Roentgenologic Changes Collagen Diseases
L. H. GARLAND,
M.D. AND M. A. SISSON,
From tbe Department of Radiology, Stanford University Medical School Service. San Francisco Hosnital. San Francisco, California.
respiratory and cardiovascuIar systems are commonIy involved in the so-caIIed coIIagen diseases. This articIe will outIine the more conspicuous pIeuropulmonary changes and the associated pericardiovascuIar changes which are encountered in this group of disorders. The collagen diseases are a group of disorders characterized anatomicaIIy by generaIized aIterations of the connective tissue, especiaIIy of its extraceIIuIar components. The currentIy accepted members of this group are periarteritis disseminated Iupus erythematosus, nodosa, dermatomyositis, scleroderma, rheumatic fever and rheumatoid arthritis. The term polyarteritis is synonymous with periarteritis nodosa. Because of the predominance of vascuIar changes, this disorder (and, to a Iesser extent, generaIized Iupus erythematosus) may also be referred to as visceral angiitis. Disseminated Iupus erythematosus is aiso known as acute Iupus erythematosus or generaIized Iupus erythematosus. Becker” and others beIieve that the systemic manifestations of SchSnIein-Henoch purpura, erythema nodosum and certain cases of gIomeruIonephritis include simiIar invoIvement of connective tissue and may belong to this group of diseases. Ehrich and associates,s on the basis of anima1 experiments, wouId aIso include serum sickness. Kampmeierl’j has suggested that the necrotic changes found in afferent renal arteries in both malignant hypertension and periarteritis nodosa have more than coincidental relationship. Stewart+ beIieves that thromboangiitis obliterans and ulcerative colitis are also coIIagen diseases. HE
of the collagen workers have
noid changes of connective tissue experimenta1Iy by mechanica and by chemical means.” These observations tend to invalidate the supposition that hypersensitivity is the sole cause of coIIagenous degeneration. Indeed, it has been observed that undue significance should not be attached to the occurrence of fibrinoid changes in IocaIized connective tissue coIIagen. PathoIogicaIIy, this is mereIy a form of degeneration, unspecified in etiology, and occurring in a wide variety of dissimilar diseases. This fact, of course, greatly minimizes the clinica usefulness of the term collagen disease. However, unti1 a better term is devised and until we know more about the fundamental nature of the diseases in question, it is probabIy justifiabIe to continue the use of the term. In this connection, it is to be noted that the microscopic findings do not consist merely of changes in the coIIagen fibers aIone, but of changes in the connective tissue elements as a whoIe. Histologically, connective tissue consists of celIuIar eIements and extraceIIuIar substances. The ceIIuIar eIements consist of fibrocytes and fibrobIasts, macrophages, Iymphoid cells, mast cells and various other leukocytes. The extraceI1uIar substances are composed of an amorphous ground substance and three known types of fibers, namely, colIagenous, reticular and eIastic. The basic lesion in the collagen diseases consists of a sweIIing of the interfibriIIary ground substance as we11 as swel1ing of the fibers themse1ves. The location of these basic lesions and the type of response of the adjacent tissues are somewhat different in the different coIIagen diseases, and constitute the anatomic basis bx which they may be at least partI>clistingmshed. Abnormal colIagen may be detected b\; suitable x-ray diffraction studies and e1ectron microscopy. KeIIgren beIieves that this will prove a useful method for diagnosing connective disorders.
diseases is not produced fibri63
Not a11 cIinica1 subdivisions of the coIIagen diseases are cIearIy demarcated. In some patients, at necropsy, lesions peculiar to or predominant in some of the different entities may be found in one and the same patient. For exampIe, a fata case may show: (I) chronic skin lesions, as in scIeroderma; (2) atrophy of skin, and degeneration of muscIe, as in dermatomyositis; (3) proliferation of endotheha capihary tissue, as in disseminated Iupus erythematosus; (4) non-bacteria1 verrucous endocarditis;* (3) infiItration and dilatation of arterioIes, as in periarteritis nodosa; (6) pericardia1 changes, as in rheumatic infection; and (7) articuIar and tenosynovia1 changes, as in rheumatoid arthritis. A case embodying a11 these diverse manifestations was recorded by Kampmeier.“j hliaIezl mentions that Krupp first emphasized a characteristic urinary finding in “viscera1 angiitis”; he found the pattern in fourteen of twenty-one cases of periarteritis nodosa and disseminated Iupus erythematosus. It consists of the simultaneous presence of eIements usuaIIy characteristic of the earIy stages of nephritis (erythrocytes and erythrocytic casts), and eIements usuaIIy seen in the chronic stage (broad casts, waxy casts, fatty casts and “ova1 fat bodies”). This finding has been referred to as a “telescopic urinary sediment.” CLINICAL
