The Schnitzler syndrome

In many aspects, the Schnitzler syndrome resembles the genetically determined auto-inflammatory syndromes involving activating mutations of the NLRP3 inflammasome. This latter point and its consequences will be addressed.The Schnitzler syndrome is a rare and acquired systemic disease which bears in common many features with a group of inherited diseases referred to as auto-inflammatory syndromes. Its main clinical features include fever, an urticarial rash, muscle, bone and/or joint pain and enlarged lymph nodes. A monoclonal IgM component is the biological hallmark of the disease. Conventional therapies including anti-histamines for the skin rash, as well as anti-inflammatory drugs, steroids and immunosuppressive drugs for the systemic signs, are usually ineffective. However, the IL-1 receptor antagonist anakinra was found to rapidly control all the symptoms of this syndrome. However, signs recur as soon as the treatment is stopped. About 15% to 20% of patients with a Schnitzler's will develop a lymphoproliferative disorder, a prevalence shared with other patients with monoclonal IgM gammopathies of undetermined significance (MGUS) [1]. AA-amyloidosis is a concern in untreated patients [2,3].This review will provide a comprehensive overview of the clinical and biological features of this syndrome, emphasizing its particular rash, and summarize our current comprehension of its pathophysiology, its complications and its treatment.The different signs of this syndrome were first reported in 1972 and then published in 1974 as an autonomous entity by Liliane Schnitzler, a French dermatologist [4,5]. In the following years, cases were reported from all over the world including North America and Japan, but mostly from Europe. The European preeminence is probably related to a better knowledge of this entity in the old World. In 1999, Lipsker et al reported 4 cases and performed an extensive literature review which allowed them to establish diagnostic criteria [6], which are