Schnitzler Syndrome: Beyond the Case Reports: Review and Follow-Up of 94 Patients with an Emphasis on Prognosis and Treatment

Objective Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash and monoclonal gammopathy, accompanied by intermittent fever, arthralgia or arthritis, bone pain, and lymphadenopathy. Our objectives are to systematically review disease characteristics of Schnitzler syndrome and collect follow-up information to gain insight into treatment efficacy and long-term prognosis. Methods PubMed and MEDLINE databases (1966-2006) were searched, using the key words “Schnitzler syndrome,” and the combination of “urticaria” with “monoclonal gammopathy,” “immunoglobulin M (IgM),” or “paraproteinemia,” as well as secondary references. Data on a total of 94 patients who met the criteria for Schnitzler syndrome were reviewed. Questionnaires sent to all authors retrieved additional follow-up data on 43 patients, resulting in a mean follow-up of 9.5 years after onset of symptoms, and a follow-up of 20 years or more in 10 patients. Results Symptoms, signs, and laboratory findings as found in the 94 patients are reviewed in detail. There have been promising developments in therapeutic options, especially antiinterleukin-1 treatment, which induced complete remission in all 8 patients treated so far. To date, no spontaneous complete remissions have been reported. Patients with Schnitzler syndrome showed no increased mortality during the present follow-up. However, they had a 10-year risk of 15% of developing a lymphoproliferative disorder, most notably Waldenström’s macroglobulinemia. Three cases of type amyloid A (AA) amyloidosis associated with Schnitzler syndrome were reported. Conclusions Schnitzler syndrome is a disabling disorder which affects multiple systems and which can be considered as an autoinflammatory syndrome. There are new, effective treatment options, but close monitoring remains warranted because of the increased risk of lymphoproliferative disease.