The pathogenesis of Schnitzler syndrome remains unclear, although it is thought to be an acquired autoinflammatory disorder in which increased interleukin (IL)-1b and IL-6 leads to loss of anti-inflammatory Th17 cell properties. The role of the paraprotein is unknown, although increased IL-1 stimulation could contribute to IgM paraproteinemia.
Schnitzler syndrome may progress to Waldenström macroglobulinemia or other lymphoproliferative disorders. Waldenström disease is the most common complication, occurring in 15% of cases after 10-20 years of symptom onset. As with several other autoinflammatory conditions, ongoing inflammation leads to production of hepatic acute phase reactants, including serum amyloid A protein, which can lead to AA amyloidosis. Overall prognosis depends on whether this progression to hematologic dyscrasia or secondary amyloidosis occurs.
D47.2 – Monoclonal gammopathy
402415001 – Schnitzler syndrome
Differential Diagnosis & Pitfalls
- Adult-onset Still disease (AOSD) – Both Schnitzler syndrome and AOSD are characterized by urticarial rash, fever, joint pain, and leukocytosis. Distinguishing features of AOSD include elevated ferritin levels, increased transaminases, and pharyngitis.
- Rheumatoid arthritis – Positive anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor; elevated inflammatory markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); synovitis on examination with pain, swelling, and warmth of small joints of the fingers, wrists, and ankles; morning stiffness lasting more than 1 hour that improves with activity.
- Cryopyrin-associated periodic syndrome – A spectrum of rare autoinflammatory genetic diseases involving the cryopyrin protein.
- Urticarial vasculitis – Presents similarly to Schnitzler syndrome with rash, fever, and joint pain. Decreased levels of complement as a result of increased consumption and anti-C1q antibodies are present in urticarial vasculitis but not in Schnitzler syndrome. Unlike true vasculitides, skin biopsy in Schnitzler syndrome will not show fibrinoid necrosis.
- Cryoglobulinemic vasculitis – Low complement values and presence of cryoglobulins causing systemic effects such as skin and renal disease; associated with hepatitis C, malignancy, or autoimmune condition.
- Systemic lupus erythematosus – SOAP BRAIN MD mnemonic (serositis, oral ulcers, arthritis, photosensitivity, blood disorders, renal involvement, antinuclear antibodies, immunologic phenomena, neurologic disorder, malar rash, discoid rash); must fulfill 4 of 11 of criteria according to the American College of Rheumatology.
- Chronic idiopathic urticaria
- Monoclonal gammopathy of undetermined significance (MGUS) – Clinically does not cause signs or symptoms; usually affects elderly patients with peak age older than 85 years.