Refractory vitiligo improving with eculizumab

Dear Editor The pathogenesis of vitiligo, an acquired depigmentation disorder with progressive loss of melanocytes, is complex, multifactorial, and polygenic (Norris, Kissinger, Naughton, & Bystryn, 1988). First-line treatments such as topical corticosteroids, topical calcineurin inhibitors, and phototherapy, either as monotherapy or in combination are mostly unsatisfactory, showing the need for the development of targeted therapies. The efficacy of other current options, including topical antioxidants and topical vitamin D analogs, remains controversial. Besides, there is limited data on alternative treatments. Moreover, some of those therapeutic options are recommended for particular instances. Systemic corticosteroids and methotrexate can be used for halting disease progression in active vitiligo, and punch graft and suction blister epidermal graft for inducing repigmentation once vitiligo has been stabilized. So far, no option has been developed for preventing vitiligo relapse. Fortunately, new promising therapeutic options such as Janus Kinase Inhibitors and topical prostaglandins have emerged due to new advances in the understanding of the pathophysiology of vitiligo. Nevertheless, we should keep questioning ourselves and continue exploring all pathways in vitiligo pathogenesis to target for more potential medical treatments. A 46-year-old male with a 25-year history of generalized vitiligo was diagnosed with paroxysmal nocturnal hemoglobinuria (PNH). Over the course of several months, he developed esophageal spasm and progressive hemolytic anemia. He commenced anticomplement therapy as a participant in the ALXN-301 clinical trial. He was treated with eculizumab, receiving a loading dose of 600 mg followed by 11 maintenance doses of 900 mg at 14-days, after which he received a 2,700 mg loading dose of ravulizumab followed by ongoing maintenance doses of 3,300 mg at 8-week intervals. Within 4 weeks of starting treatment with eculizumab, his symptoms resolved and his hemolytic indices normalized. Six months after starting the therapy, the patient noticed macules of repigmentation on his face and hands. He was on no active treatment for his vitiligo, which had been refractory to topical therapy, and he never had such an improvement in his vitiligo before starting eculizumab. The pathogenesis of vitiligo is still incompletely understood. Cellular and humoral responses, including complement-activating antimelanocyte antibodies, have been implicated in the destruction of melanocytes. Melanocyte destruction has been documented in vitro by complement-mediated damage and antibody-dependent cellular cytotoxicity (Norris et al., 1988), and in vivo, by passive immunization of nude mice (Kemp, Gavalas, Gawkrodger, & Weetman, 2007). Another in vitro study reported an increase of melanocytes destruction due to antibody-mediated complement attack when complement regulatory molecules (CRMs), expressed in melanocytes to protect them from complement damage, are decreased (Venneker et al., 1998). Moreover, one study demonstrated a reduction in the expression of CRM in vitiligo skin and perilesional skin when compared with non-lesional skin of the same patient (van den Wijngaard et al., 2002). Overall, the activation of complement plays a role in vitiligo pathogenesis. Our patient might have improved because eculizumab antagonizes the complement pathway in a patient with a suboptimal complement regulation. Eculizumab binds to the human c5 complement protein and inhibits activation of the terminal complement pathway, thereby preventing the assembly of the membrane attack complex, and blocking the lytic activity of complement. Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome and PNH. Its high cost may hamper its further use for vitiligo, except in special cases like ours. Nevertheless, our patient's improvement suggests that further research should explore targeting the complement pathway as a potential therapy for vitiligo.