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Schnitzler's syndrome is an adult-onset autoinflammatory disease characterized by a chronic urticarial-appearing rash, fever, arthralgia, myalgia, and bone pain. All patients have monoclonal IgM or IgG paraproteinemia, and 15% to 20% develop lymphoma, Waldenstrom macroglobulinemia, or IgM myeloma, and amyloidosis occurs with prolonged inflammation.
To identify disease biomarkers, the effect of treatment, and the genetic basis of Schnitzler's syndrome, investigators studied 21 patients meeting diagnostic criteria for the disorder. Results were as follows:
The rash generally covered the trunk and limbs, and symptoms included weight loss in 47% of patients, fatigue in 40%, and lymphadenopathy in 21%.
The paraprotein was IgM kappa in 86%; two patients had marginal cell lymphoma, and one had 15% plasma cells.
ASC (a speck-like protein with CARD domain) aggregates were increased in all patients compared with healthy controls (385/µL vs. 106/µL; P=0.015); IL-18 and IL-6 were also significantly increased.
Next-generation sequencing failed to identify a common mutation.
Therapy with anakinra (a recombinant IL-1 receptor antagonist) resulted in a complete response in 95% of the cohort, and none of the treated patients progressed to malignancy or developed amyloidosis.
Rowczenio DM et al. Molecular genetic investigation, clinical features and response to treatment in 21 patients with Schnitzler's syndrome. Blood 2017 Dec 28; blood-2017-10-810366; [e-pub]. (http://dx.doi.org/10.1182/blood-2017-10-810366)
Comment
Schnitzler's syndrome appears to be a distinct entity, although it bears a close resemblance to cryopyrin-associated periodic syndrome (CAPS), an urticarial disease associated with mutations in the NLRP3 gene. Both Schnitzler's syndrome and CAPS respond dramatically to treatment with IL-1 antagonists, emphasizing the importance of early identification of these disorders and of instituting therapy before disease progression to malignancy or development of amyloidosis.