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

  arthralgias, lymphadenopathy, and elevated ESR.Patient 2 met both major criteria and minor criteria of leukocytosis, fever, as well as elevated ESR/CRP.Along with fever and potential lymphadenopathy, clinical keys in patients with chronic urticaria [jddonline.com]

  We present a 56 year-old woman with respiratory allergy and pressure urticaria that started to develop episodes of urticarial rashes and fever together with diffuse arthralgias. [austinpublishinggroup.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]

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

• Lymphadenopathy

  […] fevers, arthralgias, lymphadenopathy, and elevated ESR.Patient 2 met both major criteria and minor criteria of leukocytosis, fever, as well as elevated ESR/CRP.Along with fever and potential lymphadenopathy, clinical keys in patients with chronic urticaria [jddonline.com]

  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]

  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]

  Schnitzler syndrome describes the simultaneous occurrence of monoclonal gammopathy and chronic urticaria with at least two additional minor symptoms (arthralgia, bone pain, fever of uncertain origin, hepato- or splenomegaly, lymphadenopathy, increased [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]

  Herein, we describe a case of a patient with a 2-year history of urticarial rash who then developed fevers, arthralgias, neutrophilia, and weight loss. [mdedge.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]

  loss People affected by Schnitzler syndrome also have an increased risk of developing certain lymphoproliferative disorders. [autoinflammatory.uk]

  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]

• Hodgkin Lymphoma

  Clin Lymphoma Myeloma Leuk 17S:S53-S61, 2017 Crossref, Medline, Google Scholar 5. [ascopubs.org]

  Non-Hodgkin's lymphoma. POEMS syndrome ( p olyneuropathy, o rganomegaly, e ndocrinopathy, M -protein, s kin changes). [patient.info]

  Multiple myeloma (MM) is the second most commonly diagnosed blood cancer, after non-Hodgkin lymphoma, yet few people know much about this deadly disease. Celgene. [sclero.org]

  The causes of death in the second cohort were: non-Hodgkin’s lymphoma in 2 patients, acute myeloid leukemia in one, other cancer in 2 patients, sepsis in one patient, and a cerebrovascular accident in one patient. [haematologica.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]

  Case Description A 69-year-old female experienced monthly episodes of facial swelling and a non-pruritic, erythematous rash with high fevers, nausea, headache and neck pain over 1 year. [annallergy.org]

  High fever might be there accompanied by chills and night sweating. This can give rise to further uneasiness and is usually caused when the immune system is attacked by the ailment. [lybrate.com]

  Anakinra was not interrupted because as soon as the patient stopped taking anakinra, symptoms of Schnitzler syndrome (high fever, rash, bone pain) recurred within 48 h. [jrheum.org]

• Aspiration

  An evaluation for malignancy using systemic computed tomography scan and fluorodeoxyglucose positron emission tomography revealed the retroperitoneal tumor, and a subsequent bone-marrow aspirate confirmed the diagnosis of B-cell lymphoma. [ncbi.nlm.nih.gov]

  Given the different hematological findings, a new bone marrow aspirate was performed with a negative cytogenetic study for lymphoproliferative diseases. [reumatologiaclinica.org]

  Bone marrow aspiration and trephine biopsy. Management Management will depend on the underlying cause. Prognosis This will depend on the underlying cause. Prognosis is often poor. [patient.info]

  The skin biopsy demonstrated a lymphocytic infiltrate compatible with urticaria, without evidence of vasculitis; bone marrow aspirate and biopsy were nonspecific, ruling out lymphoproliferative disease (<5% plasmocytes). [revistanefrologia.com]

• Hepatomegaly

  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]

  Hepatomegaly, splenomegaly or hepatosplenomegaly is common. [13] Lymphatic: 45% with lymphadenopathy. Splenomegaly. [13] Joints bones muscles cartilage: 80% have muscle, bone and/or joint pain, or arthritis. [autoinflammatory-search.org]

  […] after 3-4 years Recurrent fevers: 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 [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]

