Oral Medicine

Pemphigus vulgaris of the oral mueosa: report of two casesGerry M. Raghoebar* / Theo J. Brouwer* .-' Coenraad J. F, Schoots**

Two cases of pemphigus vulgaris in which oral lesions were the first signs of the diseaseare reported. The clinical signs and symptoms, histologie characteristics, and immuno-histochemistry are discussed. Early recognition of oral lesions associated with the dis-ease is of the utmost prognostic value. Treatment, which can only be .•iymptomatic. usu-ally co!}.sisls of a combination of a corticosteroid and inmmnosuppressive medication.Because side effects may be serious, these medications should be prescribed and moni-tored by an experienced dermatologist. (Quintessence lut 199!;22; 199-202.)

latroduction

Pemphigus vulgaris is an immunopalhologie derma-tologie disease that usually occurs in patients betweenthe ages of 40 and 60.' It is characterized by the de-velopment of flaccid, easily ruptured intraepithelialbullae on apparently normal skin and mucous mem-branes. It begins locally but progresses to become gen-eralized, leaving large, weeping, denuded surfaces,with little or no tendency to heal.

The oral cavity is frequently affected in the courseof the disease. Intraoral Icsionsmay appear in as manyas 50% of the patients without a simultaneous affec-tion of Che skin.' - Although any part of the oral mn-cosa may be affected, areas exposed to mechanicalirritation are most commonly involved. The lesionstend to occur most frequently on the buccal and pal-atal mueosa and on the gingiva.-

The oral lesions begin as bleblike blisters or as dif-fuse gelatinous plaques.' Rupture of the bullae occurs

Oral Surgeon, Department of Oral and M ax il lof acial Surgery,University Hospital Groningen, PO Box 30.001, 9700 RBGroningen. The Netherlands.Pathologist. Department of Pathology. University HospitalGroningen.

in an early stage and may be caused by slight rubbingor minimal mucosal trauma. The lesions are usuallypainful.

Untreated generalized pemphigus vulgaris may befatal, because of widespread infection, disturbance inthe electrolyte balance, cachexia, and toxemia. Theearlier the disease is treated, the smaller are theamounts of steroids that are needed to keep it undercontrol.'' Therefore, by recognizing the oral lesions ofpemphigus vulgaris, the dentist has a responsibility inthe early diagnosis of the disease, which is of the ut-most prognostic importance.

This report describes two eharaeteristic cases ofpemphigus vulgaris in which the first manifestationsof the disease occurred in the oral cavity.

Case reports

Ca.'ie I

A 22-year-old woman who had emigrated from Indiawas referred to our hospital by an outpatient clinicfor treatment of generalized desquamative lesions inthe mouth. The lesions had been discovered hy thepatient 8 weeks earlier. Her complaint consisted ofpain, especially during chewing, swallowing, and talk-ing.

A review of her medical history showed that thesame kind of oral lesions had appeared in India2 years earlier. She had received steroid therapy, afterwhich the lesions disappeared.

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Oral examination revealed broad areas of desqua-mation with assoelated erythema on the soft palateand the buccal mucosa on the leñ and right side (Fig1), Generalized desquamative lesions of the attachedgingiva were also noted (Fig 2), The Nikolsky's signwas negative. The skin was normal, A biopsy wastaken of the lesions of the bueeal mueosa and of theattached gingiva.

At the follow-up examination 1 week later, the pa-tient had several bullous lesions on the skin (Fig 3),Intraorally, the lesions had extended to the ventralsurface of the tongue and to the lower lip.

Microscopically the biopsy specimens revealed typ-ical histologie features of pemphigus vulgaris (Figs 4and 5). Examination by direct and indirect immuno-fiuorescence confirmed the diagnosis.

When the diagnosis was established, the patient wasreffered to the hospital's Department of Dermatology.For treatment she received systemic .steroid therapyand azathioprine. After 3 months, healing was vir-tually complete. Corticosteroid medication was con-tinued at a maintenance dose to prevent recurrence.

The patient is reexamined on a regular basis.

Case 2

A 40-year-old woman was referred by her dentist fordiagnosis and treatment of the desquamative lesionson the attaehed gingiva. The lesions had been diseov-ered for the ftrst time 6 months earlier. She complainedof intermittent painful ulcérations and burning sen-sations in her mouth that occurred when she was eat-ing citrus fruits.

Previous antibiotic medication and mouthwasheswere not successful in treating the condition. The med-ical history was negative in all respects, including al-lergic reactions.

Examination of the oral mueosa revealed hyper-emic, edematous lesions and areas of superficial ul-cération or desquamation of the epithelia of the at-tached gingiva on the buccal side in the mandible {Fig6). A characteristic Nikolsky's sign was lacking, al-though there was apparent fragility of the oral mueosasurrounding the lesions. The skin was not involved.A biopsy was taken of a lesion of the attached gingiva.

The histologie examination of the biopsy specimenand direct and indirect immunofluorescence tests re-vealed pemphigus vulgaris. The patient was referredto the Department of Dermatology for treatment.

