Schnitzler syndrome is a very rare autoinflammatory disease that seems to arise from an IgM monoclonal gammopathy [1] [2] [3] [4]. 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 [1] [2] [3]. Urticaria is the presenting manifestation in many individuals and appears years before other notable symptoms and signs of Schnitzler syndrome [3] [4] [5] [6]:

• Fever - A chronic course of fever that possesses an intermittent pattern is seen in 75% of patients [1] [3] [6] [7]. Fever often accompanies the onset of urticaria, while some cases have been described in whom the rash appeared after fever [1] [2].
• Pain - Myalgia, arthralgia, and bone pain are frequent manifestations seen in this syndrome, together with fatigue [1] [3] [4].
• Peripheral neuropathy - From 7%-56% of individuals suffer from peripheral neuropathy according to different studies [1] [3].
• Night sweats, weight loss, hepatomegaly, and splenomegaly are less commonly encountered [1] [2] [7].

Lymphadenopathy is also an important sign, being present in more than 40% of cases [1]. The clinical course of Schnitzler syndrome is often described as several-years long before the diagnosis is made [1] [6]. 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 [1] [6].

• Fever

  Fever often accompanies the onset of urticaria, while some cases have been described in whom the rash appeared after fever. Pain - Myalgia, arthralgia, and bone pain are frequent manifestations seen in this syndrome, together with fatigue. [symptoma.com]

  In approximately 90% of patients Relapsing arthralgias: Concurrent with fever; reported in 80% of patients Bone pain: Concurrent with fever; reported in 70% of patients Myalgias: Concurrent with fever Lymphadenopathy Hepatomegaly Splenomegaly Fatigue [emedicine.com]

  Clinical Commissioning Policy: Anakinra to treat periodic fevers and autoinflammatory disorders (all ages) (PDF). p. 18. Retrieved 11 July 2018. de Koning HD, Bodar EJ, van der Meer JW, Simon A (December 2007). [en.wikipedia.org]

  It is characterized by the presentation of a monoclonal band, especially IgM, as well as fever, asthenia and arthralgia. [ncbi.nlm.nih.gov]

• Weight Loss

  We describe here a 48-year-old woman with a monoclonal IgM gammopathy and a 3-year history of chronic pruritic urticarial dermatosis, unexplained fevers, chronic polyarthritis, lymphadenopathy, leukocytosis, hepatomegaly, and weight loss. [jhu.pure.elsevier.com]

  Night sweats, weight loss, hepatomegaly, and splenomegaly are less commonly encountered. Lymphadenopathy is also an important sign, being present in more than 40% of cases. [symptoma.com]

  loss Angioedema: Very rare The urticarial rash is characterized as follows: Pale-rose, slightly elevated papules and plaques Individual lesions are 0.5-3 cm in diameter New lesions appear daily Lesions last 12-24 hours and then disappear without sequelae [emedicine.com]

• Pharyngeal Edema

  We present the case of a 48-year-old man with 5 years of recurrent urticarial lesions, slight itching, as well as lip, face and occasional pharyngeal edema. The patient had also suffered from fever and right hip and left knee arthralgia. [ncbi.nlm.nih.gov]

• Eye Pain

  Pain. 61 Sadig RR...Fraser CL 30794479 2019 18 Neutrophilic urticarial dermatosis: A review. 61 Gusdorf L...Lipsker D 30224079 2018 19 [Diagnosis and treatment of Schnitzler syndrome]. 61 Zhang XR...Fang MY 30612413 2018 20 [Schnitzler syndrome]. 61 [malacards.org]

  Fraser, The First Case Report of Schnitzler Syndrome Presenting with Eye Pain, Ocular Immunology and Inflammation, 10.1080/09273948.2018.1563704, (1-3), (2019). F. F. Gellrich and C. [doi.org]

• Bone Pain

  Often, the areas of hyperostosis coincide with areas of symptomatic bone pain, such as the iliac bone, tibia, femur, and vertebral column. See Workup for more detail. [emedicine.com]

  Schnitzler syndrome encompasses monoclonal gammopathy, urticaria, inflammation, recurrent fever, bone pain and arthralgia, with occasional lymphadenopathy and/or hepatosplenomegaly. [ncbi.nlm.nih.gov]

  Main observations: A 43-year-old woman presented to an allergy and immunology clinic with a 7 year history of chronic urticaria, angioedema with anaphylaxis, monoclonal gammopathy and bone pain. [doi.org]

  Schnitzler syndrome or Schnitzler's syndrome is a rare disease characterised by onset around middle age of chronic hives (urticaria) and periodic fever, bone pain and joint pain (sometimes with joint inflammation ), weight loss, malaise, fatigue, swollen [en.wikipedia.org]

  Schnitzler syndrome - tense, generalized chronic urticaria, joint or bone pain, and monoclonal gammopathy of kappa type. [medical-dictionary.thefreedictionary.com]

• Arthralgia

  Schnitzler syndrome is an autoinflammatory disease characterized by chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a monoclonal gammopathy, most often of the immunoglobulin M (IgM) subtype. [emedicine.com]

  It is characterized by the presentation of a monoclonal band, especially IgM, as well as fever, asthenia and arthralgia. [ncbi.nlm.nih.gov]

  Schnitzler syndrome with cold-induced urticaria Abstract Background: Schnitzler syndrome encompasses monoclonal gammopathy, urticaria, inflammation, recurrent fever, bone pain and arthralgia, with occasional lymphadenopathy and/or hepatosplenomegaly. [doi.org]

