BH02 Overcoming genetic drivers in alopecia areata: hair regrowth in a patient with the <i>AIRE</i> gene mutation treated with ruxolitinib

Abstract Alopecia areata (AA) is one of the most prevalent auto­immune diseases, with an overall lifetime incidence of 2.1%. The aetiopathogenesis of AA is complex and multifactorial, and numerous studies have confirmed that genetics play an important role. A 2010 genome-wide association study of over 1000 patients with AA was pivotal in identifying genes that have been key to our understanding of disease pathogenesis. AA is also strongly associated with genetic conditions such as Down syndrome and the multiorgan autoimmune disease autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED). APECED results from sequence variants causing loss of AIRE gene function. AA occurs significantly more frequently in association with these conditions than the lifetime incidence estimated for the general population (Down syndrome overall AA risk 6.9%, 17% in female patients; APECED AA risk 30%). Familial AA, as compared with sporadic disease, has been said to have a poorer prognosis, with more rapid progression and greater resistance to treatment. We report a patient with APECED due to a biallelic AIRE gene mutation achieving a Severity of Alopecia Tool (SALT) score of 0 after 9 months of ruxolitinib treatment. A 20-year-old woman presented with patchy hair loss in keeping with AA. Over the course of 18 months this progressed to alopecia universalis. The patient had a notable history of chronic inflammatory demyelinating polyneuropathy (CIDP), Sjögren syndrome, adrenal insufficiency, hypoparathyroidism and mucocutaneous candidiasis, consistent with APECED. A biallelic AIRE gene mutation was confirmed on genetic testing. Previous treatments, including diphenylcyclopropenone and ciclosporin, were discontinued due to adverse side-effects. Ruxolitinib, 15 mg twice daily, was initiated by her neurology team, primarily with the aim of improving her CIDP. At 4 months, the patient reported early patchy regrowth of pigmented terminal scalp hair, with no significant regrowth of eyebrows or eyelashes. At 9 months, a SALT score of 0 was achieved, with partial regrowth of eyelashes, eyebrows and body hair. Significantly, there was a marked improvement in her neurological disease, resulting in cessation of intravenous steroid infusions and reduced frequency of intravenous immunoglobulin therapy. She also had a notable improvement in her quality-of-life scores (Dermatology Life Quality Index and Hospital Anxiety and Depression Scale) over the course of the 9 months. This case highlights the efficacy of Janus kinase inhibitors, in this case ruxolitinib, in severe AA associated with AIRE gene mutation.