affecting chiefly the medium-sized and smaller arteries of the body. PathologicalIy there is a degeneration of the coIIagenous tissue in the walIs of the vesseIs, sometimes with necrosis of the media, rupture of the eIastic Iamina and infiItration of inflammatory celIs and eosinophils into a11 of the vascular layers. When this infiItration of the arterial coats is Iocalized, or is foIIowed by local Fibrosis, or the development of small aneurysma dilatations, nodular changes deveiop (giving rise to the term nodosa). CIinicalIy the signs and symptoms are determined more by the distribution of the involved arteries than by the disease process itself. Almost any cIinica1 condition may be mimicked. However, a polysystemic invoIvement with chronic fever, Ieukocytosis, eosinophiIia and secondary anemia suggests the condition, and is an indication for skin and muscIe biopsy. Recurrent hemoptysis has been reported by one group (Edwards et aI.‘). RoentgenoIogicaIIy findings may or may not be present, depending on which systems happen to be invoIved, and aIso on the acuteness and degree of that involvement. Cardiac enlargement and/or pericardia1 effusion occurs. The respiratory system may show massive symmetric or non-symmetric edema in severe acute cases. In others, small hazy shadows or non-co&l uent patches of edema (puImonary hives) may be scattered throughout the Iung IieIds, usuaIIy peripheraIIy and at the bases.1 Some authorsg*25 report cases in which the noduIation is most marked centraIIy. In addition to the noduIar densities, the puImonary Iinear markings may be accentuated, particuIarIy the hiIar and basa1 ones. Doub et al.6 report hilar enIargement as a conspicuous finding in a series of ten microscopicaIIy proven cases. PIeuraI effusion, secondary to pneumonitis or puImonary infarction, is reported11 not uncommon. Roentgen examination of the abdomen is frequentIy requested since abdominal pain is one of the most common earIy symptoms. A triad of myositis, abdomina1 pain and weight Ioss has been referred to by some. The ahdomina1 fiIms usuaIIy show either no abnormaIity, or some gas coIlections suggesting paraIytic obstruction (so-calIed adynamic ileus). Very rareIy, there may be a perforated uIcer, intestina1 infarction or pancreatic necrosis. One of our cases had both intraperitonea1 and retro-
The types of coIIagen disease to be discussed in the following pages include periarteritis nodosa, generalized Iupus erythematosis, dermatomyositis and scIeroderma. Space wiI1 permit onIy brief mention of the two more common entities, rheumatic fever and rheumatoid arthritis. The cases studied were obtained by a review of the IiIes in the roentgen departments and the record rooms at San Francisco HospitaI and Stanford University HospitaI. The period covered is approximateIy fifteen years, a majority of the cases having been indexed in the last ten years. PERIARTERITIS
Periarteritis nodosa is frequentIy and more correctIy caIIed poIyarteritis as there is actually a widespread poIy- rather than periarteritis, * Non-bacterial verrucous endocarditis, as in Libman-Sacks syndrome, is now known to be part of the changes occurring in disseminated Iupus erythematosus. 64
ileus. Three cases showed peptic uIcer (one gastric and two duodenal). No cases of gross renaI enIargement were recorded, but one did show poor function by excretory urography. No bone changes were noted; three patients showed roentgen evidence of articuIar disease (two svnovia1 thickening, one rheumatoid arthritis). Biopsy or necropsy materia1 compatibIe with the diagnosis of periarteritis nodosa was avaiIabIe in twenty of the thirtytwo cases. In seven cases biopsy reports were nenative. but the cIinica1 evidence was outstanding; two of these patients died apparentIv of the disease.* The folIowing are some illustrative cases: Case E. hf. (Fig. I), a white femaIe, aged joint pains, Iowtwenty-six, had migratory grade fever, myaIgia and patchy gangrene of some of the fingers and toes. She was known to have had periarteritis nodosa for two years. On ApriI 29, 1950, a roentgenographic examination of the chest was negative. Re-examination in two and one-haIf weeks showed smaI1 bilateral pIeura1 eff usions and a pericardial effusion. One month Iater, after cortisone therapy, cIinica1 and roentgenographic improvement was present. This case showed acute deveJonment of pleura1 and nericardial lesions during the course of a chronic multiple svstem disease. Biopsy of skin and mus& positive for periarteritis nodosa. Case R. S. (Fig. 2) a sixty-three vear old man, had fainting speIIs of unknown origin for a few weeks, and pain and stiffness of the shoulders and knees since a fall one month prior to entry. Initial chest roentgenograms showed onIy sIight Ieft ventricular enlargement. Two days later, JiIms showed biJatera1 pIeural effusion and puImonary congestion. CIinicaIIy he had become acutely ill, with high fever (up to 103.1’F.), but without evidence of cardiac _faiIure. Roentgen examination four weeks later showed clearing of the congestion and effusions, despite the fact that the patient was faiIing generaIIy. The urine then showed the so-caIIed telescopic abnorma1 Jindings, sediment, and the possibiIity of “viscera1 became entertained. He recovered angiitis”
peritonea1 bIeeding due to ruptured aneurysm of a smaI1 mesenteric vesse1, secondary to “healed” arteritis. A hypertension of 200/140 was present; this patient also had muItipIe duodena1 ulcers. TABLE I
KoENTGErG FINDINGS IN OF
No evidence of disease. Evidence of disease. Cardiac enlargement. PericardiaI effusion Pleura1 effusion., Pulmonary changes. ParenchymaI nodules, patches, etc. PuImonary congestion, passive. Accentuated markings, ? arteritis.. Pulmonary edema, massive.