  These criteria include the presence of an urticarial skin rash and a monoclonal IgM component and at least two of the following signs or symptoms: fever, joint pain or arthritis, bone pain, palpable lymph nodes, spleen, hepatomegaly, accelerated ESR and [reumatologiaclinica.org]

• Hepatosplenomegaly

  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]

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

  Physical examination revealed an elevated temperature (38.4°C) and generalized urticaria but no evidence of hepatosplenomegaly, adenopathy, or arthritis. [mdedge.com]

  Hepatomegaly, splenomegaly or hepatosplenomegaly is common. [13] Lymphatic: 45% with lymphadenopathy. Splenomegaly. [13] Joints bones muscles cartilage: 80% have muscle, bone and/or joint pain, or arthritis. [autoinflammatory-search.org]

• Urticaria

  Patients typically carry a diagnosis of urticaria; however, their cutaneous symptoms fail to respond to typical urticaria therapies and lack symptoms such as pruritus. [jddonline.com]

  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]

  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]

  She was diagnosed of physical urticaria and successfully treated with oral antihistamines (OA). [austinpublishinggroup.com]

• Skin Lesion

  Following a strict elimination diet resulted in marked improvement in skin lesions in both patients. In one of our patients we observed a decrease in IgE and IgM levels after a 3 week diet. [ncbi.nlm.nih.gov]

  No skin lesions have appeared and corticosteroid therapy has been tapered off slowly. Patient 3 A 52‐year‐old woman observed urticarial skin lesions since abut 1 1/2 year, often together with fever bouts and reduced general well‐being. [onlinelibrary.wiley.com]

  The skin lesion was biopsied. [reumatologiaclinica.org]

  Anakinra 100 mg daily in all three patients led to disappearance of fever and skin lesions within 24 hours. After a follow up of 6–18 months, all patients are free of symptoms. [ard.bmj.com]

  After approximately 2 months of ibrutinib use, the patient noted a moderation of skin involvement, with the slow resolution of existing lesions and fewer new onset lesions. [ascopubs.org]

• Papule

  Authoritative facts about the skin from DermNet New Zealand Trust.Pearly Penile Papules Photos Click thumbnail to enlarge. Previous 1 2 Next. Pearly Penile Papules. pearly-penile-papules-1.jpg. [wimozatebyv.xpg.uol.com.br]

  […] pain: Concurrent with fever; reported in 70% of patients Myalgias: Concurrent with fever Lymphadenopathy Hepatomegaly Splenomegaly Fatigue Weight loss Angioedema: Very rare The urticarial rash is characterized as follows: Pale-rose, slightly elevated papules [emedicine.com]

  Grzybowski syndrome, or generalized eruptive keratoacanthoma, refers to a very rare disease in which hundreds of keratoacanthoma-like papules appear. [sclero.org]

  Recurrences are the norm within 48 to 72 hours after the discontinuation of anti–IL-1 treatment.1 Section: Case Report An 86-year-old man presented with minimally persistent urticarial papules and plaques for several years (Fig 1A). [ascopubs.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]

  Additionally, patients with SS may see multiple providers for nonspecific complaints of fever, lymphadenopathy, arthralgias, and bone pain. [jddonline.com]

  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]

  —54-year-old man with 3-year history of inflammatory bone pain localized in left thigh and both legs. [ajronline.org]

• Arthralgia

  Additionally, patients with SS may see multiple providers for nonspecific complaints of fever, lymphadenopathy, arthralgias, and bone pain. [jddonline.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 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]

• Back Pain

  Three months before our evaluation he developed back pain radiating to the left lower extremity, non-continuous but intense that prevented walking. [reumatologiaclinica.org]

  Often nonspecific presentation with fever, malaise, and bone pain. Clinical indications for screening for M-protein: [ 1 ] Malaise and fatigue. Bone disease (persistent back pain, osteopenia or lytic lesions). Impaired renal function. [patient.info]

• Neck Pain

  Case Description A 69-year-old female experienced monthly episodes of facial swelling and a non-pruritic, erythematous rash with high fevers, nausea, headache and neck pain over 1 year. [annallergy.org]

• Suggestibility

  These findings suggest that the monoclonal gammopathy plays a part in the pathophysiology of the skin rash. They also suggest patient heterogeneity both in the skin antigens that are recognized as well as in their localization. [ncbi.nlm.nih.gov]

• Facial Swelling

  Case Description A 69-year-old female experienced monthly episodes of facial swelling and a non-pruritic, erythematous rash with high fevers, nausea, headache and neck pain over 1 year. [annallergy.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.

