JAK inhibition in Schnitzler syndrome: A case report of successful treatment with upadacitinib and literature review

Schnitzler syndrome (SchS) is a rare, acquired, adult-onset autoinflammatory disorder characterized by chronic urticarial rash, monoclonal gammopathy, and systemic inflammation with bone pain and osteosclerosis. Although IL-1 blockade is highly effective and represents first-line therapy, it is not disease-modifying and remains unavailable in many countries, underscoring a need for oral alternatives. Here, we report a 65-year-old man with SchS who, following treatment with upadacitinib (a selective JAK1 inhibitor) combined initially with prednisone, achieved sustained clinical improvement that permitted complete discontinuation of glucocorticoids, with remission subsequently maintained on upadacitinib monotherapy. The patient presented with a three-year history of bilateral knee arthralgia and chronic urticaria, markedly elevated inflammatory markers, and a monoclonal IgM κ gammopathy. Magnetic resonance imaging and whole-body bone scintigraphy demonstrated the “hot knees” sign and, together with bone histopathology and exclusion of alternative dermatoses on skin biopsy, established the diagnosis. Treatment with upadacitinib 15 mg daily and prednisone 20 mg daily led to complete resolution of the cutaneous lesions and a reduction in knee pain (visual analogue scale 8 to 1) with substantial improvement in inflammatory markers at 21 months; prednisone was tapered and discontinued at month 16, after which remission was maintained on upadacitinib monotherapy. We also reviewed the literature (PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure) on JAK inhibitor therapy in SchS, identifying only three previously reported cases, all treated with tofacitinib. Collectively, these preliminary observations suggest that JAK inhibition may represent a potential therapeutic option in Schnitzler syndrome, particularly in patients for whom IL-1 blockade is unavailable or unsuitable. Further studies are required to determine its efficacy and safety.