A Chinese Case Series of Schnitzler Syndrome and Complete Remission in One Tocilizumab-treated Patient

Abstract

Background: Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disease. The major clinical features of SchS are urticarial rush and monoclonal gammopathy, accompanied by fever, joint pain and lymphadenopathy. There were few reports about SchS in Chinese population.Herein, we describe two patients with SchS in China and conducted a systematic literature review about SchS.Methods: Two Chinese Han patients were diagnosed as SchS in our department from 2017 to 2019.Their phenotype and genotype were carefully documented and studied. We also conducted a systematic literature review about SchS.Results: There were one man and one woman with an average disease-onset age of 52. Recurrent fever and urticarial rash occurred in both of them during the febrile attacks and normalized in asymptomatic intervals. Other manifestations included arthritis/arthralgia, lymphadenopathy and hearing loss. Hepatic cirrhosis and epilepsy were seen in one patient. None of them had bone pain or family histories. Serum monoclonal IgM gammopathy was found in both patients. MyD88 gene mutation L258P was identified in one patient. They were treated with tocilizumab and tripterygium wilfordii Hook F (TwHF) respectively and both showed good response.Conclusions: The rarity and diversity of SchS makes it difficult to be recognized. The patient in our study was the first SchS with concomitant liver and neural damage. Anti-IL-6 agents and TwHF may be alternative therapies when anti-IL-1 therapy is unresponsive or unavailable.

Schnitzler syndrome and Schnitzler-like syndromes

“…Eleven out of 30 patients with classical Schnitzler syndrome carry p.L265P mutation [32] . In two independent case reports, two patients with classical Schnitzler syndrome also carry p.L265P mutation [10,37] . These findings do not explain the profound inflammation is Schnitzler syndrome, but may be useful to guide clinical monitoring since a significant proportion of patients with Schnitzler syndrome might develop lymphoproliferative malignancy.…”

“…Hearing loss is infrequently presented in classical Schnitzler syndrome although it is a common feature in cryopyrin-associated periodic syndrome (CAPS) [10,25,26] . Like in CAPS, the hearing loss in Schnitzler syndrome appears to be sensorineural and responsive to IL-1 blocking treatment [25,26] …”

Does tocilizumab have a role in dermatology? A review of clinical applications, its adverse side effects and practical considerations

“…patient with Schnitzler's syndrome when tocilizumab was added to methotrexate and methylprednisolone. 35 A case series of four patients (who all had urticaria) reports mixed response to tocilizumab, where only two patients completely responded. 36 The two responders both received tocilizumab in combination with corticosteroids and colchicine, and additionally azathioprine in one patient.…”

“…Clinical features of Schnitzler's syndrome include urticaria, recurrent fever, arthralgia and hepatosplenomegaly. Yan et al report a complete response of refractory urticaria in a patient with Schnitzler's syndrome when tocilizumab was added to methotrexate and methylprednisolone 35 …”

Transformation of IgM-MGUS into Waldenström´s macroglobulinemia in two of six patients treated for Schnitzler´s syndrome

“…Léčba pomocí protilátky proti interleukinu-6 zvaná tocilizumab byla popsána taktéž jako účinná u syndromu Schnitzlerové, nicméně v roce 2021 je průběh léčby tocilizumabem popsán v nevelkém počtu popisů případů. V jedné publikaci je sice popsána kompletní léčebná odpověď, další publikace hodnotí léčebný efekt jako variabilní (42)(43)(44)(45)(46). V roce 2021 byla publikována berlínskými autory klinická studie, v níž bylo 9 pacientů léčeno tocilizumabem.…”