6 6 7 16
(6 .6 .4 .4
Note: Some of the cases with “cardiac” enlargement may also have had some pericardial effusion.
Rena1 lesions are the most common of all the systemic Iesions, being present in 80 per cent of the cases.lg OccasionaIIy hypertension or hematuria may be so prominent that intravenous urograms are requested. These usuaIIy show either norma or decreased function. The records of thirty-two cases of periarteritis nodosa were reviewed. In thirty-one of these, chest films were avaiIabIe and disclosed the findings shown in TabIe I. It is to be noted that some cases had more than one finding (~e.g., pericardia1, pIeura1 and pmmonary lesions). At autopsy one of our patients had both poIyarteritis and rheumatic heart disease (mitra1 and aortic stenosis with insufhciency). His roentgenograms showed an enIarged heart, pulmonary congestion and pIeural effusion. None of the foregoing roentgen findings are diagnostic per se of periarteritis nodosa, but the presence of pulmonary, pIeura1 or cardiopericardia1 changes in a patient with invoIvement of other systems, shouId cause one to bear the possibiIity of a coIIagen disease in mind. In the entire thirty-two cases adequate roentgenoIogic records of systems other than the cardiorespiratory were Iimited. In two cases hepatomegaly and in two cases spIenomegaIy were noted by our department. One case showed roentgen evidence of miId paraIytic
* Most of the histopathoIogic studies referred to in connection with the cases reported in this paper were made bv members of the Stanford Universitv MedicaJ School -Department of Pathology staff; in -a few instances material was reported by the University of CaIifornia staff at the San Francisco HospitaI, to whom we are indebted.
FIG. I. Case E. M. Periarteritis nodosa. Development of acute pericardial and bilateral pleura1 effusions during a chronic illness of two years. Biopsy positive. White, female, aged twenty-six, with arthralgia, myaIgia, fever and gangrene of tips of fingers and toes. A, chest fiIm negative; pericardial friction rub present. B, pericardia1 and biIatera1 pIeura1 effusions. C, improvement: also improved cIinicaIIy, under cortisone therapy. (Courtesy of Am. J. Roentgenok)
FIG. 2. Case R. S. Periarteritis nodosa. Rapid development of pericardia1 and biIatera1 pIeura1 effusions. Negro, maIe, aged sixty-three, with fainting speIIs, fever, pain and stiffness of shouIders and knees. A, lungs clear; questionabIe Ieft ventricuIar enlargement. B, puImonary congestion, pericardial and pIeura1 effusions; patient now acuteIy iI1. C, improved. (Courtesy of Am. J. Roentgenok)
his Ieg for two years, with IocaI uIceration. Pain in the right upper abdomina1 quadrant, a markedIy enIarged Iiver and massive hematuria were present. He had a hypertension of 18oj80; his bIood urea was 27 mg. per cent; the white Mood ceI1 count was normaI. Roentgenograms showed cIouding of the right upper Iobe and of the Ieft mid-Iung fieId, interpreted as puImonary edema; moderate spIenomegaIy was noted on abdomina1 fiIm. Nine days after entry the patient was cIinicaIIy and roentgenoIogicaIIy improved. Biopsy was not performed. A year Iater his chest fXm continued to be negative. Case G. H. B., a white maIe, aged forty, was cIinicaIIy diagnosed as having rheumatoid arthritis. Roentgenograms showed cardiomeg-
partiaIIy and was discharged. Biopsy of skin and muscIe was reported negative. Case L. E. L. (Fig. 3), a white femaIe, aged thirty-four, had asthma for one year and numbness of the Ieft Ieg and pain in the Ieft foot for six months. She was found to have spIenomegaly, eosinophiIia and a renaI Iesion, with casts and ceIIs. Chest fiIms showed pulmonary noduIation, fibrosis and emphysema. Biopsy of skin and muscIe was negative. h/larked clinica and roentgenoIogic improvement occurred within three days after cortisone was started. She was discharged improved. Case R. C. (Fig. 4), a white Iongshoreman aged forty-five, entered on August 12, 1948, with chiIIs, fever (IOI’F.), miId cough, chest pain and dyspnea. He had had a dermatitis of 66
FIG. 3. Case L. E. L. \\‘hite, female, aged Irsion with casts and right mid-lung field.
