Bullous Diseases

Bullous Pemphigoid

A chronic bullous eruption characterized by tense bullae on normal or erythematous skin.

Bullous pemphigoid occurs predominantly in the elderly. Men and women are equally affected. Autoantibodies directed against a protein on the basal surface of keratinocytes, the bullous pemphigoid antigen, cause the blisters to form.

Symptoms, Signs, and Diagnosis

Pruritus and plaques of erythema often develop before blistering. Tense and intact bullae may be localized or generalized, and mucous membranes are involved in about 50% of cases. The patient usually feels well. Individual bullae heal without scarring while new ones appear.

The clinical presentation is usually characteristic, but confirmatory skin biopsy is recommended. Routine histologic examination reveals subepidermal bullae, and immunofluorescent staining reveals deposits of complement C3 in all patients and IgG along the dermal-epidermal junction in lesional and perilesional skin in many patients. Autoantibodies can be detected in the serum of about 45% of patients with active disease.

The differential diagnosis includes pemphigus vulgaris, dermatitis herpetiformis, erythema multiforme, benign mucosal pemphigoid, and drug-induced eruptions.

Prognosis and Treatment

Bullous pemphigoid is chronic and recurrent. Before the availability of corticosteroids, the disseminated disease was fatal in about 33% of patients as a result of sepsis.

Mild, localized bullous pemphigoid can often be controlled with potent topical corticosteroids; widespread bullous pemphigoid may require hospitalization until the epidermal barrier is restored. Systemic prednisone 40 to 60 mg/day po is needed to control severe disease. The total dose can be given every morning or every other morning to minimize adrenal suppression. After the skin lesions have resolved, the corticosteroid dosage should be decreased by about 50% over 1 month and then tapered more gradually. Patients should be observed for signs of recurrence as the prednisone dosage is reduced. Topical or intralesional corticosteroids may be used for recalcitrant lesions as a supplement to oral therapy.

Elderly patients receiving high-dose corticosteroid therapy should be monitored for corticosteroid-induced diabetes and other corticosteroid complications, including upper GI bleeding, fluid retention, hypertension, and psychiatric disturbances (most commonly hypomania).

Because of the risks of prolonged corticosteroid therapy in the elderly, an immunosuppressant is usually given concomitantly for its corticosteroid-sparing effect--eg, azathioprine 50 to 150 mg/day po, methotrexate 25 to 35 mg/week po or IM, or cyclophosphamide 2 to 3 mg/kg/day po initially, followed by a maintenance dose of 100 mg/day po. Because immunosuppressants require 6 to 8 weeks to become effective, the corticosteroid dosage cannot be reduced immediately. Adverse effects of immunosuppressants include bone marrow suppression and hepatotoxicity.

Patients occasionally respond to a combination of tetracycline and nicotinamide, drugs that have a better long-term safety profile than systemic corticosteroids or immunosuppressants.

After several months of systemic treatment, about 50% of patients with bullous pemphigoid have complete remission and then require no medication.

Pemphigus Vulgaris

A rare, potentially life-threatening condition characterized by intraepidermal bullae on the skin or mucous membranes.

Although the incidence is highest among middle-aged persons, many people with pemphigus vulgaris are elderly.

Histologically, the bullae are intraepidermal; immunofluorescent staining reveals intercellular deposits of complement and immunoglobulin directed against the glycoprotein that forms the intercellular cement.

Symptoms and Signs

Pemphigus vulgaris is characterized by flaccid bullae that rupture easily and leave superficial erosions on the trunk, limbs, and mucous membranes. The surrounding skin looks normal. Many patients present with mouth pain; oral lesions may dominate the clinical picture, especially early in the disease process. Blistering can progress from localized to generalized, and patients are at high risk of secondary infection and sepsis.

Often, applying a lateral force to the skin causes the overlying epidermis to shear off (Nikolsky's sign).

Diagnosis

Diagnosis is suggested clinically. Confirmation requires a Tzanck smear, which involves scraping the base of a vesicle and using a vital stain such as Wright's or Giemsa to highlight nuclei of epidermal cells. In pemphigus, the acantholytic cells typical of pemphigus are unattached and basal cell-like, with large centrally placed nuclei and condensed cytoplasm. Differential diagnosis includes bullous pemphigoid, benign mucous membrane pemphigoid, toxic epidermal necrolysis, drug-induced eruptions, and erythema multiforme.

Prognosis and Treatment

Before the advent of corticosteroids, the disease was always fatal, with a mean survival of about 1 year. The mortality rate is now about 25%, with death usually resulting from complications of therapy. Long-term follow-up and prolonged treatment are required.

Widespread pemphigus may require hospitalization until the epidermal barrier is restored. Usually, prednisone 60 to 100 mg/day po is needed to control the disease. Other details of treatment, including alternative treatments, are as for bullous pemphigoid, including the need for close monitoring of high-dose corticosteroid therapy in elderly patients.

Remission may last many months or indefinitely, but some patients require lifelong treatment.