Clinical Pearls & Morning Reports

Posted by Carla Rothaus, MD

Published December 6, 2023


What are the clinical and laboratory features of Schnitzler’s syndrome?

Many patients with Schnitzler’s syndrome have a delay in diagnosis of 5 years or more from the time of the first symptom or symptoms. Read the NEJM Clinical Problem-Solving Article here.

Clinical Pearls

Q: Is Schnitzler’s syndrome an autoimmune disease?

A: Schnitzler’s syndrome is a rare autoinflammatory disease that typically appears in the fifth decade of life and has a slightly higher incidence among men than among women. Diagnosing Schnitzler’s syndrome is a challenge owing to its rarity and overlap in symptoms with other conditions.

Q: Is Schnitzler’s syndrome associated with lymphoproliferative disorders?

A: Patients with Schnitzler’s syndrome are at increased risk for lymphoproliferative disorders, which develop in approximately 15 to 20% of patients typically 10 years or more after the initial disease manifestations. Among these disorders, lymphoplasmacytic lymphoma is the most common, and elevated levels of monoclonal components should arouse suspicion for this condition.

Morning Report Questions

Q: What are the clinical and laboratory features of Schnitzler’s syndrome?

A: All patients with Schnitzler’s syndrome have chronic recurring urticarial rashes. The duration of these episodes vary, and individual lesions are reported to last from less than 24 hours to 48 hours; angioedema is rare. In case series, approximately 55 to 75% of patients with Schnitzler’s syndrome have bone or joint pain. The femur, tibia, and iliac bones are most commonly affected, and bone scintigraphy is the preferred method for showing bone remodeling. Fever is also common and is typically intermittent, without a set pattern; fatigue is common during fever episodes. Lymphadenopathy, weight loss, and hepatomegaly or splenomegaly may also be present. Laboratory testing in nearly all patients reveals elevated inflammatory markers and IgM-κ monoclonal gammopathy; IgG monoclonal gammopathy is present in less than 10% of cases. Other findings may include neutrophilic leukocytosis, anemia, thrombocytosis, and elevated markers of bone remodeling, such as bone-specific alkaline phosphatase and osteocalcin.

Q: How would you treat a patient with Schnitzler’s syndrome?

A: Management of Schnitzler’s syndrome aims to alleviate symptoms, reduce inflammation, and improve quality of life. Although there is no Food and Drug Administration–approved medication for Schnitzler’s syndrome, anakinra — an interleukin-1 receptor antagonist — is approved in the United Kingdom for treating the disease. In a retrospective cohort study, the clinical condition of all 29 patients who had been treated with anakinra improved, and a complete remission was reported in 83%; none of the 13 patients who did not receive this therapy had remission. Studies have also supported benefits of other interleukin-1 inhibitors, including a small open-label study of rilonacept, and a small, randomized, placebo-controlled trial of canakinumab that included a long-term open-label extension.

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