Oral pathology American
Donald Kerr, Editor
Recurrent intraoral herpes simplex virus infection James 3’. Griffin, D.D.S., N.S.D.,* Athta, DEPARTMENT
erpes simplex virus is classically described and established as the etiologic agent in acute primary herpetic stomatitis and recurrent herpes labialis. Some degree of confusion has existed concerning the relationship of herpes simplex virus to intraoral recurrent aphthae. Various a.uthorslT2 and myself3 have reported the lack of any evidence relating this virus to recurrent aphthae. In view of the four cases to be presented, however, there is a true form of intraoral recurrent herpes simplex virus disease. CASE CASE
A 22year-old white woman was referred to Emory University School of Dentistry for diagnosis and treatment of vesicular lesions involving the labial gingiva. Clinical examination revealed a cluster of small ulcers involving the marginal labial gingiva of the right maxillary cuspid. The patient stated that she was frequently affected by ‘I fever blisters” but these had always heen present on the vermilion border of the lower lip. She also said that she occasionally experienced a ‘ ‘ canker sore. ’ ’ The clinical diagnosis was questionable. Routine Papanicolaou smears were taken and fixed in alcohol-ether. Additional smears were made and fixed in acetone for fluorescent ant.ibody evaluation. CASE
A 26.year-old lvhite woman initially presented with a “sore gum” following a restorative procedure on the lower left second molar. Examination revealed multiple small 1 to 2 mm. vesicles located on the lingual marginal gingiva of the aforementioned tooth. Approximately one year later the patient was reexamined following crown preparations on the upper right *Assistant Professor tCases 1 and 2 were
of Pathology, included in
Emory a previous
School of Dentistry. the author.3
cuspid and first molar; the lingual gingiw o C tlotlt tcvbth l)r(w~nfcvl c1ustc.w of mlall vesicles and shallow ulcers. The patient, was warninrrl arain approximatc~ly 2 years after the initial examination, and identical lesions wcr’c pwwnt aroun~l the, ling’“al marginal gingiva of the lower left first premolar and first molar whicall 11acI twcw prepared for cvrown and bridge restorations (Fig. 1). The patient Ilad lw~~n examine11 on wvrral owasions for recurrent herpes labialis. Each of the above examinations was followccl I)y routine Pnpanicolaou smwrs with alcohol fixation and additional srrwars fiwtl i II awtonc. CASE
A 20.year-old white woman came to my ORW complaining of a “gum boil”’ in the roof of the mouth. Examination revealed a I cm. cluster of I to 2 mm. vesicles and shallow ulcers on the lingual marginal gingiva of the upper right second premolar. The patient stated that she occasionally had ‘ ( fever blister9 L ’ ’ on hrr lips. Once before she had experienced a similar sore place in her mouth and her dentist had told her that he was uncertain as to what caused the lesion. Smears of the types tlescril~~d previously wtre taken. CASE
A 40-year-old associate an irritated palate. Clinical ulcers in three areas of the by recurrent herpes labialis Smears were taken and fixed
professor of periodontics presentrd with the chief complaint of examination revealed 0.5 t,o 1 cm. clusters of vesicles and shallon hard palate. The pat,ient stated that he was frequently affected but had not previously experienced an episode of intraoral lesions. in alcohol and acetone (Figs. 2, 3, and 4).
Smears fixed in 95 per cent alcohol or alcohol-ether were stained by routine Papanicolaou procedures.” Acetone-fixed preparations for fluorescent antibody study were washed in saline solution #and air dried. Stainings were accomplished initially with commercial fluorescein isothiocyanate labeled herpes simplex virus immune gamma globulin.* The lesions from episodes 2 a.nd 3 in Case 2 and from Cases3 and 4 “Sylvania
3. Case 4. Right 4. Case 4. MidIine
side of hard palate. Note the larger ulcer. of hard palate. Kate the definite vesicle present.
