Approach Considerations
Evaluation of urticarua patients with symptoms of fever or lack of response to antihistamines should include testing for Schnitzler syndrome. Definitive diagnosis requires 2 major criteria and at least 2 minor criteria. [17]
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The diagnosis of Schnitzler syndrome is made by using the Strausborg criteria [1] :
Major criteria:
Recurrent urticarial eruption
Monocolonal gammopathy. Titers may be low (< 10 g/L).
Minor criteria:
Recurrent fever - present in ~ 90%
Elevated CRP and/or ESR
Leukocytosis,
Skin biopsy showing a neutrophilic infiltrate without vasculitis
Evidence of abnormal bone remodeling with or without bone pain ( abnormal MRI, elevated bone alkaline phosphatase or bone scintigraphy)
For a definitive diagnosis:
2 major and 2 minor criteria if the monoclonal gammopathy is IgM.
2 major and 3 minor criteria if the monoclonal gammopathy is IgG.
Laboratory Studies
Serum immunoelectrophoresis to investigate for monoclonal gammopathy. 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. [19, 20]
ESR and CRP are elevated in most cases.
CBC with differrntial and platelets: Leukocytosis (70%), thrombocytosis (20%), and anemia (50%) may be found.
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. X-rays of painful joints should be considered as joint destruction may be present. [21]
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. [22]
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. [22]
One report of 22 patients suggested that the most sensitive and cost-effective test for Schnitzler bone lesions is technetium (Tc)-99 nuclear scintigraphy. [22]
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, thus true vasculitis is absent, 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.
Procedures
Bone marrow biopsy should be considered, and abnormal lymphoid proliferation can be seen in 20% of bone marrow biopsy samples, with nonspecific polyclonal lymphocytic and plasmacytic infiltrates.
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Rash of Schnitzler syndrome. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/systemic/schnitzler.jpg).