• Erythrocyte Sedimentation Rate Increased

  erythrocyte sedimentation rate, increased levels of C-reactive protein, or increased amount of white blood cells) marked changes in the bone structure (e.g. on X-ray or scan) skin biopsy shows neutrophilic granulocytes (type of white blood cells) in [bjh.be]

• 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]

• Lymphocytic Infiltrate

  One of the findings that did not support the diagnosis was the lymphocytic infiltrate on the skin biopsy, instead of a neutrophilic one. [revistanefrologia.com]

  Skin biopsy showed mild perivascular and interstitial neutrophilic infiltrates in the dermis without vasculitis (Fig 1b), indicative of urticarial neutrophilic dermatosis. [rcpjournals.org]

  Histologic examination showed a superficial perivascular lymphocytic infiltration, interstitial dispersion and some neutrophils along collagen bundles.1 A cervical, thorax and abdomen computed tomography was performed, which showed no significant findings [reumatologiaclinica.org]

  Infiltration of the Skin Kimura Disease Lymphomatoid Papulosis Pityriasis Lichenoides Malignant Neoplasms Actinic Keratosis Arsenical Keratosis Basal Cell Carcinoma Bowen Disease Cutaneous Melanoma Dermatofibrosarcoma Protuberans Dermatologic Manifestations [dokterairlangga.com]

However, patients with other diseases can develop rashes that resemble CIU and are thus prone to misdiagnosis and treatment delay. [austinpublishinggroup.com]

Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections. [scienceopen.com]

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 cause and treatment are still unknown. Objective: To assess treatment with thalidomide and an interleukin 1 receptor antagonist, anakinra, in Schnitzler’s syndrome. [ard.bmj.com]

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]

Schintzler's syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum, 37 (2007), pp. 137-148 Please cite this article as: Gallo J, Paira S. Síndrome de Schnitzler. [reumatologiaclinica.org]

Prognosis The life span in patients with Schnitzler syndrome has not been shown to differ much from the general population.[1] Careful follow-up is advised, however. [dictionnaire.sensagent.leparisien.fr]

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: 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]

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]

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]

While only rarely reported, the neurologic findings, as described in this series, are helpful in evaluating for a systemic inflammatory etiology of recurrent urticaria.2;5-8 Histopathology in most cases demonstrates perivascular and interstitial neutrophilic [jddonline.com]

She had not identified any etiological or pathogenic agents. There were no relevant findings on examination and she presented a good general state of health. Dermographism was negative. [actasdermo.org]

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]

Continue Related Articles Skin Cancer Epidemiology and Sun Protection Behaviors Among Native American.... [jddonline.com]

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]

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]

Pathophysiology The pathophysiology of Schnitzler syndrome is largely unclear. [onlinelibrary.wiley.com]

Three months before our evaluation he developed back pain radiating to the left lower extremity, non-continuous but intense that prevented walking. [reumatologiaclinica.org]

Medical condition: Treatment and prevention of gout flares in patients with frequent flares and for whom NSAIDs and/or colchicine are contraindicated, not tolerated or ineffective Disease: Version SOC Term Classification Code Term Level 12.0 10018627 [clinicaltrialsregister.eu]

The mannitol reduces vitreous volume and could prevent iris strangulation. YAG laser iridotomy performed one day prior to PKP was shown to prevent UZS. Intraoperative Some steps are needed to be taken during surgery to prevent the occurrence of UZS. [eyewiki.aao.org]

We hope that early treatment may prevent development of complications of CAPS such as deafness and eye damage. [ucl.ac.uk]

When given at the start of an attack, the effect is dramatic, as the attack is usually completely prevented. There is some evidence that tonsillectomy can cure this syndrome, especially in children with persistently enlarged tonsils. [amyloidosis.org.uk]

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.