Oral Mucous Membrane Pemphigoid

Abstract

Pemphigoid is a group of rare autoimmune diseases affecting the skin and the mucous membrane in which the autoantibodies are directed against the basement membrane zone target antigens causing subepithelial blistering. Oral health professionals are usually the first to identify as more than 90% of cases show oral lesions initially. A lack of diagnostic criteria can lead to misdiagnosis and delay in treatment. We report a unique case of mucous membrane pemphigoid devoid of ocular or cutaneous involvement.

INTRODUCTION

Pemphigoid is a group of rare autoimmune diseases affecting the skin and the mucous membrane in which the autoantibodies are directed against the basement membrane zone target antigens causing subepithelial blistering.[1] This interesting title “pemphigoid” arises from the Greek word “pemphix,” which means “blister” or “bubble.” Since this disorder manifests clinically as pemphigus, it is called as pemphigoid.[2] The sites affected include the nasopharynx, esophagus, larynx, and anogenital area, most commonly, the oral cavity. Oral health professionals are usually the first to identify as more than 90% of cases show oral lesions initially.[3,4] Lack of diagnostic criteria can lead to misdiagnosis and delay in treatment. We present a unique case of oral mucous membrane pemphigoid (MMP), devoid of any ocular or cutaneous involvement.

CASE REPORT

A female patient, aged 66 years, visited our dental wing with a chief complaint of a painful ulcer in the upper back region of the mouth for the past 2–3 days. The ulcer presented as a fluid-filled swelling that burst, leaving a raw, eroded area. The ulceration was solitary and irregular in shape and <1 cm on the posterior aspect of the hard palate [Figure 1]. She gave a history of repeated episodes of ulcerations in different parts of her mouth which regressed over time. Topical medication was prescribed, and the patient was asked to report back after 7 days.

Figure 1.

Solitary and irregular-shaped ulceration on the posterior aspect of the hard palate

A follow-up inspection revealed another irregular ulcer on the attached gingiva extending from 23 to 25 region [Figure 2]. On further follow-up, after obtaining informed consent from the patient, an incisional biopsy was performed at the upper right buccal mucosa site, adjacent to 14–15 region.

Figure 2.

Follow-up revealed another irregular ulcer on the attached gingiva extending from 23 to 25 region

Hematoxylin and eosin staining of the sectioned biopsied specimen showed a nonkeratinized stratified epithelium of squamous cells, detached away from the underlying connective tissue stromal component. The connective tissue stroma was seen to be fibrocellular with mild inflammatory cell infiltrates and blood vessels. The deeper part of the connective tissue showed salivary gland ducts, adipose cells, and muscle bundles [Figure 3]. The detachment of the basement membrane from the stroma was prominently evident in the periodic acid–Schiff-stained section [Figure 4]. Overall features were suggestive of MMP. As there were no systemic manifestations and recurrences, the patient was not willing to go ahead with further advanced techniques such as the immunofluorescence test.

Figure 3.

(a and b) Hematoxylin and eosin-stained soft tissue section shows nonkeratinized stratified squamous epithelium detached from the underlying connective tissue stroma (a, ×10; b, ×40)

Figure 4.

(a and b) The detachment of basement membrane from the stroma prominently evident with periodic acid-Schiff stain (a, ×10; b, ×40)

DISCUSSION

MMP belongs to a myriad group of long-standing, autoimmune, subepithelial blistering diseases, reported with an incidence of 1.5–9.5 cases per 100,000 inhabitants every year.[5,6] MMP involves the mucous membrane mainly of mouth and, occasionally, the skin.[5] Having only oral lesions without any cutaneous manifestation stands out in our case, and few cases have been reported with this finding in India.[3,7] Other sites involve the ocular, genital, and anal mucosa, pharynx, esophagus, and larynx. Its manifestations in the oral cavity can be seen on the gingiva, buccal mucosa, palatal mucosa, tongue, and seldom on the lips.[5,8] MMP is rarely seen in children but majorly affects the elderly population of the 6^th to 8^th decade of life, with the majority being females (2:1). No racial or geographic predilection has been observed.[5,9]

Many circulating antibodies directed against the basement membrane zone target antigens have been identified, the underlying reason for which is unknown. With the emergence of molecular techniques in medicine, about six autoantigens have been discovered which include bullous pemphigoid antigen of 180 kDa (BP180/collagen type XV11) and of 230 kDa (PB230), subunits of integrin a6b4, laminin 332, and type VII collagen.[5,8]

MMP starts as fluid-filled vesicles or bullae on the cutaneous or mucous membrane which ruptures and leaves the patient with raw and extremely tender ulcers which heals over many days or weeks.[6] The cutaneous lesions have tendency for scar formation. Oral manifestation on the gingiva is seen as patches or slough formation with ulcers and erosions superficially, which is referred to as desquamative gingivitis.[3,7] Ocular involvement begins as erythema with burning, irritation, and continuous tearing. The fusion of palpebral and bulbar conjunctiva along with inward turning of the lid margin onto the corneal surface causes inflammation of the area which eventually leads to blindness.[9] Scarring of laryngeal mucosa leads to hoarseness of voice and progressive asphyxiation, whereas scarring of esophagus and anogenital mucosa leads to dysphagia and morbidity, respectively.[5,6]

MMP can be diagnosed based on the history given by the patient and the clinical presentation of the disease.[9] Biopsy is recommended to be taken from the edge of the blister or erythema, giving special attention to involve the perilesional tissue. Histopathological features include subepithelial split with moderate-to-severe inflammatory cell infiltrate predominated by eosinophils, neutrophils, and lymphocytes.[6,9] Direct immunofluorescence shows continuous linear deposition of immunoglobulin G (IgG), IgA, and complement component 3 along the basement membrane zone, whereas indirect immunofluorescence usually gives a negative result.[3,4] Immunoblotting and ELISA can also be used in difficult cases.

The administration of medications for MMP varies according to the pathogenic pathway as well as course and severity of the disease progression. As per the international comprehensive treatment guidelines published in 2002, site(s) involved, severity, and progression can help with the clinician’s decision-making.[10] Due to the adverse effects of long-term systemic corticosteroids, their value has been limited and should only be administered when there is multiple organ involvement and in cases where topical therapy has proven to be ineffective.[9]

Topical administration of corticosteroids such as clobetasol propionate and betamethasone dipropionate has been suggested. Desquamative gingivitis can be effectively tackled with the usage of a gel-based topical corticosteroid in a resilient occlusive splint that covers whole of the affected gingiva.[6,9]

Intralesional injection of triamcinolone along with topical approach can accelerate the healing process. Topical anesthetic agents such as lidocaine and benzocaine can help reduce pain and improve patient’s ability to ingest food.[9]

Immunosuppressants include usage of azathioprine, cyclophosphamide, cyclosporine, methotrexate, and mycophenolate mofetil. Rituximab and intravenous Ig can reduce autoantibody production, and infliximab, which is a tumor necrosis alpha inhibitor, can reduce inflammation. MMP can also be treated using low-energy phototherapy and cryotherapy.[3,9]

CONCLUSION

Early detection of oral MMP by a dental practitioner prevents the progression of the condition into a severe state. In our case, the patient did not have any cutaneous lesions and had no flare-up of the oral manifested lesions. Multidisciplinary care would be needed for patients exhibiting oral and cutaneous manifestations, which include routine follow-up with a dentist, ophthalmologist, and dermatologist to prevent periods of exacerbation and remission.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient’s spouse has given his consent for her images and other clinical information to be reported in the journal. The patient’s spouse understands that her names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.