  Presenting signs and symptoms are an urticarial rash, intermittent fevers, myalgia, arthralgia, bone pain, lymphadenopathy, and peripheral neuropathy. [symptoma.com]

• Episodic Arthralgia

  BACKGROUND: Schnitzler syndrome (SchS) is a rare disease with suspected autoinflammatory background that shares several clinical symptoms, including urticarial rash, fever episodes, arthralgia, and bone and muscle pain with cryopyrin-associated periodic [ncbi.nlm.nih.gov]

• Urticaria

  From Wikidata Jump to navigation Jump to search Human disease Schnitzler syndrome (disorder) Chronic urticaria with macroglobulinemia Chronic urticaria with gammopathy Chronic urticaria with gammapathy edit English Schnitzler syndrome Human disease Schnitzler [wikidata.org]

  Her urticaria was triggered by cooler temperatures and an ice cube test for cold induced urticaria was positive. In spite of aggressive therapies this patient remains symptomatic. [doi.org]

• Night Sweats

  Night sweats, weight loss, hepatomegaly, and splenomegaly are less commonly encountered. Lymphadenopathy is also an important sign, being present in more than 40% of cases. [symptoma.com]

  A 63-year-old man reported having night sweats and fatigue but had no arthralgia or arthritis. [mdedge.com]

  The fever may be accompanied by chills and night sweating. Organomegaly Organomegaly refers to enlarged internal organs, i.e., large lymph nodes (lymphadenopathy) in 40% of patients, and enlarged liver and spleen (hepatosplenomagaly) in 30%. [dermnetnz.org]

• Red Skin Lesion

  Patients describe red skin lesions covering the trunk and extremities, sparing head, neck, palms and soles. Individual lesions persist less than 24 to 48 h. [doi.org]

• Pierre Robin Syndrome

  Robin syndrome ピエール　ロバン症候群 Pirquet ピルケー Pirquet reaction ピルケー反応 Plummer プラマー Plummer's disease プラマー病 HenryStanley Plummer （1874-1937） American internist and endocrinologist Plummer-Vinson プラマー・ヴィンソン Plummer-Vinson syndrome プラマー・ヴィンソン症候群 HenryStanley [jams.med.or.jp]

• Polyradiculoneuropathy

  POEMS syndrome is characterized by polyradiculoneuropathy, a clonal plasma cell disorder, sclerotic bone lesions, elevated VEGF, the presence of Castleman’s disease, and a few minor criteria. [doi.org]

A high index of suspicion is necessary in order to make the diagnosis of Schnitzler syndrome [1]. 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) [1] [4]. 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 [1] [2] [4] [6]. Skin biopsy and subsequent histopathological examination is an equally important diagnostic tool, showing a neutrophilic infiltrate in a significant portion of tested patients [7]. Bone marrow biopsy could be recommended in some cases.

• C-Reactive Protein Increased

  One might consider an approach analogous with temporal arteritis where either sedimentation rate or C-reactive protein increases can be used to assess systemic inflammation in diagnosing the disorder (6). [ispub.com]

• Fibrinoid Necrosis

  Urticarial vasculitis can also mimic Schnitzler syndrome; however, with urticarial vasculitis, skin biopsy should reveal features of true vasculitis with fibrinoid necrosis of small vessel walls, which should not be present in Schnitzler syndrome. [hindawi.com]

  For example, the picture published by Tanneberger et al and interpreted as vasculitis lack the typical features of the latter, as there is no fibrinoid necrosis of vessel wall [ 13 ]. [ncbi.nlm.nih.gov]

  Urticarial vasculitis should be excluded; even though vasculitis was reported in 20% of SchS cases, true fibrinoid necrosis of the vessel walls was absent in 5 re-examined cases, as indicated before. [doi.org]

  For example, the picture published by Tanneberger et al and interpreted as vasculitis lack the typical features of the latter, as there is no fibrinoid necrosis of vessel wall [13]. [ojrd.biomedcentral.com]

  However, fibrinoid necrosis, the hallmark of fully developed leukocytoclastic vasculitis, was not seen. Immunofluorescence studies were negative. [journals.lww.com]

1. Jain T, Offord CP, Kyle RA, Dingli D. Schnitzler syndrome: an under-diagnosed clinical entity. Haematologica. 2013;98(10):1581-1585.
2. De Koning HD. Schnitzler’s syndrome: lessons from 281 cases. Clin Transl Allergy. 2014;4:41.
3. Lipsker D. The Schnitzler syndrome. Orphanet J Rare Dis. 2010;5:38.
4. Simon A, Asli B, Braun-Falco M, et al. Schnitzler's syndrome: diagnosis, treatment, and follow-up. Allergy. 2013;68(5):562-568.
5. Gouveia AI, Micaelo M, Pierdomenico F, Freitas JP. Schnitzler Syndrome: A Dramatic Response to Anakinra. Dermatol Ther (Heidelb). 2016;6(2):299-302.
6. Kurian A, Lee JK, Vadas P. Schnitzler syndrome with cold-induced urticaria. J Dermatol Case Rep. 2010;4(4):50-53.
7. Sokumbi O, Drage LA, Peters MS. Clinical and histopathologic review of Schnitzler syndrome: the Mayo Clinic experience (1972-2011). J Am Acad Dermatol. 2012;67(6):1289-1295.