovered in cultures of blood, cerebrospinal fluid, urine, meconium, placenta, lochia, milk, exudates, and contents of pustules. Blood cultures, however, are often sterile even in generalized cases. In the Anton eye test, conjunctivitis always occurs when the eye of a rabbit is gently swabbed with a culture of L. monocytogenes. The diagnosis can be further established by animal inoculation, but animal tests are used only rarely now. A high or rising titer in the agglutination test is significant. The titer falls rapidly after recovery so the test cannot serve reliably for late diagnosis. Complement fixation tests have proved helpful only in skilled hands. The infection produces monocytosis in a small percentage of patients and polymorphonuclear leukocytosis in some.

Livedo Reticularis SYN:cutis

IKWmOrata

Most cases occur without evidence of other disorder, although livedo reticularis may occur with any of a host of diseases. Cryoglobulins may be present. Circulating immune complexes and decreased complement levels suggesting an immunologic abnormality have been reported.

Loaiasis SYN: loa loa, Calabar phantiasis, p. 22)

swelling

(see also Ele-

If fresh thick blood films are examined between the hours of 10:00 AM and 2:00 PM, Microfilaria loa sometimes can be demonstrated. The organism also can be found in aspirates of the swellings. An eosinophilia averaging 15-30%, but sometimes much higher, is an absolutely constant finding. Immu-

Cllnlcs I”

Butterworth and Cawley

46

noglobulin E levels are elevated. Strong serologic positivity with hemagglutination and bentonite flocculation support the diagnosis. Intradermal and complement fixation tests are of less value. Definite diagnosis can be made only by recovering the parasite itself.

Lupus Erythemafosus Discoid Lupus Erythematosus (DLE) Hematologic findings may include a chronic normochromic anemia, leukopeniaof fewer than 5,000 cells, and, rarely, thrombocytopenia. Elevated erythrocyte sedimentation rates and serum y-globulin levels are found commonly. The LE cell test result is usually negative in DLE, but 4 or 5% are positive for antinuclear antibodies: an equal number have low total hemolytic complement. A few show anti-double-stranded DNA antibodies: some have biologic false-positive serologic test results for syphillis. The result of the lupus band test (LBT). which demonstrates granular deposits of IgM, IgG, and complement along the dermoepidermal junction, is positive in involved cutaneous areas in 90% of patients with DLE but not in their normal-appearing skin (as in SLE). Most of the laboratory findings in DLE are transient; their persistence increases the possibility of subacute cutaneous lupus erythematosus or systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) All three blood elements are depressed. There is a mild to moderate anemia of the normocytic, normochromic, hypochromic, or hemolytic type. Most significant for SLE is a hemolytic anemia due to anti-red cell antibodies. A positive Coombs’test result is often observed. Leukopenia, with depression of the granulocyte and lymphocyte count, is frequently recorded, although leukocytosis may be present with disease exacerbations. T lymphocytes are decreased in number, with elimina-

Dermatology

tion or block of suppressor types. B lymphocytes are increased and unsuppressed, and form numerous autoantibodies. One third of the patients have thrombocytopenia owing to platelet autoantibodies. Circulating anticoagulants in SLE produce a slight prolongation of the thromboplastin time. Kidney involvement may be of the nephritic or nephrotic type. Urinalysis reveals proteinuria, hematuria, pyuria, and casts frequently. Elevation of blood urea nitrogen occurs. The creatinine clearance test is most informative of kidney function in these cases. In nephrotic-type involvement, there is hypercholesterolemia. Total complement, C3, and C4 levels are frequently decreased in active lupus nephritis. Acute-phase nonspecific reactions include elevated C-reactive protein (CRP), fibrinogen, and erythrocyte sedimentation rate. The latter, however, is unreliable for following the activity of the disease. The serum protein electrophoresis may also be informative about nonspecific reactions in the body. There may be a low albumin and a high az-globulin level, and diffuse hypergammaglobulinemia. The A/G ratio is reversed. Antibodies against a wide spectrum of nuclear constituents can be detected in the serum of patients with SLE. A positive LE prep result denotes the presence of a specific anti-DNA antibody in serum and is found in 75% of cases of SLE. The LE prep test has been largely abandoned in favor of the fluorescent antinuclear antibody (ANA) test, which detects a wider spectrum of antinuclear factors (Ig types G, M, and A and four IgG subclasses). Although the test is not specific, it is very sensitive and its result is positive in perhaps 95% of all patients with SLE. It is the chief screening test for lupus erythematosus. An antinuclear antibody against genetic material, DNA, is more specific for SLE, especially if its specificity is for the native or double-stranded form of DNA (Farr test). This antibody virtually occurs only in systemic lupus and might be considered the most specific test for this condition. Some,

July-September Volume 4 Number 3

1986

47

Cutaneous Diseases

however, think it is rivaled in specificity by determination of antibodies to Sm antigens. There appears to be a correlation between DNA antibody titer and disease activity. High levels of anti-double-stranded DNA, decreased serum complement levels, and the presence of circulating cryoglobulins frequently accompany nephritis. Other antibodies are related to the several SLE subsets. Thus, anti-RNP is linked with overlapping features of SLE, scleroderma, myositis, and lower incidence of renal disease (mixed connective tissue disease, MCTD). Anti-Sm relates to milder involvement of the central nervous system and kidneys but with more Raynaud’s phenomena, pulmonary lesions, and skin changes (vasculitis). The patients generally have favorable prognoses. Se-1 is associated with scleroderma; PM-l, with dermatomyositis. AntiMa manifests as widespread skin disease and severe nephritis without dsDNA antibodies. Anti SS-A(Ro) and SS-B(La) have increased incidence of subacute lupus erythematosus (SCLE) and Sjiigren’s syndrome. The same pair of antibodies in both mother and child have been demonstrated to be markers of neonatal lupus syndrome. Both individuals generally show a speckled pattern of fluorescent antinuclear antibodies (ANA) but are usually negative for antibodies against native DNA. On the other hand, negative ANA is associated with photosensitive lupus skin disease, rheumatoid factor, and anticytoplasmic antibodies (anti-R0 and anti-La). Antibodies against histones are indicative of druginduced lupus. Antithyroid antibodies are common. A significant number of patients have falsepositive syphilitic serology. Immune complexes play a role in the production of tissue injury in SLE and, in so doing, complement is fixed. In the absence of readily available tests for measuring immune complexes, their presence is determined by measuring total hemolytic complement (CH50) as well as C3 and C4. A strikingly consistent depression of C4 relative to other components of complement characterizes SLE. Cerebrospinal fluid hemolytic C4 titers

are a sensitive assay for central nervous system lupus erythematosus. Direct immunofluorescent microscopy reveals the presence of IgM and some componentsof complement and fibrin in the tissues. The presence of these factors may be presumptive evidence for immune complexes. Positive-staining reactions at the dermoepidermal junction can be diagnostic criteria for the presence of SLE. This “lupus band test” (LBT) can be found in both involved skin and, in a significant number of patients, uninvolved non-sun-exposed skin in SLE. Similar staining in renal glomeruli may indicate lupus nephritis even in the absence of a very active urinary sediment. Most studies have reported weak or negative association of SLE and HLA antigens. At best, the reports have been conflicting.

lupus Vulgaris Definite diagnosis is made by culture and animal inoculation of tissue from the lesions. In all forms of lupus vulgaris, the tuberculin test result is almost invariably positive. Old tuberculin or tuberculin purified protein derivative (PPD) is injected intradermally into the forearm in appropriate dilutions. In children, the Vollmer patch may be used, but this is far less satisfactory.

Lymphadenopathy, Angioimmunoblastic The distinctive laboratory features polyclonal hypergammaglobulinemia Coombs’-positive hemolytic anemia.

are and

Lymphangitis Group A /3-hemolytic usual cause.

streptococci

are the

Lymphogranuloma Venereum SYN: lymphopathia uloma inguinale

venereum,

lymphogran-

This venereal disease is caused by Chlamydia trachomatis (Bedsoniae lymphogranulomatis). The organism may be cultivated

Cllnlcs In Dermatology

Buttetworth and Cawley

48

on yolk sacs of embryonated chicken eggs, in cornea1 or HeLa tissue cultures, or by injections into the brains of mice. The antigen for the Frei test is no longer commercially available. Hyperglobulinemia is usually seen, often with reversal of the A/G ratio. IgA and IgG are the immunoglobulins usually elevated. In both acute and chronic cases. a high percentage show autoimmune serum factors such as cryoglobulins, rheumatoid factor, antinuclear antibodies, positive Coombs’test result, and anticomplementary factors. Falsepositive results of serologic tests for syphilis may occur. The erythrocyte sedimentation rate is usually elevated, and serum lipids are commonly depressed. In active cases, there are mild anemia and moderate leukocytosis. The most useful serologic test is the microimmunofluorescence test for Ch/a~rydin. The complement fixation test result becomes positive within 4 weeks of infection. It is not species specific and so indicates only a present or past infection with one of the Chlamydiaceae. Recent tests introduced commercially include Abbott’s (Abbott Laboratories. Chicago, IL) enzyme-linked immunoassay and Syva’s (Syntex, Mountain View, CA) fluorescein-labeled monoclonal antibody test.

Mastocytosis SYN: urticaria

pigmentosa

In the bullous type, smears from the base of a deroofed blister demonstrate the presence of great numbers of mast cells with metachromatic granules. In severe disease, tissue mast cells may sometimes be demonstrated in the peripheral blood. Large numbers of mast cells are also found in the bone marrow. The blood picture is variable. Anemia, leukocytosis, leukopenia, eosinophilia, basophilia. monocytosis, and thrombocytopenia have been noted. Bone marrow involvement may lead to anemia. On the other hand, polycythemia has been reported in a few patients. Blood levels of heparin may be raised. There is increased urinary excretion of free histamine, but the major histamine metabolite, 1-methyl-4-imidazoleacetic acid, has recently been considered to be a better reflection of the body’s histamine pool. Paper electrophoresis of the urine, stained for mucopolysaccharides, reveals excretion of hyaluronic acid, chondroitin sulfuric acid, and traces of heparin. Hypocholesterolemia occurs in lo-2096 of patients. In some, systemic mastocytosis has been associated with the presence of rheumatoid factor.

Mauriac’s Syndrome Hyperglycemia and hyperlipidemia are constant features; abnormal liver function findings occur in some patients.

M

Measles

Mal Perforans Pedis SYN: perforating Laboratory the diagnosis

SYN: rubeola,

ulcer of the foot

studies are of value in making of diabetes, syphilis, or leprosy.

Marfan’s Disease Some authors reported an increased tion of urinary hydroxyproline.

excre-

Marinesco-Sjijgren Syndrome Occasionally, low.

the serum

calcium

may be

morbilli

With the use of the direct fluorescent antibody staining technique, a rapid diagnosis of measles infection may be established by examination of nasopharyngeal aspirates or urinary smears from patients. Intracellular viral antigen is usually revealed. Measles hemagglutination-inhibition and neutralizing antibodies appear earlier and persist longer than complement-fixing antibodies following vaccination or natural infection. The hemagglutination-inhibition test is the simplest and most practical test to per-

July-September 1986 Volume 4 Number 3

form. The leukocyte count tends with a relative lymphocytosis.

Cutaneous

to be low

Measles, German SYN:

rubella

The diagnosis may be established by isolating the virus from throat swabs or blood by inoculation into primary Africangreen monkey kidney cells, primary cultures of human amnion, or embryonic skin muscle. Cultures are positive from both sources a week before the onset of the eruption but only from the throat after the rash has appeared. Hemagglutination-inhibition, complement fixation, and fluorescent antibody titers begin to rise in the first and second weeks after the exanthem begins. The first is the most rapid and sensitive examination for rubella. Such antibodies persist for a long time and give protection to pregnant women who are exposed to German measles. The presence of rubella IgM antibody means recent acute infection. The hemagglutination-inhibition (HI) test is now being supplanted by a number of equally or more sensitive assays to determine rubella immunity. These include latex agglutination, fluorescence immunoassay, passive hemagglutination, hemolysis-in-gel, and enzyme immunoassay tests. The white blood cell count is characteristically leukopenic with a relative lymphocytosis. Later, a few patients may develop leukocytosis. The platelets may be mildly depressed, and hematuria may occur. The erythrocyte sedimentation rate is slightly elevated. Capillary fragility is increased. Infants of mothers with German measles may have neonatal rubella. A small number of these babies have a “dysgammaglobulinemia” with very high levels of IgM, low levels of IgG, and no IgA. These defects tend to improve in time, except that some infants carry and excrete the virus for up to 2 years, and the IgA deficiency is persistent. Patients with neonatal rubella are prone to thrombocytopenia. The platelet counts range from low normal to 10,000/J, and the bone marrow shows few megakaryocytes.

49

Diseases

Melanoma, Malignant Depressed monocyte chemotaxis has been reported. Indirect immunofluorescence has shown antibodies directed against intracellular and cell membrane antigens of human malignant melanoma.

Melanosis, Transient Neonatal Pustular The vesicopustules contain large numbers of polymorphonuclear leukocytes with few or no eosinophils. Bacterial cultures of the contents are sterile.

Melioidosis SYN: Whitmore’s

disease

The causative organism is Pseudomonas (Malleomyces) psuedomallei. The bacillus may be seen on direct smears from the cutaneous abscesses or ulcers. Cultures may be taken from the blood, sputum, urine, pus, cerebrospinal fluid, or excised surgical specimen. The organism produces a fatal infection in guinea pigs, rabbits, and other laboratory animals. Flourescent antibody tests afford a rapid and accurate means of diagnosis. Serum agglutination tests are useful when acute and convalescent serologic titers are compared, but agglutinins have been found in the serum of normal persons. Complementfixing antibodies appear after several weeks. The white blood cell count varies from normal to 20,000 02 more. The erythrocyte sedimentation rate is almost always increased. Urinalysis may show pyuria and hematuria.

Meningococcemia Neisseria meningitidis may be cultured from the blood, cerebrospinal fluid, or nasopharynx. The diplococci may be seen in smears of the cerebrospinal fluid but probably not from the skin lesions. Leukocytosis is common sometimes during the course of the disease, but early leukopenia is a poor prognostic sign. Transient

Clmics

50

I” Dermotology

Butterworth and Cawley

hyperglycemis, proteinuria, hematuria, pyuria. and mild azotemia are frequent findings.

leucine. isoleucine, tyrosine, and phenylalanine. a-Hydroxybutyric acid is excreted in the urine and gives it an offensive odor.

Menkes’ Kinky Hair Disease

Milkers’ Nodules

SUN: kinky hair syndrome, Menkes’ hair disease. trichopoliodystrophy

steely

In the neonatal period, serum copper is either normal or elevated. The serum copper level falls steadily after birth, reaching its typically low level within a few weeks. Serum ceruloplasmin level generally varies with the serum copper level, being normal at birth, and falling to low or undetectable levels thereafter. Impaired intestinal absorption of copper is seen. Fibroblasts from patients with Menkes’ syndrome, including those from amniotic fluid, have a marked affinity for copper. Red blood cells incorporate orally administered copper preferentially, and, thus, anemia is avoided. As indicated above, prenatal diagnosis is possible. Heterozygote mothers show significantly higher than normal copper uptake by their skin fibroblasts. The tocopherol content of the serum is depressed, and an abnormal pattern of autofluorescence of the hair is observed. The amino acid composition of the hair, serum, and urine is normal.

Methemoglobinemia, Familial Idiopathic Two types are recognized. In one, the biologic defect is a deficiency of erythrocyte methemoglobin reductase activity. In the other type of familial idiopathic methemoglobinemia, there is an abnormality in the molecular structure of hemoglobin designated “hemoglobin M” disease. There is generally a secondary polycythemia with an accompanying reticulocytosis.

Methionine Malabsorption Syndrome SYN: Oasthouse

urine

disease

The aminoaciduria shows an increase of methionine and smaller amounts of valine,

A poxvirus has been grown in cultures of bovine kidney cells and human skin fibroblasts. Diagnosis can also be made by electron microscopy. Complement fixation is available.

Molluscum Contagiosum The molluscum virus is the largest member of the pox group of viruses infectious to man. Although diagnosis can usually be made readily on clinical grounds, the virus may be identified by tissue culture, demonstration of fluorescent antibodies, neutralization tests, and electron microscopy.

Monilethrix Argininosuccinicaciduria has been demonstrated by paper chromatography. The abnormal amino acid is not always present in the urine, and the quantity excreted varies. An increase in serum alkaline phosphatase has also been reported. Elevated levels of glutamic acid have been found in the blood of a few patients.

Mononucleosis, Infectious The Epstein-Barr virus is the etiologic agent of infectious mononucleosis. The total white blood cell count is usually between 10,000 and 20,000, but it may be normal or lower than normal. Late in the illness, neutropenia is common. Atypical lymphocytes constitute 20-67% (average 40%) of the white blood cells during the febrile stage of the disease. The platelet counts are often reduced in the first weeks of illness. Anemia is rare. Cold agglutinins are frequently present. The Paul-Bunnell test for heterophil antibodies (agglutinins) in the blood is of great value in infectious mononucleosis. A minimal heterophil antibody titer for diagnosis is 156. After guinea pig kidney absorption, a titer of 1:28 but at least 1:14 is considered

July-September

1986

Volume 4 Number 3

Cutaneous

diagnostic in conjunction with the hematologic findings. Rapid slide tests are available. With liver involvement, bilirubin and hepatic enzymes are elevated (ALT, AST, ALP, LDH). Biologic false-positive reactors for syphilis are infrequent. Rheumatoid factor may be found. Renal involvement with hematuria occurs in 56% of cases.

Moschcowitz’s Syndrome SYN: thrombotic

thrombocytopenia

purpura

Thrombocytopenia and hemolytic anemia are constant manifestations of this syndrome.

Muckle-Wells Syndrome Increased erythrocyte sedimentation rate, leukocytosis, and hypergammaglobulinemia are almost constant findings. Hyperglycinuria may be encountered. Finally, azotemia with substantial proteinuria occurs.

