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. Background Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disease, which was first described in 1972 by Liliane Schnitzler[1]. It always occurs in patients around 50 years. The main clinical features include urticarial rash and monoclonal gammopathy (usually of the IgM class, rarely IgG), accompanied by fever, bone/ joint pain, and lymphadenopathy. Lymphoproliferative disorders and amyloidosis may happen in some patients with SchS[2, 3]. Since the central pathogenesis of SchS is activation of innate immune system and release of interleukin (IL)-1 β, IL-1 antagonists are effective in about 90% patients with SchS[4].

Schnitzler syndrome and Schnitzler-like syndromes

“…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 ]…”

“…[ 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.…”

“…[ 66 ] In another report, one case of a Chinese patient also achieved complete remission on treatment with tocilizumab 8 mg/kg monthly infusion in combination with methylprednisolone and methotrexate. [ 10 ] Claus and Vanderschueren [ 71 ] reported experience with four cases of Schnitzler syndrome treated with tocilizumab at 8 mg/kg infusion; two patients showed effectiveness; and two had no effect. Patient 1 achieved complete remission on anakinra but symptoms relapsed after 4 months.…”

Improving Diagnosis and Clinical Management of Acquired Systemic Autoinflammatory Diseases

“…35 IL-6 blockade may offer an alternate treatment option, as illustrated in an increasing number of case series and reports. 36,37 Notably, it may be an option in patients who fail IL-1 blockade. More recently, Huang et al 38 described a patient with SchS who received Ibrutinib (there was no lymphoplasmacytic lymphoma on bone marrow examination) with the intent of treating his autoinflammatory symptoms, and there was a dramatic symptom improvement in parallel with a reduction in paraprotein levels.…”

Efficacy of interleukin-1 blockade in Schnitzler’s syndrome without detectable monoclonal gammopathy: a case-based review

“…A great variety of treatments have been proposed for SchS, encompassing colchicine, dapsone, steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), thalidomide, TNFblocking agents (anti-TNF), antihistamines, intravenous immunoglobulins, plasma exchange, methotrexate, azathioprine, pefloxacin, cyclophosphamide, tocilizumab, rituximab, and others, including traditional Chinese medicine [5,6].…”