Biologic Agents and Alopecia Areata

hibited hair growth and EGF, TNFand IL-1 completely abrogated it. All these evidences are in favor of an autoimmune phenomenon occurring in AA, with the TNFappearing as a potent inhibitor of hair growth. In the last few years, several biologic agents acting on TNFor involving ICAM 1-LFA1 or CD2-LFA3 interactions have been considered as possible treatments for AA. Cases of AA have been described in which etanercept has been proven ineffective, or AA recurred during etanercept therapy for other disease [5] . Strober et al. [6] found that no hair regrowth occurred after treatment of AA with etanercept in 17 otherwise healthy patients. In addition, infliximab did not prevent AA development in a patient with no previous history of this disease [7] . Fabre and Dereure [8] reported worsening of AA in a patient receiving infliximab. Adalimumab is a fully humanized recombinant anti-TNFmonoclonal antibody which has been approved for rheumatoid arthritis, active ankylosing spondylitis, psoriatic arthritis and Crohn’s disease. To our knowledge, our patient is the third reported case of AA developing during adalimumab therapy. Pelivani et al. [9] described a case of AA universalis elicited after 6 months of adalimumab monotherapy in a patient with a longstanding history of psoriatic arthritis and psoriasis. Garcia Bartels et al. [10] published a case of AA universalis, occurring 4 months after adalimumab was added to a regimen of prednisone and leflunomide. In our patient, apart from the introduction of adalimumab, other factors, namely serious psychological stress, might have played an important part in eliciting AA. Our patient is the second reported case in which the introduction of adalimumab in a patient already under treatment with leflunomide was followed by AA development. Leflunomide is a new immunomodulatory drug that selectively acts on activated autoimmune lymphocytes by inhibiting dihydroorotate dehydrogenase, an enzyme required for de novo pyramidine synthesis. These 2 cases suggest that leflunomide has probably no prophylactic or therapeutic effect on AA. On the other hand, there is evidence suggesting that other biologic therapies that target T cells may represent an effective treatment modality for AA. Heffernan et al. [11] tried alefacept in 4 patients with AA. All 4 patients improved, indicating that alefacept may be effective. A case of AA successfully treated with efalizumab has been reported [12] , however subcutaneous injections of efalizumab did not seem to be effective in 62 patients with AA [13] . Furthermore, in one case of AA, efalizumab was proven ineffective [7] . In light of the suggested pathogenetic relationship of AA and TNF, it is noteworthy to report cases of AA that occurred and progressed during treatment with TNF-blocking agents. The understanding gained from this experience should redirect the therapeutic aims toward alternate interventions.