Mucopolysaccharidoses SYN: gargoylism,

lipochondrodystrophy

This group of diseases is characterized by the widespread, excessive intracellular accumulation and urinary excretion of derma-

TABLE

51

Diseases

tan, heparan, and keratan sulfates. They also share metachromatic staining of granules in leukocytes and cultured fibroblasts. Many carriers show the same phenomenon. The specific enzymatic defect may be demonstrated in tissue culture of skin biopsy fibroblasts. Prenatal diagnosis is possible by study of cultured amniotic fluid cells. Acid mucopolysaccharides are found in the cerebrospinal fluid. The urine, plasma, and cultured fibroblasts of each of types I, II, III, and VI contain “correction factor” for the other three types. Table l-2 summarizes the names, urinary findings, and the enzymatic deficiencies of the several varieties of mucopolysaccharidoses.

Mycetoma SYN: Madura

foot, Maduromycosis

Mycetomas are most commonly due to true fungi in the order Eumycetes (usually species of the genera Madurella, Exophilia, and Pseudoallescheria) or to filamentous bacteria in the order Actinomycetales (usually species of the genera Actinomyces, Nocardia, Streptomyces, and Actinomadura). Rarely, true bacteria, such as Staphylococcus aureus, Pseudomonas aeruginosa, and streptococci

1-2. Mucopolysaccharidoses

Type

Syndromic

I

Hurler’s Scheie’s Hurler-Scheie

Eponym

Dermatan sulfates

and heparan

(Y L-iduronidase

II

Hunter’s, severe Hunter’s, mild

Dermatan sulfates

and heparan

Sulfoiduronate

III

Sanfilippo’s Sanfilippo’s

Heparan sulfate

A. Heparan sulfate sulfatase B. N-acetyl+D-Glucosaminidase

IV

Morquio’s

Keratan sulfate

Chondroitin

Dermatan

sulfate

Arylsulfatase

Dermatan sulfates

and heparan

p-Glucuronidase

A B

V

Formerly,

VI

Maroteaux-Lamy

VII

/I-Glucuronidase

Urinary

Findings

Enzymatic

Deficiency

sulfatase

sulfatase

Scheie’s

deficiency

B

52

Clinics in Dermatology

Butterworth and Cawley

in the order Eubacteriales, or various dermatophytes may cause mycetoma. Acrernoniumfalciforme has been a rare finding. The organism is found in KOH mounts and Gram-stained specimens of the tiny granules that are found in the exuding suppurative fluid. The granules may also be cultured on Sabouraud’s agar. The gel precipitin method differentiates eumycetic and actinomycetic infections. Serologic tests that probably will be more readily available in the future include immunodiffusion, countercurrent immunoelectrophoresis, and an enzyme-linked immunosorbent assay.

Mycobacteriosis, Sporotrichoid Cultures show Mycobucterium less often, M. kansasii.

murium,

Mycosis Fungoides SYN: granuloma

fungoides

In this T-cell lymphoma, most patients show an absolute lymphopenia with a decreased number of circulating T cells. Monocytosis is not common, but the monocytes exhibit defective chemotaxis. Some authors have reported abnormal circulating monocytoid cells indistinguishable from Skzary cells. Eosinophilia, 6-50%. is found in some patients. Anemia is one of the signs of systemic spread. Increased serum a-globulin has been reported by some investigators. IgG and IgM usually have normal levels, but IgA and IgE may be elevated. Anti-T-cell antibodies and lymphocytotoxicity against epidermal cells of the lesional skin have been described. Delayed hypersensitivity test results may be depressed. Experimental contact sensitization with dinitrochlorobenzene is unsuccessful in some patients. In vitro response to mitogen stimulation may also be depressed. With chemotherapy, hyperuricemia often occurs.

requires

bone-marrow

Myxedema Thyroxine (Td), triiodothyronine (T3), and radioactive iodine uptake are below the lower limitsof the normal range of findings. Hypercholesterolemia and carotenemia are the rule. The vitamin A content of the blood is low. Bl-Globulin is increased. Anemiaoccurs in about one third of the patients, and proteinuria is an occasional finding. Myxedematous children usually excrete less than normal urinary creatine or, at times, none at all. Antithyroid antibodies are found in cases secondary to thyroiditis. Myxedema, Pretibial

Myeloma, Multiple Diagnosis

that demonstrate an increase in plasma cells. Characteristically, plasma cells make up more than 15%, and often up to 90%, of marrow cells. These observations are supported by finding a homogeneous monoclonal globulin spike in serum or urine electrophoresis. The myeloma globulins are two-thirds IgG, one-third IgA, and rarely IgD, and, in a few cases, IgE. The patients are deficient in normal immunoglobulins. Bence Jones protein is demonstrable in the serum and urine in half the cases. Cryoglobulins are found in about 5% of patients. Coldagglutinating antibodies may be present. The A/G ratio is reversed. Anemia and, when severe, leukopenia and thrombocytopenia are common findings due to replacement of the bone marrow by myeloma cells. Rouleaux formation, circulating plasma cells, and an elevated erythrocyte sedimentation rate are other features. There is often increased blood viscosity. The prothrombin time may be prolonged. Hypercalciuria and hypercalcemia may occur. The concentration of serum uric acid increases and leads to secondary gout. Signs of uremia appear in some cases. Systematized amyloidosis develops in 15% of cases. Occasionally, carotenemia is present. Xanthomatosis is unusual and may be associated with normolipidemia or hyperlipidemia.

studies

High serum long-acting thyroid stimulator (LATS) levels are present with pretibial

July-September Volume 4 Number 3

1906

Cutaneous

myxedema in about 90% of patients. LATS is an established circulating immunoglobulin (7s-IgG) whose serum titers show poor correlation with the severity of the pretibial myxedema.

N Nails Nails, Green Cultures frequently reveal the presence Pseudomonas aeruginosa.

of

Nails, Half-and-Half The patients have urinary casts, reduced creatinine clearance, and definite azotemia.

53

Diseases

Necrolysis, Toxic Epidermal SYN: Lyell’s syndrome,

scalded

skin

syndrome Cases may be classified as idiopathic or drug-induced. Leukocytosis is usual, lymphocytosis occurs, and leukopenia and thrombocytopenia may be found. In cases ascribed to drugs, persistent neutropenia due to granulocytopenia has been cited as a poor prognostic finding. In drug-induced cases, the liver enzymes are usually elevated. Hypocalcemia is present in a majority.

Necrosis, Subcutaneous Fat, of the Newborn There may be transient thrombocytopenia, which returns to normal as the skin lesions spontaneously resolve. Diabetes may be found in the mother.

Nail, Yellow Syndrome (see p. 94) Nail-Patella-Elbow Syndrome The associated nephropathy manifests persistent albuminuria, casts of all types, and hematuria. There are increased blood urea nitrogen and reduced creatinine clearance. Significantly elevated proline excretion has been found in a number of cases.

Necrobiosis Lipoidica About two thirds of the patients have diabetes. If results of routine fasting blood sugar and urinalysis are normal, a 2-hour postprandial blood sugar and a glucose tolerance test are indicated. If results of these are also within normal limits, a cortisone glucose tolerance test may reveal a diabetic tendency. The prednisone glycosuria test result may also be abnormal. Some investigators have reported elevation of the total serum protein-bound hexose, crz-globulin and az-glycoprotein in necrobiosis lipoidica. Others have found significant increases in a2 and p-lipoproteins. One study has shown C3 and/or IgM in the vessel walls of necrobiotic lesions. Defective neutrophil migration has also been demonstrated.

Netherton’s Syndrome An inconstant aminoaciduria has been reported in about a quarter of the cases, with increased elimination of histidine, serine, glycine, and argininosuccinic acid. Hypogammaglobulinemia has been a rare finding.

Neuropathy Congenital Sensory Neuropathy with Anhidrosis Chromosomal abnormalities have been reported but have not been a consistent finding.

Hereditary Sensory Neuropathy SYN:Thevenard’s syndrome, sensory radicular neuropathy (hereditary type) The results of laboratory studies are generally normal. Hypergammaglobulinemia has been reported, with a moderately increased IgG level, a normal IgM level, and a slightly increased IgA level.

Neutropenia Neutropenia, Chronic Familial This abnormality

is characterized

by con-

54

Chnics I” Dermatology

Butterworth and Cawley

sistent neutropenia, normal to decreased leukocyte counts. and. usually, relative Iymphocytosis, monocytosis, and variableeosinophilia. The red blood cells and thrombocytes are generally within normal limits. In the bone marrow. granulopoiesis is well represented to the myelocyte stage with a marked reduction in the more mature forms. Lymphocytes are increased, and the monocytoid cells are numerous. There are no abnormalities in the erythrocytic or megakaryocytic series. Neutropenia,

Cyclic

cytoplasm of circulating lymphocytes and monocytes. Moderate anemia is usually present. Thrombocytes areoften elevated markedly, although late in the disease they may be decreased. Serum lipids are usually normal, with occasional exceptions. There are decreased concentrations of cephalin and sphingomyelin in the red blood cells, but the lecithin level remains normal. Bone marrow aspirates show typical Niemann-Pick cells. The cause of the disease is a deficiency of the enzyme sphingomyelinase, which may be demonstrated in tissue culture of fibroblasts.

SE’N: cyclic leukopenia A rapid diminution in the number of neutrophils in the blood occurs at intervals averaging 21 days, but with extremes of about 14 to 45 days. The white blood cell count falls to 2,000-4,000, with the neutrophils dropping to O-16%. Usually there is a compensatory increase in lymphocytes and/or monocytes. Eosinophilia frequently appears in the recovery phase. Within a week, the white blood cell count may be back to the low-normal range, where it remains until the next episode. Slight decreases in -y-globulin have been observed. Bone marrow studies indicate that even immature granulocytic forms disappear from the marrow about 3-4 days prior to their absence from the peripheral blood.

Nocardiosis ,V~wrdia usteroides is the overwhelmingly predominant human pathogen in the United States and Europe. A few cases have been caused by Nocardia brasiliensis. Laboratory studies other than bacteriologic are of little aid to the clinician. Diagnosis is made, in most cases, from smears and cultures of sputum or pus from subcutaneous abscesses. Positive cultures have also been obtained from blood, pleural fluid, synovial fluid of the knee, and, rarely, the cerebrospinal fluid. Anemia is usually present with a normal or moderately elevated leukocyte count. The cerebrospinal fluid may be normal or have changes reflecting an infectious process. There is no reliable skin or serologic test.

Neutrophil Actin Dysfunction Recurrent Staphylococcus aureus infections occur. Neutrophil random migration and chemotaxis are impaired.

Nevus, White Sponge Smears may be supportive of the clinical impression by showing abnormal keratinization. Intracytoplasmic eosinophilic inclusions may be seen.

0 “Oid-Oid” Dermatosis STN: exudative

discoid and lichenoid

derma-

tosis A marked blood eosinophilia appears the consistent laboratory finding.

to be

Niemann-Pick Disease

Onchocerciasis

There is moderate leukocytosis with a relative increase in lymphocytes. A characteristic feature is the presence of vacuoles in the

The causative organism is the filarial parasite, Onchocerca volvulus. Microfilariae may be visualized under the microscope byexam-

July-September Volume 4 Number 3

1986

Cutaneous Diseases

ining a piece of skin teased in saline. Skin “snips” or thin pieces of skin obtained by means of a razor may be used. Blood eosinophilia appears to be the rule. Hypergammaglobulinemia E may occur in some patients.

Onycholysis The laboratory can help in diagnosing cases due to hyperthyroidism or hypothyroidism; syphilis; and mycotic, pyogenic, or viral (herpetic) infection.

55

Material aspirated by syringe, from beneath the indurated border, may be used to prepare smears or cultures of N.N.N. medium. Mexican cutaneous leishmaniasis is caused by L. mexicana. The result of an intradermal skin test, the Montenegro-Jessner-Leishmanin test, is positive in 48 hours in 95%of all individuals with early cutaneous leishmaniasis and in 98% of patients with late leishmaniasis. Complement fixation and both test-tube and slide agglutination tests are also available as diagnostic aids. Indirect immunofluorescence has been a helpful tool in recent years.

Onychomycosis Trichophyton rubrum and T. mentagrophytes infect the nails most commonly. Less often, Candida albicans, T. schoenleini, or Aspergillus spp. are found. Other species of dermatophytes invade the nails uncommonly with the possible exception of T. violaceum in the Far Eastern nations. Trichosporon beigelii (T. cutaneum) has been a rare finding in infected nails. Scrapings for direct KOH examination or culture of the nails are taken from the subungual keratinized debris and not from the nail surface.

Orf SYN: ecthyma

contagiosum,

scabby

mouth

The etiologic agent is a DNA virus of the poxvirus group, which can be readily isolated on chick chorioallantoic membrane or cell cultures. Electron microscopy reveals cigar-shaped viral particles. Complement fixation and neutralizing antibodies tests are of diagnostic and epidemiologic value. There is a four-fold rise in titer between acute and convalescent sera of patients.

Osteodystrophy, Albright’s Hereditary SYN: pseudohypoparathyroidism, pseudohypoparathyroidism

pseudo-

Serum calcium is decreased and serum phosphorus increased in pseudohypoparathyroidism. Normal findings occur in those with pseudopseudohypoparathyroidism. Individual cases vary back and forth between these two variants from day to day. Those with low serum calcium have a high concentration of circulating parathyroid hormone. Infusion of parathyroid extract, 200 units, fails to elicit normal phosphorus diuresis (Ellsworth-Howard test). Likewise, in controls, parathyroid hormone causes the rapid excretion of cyclic adenosine 3’,5’-monophosphate (3’,5’-AMP), but a flat response occurs in those with Albright’s hereditaryosteodystrophy. Additional findings include hypocalciuria. Some patients have hypothyroidism and both diabetes mellitus and diabetes insipidus.

Otitis Externa Oriental Sore (see also Leishmaniasis) SYN: Delhi boil, aleppo boil Leishmania tropica may be visualized in Wright’s_stained smears prepared from curettings of the sides or the bases of the ulcers.

Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, coliforms, Streptococcus pyogenes, and Corynebacterium diphtheriae are found in descending order of frequency. Among fungi and yeasts, Aspergillus niger and Candida albicans occur most often.

56

Butterworth

and Cawiey

PLATE 3. Metabolic

Clinics In Dermatology

Disorders

FIG. 1. Angiokeratoma corpons dlffusum (Fabry’s disease) rn a 33-year-old woman (above, left). In this hereditary disorder, the enzymatic deficiency can be demonstrated in the patlent’s leukocytes and serum Glycolipids are deposited in various tissues, mainly kidney, as in the photomicrograph (above, right) showmg foamy cells In a glomerulus (see p. 7). FIG. 2. (left, top). Hemochromatosls, a disorder of iron metabolism, is characterized by excess deposetion of iron In tissues, especially liver, pancreas, and skin-resulting in “bronze”skin. The only definite test is liver biopsy (see p 33) FIG. 3. (left, middle). Porphyria cutanea tarda, a chronic form of a hepatic porphyrin-metabolism dlsorder, IS characterized by skin fragility, particularly in light-exposed areas (see p. 64). FIG. 4. (left, bottom). Lipodystrophy is an intense hyperlipemia that usually precedes diabetes mellitus (see p. 1). FIG. 5. (below). Test for alkaptonuna (p. 4): Tubes (left to right)-fresh urine, after 24 h, fresh + KOH, fresh + AgNO,, fresh urine layered in Benedict’s reagent in the cold, fresh urine boiled with Benedict’s reagent

July-September Volume 4 Number 3

1986

Cutaneous Diseases

57

PLATE 4. Bullous Conditions

FIG. 1. Erythema multiforme bullosum has varying causes and grades of severity. Because of many associations, laboratory findings show no consistent pattern (see p. 24).

FIG. 2. Epidermolysis bullosa is genetically transmitted. In the dominant form of epidermolysis bullosa dystrophica, scarring following healing may be associated with loss of nails. Laboratory findings show various biochemical defects, depending on type of disease (see p. 23).

FIG. 3. In bullous pemphigoid, blisters are tense (left) and there is separation at the dermoepidermal Direct immunofluorescence (right) shows linear C3 along the basement membrane (see o. 59).

FIG. 4. Blisters are subepidermal (below) in chronic bullous dermatosis of cf rildhood (rig/V). IgA anti-basement membrane antibodies are fat lnd in indirect immunofluorescence (see p. 20).

,

junction.

Cllnlcs

58

I”

Butterworth and Cowley

P

protein and collagen synthesis by the involved gingival fibroblasts when compared with controlled gingiva.

Pachydermoperiostosis SYN: Touraine-Solente-Go16

Syndrome

No pathognomonic abnormalities have been demonstrated in the blood or urine. Disturbances in the basal metabolic rate: increased urinary gonadotropin, estrogen. or aldosterone excretion; decreased serum sodium: or increased capillary lactic acid has been noted in a few patients. Severe anemia and IgG paraproteinemia have been rare findings.

Panniculitis Panniculitis,

Cold

There are no significant laboratory findings, as a rule, although the presence of cryofibrinogen has been reported. Qualitative abnormality of the platelets and excessive fibrolytic activity have been found. Panniculitis, Relapsing Febrile Nodular Nonsuppurative

SYN: Weber-Christian

disease

Panniculitis, Subacute Nodular Migrating There are no consistent laboratory findings. About half the patients show an elevated erythrocyte sedimentation rate, positive test result for rheumatoid factor, and an increased antistreptolysin 0 titer. Occasionally, al-globulin is slightly increased and Bglobulin slightly decreased.

