Partial Response of Severe Alopecia areata to Cyclosporine A

Alopecia areata (AA) is a chronic cutaneous disease in which an autoimmune origin has been demonstrated. Peribulbar, inflammatory infiltrates are mainly composed by T4 lymphocytes, macrophages and Langerhans cells [1]. Autoantibodies directed to specific hair follicle antigens have also been demonstrated [2].In some patients AA can be very extensive: patchy AA affecting more than 50% of the scalp, AA totalis and AA universalis. In these cases most patients do not respond to standard treatment and suffer from severe social disabilities and psychiatric disturbances. Oral steroids and topical sensitizers are the main therapeutic options in these patients but sometimes fail to achieve any response.Cyclosporine A (CsA) is a specific inhibitor of T4 lymphocyte activation and therefore may be useful in treating patients with AA [3]. This drug has been reported to not only clear immune cells from the hair follicles but also to alter the balance of regulatory lymphocytes. On the other hand, the well-known hypertrichotic side effect of CsA has been suggested to be due to prolongation of the anagen phase of the hair cycle [4]. CsA has been reported to restore hair growth in the DEBR rat model for AA [5], and some trials recommend its use in combination with oral steroids [6, 7]. On the other hand, AA has been described in renal or liver transplant recipients on high doses of CsA [8, 9, 10], and CsA failed to restore hair growth after 3 months in a case of severe AA [11]. Large studies on severe AA treated with CsA alone are lacking.In the present study, we treated 15 cases of severe AA with CsA (table 1): 8 patients with AA universalis, 2 patients with AA totalis and 5 patients with patchy AA involving more than 50% of the scalp. There were 7 males and 8 females between the ages of 18 and 51 years (mean 28.8 years). AA had started between 1 and 24 years prior to treatment (mean 9.8 years). None of the patients suffered from thyroid disease.CsA was started at a dose of 5 mg/kg/day, and the dose was adjusted at every follow-up to achieve a therapeutic blood level between 100 and 350 ng/ml of CsA. The average dose was 150 mg twice a day for 6–12 months.One patient (case No. 15) discontinued the treatment due to hypertension. In 12 of the other 14 patients, vellus hair appeared in 1–3 months. Seven of these patients (50% of the series) developed intermediate hair at 2–5 months of the treatment and terminal hair after 3–8 months. Two of them (cases 5 and 8) achieved a complete hair regrowth. Case No. 5 was a 34-year-old white woman, who still maintains her regrowth 4 years after finishing treatment with CsA. She developed gingival hyperplasia with residual diastema. Case 8 was a 33-year-old white female who lost her hair 2 months after treatment had been stopped. Five other patients obtained a cosmetically acceptable response with regrowth of 70% of the hair. The other 7 patients did not show any regrowth after 4 months of therapy. Except for cases 5 and 15, side effects were minimal (asthenia or hypertrichosis).We could not find in our series any factor (sex, age, type of AA or disease duration) that could be correlated with responsiveness to CsA. A good response to this treatment was seen as early as 1–4 months, so CsA was discontinued if there was no response after 4 months. In any case, treatment with CsA for more than 6 months is not recommended. Since the natural evolution of severe cases of AA (AA totalis, AA universalis and patchy AA affecting more than 50% of the scalp) is chronic and usually does not regress spontaneously, as was observed in our series (mean duration of the disease before treatment 9.8 years), we believe that a partial regrowth in 50% of the cases is significant. CsA can be an alternative treatment for cases of severe AA not responding to other therapies. Further studies with larger numbers of patients comparing CsA with placebo need to be done in order to clarify the role of this drug in the management of severe AA.