Treatment of Hailey-Hailey disease with tacrolimus ointment and clobetasol propionate foam

Journal of Drugs in Dermatology, March-April, 2004 by Saleem A. Umar, Pradip Bhattacharjee, Robert T. Brodell

Discussion

Hailey-Hailey disease, or familial benign chronic pemphigus, is a rare autosomal dominant condition that involves recurrent blistering of the skin (6,9). The pathomorphology of Hailey-Hailey disease originates in the epidermis of the skin (10), where there is suprabasal keratinocyte acantholysis (12) usually involving all layers of the epidermis. This acantholysis results in a 'dilapidated -brick- wall appearance' (6,11). At the molecular level, the manifestation of Hailey-Hailey disease has been attributed to the genetic defect of the ATP2C1 gene involving a calcium pump driven by adenosine triphosphate, resulting in altered levels of cytosolic calcium (7,8).

A variety of therapeutic modalities have been recommended for the treatment of Hailey-Hailey disease. Though none of these regimens represent a "cure," they can suppress flare-ups. Recommendations range from antibiotics and topical corticosteroids, to systemic corticosteroids and immunosuppressants (13). More drastic measures that have been attempted include dermabrasion (21,22), C[O.sub.2] laser therapy (23-26), and surgical excision (27-29). The broad scars from these treatments seem to resist blistering and provide relief for patients with Hailey-Hailey disease.

A common approach to the treatment of Hailey-Hailey disease is the use of topical steroids. The greatest benefit has been observed when topical corticosteroids are used promptly during the initial phases of eruptions (17). Clobetasol propionate is a super-potent synthetic corticosteroid. There are a variety of formulations of this drug that can be applied topically, and different formulations usually imply different bioavailabilities of the drug (14). Our patients used the foam formulation of clobetasol propionate and appreciated the ease of application even on blistered skin. Clobetasol propionate should only be used for a limited time due to its local side effects such as folliculitis, skin atrophy, and striae, and the less-likely potential inhibition of the hypothalamic-pituitary-adrenal (HPA) axis (15,16). Current guidelines recommend that patients should not exceed usage beyond 2 consecutive weeks, and weekly dosages should not exceed 50 g. For patients who seem to benefit solely from the application of highly potent topical corticosteroids, intermittent dosing and decreased frequency of application may decrease the occurrence of undesired side effects (15).

Immunosuppressive agents have also been successfully used in treating Hailey-Hailey disease. The immunosuppressive agent cyclosporine, for example has been proven to be effective in the treatment of Hailey-Hailey disease pemphigal lesions (18-20). The problem with potential long-term cyclosporine utilization, however, lies in the dangers of developing hypertension and nephrotoxicity (18,19). Tacrolimus (Protopic[R]), also known as FK506, is another immunosuppressive agent that suppresses cellular immunity by inhibiting T-lymphocyte activation. It is indicated for the treatment of moderate to severe atopic dermatitis that is unresponsive to conventional modes of therapy. It has been shown to penetrate the epidermal barrier and to suppress experimental contact hypersensitivity reactions in humans and animals (2-5). When used on a patient inflicted with Hailey-Hailey disease which is refractory to numerous recommended therapies, topical tacrolimus was shown to have noticeably reduced the symptoms of the disease (1). When compared to topical cyclosporine, topical tacrolimus has a lower molecular weight. This may be the underlying reason for its ability to penetrate the human skin more efficiently than topical cyclosporine, consequently leading to its significantly higher clinical efficacy (3).