Cicatricial pemphigoid (mucous membrane pemphigoid): current and emerging therapeutic approaches

The treatment of cicatricial pemphigoid, also called mucous membrane pemphigoid (MMP), poses a great challenge, because the condition often takes an intransigent course despite all therapeutic efforts. Because of its diverse clinical manifestations, patients with MMP often have to be treated by a variety of specialists, including dermatologists, ophthalmologists, ear, nose, and throat specialists, and dentists. Since there are almost no randomized, controlled, double-blind studies comparing the use of various therapeutic agents in this condition, treatment decisions still rely heavily on individual clinicians' experience. Many different therapeutic regimens have been described in the literature, but only a few seem to hold up as valid alternatives. Systemic corticosteroids are still the agent of first choice, especially as rescue medication, for curtailing acute exacerbations. However, because of their well known long-term adverse effects, corticosteroids must be combined with immunosuppressive and/or anti-inflammatory agents. To determine which drug to choose, it is helpful to categorize patients -- as recommended by the First International Consensus -- in terms of high- and low-risk depending on the site and severity of their disease and on how rapidly it progresses. The recommended treatment for high-risk patients (i.e. patients with ocular, genital, laryngeal, esophageal or nasopharyngeal involvement) is a combination of prednisone and cyclophosphamide, or alternatively azathioprine. Once clinical improvement is evident, the corticosteroids should be slowly tapered. Dapsone is another alternative that may be used in high-risk patients, but patients who do not show any short-term improvement on this regimen should be switched to cyclophosphamide. Intravenous immunoglobulins are another effective, but expensive, treatment option in high-risk patients. Low-risk patients may well be managed with topical therapy alone, such as corticosteroids or cyclosporine. Other systemic options include dapsone, tetracycline, and nicotinamide as well as azathioprine in combination with low doses of corticosteroids. Various other systemic and topical agents, and recently biologics such as etanercept, have been reported to be effective in the treatment of MMP. However, most of the reported cases consisted of only small patient numbers and the true benefit of such agents in the condition is therefore not yet clear.