BH08 Unprovoked pulmonary emboli in a patient with alopecia areata treated with ritlecitinib: a case report

Abstract Alopecia areata (AA) is a chronic autoimmune condition characterized by nonscarring hair loss due to an aberrant immune response targeting hair follicles. The results of large clinical trials have demonstrated Janus kinase inhibitors to be promising treatments for severe AA. The efficacy of ritlecitinib, an oral Janus kinase 3/TEC family inhibitor, has been demonstrated in the Allegro clinical trials. However, safety concerns remain, particularly regarding serious adverse events such as infections and thromboembolism. The US Food and Drug Administration issued black box warnings, citing increased risks of major adverse cardiovascular events, malignancies, venous thromboembolism (VTE) and mortality based on data from tofacitinib, baricitinib and upadacitinib in rheumatoid arthritis. A 63-year-old woman with a 3-year history of AA (Severity of Alopecia Tool score 97.5) presented with acute symptoms requiring high-dependency unit care 3 weeks after initiating ritlecitinib 50 mg once daily. Pretreatment evaluation included normal chest X-ray, pre­immunosuppression screening, and vaccinations against shingles, influenza and Pneumococcus. The patient had no prior history of venous thromboembolism or malignancy, had not smoked for a long time and was normally active (body mass index 26 kg m−2). Her medical history included anaemia and hypothyroidism. Two weeks after initiating ritlecitinib, she developed ‘flu-like symptoms’, including fever, myalgia, diarrhoea and vomiting, leading to temporary discontinuation of ritlecitinib. Upon resumption, she experienced acute-onset pruritus, throat discomfort, severe diarrhoea and vomiting, extreme lethargy and confusion, prompting emergency admission. Clinical evaluation revealed an acute kidney injury (creatinine 381 µmol L−1), new-onset atrial fibrillation (rate 137 bpm), and hypotension requiring haemodynamic support. Contrast-enhanced computed tomography identified bilateral acute pulmonary emboli. Laboratory investigations showed C-reactive protein 242 mg L−1, lactate 3.5 mmol L−1, albumin 22 g L−1 and white blood cells 30.4 × 109 cells L−1 (lymphocytes 0.8 × 109 cells L−1). Viral polymerase chain reaction was negative for COVID-19 and influenza A and B. Two blood cultures were negative. The patient received intravenous broad-spectrum antibiotics for sepsis of unknown origin, hydrocortisone and vasopressor support for hypotension. She was anticoagulated with dalteparin and transitioned to apixaban as per respiratory advice for unprovoked pulmonary emboli. Ritlecitinib was permanently discontinued, and a yellow card report was submitted to the Medicines and Healthcare products Regulatory Agency. The patient was discharged in a stable condition, with follow-up in the VTE clinic and further investigations planned to exclude malignancy as a cause. This case highlights a probable severe adverse event associated with ritlecitinib therapy, including pulmonary emboli and infection of unidentified source, associated with new-onset atrial fibrillation and acute kidney injury in a patient without known risk factors for VTE. Ongoing pharmacovigilance is essential to understand the potential risks associated with Janus kinase inhibitors in AA treatment.