Oral lesions as the initial sign in pemphigus vulgaris

Oral lesions as the initial sign in pemphigus vulgaris Report

of a case

L. R. Eversole, D.D.S., M.H.D.,+ E. B. Kenney, B.D.Sc., D.D.S., M.S.,** and W. R. Sabes, D.D.S., M.S.D.,*“* Lexington, Ky. UNIVERSITY

OJ? KENTUCKY

COLLEGE

OF DENTISTRY

The histopathologic features of pemphigus vulgaris are quite ever, other diseases may display intraepithelial vesiculation the case presented here, indirect immunofluorescent staining junctive diagnostic procedure that confirmed the diagnosis of which at this time was confined to oral mucous membrane.

characteristic; howand acantholysis. In was used as an adpemphigus vulgaris

I

n developing a differential diagnosis of vesiculobullous lesions, certain diseases and their features are considered. These include pemphigus vulgaris, erythema multiforme, bullous pemphigoid, herpes simplex, bullous lichen planus, and Darier’s disease. Early diagnosis and determination of a definitive diagnosis are important because therapy for one disease may be ineffective or even harmful to the person with another disease. Biopsy, cytologic study, and immunologic studies are means by which a definitive diagnosis can be reached. The purpose of this article is to present a case in which bullous lesions were initially confined to the oral mucosa. Oral biopsy and immunologic studies provided an early diagnosis of pemphigus vulgaris. Steroid therapy was initiated and future management of the patient as severity increased was anticipated. CASE REPORT A 48-year-old Dentistry by her the oral mucosa. *Assistant **Associate ***Associate

354

white dental

woman was referred to practitioner for diagnosis

Professor, Department of Oral Pathology. Professor and Chairman, Department Professor and Chairman, Department

the University and treatment

of Kentucky of vesicles

of Periodontics. of Oral Pathology.

and

College bullae

of of

Oral lesions in pemphigus

Fig. erythema

1. Large bulla is present and desquamation.

Fig.

2. Marginal

Medical

history

gingival

in buccal

erosions

vestibule,

and desquamation

and the attached

in oral

gingiva

vulgaris

shows

355

marginal

pemphigus.

The patient indicated that she had had the routine infectious diseases of childhood and denied ever having had rheumatic fever. To her knowledge, she was free of allergy and had never reacted adversely to antibiotic therapy. She had previously been hospitalized for pregnancy, removal of a Bartholin cyst, and surgical repair of a rectal fissure.

Chief

complaint

The patient had scalp, axillary, and oral lesions for which she was under tetracycline treatment by a dermatologist. She had also received 106 units of penicillin intramuscularly 2 days previously. The clinical diagnosis of the scalp lesions aa related by her dermatologist was folliculitis, whereas the axillary lesion was believed to represent contact allergy or irritation dermatitis.

Physical scalp

examination

Examination dermis.

The

of the scalp lesions revealed numerous waxy erythematous, axillary lesion was edematous,

solid nodules embedded in the and weeping in areas; yet,

356

Evewole,

Kemey,

awl

Oral surp.

Sabes

Fig. 3. Biopsy of oral mucosn displays suprnbasilnr stain. Magnification x50.)

hlnrch, 1972

ncantholysis.

(Hematoxylin

and eosin

according to the patient, it was undergoing resolution. No vesicles or bullae were present on the remaining skin surfaces. Intraoral examination revealed numerous extensive plaquelike bullae with mildly erythematous bases on the soft palate, buccal mucosa, and mandibular labial vestibule; these had been present for 2 months (Fig. 1). The attached gingiva showed evidence of rather severe marginal desquamation, with no intact bullae or vesicles (Fig. 2). Palpation of the submandibular and cervical lymph nodes proved negative for lymphadenopathy, and the patient was afebrile. The clinical differential diagnoses included benign mucosal pemphigoid, benign mucous membrane pemphigus (Hailey and Hailey disease), pemphigus vulgaris, erythema multiforme, desquamative gingivitis, and bullous lichen planus. Specimens for biopsy were obtained from the soft palate and maxillary gingiva. Samples of blood serum were secured for laboratory studies. MATERIALS

