Concomitant management of alopecia universalis and ulcerative colitis with upadacitinib

Alopecia areata (AA) is an autoimmune disorder characterised by nonscarring hair loss mediated by T lymphocytes against the hair follicular unit. Its most severe form, alopecia universalis (AU), is characterised by complete body hair loss.1 The association between AA and other autoimmune conditions, including inflammatory bowel disease (IBD), is well established and likely due to shared immune dysregulation pathways.2, 3 Immunosuppressive and biologic agents used to treat IBD, including thiopurines, methotrexate and tumour necrosis factor-α inhibitors (TNFIs), have also been linked to other forms of alopecia.4 AA has traditionally been managed with topical or systemic corticosteroids, although Janus kinase (JAK) inhibitors are emerging as promising therapies. The JAK–STAT signalling pathway mediates cytokines crucial for the proliferation of autoreactive CD8+ T-cells implicated in the pathogenesis of both AA and IBD.2, 3 Baricitinib (JAK-1 and 2 inhibitors) and ritlecitinib (JAK-3 and TEC kinase inhibitor) are FDA-approved for severe AA. However, evidence supporting their use in IBD is limited. Conversely, while upadacitinib (selective JAK-1 inhibitor) is approved and PBS-listed for the treatment of ulcerative colitis (UC) and Crohn disease, it is not currently approved for use in AA, though several case reports support its efficacy in AA.5 The optimal treatment approach for patients with concurrent AA and UC is unknown. We present the case of a 32-year-old Caucasian female with a history of Graves disease (post-thyroidectomy on thyroid hormone replacement), Addison disease (on prednisolone and fludrocortisone) and scalp psoriasis, who was diagnosed with extensive moderate to severe UC. As a result of azathioprine intolerance, her UC was initially managed with mesalazine and standard-dose 5 mg/kg 8-weekly intravenous infliximab. Poor symptom control led to the addition of mercaptopurine 50 mg daily and escalation of infliximab to 5 mg/kg 4-weekly dosing. Two weeks after these medication changes, the patient experienced significant scalp hair loss. Although no bone marrow suppression was noted, mercaptopurine was discontinued after 2 months as her UC was in remission and because of concerns about its role in alopecia. Despite stopping mercaptopurine, hair loss worsened, resulting in complete body hair loss. At dermatology review, a diagnosis of AU was made following unremarkable autoimmune and nutritional screens. Although the addition of baricitinib for AU was initially considered, safety concerns about dual JAK inhibitor and infliximab use prompted us to cease infliximab and initiate upadacitinib instead. Remarkably, significant hair regrowth was observed after 4 months of upadacitinib 45 mg daily induction, followed by 30 mg daily maintenance, while maintaining clinical remission of UC (Fig. 1). The aetiology of alopecia in this patient was likely multifactorial, involving immune dysregulation in the setting of multiple autoimmune diseases and potential medication side effects. TNFi-associated alopecia was thought to be more likely given the absence of bone marrow suppression and continued hair loss despite thiopurine cessation. The JAK–STAT signalling pathway is implicated in the pathogenesis of both AA and UC, supporting the use of JAK inhibitors in this case. Upadacitinib, with relative JAK-1 selectivity, was well tolerated and yielded excellent therapeutic outcomes for our patient, holding promise for the management of future patients with a dual diagnosis of UC and AA.