Alopecia areata (AA) is an autoimmune T CD8 cell mediated condition clinically characterized by hair loss from single or few small patches to complete hair loss. The management of AA is challenging and all available therapies does not ensure a longterm remission. To assess the safety and efficacy of both systemic and topical brevilin A, a natural compound, in AA patients not responding to other treatments. After obtaining informed consent, we administered off-label brevilin A to 13 adult patients affected by AA, for a period ranging from 6 to 18 months. Medical records for each patient and the severity of alopecia tool (SALT) score before and after brevilin A administration were recorded. The mean SALT score of our patients was 81.03 (SD 34.9) at baseline and 75.8 (SD 37.4) after brevilin A therapy, meaning no statistically significant improvement was observed (P = .2385 Paired t test). However, three multifocal AA (MAA) patients out of four attained an improvement (75%) suggesting that brevilin A may be represent an alternative therapy in this form of AA. Authors conclude that brevilin A could represent in the future a possible effective treatment in MAA forms but further studies are required. K E Y W O R D S alopecia areata, brevilin a Alopecia areata (AA) is an autoimmune nonscarring hair loss mediated by CD8 T cells, with chronic-relapsing course. Clinical aspects range from single patches to whole scalp hair loss (alopecia totalis [AT]) and body hair loss (alopecia universalis [AU]). 1 Disease severity is mutually related with psychological consequences, including anxiety and depression, which commonly afflict AA patients, especially in case of young females. Unfortunately, available therapies have been unsuccessful in influencing the long-term course of AA; thus, treatments of AA represent a challenge and a drug with specific indication is still missing. 2 Autoreactive CD8 + NKG2D+ T cells are the main actors in the pathogenesis of AA, responsible for hair loss, thus all common treatments share a regulatory effect upon the immune system. Among them, two JAK inhibitors have been tested, including tofacitinib (JAK 1/3 inhibitor) and ruxolitinib (JAK 1/2 inhibitor) in oral and topical formulations, with promising results. 3-5 These data could be explained by the evidence that JAK-STAT dependent cytokines, IFN-γ and IL-15, activate autoreactive CD8 + NKG2D+ T cells, and also by JAK inhibitors ability in inducing anagen phase. 6,7 However, these drugs could show adverse effects, especially in case of longterm use. Interestingly, a natural molecule named brevilin A shows a strong effect in JAK-STAT signal inihibition, both in vitro and in vivo studies. 8 Brevilin A is a sesquiterpene lactone isolated from Centipeda minima (CM), a medicinal plant of Asteraceae family distributed in China,