AND METHODS

Special laboratory scopic impressions. Indirect

immunofluorescent

tests were undertaken

to confirm the clinical

and micro-

microscopy

A specimen for biopsy was taken from the maxillary gingiva and frozen on COZ ice. Frozen sections were cut on a Harris cryostat at 10 microns and placed on glass slides. The sections were overlayed with serial serum dilutions (patient’s serum) of 1 :l, 1:2, 15, 1 :lO, 1:25, and 1:50 and incubated in a moist chamber at 37O C. for 30 minutes. Slides were subsequently rinsed in saline solution, three changes 5 minutes each, air dried, and covered by full-strength fluoresceinlabeled rabbit anti-human gamma globulin (Pentax, commercially separated by gel-filtration chromatography). The sections were stained 30 minutes at 37O C., rinsed in three changes of saline solution, and covered-slipped with glycerine. The sections were examined under a Wild fluorescent microscope utilizing an Osram HBO-200 mercury vapor source with UG-1 and BG-38 filters transmitting an ultraviolet spectrum of 325 to 405 m p. A GG-13 Barrier filter was interposed between the objective and ocular lenses.lG

Volume Number

Oral lesions in pemphigus

33 3

Fig. 4. Histologic section shows within the bullous cavity. (Hematosylin

Pig. 5. Fluorescent lining the bullous cavity. Magnification, x400.)

Radial

immunodiffusion

basal cell layer and acantholytic and eosin stain. Magnification,

photomicrograph (Rabbit anti-human

“Tzank” x300.)

shows positive immunofluorescence y-globulin labeled mith fluorescein

vulgaris

cells

357

present

of basal cells isothiocyanate.

for class globulins

Agar diffusion gels containing anti-IgG, IgM, and IgA (Hyland Laboratories) were charged with serum and incubated with control and standard globulins for 24 hours at 25O C. for IgM and IgA, and for 4 hours at 37O C. for IgG. After the appearance of precipitin rings, the diameters were measured and quantitated against a standard curve.17 Antinuclear

factor

Serum was sent to the clinical laboratory for testing.

358

Eversole,

Fig. 6. Fluorescent photomicrogrsph stance. (Rabbit anti-human y-globulin x400.)

RESULTS Microscopic

Oral March,

Kenney, and Sabes

shows immunofluorescence labeled with fluorescein

of interepithelial isothiocyanate.

Surg. 1972

cement subMagnification,

features

The surface mucosal epithelium evinced an intraepithelial cleft, and acantholytic cells could be identified in the bullous cavity (Figs. 3 and 4). Dyskeratotic cells were not encountered. Diagnosis: Changes highly suggestive of pemphigus vulgaris. lmmunofluorescence

Autoantibody was detected in the cytoplasm of the basal cells, acantholytic cells, and in the intercellular areas of the spinous cell layer (Figs. 5 and 6). Serum titrations of 1:50 continued to yield positive fluorescence. Radial

immunodiffusion

Precipitin rings for IgG, IgM, and IgA were quantitated at 910, 135, and 340 mg. per cent, respectively (Fig. 7). Normal ranges for class globulins are: 860-1,450 IgG, 70-125 IgM, and 110-255 1gA.l” Antinuclear

factor

Laboratory

results concerning

the presence of the antinuclear

factor were

negative.

The patient was referred to a dermatologist for treatment of her disease. Steroid therapy was initiated. Approximately 2 months after the diagnosis of pemphigus vulgaris was made, widespread skin lesions developed. The patient

Volume 33 Number 3

Oral lesions in pemphigus vulgaris

359

Fig. 7. Mancini radial immunodiffusion rings for the quantitation of serum IgA. Left: Control plate for IgA, 165 mg. per cent (black dot in lower right corner is artifact). Right: Precipitin ring for IgA from serum of patient with oral pemphigus, 340 mg. per cent.