Papillon-Lefevre Syndrome is greater

than twofold elevation

Papulosis Papulosis Atrophicans

Maligna

SYN: Degos disease (see also Granulomatous Vasculitides), cutaneointestinal syndrome The changes are those of most inflammatory disorders and include a decreased serum albumin level. and increased serum globulin and cuz-macroglobulin levels. Immunoglobulins are elevated, with the IgA fraction being the most consistently increased. Many patients have an increased level of plasma fibrinogen. Those with neurologic symptoms have markedly elevated cerebrospinal fluid protein. Papulosis, Lymphomatoid No consistent have been found.

laboratory

abnormalities

Paracoccidioidomycosis SYK: Blastomycosis, South American

The white blood cell count may be within normal limits or there may be a leukopenia. Sometimes there is a mild anemia. Involvement of the bone marrow may result in pancytopenia. The erythrocyte sedimentation rate is elevated during febrile periods. Diabetes and nephritis are frequent associated findings. Marked cui-antitrypsin deficiency has been reported in a few cases.

There

Dermatology

of

Pnrucoccidioides brasiliensis is the causative species of this disease. These organisms are found in curettings from the mucous membrane lesions. Pus may be aspirated from the enlarged lymph nodes for microscopic examination and culture. A fluorescent stain is available. There is reversal of the A/G ratio, with an increase in NI-, LYP,and y-globulins. Serum levels of IgG, IgM, IgM-specific, IgE, and IgE-specific antibodies are elevated. C-reactive protein is positive in 95% of patients with active lesions. Plasmacytosis is an additional sign of humoral immunity. Various serologic tests to reveal the presence of antibody include complement fixation, precipitin, immunoelectrophoresis, immunofluorescence, and immunodiffusion. The result of the precipitin test is the first to become positive after the onset of infection and the first to appear negative following successful treatment. Intradermal test results are positive in

July-September

Volume 4 Number 3

1986

Cutaneous Diseases

about two thirds

of less severe cases, but in more serious cases, the test, as a rule, is negative, Cross-reactions with histoplasmin are expected.

Parapsoriasis There are no distinctive findings.

clinical

pathologic

Paronychia Staphylococcus aureus may be cultured from most cases of acute paronychia. On the other hand, Candida albicans can be found in over 95% of cases of chronic paronychia. In addition, other species of Candida, Streptococcus pyogenes, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Blastomyces spp., and other oranisms may be found singly or in combination in the chronic group of cases. In some patients, C. albicans may be found in stool cultures. Recently, there has been a greater awareness of paronychia due to herpes simplex virus infection. In long-standing cases, the possibility of syphilis must be considered. Paronychia is more common among persons with diabetes.

Pellagra Blood studies may reveal hypoproteinemia and anemia, which may be microcytic or macrocytic depending on the predominant associated deficiency. Patients with pellagra have higher levels of serotonin in the serum and 5-hydroxyindoleacetic acid in the urine than do normal controls.

Pemphigold In all types of pemphigold, direct immunofluorescence reveals the linear deposition of IgG and/or C3 at the basement membrane zone (BMZ). In ‘70-80% of cases of bullous pemphigold, but rarely in cicatricial pemphigold, there are circulating IgG autoantibodies to the BMZ, demonstrable by indirect immunofluorescence. Those who lack such antibodies frequently show high titers

59

of circulating immune complexes and possibly Clq and C4. There have been frequent reports of elevated IgE levels and eosinophilia. Adultonset diabetes is a frequent complication. Circulating autoantibodies directed against thyroid elements and gastric parietal cells have been reported.

Pemphigus Included in this group are pemphigus erythematosus (Senear-Usher syndrome), pemphigus foliaceus, pemphigus vegetans, and pemphigus vulgaris. The Tzanck test demonstrates acantholytic cells in all types of pemphigus. Leukocytosis is present, often with eosinophilia. Secondary anemia is a constant finding. The erythrocyte sedimentation rate is increased in advanced cases. The amounts of sodium chloride and calcium in blood serum are often considerably reduced, while the amount of potassium may be increased. Liver function test results are abnormal in many patients. Serum albumin and prealbumin levels are low. Owing to a great loss of albumin, the total protein in the blood serum may be decreased to half the normal value. The amounts of a-globulins are increased considerably, but transferrin is decreased; y-globulin tends to increase slowly as the disease progresses. Electrophoretic analysis of blister fluid reveals a pattern resembling that of blood serum in all cases and indicates that all fractions of protein are lost. The globulins, however, are regenerated in adequate amounts. Upon indirect immunofluorescence, the sera from patients with all types of pemphigus show circulating IgG antibodies against intercellular substance of stratified squamous epithelium (ICS antibodies). Antibodies are found in all four IgG subclasses and rarely in the IgA and IgM classes. In addition, in all types of pemphigus, direct immunofluorescence demonstrates in viva bound immunoglobulins (predominantly IgG), complement components (Cl, C4, C3), factor B, and, to a lesser extent, proper-

Clmics

din at the epithelial spaces. Pemphigus erythematosus (Senear-Usher syndrome) differs, however, in that direct immunofluorescence demonstrates the presence of a basement membrane zone (BMZ) IgG band in addition to the ICS pattern. Antinuclear antibodies and positive rheumatoid factor may also be found in pemphigus erythematosus. Elevated serum copper and antistreptolysin titers have been reported in some cases of Brazilian pemphigus foliaceus. Pemphigus, SYN:

I” Dermatology

Butterworth and Cawley

60

Familial Benign Chronic

Hailey-Hailey

disease

The organism most consistently cultured from the lesions has been Staphylococcus aureus, although other organisms such as streptococci, Staphylococcus epidermidis, and Candida albicans are occasionally cultured alone or in association with S. aureus. Cytologic examination may reveal the presence of corps ronds and grain cells.

Periadenitis fvlucosa Necrotica Recurrens Hyperchlorhydria has been noted. Secondary infection with Vincent’s organisms and other bacteria occurs frequently. Some authors consider this to be the same disease as cyclic neutropenia.

Periarteritis Nodosa

nodosa is associated with asthma, eosinophil counts as high as 70% may be found. Eosinophilic hyperplasia occurs in the bone marrow of such patients. Characteristically, there is hypoalbuminemia and an increase in (YZ-and r-globulin. A frequent association with generalized elevation of immunoglobulins has been noted. Elevated IgE has been reported in infantile cases. Macroglobulins and cryoglobulins have been found. Urinalysis reveals the presence of protein and red and white blood cells. Blood urea nitrogen increases, and uremia is frequent. In some cases, the cerebrospinal fluid shows increased protein and a high cell count composed principally of lymphocytes. A third or more of the patients have chronic hepatitis B antigenemia(HBsAg), also called Australian antigenemia. Many show circulating immune complexes composed of HBsAg and immunoglobulin. The ANA test result is positive in 20-25% of cases.

Perifolliculitis Abscedens et Suffodiens SYN:

dissecting

cellulitis

Unopened abscesses are frequently found to be sterile. More commonly, cultures show Staphylococcus aureus, p-hemolytic streptococci. or Staphylococcus epidermidis. Usually the A/G ratio is reversed and the erythrocyte sedimentation rate is increased.

SYN: polyarteritis nodosa (see also Granulomatous Vasculitides and HBV Syndromes)

Periarteritis nodosa is included by some among the collagen diseases; by others, it is placed in the group of granulomatous vasculitides. Almost all patients show an elevated erythrocyte sedimentation rate. A high percentage exhibit anemia. Increased rouleaux formation is a common finding. In more than half the eases, leukocyte counts are in excess of 10,000 cells, with polymorphonuclear cells up to 80%. In some cases, there are leukemoid reactions with white blood cell counts of up to 50,000/~1. Eosinophilia of 5%or more is noted in a third of the cases. When periarteritis

of the scalp

Periporitis The causative agulase-positive

organisms are usually staphylococci.

co-

Perleche SYN:

angular

cheilitis

Candida albicans, staphylococci, and streptococci are found in cultures of the lesions.

Perniotic Syndrome The laboratory and monocytosis.

findings

are neutropenia

July-September 1986 Volume 4 Number 3

Cutaneous

Peutz-Jeghers Syndrome For years, the only laboratory findings may be blood in the stools and hypochromic anemia.

Phaeosporotrichosis Phialophora dermatitidis (gougerotii) may be demonstrated in KOH preparations and cultures from an abscess. This organism is now classified as Exophiliajeanselmei.

Phenylketonuria SYN: phenylpyruvic

oligophrenia

Phenylketones may be detected in the acidfied urine by the development of a deep bluish-green color upon the addition of fresh 10% ferric chloride solution or by the use of Phenistix (Ames Company, Elkhart, IN), but these tests are not specific. Chromatographic examination of the urine reveals the presence of ketoacids, amino acids, and indole derivatives. Elevated levels of plasma phenylalanine may be determined by the Guthrie blood inhibition assay procedure, the La Du spectrophotometric method, or the McCamanRobins fluorometric test. Phenylalanine tolerance is low. Persons with phenylketonuria excrete considerably less serotonin and tryptamine and somewhat less normetanephrine and p-tyramine than normal children.

Phrynoderma Vitamin A blood levels below normal.

are significantly

Phycomycosis SYN: mucormycosis

Various fungi belonging to the class Phycomycetes may be cultured from fragments of infected subcutaneous tissue planted in Sabouraud’s medium or blood agar. Basidiobolus haptospwus has been a common finding in Asia and Africa in subcutaneous phycomycosis. Authors differ on the occurrence of leu-

61

Diseases

kocytosis, eosinophilia, and an increased erythrocyte sedimentation rate. Phycomycosis occurs in patients with a variety of debilitating diseases such as diabetes, leukemia, lymphoma, and uremia. It is also found in patients taking corticosteroids, cytotoxic agents, or immunosuppressive therapy. Species of Mucor, Rhixopus, and Absidia are found.

Piedra Piedraia hortai (black piedra) or Trichosporon cutaneum (beigelii) (white piedra) may be found by direct examination or culture of an infected hair.

Pinta SYN: ma1 de1 pinto

Treponema carateum is demonstrable from all active dyschromic lesions of pinta by abrading the epidermis and examining the serum thus obtained. The organism may also be found in draining lymph nodes and occasionally in the sweat. Results of serologic tests for syphilis in current use are positive in 70% of primary cases, in 100% of those with generalized lesions, and in 90% of patients in the late stage of the disease. All test results are universally negative with cerebrospinal fluid.

Pityriasis Pityriasis Lichenoides et Varioliformis Acuta SYN: Mucha-Habermann

disease

IgM and C3 are found along the dermalepidermal junction. Vascular and perivascular deposits of IgM, C3, and fibrin increase with the age of the lesions. Most of the infiltrating are T lymphocytes, with a predominance of cytotoxic/suppressor phenotypes. Most eases show a reduction of the ratio of circulating helper T lymphocytes to suppressor phenotypes.

Pityriasis Rosea Although

the laboratory

is seldom

asked

Clinics

Buttetworth and Cawiey

62

for assistance in the diagnosis of pityriasis rosea, one group of 50 patients showed a statistically significant decrease in red blood cells and thrombocytes. increase in monocytes. elevation of the erythrocyte sedimentation rate, rise in total protein, reduction in bleeding time, and shift to the left in the white blood cell picture. Other studies have shown a decrease in lymphocyte T suppressor cells, an increase in helper cells, and increased natural killer function of T cells. Pityriasis Rubra Pilaris Serum vitamin A and carotene levels ma>beeither normal or low. Similarly. theserum vitamin A tolerance test results may be quite variable, sometimes showing a flattened curve and sometimes a normal one. Results of dark adaptation tests have been found abnormal in some patients. An increase of -,+globulin has been reported. Recently, a group of investigators found a significant decrease in serum retinal-binding protein in 11 patients with pityriasis rubra pilaris.

Plague SYN: bubonic

plague

Ywsiniu (Pastpurellu)lJ~stis may be found in smears and cultures of aspirates of the bubo or from blood, sputum, or cerebrospinal fluid. Immunofluorescence allows rapid identification. A guinea pig also produces buboes when scarified with infected material. An early leukopenia may be followed by leukocytosis.

Plummer-Vinson Syndrome SYN: Patterson-Kelly

syndrome

An iron-deficiency anemia is the rule in almost all patients. Many show varying degreesof anisocytosis, poikilocytosis, and hypochromia. There is no demonstrable leukopenia. Achlorhydria is a frequent finding.

Poikiloderma Poikiloderma, Acrokeratotic

Hereditary

Almost all patients have elevated levels of Ig(;. A few have positive test results for rheumatoid factor. Poikiloderma Atrophicans

Vasculare

Results of routine laboratory studies are usually normal. Some of these patients die of lgmphoma.

Polychondritis, Relapsing There are no laboratory findings specifically diagnostic of relapsing polychondritis. Many abnormalities may be noted: in descending order of frequency, these include elevated erythrocyte sedimentation rate, anemia, serum protein abnormalities (hypoalbuminemia, hyperglobulinemia), leukocytosis. hyperglycemia, albuminuria, presence of rheumatoid factor, eosinophilia. elevated antistreptolysin 0 titer. reactive serologic tests for syphilis, and positive LE prep. Urinary acid mucopolysaccharides have been significantly increased during acute flares in some patients. Circulating antibodies to Type II collagen have been detected.

Polycythemia Vera Men show a hematocrit of 55% or greater, hemoglobin of 18.0 gor more, and a red blood cell count in excess of 7.0 million. In women one finds a hematocrit of 52% or over. a hemoglobin of 17.0 gor more, and a red blood cell count exceeding 6.5 million. The white blood cell count is greater than 10,000 in more than half the cases, frequently over 25,000, and rarely as high as 50,000. There is a shift to the left in the leukocyte differential. Thrombocytes number 400,000 and more. The total blood volume is two to three times normal, while the viscosity of the blood ranges from five to eight times normal. More than a third of the patients have plasma uric acid concentration in excess of

July-September Volume 4 Number 3

1986

Cutaneous Diseases

6.0 mg/dl. Leukocyte alkaline also high. The bone marrow hypercellular.

phosphatase is is found to be

Polymorphous Light Eruption There is an increase in T lymphocytes in peripheral blood and affected skin. Some authors have found a preponderance of T helper cells, while others have found the T suppressor/cytotoxic cells increased.

Pork Tapeworm Infection Diagnosis is made by finding the ova of Taenia sol&m in the stools by direct smear or concentration methods. The blood picture at first shows a leukocytosis with moderate eosinophilia; later there is slight neutropenia with monocytosis and, at times, a secondary anemia.

Porphyria Since the metabolic defects of heme synthesis can be traced to the erythroid cells in the marrow or to the liver or both, the porphyrias may be divided (Fig. l-l, Table l-3) into three erythroipoietic types and four hepatic varieties. Erythropoietic

Porphyria (EP)

SYN: congenital

photosensitive

Gunther’s

porphyria,

disease

Evidence points to a deficiency of uroporphyrinogen III cosynthetase. In addition, there may possibly be increased aminolevulinic acid synthetase activity. Decreased activity of uroporphyrinogen cosynthetase may be found in the red blood cells of asymptomatic carriers as well as in persons affected with the disease. Excessive uroporphyrin and coproporphyrin formation occurs in the developing red blood cells of the bone marrow. The latter shows marked normoblastic hyperplasia. Large quantities of uroporphyrin I and increased amounts of coproporphyrin I are found in the circulating erythrocytes and eliminated in the stools and urine. The latter is red or pink and fluoresces under the

63

Wood’s light. Lesser, but highly significant, amounts of the porphyrins may be demonstrated in the plasma. A small fraction of the uroporphyrin and coproporphyrin is also excreted as the III isomers. Elimination of porphobilinogen is not altered. Hemolytic anemia is a usual finding. Nucleated red cells, reticulocytes, hypochromia, polychromasia, poikilocytosis, anisocytosis, and targeting are frequent findings in the peripheral blood. Spectrofluorometric examination of the bone marrow and the circulating blood reveals fluorescent normoblasts. Thrombocytopenia may also occur. Erythropoietic

Protoporphyria

SYN:erythrohepatic

(EPP)

protoporphyria

Heme synthetase (ferrochelatase) has reduced activity in the bone marrow, reticulocytes, liver, and cultured fibroblasts of patients with protoporphyria. Fibroblasts of asymptomatic or mildly involved parents may also have deficient heme synthetase activity. Excessively high levels of protoporphyrin are found in the red blood cells, plasma, liver, and feces. In some, the coproporphyrin levels may also be elevated. Asymptomatic parents may have an increase of either red blood cell or fecal protoporphyrin levels. In patients and their relatives, the red blood cells and bone marrow frequently fluoresce under Wood’s light. Abnormal in vitro red blood cell photohemolysis may be used as a diagnostic aid. The urinary porphyrins are consistently normal. Hemolytic anemia has been reported rarely; however, mild anemia is common. Slight thrombocytopenia is found in some patients. Direct immunofluorescence has shown deposits of IgG in and around the blood vessels in the papillary dermis. In addition, IgG and IgM may be present at the dermoepidermal junction. Erythropoietic

Coproporphyria

(EC)

This abnormality closely resembles erythropoietic protoporphyriaclinically, but differs in the laboratory findings. In addition to

Clinics in

64

Butterworth

glycine

and Cawley

+ succmyl

ir-amlnolevulinic

Dermatology

CoA

I

acid synthetase

4 S-amlnolevuline

acrd

I 6-amlnolevulinic’acld

dehydrase

1 4-porphobtlinogen uroporphyrinogen

/

I synthetase (JAIP)

\

I synthetase (IAIP)

uropolphyrinogen

\ uroporphynnogen

III cosynthetase (IEP) (i PCT)

/ uroporphyrinogen Uroporphyrinogen decarboxylase c coproporphyrinogen

\ uroporphyrinogen

I I (I PCT)

I

Ill

I

uroporphyrinogen decarboxylase

III (IPCT)

1 coproporphyrinogen

I

coproporhyrinogen oxidase

III III (?EC) (IHC)

i protoporphyrin

IX

I ferrochelatase (IEPP)

1

(IEC)

FIG. 1. Blosynthetlc pathway of porphyrins and heme. In prlnclple. the dImInIshed actlvlty of an enzyme leads to the accumulation and elimtnatlon of the preceding element in the chain. The disease produced IS shown in parentheses opposite the deficient enzyme. Possibly due to a failure of a feedback mechanism, amlnolevulinlc acid synthetase activity is increased in EP, AIP, and PV and suspected In others. Not shown IS the Inhibiting effect of iron on uroprophyrlnogen cosynthetase and uroporphynnogen decarboxylase. EP = erythropoietic porphyria; EPP = erythroprotoporphyria, EC = erythropoietic coproporphyria; PCT = porphyria cutanea tarda; AIP = acute Intermittent porphyria varlegata: and HC = hereditary coproporphyria. Reprinted with permisston from Butterworth T, Ladda RL Clinical genodermatology. New York: Praeger Scientific, 1981.

a small increase in protoporphyrin, the erythrocytes of patients with erythropoietic coproporphyria contain very large amounts of coproporphyrin and lesser amounts of uroporphyrin. Since the red blood cells of some patients with erythropoietic protoporphyria have an increased amount of copropor-

phyrin, the biochemical quantitative.

difference

may be

Porphyria Cutanea Tarda (PCT) SYN: chronic

porphyria

The enzymatic

fault

is decreased

uropor-

July-September Volume 4 Number 3

TABLE

l-3.