were stained with fluorescein isothiocyan;ttc~ Ialwlf~tl wI)l)it in~wwi(* g:~tunr;r globulin prepared in my laboratory, utilizing tlic~th!-lanli~lo-(~tl~~l c~cll~~losc~colum tL as described by Levy and Sober: and Riggs.” Slides wero stained 1’01’ 30 millutes, t.hen rinsed in three changes of saline solution ant1 coverslippcd with bui’fered glycerol-saline. Examination for fl~~orwrcr~ce was carried out, with ;L Reich& Zetopan microscope with a 200 wat.t rn~rcury wrc lamp and KG I:! and O(: 1 filtration. RESULTS
All casesand recurrences exhibited typical ballooning degeneration cells and multinucleated giant cells with ordinary cytologic staining and microscopy. All material stained with fluorescein isothiocyanate labeled herpes simplex immune gamma globulin exhibited positive fluorescence of ballooning degeneration cells and multinucleated cells. The fluorescence wa.s discretely located in particle form along the nuclear membranes and in the cytoplasm of tho cells. These cytologic findings are identical to those seen in acute primary disease and in recurrent. herpes labialis. DISCUSSION
Differentiation between acute herpetic stomatitis and the recurrent disease described here is based on the clinical appearance of the lesions and the degree or amount of infection. Acute disease generally involves multiple areas of the oral cavity, whereas the intraoral recurrent form is localized and t,he patient is not acutely ill. The character of the lesions is also different in the recurrent form, in which the lesions appear as a cluster of small vesicles ( 1 to 2 mm.) and ulcers (1 to 2 mm.) with t,hc ulcer base apparently lined by intact epithelium. The latter would indicate intraepit,helial vesicle formation. All patients stated that they had previously had “fever blisters” on their lips, and in Case 2 the patient was examined with recurrent herpes labialis. Case 2 also had verified intraoral recurrences. Obviously, the term recurrelit i&raorul disease is just,ified. It has been my cxprrience that acute disease is not necessarily primary disease, particularly in young adults. I have seen several casesof acute disease in adults with histories of recurrent herpes labialis. Isolation of virus from the lesions was not attempted because of the &al)lished reliability of fluorescent antibody for identification.“~ ‘-’ The clinical course of the intraoral recurrent lesions corresponded identically to that of recurrent herpes lahialis in that the lesions’healed within 7 to 9 days without scarring. SUMMARY
Four cases of intraoral recurrent herpes simplex virus disease have been presented. The cause of the lesions was verified by routine cytologic and fluorcscent ant,ibodg techniques. REFERENCES
1. Ship, T. T., Ashe, W. K., and Scherp, sore ’ ’ ; Tests for Herpes Simplex and Oral Riol. 3: 117, 1961.
H. W. : Recurrent Other Viruses With
((Fever Blister” Mammalian Cell
a.nd (lCanker Cultures, Arch.
2. Sircus, W., Church, R., and Kelleher, J.: Recurrent Aphthous Ulceration of the Mouth, Quart. J. Med. 26: 235. 1957. 3. Griffin, J. W.: Fluorescent Antibody Study of Herpes Simplex Virus Lesions and Recurrent Aphthae, ORAL SURG., OBAL MED. & ORAL PATH. 16: 945, 1963. 4. Papanicolaou, G. N.: Atlas of Exfoliative Cytology, Cambridge, 1954, Harvard University Press. 5. Levy, H. B., and Sober, H.: A Simple Chromatographic Method for Preparation of Gamma Globulin, Proc. Sot. Exper. Biol. SC Med. 103: 250, 1960. 6. Riggs, J. L., Loh, P. C., and Eveland, W. C.: A Simple Fractionation Method for Preparation of Fluorescein Labelled Gamma Globulin, Proc. Sot. Exper. Biol. & Med. 105: 655, 1961. 7. Biegeleisen, J. Z., and others: Rapid Diagnosis of Herpes Simplex Virus Infections With Fluorescent Antibody, Science 129: 640, 1959. 8. Lrbrun, Jaqueline: kellular Localization of Herpes Simplex Virus by Means of Fluorescent Antibody, Virology 2: 496, 1956. 9. meller, T. H., and Coons, A. H. : Fluorescent Antibody Studies With Agents of Varicella and Herpes Zoster Propagated In Vitro, Proc. Sot. Exper. Biol. & Med. 86: 789, 1954.