was hospitalized for intensive steroid therapy and regulation. Skin and oral mucous membrane lesions responded. The patient, however, developed streptococcal septicemia and pneumonitis. High-dose antibiotic and electrolyte therapy was instituted. The patient remained in intensive care for 10 days and responded to antibiotic therapy ; however, her present status 3 months after the initial diagnosis is somewhat unstable. DISCUSSION Oral lesions have been widely reported to have great significance in the diagnosis of the pemphigus group of diseases.l-l* The oral cavity was the site of the first evidence of vesicles and bullae in 25 per cent of all cases of pemphigus reported by Lever.5 In one review of pemphigus vulgaris, 36 of 100 patients presented with primary oral lesions12; in another report, 18 of 33 patients with the acute type of pemphigus vulgaris had primary oral lesions, and 4 of 35 patients with the chronic type of pemphigus vulgaris had their first lesions in the mouth.5 Oral lesions become more prominent as the clinical course of pemphigus vulgaris develops, with reports of 74 of 80 patients eventually having oral lesions.12 Because of this common occurrence of typical pemphigus vulgaris vesicles and bullae in the oral cavity, some authors s95*Ghave suggested that biopsy of oral lesions is the best method to confirm the diagnosis, because both the skin and oral lesions show a similar clinical and histopathologic appearance. Skin lesions generally occur either at the same time as oral lesions or within a few months. The clinical appearance of vesicles in pemphigus vulgaris can be similar to that of those seen in benign mucous membrane pemphigoide; however, the histopathologic picture is quite different. In pemphigus vulgaris the basement membrane is intact and cleavage occurs in the stratum spinosum of the epithelium, whereas in benign mucous membrane pemphigoid the basement membrane is disrupted and cleavage occurs between the connective tissue and the epithelium.2949 6910

360

Eversole,

Kenney, and Sabes

Oral March,

Surg. 1972

Skin autoantibodies, as evidenced by utilizing immunofluorescent staining methods, have been demonstrated in previous studies.13-l5 Beutner and coworkers13l I4 demonstrated the presence of autoantibody to epithelial intercellular substance in pemphigus vulgaris. Recently, Peck and associates’5 quantitated antiepithelial autoantibody by using serum titrations in patients suffering from pemphigus and bullous pemphigoid (basal lamina autoantibody). They noted a correlation in titer activity with clinical severity of disease. Autoantibody was present in pemphigus rulgaris in 30 per cent of the cases. Application of this technique in the diagnosis of oral mucosal pemphigus has been reported by Bean, Alt and Katz.lg These authors were able to detect antibody by utilizing a direct immunofluorescent procedure and indicated that circulating antiepithelial autoantibody could not be detected by indirect methods. The patient in our study displayed positive indirect immunofluorcscence with serum titers up to 150 dilution. Interestingly, quantitative class immunoglobulin assay demonstrated a twofold elevation in serum IgA, whereas IgG was found to be within normal iimits and IgM was slightly elevated. Immunoglobulin A is the principal globulin present in salivary secretionsCo Whereas no direct evidence has been presented to suggest a prominent role for IgA in the pathogenesis of oral mucosal lesions, the possibility exists that this may be the case. Selective indirect staining of oral bullae in pemphigus with the use of appropriate fluorescein-labeled antibody to specific class globulins in conjunction with selective blocking and control agents may be useful in determining the role of IgA in the pathogenesis of oral epithelial acantholysis in pemphigus vulgaris. SUMMARY Reported is the case of a 4%year-old woman in whom oral mucosal bullae developed as the initial lesions of pemphigus vulgaris. Diagnosis was established through biopsy and immunologic studies. The histologic features were consistent with the diagnosis of pemphigus vulgaris. Aut.oantibody was detected in the cytoplasm of basal cells, acantholytic cells, and the intercellular areas of spinous cells. This was positive in a dilution of 1:50. Radial immunodiffusion revealed a twofold increase in the patient’s serum IgA. The early diagnosis prior to skin eruption helped the dermatologist to prepare in advance for increased severity of the disease. REFERENCES 1. Zamet,

2. 3. 4. :: 7. 8.