1986

Cutaneous

Diseases

65

Chemical Manifestations 01 the Porphyrias Urine

Stool

mg/day

Normal

pg/g dry weight

rg/day

ALA

PEG

Red Blood Cells

URO

COPRO

URO COPRO

pg/lOO ml

PROTO

COPRO

PROTO <60

<4

<3

<60

<300

<4

<33


<2

Erythropoietic

porphyria

N

N

+++

++

++

+++

N

++

i-

Erythropoietic

protoporphyria

N

N

N

N

N

i

++

-t

+++

Erythropoietic

coproporphyria

N

N

N

N

N

N

+

++

++

N

N

+++

+

N

+++

+

N

N

++

++

+

F

N

N

N

N

N

++

++

++

+

N

+++

+

N

N

++

++

N

++

N

+++

*

N

N

Porphyria

cutanea tarda

Acute intermittent Porphyria Hereditary

porphyria

variegata coproporphyria

N = normal. ALA = aminolevulinic

acid.

PBG = porphobillinogen. URO = uroporphyrin. COPRO = coproporphyrin. PROTO = protoporphyrin. From Butterworth T, Ladda RL. Clinical genodermatology.

phyrinogen decarboxylase activity in the liver tissue and erythrocytes. The gastrointestinal tract absorption of significantly increased amounts of ferrous iron is a possible second genetic defect in porphyria cutanea tarda. Ferrous ions aggravate the problem by inhibiting the activity of uroporphyrinogen III cosynthetase that converts porphobilinogen to uroporphyrinogen III. During periods of activity of the disease, the urine may be red or may fluoresce under the Wood’s light. Abnormal increased amounts of uroporphyrin and coproporphyrin are excreted in the urine, but porphobilinogen is not changed. Protoporphyrin and coproporphyrin are increased in the stools even in the absence of cutaneous manifestations. During exacerbations, the urinary excretion rises at the expense of the fecal. Liver porphyrins are greatly elevated. The red blood cell porphyrins are not increased except for negligible amounts of uroporphyrin absorbed from the plasma. Corresponding to the degree of liver disturbance, there may be hypoalbuminemia, high r-globulin, IgM, ceruloplasmin, and ALT, and a positive rheumatoid factor. Diabetes mellitus, hemochromatosis (espe-

New York: Praeger Publishers,

1981.

cially in the male), and polycythemia are frequent associated findings. High hemoglobin levels, packed cell volumes greater than 50%, and extremely high serum iron levels with marked transferrin saturation are reported commonly. Exceptionally, a refractory anemia has been found. Direct immunofluorescence has shown deposits of IgG in and around the blood vessels in the papillary dermis. In addition, IgG and IgM may be present at the dermoepidermal junction. Acute Intermittent Porphyria (Alp) SYN: Swedish porphyria, acute toxic porphyria

pyrroloporphyria,

A deficiency of uroporphyrinogen synthetase inhibits the conversion of porphobilinogen to uroporphyrinogen. As a result, there is excessive accumulation of aminolevulinic acid and porphobilinogen in the urine. The urine is usually colorless when voided, but upon standing it becomes oxidized and assumes the wine red color associated with porphyria. The marked deficiency of the uroporphyrinogen synthesase activity can easily be detected in cultured skin fibro-

Buttetworth

66

blasts. In addition, hepatic aminolevulinic acid synthetase activity is increased in these patients. thus aggravating t,he problem. A glycine loading test has been reported useful In diagnosing acute intermittent porphyria in remission but not for detecting genetic carriers of the disease trait. Hyperbetalipoproteinemia has also been found in this disorder of porphyrin metabolism. Porphyria

Variegata

SYN: mixed porphyria, porphyria

Pott’s Puffy Tumor Osteomyelitis of the skull is most often caused by Sfaphylococclrs arrrr~ts. Leukocytosis may or may not be present and, in more than 50% of reported cases, the erythrocyte sedimentation rate is normal.

Progeria SY~: Hutchinson-Gilford

(PV) South Africa genetic

Increased levels of hepatic aminolevulinic acid synthetase have been demonstrated. The stools show an increased content of coproporphyrin and protoporphyrin even when the patient is asymptomatic. For this reason, a diagnosis can be established in the absence of clinical manifestations by quantitative fecal porphyrin determination. During the acute stage, the urine contains large amounts of &aminolevulinic acid, porphobilinogen, uroporphyrin, and coproporphyrin. In the quiescent phase, the urinary findings may be normal. Direct immunofluorescence has shown deposits of IgG in and around the blood vessels in the papillary dermis. In addition, IgG and IgM may be present at the dermoepidermal junction. Hereditary Coproporphyria

Clinics I” Dermatology

and Cawley

(HC)

Reduced coproporphyrinogen oxidase activity is the apparent primary defect in patients with hereditary coproporphyria. There may also be greater activity of hepatic 6aminolevulinic acid synthetase. Increased amounts of aminolevulinic acid, porphobilinogen, and coproporphyria are found in the urine at all times but in much greater quantities during the acute attacks. In some patients, urinary uroporphyrin may also be elevated during the active manifestations. Likewise, fecal coproporphyrin is increased, most markedly during the acute phases. Fecal protoporphyrin levels may be normal or raised slightly. The erythrocyte porphyrin levels remain normal.

syndrome

Laboratory findings are inconstant. Glucose tolerance test results have been mildly to moderately abnormal. Plasma cholesterol and lipoprotein patterns have likewise been reported as normal or slightly elevated in some patients. Blood amino acids may be below normal, and a generalized aminoaciduria has been seen in a few individuals. A mild eosinophilia may be noticed. Endocrine studies show no pituitary or multiglandular dysfunction. No chromosomal abnormalities have been found.

Prolidase Deficiency Massive amounts of iminodipeptides are excreted in the urine. There is a high urinary excretion of proline in relation to that of hydroxyproline. A deficiency of prolidase is found in the erythrocytes, leukocytes, and fibroblasts cultured from these patients. Intermediate enzyme activity is found in carriers. Anemia, thrombocytopenia, and elevated y-globulin are found frequently. The chronic leg ulcers may yield Pseudomonas aerugiHO,S(T.

Proteinosis, Lipoid SYX: Urbach-Wiethedisease, hyalinosiscutis et mucosae, lipoidosis cutis et mucosae The results of the usual laboratory studies of the blood and urine are normal. There are no consistent abnormalities of the serum lipids or proteins. Reports have indicated an increase in (~2and y-globulins with a relative decrease in albumin. There may be considerable elevation of total lipoproteins as well as S O-10 and S 20-80 lipoproteins. Slightly elevated serum cholesterol, total serum lip-

July-September 1986 Volume 4 Number 3

Cutaneous Diseases

67

ids, and triglycerides are sometimes found. Serum lipid phosphorus may also be increased. Some authors describe a “diabetic tendency” in the patient and a family history of diabetes mellitus.

pruritus has been related to the existence of blood iron deficiency. Hypothyroidism and hyperthyroidism are extremely rare causes of general pruritus.

Protothecosis

Liver function tests are helpful only in severe cases. Serum bilirubin may be normal or slightly increased. Serum alkaline phosphatase, 5’-nucleotidase and y-glutamyltranspeptidase levels may be elevated above those of normal pregnancy, but serum aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and serum alanine aminotransferase (ALT) remain normal or only very slightly raised. Prothrombin time may be lengthened in very severe cases with vitamin K malabsorption and complete absence of bile flow.

Cultures of this algal infection taken from exudate of ulcers, skin, or regional lymph glands show Prototheca wickerhamii. Prototheca grows readily in Sabouraud’s agar. blood agar, or brain-heart infusion agar. Laboratory findings are insignificant in the localized cases, but in those with disseminated infection there are anemia, mild leukocytosis with eosinophilia, and elevated erythrocyte sedimentation rate. Also increased are serum bilirubin, alkaline phosphatase, AST, and IgG. Leukocyte motility is inhibited, and neutrophilic response to chemotactic stimulus is reduced.

Pruritus Pruritus, Anogenital Evidence of diabetes mellitus, gout, uremia, and polycythemia should be sought in the blood and urine. The ova of pinworms may be found in the perianal region by means of a cellophane tape or paraffin swab. Scrapings and cultures for fungi, bacteria, and yeasts are indicated. Search for ova, parasites, and yeasts in the stools. Lesions of erythrasma may fluoresce under the Wood’s light. A hanging-drop preparation of vaginal secretion may reveal Trichomonas vaginalis. Pruritus, General The blood should be examined for evidence of elevation of sugar, bilirubin, and urea nitrogen. Hematologic studies may establish polycythemia, leukemia, or lymphoma as the cause of the itching. Urinalysis may reveal sugar or evidence of diseases of the kidneys. A diagnosis of intestinal parasitosis may be made by finding ova or worms in the stool. In some reported series of cases, Entamoeba histolytica has played a prominent role. Sputum examination may explain the itching on the basis of pulmonary tuberculosis. General

Pruritus Gravidarum

Pseudolymphoma Syndrome SYN: phenytoin drome,

Dilantin

syndrome, syndrome

hydantoin

syn-

Leukocytosis is the rule with counts as high as 38,000 white blood cells. The differential count shows an eosinophilia in the 5-50% range, and atypical lymphocytes are common. Hemolytic anemia has been associated occasionally. ALT, lactic dehydrogenase, and alkaline phosphatase levels may be elevated. In those with associated nephritis, there are proteinuria, hematuria, polyuria, and azotemia. Abnormal electrophoretic patterns have been recorded.

Pseudoxanthoma Elasticum Other than histologic examination, there are currently no laboratory tests of value in the diagnosis of this condition. Increased serum a-globulin may be found. The disease may be associated with hypothyroidism, diabetes mellitus, diabetes insipidus, sickle cell anemia, and others.

Psittacosis SYN: ornithosis,

parrot

fever

Complement fixing antibodies the cause as Chlamydia psittaci.

establish A rise in

Clfnlcs r Dermatology

Butterworth and Cawley

68

antibody titer is diagnostic. The organism may be isolated by tissue culture or inoculation of titrated blood or sputum into mice. The leukocyte count is normal or subnormal; a definite leukopenia is present in only 25% of the patients. Leukocytosis occurs late in the disease or in early convalescence.

white blood cell count rises to a level of 25.000-40,000/~1, and the lymphocyte count drops from a normal level to an absolute lymphopenia. Hypoalbuminemia, hypocalcemia, and an elevated erythrocyte sedimentation rate are other consistent findings.

Purpura Psoriasis Many contradictions have been reported in the laboratory findings of this disorder. Results have varied from patient to patient and often with the severity of the disease process. Thus, some have reported serum uric acid to be elevated in about 50% of patients, while others state that hyperuricemia is insignificant in psoriasis. Serum cholesterol is raised in 20% of the patients. As many as a quarter of persons with severe psoriasis may have a positive prednisone glucose tolerance test result. Glucose-6-phosphate dehydrogenase (GGPD) is elevated in psoriasis, as well as in other skin diseases, and the level depends on the extent of the disease. In addition. the copper content of blood serum of patients with psoriasis is, on an average, significantly higher than that of control subjects. It appears likely that the increase is in the nonceruloplasmin copper. The neutrophils and monocytes of patients with psoriasis have enhanced chemotactic and phagocytic activities. Also found is a tendency to high (Y-,p-. and y-globulin and low albumin, prealbumin, and transferrin values. C-reactive protein may be positive. There is a significant increase of serum IgA. whereas IgG and IgM remain unchanged. Upon clearing, IgA levels return to normal. Direct immunofluorescence studies demonstrate the presence of IgG deposits within the stratum corneum, but its significance is not known. In psoriatic arthropathy, the serum rheumatoid factor is absent (negative RoseWaaler and latex fixation test results). Psoriasis, Pustular In pustular psoriasis, cultures are invariably sterile. At the onset of each flare, the

Purpura Cryoglobulinemica Abnormal serum proteins behaving as cryoglobulins may be IgG or IgM antibodies. This type of purpura is seen most frequently in multiple myeloma, less often in systemic lupus erythematosus and malignant lymphomas. Purpura Fulminans SYN:

purpura

gangrenosa

After a resolving infectious process, a consumptive coagulopathy develops, with low normal to severely reduced platelet counts, hypofibrinogenemia, hypoprothrombinemia, reduced Factor V and Factor VIII levels, and the activation of the fibrinolytic enzyme system. Leukocytosis with ashift to the left is common. An anticoagulant, antithrombin, also appears. Anemia and hematuria are additional findings. Purpura Hyperglobulinemica SYK: hyperglobulinemic striim

purpuraof

Walden-

Polyclonal hypergammaglobulinemia, as high as 4.0 g/dl, is a sine qua anon of this syndrome. Ultracentrifugel findings show proteins between 7s and 19s. Cryoglobulins may be slightly elevated in some patients. The albumin fraction is normal or slightly lowered, and the total protein is normal or high. Immunoglobulin quantitation reveals increases in IgG primarily, with lesser elevations of IgA and IgM. Fluorescent antibodies may be present. There is usually a mild normochromic, normocytic anemia. Slight leukopenia may be noted, but the platelet count is usually normal. The erythrocyte sedimentation rate is elevated. Results of bleeding and clotting

July-September Volume 4 Number 3

1986

Cutaneous

studies are within normal limits, but there is often evidence of increased capillary fragility. In an occasional case, hyperuricemia has been found. The rheumatoid factor is frequently positive. Bone marrow biopsy specimens are normal.

Purpura, Idiopathic Thrombocytopenic Bleeding occurs when the platelet count drops below 25,000. The coagulation time is normal, but the bleeding time is usually prolonged. Clot retraction is abnormal and capillary fragility is increased. The bone marrow shows an increased number of megakaryocytes.

Purpura Simplex, Hereditary Familial There is a positive result of the capillary fragility test, performed by inflating the sphygmomanometer cuff midway between diastolic and systolic arterial pressures and allowing it to remain for 8 minutes. Other hematologic test results are within normal limits.

Pustulosis, Sterile Eosinophilic Contents of the pustules are sterile, but smears reveal numerous eosinophils. Hematologic studies show leukocytosis with eosinophilia. Serum IgE is increased. No allergy to bacterial or fungal allergens can be demonstrated.

Diseases

69

Corynebacterium species, Proprionibacteriand viridans streptococci. Elevated erythrocyte sedimentation rate and mild anemia have also been reported. urn awes,

Pyoderma Gangrenosum Hemolytic Staphylococcus aureus is the most common cultural finding in the ulcers. Less often, Proteus vulgaris, Pseudomonas aeruginosa, or Hemophilus influenxae is recovered. Those patients having ulcerative colitis have a tendency to amass basophilic leukocytes in their cutaneous exudates. Other associated disorders are Crohn’s disease, paraproteinemia, arthritis, chronic hepatitis, polycythemia, leukemia, and diabetes mellitus. Both elevated and decreased levels of immunoglobulins have been reported. Occasionally a paraprotein is present. IgA has been reported most frequently; IgG or IgM, rarely. The erythrocyte sedimentation rate is often increased. Various cellular abnormalities have been reported, including altered leukocyte migration, defective neutrophil chemotaxis, random mobility, and phagocytosis. Decreased T-helper/inducer and increased T-suppressor/cytotoxic cells have recently been described. Failure of delayed hypersensitivity has been demonstrated in patients with pyoderma gangrenosum when challenged by PPD, Candida, mumps, or streptokinase-streptodornase antigens, and none of these patients could be sensitized to dinitrochlorobenzene.

Pyoderma Staphylococcus aureus and group A phemolytic streptococcus are most commonly found, but Corynebacterium diphtheriae or Pseudomonas aeruginosa may be recovered. C3 deficiency has been associated with increased susceptibility to pyogenic infections. A neutrophil chemotactic inhibitor has also been recorded in recurrent pyoderma.

Pyoderma Faciale Bacterial cultures recover a number of organisms singly or in combination, including Staphylococcus aureus, S. epidermidis,

Q Q Fever It is not advisable to attempt isolation of the causative organism, Coxiella burnetii by inoculation of animals, since this procedure frequently results in infection among the laboratory personnel. Diagnosis is made by rising titers in complement fixation and microscopic slide agglutination tests. The Weil-Felix reaction remains negative.

Clfnlcs in Dermatology

Butterworth and Cawley

70

The total vvhite blood cell and differential counts remain essentially normal, although the hematologic features in a few cases may suggest infectious mononucleosis. The erythrocyte sedimentation rate is moderately elevated. In the more severely affected patients. there may be reversal of the A,‘(; ratio, anemia, albuminuria, hematuria. and abnormal liver function test results.

a raised plasma fibrinogen concentration has been found in many patients. A high titer of (*old hemagglutinins may also be present in the patient’s serum. Paroxysmal hemoglobinuria is another occasional finding. It is frequently advisable to include serum electrophoresis, as well as cryoglobulinemic, macroglobulinemic. and LE tests to detect assoviated diseases. Deficiencies of complement caomponents are reported.