The patient is presently on a sehedule of follow-upappointments.

Discussion

The designation pemphigus is used for a group ofchronic relapsing skin diseases characterized clinicallyby blister formation and positive autoitnmune reac-tions. There are four types of pemphigus: pemphigusvulgaris, pemphigus vegetans, pemphigus foliaeeus,and pemphigus erythematosus.''' Pemphigus vulgarisis the most eommon form.

The etiologic factors of pemphigus vulgaris are stillunknown. Numerous attempts to implicate specificmicroorganisms have failed. It is evident that an auto-immune meehanism is involved, beeause of the pres-ence of specific intercellular antibodies in the epitheliaof the skin and oral mueosa and the circulation ofintercellular antibodies in the serum.

It is generally believed that there is no dIfTerencebetween the sexes in frequency of pemphigus,'''-* huta higher frequency among women has been reportedin some studies.''' Pemphigus vulgaris seldom occursin a person younger than the age of 30; however, pem-phigus vulgaris of childhood is well recognized andshould also be considered,** One of the patients in thesecase reports was younger than 30 years old, and bothwere women. This disease has been reported to occurmore frequently in Jewish persons, particularly in theAshkenazi group,'

The ftrst symptom of pemphigus is often burningand painful erosions of the mucous membrane of theoral cavity. The loss of epithelia, because of reducedcohesion among the epidermal cells, when the appar-ently unaffected skin and/or mueosa are rubbed istermed Nikolsky's sign.^-^ The orai lesions may con-tinue for weeks before cutaneous lesions appear. Dur-ing this period, the disease may remain undiagnosed,^In cases in whieb the skin is not affected, and oniyoral bullae are present, pemphigus may be clinicallyindistinguishable from other bullous diseases, such asdermatitis herpetiformis, erythema multiforme buUos-um, bullous lichen planus, and epidermolysis bnllosa,and other chronic bullous dermatoses, such as bullouspemphigoid and cicatricial pemphigoid.^ For differ-ential diagnosis, histologie and immunohistochemicexaminations are indispensable.

Biopsy speeimens of the oral lesions in histologieexamination show eharaeteristic patterns of bullae for-mation because of acantholysis. The cleft formationis intraepithelial on a suprabasal level,̂ Cytologie ex-amination may also help in differential diagnosis, al-though the results are not as eonclusive as those basedon a biopsy specimen. Immunoflnoreseent examina-

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Oral Medicine

Fig 1 Intraoral view of a 22-year-old woman with shallow,irregular erosions on the soft palate and buccal mucosathat have been attributed to pemphigus vulgaris.

Fig 2 The same patient as in Fig 1 showing areas of gin-gival erosion.

Fig 3 Bullae and crustae of the skin in the same patient. Fig 4 Biopsy specimen of an oral lesion with intraepithe-lial cleft formation because of acantholysis, (Hematoxylinand eosin stain; original magnification >;20,)

Fig 5 Same specimen as in Fig 4 showing epithelialsuprabasal bulla. Note the subepithelial inflammatoryInfiltrate ol lymphocytes, plasma cells, and granulocytes,including eosinophiis, ¡Hematoxylin and eosin stain; origi-nal magnification i<80.)

Fig 6 Intraoral aspect of a 40-year-old woman with pem-phigus vulgaris, (arrows) Smali areas of erosion on theattached gingiva.

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tion of sera and the biopsy specimen reveal a diag-nostic finding of antibodies confined to the inter-cellular substance of the epitheiia and intercellulardeposits of immunoglobulin G.'""

Although there is no real cure for pemphigus vul-garis, the disease can usually he successfully controlledwith immunostippressive drugs, such as azathioprineand prednisone. Since these medications may producesubstantial side effects, however, it is recommendedthat patients with pemphigus vulgaris be managed pri-marily by a dermatologist. Levamisolc in combinationwith prednisone has been reported to provide favor-able results, enabling lower dosage of prednisone.'-

The oral lesions are the first lesions to appear in upto 50% of patients and are the last to recede. A reg-imen of local oral treatment may be needed to allaythe oral discomfort and pain. It should be emphasized,however, that topical treatment is only supportive andis not a substitute for systemic eorticosteroid medi-cation. Painful oral lesions can be treated with topicalanesthetics, topical steroids, or both. Mild antisepticmouthwashes are often justified to prevent superin-fection. In case of superimposed candidal infections,antifunga! agents are often effective.

Dental treatment of these patients should be exer-cised with extreme care. The mucosa is fragile andexcessive pressure may cause an erosion. When ex-tractions or other snrgical procedures are indicated,the dermatologist should be consulted because of theprednisone therapy.

The earlier the diagnosis of this disease is made andtreatment is started, the less the suffering ofthe patientand the more favorable the prognosis. The alert dentistcan recognize the oral lesions and may, therefore, con-tribute to the patient's "quality of life."

Acknotvledgment

Ttie authors wish to thank Prol' Dr G. ßoi^ring ÍI>Í his critical re-marks and suggestions for this articie.

References

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