Schnitzler Syndrome

Updated: Sep 19, 2016
  • Author: Brian J Thomas, MD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Practice Essentials

Schnitzler syndrome is characterized by chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a monoclonal gammopathy, most often of the immunoglobulin M (IgM) subtype. Approximately 10-15% of patients eventually develop a lymphoproliferative disorder, such as lymphoplasmacytic lymphoma, Waldenström macroglobulinemia, or IgM myeloma. See the image below.

Rash of Schnitzler syndrome. Courtesy of DermNet N Rash of Schnitzler syndrome. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/systemic/schnitzler.jpg).

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
  • Lymphadenopathy
  • Hepatomegaly
  • Splenomegaly
  • Fatigue
  • Weight loss
  • 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.

Diagnosis

Laboratory studies

  • Immunoglobulin M (IgM) or rarely IgG monoclonal 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

Imaging studies

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.

Management

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. [1]

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. [2]

See Treatment and Medication for more detail.

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Background

Schnitzler syndrome (SS), first reported in 1972, [3] is characterized by chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a monoclonal immunoglobulin gammopathy in a concentration that is usually less than 10 g/L. Since 1972, approximately 200 cases of Schnitzler syndrome have been reported. [1, 4, 5, 6, 7]

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Pathophysiology

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).

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Epidemiology

United States

Only a few cases of Schnitzler syndrome have been reported from the United States.

International

Schnitzler syndrome is rare, with approximately 200 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.

Race

The majority of Schnitzler syndrome cases are in white western Europeans.

Sex

Males have a slight predominance.

Age

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, [5, 1] although the average delay to diagnosis is more than 5 years.

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Prognosis

Most Schnitzler syndrome patients have a chronic benign course. No spontaneous complete remissions have been reported. Overall, the prognosis for Schnitzler syndrome is good. However, approximately 10-15% of patients develop a lymphoplasmacytic malignancy.

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.

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