Refsum’s Disease

R Rat-Bite Fever The two forms are so similar clinically that differentiation is possible only by demonstration of the causative organism. Sodoku: Spiriiluvl mirrrls may be demonstrated in the serous fluid obtained from the site of the bite, from the exanthem. or from an enlarged lymph node. Darkfield examination of blood occasionally reveals typical organisms. Mice and guinea pigs inoculated intraperitoneally with titrated blood have organisms visible on darkfield examination of peritoneal fluid or blood. False-positive results of serologic tests for syphilis occur in about half the cases. There is moderate leukocytosis with eosinophilia. Albuminuria is common. Agglutination and complement fixation tests are not available. Haverhill Fever (erythema arthriticum epidemicum). Streptobacillus ~~oni/~~o~~is may be isolated from blood or from joint fluid. Mice inoculated with thisorganism die with polyarthritis. False-positive results of serologic tests for syphilis occur in a quarter of the cases. Anemia is present, and leukocytosis is higher than in the spirillary form. Agglutinins for S. moniliformis may usually be demonstrated after the second week. A complement fixation test is also available. For S. moniliformis, fluorescent antibody techniques are use:ful.

Raynaud’s Disease High viscosity

of the blood associated

with

Deficient u-oxidation of phytanic acid to pristanic acid results in accumulation of phytanic acid in the plasma, cerebrospinal fluid. and tissue. The cerebrospinal fluid shows albuminocytologic dissociation, with a normal cell count and a marked increase of protein.

Reiter’s Disease SYN:

keratosis

blennorrhagica

(see p. 41).

Reiter’s disease usually appears following a sexually transmitted disorder, in particular nongonococcal urethritis, with Chlamydia (Brdsonia) trachomatis suspected as the major incitant. Antichlamydia complement fixation antibodies are found in the sera. Recent tests to detect C. trachomatis, introduced commercially, include Abbott’s enzyme-linked immunoassay and Syva’s (Syntex, Mountain View. CA) fluorescein-labeled monoclonal antibody test. Mycoplasmas have also been implicated. Some cases have been reported to follow bacillary dysentery. There is mild to moderate leukocytosis and moderate normochromic normocytic anemia. The erythrocyte sedimentation rate is elevated. Serum albumin is decreased, but globulin is increased. Uric acid and nonprotein nitrogen are generally unchanged. Pyuria and hematuria are present. Prostatic and urethral secretions show abundant pus cells. Experimentally a specific antibody to a prostatic antigen has been detected in the serum of 15 out of 28 cases of Reiter’s disease. At times, there may be grossly bloody urine with a bacterial cystitis. Synovial fluid, aspirated from a joint, is yellowish turbid

July-September 1986 Volume 4 Number 3

Cutaneous

and clots on standing. The white blood cell count of the fluid varies from 5 to 50 times the normal and, initially, is composed mainly of polymorphonuclear cells and, subsequently, of lymphocytes. The consensus is that histocompatibility antigen HLA-B27 is present in about 90% of those with Reiter’s disease.

71

Diseases

Rhinosporidiosis Scrapings from the surface of the tumors show great numbers of large spores. The causative fungus, Rhinosporidium seeberi, has not been cultured or transmitted successfully to experimental animals.

Rickettsialpox Relapsing Fever One of the several species of spirochete of the genus Borrelia may be identified in a peripheral blood smear stained by the Wright’s or Giemsa technique. A monocytosis may be noted. In the louse-borne variety, over 30% of patients show a high titer of Proteus OX-K agglutinins, while the percentage and titers are considerably lower in the tickborne type. Jaundice and thrombocytopenia may be encountered.

Diagnosis is made by a specific complement fixation test with Rickettsia akari. The Weil-Felix test (Proteus agglutination), which becomes positive in patients with most rickettsial diseases, remains negative. Rickettsiae may be propagated by inoculating susceptible experimental animals or the developing chick embryo, but these are research laboratory methods. Leukopenia with relative lymphocytosis occurs early in the disease. The erythrocyte sedimentation rate may be slightly elevated.

Reticulohistiocytosis, Multicentric

Ritter’s Disease

SYN: lipoid dermatoarthritis

SE’N:exfoliative

Anemia and elevated erythrocyte sedimentation rate are the rule. Serum contains higher concentrations of total lipids, triglycerides, and free and esterified cholesterol and a lower concentration of phospholipids than normal serum. Serum electrophoresis reveals an increased proportion of p-lipoprotein. Rheumatoid factor and increased (Yglobulin are sometimes found.

The etiologic agent is Staphylococcus awreus group II, phage type 71. In most instances, the blood counts are within normal limits; but in some, there is leukocytosis with eosinophilia. Ritter’s disease is probably identical with the staphylococcal scalded skin syndrome.

The common laboratory findings are severe anemia, leukopenia, and thrombocytopenia. Abnormal histiocytes are found in the peripheral blood of some patients. Elevation of serum lysozyme is seen.

Rhinoscleroma SYN:

scleroma

Klebsiella rhinoscleromatis may be found in smears and cultures from the deeper recesses of the lesion. A complement fixation test is available but is not very reliable.

of the newborn

Rocky Mountain Spotted Fever SYN: exfoliative

Reticulosis, Histiocytic Medullary

dermatitis

dermatitis

of the newborn

The etiologic agent is Rickettsia rickettsii. The Weil-Felix reaction and the specific complement fixation test result become positive between the 10th and 15th day and are the most important diagnostic criteria. Antibodies appear to Proteus OX-19 or OX-2 but not to OX-K. The indirect fluorescent antibody method is a good screening test. Specific agglutination tests are of less practical value. Further confirmation of the diagnosis may be obtained by inoculation of guinea pigs or the developing chick embryo in research. The pathogen may be demonstrated by direct immunofluorescence in skin biopsy specimens.

Clfnics I” Dermatology

Butterworth and Cowley

72

Early in the disease, there may be leukopenia with a neutropenia. Eosinophils are decreased or absent. As the infection progresses, a leukocytosis of lZ,OOO-15.000;~1 develops, with an increase in the polymorphonuclear cells, which frequently show toxic granulation. The Schilling hemogram shifts to theleft. An increase in mononuclear cells is common. During the second week. a normochromic, normocytic anemiagenerally appears. Hemoglobin values of 9.0 g/d1 and red blood cell counts of 3,000,000/~1 are frequent. Occasionally there are hypofibrinogenemia. thrombocytopenia, and an elevated prothrombin time. Increased capillary fragility is usually demonstrable by the tourniquet test. As the disease progresses, the blood chlorides drop and nonprotein nitrogen rises. The urine is highly acid and slight albuminuria is present. Abnormal liver function test results may appear.

Rosacea Hypochlorhydria is a frequent finding. Serum alkaline phosphatase levels have been reported aselevated, particularly in patients with abnormal jejunal mucosa. Some authors have ascribed an etiologic role to Demodrr folliculorum found in sebaceous material.

Roseola lnfantum STN: exanthema

subitum

Coxsackie virus B5 is suspected to be the cause of this disease, although this is not proven. Early in its course, a transient granulccytosis may occur. Later, many patients develop agranulocytopenia with a mild leukopenia of 3,000-7,000 cells.

Rothmund-Thomson Syndrome SYN: poikiloderma

congenitale

The laboratory affords little help in the diagnosis of this syndrome. Urinary 17-ketosteroids and hydroxyketosteroids have been found to be low. In several patients, electrophoretic studies of blood serum showed an abnormal peak in the an-globulin fraction.

Aminoaciduria cases. . L

has been noted in one or a few

Rubinstein-Taybi Syndrome SYN: broad thumb-great

toe syndrome

Results of chromosome studies have been normal. Some patients have shown abnormal carbohydrate metabolism.

Rud’s Syndrome Macrocytic an associated

anemia finding.

has been reported

as

S Sarcoidosis The Kveim test consists of the intradermal injection of a 10% suspension of sarcoid tissue. The incidence of positive Kveim reactions is greatest in early cases of sarcoidosis, diminishes with chronicity, and becomes negative in a high percentage of inactive cases. The test yields a variable number of false-positive results and may fail to detect 20-25% of individuals with clinically and histologically apparent sarcoidosis. Its result may be negative in remission or during corticosteroid therapy. Cutaneous anergy is manifested by impaired delayed type of sensitivity with trichophytin, oidiomycin, tuberculin, and pertussis and mumps antigens. Defective neutrophil migration has been demonstrated. These individuals produce significantly higher titers of isoagglutinins in response to the intravenous administration of mismatched blood. False-positive results of tests for syphilis are sometimes seen. Serum proteins are high in at least half of those affected. Elevations occur in a~-, ,&, and y-globulins. Less frequently, there is a decrease in the albumin fraction. Elevation of serum IgG, IgM, and IgA commonly have been reported in sarcoidosis. IgD levels have been observed to be lower than normal. whereas IgE has been found to be both elevated and decreased.

July-September 1986 Volume 4 Number 3

Cutaneous

About two thirds of the patients show an elevated erythrocyte sedimentation rate. Mild anemia and leukopenia occur often. Eosinophilia and monocytosis have been reported in a number of cases. An increase in the relative number of B cells has also been demonstrated. The number of platelets may be increased or decreased in sarcoidosis. Sickle hemoglobin is significantly higher in Negro patients with sarcoidosis than in controls. Disturbed calcium metabolism is manifested by hypercalcemia, hyperealciuria, and low fecal calcium. Low levels of parathyroid hormone are found by radioimmunoassay in some patients. Hydroxyprolinemia and increased output of urinary hydroxyproline have been reported in active sarcoidosis. Hyperuricemia, elevated serum alkaline phosphatase, and increased creatine phosphokinase are found with kidney, liver, and muscle involvement, respectively. An elevated level of serum angiotensin I-converting enzyme occurs, but a similar finding in a number of other diseases makes it a questionable diagnostic aid.

Scabies This disease is produced by Sarcoptes scabiei, which occasionally can be found at the blind end of a burrow. IgA levels are decreased significantly during infestation. Conversely, comparable increases of IgG and IgM are found in serum of patients with scabies.

Staphylococcal Scalded Skin Syndrome (SSSS) SYN: staphylococcal epidermolytic toxin syndrome (see Ritter’s Disease, p. 71).

Staphylococcus aureus, group II, phage type 71, may be cultured from the skin, nasopharynx, vagina, and blood. Leukocytosis up to 28,000 may be found, but leukopenia and thrombocytopenia have been noted. The erythrocyte sedimentation rate iselevated. Various abnormalities in the serum proteins have been found by different authors.

Diseases

73

Scarlatina SYN:

scarlet

fever

Throat cultures yield a p-hemolytic Streptococcus, group A. There is leukocytosis of 12,000-30,000 cells, reaching its height about the fourth day. Polymorphonuclears range from 70 to 95%. After the fifth or sixth day, there is a rapid increase in eosinophils, which may reach lo-20%. Sometimes there is rapidly progressing anemia that lasts into convalescence. The Schultz-Charlton phenomenon is a diagnostic aid. The result of the Dick test, positive at the beginning, becomes negative in convalescence. The Rumpel-Leede test result is usually positive.

Schamberg’s Disease SYN:

progressive

Hyperlipidemia disorder.

pigmentary

dermatosis

has been observed

in this

Schistosomiasis Schistosomiasis, Cutaneous SYN:

swimmer’s

itch

This eruption is caused by nonhuman schistosomes of birds and mammals. Persons who have had swimmer’s itch develop an immediate wheal in response to the intradermal injection of cercarial antigens.

Schistosomiasis, Visceral SYN:

bilharziasis

The ova of the human blood flukes Schistosoma mansoni and S. japonicum may be found in the stools; the eggs of S. haematobium in the urine and stools of those affected. The fluorescent antibody tests are also of great diagnostic value. A good complement fixation test is available. Eosinophilia is common.

Schijnleln-Henoch Purpura SYN:

Henoch-Schonlein disease; allergic, phylactoid, or rheumatoid purpura In this purpura,

the organism

ana-

implicated

Butterworth

74

and

in one third to one half of all patients is /3hemolytic Str~ptococcr~s proved either by a rise in antistreptolysin 0 titer or by culture of the throat, or both. The Rumpel-Leede tourniquet test. complete blood count, and erythrocyte sedimentation rate are variable. Results of bleeding and clotting studies and platelet counts are normal. Microscopic hematuria and proteinuria occur in almost all patients: frank blood is noted in slightly less than half of them. Azotemia occurs occasionally. Melena may be found. Cryoglobulinemia is common in both acute SchBnlein-Henoch purpura and the chronic nephritis that may follow it. The alternative complement pathway appears to be activated in this condition. Finely granular deposits of IgA, C3, and C5 may be found in the walls of the superficial dermal capillaries. Elevated IgA circulating immune complexes have been reported.

Scleredema Adultorum SW: Buschke’s

disease

Routine laboratory studies are not very helpful. In many cases, all test results have been entirely normal; in others, elevated leukocyte counts, moderate anemia, and increased erythrocyte sedimentation rates seem to reflect the activity of the accompanying infections. Leukopenia, hyperglobulinemia, and abnormal electrophoretic patterns have been uncommon findings. Serum protein electrophoresis may show a monoclonal IgG paraprotein. Association with maturityonset diabetes has been frequent. especially in obese patients. A significant elevation of the antistreptolysin 0 titer occurs in the pediatric age group.

Sclerema Neonatorum There is an increased ratio of saturated to unsaturated fatty acids in the subcutaneous fat. The blood serum has markedly raised urea and potassium levels, while the COz content is frequently depressed.

Clinics In Dermatology

Cawlev

Scleroderma Scleroderma,

Diffuse Systemic

SYN: diffuse progressive sive systemic scleroderma

sclerosis, (PSS)

progres-

The serum proteins show low albumin and high W- and y-globulin with reversal of the A/G ratio. Some have shown increases in the ar-glycoproteins and lowering of the /? fraction. C-reactive protein may be positive. Immunologic features are varied. Approximately half the patients have polyclonal hypergammaglobulinemia. An increase in serum immunoglobulins IgG, IgM, or IgA alone or in combination has been noted, although a generalized elevation of immunoglobulins is not common. There is a high incidence of rheumatoid factor and antinuclear antibodies. The latter are mostly IgG and IgM types and often react with nucleoli. Antibody to Scl-70 antigen and antinucleolar antibody are highly specific for PSS. LE cells are rarely seen in the blood. Uncommon also are nDNA antibodies and low complement levels. Cryofibrinogen may be encountered. Antibodies to single-stranded RNA and to smooth muscle fibers have been reported frequently. Antibodies directed against interstitial (type I) and basement membrane (type IV) collagens in the sera of patients with PSS also have been observed. Circulating immune complexes are found in almost half of the patients. Anticentromere antibodies are found in most patients with the CREST syndrome (see p. 16). There is a decrease in circulating T cells. Results of delayed hypersensitivity, lymphocyte transformation with mitogens, and leukocyte migration inhibition studies are normal. Biologic false-positive results of tests for syphilis may also occur. Serum calcium is usually normal. The aminotransferases, most frequently the alanine (ALT) form, and the serum hexamine levels are usually increased. Significant hypercreatinemia is found. There is depression of serum carotene values in some cases. Abnormal results of liver function tests may also occur. A mild hypochromic anemia may be noted,

July-September Volume 4 Number 3

1986

Cutaneous

and the erythrocyte sedimentation rate is ordinarily increased. Eosinophiliaoccurs relatively frequently. The disease may be complicated by bone marrow aplasia and pancytopenia. Albuminuria is sometimes noted. A low urinary level of 17-ketosteroids is found in about half of the cases. Other findings include increased urinary glycosaminoglycan and reduced creatinine and hydroxyproline excretion. Immune complexes and complement deposition have been demonstrated in the glomeruli and intralobular arteries of the sclerodermatous kidney. In those with intestinal involvement, malabsorption may be proved by D-xylose absorption test and by quantitative measurement of fecal fat excretion. Bacterial proliferation in the upper small intestine is suggested by increased urinary excretion of the tryptophan metabolite, indican, and confirmed by culture of aspirated duodenal contents. The &hilling test demonstrates diminished absorption vitamin Blz. Evidence of chromosomal breakage has been found in cultured peripheral blood cells and fibroblasts and in vivo in the bone marrow of patients with scleroderma. Abnormal serum proteins and a high incidence of antinuclear factor occur among relatives.

Scleroderma, Localized SYN: morphea,

circumscribed

scleroderma

Immunologic features resemble those of diffuse systemic sclerosis. Thus, frequent findings are rheumatoid factor and antinuclear antibodies. Other laboratory observations include antibodies to ssDNA in the IgG or IgM fractions, low serum complement, and antibodies to smooth muscle fibers. Eosinophilia may be present. scurvy Ascorbic acid determinations on plasma, whole blood, and buffy coat have varying clinical significance. Analysis of the buffy coat is probably most informative. Several load tests are available based on the oral or intravenous administration of standard test

Diseases

75

doses of ascorbic acid with subsequent determinations of vitamin C content of the blood and urine. There is normocytic or slightly macrocytic normochromic anemia with high initial reticulocyte count, normal leukocyte and platelet count, and hyperbilirubinemia of the indirect-reacting type that is out of proportion to the amount of bleeding into the skin and viscera. The serum iron levels are normal or high. The Rumpel-Leede test demonstrates capillary fragility. Stool specimens may contain occult blood. In infants, alkaline phosphatase tends to be low, but this is not the case in adults even though they may develop osteoporosis. Bone marrow is usually normal or slightly hypercellular with a relative increase in normoblasts.

Serum Sickness Leukopenia, hypocomplementemia, and albuminuria are the characteristic laboratory findings.

