AUTOINFLAMMATORY DISEASES IN HEMATOLOGY FROM DIAGNOSIS TO TREATMENT

AUTOINFLAMMATORY_DISEASES_IN_HEMATOLOGY_FROM_DIAGNOSIS_TO_TREATMENTkapak

SCHNITZLER’S SYNDROME (SCHS)

Fatma Aykaş

Antalya Training and Research Hospital, Department of Hematology, Antalya, Türkiye

Aykaş F. Schnitzler’s Syndrome (SchS). In: Kurt Yüksel M, editor. Autoinflammatory Diseases in Hematology from Diagnosis to Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.161-171.

ABSTRACT

Schnitzler’s syndrome (SchS), first described by Dr. Liliane Schnitzler in 1972, is an uncommon, late-onset, acquired autoinflammatory disease, which is descriptived by chronic urticarial rash and monoclonal gammopathy (particularly of the IgM type). It is a multisystemic disease with other common clinical findings including recurrent fever, arthralgia, bone pain, myalgia, and lymphadenopathy. The exact prevalence and incidence of SchS are not known. However, more than 300 cases have been reported since its initial description. Clinical symptoms and findings typically begin in individuals aged 50-55 years, with urticarial rash often being the first symptom. While the exact etiopathogenesis remains unclear, it is known to be an autoinflammatory disease characterized by recurrent inflammation mediated by interleukin-1 (IL-1). There is no specific test for diagnosis, and no diagnostic genetic mutation has yet been identified. Lipsker or Strasbourg criterias are used for diagnosis. Although the prognosis is generally good, there is a 15% risk of developing lymphoproliferative disease within 10 years. There is no curative treatment; however, IL-1 blocking drugs, particularly anakinra and canakinumab, have been shown to provide rapid, efficacious, and sustained responses. Unfortunately, many patients today remain undiagnosed, misdiagnosed, or diagnosed too late. As with many diseases, early diagnosis and treatment are crucial in terms of morbidity and mortality.

Keywords: Schnitzler’s syndrome; Chronic urticarial rash; Monoclonal gammopathy; Interleukin-1; Anakinra.

