Schnitzler syndrome is a rare acquired autoinflammatory disease characterized by relapsing urticarial rashes, periodic fevers, arthralgias, lymphadenopathy and IgM paraproteinaemia, which can be very low level. Fewer than 100 patients have been reported and in general chemotherapy directed at the B cell clone has not been effective in controlling the inflammatory symptoms.
We describe our series of six patients, their phenotype and response to treatment. The median age at symptom onset was 55.6 years (range 52.8–78.9 years) and 4 of the patients were male. All patients presented with rash, recurrent fever, constitutional upset with appetite loss, fatigue and myalgia. The rash was urticarial in appearance but non itchy and on biopsy demonstrated a marked neutrophil infiltrate. Three patients had intermittent lymphadenopathy and one disabling bone pain. An IgM paraprotein was detected in all cases, median 7g/L (range: detected on immunofixation only – 8g/L). The IgM paraprotein was kappa in 5 cases and only one patient had abnormal serum free light chains. The Hevylite™ assay was abnormal in all 4 cases in whom the test was performed. Of note the patient with an IgM lambda paraprotein detected only on immunofixation has a clear IgM lambda excess on Hevylite™ assay. Baseline bone marrow demonstrated significant abnormalities in three patients: one has a 10% infiltrate of clonal cells consistent with lymphoplasmacytic lymphoma, one demonstrated a myeloproliferative picture with dysplastic features but no obvious plasma or lymphoid infiltrate and one was reported as reactive. Three patients had been treated with broad spectrum immunosupression without benefit and all had had corticosteroids with only partial benefit. In all cases treatment with anakinra (recombinant IL-1 receptor antagonist) as monotherapy produced a complete clinical response with normalisation of inflammatory markers. The median duration of treatment has been 9 months (range 0.1–2.7 years) and no patients have lost their response to daily ankinra injections. Median follow up from presentation has been 7.1 years with no evidence of evolution of overt lymphoproliferative disease nor change in the paraprotein concentration. In conclusion Schnitzler's syndrome is a rare acquired autoinflammatory disease which can be very effectively treated by anakinra suggesting that IL-1 is central to its pathogenesis. Treatment does not appear to have had any direct effect on clonal markers and the role of the IgM paraprotein in this disease remains unclear.
Off Label Use: Anakinra - IL-1 receptor blockade, used off licence in Schniztlers syndrome.
Asterisk with author names denotes non-ASH members.