Sbzary Syndrome (See also myocosis fungoides, p. 52) SYN:Sezary reticulosis syndrome, reticulemic erythroderma

malignant

This syndrome appears to be a malignant proliferation of helper T cells. Leukocytosis varies from 12,000 to as high as 142,000 cells. It is distinguished by the presence of the “S&zary cell,” an abnormal “monster” monocytic cell that may constitute 2-60% of the total white blood cell count. Polymorphonuclear leukocytes are decreased, while the eosinophils are increased in number. The lymphocyte count may be elevated or depressed. Platelets are generally normal. The red blood cells and hemoglobin are within normal limits or slightly lowered, especially late in the disease. The erythrocyte sedimentation rate is unchanged. Sternal puncture reveals a normal marrow. The A/G ratio tends to be 1 or lower. Monoclonal gammopathy has been reported in about a dozen cases.

Clrfcs r Dermatology

Butterworth and Cawley

76

Shulman’s Syndrome Eosinophilia and hypergammaglobulinemia are consistent findings. Some patients may show rheumatoid factor, antinuclear antibodies, and deposits of IgM along the dermal-epidermal junction in direct immunofluorescence.

Sialidosis In this disorder, there is a deficiency in neuraminidase, which results in the intracellular accumulation of sialilated oligosaccharides. There is frequently an associated reduction in the activity of p-galactosidase.

@Sitosterolemia SYN: phytosterolemia High concentrations of plant sterols, especially p-sitosterol and campesterol. are found in the plasma, red blood cells, xanthomas. adipose tissue, and skin. Most of the plant steroid in the plasma is carried in the lowdensity fraction.

Sjtigren-Lawson Syndrome There is pathologic urinary excretion of 3-hydroxykynurenine and of kynurenine after administration of tryptophan. An altered composition of polyunsaturated fatty acids in serum, due to a disturbance in the 16 desaturation of essential fatty acids, has been found.

protein and cryoglobulin are found in some patients. Results of many immunologic tests are positive. The most characteristic autoantibodies are SS-A and SS-B in both primary Sjijgren’s syndrome and cases associated with SLE. iiheumatoid factors are found commonly. Antinuclear factors are demonstrable by the indirect fluorescent antibody technique in two thirds of cases. Antibodies to nDNA occur in 25% of cases. Results of complement fixation tests with parotid tissue extracts and passive cutaneous anaphylaxis tests are positive in slightly less than half of patients. Thyroglobulin antibodies have been found in about 25%. Antibodies to parotid tissue have been reported often. Precipitating antibodies identified as r-globulins, and LE cells have been noted in a few instances. The Coombs’ test result has also been positive in some cases. Biologic false-positive results of tests for syphilis are not uncommon. A moderate persistent anemia and leukopenia are found commonly. There is relative eosinophilia. A few patients present thrombocytopenia. The erythrocyte sedimentation rate is elevated. A few cases show albuminuria and persistent microscopic hematuria. The urinary 17. ketosteroid values are consistently lowered. Diabetes mellitus and lymphomas may be associated findings.

Smallpox SYN: variola

Sjiigren’s Syndrome SYN: sicca syndrome The enzyme lysozyme is decreased in the tears, and its quantitive determination is probably the most sensitive test for the diagnosis of SjSgren’s syndrome. The total serum proteins may be elevated or decreased, but the A/G ratio is reversed. There are hypoalbuminemia and hyperglobulinemia, the major increase in the latter being in the 7-S factor. Frequently, there is a generalized elevation of the immunoglobulins of the three major classes. C-reactive

Electron microscopy can be used for rapid diagnosis and to differentiate the brickshaped smallpox virus from the smaller spherical virus of chickenpox. The virus may be demonstrated in stained smears of vesicular fluid. It may be grown successfully on chick embryo membrane, but it propagates poorly in the rabbit’s eye. Good viral neutralization and complement fixation tests are available. Complement fixation may be used for detection of antibodies in the serum early in the eruptive phase and for the serologic demonstration of viral antigen in material from cutaneous lesions.

July-September 1986 Volume 4 Number 3

Cutaneous

In the early stages of smallpox, there is leukopenia with a relative mononucleosis. Later, a leukocytosis develops and anemia usually occurs. Thrombocytopenia is commonly seen.

Sparganosis The sparganum larva of some species of the tapeworm Diphyllobothrium, subgenus Spiwmetra, may be expressed from the acneiform lesions.

Sporotrichoid Infections Cultures may show Mycobacterium nei, M. kansasii, or M. marinum.

chelo-

Sporothrix schenckii is difficult to demonstrate in direct smears of pus, but it may be cultured on Sabourauds’s medium. Pus may be injected intraperitoneally into male white rats, from which the fungus can later be demonstrated by direct smear and culture. Results of tube agglutination and slide latex agglutination are highly sensitive, specific, and positive in more than 90% of cases. The indirect fluorescent antibody test is also positive in about 90% of patients but gives 10% false-positive reactions. Results of complement fixation and immunodiffusion procedures are positive in less than half of the cases and have a much smaller potential for diagnosis. Sporotrichin skin test has extensive cross-reactions to antigens of several common fungal species, which limits its value as a diagnostic tool. Hyperuricemia and an increased erythrocyte sedimentation rate are associated findings. The white blood cell counts are usually within normal limits.

Spotted leg Syndrome manifestation

Stein-Leventhal Syndrome Hormonal findings vary greatly in this disease. The urinary concentration of gonadotropin (ICSH)-inhibiting substance has been found to be markedly reduced in a number of patients with this syndrome. Usually, urinary 17-ketosteroids are normal although an occasional moderate rise of these is found. There may be elevation of pregnanediol and luteinizing hormone, but this too is inconstant. Plasma testosterone levels vary widely with values extending from the normal female to the normal male range.

Stevens-Johnson Syndrome

Sporotrichosis

This is a clinical mellitus.

77

Diseases

of diabetes

SYN: erythema

multiforme

exudativum

Although the exact cause of this disease is unknown, etiologic roles have been ascribed to many organisms. Pure streptococcus cultures have been obtained from the nasopharynx, blood, blister fluid, and prostatic secretion. Staphylococcus aureus has often been cultivated from the conjunctival sac, throat, and urethra. Tuberculous involvement has been frequently mentioned in the literature. High titers of complement fixation to Mycoplasma pneumoniae have been reported in one group of cases. Type A (Japanese) Asian influenza virus has also been suggested as a possible cause, based on an eightfold titer increase in the hemagglutination inhibition test result on paired blood samples. Some investigators think that as many as a third of the cases are due to herpesvirus because of a fourfold increase in complement-fixing antibody titer in the blood during the acute phase of the disease. Furthermore, the disease has been observed to occur in the initial stages of viral pneumonia and after smallpox vaccination. The white blood cells frequently number 12,000-30,000, with polymorphonuclear leukocytes predominating. Eosinophilia occurs in a few cases.

Still-Chauffard Syndrome SYN: Still-Chauffard-Felty Anemia,

leukopenia,

syndrome and frequently

throm-

Clinics

I”

78

Butterworth

bocytopenia are the outstanding findings in this disease.

rheumatoid

arthritis

Serum immunoglobulin and complement component values are commonly normal, but elevated (YP-and r-globulins have been reported. Synovial fluid analysis may show low C3 and total hemolytic complement values and the presence of immune complexes and IgG rheumatoid factor. Leukocytosis and anemia are seen frequently. The erythrocyte sedimentation rate may be elevated. Most cases are rheumatoid factor negative.

Stomatitis Stomatitis,

Recurrent Aphthous

The cause of this disease is not known. Several microbial agents have been incriminated including herpes simplex and other viruses, Z’oxop/asma, the organisms that cause Vincent’s angina, and other bacterial agents, including the pleomorphic, transitional L-forms of the a-hemolytic Stre~fococ~ZLSsanguis. Both IgE and IgD concentrations are substantially increased. IgG and IgM are usually unchanged, while IgA levels may be raised. Delayed-type skin reactions to streptococcal vaccines are common. Hemagglutinating antibodies to saline extracts of fetal oral mucosa have been reported. A substantial number of patients with recurrent aphthous stomatitis have hematologic deficiencies such as primary anemia. Stomatitis,

Infectious

A streptococcus upon culture. Stomatitis,

can usually

Strongyloidiasis

laborator>

Still’s Disease SYN: juvenile

Dermatology

and Cawley

be recovered

Membranous

This condition is usually caused by streptococcus infection and Pseudomonas aeruginosa. In all cases, smears and cultures should be made to rule out diphtheria. There may be slight leukocytosis.

Diagnosis is made by finding typical larval forms of Strongyloides stercoralis in the stool. If unsuccessful, examination of the duodenal aspirate may be performed. About half the cases show moderate anemia and/or eosinophilia. The white blood cell count is usually normal.

Stryker-Halbeisen Syndrome Macrocytic

anemia

is a constant

feature.

We SYN: hordeolum The cause is Staphylococcus aureus. A large percentage of patients with recurrent styes carry Staphylococcus tmreus in the anterior nares. Dermatophytes have been implicated rarely.

Sycocis Vulgaris SYK: barber’s

itch

The cause is coagulase-positive staphylococci. Gram-positive cocci may be seen in smears. Nasal carriage of staphylococci occurs in more than 75% of cases. Anemia is frequently present.

Syphilis The darkfield microscope examination frequently gives a prompt diagnosis in primary and secondary syphilis. Material for the test may be obtained from the surface of the chancre, mucous patch, or condyloma. Fluid containing spirochetes may also be aspirated from the base of the suspected. lesion or from the lymph glands. There are many serologic tests for syphilis (Table l-4). Tests of the cerebrospinal fluid in syphilis usually include a VDRL, cell count, and total protein determination. In all stages of syphilis, the serum shows low albumin and high r-globulin. IgM and IgG are generally elevated, whereas IgA is increased only in the secondary phase. Creactive protein, cryoglobulins, and rheuma-

July-September Volume 4 Number 3

TABLE

1986

Cutaneous

1-4. Classification of Serologic Tests for Syphilis

Nontreponemal Flocculation ‘VDRL “RPR ART Complement Kolmer

Antigen tests

(Reagin) Tests

Veneral Disease Research Laboratory Slide test Rapid plasma reagin test Automated reagin test - fixation tests No longer used in the United States

Treponema TPI

Antigen Tests Treponemal pallidurn immobilization test [No longer a routine service test, but remains an important research tool] ‘FTA-ABS Fluorescent treponemal antibody absorption test Automated fluorescent treponemal AFTA antibody test (less sensitive than the manual FTA-ABS procedure) TPHA T. pallidurn hemagglutination test ‘MHA-TP Microhemagglutination assays for antibodies to T. pallidurn 19S-IgMFTA-ABS No longer advocated as a confirmatory test in congenital syphilis

“In most common

use today.

toid factor may be positive. The erythrocyte sedimentation rate is usually elevated. Children with congenital syphilis have anemia and leukocytosis.

T Tangier Disease SYN: high-density

lipoprotein

79

Diseases

Telangiectasia, Hereditary Hemorrhagic SYN: Rendu-Osler-Weber

Bleeding, clotting, and prothrombin times are normal. The result of capillary fragility test is also within the usual limits. The stools and urine may show blood. Women with low estrogen levels in their blood have a greater tendency to bleed in this disorder. Following repeated hemorrhages, patients may develop a chronic hemolytic anemia. In the presence of pulmonary arteriovenous fistulas, however, there may be a secondary polycythemia as a result of decreased oxygen saturation.

Thrush Budding cells and filaments of Ca~~dida albicans may be seen in oral swabs both by the direct film method and by means of Gram-stained smears. The organism may be cultured on Sabouraud’s agar. When the condition occurs in a neonate, the vaginal secretion of the infant’s mother should be checked for C. albicans. Serologic and immunologic studies such as complement fixation tests, slide agglutination tests with mono-specific immune sera, and dermal tests with autogenous or commercially available vaccines (oidiomycin) have also been used in identification of the organism of candidiasis. Since exposure is so widespread and many normal persons have positive reactions, results must be correlated with cultural and clinical findings. Although C. albicans is the causative organism in most cases, C. tropicalis, C. pseudotropicalis, C. krusei, C. parapsilosis, and C. guilliermondi have all been reported as pathogenic agents for man.

deficiency

Plasma high-density lipoproteins are less than 10% of normal. Cholesterol and phospholipid levels are markedly depressed (cholesterol level equals 50-100 mg/dl), while plasma triglyceride concentrations are somewhat elevated (150-250 mg/dl). The usual ratio of free to esterified cholesterol is found.

syndrome

Tinea Tinea Barbae SYN: tinea

sycosis

The deep inflammatory type is caused by Trichophyton mentagrophytes, Microsporum canis, and T. verrucosum. The superficial

80

Clrlcs I” Dermatology

Butterworth and Cawley

sycosiform cases are due to T. violuceun~ and T. rubrum. Diagnosis is made by KOH preparations and culture on Sabouraud’s medium. Tinea Capitis SYN: tinea tonsurans Diagnosis is made by KOH examination and culture, preferably of Wood’s-light-positive plucked hair. Microsporum audouki, M. canis, and Trichophyton tonsurans are found most commonly. Less frequently, T. mentagrophytes, T. schoenleini, and T. ~~iolaceum are recovered. Among the rarer causes of tinea capitis are M. gypseum, M. nanum, M. equinum, T. rubrum, M. ferrugineum, T. verrucosum, T. yaoundei, and T. megninii. In one series of 52 patients with T. tonsurans infections, 16 had kerion. Of these, 15 had a 48-hour reaction greater than 10 mm with trichophytin antigen; the remainder of the 52 did not. Tinea Corporis SYN: tinea circinata Diagnosis is made by KOH examination and culture of skin scrapings. M. canis, T. mentagrophytes, T. rubrum, and T. tonsurans are found most commonly. Less often, hf. audouini and T. verrucosum may be recovered. Rarely, M. nanum, T. simii, and Paecilomyces lilacinus have been found. Tinea Cruris SYN: jock itch, dhobie itch Diagnosis is made by KOH examination and culture of skin scrapings. The organisms found most frequently are Epidermophyton floccosum (inguinale), T. mentagrophytes, T. rubrum, and Candida albicans. In India, infections by T. simii are frequent.

Tinea Favosa SYN: favus 7: schverbleini may be found upon KOH examination and culture. Mouse favus caused by T. me’ntagrophytes may occur in man. Rare cases due to T. Aolaceunr and M. {gypSCUV~are known to occur. Tinea lmbricata Trichophyton concentricunr may be found upon KOH examination of scrapings. It is said that eosinophilia is common. Tinea Manus T. mentagrophytes or T. rubrum is found on KOH examination and culture. Rarely, M. nanurn has been recovered. Tinea Nigra Palmaris (and Plantaris) EGophiala (Cladosporium) cc~erneckii is found in KOH preparations and cultures in the western hemisphere, and E. mansoni is the usual cause in the eastern hemisphere. Tinea Pedia SYN: athlete’s foot (See also Erythrasma Erosio Interdigitale Blastomycetics)

and

KOH examination and culture of material from the eruption usually show Epidermophyton floccosum, Trichophyton mentagrophytes, or T. rubrum. In severe interdigital types. one may also find cocci, large colony diphtheroids, Pseudomonas spp., Proteus spp., Enterococcus spp., and Candida. Some chronic cases will have elevated IgE; a few are atopic. Tinea Profunda Trichophyton ‘uerrucosuw1 is found most commonly on KOH examination and culture. T. mentagrophytes may be the causative fungus in tropical climates.

Tinea Faciei

Tinea Versicolor

SYN: tinea facialis

SYN: pityriasis

The organisms most commonly isolated have been T. rubrum and T. mentagrophytes. Cases due to M. gypseum have been reported.

Diagnosis is established by demonstration of the spores and mycelia of Malassezia furfur on direct KOH preparations.

versicolor

July-September 1986 Volume 4 Number 3

Cutaneous

Tongue Tongue, Black Hairy Candida albicans, C. krusei, Aspergillus, and other pigment-producing bacteria, molds, and fungi may be cultured from the dorsum of the tongue.

Tongue, Scrotal Persons with this trait may have lower vitamin A levels and flatter vitamin A absorption curves than normal.

Toxic Shock Syndrome The cause is an exotoxin produced by Staphylococcus aureus, phage group 1. It may be isolated from the nasopharynx, trachea, vagina, abscesses, or empyema, but not from the blood. Leukocytosis is usually found, with a shift toward immature neutrophils (lo-54% band forms). Thrombocytopenia is almost always present, with platelets numbering fewer than lOOO/~l. With renal involvement, blood urea nitrogen and creatinine are elevated. The urinary sediment shows more than 5 white blood cells/hp field, with negative urine cultures. Hyperbilirubinemia and increased AST and ALT reflect changes in the liver. Hypocalcemia, hypophosphatemia, hypoproteinemia, and elevated creatine phosphokinase levels are additional findings. Anemia, proteinuria, oliguria, and hypoalbuminemia are rarely observed.

Toxoplasmosis Toxoplasma gondii may be demonstrated in blood, bone marrow, cerebrospinal fluid, and exudates from serous cavities in smears stained with Wright’s or Giemsa stain. T. gondii has also been isolated from a lymph node at the time of acute symptoms. Confirmation may be had by intracerebral or intraperitioneal inoculations of above materials into mice. Later, T. gondii may be observed in a smear from the peritoneal cavity. The result of the Sabin-Feldman methylene blue dye test for toxoplasma antibody becomes positive l-4 weeks following inocu-

81

Diseases

lation of the organisms and remains positive for many years if not throughout life. The titer may be very high in the early stages but falls to very low levels with increasing age. Significant titer levels are generally considered 1:16 or higher as indicative of past infection and 1:64 or higher as indicative of an acute infection. The indirect fluorescent antibody test is the most commonly used present-day serologic procedure. It detects the same antibody as the Sabin-Feldman dye test but does not require live Toxoplasma organisms. The immunofluorescence procedure can be used to detect either IgM or IgG antibody. The former begins to rise about 7 days after infection, reaches a peak in 3 or 4 weeks, and usually disappears after about 1 year. The IgG antibody titer begins to rise 4-7 days after the IgM antibody, reaches a peak in l-3 weeks, and begins to fall in about 6 months. Low titers persist for many years. A hemagglutination test is also used. Its titer begins to rise shortly after the appearance of the IgG antibody titers and parallels the rise and decline of the latter. The complement fixation titer levels appear about a week after the IgG antibody titer, reach a peak at the same time, and disappear after 6-8 months. Complement fixation must have a rising titer to be of significance. It is not as sensitive as other tests. The result of the toxoplasmin skin test becomes positive 4-12 months after the original infection, remains positive for long periods, but may revert to negative many years later. A number of case reports have suggested an association between toxoplasmosis and dermatomyositis.