Periarteritis nodosa. Pulmonary nodulation and improvement under cortisone therapy. thirty-four. Asthma for one year; then Ieg pains, eosinophilia, splenomegaly, and renal ceils. A, pulmonary noduIation and possible emphysema. B, Iateral view. C, close-up of D, marked improvement on fourth day of cortisone therapy. Ieft
(2) PuImonary emphysema (and fibrosis). (3) Generalized arteriosclerosis (coronary, aortic and renal). This case iIIustrated a combination of four notypes of “coIlagen ” disease-periarteritis doss, Iupus erythematosus, rheumatoid arthritis and rheumatic carditis. Case I. S. (Fig. s), a femaIe singer, age thirtyone, was hospitahzed for mental disturbance. She stated that she had had severe asthma for
died shortly after examination, apparentIy from cardiac failure. Autopsy showed: (I) diffuse collagen disease with poIyserositis (peritoneal, pleural and pericardia1 fluid); rheumatic heart disease (aortic valve stenosis); “wire-1ooping” of renal gIomeruIi (as in Iupus erythematosus); rheumatoid arthritis; periarteritis nodosa (of puhnonary, thyroid and testicular arteries). Matera
FIG. 4. Case R. C. Acute periarteritis
nodosa, with asymmetric puImonary “edema.” White, male, Iongshoreman, miId non-productive cough; then right aged forty-five. Four days previously onset of chilliness, fever (IOI’F.), upper quadrant pain, massive hematuria, some hepatomegaIy. EosinophiIia 9 per cent, bIood urea 27 mg. per cent. A, on fourth day of illness showing densities suggesting puImonary edema. B, improved, roentgenoIogicaIIy and cIinicaIIy. C, one year Iater, chest negative.
sixteen months with muscIe and joint aches, abdomina1 pain and nervousness. She was found to have “spIinter” hemorrhages of the finger naiI beds, conjunctiva1 petechiae, a grade II puImonic systoIic murmur, raIes at the lung bases, spIenic and hepatic enIargement, and a temperature spiking to 103’~. The white blood count was 21,000 with 30 per cent eosinophils; the urine contained aIbumin, granular and hyaline casts, and a few red and white bIood ceIIs. Chest x-rays showed a puImonary edema pattern, with a small area of Ieft upper Iobe consoIidation; six days Iater there “bat-wind” edema with smaI1 was extensive noduIes in the right costophrenic area; there was aIso a smaI1 pIeura1 and a pericardia1 effusion. Biopsy of calf muscIe was reported perivascuIar inflammation, and of skin as chronic dermatitis. Cortisone resuIted in exceIIent subjective response. Fever stopped, strength improved, but the spIenomegaIy and hepatomegaIy persisted. She was discharged as improved. DISSEMINATED
worse by sunIight or uItravioIet Iight or such Iight-sensitizing drugs as the sulfonamides. Patients may show fatigue, arthraIgia and fever. The Iaboratory findings incIude Ieukopenia, an eIevated sedimentation rate, a “teIescopic” urinary sediment and the presence of so-caIIed Iupus erythematosus ceIIs. l5 These Iupus erythematosus ceIIs, found onIy in this disease, are seen in various preparations of Hood and bone marrow and are reportedIy Iarge Ieukocytes containing phagocytosed materia1 resuIting from Iysis of the nucIei of other Ieukocytes. PathoIogicaIIy, there is predominant invoIvement of the smaIIer arteries and arterioIes. PoIyserositis is common, with pericardia1 Iesions the most frequent. In the heart itseIf, Iesions predominate in the vaIvuIar structures and the mura1 endocardium. The kidneys, when invoIved, tend to be enlarged. The gIomeruIar vesseIs show the so-caIIed “wire-1oop” appearance due to eosinophilic thickening of the vascuIar Ioops within the gIomeruIi. OccasionaIIy, the renaI changes resembIe those of gIomeruIonephritis or periarteritis nodosa. The spIeen shows microscopic invoIvement in at Ieast haIf of the cases (periarterial fibrosis). The Iymph nodes are said aIso to be frequentIy invoIved, showing “free hematoxyIin-staining bodies.“* RoentgenoIogicaIIy, findings may be noted in the urinary and respiratory tracts. In the urinary tract, when a case of hypertension
Disseminated Iupus erythematosus, or systemic lupus erythematosus, is a disease most commonIy seen in women, and in the ages of twenty to forty. It is characterized by a cutaneous eruption, most often in the form of discoid Iesions-with a butterfly distribution over the nose and cheeks-aIong with varying degrees of viscera1 manifestation, notabIy in kidneys, heart, spIeen and Iungs. The skin Iesion is frequentIy photosensitive, being made
* Klemperer, P. et al. CytochemicaI changes of acute lupus erythematosus. Arch.Path., 49:503-316,1950. 68
FIG. 5. Case I. S. Periarteritis nodosa, with pulmonary “edema,” small nodules and patchy den&tics and pleural and pericardial eftusions. FemaIe, aged thirty-one, with asthma, muscle, joint and abdominal pains, conjunctival and nail-bed petechiae, enlarged liver and spleen, spiking fever, leukocvtosis w-ith 30 per cent twsinophilia, and telescopic urinary findings. Muscle biopsy consistent with diagnosis. Partial response to cortisone. A, moderate putmonary “edema” with small area of consolidation in Ieft upper lobe. B, six days later extensive “edema,” smaII noduIes in right costophrenic area and small right pleura1 and pericardial effusion. C, sixteen days later, after being on cortisone for about one week. Lungs improved but pericardial eftusion slightly increased. D, three months later; residual prominence of pulmonary markings, and increased pcricardial effusion. Iarne kidnevs. the Dossibilit\ sheMS unusuaIIv Iupus erythematosus rather of disseminate2 nephritis must be th; in a chronic gIomeruIar Patients with the Iatter condition COIlsidered. kidneys. ter ~tl to have sma11 or contracted
