Schnitzler Syndrome: the paradigm of an acquired adult-onset auto-inflammatory disease.

Schnitzler Syndrome is a rare acquired auto-inflammatory syndrome defined by an urticarial eruption and a monoclonal gammopathy, mainly of the IgM kappa isotype. It shares many clinical and biological features with other autoinflammatory disorders such as NLRP3-auto-inflammatory disorders (NLRP3-AID, formerly cryopyrin associated periodic syndromes or CAPS) or adult-onset Still disease (AOSD). Hence, recurrent fever, urticarial rash with a neutrophilic infiltrate on skin biopsy (i.e. neutrophilic urticarial dermatosis or NUD) and a significant elevation of blood inflammation markers are commonly found in Schnitzler Syndrome as well as in NLRP3-AID or AOSD. IL-1ß plays a crucial role in the pathogenesis and explains the clinical symptoms of Schnitzler Syndrome. This is emphasized by the spectacular effectiveness of IL-1 blocking therapies, especially anakinra. IL-1 blocking therapies are efficient on the inflammation-linked symptoms but not on the monoclonal component. The evolution is chronic and about 15-20% of patients may develop lymphoproliferative disease, in particular Waldenström disease, a proportion similar to patients with IgM monoclonal gammopathy of undetermined significance, and more rarely AA-amyloidosis.