Original article
Clinical and histopathologic review of Schnitzler syndrome: The Mayo Clinic experience (1972-2011)

Presented at the Annual Meeting of the International Society of Dermatopathology, San Diego, California, March 14-15, 2012.
https://doi.org/10.1016/j.jaad.2012.04.027Get rights and content

Background

Schnitzler syndrome is a rare multisystem disorder, defined by urticaria and monoclonal gammopathy, that is associated with malignancy. Considered a neutrophilic urticarial dermatosis, previous reports have included patients with leukocytoclastic vasculitis.

Objective

We sought to better define the clinical features, histopathology, and outcomes of Schnitzler syndrome.

Methods

We retrospectively reviewed clinical records and cutaneous histopathology of all patients with Schnitzler syndrome seen at our institution from January 1, 1972, through July 31, 2011.

Results

Of the 20 patients identified, 80% had IgM κ monoclonal gammopathy; others had IgG λ (10%), IgG κ (5%), or IgM κ+λ (5%). Patients had fevers (85%), arthralgias (70%), leukocytosis (70%), increased erythrocyte sedimentation rate (70%), bone pain (50%), lymphadenopathy (40%), and organomegaly (5%); 45% developed a hematologic malignancy. Histopathologic examination (n = 14) showed predominantly neutrophilic perivascular and interstitial inflammation (57%) or predominantly mononuclear cell perivascular inflammation (29%), with eosinophils in 50% of cases. None showed leukocytoclastic vasculitis.

Limitations

Our study was limited by its retrospective design.

Conclusion

We added 20 patients to approximately 100 reported cases of Schnitzler syndrome. Neutrophilic urticarial dermatosis was the most common histopathologic pattern, but mononuclear cells were predominant in many cases and the infiltrates often contained eosinophils. A high index of suspicion and careful clinicopathologic correlation are needed to avoid diagnostic delays in this syndrome associated with hematologic malignancy.

Section snippets

Methods

This study was approved by our institutional review board. Patients were evaluated from January 1, 1972, through July 31, 2011.

Diagnosis of Schnitzler syndrome was established on the basis of documentation of an urticarial rash and monoclonal gammopathy (major criteria) plus at least 2 of the following minor criteria: fevers (recurrent or intermittent), arthralgias or arthritis, bone pain, lymphadenopathy, hepatomegaly and/or splenomegaly, elevated erythrocyte sedimentation rate, leukocytosis,

Results

We initially identified a preliminary cohort of 72 patients. Those who did not meet the above diagnostic criteria were excluded. The final cohort included 20 patients (65% male; mean age of 59 years [range, 37-84 years]). All fulfilled the 2 major criteria and 3 to 7 minor criteria (fevers [85%], arthralgias [70%], leukocytosis [70%], increased erythrocyte sedimentation rate [70%], bone pain [50%], lymphadenopathy [40%], and organomegaly [5%]). Sixteen patients (80%) fulfilled at least 3 minor

Discussion

The major diagnostic hallmarks of Schnitzler syndrome are urticarial skin eruptions and monoclonal gammopathy (IgM κ light chain in >90%).1, 3 Recurrence of urticarial lesions varies in frequency. Most commonly involving the trunk and extremities, and sparing the head and neck, the typical eruption consists of rose-colored, slightly elevated papules and wheals that may become confluent (Fig 3).1 Although classically nonpruritic, the urticarial lesions were associated with pruritus in 60% of our

Summary

To our knowledge, this study represents the largest case series of Schnitzler syndrome reported from a single institution. Diagnosis requires a high index of suspicion and consideration of clinical, serologic, and histopathologic data to exclude other diseases in the differential diagnosis. The cutaneous histopathology may be categorized as a NUD but also may resemble common urticaria, with a mild, mainly mononuclear cell infiltrate. Development of a hematologic malignancy is the most serious

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    Funding sources: None.

    Conflicts of interest: None declared.

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