Pulmonarv involvement is remarkable its frequency and its atypical course. Ral and TavIor,2J and FoIdes” describe a chro intersti&aI pneumonitis which Ieads to ateIec sis (due to interstitia1 edema and inffammat
resuIting in obliteration of some aIveoIi)-termed ateIectasizing pneumonitis. These Iesions are regarded as different from the ordinary pyogenic and fibrinous types of bronchopneumonia which so frequently compIicate the termina1 stages of lupus erythematosus. TABLE CHEST
No evidence of disease. Evidence of disease, Cardiac enIargement PericardiaI effusion PIeuraI effusion. PuImonary changes. (Accentuated markings, or edema)
patients had clinica evidence of joint disorder, none were so reported roentgenoIogicaIIy (IargeIy because examination was not regarded as necessary by the ward physician). Biopsy or necropsy materia1 compatibIe with the diagnosis of disseminated Iupus erythematosus was avaiIabIe in twenty-four of the thirty-live cases. In two cases biopsy reports were negative. It is currently beIieved that search of the bIood or bone marrow shouId repIace biopsy, being an easier and more accurate method of diagnosis. The folIowing are iIIustrative case reports: Case N. F. (Fig. 6), aged nineteen, white, had a facia1 rash of butterfly shape, fever, joint pains for six months and generalized edema (nephrotic syndrome?) for four weeks. Chest fiIms showed a smal1 amount of fluid in the costophrenic suIci. This minima1 bilateral effusion, without other roentgen evidence of chest disease, is one of the more suggestive findings of disseminated Iupus erythematosus in patients with concomitant cIinica1 hndings. Biopsy was not performed. Case T. S. (Fig. 7), a thirteen year old boy, entered with high fever and weakness, splenomegaIy and Iymphadenopathy of two months’ duration and a butterfly facia1 rash of one month’s duration. The initia1 chest Mm showed markings. sIightIy accentuated pulmonary Three days Iater bedside fiIms showed a biIateraI pneumonitis, and six days later the patient died. Autopsy showed a disseminated and aIso a biIatera1 lupus erythematosus atypical Iobar pneumonia with features suggesting the anaphyIactic pneumonia of Rich. This is a type reported by Rich as occurring in rheumatic fever and suIfonamide sensitivity. Case F. R. (Fig. S), a schoo1 gir1, aged Fifteen, deveIoped painfu1, swo1Ien joints and fever. Chest roentgenograms showed a “waterbottle” shaped heart suggesting pericardial effusion (this was confirmed by roentgenoscopy) ; she also had minima1 bilateral pIeural effusions. Examination eighteen days Iater showed a marked decrease in heart size; the pIeura1 effusions were unchanged. The clinical diagnosis was disseminated lupus erythematosus. No biopsy was performed. Case R. P. W., a thirty-six year oId white man, gave a history of chorea at the age of tweIve, and had developed a butterffy rash two and one-haIf years ago, then hematuria and fever, weakness and fatigue. Ten months ago he
12 23 5 5 I5 II nodules,
ThoreI130 reviewed the roentgenograms of fifteen cases of disseminated Iupus erythematosus and found eight with pIeura1 or puImonary parenchyma1 changes, or both. The pIeura1 effusions were generalIy smaI1; the pleura1 thickening more or Iess irreguIar. These pleura1 changes varied in extent in reIativeIy short periods of time. The parenchyma1 changes consisted of smaI1 areas or patches of increased density, mostIy subpIeura1, especiaIIy in early and moderate1-y advanced cases. (He used different obIique projections to bring out the subpIeura1 Iocation of the Iesions.) He beIieved that a combination of pIeura1 and subpIeura1 change ought to Iead to the correct diagnosis even if the changes in themseIves were not characteristic. In our experience pIeura1 and pericardial effusions were the most common Iindings in this group. The puImonary parenchymal changes varied from IocaIized accentuated markings, noduIes and patches to extensive edema. We have reviewed the records of thirty-eight cases, in thirty-five of which chest fiIms were avaiIabIe. (TabIe II.) In these cases the puImonary changes consisted of accentuated basa1 bronchovascuIar markings in two instances, of noduIar or patchy pulmonary densities (edema?) in seven instances, and of diffuse puImonary density (edema) in two instances. As far as other anatomic sites are concerned, our roentgenoIogic findings are Iimited. In one case hepatomegaIy was reported; in two cases ascites was noted. No gastrointestinal Iesions were detected. In one case sIight osteoporosis of the hands was noted. WhiIe many of our 70
FIG. 6. Case N. F. Disseminated lupus erythematosus, with small bilateral pleural eflusions. LVhite, female, aged nineteen, with facial rash, fever and joint pains for six months. “Nephrotic syndrome” for four weeks. A, bilateral pleura1 effusions. B, right oblique view; fluid seen posteriorly. Similar findings wcrc present in left oblique view. (Courtesy of Am. J. Roenrgenol.)
