The Schnitzler syndrome

Abstract

The Schnitzler syndrome is a rare and underdiagnosed entity which is considered today as being a paradigm of an acquired/late onset auto-inflammatory disease. It associates a chronic urticarial skin rash, corresponding from the clinico-pathological viewpoint to a neutrophilic urticarial dermatosis, a monoclonal IgM component and at least 2 of the following signs: fever, joint and/or bone pain, enlarged lymph nodes, spleen and/or liver, increased ESR, increased neutrophil count, abnormal bone imaging findings. It is a chronic disease with only one known case of spontaneous remission. Except of the severe alteration of quality of life related mainly to the rash, fever and pain, complications include severe inflammatory anemia and AA amyloidosis. About 20% of patients will develop a lymphoproliferative disorder, mainly Waldenström disease and lymphoma, a percentage close to other patients with IgM MGUS. It was exceedingly difficult to treat patients with this syndrome until the IL-1 receptor antagonist anakinra became available. Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections.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.

Figure 1

the typical rash of the Schnitzler syndrome, which corresponds to a neutrophilic urticarial dermatosis: rose to red macules and/or slightly raised plaques. The lesions are usually not itchy and vanish within hours without sequel.

Figure 2

(HE, × 200): a neutrophilic infiltrate of the dermis without vasculitis and without significant edema.

Figure 3

(HE, × 200): significant neutrophilic infiltrate (arrow, thin) with interstitial dispersion and leukocytoclasia (arrow, thick).