5. S.: Periodontal Therapy in a Case of Pemphigus Vulgaris, Periodontics 5: 47-48, 1967. Shklar, 0.: The Oral Lesions of Pemphigus Vulgaris, ORAL SURG. 23: 629-637, 1967. Shklar, ct.: Oral Manifestations of Benign Mucous Membrane Pemphigus (Mucous Membrane Pemphigoid), ORAL SURG. 12: 950-966,1959. Perry, H. 0.: Skin Diseases With Mueocutaneous Involvement, ORAL SURG. 24: 800-807, 1967. Lever, W. F.: Oral Lesions in Pemphigus, Am. J. Orthod. Oral Surg. 28: 569-580, 1942. Shafer, W. G., Hine, M. K., and Levy, B. M.: A Textbook of Oral Pathology. Diseases of the Skin, ed. 2, Philadelphia and London, 1963, W. B. Saunders Co., pp. 701-703. Baer, P. N., Archard, H. D., Gant, J. Q., and Talpers, 8. J.: Pemphrgus Vegetans, ORAL SURG. 28: 282-286, 1969. Rice, J. S., Hickory, N. C., Hurt, W. C., and Rovin, S.: Pemphigus Vegetans, ORAL BURG. 16: 1383-1394,1963.

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9. Schweeks, L. A., Hurt, W. C., gus Vegetans, ORAL SURG. 28: 10. Bhaskar, C. N., and Bell, W. 392-398, 1965. 11. Hurt, W. C.: Observations on 12. C&rrb;;50F. C., and Can&ares,

vulgaris

361

and Vanderploeg, D. E.: Further Observations on Pemphi442450, 1969. B.: Benign Mucous Membrane Pemphigus, ORAL SURG. 20: Pemphigus Vegetans, ORAL SURG. 20: 481-487,1965. 0.: Pemphigus Vulgaris, Arch. Dermatol. Syphilol.

62:

786-

13. Be&ner, ‘E. H:, and Jordan, R. E.: Demonstration of Skin Antibodies in Sera of Pemphigus Vulgaris Patients by Indirect Immunofluorescent Staining, Proc. Sot. Exp. Biol. Med. 117: 505-510, 1964. 14. Beutner, E. H., Lever, W. F., Witebsky, E., Jordon, R., and Chertock, B.: Autoantibodies in Pemphigus Vulgaris: Response to Intercellular Substance of Epidermis, J. A. M. A. 192: 682-688, 1965. 15. Peck, S. M., Osserman K. E., Weiner, L. B., Lefkovits, A., and Osserman, B. S.: Studies in Bullous Diseases: l!mmunofluorescent Serologic Tests, N. Engl. J. Med. 279: 951-958, 1968. 16. Coons, A. H., and Kaplan, M. H.: Localization of Antigen in Tissue Cells. II. Improvements in Method for Detection of Antigen by Means of Fluorescent Antibody, J. Exp. Med. 91: l-13, 1950. 17. Mancini, G., Vaerman, J. J., Carbonara, A. O., and Hermans, J. F.: A Single-RadialDiffusion Method for the Immunological Quantitation of Proteins. Proceedings of the 11th Colloquium Protides of the Biological Fluids, Amsterdam, 1964, Elsevier, p. 370. 18. Stiehm, E. R., and Fudenberg, H. H.: Serum Levels of Immune Globulins in Health and Disease: A Survey, Pediatrics 37: 715-727, 1966. 19. Bean, S. F., Alt, T. H., and Katz, II. I.: Oral Pemphigus and Bullous Pemphigoid; Immunofluorescent Studies of Two Patients, J. A. M. A. 216: 673.674,197l. 20. Tomasi, T. B., Jr., and Zigelbaum, S. D.: The Selective Occurrence of Gamma A Globulins in Certain Body Fluids, J. Clin. Invest. 42: 1552-1566, 1963. Xeprint Tequests to: Dr. L. R. Eversole Department of Oral Pathology University of Kentucky College Lexington, Ky. 40506

of Dentistry