Frc;. 7. Case T. S. Disseminated lupus erythematosus, with development of atypical pneumonia or pneumonitis. R’hite, male, aged thirteen. Fever, weakness, splenomegaly and lymphadenopathy for two months. ButterAy facial rash one month. A, sIightIy accentuated pulmonary markings. B, bedside film. Consolidation right (? pneumonia) ; patchy basal densities on left (? pneumonitis). Patient died six days later. Autopsy showed disseminated luaus ervthematosus and bilateral atypical Iobar pneumonia, with features suggesting anaphylactic pneumonia. (&urte& of Am. J. Roentgenol.) .. \vas
nated Iupus erythematosus and aortic insufficiency was made. The blood pressure was I 70: 96. Recently marked orthopnea and minimal edema developed. The blood pressure
varied from 16oj90 to ZOO/I IO. Roentgenograms ten days before death showed cardiac enlargement. The patient died in cardiac faiailure. Autopsy showed a chronic gIomeruIar nephritis (without evidence of disseminated
FIG. 8. Case F. R. Disseminated Iupus erythematosus showing marked pericardial efi usion and minimal pIeura1 effusion. White, femaIe, aged fifteen. Painful swollen joints and fever. A, “ water-bottIe” heart due to pericardial effusion; smaI1 biIatera1 pIeural effusions. B, IateraI view. C, marked decrease of pericardial effusion; minima1 pIeura1 effusions persist. (Courtesy of Am. J. Roentgenol.)
Iupus erythematosus) and spIeen Iesions consistent with disseminated lupus erythematosus. There was microscopic evidence of active rheumatic Iesions. This case again showed a combination of “coIIagen” diseases.
A. GastrointestinaI tract: I. Esophagus a. Loss of peristaIsis due to rigidity b. VariabIe degrees of dilatation c. Occasiona narrowing of dista1 esophagus d. Occasiona shortening of esophagus 2. Stomach: a. PeristaIsis may be decreased b. Hiatus hernia may deveIop 3. SmaII intestine: a. PeristaIsis decreased or absent b. Widening, especiaIIy of duodenum and jejunum; this may be segmenta 4. CoIon: a. Feristalsis decreased b. SegmentaI narrowing B. Lungs: I. Diffuse or IocaIized fibrosis 2. Diffuse or IocaIized noduIation 3. SubpIeuraI “cystic disease” (basa1) 4. CaIcification (caIcinosis) C. Heart: I. Decreased ampIitude or excursion 2. Heart may be smaI1, norma or Iarge D. Phalanges: I. Absorption of dista1 phaIanges in advanced cases 2. Occasiona increased density of phalanges 3. Occasiona synostosis, dista1 and middIe phaIanges E. Soft tissues: I. CaIcinosis-fairIy frequent and often accompanies phaIangea1 absorption a. Varies from “sand” to pIaques 6. UsuaIIy in pressure areas: fingertips, elbows, ischial tuberosities c. UsuaIIy seen onIy where there is cutaneous scIerosis F. Teeth I. Uniform widening of the periodontal spaces (reported in 7 per cent of cases)
Dermatomyositis is the rarest of the coIIagen disease group and is characterized by a nonsuppurative inflammation of the skin, subcutaneous tissues and skeIeta1 muscIe. There aIso may be inflammatory changes in the vesseIs, myocardium and muscIes of degIutition. LittIe is known about the roentgenoIogic features. We have had onIy one autopsy proved case, this showing a cIoudy sweIIing of the myocardium and a congestive faiIure. Chest roentgenograms taken a year before death showed the heart to be sIightIy Iarger than normaI, but severa weeks before death the heart vesse1 shadow was norma in size. The Iungs were cIear. SCLERODERMA
ScIeroderma is a poIysystemic disease, with fairIy we11 known roentgen findings. (TabIe III.) Large series of cases have been reported in the Iiterature, one of the most comprehensive, from the roentgenoIogic viewpoint, being that by Pugh.23 Based on this materia1 plus our own experience we beIieve that TabIe III summarizes the more important roentgenoIogic changes in this disease. We have reviewed ten microscopicaIIy proved cases of scIeroderma in our hospita1, five of 72
disease of the lung bases. Negro, female, aged thirty. FIG. g. CaseD. R. ScIeroderma, with “cystic” Scleroderma for twelve years. A, mottIed radioIucencies (? cysts) in lung bases. B, IateraI view. C. tuft absorption and cakinosis. D, detai1 view of “cystic” appearance; the lesions are smaI1, resulting in a “spongy” appearance on the films. (Courtesy of Am. J. Roentgenol.)
