Many autoimmune skin disorders are characterized by formation of bullae, or blisters. These include bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, and pemphigoid gestationis.
Bullous pemphigoid is a relatively benign pruritic disease characterized by tense blisters in flexural areas, usually remitting in 5 or 6 years, with a course characterized by exacerbations and remissions (eFigure 6–65) (eFigure 6–66). Most affected persons are over the age of 60 (often in their 70s or 80s), and men are affected twice as frequently as women. The appearance of blisters may be preceded by pruritic urticarial or edematous lesions for months. Oral lesions are present in about one-third of affected persons. The disease may occur in various forms, including localized, vesicular, vegetating, erythematous, erythrodermic, and nodular. Drugs may induce bullous pemphigoid. The most common offender is furosemide. PD-1 inhibitors are an emerging cause of drug-induced bullous pemphigoid in patients receiving this immunotherapy for malignancies.
The diagnosis is made by biopsy and direct immunofluorescence examination. Light microscopy shows a subepidermal blister. With direct immunofluorescence, IgG and C3 are found at the dermal-epidermal junction. ELISA tests for bullous pemphigoid antibodies (BP 180 or BP 230) are 87% sensitive and 95% specific. If the patient has mild disease, ultrapotent topical corticosteroids may be adequate. Prednisone at a dosage of 0.75 mg/kg orally daily is often used to achieve rapid control of more widespread disease. Tetracycline (500 mg orally three times daily) or doxycycline (100 mg orally twice a day), alone or combined with nicotinamide—not nicotinic acid or niacin—(up to 1.5 g orally daily), may control the disease in patients who cannot use corticosteroids or may allow for decreasing or eliminating corticosteroids after control is achieved. Dapsone is particularly effective in mucous membrane pemphigoid. If these medications are not effective, methotrexate (5–25 mg orally weekly), azathioprine (50 mg one to three times orally daily), or mycophenolate mofetil (1–1.5 g orally twice daily) may be used as steroid-sparing agents. Intravenous immunoglobulin, rituximab, and omalizumab have been used with success in refractory cases.
et al. Bullous pemphigoid. Autoimmun Rev. 2017 May;16(5):445–55.
et al. Bullous pemphigoid: a review of its diagnosis, associations and treatment. Am J Clin Dermatol. 2017 Aug;18(4):513–28.
et al. First-line combination therapy with rituximab and corticosteroids provides a high complete remission rate in moderate-to-severe bullous pemphigoid. Br J Dermatol. 2015 Jul;173(1):302–4.
et al. Atypical presentations of bullous pemphigoid: clinical and immunopathological aspects. Autoimmun Rev. 2015 May;14(5):438–45.
K. Importance of serological tests in diagnosis of autoimmune blistering diseases. J Dermatol. 2015 Jan;42(1):3–10.
et al. Rituximab and omalizumab for the treatment of bullous pemphigoid: a systematic review of the literature. Am J Clin Dermatol. 2018 Nov 13. [Epub ahead of print]