Trench Fever Rochalimaea quintana has been cultured on 10% fresh blood agar. A specific microagglutination test is available.

Trichinosis SYN:trichiniasis, The causative

trichinellosis organism

is Trichinella spi-

Butterwotih

82

and Cawley

tolis. Many immunologic tests are available. The immunofluorescenceantibody test result becomes positive in 2 weeks. Precipitin and complement fixation test results are positive at the end of the fourth week. Also employed are a bentonite flocculation test and a slide latex particle agglutination test. An intradermal skin test for trichinosis is available. There are moderate leukocytosis. marked eosinophilia, an increased erythrocyte sedimentation rate, and elevated levels of AST and ALT.

Trichomoniasis Diagnosis is made by finding 2’rickol~o)~tr.s c~yinalis in a hanging-drop preparation or stained smear of vaginal secretion. Urine may be centrifuged and the sediment examined by the hanging-drop technique. In the male, secretions obtained from the prepuce. urethra, prostate, and seminal vesicles may be studied in like fashion. The organism may be cultured on specialized media.

Trichomycosis Axillaris et Pubis SYN:

lepothrix

Corynebacterium

tennis or other species of corynebacterium may be demonstrated easily be staining affected hairs with Gram’s stain or treating them with KOH.

Trichorrhexis Nodosa Chromatography of urine for argininosuccinic acid and amino acid analysis of hair do not support the theory that this hair abnormality is a metabolic defect.

Trichosporosis, Systemic Trichosporo,n cutaneum (beiyelii) may be cultured from skin lesions and blood of compromised hosts. This fungus is more commonly linked to white piedra.

Troissier’s Syndrome Diabetes syndrome.

mellitus

is an integral

partof

Clintcs in

this

Dermatology

Trypanosomiasis, African SYN: sleeping

sickness

is made by finding Trypanoor T. rhodesierw in smears of peripheral blood, serous exudate from the chancre, lymph node aspirates, cerebrospinal fluid, or bone marrow aspirations from a sternal tap. An increased yield of positive smears can be obtained by examining the buffy-coat layer of centrifuged blood specimens. Trypanosomes have been cultured in a medium containing blood, glucose, and lactalbumin. Antitrypanosome antibodies in the serum may be demonstrated by an indirect fluorescent antibody test, an enzyme-linked immunosorbent assay, an indirect hemagglutination test. and complement fixation. Elevated serum IgM is a consistent finding. In the cerebrospinal fluid, an IgM level greater than 100 mg/ml is virtually diagnostic of the disease (normally IgM is absent in the CSF). There may also be an increased number of cells and an increased protein level in the spinal fluid. The cells found may be lymphocytes, monocytes, or a histiocytic cell called the morular cell or Mott cell. The ESR is elevated in the majority of patients. Diagnosis

,ss’r)m(~ gumbiense

Trypanosomiasis,

South American

SYN: Chagas’ disease Trypunosomu cruzi may be found in wetcoverslip preparations of titrated or heparinized blood. Thick film smears from the buffy layer may be examined as wet preparations or stained with Wright’s or Giemsa stain. Blood may be cultured on NNN medium. Another diagnostic procedure is the inoculation of titrated blood intraperitoneally into rats, hamsters, or guinea pigs. The blood of the animal is checked periodically for 60 days. Complement fixation tests and hemagglutination tests are available. The indirect fluorescent antibody test is also recommended as a practical method for routine serologic diagnosis of South American trypanosomiasis. Xenodiagnosis consists in allowing laboratory-bred Reduviidae to feed

July-September 1986 Volume 4 Number 3

Cutaneous

on a suspected individual and the subsequent demonstration of the parasite in the intestinal tract of the bugs. There is generally leukocytosis with lymphocytosis and sometimes monocytosis.

Tuberculosis Cutis Historically, a number of cutaneous tests have been employed including (1) von Pirquet scratch method with Old Tuberculin Koch (OTK), (2) Mantoux intracutaneous test with Old Tuberculin or purified protein derivative (PPD), (3) Moro inunction method with tuberculin incorporated in an ointment, (4) Vollmer patch test, and (5) tine test. Hyperergic reactions are found in tuberculosis verrucosa cutis, scrofuloderma, tuberculosis cutis orificialis, rosacea-like tuberculid, lichen scrofulosorum, and lupus vulgaris. At first negative, the test results become hyperergic later in primary inoculation tuberculosis. Hypergic reactions are obtained in lupus miliaris disseminatus faciei, papulonecrotic tuberculid, and erythema induratum. Mycobacterium tuberculosis may be recovered on culture from primary inoculation tuberculosis, tuberculosis verrucosa cutis, scrofuloderma, and tuberculosis cutis orificialis. In other forms of cutaneous tuberculosis, the organism may be found with great difficulty or not at all. The chances of recovering M. tuberculosis are enhanced by guinea pig inoculations.

Tularemia Francisella (Pasteurella) tularensis may be isolated by direct culture or by the subcutaneous or intraperitoneal inoculation of exudate into mice or guinea pigs. Material may be obtained from local ulcer, regional lymph nodes, nasopharyngeal or gastric washings, pleural fluid, and bronchial secretions. Isolation of the organism from the blood is very difficult. The serum agglutination test result becomes positive within 8-10 days from onset of illness, and the maximum titers are reached

a3

Diseases

in about 4 weeks. An agglutination titer of 1530 or greater is considered diagnostic. The result of Forhay’s intradermal test is highly specific. It may be positive as early as the third day, and 92% are positive by the end of the first week. The test result remains positive for years. Unfortunately, the antigen is not comercially available. An immunofluorescence test has been employed recently. Complement-fixing antibodies have been reported. The erythrocyte sedimentation rate and Creactive protein are elevated during the active stages of the disease. The white blood cell count is usually normal or low. Occasionally, there may be moderate leukocytosis. Mild albuminuria may occur during the height of illness.

Tungiasis The eggs and larvae of Tunga penetrans may be found in scrapings of the skin.

Turner’s Syndrome SYN: Bonnevie-Ullrich syndrome, Turner syndrome, X0 syndrome

Ullrich-

About half of the patients have the classic X0 chromosomal complement with absence of sex chromatin in both circulating neutrophils and buccal mucosal cells. In the remainder, various kinds of chromosomal constitution are found. Mosaicism is frequent. There is an increase of pituitary gonadotropin and diminution of 17-ketosteroid in the urine.

Typhoid Fever Salmonella typhi may be cultured from the blood or stools. The diagnostic value of the Widal test is limited. There is cross-reactivity with other Salmonella organisms, and with antibiotic therapy there may be no rise in titer. ELISA tests are under development, and this or another new technique probably will replace agglutination reactions. Leukopenia is usual with lymphocytosis and monocytosis.

84

Butterworth

and Cawley

Clinics I” Dermatology

PLATE 5. Hair

FIG. 1. Menkes’ kinky hair disease, a hereditary iIbnormality of copper absorption, results in sparse, brittle hair (left). Characteristic twisting of the hair is seen (above) under a dissectir 1g microscope with reflected light.

FIG. 2. Monilethrix, an autosomal-dominant inherited condition, is characterized by brittle hairs with multiple, marked constrictions, creating a beaded effect.

FIG. 3. Nit attached to hairshaft. Theencapsulated louse egg can be confused, grossly, with psoriatic or seborrheic scale.

FIG. 4. Trichorrexis nodosa, characterized by what appear to be white nodes (below, left), is a condition in which these are actually sites where the cortex of the shaft has broken and split into strands (below, right) so that hairs break at these “nodes.”

July-September Volume 4 Number 3

1986

Cutaneous

Diseases

85

PLATE 6. Genetic Disorders

FIG. 2. Peutz-Jehgers syndrome is associated with polyps of the small intestine and excess melanin pigmentation of the lips.

FIG. 1. Xeroderma pigmentosum is a rareanc j often fatal photodermatitis. It appears early in chili (top) with photosensitivity and development of freckles, and progresses (above) to tumors of the ! eyes, basal cell and squamous cell cancer, and mela noma. Prenatal diagnosis is possible.

FIG. 3. For pseudoxanthoma elasticum, there is currently no diagnostic laboratory test. The condition is marked by yellowish maculesand papules-individual, confluent, or massed into plaques-and exaggeration of normal folds and creases of skin. FIG. 4. Acrodermatitis enteropathica (postmortem photograph) is an autosomal recessive disorder of zinc uptake. Once thought to be due to Candida albicans, it is characterized by pustulous dermatitis. Many serum protein abnormalities have been found in this zinc-responsive disorder.

Butterworth

86

and Cawlev

Typhus Typhus, Epidemic The etiologic agent is Ki~/irt~g
Typhus, Murine SYN:

endemic

Clinics I” Dermatology

typhus

Rickettsia typhi (mooseri) causes this milder form of typhus. The laboratory data are

similar to those described for epidemic typhus except that abnormal findings tend to be slight or absent in murine typhus. Immunologic test results become positive at the same time as with epidemic typhus. Typhus, Scrub SIN: tsutsugamushi

fever

Kidettsia fsutsuyamcush i may be recovered from the blood by inoculation of white mice during the first 10 or 12 days of fever. The indirect fluorescent antibody test is the best serologic technique for diagnosis. Late in the second week, agglutinins for the OX-K strain of H. proteus (Weil-Felix) appear in the patient’s blood. OX-2 and OX-19 titers remain negative. The white blood cell count remains within the normal range unless secondary bacterial infection occurs. Anemia is rarely observed. Plasma proteins may be slightly lowered. leading to reversal of the A/G ratio. Hypochloremia develops late in the disease. Plasma fibrinogen may be decreased and serum bilirubin slightly elevated in cases with impairment of liver function.

Tyrosinemia II SYN: Richner-Hanhart taneous tyrosinemia

syndrome,

oculocu-

Tyrosinuria, tyrosyluria, and tyrosinemia are the significant laboratory findings. The plasma levels of phenylalanine are also elevated. The basic abnormality is defective hepatic tyrosine aminotransferase.

U Ulcer Ulcer, Chronic Leg The hemolytic anemias, syphilis, tuberculosis, and diabetes should be eliminated by appropriate laboratory studies. Candida albicuns may be found in some ulcers in addition to various other organisms.

July-September Volume 4 Number 3

1986

Cutaneous Diseases

Ulcer, Meleney’s Undermining This ulcer is due to a combination of a microaerophilic or anaerobic streptococcus in the spreading periphery of the lesion associated with staphylococci, streptococci, or gram-negative rods in the zone of gangrene. Ulcer, Mycobacterial Phagedenic The ulcers teem with Mycobacteriuw ulceraw, which is cultured best at 33” C. Guinea pigs are not susceptible to infection. The tuberculin test result may become positive late in the disease. Cases due to M. kansasii have been reported. The “Buruli ulcer” in Africa was formerly thought to be due to M. buruli. The latter is now considered to be M. ulcerans. Ulcer, Tropical Anaerobic gram-positive fusiform bacilli are found in smears of pus from the ulcer. Occasionally a spirochete is found. Laboratory studies are indicated to eliminate diphtheria, syphilis, yaws, leishmaniasis. leprosy, and tuberculosis.

Urethritis The diagnosis of gonococcal urethritis may be established by urethral smears, culture on Thayer-Martin plate, the Gonosticon DriDot (Organon, Inc., West Orange, NJ) blood test, or the Gonozyme (Abbott Laboratories, North Chicago, IL) test, an enzyme-linked immunoassay. Nongonococcal urethritis has a number of causes. About half of the cases are due to Chlamydia trachomatis and a quarter to Ureaplasma urealyticum,. Recent tests for chlamydia introduced commercially include Abbott’s enzyme-linked immunoassay (Abbott Laboratories, North Chicago, IL) and Syva’s (Syntex, Mountain View, CA) fluorescein-labeled antibody test. Herpes simplex virus and Trichomonas vaginalis each cause less than 5% of cases. Corynebacterium genitalium and Candida albicans are occasional etiologic agents, but the remainder are of unknown origin.

87

Mean levels of IgG, IgA, and IgM are elevated in both gonococcal and nonspecific urethritis.

Urticaria Urticaria, Chronic Laboratory findings vary according to cause. Stool examinations may reveal ova and intestinal parasites such a Giardia organism, roundworms, amebas, or pinworms. Vaginal smears should be examined for candida and trichomonas. Sarcoptes scabiei has been a rare cause. Liver function studies may uncover viral hepatitis. Hyperthyroidism, lymphomas, and even Trichophyton rubrum infections may account for a few cases. Routine blood and urine studies seldom uncover the cause of chronic urticaria, but they often give a clue to the direction that additional studies should take. Urticaria, Cold (See Cold Sensitivity,

p. 14)

In familial cold urticaria, neutrophilic leukocytosis precedes and accompanies the delayed cold reaction. During cold exposure, there is a sharp decrease in the plasma level of chymotrypsin-inhibiting capacity. Plasma bradykinin is also reduced during the cold reaction, and histamine is diminished in urticarial lesions compared with normal unexposed skin. The reaction cannot be passively transferred. Acquired cold urticaria occurs immediately upon exposure to cold. The reaction is mediated by histamine, and results of passive transfer tests are positive in 50% of cases. Mast cell degranulation is observed. There is no leukocytosis. A VDRL test and a search for cryoglobulins, cryofibrinogens, and cold hemolysins should be made for possible etiologic factors. Urticaria, Hypocomplementemic

Vasculitic

Total primary-pathway hemolytic ment activity is reduced, whereas tive-pathway hemolytic activity is Levels of early-acting components classic pathway are decreased in all

complealternanormal. of the patients

Butterworth and Cawlev

88

(Clq, C4, C2). A marked selective reduction in Clq is noted. Circulating immune complexes are evidenced by the Clq binding assay, monoclonal rheumatoid factor assay, or Raji cell assay. ESR is elevated in almost all patients. About a third have a low titer of antinuclear antibodies. A very few patients have detectable cryoglobulins, false-positive test result for syphilis, elevated immunoglobulin levels. or positive rheumatoid factor. Urticaria, Pressure Neutrophilic leukocytosis with persistent eosinophilia may occur with severe episodes. Urticaria, Pruritic Papules and Plaques of Pregnancy Generally, no abnormalities have been reported in the CBC, liver function tests, urinary chorionic gonadotropin, serologic tests for syphilis, or serum levels of estrogen and progesterone. A few patients have shown mild leukocytosis and elevated erythrocyte sedimentation rates.

V Varicella SYN:

Cllnlcs I” Dermatoloav

chickenpox

Tzanck smears from the floor of a fresh vesicle reveal the presence of multinucleate giant cells and balloon cells. Varicella virus may be isolated from vesicle fluid in primary culture of human amnion cells or on a culture of human embryonic lung fibroblasts during the first 3 days of the rash, but not later. The virus present in the vesicles may also be identified by electron microscopy as belonging to the herpes zoster/varicella group. Attempts to isolate virus from the respiratory tract have been generally unsuccessful. Immunoglobulin classes IgG, IgA, and IgM are induced 2-5 days after the rash begins and may be detected by flourescent antibody to membrane antigen (FAMA). High IgG

levels persist throughout childhood, although levels of IgM and IgA decrease to undetectable amounts. Microscopic agglutination tests may be performed with fluid from early vesicles and varicella convalescent serum. Complement fixing and neutralizing antibodies are present. Varicella may be distinguished from smallpox by immunofluorescent tests. There may be mild leukocytosis. The disease is occasionally accompanied or followed by thrombocytopenic purpura. Vesicles located in the bladder may cause transient hematuria. When meningoencephalitis occurs, there is an increase in the lymphocytes and protein in the spinal fluid. In varicellagangrenosa, various organisms including p-hemolytic streptococcus, Staphy/OCYK~/~S(~~(I‘PILs,S. nlbus. Cor.y~cebucterurrr ~Iiphth~~riw. Esch~rich icr coli, and Proteus spp. have been recovered.

Vasculitis, Necrotizing STN:allergic

vasculitis

Laboratory findings are variable according to categories. The most frequent abnormality is a moderately to markedly elevated erythrocyte sedimentation rate. About a quarter of the cases show leukocytosis with eosinophilia: a tenth have leukopenia. An occasional patient has transient depression of the platelets. Hemolytic anemia may occur. Leukocytoclastic vasculitis (angiitis). There is renal involvement manifested by proteinuria or hematuria or both. If persistent, additional studies indicated include BUN, creatinine clearance, 24-hour urinary protein, and possibly a renal biopsy. Sj6gren’s syndrome and RO/SSA antibodies may be associated. Hypocomplementemic (urticarial) vasculitis. This form shows an elevated ESR and a very low total hemolytic complement level (See also Urticaria, Hypocomplementemic Vasculitic, p 87). Essential mixed cryoglobulinemia, in addition to markedly elevated cryoglobulin, may show nephritis. Additional laboratory abnormalities include elevated rheumatoid factor

July-September Volume 4 Number 3

1986

Cutaneous

and a low total hemolytic complement. These patients may also have positive antinuclear antibody, but lack other features of SLE. Hypergammaglobulinemic purpura of Waldenstrijm. One finds an elevated ESR and polyclonal hypergammaglobulinemia as high as 4.0 g/dl. Cryoglobulins may be slightly elevated. (See p. 90).