which showed some degree of smaII intestina1 abnormaIity. One of the ten cases showed pulmonary disease. Case R. L. P., a seventy-five year oId Chinese man, had weight Ioss (from 130 to I 16 pounds), marked weakness, dyspnea, ankIe edema and a cough productive of white, frothy phIegm. The skin of the face and fingers appeared drawn, tense and shiny. He died of a ruptured diverticuIum (diverticuIitis) of the mid-ascending coIon eight days after starting on corticotropin. Chest roentgenograms five
months before death showed minimal prominence of the Iower Iobe puImonary markings and slight cardiac enIargement. Examination three days before starting corticotropin showed hazy widening of the puImonary markings throughout both lung lieIds, with a few areas of smaI1 (2 to 3 mm.) hazy noduIes aIong the course of these markings. The changes were more evident in the right upper lobe, where one patchy density (1.5 by 3 cm.) was also present. The left costophrenic suIcus was bIunted by fIuid. 73
and Sisson ence in connection with so-caIIed “rheumatic many writers do beIieve that pneumonitis,” such an entity is common and diagnosable. For exampIe, BIand and Jones3 mention that “areas of consoIidation in the Iungs, pecuIiar in their cIinica1 behavior, occur in rheumatic pneumonia.” Ch ancey4 describes three types of rheumatic pneumonitis: a primary acute type which may be the presenting sign of rheumatic fever, a secondary acute type which occurs in the estabIished case of rheumatic fever and a “subcIinica1 pneumonitis” which is often discovered accidentaIIy in patients with subacute, monocycIic rheumatic fever. Part of the confusion may arise from the fact that pathoIogicaIIy there appears to be a distinct entity. Neubuerger et aI. reviewed the pathoIogic tindings on sixty-three cases of active and quiescent rheumatic fever, and noted eight in which there was puImonary inff ammation with .distinctive microscopic features. These incIu&ed .pecuIiar granuIomas in the aIveoIar ducts and .aIveoIi, foca1 aIveoIitis with necrosis, mononucIear ceI1 exudation and septa1 ceI1 proIiferation. The rheumatic puImonary granuIoma has been referred to as the Masson body, aIIegedIy simiIar to the Aschoff body which is found in the heart. SeIdin et aLz7 beIieve that there is IittIe dificuIty in microscopicaIIy distinguishing rheumatic pneumonia from bacteria1 or vira1 forms. Rheumatoid arthritis is frequentIy compIicated by myositis, neuritis and arteritis, as demonstrated in 70 per cent of muscIe biopsies by Traut3* and Campoine. Traut also states that these biopsies show aggregates of Iymphocytes, epitheIiod ceIIs and pIasma ceIIs somewhat similar to those in dermatomyositis, Iupus erythematosus and scleroderma. Pericarditis is the onIy unusuaIIy frequent cardiac compIication, being especiaIIy common in juveniIe rheumatoid arthritis (StiII’s disease). In addition, a pneumonitis and pIeuritis may occur aIong with the inflammatory reaction in the joints but is rare. The roentgen findings in the bones and joints of patients with rheumatoid arthritis are we11 known. WhiIe we have seen no convincing evidence of specific pneumonitis in connection with rheumatoid arthritis, EIIman and BalIlO report three cases in which they beIieve there was such reIationship. The roentgen findings in one case consisted of “fine reticulation” with chronic bronchopneumonia. In one there was
Among severa cIinicaIIy diagnosed cases of scIeroderma, we have seen one with subpleural cystic changes. Case D. R. (Fig. 9), a thirty year oId Negro woman, had definite scIeroderma for tweIve years. Chest roentgenograms showed a pecuIiar “spongy” appearance in the bases, presumabIy due to cystic changes, as described by Getzowa’3 in two cases. These were cases interpreted as exampIes of “cystic and compact puImonary scIerosis.” The “cysts” varied from pinhead size up to 1.5 cm. in diameter. OnIy one showed concomitant extensive fibrosis. The cyst-Iike changes were believed to be due to a disappearance of aIveoIar tissue in the Iung secondary to Iysis of the aIveoIar waIIs and progressive sclerosis. This scIerosis is reportedly on a basis of a “ hyaIine process invoIving the aIveoIar waIIs, accompanied by the disappearance of capiIlaries, superimposed on a generaIized, diffuse simpIe fibrosis of the aIveoIar waIIs.” Shuford et aI. found that six of thirty-seven patients cIinicaIIy diagnosed as scIeroderma had abnormal chest x-rays. One had puImonary edema (as a termina1 phenomenon). Five had widespread Iinear reticuIated infiltration, more marked in the Iower haIves of the Iung fieIds. They beIieve that differentiation from other diseases causing diffuse interstitia1 puImonary fibrosis is diffIcuIt, if not impossibIe. The pneumoconioses cIassicaIIy have a noduIar rather than Iinear type of fibrosis, with emphysema (which is absent in scIeroderma). HiIar adenopathy is frequent in sarcoid but rare in scIeroderma. RHEUMATIC
