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Schnitzler Syndrome

Chronic Urticaria with Gammopathy

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.


Presentation

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]
  • Fever, arthralgia, and bone pain often respond to nonsteroidal antiinflammatory drugs.[ncbi.nlm.nih.gov]
  • 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]
  • 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]
  • 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]
  • Patients suffer from felling ill, and fatigues, and can experience weight loss. Around 45% of patients may have enlarged lymph nodes, enlarged liver and/or spleen.[autoinflammatory.org]
High Fever
  • We controlled the urticarial rash and high fever only with higher doses of prednisone (0.5 mg per kg or more).[archivesofrheumatology.org]
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
  • 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]
  • Fever, arthralgia, and bone pain often respond to nonsteroidal antiinflammatory drugs.[ncbi.nlm.nih.gov]
  • 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]
Arthralgia
  • 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 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]
  • 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]
  • Schnitzler's syndrome is an autoinflammatory disorder characterized by the association of a monoclonal IgM (or IgG) gammopathy, a chronic urticarial rash, and signs and symptoms of systemic inflammation, including fever, arthralgias and bone pain.[ncbi.nlm.nih.gov]
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
  • 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]
  • Patients typically carry a diagnosis of urticaria; however, their cutaneous symptoms fail to respond to typical urticaria therapies and lack symptoms such as pruritus.[ncbi.nlm.nih.gov]
  • We described two cases of chronic non itching urticaria with the same symptoms above mentioned, but an IgG monoclonal paraprotein instead of IgM gammopathy.[ncbi.nlm.nih.gov]
  • 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]
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]
Meningism
  • […] musculoskeletal manifestations (arthritis and transient arthralgia affecting the hands, elbows, knees, ankles, and feet), ocular inflammation (episcleritis, uveitis and conjunctivitis) and, more rarely, neurological findings (pseudotumor cerebri, aseptic meningitis[orpha.net]
  • CAPS constitutes a spectrum from cold-induced urticaria to severe neonatal-onset disease with meningitis and debilitating arthritis.[doi.org]
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]

Workup

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.

Treatment

  • These effects, which were accompanied by reductions in CRP and SAA, continued over the treatment duration. Rilonacept treatment was well tolerated.[ncbi.nlm.nih.gov]
  • The exact pathogenesis is still unclear and treatment remains a challenge.[ncbi.nlm.nih.gov]
  • This treatment controls the condition but does not cure it.[en.wikipedia.org]
  • There are new, effective treatment options, but close monitoring remains warranted because of the increased risk of lymphoproliferative disease.[ncbi.nlm.nih.gov]
  • Treatment is symptomatic and unsatisfactory. The skin rash is unresponsive to treatment, and nonsteroidal antiinflammatory drugs, antihistamines, dapsone, colchicine, and psoralens and ultraviolet A (PUVA) therapy give inconstant results.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis The overall prognosis depends on the development of lymphoproliferative complications such as lymphoma, IgM myeloma or Waldenström's disease (see these terms).[orpha.net]
  • Our objectives are to systematically review disease characteristics of Schnitzler syndrome and collect follow-up information to gain insight into treatment efficacy and long-term prognosis.[ncbi.nlm.nih.gov]
  • : Schnitzler syndrome has a favourable prognosis in term of mortality with a survival rate of 94% after 15 years.[flipper.diff.org]
  • Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. [Review] Seminars in Arthritis and Rheumatism. 37(3):137-48, 2007 Dec. Almerigogna F. Giudizi MG. Cappelli F. Romagnani S.[dermnetnz.org]
  • "Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment". Seminars in Arthritis and Rheumatism. 37 (3): 137–48. doi : 10.1016/j.semarthrit.2007.04.001.[en.wikipedia.org]

Etiology

  • Our case may contribute to a better understanding of the etiology of Schnitzler syndrome as his history could suggest a hereditarypredisposition for the disease.[ncbi.nlm.nih.gov]
  • The etiology of Schnitzler syndrome is unclear, but the rapid response to the interleukin-1 receptor inhibitor anakinra underlines the pivotal role which the proinflammatory cytokine interleukin-1 may play in the pathophysiology of this potentially autoinflammatory[ncbi.nlm.nih.gov]
  • Etiology Etiology remains unclear but the syndrome is probably an acquired auto-inflammatory disorder. It shares many features with genetically determined auto-inflammatory diseases.[orpha.net]
  • Although the etiology of the syndrome is unknown, current evidence suggests this is an autoinflammatory syndrome. Recognition of this syndrome is critical since it is highly responsive to anakinra.[dovepress.com]
  • Rheumatology, Dubrava University Hospital, Zagreb, Croatia Keywords: Anakinra, canakinumab, colchicine, glucocorticoids, Schnitzler’s syndrome Abstract Schnitzler’s syndrome is a rare autoinflammatory syndrome with unidentified mechanism of disease and etiology[archivesofrheumatology.org]

Epidemiology

  • Summary Epidemiology Prevalence is unknown and about 150 cases have been reported, primarily in Europe. Clinical description There is a slight male predominance and mean age of disease onset is 51 years. Time to diagnosis often exceeds 5 years.[orpha.net]
  • AA amyloidosis has also been reported in people with Schnitzler syndrome. [1] The life span in patients with Schnitzler syndrome has not been shown to differ much from the general population. [6] Epidemiology [ edit ] It is a rare condition; as of September[en.wikipedia.org]
  • Continue Related Articles Skin Cancer Epidemiology and Sun Protection Behaviors Among Native American....[jddonline.com]
Sex distribution
Age distribution

Pathophysiology

  • It is not yet firmly established whether the monoclonal immunoglobulin component plays a part in the pathophysiology of the urticarial lesions.[ncbi.nlm.nih.gov]
  • The etiology of Schnitzler syndrome is unclear, but the rapid response to the interleukin-1 receptor inhibitor anakinra underlines the pivotal role which the proinflammatory cytokine interleukin-1 may play in the pathophysiology of this potentially autoinflammatory[ncbi.nlm.nih.gov]
  • Recent reports of remissions induced by IL-1 receptor antagonist therapy shed new light on the pathophysiology of the disease.[ncbi.nlm.nih.gov]
  • The pathophysiology is still unknown, although various autoantibody-mediated mechanisms have been described.[ncbi.nlm.nih.gov]
  • , 2012 PATHOGENESIS The pathophysiology of Schnitzler syndrome is largely unclear.[flipper.diff.org]

Prevention

  • It investigates links to lifestyle and presents research on how the suppression of proinflammatory pathways may provide opportunities for both prevention and treatment of chronic diseases.[books.google.com]
  • Screening and prevention of colorectal cancer Source: Finnish Medical Society Duodecim This article is freely available only to users in the UK.[evidence.nhs.uk]
  • […] treat periodic fevers and autoinflammatory disorders (all ages) which stated that "Anakinra may be used as a first line treatment in patients with a documented diagnosis of Schnitzler syndrome". [5] Outcomes [ edit ] Generally treatment with anakinra prevents[en.wikipedia.org]

References

Article

  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.

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Last updated: 2019-06-28 11:26