- Author: Joel G DeKoven, MD, MHSc, FRCPC; Chief Editor: Dirk M Elston, MD more...
Schnitzler syndrome is characterized by chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a monoclonal immunoglobulin M (IgM) gammopathy in a concentration of usually less than 10 g/L. Approximately 10-15% of patients eventually develop a lymphoproliferative disorder, such as lymphoplasmacytic lymphoma, Waldenström macroglobulinemia, or IgM myeloma.
Signs and symptoms
Schnitzler syndrome is characterized by the following signs and symptoms:
Chronic, recurrent, urticarial eruption: Occurs in all patients, usually as the first sign of the disease; primarily affects the trunk and the extremities and spares the palms, soles, and head and neck areas
Pruritus: Usually absent at disease onset, but lesions may become mildly pruritic in approximately 45% of patients after 3-4 years
Recurrent fevers: In approximately 90% of patients
Relapsing arthralgias: Concurrent with fever; reported in 80% of patients
Bone pain: Concurrent with fever; reported in 70% of patients
Myalgias: Concurrent with fever
Angioedema: Very rare
The urticarial rash is characterized as follows:
Pale-rose, slightly elevated papules and plaques
Individual lesions are 0.5-3 cm in diameter
New lesions appear daily
Lesions last 12-24 hours and then disappear without sequelae
See Clinical Presentation for more detail.
Immunoglobulin M (IgM) gammopathy: Detected with serum immunoelectrophoresis; occurs in all patients; in 51% of cases, however, serum protein electrophoresis may not detect it
Elevated erythrocyte sedimentation rate (ESR): Found in most cases
Elevated C-reactive protein level: Also detected in most cases
Leukocytosis: 70% of patients
Thrombocytosis: 20% of patients
Anemia: 50% of patients
Abnormal lymphoid proliferation: 20% of bone marrow biopsy samples, with nonspecific polyclonal lymphocytic and plasmacytic infiltrates
Radiologic evaluation shows evidence of hyperostosis in 35% of Schnitzler syndrome patients. Often, the areas of hyperostosis coincide with areas of symptomatic bone pain, such as the iliac bone, tibia, femur, and vertebral column.
See Workup for more detail.
Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive agents have been reported to provide variable relief from the symptoms of bone pain and arthralgias associated with Schnitzler syndrome.
Systemic steroids may be somewhat effective at controlling the cutaneous eruption, but usually at doses that can cause significant, long-term adverse effects.
Pefloxacin mesylate may be a therapeutic option. In a case series of 11 patients, it was shown to significantly reduce the intensity and frequency of many of the manifestations of Schnitzler syndrome in a majority of the group, and it provided a steroid-sparing effect for some patients being treated with systemic corticosteroids.
Anakinra, a recombinant form of the naturally occurring interleukin-1 (IL-1) receptor antagonist, and rilonacept, a dimeric fusion protein that acts as a decoy IL-1 receptor, reportedly benefit patients with Schnitzler syndrome.
Schnitzler syndrome (SS), first reported in 1972, is characterized by chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a monoclonal immunoglobulin M (IgM) gammopathy in a concentration that is usually less than 10 g/L. Since 1972, approximately 100 cases of Schnitzler syndrome have been reported.[4, 1, 5, 6]
The exact pathogenesis of Schnitzler syndrome is unclear. Some hypothesize that the deposition of the IgM paraprotein, leading to the formation of immune complexes and the activation of the complement cascade, is responsible for the cutaneous manifestations of Schnitzler syndrome. Another proposed mechanism involves the uncontrolled activation of interleukin 1-alpha (IL-1alpha).
Only a few cases of Schnitzler syndrome have been reported from the United States.
Schnitzler syndrome is rare, with approximately 100 cases reported in the literature. The original case was from France, with the greatest number of cases originating from the same country. The vast majority of cases come from Western Europe.
Most Schnitzler syndrome patients have a chronic benign course. Spontaneous remissions have not been reported. Approximately 10-15% of patients eventually develop a lymphoproliferative disorder, including lymphoplasmacytic lymphoma, Waldenström macroglobulinemia, or IgM myeloma. Schnitzler's original patient died at age 88 years, with a diffuse lymphoplasmacytic infiltration of his liver and bone marrow. Thus, the initial workup of a Schnitzler syndrome patient should include an examination of the bone marrow, immunoelectrophoresis of serum, and a urinary protein level. A lymph node biopsy should be performed if the nodes are enlarged.
The majority of Schnitzler syndrome cases are in white western Europeans.
Males have a slight predominance.
Patients with Schnitzler syndrome have ranged from age 13-71 years at the time of diagnosis. The average age of onset is approximately 52 years,[4, 1] although the average delay to diagnosis is more than 5 years.
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