Schnitzler Syndrome Workup

Updated: Mar 12, 2019
  • Author: Brian J Thomas, MD; Chief Editor: Dirk M Elston, MD  more...
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Approach Considerations

In 2013, an expert consensus panel proposed criteria for diagnosis of suspected Schnitzler syndrome. Definitive diagnosis requires two major criteria and at least two minor criteria. Probable diagnosis is the presence of two major criteria and at least one minor criteria if IgM or two minor criteria if IgG. [14]

Major criteria are as follows:

  • Chronic urticarial eruption

  • Monoclonal IgM or IgG

Minor criteria are as follows:

  • Recurrent fever

  • Bone pain with objective findings of abnormal bone remodeling with or without bone pain (assessed by scintigraphy, MRI, or alkaline phosphatase)

  • A neutrophilic dermal infiltrate seen on skin biopsy

  • Leukocytosis and/or elevated C-reactive protein (neutrophils >10,000/µL or C-reactive protein >30 mg/L


Laboratory Studies

All cases are associated with a monoclonal gammopathy, most commonly IgM and rarely IgG. This is typically demonstrated by serum immunoelectrophoresis. Most cases are of the IgM-kappa isotype. A few cases of IgM-lambda and IgM-kappa/lambda have occurred. The serum IgM levels are usually less than 10 g/L. In 51% of cases, serum protein electrophoresis may not detect the IgM gammopathy because the levels can be very low. A small number of cases have been presented in the literature wherein the patient had clinical features of Schnitzler syndrome but had an associated IgG gammopathy rather than an IgM gammopathy—an IgG variant of Schnitzler syndrome. [16, 17]

The ESR and C-reactive protein level are elevated in most cases. Leukocytosis (70%), thrombocytosis (20%), and anemia (50%) may also be found.

Abnormal lymphoid proliferation can be seen in 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 columns.

Various radiologic findings have been reported with Schnitzler syndrome, including osteosclerosis, hyperostosis, and periosteal reaction.

Typical modalities that have been used include plain radiographs (including skeletal survey), bone scans, CT, MRI, and positron-emission tomography (PET)/CT.

The most common locations for positive findings are the distal femora, proximal tibia, and iliac bones. [18]

The finding of increased signal in the distal femur and proximal tibia is sometimes referred to as the "hot knees" sign and has been reported in multiple cases of Schnitzler syndrome. [18]

One report of 22 patients suggested that the most sensitive and cost-effective test for Schnitzler bone lesions is technetium Tc-99 nuclear scintigraphy. [18]


Histologic Findings

A review of the pathology of Schnitzler syndrome shows that the histopathologic findings are not consistent; features in some patients include a superficial dermal and perivascular infiltrate of polymorphonuclear cells, mostly neutrophils, suggestive of neutrophilic urticaria. A small percentage of specimens demonstrate a superficial perivascular mononuclear infiltrate suggestive of chronic urticaria and lymphocytic inflammation. Vessels are intact, and dilatation of dermal lymphatics with mild superficial edema may present.

Rare cases show fibrin deposition, extravasation of erythrocytes, or leukocytoclastic vasculitis.

Deposits of IgM and complement in the upper dermis and/or at the dermoepidermal junction are seen in 45% of cases. Rarely are IgM deposits found within vessel walls.