Alefacept in Patients With Severe Scalp Alopecia Areata

Alopecia areata (AA) is an autoimmune condition characterised by a T-cell mediated attack on the hair follicle. The inciting antigenic stimulus is unknown. A dense peribulbar lymphocytic infiltrate and reproducible immunologic abnormalities are hallmark features of the condition. The cellular infiltrate primarily consists of activated T-lymphocytes and antigen-presenting Langerhans cells. T-lymphocytes play a critical role in the pathogenesis of disease. The observance of hair regrowth in those with alopecia areata who are treated with cyclosporine, a known inhibitor of T-cell function, further confirms the central role of the T-lymphocytes in the development of the disease. Activation of T-cells is initiated by interaction of the T-cell receptor with the antigen/major histocompatibility complex on the antigen-presenting cells. Co-stimulatory interactions occur secondarily, including binding of the T-cell CD2 receptor to the antigen-presenting cell ligand LFA-3 (lymphocyte function-associated antigen-3 CD58). Induction of a molecular signaling cascade with resultant T-cell activation and proliferation ensues. Abrogation of this activation may result in diminished or aborted expression of disease, and thus suggests a potential therapeutic role for alefacept in the treatment of alopecia areata. Alefacept is a bioengineered LFA-3/Immunoglobulin fusion protein that binds to the CD2 T-cell receptor and interferes with the ligation of LFA-3. Binding of the immunoglobulin portion of the fusion protein to the FCy receptor on antigen-presenting cells potentiates apoptosis of CD-2 T-cells to thereby reduce the population of activated T-cells. Psoriasis is a T-cell mediated disorder that shares many immunologic features with alopecia areata. Accordingly, treatments that are effective in psoriasis often prove to be beneficial in alopecia areata. Anthralin, topical and intralesional steroids and cyclosporine are among several therapeutic agents that have efficacy in both disorders. Based on the impressive therapeutic responses seen in those with psoriasis treated with alefacept, a similarly beneficial outcome is tentatively anticipated with treatment of those with alopecia areata.