Verruga Peruana SYN: Carrion’s

disease,

bartonelliasis,

Oroya

fever Bav?onella bacilliformis has been demonstrated in the blood during the pre-eruptive period. The blood count may drop in 3 days from normal down to 1 million erythrocytes. There is often an accompanying decrease in the leukocytes, with the appearance of immature forms. The red blood cells show an increase in their diameters, shortened life span, increased mechanical fragility, and a greater amount of free protoporphyrins. Reticulocytosis and bone marrow hyperplasia are also found. There are increases in indirect bilirubin and fecal urobilinogen. Organisms may be demonstrated adhering to the red blood cells.

Vibrio Vulnificus Infection Vibrio vulnificus is readily isolated from cutaneous lesions and blood. Other sources of clinical isolates have been cerebrospinal fluid, sputum, surgically debrided tissues, cornea, and pelvic peritoneum. Other laboratory findings include leukopenia and thrombocytopenia.

Vincent’s Infection This is an infection by Bacteroides and Fusobacterium species in association with Borrelia vincentii and other organisms.

Vitiligo SYN: acquired

leukoderma

Although the diagnosis of vitiligo usually may be made readily on a clinical basis, many abnormal laboratory findings have

Diseases

09

been recorded. AST and serum alkaline phosphatase are elevated in almost half the patients. The ALT is normal. The ascorbic acid in whole blood is frequently found to be lowered. Bleeding time is longer in the vitiliginous than in the adjacent normal skin. Hypochlorhydria occurs in many patients, and a substantial number of this group have low serum vitamin BU owing to impaired absorption related to intrinsic-factor deficiency. The urinary 17-ketosteroids may be lowered. Vitiligo appears more common in persons with blood group AB. Many diseases are linked to vitiligo including late-onset diabetes mellitus and primary pernicious anemia. Also frequently associated are hyperthyroidism, hypoparathyroidism, Addison’s disease, regional enteritis (Crohn’s disease), and IgA deficiency. In keeping with these clinical relationships, the laboratory finds organ-specific antibodies to thyroglobulin, adrenal tissue, gastric parietal cells, and sometimes smooth muscle. Antinuclear and antimitochondrial antibodies occasionally are encountered. Circulating antibody bound to melanocytes in skin, nevus cells, and melanoma cells have been demonstrated by immunofluorescent complement fixation tests. Results of direct and indirect immunofluorescence are usually normal.

Vogt-Koyanagi-Harada Syndrome There is lymphocytic pleocytosis and slightly increased protein in the cerebrospinal fluid in the early stages of the disease.

von Recklinghausen’s Disease SYN: neurofibromatosis

A recent report has documented increased nerve growth-stimulating activity in the serum of patients with neurofibromatosis.

Vulvovaginitis, Candidal Candida may be demonstrated by KOH microscopic examination and culture.

Butterworth and Cawley

90

w Waldenstrom’s Macroglobulinemia SYN: essential

macroglobulinemia

In this monoclonal IgM gammopathy. electrophoresis shows a decrease of albumin. a~‘and p-globulins, and elevated serum y-globulins. Abnormal 19S-globulins constitute over 15% of the serum proteins. These paraproteins are found within the par y fractions and are usually IgM. Hyperproteinemia occurs. Fibrinogenopenia has been reported. There is normochromic anemia. Rouleaux formation occurs frequently. The white blood cell count is usually normal. although mild leukopenia may occur. Thrombocytopenia is the rule. Bleeding and clotting times are abnormal. Increased serum viscosity and a greatly accelerated erythrocyte sedimentation rate are usual. Numerous atypical plasmacytoid lymphocytes are found in the bone marrow and peripheral blood. About lo-15%of patients have Bence Jones proteinuria. Increased capillary fragility is noted. Biologic false-positive results of serum test for syphilis and latex fixation test are found frequently. Hyperuricemia is another finding.

Warts SYN:

Clinics in Dermatology

Warts are caused by a papovavirus. Viral antibodies have been measured with various techniques such as direct visualization of virus antibody complexes under the electron microscope, the complement fixation test, immunodiffusion, passive hemagglutination. and immunofluorescence. The appearance of complement-fixing antibodies, which are of the IgG type, frequently correlates with the regression of warts. Widespread warts have been seen in some cases of dysgammaglobulinemia. These individuals usually have absent IgA and IgG and elevated IgM.

Waterhouse-Friderichsen Syndrome meningitidis

Wells’ Syndrome S~,N: recurrent granulomatous dermatitis with eosinophilia, eosinophilic cellulitis (see also Chur-Strauss Syndrome, p. 14) Eosinophilia is aconstant feature. mentation rate may be elevated.

may

be cultured

The sedi-

Werner’s Syndrome SYN: dyshormonal

dermatosis

Hypogonadism is manifested by low urinary level of 17.ketosteroids. mildly elevated 17-hydroxysteroids, and markedly elevated urinary gonadotropins. About half of the patients have diabetes of an insulin-resistant type. Other biochemical abnormalities commonly found include increased blood levels of uric acid, calcium, cholesterol, and triglycerides as well as proteinuria.

Wilson’s Disease SYN: hepatolenticular

Verrucae

Neisseria

from the blood. cerebrospinal fluid, or nasopharynx. The organism may be seen in smears of the spinal fluid. Leukocytosis occurs at some time during the disease, but early leukopenia is an unfavorable sign. Proteinuria. hematuria. pyuria. and azotemia are common. Hyperglycemia may be found.

degeneration

Plasma ceruloplasmin is decreased to less than 20 mg/dl. Plasma copper is strikingly decreased although the small fraction of copper bound to serum albumin, “directreacting copper,” is increased. This may be considered to be copper in transport to various parts of the body. The urine shows a great increase in the amount of copper. There is decided aminoaciduria, with urinary excretion of threonine, cystine, serine, glycine, valine, tyrosine, and lysine. The plasma levels of amino acids are not increased. Glycosuria may also occur, and the blood glucose levels are usually in the low normal range. Phosphaturia and uricosuria are common findings and are associated with low plasma phosphate and urate levels. Hypercalciuria occurs in almost half of the cases.

July-September Volume 4 Number 3

1986

Cutaneous Diseases

Tissue levels of copper are elevated. That of the liver exceeds 100 pg/g dry weight. There are accompanying liver function test results, anemia, and thrombocytopenia.

Wiskott-Aldrich Syndrome SYN: Aldrich’s

syndrome

The platelets are decreased in size and total about 20,000-100,000 ~1. They show a lack of granulation by light microscopy and a decrease in organelles by electron microscopy. There is defective adhesiveness of platelets to glass as well as poor aggregation to collagen, adenosine diphosphate, and epinephrine. Platelet agglutinins are absent, and donor thrombocytes have a normal survival time. Megakaryocytes may or may not be present in bone marrow aspirates. Eosinophilia is the rule, but there is a deficiency of both circulating and tissue lymphocytes. Decreased leukocyte chemotaxis is noted. Delayed hypersensitivity responses may be absent. Serum -y-globulin levels are normal. IgM is decreased or absent, but IgA is almost invariably elevated. IgG is normal or low, while IgE has been found increased consistently in the reported cases. The catabolism of IgG, IgA, and IgM is markedly increased but masked by increased synthesis. Isohemagglutinins are significantly reduced or absent. A constant feature is the inability to form antibodies to certain polysaccharide antigens. Specific antibody responses are impaired, at times, and unusual antibodies to bovine and goat proteins or rheumatoid factor have been found in the serum. IgG paraproteins, usually precipitins or cryoglobulins, have been found in the sera of some patients.

Wissler’s Syndrome There are polymorphonuclear leukocytosis up to 15,000-25,000 ~1 often an eosinophilia, and a raised ESR.

91

X Xanthelasma Palpebrarum About half the cases show increased serum levels of cholesterol, cholesterol esters, and phospholipids. The serum triglycerides are normal. Lipoproteins of a type suspected of being associated with atherosclerosis are elevated in those patients with hypercholesteremia. Clinical or latent diabetes mellitus is common in patients with xanthelasma.

Xanthoma Xanthoma

Diabeticorum

The serum is milky and always hyperlipemic. Free and total fatty acids are elevated. Total cholesterol and phospholipids are high, but not in proportion to the fatty acids. There are hyperglycemia and glycosuria. Carotenemia is frequent. The A/G ratio has been reversed in some patients. Xanthoma

Disseminatum

Blood lipids are normal. Diabetes insipidus may be the earliest manifestation, with a urinary specific gravity of 1.004 to 1.008. Xanthoma,

Juvenile

SYN: nevoxanthoendothelioma Serum

lipid levels are normal.

Xanthoma

Tuberosum

Multiplex

SYN: familial hypercholesterolemia, hyperlipoproteinemia

type II

The fasting serum remains clear after refrigeration overnight @-lipoprotein contains 47% cholesterol and only 9% triglycerides). Serum cholesterol is two to five times as high as normal, with the usual cholesterol-cholesterol ester ratio. Triglycerides show a small increase to a mean of 150 mg/dl with an upper limit of about 500 mg/dl. Serum low-density P-lipoproteins (LDL) are increased while pre-S-lipoproteins (very lowdensity, VLDL) are raised proportionately to the triglycerides. Plasma vitamin A may be increased. Caro-

92

Butterworth

tene concentrations are high, but the glucose tolerance test result is usually normal. Serum uric acid and postheparin lipolytic activity are within the usual range. Some authors divide familial hypercholesterolemia into two classes. In type II A, there are only elevated levels of low-density lipoprotein: whereas in type II B. both low density lipoprotein (p) and very low-densit) lipoprotein (pre-P) are increased. Prenatal diagnosis is possible using cultured amniotic fluid cells. Serum cholesterol level has been reported high in cord blood, although it is usually normal with a gradual increase into the abnormal range during the first year.

Xanthomatosis Xanthomatosis,

Biliary Disease

The serum is clear and bile-stained. Total fatty acids are high. There is marked increase in phospholipids followed by free cholesterol and triglycerides in order of decreasing magnitude. Late in the disease, the cholesterol ester fraction may drop concomitantly with decompensation of liver function. /31- and r-globulin are increased. There is an elevation of P-lipoproteins, while the (Ylipoproteins are reduced or absent. Anemia, mild leukocytosis, bilirubinemia. bilirubinuria with reduction in urinary urobilinogen, low fecal urobilingen, and high serum alkaline phosphatase are common findings. Liver function test results become altered during the late stage of the disease. Both AST and ALT are elevated. Xanthomatosis,

Broad Beta Disease

SYN: Type III hyperlipoproteinemia. ing Beta” Syndrome

Clinics in Dermatology

and Cawley

“Float-

The serum is opalescent or turbid after being refrigerated over night. Sometimes, there is a creamy layer. Serum cholesterol and triglycerides are increased in the ratio of 1:l with both possibly reaching 1400-1500 mg/dl or more. Electrophoresis reveals a “broad beta band”composed of p- and pre-/_+lipoproteins, beginning in the normal beta zone but ex-

tending continuously into the prebata region. Both lipoproteins are not normal and are referred to as “floating beta”or intermediatedensity lipoproteins. (ilucose intolerance is the rule. Postheparin lipolytic activity is normal. Xanthomatosis,

Cerebrotendinous

Serum cholesterol is normal or slightly elevated. Although heavily deposited in many tissues, cholestanol is not increased in the plasma. Xanthomatosis, Familial Combined Hyperlipidemia SJ’N: multiple mia

lipoprotein

type hyperlipide-

Refrigerated serum is usually turbid but rarely creamy. One third of the patients have hypercholesterolemia and another third hypertriglyceridemia, while the remainder have elevation of both lipids. Most commonly, the subject has an elevation in both lowdensity lipoprotein (type IIA) and very lowdensity lipoprotein (type IIB); however, within a family, the presence of hyperlipoproteinemia (type IIA) and hyperprebetalipoproteinemia (type IV) is found affecting different individuals. Patients frequently have diabetes and a tendency to hyperuricemia. Xanthomatosis, Familial Hypertriglyceridemia STK: type IV hyperlipoproteinemia, familial hyperprebetalipoproteinemia, endogenous hyperlipemia, carbohydrate-induced hyperlipemia Overnight plasma is found to be cloudy. Plasma triglycerides are markedly increased. Cholesterol may be normal, although it is commonly elevated in the order of about 1 mg for each 5-mg increase in triglycerides. Lipoprotein electrophoresis shows an increase in the pre-p fraction. Q- and plipoproteins are usually below normal, and chylomicrons are generally not present. Glucose intolerance is almost universal,

July-September Volume 4 Number 3

1986

Cutaneous Diseases

and hyperuricemia is common. The postheparin lipolytic activity is within normal range.

Xanthomatosis, Glomerulonephritis, Nephrotic Stage The cutaneous xanthomata seen in this disease are accompanied by a milky serum owing to an increase in triglycerides. The levels of cholesterol and phospholipids are also raised but to a lesser degree than the neutral fats. Plasma amino acids and serum albumin and globulin are decreased. Serum p-globulin is increased. P-Globulin is present in the urine of patients with nephrotic syndrome who have protein excretion of more than 2 g/day. The serum T4 level is decreased. Serum calcium is also low, and albuminuria is the rule.

Xanthomatosis, Glycogen Storage Disease SYN: von Gierke’s disease The cutaneous xanthomatosis is due to hyperlipemia. Serum triglycerides and total fatty acids are very high. The serum levels of cholesterol are also raised but to a lesser degree. The specific enzyme, glucose-6-phosphatase, is either completely lacking or markedly decreased in activity in the liver. As a result, there is no response or only small and delayed increases in blood glucose concentration after injection of epinephrine or glucagon. Also lacking is the expected hyperglycemia after galactose or fructose injections. The blood glycogen levels are elevated. Further laboratory studies show fasting hypoglycemia, high blood lactate levels, acidosis, and acetonuria. In addition, these patients manifest impaired glucose tolerance, hypersensitivity to insulin, decreased or absent neutral serum phosphatase, a rise in (Yand p-globulins in the serum, and aminoaciduria. Hyperuricemia may be found with or without symptoms of gout.

93

Xanthomatosis, Hemochromatosis (see Hemochromatosis, p, 33) Xanthomatosis, Hypothyroidism Cholesterol, triglycerides, and phospholipids are elevated to varying degrees. Lipoprotein electrophoretic pattern may resemble Type III hyperlipoproteinemia(broad beta disease). Serum T4 is low. Anemia is common. Carotenemia and low serum vitamin A level may be found.

Xanthomatosis, Lipoprotein Lipase Deficiency SYN: type I hyperlipoproteinemia, duced hyperlipemia, Buerger-Grutz

fat-indisease

Freshly drawn blood resembles cream of tomato soup. Following refrigeration overnight, the chylomicrons have risen to the surface, giving rise to a creamy top layer and a clear infranatant. Triglycerides are greatly increased, and cholesterol is much less so (chylomicrons contain about 81% triglycerides and 9% cholesterol). Fat tolerance test results are abnormal, indicating a delay in the removal of triglycerides from the serum. Lipoprotein electrophoresis shows a prominent chylomicron band (S 400). Very lowdensity lipoproteins may be slightly increased, but high- and low-density lipoproteins are decreased as a rule. Hyperglycemia and glycosuria may occur in adults. Serum uric acid may be increased in a few patients. Low postheparin lipolytic activity is the rule. The disease is due to a decrease in the activity of the enzyme lipoprotein lipase.

Xanthomatosis, Pancreatitis, Chronic Usually related to alcoholism, the very low-density lipoproteins and, later, the chylomicrons are elevated, creating a pattern that may resemble type I or V hyperlipoproteinemia. Cholesterol, triglycerides, and phospholipids all may be elevated. In acute exacerbations, free fatty acids may be present. Also found are hyperglycemia, glycosuria, decreased serum calcium, and increased fecal fat.

Butterworth

94

Clinics In Dermatology

and Cowley

Diagnosis of pancreatic insufficiency ma! be made by secretin stimulation, feeding stimulation, and tripeptide function tests. Lactoferrin levels in pancreatic juice have been measured and found helpful although the procedure is not yet proven.

I’renatal diagnosis may be accomplished by using midtrimester transabdominal amniocentesis and demonstrating defective DNA repair in cultured amniotic fluid fibroblasts.

Xanthomatosis,

(‘heck for laboratory mellitus and Sjtigren’s

fl-Sitosterolemia

Plasma cholesterol levels are normal. High concentrations of plant sterols, especially fl-sitosterol and campesterol are found in the plasma, red blood cells, xanthomas. adipose tissue, and skin. Most of the plant steroid in the plasma is carried in the lolvdensity fraction.

Xeroderma Pigmentosum A deficiency of endonuclease leads to an inability of the cells to normally repair the damage to deoxyribonucleic acid (DNA) that is caused by short exposures to ultraviolet light. Most authors agree on the presence of nonspecific aminoaciduria. renal impairment (low renal urea clearance), and abnormally low urinary excretion of 1’7ketosteroids and 17-hydroxycorticosteroids. Less agreement has occurred on a possible low erythrocyte glutathione content and prolonged erythrocyte glucose-&phosphate dehydrogenase activity. Increases in serum az-globulin. copper. ceruloplasmin, AST. and ALT have been reported by some authors but not confirmed by others. Low levels of serum vitamin A and ACTH deficiency have been recorded. The occurrence of leukemia has been noted in patients with this disease.

Address for correspondence:

Thomas ButterLvorth,

Xerostomia evidence of diabetes syndrome.

Y Yaws SF’K: Frambesia Twpo~cma pertenue may be demonstrated in darkfield examinations of primary and secondary lesions. The organism may also be identified by staining the exudate with hot carbolfuchsin or by Tribondeau-Fontana’s method. STS, including both FTA-ABS and TPI. are reactive.

Yellow Nail Syndrome The erythrocyte sedimentation rate is slightly elevated in about half of the patients. Serum abnormalities such as hypogammaglobulinemia, lymphopenia, and depressions of IgA and IgM have been noted but are rare.

Yersiniosis Positive cultures

of feces for Yersinia

ente-

roditicu or Y. pseu,dotuberculosis or Yersir~iu agglutinin antibody titers of 160 or over

are diagnostic.

MD. 411 Walnut

Street, Reading, PA 19601.