BH14 Multiple sclerosis and alopecia areata: drug-induced alopecia areata or coexisting autoimmune phenomena?

Abstract

Abstract Alopecia areata (AA) is an autoimmune condition characterized by well-demarcated patches of nonscarring alopecia. AA shares multiple gene loci with other autoimmune conditions, including multiple sclerosis (MS). There are limited data on drug-induced alopecia areata (DIAA); however, the literature is expanding, with several targeted therapies implicated including dupilumab, nivolumab and multiple disease-modifying MS treatments, namely, alemtuzumab and ocrelizumab. Alemtuzumab is monoclonal antibody against CD52, which is expressed on T and B lymphocytes, natural killer (NK) cells, monocytes and macrophages. It is considered a highly efficacious treatment; however, there are increasing reports of secondary autoimmunity in up to 40% of patients (Tuohy O, Costellow L, Hill-Cawthorne G et al. Alemtuzumab treatment of MS: long-term safety and efficacy. J Neurol Neurosurg Psychiatry 2015; 86:208–15). A 35-year-old man was referred by his neurologist with concerns of alemtuzumab-induced alopecia universalis (AU). He has relapsing-remitting MS, diagnosed in 2018. His first alemtuzumab course was in 2018 and the second in June 2019, which achieved remission. He reported AU approximately 10 months after this second course with complete spontaneous regrowth. A further episode of AU occurred 6 months later with only minimal eyebrow regrowth. He had no previous history of alopecia or thyroid disease. He had vitamin D insufficiency. There are 12 cases of alemtuzumab-induced AA reported in the literature with variable timeframes of onset, ranging between weeks to over 6–9 months postinfusion. The majority of patients received more than one infusion prior to the onset of AA. Our case echoes other case reports, including one case of AU manifesting 9 months post-alemtuzumab (Zimmermann J. Buhl T, Muller M. AU following alemtuzumab treatment in MS: a barely recognized manifestation of secondary autoimmunity – case report and review of literature. Front Neurol 2017; 8:569). AA pathogenesis, like MS, is hypothesized to be multifactorial with genetic, environmental and autoimmune aspects. It is believed that AA hair follicle cells have increased major histocompatibility complex class I and II activity, presenting autoantigens to CD8+ T cells, CD4+ T cells and NK cells. Interferon (IFN)-γ is considered key in AA pathogenesis. Patients with AA are found to have raised serum levels, along with reports of raised interleukin (IL)-6 levels. Alemtuzumab-induced immunosuppression precedes a phase of immune reconstitution. Cytokines are released post-treatment, including IFN-γ, tumour necrosis factor-α, IL-6 and IL-2. It is plausible that alemtuzumab could trigger AA as a sequela of the immune reconstitution. However, DIAA has been poorly described and the genetic overlap raises the question of both conditions occurring spontaneously. Accurate phenotyping and a multidisciplinary approach will enable us to gain greater clarity, inform our decision-making in the management of these complex patients and provide insights into pathogenic AA pathways.