We have reviewed some of the recent Iiterature on rheumatic fever and rheumatoid arthritis, but have not anaIyzed in detai1 our cases of these diseases. Acute rheumatic fever is regarded as a coIIagenous degeneration which IocaIizes seIectiveIy in the heart. The changes may be found in many other organs, as shown by the arthritic, derma1, serosa1, intestina and puImonary manifestations of the disease. In acute fuIminating form, puImonary compIications are reportedIy found in as high as 50 per cent of cases.14 “Rheumatic pneumonitis” has no specific diagnostic features, in our experience. Pericarditis is not uncommon. The invoIved joints tend to show onIy articuIar and periarticuIar swelIing. While the foregoing has been our own experi74
bilateral patchy consolidation in the bases, with “reticular shadows” in the middle thirds of the lungs. In the third case there was widespread “heavy reticuIation and miliary mottling.” The first and second cases were autopsied and showed interstitia1 pneumonitis and tcrmina1 bronchopneumonia; the pneumonitis had we11 marked fibrinoid necrosis between the lung aIveoIi, similar to that described in other collagen diseases. COMMENTS
The skin and muscles may show microscopic evidence of involvement in any of the four types of collagen disease discussed in this paper.* HistopathoIogic changes are reported13 fairly decisive in a11 except dermatomyositis, about which not enough is yet known; they are said to be most clear-cut in periarteritis, but there is divergence of opinion as to their clarity in scIeroderma. The cardiac and pIeuropuImonary changes are many and non-specific. PericardiaI effusion, cardiac enlargement, pIeura1 effusion, puImonary nodular changes and variabIe degrees of pulmonary edema or fibrosis may occur. These changes may be reversibIe. AbdominaI distention, Lvith paralytic obstruction, may occur in the first two conditions. Renal eniargement may also be seen in these two (periarteritis nodosa and disseminated lupus erythematosus). The intestina1 tract changes are most conspicuous in scIeroderma, notabIy in the esophagus and smal1 intestine (variabIe degrees of rigidity, dilatation and narrowing occur in about 50 per cent of cases). The articular and osseous changes occur in Iupus and especially periarteritis nodosa, scIeroderma. RoentgenoIogicaIIy, they are characteristic only in the Iatter condition. CaIcinosis is aIso confined IargeIy to this disorder.
Collagen diseases constitute an interesting group of disorders-from the clinical side because of their diagnostic and therapeutic challenge, from the pathoIogic viewpoint because of recent interest in the interceIIular substances, and from the roentgenoIogic viewpoint because of their widespread but unfortunately non-specific nature.* The Iatter is particularly true of the pulmonary manifestations of the colIagen diseases. We believe, however, that diagnostic possibilities, sIim as they are, depend on an awareness of these conditions, pIus a knowledge that the patient has a polysystemic disease. It is desirabIe that radioIogists, as clinicians, be able occasionally to suggest the consideration of one of these diseases, on logical grounds, and be cognizant of the further studies, cIinica1, laboratory or pathoIogic, required to confirm the diagnosis. From a review of our roentgenologic findings, \ve believe that pulmonarv changes occur more frequently in periarteritis nodosa and disseminated lupus erythematosus than one would gather from the literature. Further, from a survey of the histories of over eighty patients with established or clinically diagnosed coIlagen disease, we have the distinct impression that peptic ulcers occur with relatively greater frequency in these conditions than in the rest of the hospital population in general. In studying a patient for possibIe coIIagen disease it is desirable that particular attention he paid to the following structures: (I) the skin and muscles; (2) the heart and pericardium; (3) the lungs and pleura; (4) the anti
We have reviewed currentIy accepted criteria conceining the pathoIogy, cIassification and diagnosis of the so-called coIIagen diseases. We have reviewed our persona1 experience with the roentgenologic aspects of these diseases, and have summarized our findings in thirty-one cases of poIyarteritis; thirty-five cases of generalized lupus erythematosus; one and twenty-fi\-e case of dermatomyositis; cases of scleroderma. In this entire group pathoJogic material was availabIe for study in sixty-four cases and was interpreted as “positive” for the particular disease in question in fifty-four instances. It is believed that awareness of the roentgenologic findings in these disease entities will give the clinical radiologist greater opportunity for reaching or suggesting the correct diagnosis in everyday practice.
* At the same time, it is believed that the term “coIIagen” disease is one of high abstraction, to be modified or abandoned as soon as the etiology and fundamental nature of these conditions becomes cst;rblishcd.
* Periarteritis nodosa, matosus, dcrmatomyositis 75
disseminated lupus and sclerodcrma.
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