Refractory Dupilumab-Induced Inflammatory Arthritis Treated by Upadacitinib: A ‘Janus Kinase (JAK)’ of All Trades

Dupilumab, a monoclonal interleukin (IL)-4 receptor α antagonist, is used to treat moderate-to-severe atopic dermatitis. Uncommonly, inflammatory arthritis and enthesitis may occur upon initiation of dupilumab. Upadacitinib, a Janus kinase (JAK) inhibitor, is an alternative medication approved for moderate-to-severe atopic dermatitis but is also used to treat inflammatory arthritis. We report a case of dupilumab-induced inflammatory arthritis that was refractory to oral nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids and was successfully treated by upadacitinib, which also treated the atopic dermatitis. A 40-year-old female with moderate-to-severe atopic dermatitis was treated with dupilumab for 10 months, showing improvement in her skin. However, she then developed recurrent right knee effusions, polyarthritis in her hands, feet, and knees, and prolonged stiffness. She noticed swelling which developed abruptly in her right knee, then progressed to multiple joints including fingers, wrists, ankles, and persisted for four weeks prior to seeking additional medical care. She denied any recent preceding trauma. Joint pain was worsened by movement and morning stiffness lasted over two hours. Trials of ibuprofen or celecoxib and application of ice did not alleviate it. She had an elevated erythrocyte sedimentation rate of 29 mm/hr and C-reactive protein of 21.6 mg/dL. She tested negative for antinuclear antibody, rheumatoid factor, anti-cyclic citrullinated protein, human leukocyte antigen B27, Lyme enzyme-linked immunosorbent assay (ELISA), and Western blot. She was initially treated with a prednisone taper, but the symptoms returned upon reaching 10 mg daily. She continued on dupilumab for four weeks, but stopped as the joint symptoms progressed. With cessation, her atopic dermatitis also became active again. Despite stopping the dupilumab, she continued to have diffuse swelling and tenderness in her hands, feet, knees, and wrists over the next 12 weeks. Upadacitinib, within one month of initiating, led to improvement in both joints and skin. She was able to taper off the corticosteroids. At five months, she continued to not have swelling or tenderness in her joints, and her skin was well-controlled. We report the first successful use of upadacitinib for the treatment of refractory dupilumab-induced inflammatory arthritis as well as atopic dermatitis. The use of JAK inhibitors should be considered to treat this uncommon condition, given that they also treat atopic dermatitis.