Unexpected Effect of Baricitinib Use: Observation of a Case of Hypertrichosis

Dear Editor, Alopecia areata is an autoimmune disorder affecting the hair follicle, leading to varying degrees of hair loss across different areas. The pathogenesis sees a loss of the ‘immunological privilege’ of the hair follicle in the anagen phase, with induction of an immunological cascade mediated by cytotoxic T lymphocytes.[1] The presence of a dysregulation of the immunological response is further confirmed by the coexistence of other autoimmune diseases in affected patients, such as thyroiditis.[2] The Janus kinase (JAK) family includes a group of enzymes that, coupled to tyrosine kinase receptors mediate the intracellular signal; they are involved in different cellular phases such as proliferation, modulation of the immunological response. Specifically for Alopecia Areata (AA), JAK inhibitors can modulate the activation of certain cytokines on T-cell receptors. This modulation affects the interaction with other mediators of the immune response, leading to follicular damage. Traditional treatments have included the use of topical and/or systemic corticosteroids and immunosuppressants. In 2022, the FDA approved the first drug specifically for alopecia areata, baricitinib, which is a JAK1/2 inhibitor. Pilot studies have demonstrated significant effectiveness in promoting follicle regrowth within 36 weeks of treatment.[2] Case Presentation We report the case of a 48-year-old Caucasian woman who was referred to our dermatology clinic due to areas of hair loss. She also reported suffering from Brocq’s pseudopelade. There was no personal or family history of alopecia. During the cutaneous examination, a well-demarcated, irregular patch of hair loss was observed on the vertex and temporal regions of the scalp. Trichoscopic analysis revealed the presence of exclamation point hairs at the borders. A 4 mm punch biopsy was performed, revealing elements that, combined to trichoscopy, were indicative of alopecia areata. After the diagnosis was confirmed, we initially treated the patient with daily applications of topical corticosteroids, which did not yield any improvement. Subsequently, we started treatment with Baricitinib at a dosage of 4 mg daily. At 3 months follow-up we observed an improvement in alopecia patches, with a complete resolution observed at 6 months follow-up. Additionally, we observed hair growth in other regions, including the forehead, cheeks, and neck, indicative of hypertrichosis. This is likely a side effect of the medication, a phenomenon not previously documented in the literature [Figures 1 and 2].Figure 1: Note the presence of hairs in the zygomatic areaFigure 2: Note the presence of hair on the foreheadConclusion The efficacy of baricitinib in alopecia areata underscores its significant impact on the JAK-mediated intracellular signalling cascade within this autoimmune pathology. The capability of baricitinib to promote follicle regrowth is well-established. However, the emergence of hypertrichosis as a side effect has not been previously reported. This phenomenon in our case may be elucidated by examining the role of the JAK/STAT pathway in follicular dynamics during the anagen (growth) phase of hair. Hypertrichosis is characterized by the action of androgens, which are known to stimulate hair growth, increase follicle size, and prolong the anagen phase. Furthermore, studies conducted on mouse models have indicated a reciprocal activation between androgen receptors (AR) and the Wnt/β-catenin pathway. Notably, the modulation of the Wnt/β-catenin pathway is mediated by JAK/STAT.[1,3] The use of baricitinib, by inhibiting the ongoing immunological reaction, induces a ‘reverse’ in the follicular state, guiding it into a prolonged anagen (growth) phase. This effect is achieved through the modulation of the Wnt/β-catenin pathway, which is itself orchestrated by JAK/STAT.[4] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.