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Cicatricial Pemphigoid

Definition

Cicatricial pemphigoid or mucous membrane pemphigoid is a chronic, recurrent, autoimmune blistering disease that primarily affects mucous membranes and rarely the skin. Cicatricial pemphigoid represents a heterogeneous group of diseases with respect to disease severity, clinical site of involvement, and the isotype of the associated autoantibodies.

Etiology

Cicatricial pemphigoid is an autoimmune condition. Hemidesmosome and lamina lucida proteins, bullous pemphigoid antigen 180 (BP180). laminins 5, β₄ integrin, and type VII collagen have been identified as the target antigens in cicatricial pemphigoid.

Main Clinical Features

The oral mucosa is almost always affected, followed by other mucosae (ocular, nose, pharynx, larynx, esophagus, genitalia, anus) and rarely the skin (5-10%).

Oral Mucosa

Erythema and bullae that rupture leaving painful erosions. The lesions usually recur, persist for a long time, and occasionally lead to atrophy or scarring. The soft palate, buccal mucosa, and the gingiva are more frequently affected in the form of desquamative gingivitis. The oral lesions may be the only manifestations of the disease

Ocular Mucosa

Conjunctivitis, symblepharon. trichiasis, dryness, and opacity of the cornea—occasionally leading to blindness

Other Mucosae

Bullae that rupture leaving erosions that may lead to scarring

Skin

Bullae that usually develop on the scalp, face, and neck and may heal with or without scarring

Diagnosis

The clinical diagnosis should be confirmed by histopathologic examination and direct and indirect immunofluorescence tests.

Differential Diagnosis

•Lichen planus (erosive and bullous forms)

•Bullous pemphigoid

•Linear IgA disease

•Chronic ulcerative stomatitis

•Epidermolysis bullosa acquisita

•Pemphigus

•Dermatitis herpetiformis

•Erythema multiforme

•Herpetic stomatitis

•Plasma cell stomatitis

Treatment

Basic Guidelines

•Systemic or topical treatment is for the management of cicatricial pemphigoid depending on the severity of the disease and the organs involved.

•Patients with oral lesions should avoid mechanical injuries from hard and rough foods, toothbrushes, broken teeth, fillings with rough margins, and dentures. Dentists must use dental instruments gently.

•Systemic or topical corticosteroid administration is the mainstay of treatment. Immunosuppressive drugs should also be used as adjuvant therapy in severe and resistant cases.

•One of the most serious morbidities of cicatricial pemphigoid is ocular involvement. These patients must be managed in consultation with an expert ophthalmologist.

Suggested Therapies

Systemic Treatment

Oral Corticosteroids

Oral corticosteroids (prednisone or prednisolone) are the cornerstone of therapy for cicatricial pemphigoid. The initial dose varies from 30 mg/day to 60 mg/day depending on the severity of the disease. It usually takes 2-3 weeks to stop new bullae formation and for old ones to heal. The dose is subsequently tapered by 20% every 2-3 weeks until the dose of 10 mg/day is reached. This dose is subsequently maintained on alternate days and reduced by 5 mg every 2 weeks until it is completely stopped. Recurrence of oral lesions is not uncommon and may be treated with local corticosteroids or low doses of systemic corticosteroids.

Immunosuppressants

Corticosteroid-sparing immunosuppressants are usually required only in severe cases that present with ocular, laryngeal, or esophageal involvement because of the increased risk for blindness and scar formation. Azathioprine 100 mg/day and cyclophosphamide 100-200 mg/day are most frequently used. Mycophenolate mofetil 2 g/day may also be used in some cases.

Dapsone

50-100 mg/day is beneficial in mild to moderate diseases, particularly for patients with oral lesions alone.

Topical Treatment

Localized, mild, oral lesions or recurrences may be treated with topical corticosteroids alone: 0.1% triamcinolone acetonide in an oral adhesive base (Orabase), or 0.5% fluocinonide gel, or 0.05% clobetasol propionate gel applied to the lesions two to three times a day for 2-6 months or more is particularly effective for gingival lesions (desquamative gingivitis). Recently. 0.05% clobetasol mouthwash in aqueous solution has been shown to be effective for localized oral lesions. Intralesional injection of triamcinolone acetonide retard or betamethasone dipropionate and sodium phosphate retard may be beneficial for localized resistant oral lesions. Topical cyclosporine is another feasible therapy for patients with oral lesions.

Alternative Therapies

Recently, new immunomodulators for topical use, with anti-inflammatory action, such as tacrolimus and 0.1 % pimecrolimus ointment, have been used with promising results in the treatment of oral lesions of autoimmune diseases. Combination therapy with tetracyclines (minocycline or doxycycline) 1-2 g/day and nicotinamide 1-2 g/day may be effective.

References

Chan LS, Ahmed AR, Anhalt GJ, et al. The first international consensus on mucous membrane pemphigoid: Definition, diagnostic criteria, pathogenic factors, medical treatment and prognostic indicators. Arch Dermatol 2002;138:370–379.

Eisen D, Ellis CN, Woorhees JJ. Topical cyclosporine for oral bullous disorders. J Am Acad Dermatol 1990;23:936–937.

Gonzalez-Moles MA, Morales P, Rodriguez-Archilla A, et al. Treatment of severe chronic oral erosive lesions with clobetasol propionate in aqueous solution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:264–270.

Korman NJ. New immunomodulating drugs in autoimmune blistering diseases. Dermatol Clin 2001;19:637–648.

Reiche L, Wojnarowska F, Mallon E. Combination therapy with nicotinamide and tetracyclines for cicatricial pemphigoid: Further support for efficacy. Clin Exp Dermatol 1998;23:254–257.

Schmidt E, Skrobek C. Kromminga A, et al. Cicatricial pemphigoid: IgA and IgG autoantibodies target epitopes on both intra- and extracellular domains of bullous pemphigoid antigen 180. Br J Dermatol 2001;145:778–783.

Wojnarowska F, Kirtschig G, Khumalo N. Treatment of sub-epidermal immunobullous diseases. Clin Dermatol 2001;19:768–777.