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Therapeutic Strategies

Bullous Pemphigoid

Timothy Berger Bruce Wintroub

Saturday, January 01, 2011

Overview

Bullous pemphigoid is usually a self-limited inflammatory subepidermal blistering disorder of the elderly, in which circulating auto antibodies to epitopes in the basement membrane zone bind to this region and initiate a cascade of inflammatory events resulting in urticarial and bullous lesions. The therapeutic strategy is to reduce auto antibody production and to control the inflammatory reaction. Because bullous pemphigoid is not life-threatening and agents that reduce auto antibody formation are inherently high risk, the initial goal of therapy is to control inflammation and reduce blister formation to a level consistent with individual patient comfort.

First Steps

  1. Treat with oral prednisone alone at 40-60 mg/ day in a single morning dose. A dramatic clinical response will be seen in 70-80% of patients after 2-3 weeks.
  2. Clobetasol ointment or another superpotent topical steroid is applied to the affected areas twice daily.

Subsequent Steps

Over 2-8 weeks, taper the prednisone dose to 30 mg/day by reduction of the daily dose by 10 mg every 2-3 weeks. Then, over the next 2-3 months, reduce prednisone to 10-20 mg daily. After several months, shift the patient to alternate steroid therapy, reaching 10 mg every other day. When 10 mg every other day is reached, taper dose by 1 mg every other day every 1-4 weeks until the lowest amount of prednisone controlling the appearance of new lesions is reached.

Alternative Steps

Alternative agents may be used in patients who do not rapidly respond to systemic steroids or in patients in whom the use of systemic steroids is contraindicated.

  1. If the patient has complications or side effects from the prednisone, has persistent severe disease, or if sufficient clinical response is not achieved after 3 weeks, begin an immunosuppressive agent in combination with prednisone. In each case, continue the immunosuppressive agent for at least 2 months before abandoning it as ineffective. Once the steroid-sparing agent has begun to work, the dose of systemic steroids is gradually tapered following the protocol above. The choice of immunosuppressive agent is determined by the patient's coexistent medical conditions, the risk of complications, and the cost. There is no evidence that one agent is superior to another. Steroid-sparing immunosuppressives include:
    1. Mycophenolate mofetil 500 mg - 1.5 mg twice daily (1.0-3.0 g daily)
    2. Azathioprine 100-150 mg/day
    3. Methotrexate 5mg to 25 mg once weekly as a single oral dose
    4. Cyclophosphamide 50-150 mg/day
  2. Adjunctive measures that may be added to prednisone or prednisone plus immunosuppressive agents.
    1. Tetracycline 500 mg three or four times daily plus niacinamide 500 mg three times daily. This may be adequate alone to control mild disease or may provide additional antiinflammatory effect without causing additional immunosuppression.
    2. Plasmapheresis to remove circulating pemphigoid autoantibody may be of value, but should be combined with cyclophosphamide 50-150 mg to inhibit antibody production.
    3. Intravenous immunoglobin infusions (IVIG) may be used in refractory cases. The dose is 2g/kg given over 3-5 days. This is very costly and is less frequently required than in pemphigus vulgaris.

Pitfalls

  1. Patients with bullous pemphigoid are often elderly and frail. They tolerate high-dose systemic steroid therapy poorly. Do not be reluctant to add low doses of a steroid-sparing agent to allow for reduction in the systemic steroid dose. Complications usually occur when systemic steroid dose is not reduced judiciously.
  2. Potential complications of systemic steroids and immunosuppressants must be carefully sought in all patients so treated.
  3. Other bullous diseases such as epidermolysis bullosa acquisita, erythema multiforme, and bullous drug eruptions may clinically resemble pemphigoid and may explain atypical therapeutic responses.
  4. Immunosuppression may result in reactivation of herpes simplex or varicella zoster virus infection. These bullous infectious diseases may be generalized and simulate a flare of the pemphigoid.

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