Schnitzler syndrome is a very rare immunological disease. Presenting signs and symptoms are an urticarial rash, intermittent fevers, myalgia, arthralgia, bone pain, lymphadenopathy, and peripheral neuropathy. Monoclonal IgM gammopathy is the main pathological feature that leads to symptoms while a chronic relapsing course is usually observed. The diagnosis rests on clinical criteria, a thorough laboratory assessment (frequently showing anemia and neutrophilia, along with abundant IgM levels), and a biopsy of the skin that confirms the presence of a neutrophilic infiltrate.
Schnitzler syndrome is a very rare autoinflammatory disease that seems to arise from an IgM monoclonal gammopathy    . The pathogenesis still remains incompletely understood, but the clinical presentation has been well-documented in the literature. The cardinal feature of patients suffering from Schnitzler syndrome is a chronic urticarial rash   . Urticaria is the presenting manifestation in many individuals and appears years before other notable symptoms and signs of Schnitzler syndrome    :
Lymphadenopathy is also an important sign, being present in more than 40% of cases . The clinical course of Schnitzler syndrome is often described as several-years long before the diagnosis is made  . It is important to mention that similarly to other monoclonal gammopathies, a significant risk exists toward the development of a lymphoproliferative disorder, such as IgM myeloma or marginal B-cell lymphoma  .
A high index of suspicion is necessary in order to make the diagnosis of Schnitzler syndrome . A thorough history should be obtained first, during which the onset of symptoms (particularly the rash and relapses of fever), their progression, as well as severity must be covered. The physical examination can only confirm the nonspecific findings, which is why laboratory studies are the crucial step in the workup. A complete blood count (CBC) will show anemia and leukocytosis with neutrophilia in a significant number of patients, whereas basic inflammatory parameters will reveal elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)  . The detection of an IgM kappa chain raises solid evidence toward Schnitzler syndrome (the presence of IgG is also reported but in very few patients), although their levels may be paradoxically low at the time of diagnosis    . Skin biopsy and subsequent histopathological examination is an equally important diagnostic tool, showing a neutrophilic infiltrate in a significant portion of tested patients . Bone marrow biopsy could be recommended in some cases.