Referanslar

  1. Matsuda T, Takimoto-Ito R, Lipsker D, Kambe N. Similarities and differences in autoinflammatory diseases with urticarial rash, cryopyrin-associated periodic syndrome and Schnitzler syndrome. Allergology International. 2023;72(3): 385-393. [Crossref]  [PubMed]
  2. Gusdorf L and Lipsker D. Schnitzler Syndrome: a Review. Curr Rheumatol Rep. 2017;19(8):46. [Crossref]  [PubMed]
  3. Patel V, Balasubramaniam D, Cavero-Chavez V, Cuervo-Pardo L and Sanchez-Alvarez C. Clinical Presentation of Schnitzler's Syndrome: A Rare Autoimmune Disease. J Investig Med High Impact Case Rep. 2023;11:1-5. [Crossref]  [PubMed]  [PMC]
  4. Singh G, Goswami K, Trehan S, Kachhadia MP, Farooq A, Puri P, et al. Schnitzler-Like Syndrome Presenting With IgG Kappa Monoclonal Gammopathy: A Case Report and Review of Diagnostic and Therapeutic Challenges. Cureus. 2024;16(7):e64440. [Crossref]
  5. Braud A and Lipsker D. Schnitzler Syndrome: Insights into Its Pathogenesis, Clinical Manifestations, and Current Management. Biomolecules. 2024;14(6):646. [Crossref]
  6. Chu CQ. Schnitzler syndrome and Schnitzler-like syndromes. Chinese Medical Journal. 2022;135(10):1190-1202. [Crossref]  [PubMed]  [PMC]
  7. De Koning HD, Bodar EJ, van der Meer JWM, and Simon A, on behalf of the Schnitzler Syndrome Study Group et al. Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum. 2007;37(3):137-148. [Crossref]  [PubMed]
  8. Więsik-Szewczyk E, Felis-Giemza A, Dziuk M and JahnzRóżyk K. Schnitzler Syndrome in a 27-Year-Old Man: Diagnostic and Therapeutic Dilemma in Adult Auto-Inflammatory Syndromes A Case Report and Literature Review. International Journal of General Medicine. 2020;13:713719. [Crossref]  [PubMed]  [PMC]
  9. De Koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014;4:41. [Crossref]  [PubMed]  [PMC]
  10. Kacar M, Pathak S, and Savic S. Hereditary systemic autoinflammatory diseases and Schnitzler's syndrome. Rheumatology. 2019;58(6):31-43. [Crossref]  [PubMed]  [PMC]
  11. Henrie R, Cherniawsky H, Marcon K, Zhao EJ, Marinkovic A, Pourshahnazari P, et al. Inflammatory diseases in hematology: a review. AmJPhysiol Cell Physiol:2022; 323: C1121- C1136, 2022. [Crossref]  [PubMed]
  12. Digital Academy (Internet). ASH Clinical News | American Society of Hematology. ©June 2023 [Access date: 26 October 2024].
  13. Lipsker D. The Schnitzler syndrome. Lipsker Orphanet Jour nal of Rare Diseases. 2010;5:38.38. [Crossref]  [PubMed]
  14. Chu C.Q. Schnitzler syndrome -An underdiagnosed adultonset autoinflammatory disease. Int J Rheum Dis. 2024; 27: e14925. [Crossref]  [PubMed]
  15. Nandi K, Sarkar S, Bakshi P, Saha S, Sen DJ, Dholwani K, et al. The Schnitzler Syndrome: An Acquired Autoinflammatory Syndrome by monoclonal immunoglobulin. World Journal of Pharmaceutical Research. 2021;10(3):908-918.
  16. Alixa L, Neelb A, Cadora B, Smailc A, Serratriced J, Closs-Prophette F, et al. Diagnostic value of 18-F fluorodeoxyglucose PET/CT and bone scan in Schnitzler syndrome. Autoimmunity. 2019;52:264-271. [Crossref]  [PubMed]
  17. Barata R, Pereira T.A, Carvalho T, Kardoso F, Moraes-Fontes M.F, Fernandes A, et al. Revisiting Schnitzler syndrome: A rare severe form of acute kidney injury and monoclonal gammopathy. Nefrologia. 2023;43(S2):96-137. [Crossref]
  18. Kaganov E, Jhaveri D, Peters P, IJdo JW. An unusual presentation of immunoglobulin A gammopathy in a patient with Schnitzler's syndrome. Int J Rheum Dis. 2023;26(10): 2085-2088. [Crossref]  [PubMed]
  19. Ghali H, McClure EM. and Foster EL. A case of Schnitzler-like syndrome with basement membrane IgM deposition but without monoclonal gammopathy. JAAD Case Reports. 2024;47:10-3. [Crossref]  [PubMed]  [PMC]
  20. Puxkandl V, Currie A, Hoetzenecker W, and Altrichter S. Therapy resistant urticaria as a long-term symptom of an incomplete Schnitzler syndrome. Allergy, Asthma & Clinical Immunology. 2023; 19(1): 64. [Crossref]  [PMC]
  21. Regnault MM, Frouin E, Jeru I, Delwail A, Charreau S, Barbarot S, et al. Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression. Frontiers in Immunology. 2020; 11: 588322. [Crossref]  [PubMed]
  22. Louvrier C, Awad F, Amselem S, Lipsker D, Giurgea I. Absence of NLRP3 Somatic Mutations and VEXAS-Related UBA1 Mutations in a Large Cohort of Patients with Schnitzler Syndrome. Allergy 2022;77:3435-3436. [Crossref]  [PubMed]
  23. Rowczenio, DM, Pathak S, Arostegui JI, Mensa-Vilaro A, Omoyinmi E, Brogan P, et al. Molecular Genetic Investigation, Clinical Features, and Response to Treatment in 21 Patients with Schnitzler Syndrome. Blood. 2018;131:974-981. [Crossref]  [PubMed]
  24. Pathak S, Rowczenio DM, Owen RG, Doody GM, Newton DJ, Taylor C, et al. Exploratory study of MYD88 L265P, rare NLRP3 variants, and clonal hematopoiesis prevalence in patients with Schnitzler syndrome. Arthritis Rheumatol. 2019;71(12):2121-2125. [Crossref]  [PubMed]
  25. Lipsker D, Veran Y, Grunenberger F, Cribier B, Heid E, Grosshans E. The Schnitzler syndrome. Four new cases and review of the literature. Medicine (Baltimore). 2001;80: 37e44. [Crossref]
  26. Simon A, Asli B, Braun-Falco M, De Koning H, Fermand J-P, Grattan C, et al. Schnitzler's syndrome: diagnosis, treatment, and follow-up. Allergy. 2013;68:562-8. [Crossref]  [PubMed]
  27. Wesselmann AS, Künstner A, Fähnrich A, Rose C, Lamprecht P, Busch H, et al. Case report: Schnitzler -like syndrome without monoclonal gammopathy. Front. Immunol. 2023;14:1166620. [Crossref]  [PMC]
  28. Kieffer C, Cribier B, Lipsker D. Neutrophilic urticarial dermatosis: a variant of neutro philic urticaria strongly associated with systemic disease. Report of 9 new cases and review of the literature. Medicine (Balti more) 2009;88:23-31. [Crossref]  [PubMed]
  29. Mamadgia J, Babara L, Bhagavatula R, Sadashiva S, Danteya K, Apostolova M. Schnitzler's Syndrome: A Diagnostic Consideration in Evaluating the Constellation of Monoclonal Gammopathy and Chronic Urticaria. J Hematol. 2021;10(3):143-146. [Crossref]  [PubMed]  [PMC]
  30. De Macêdo Cruz K.C, de Abreu e Silva Martinez D, Quintella DC, Cuzzi T, Dortas Junior SD, Rodrigues Valle SO. Mimicking urticaria: a Schnitzler syndrome case. Anais Brasileiros de Dermatologia. 2023;99(6):967-969. [Crossref]  [PubMed]  [PMC]
  31. Salcedo-Mingoarranz AL, Dorado-Fernández M, GarcíaMartínez S, Collado-Ramos P & Silvestre-Torner N. Schnitzler syndrome refractory to anakinra: successful treatment with canakinumab. Journal of Dermatological treatment. 2023; 34(1): 2242705. [Crossref]  [PubMed]
  32. Martinez-Taboada VM, FontalbaA, Blanco R, Fernandez-Luna JL. Successful treatment of refractory Schnitzler syndrome with anakinra: comment on the article by Hawkins et al. Arthritis Rheum. 2005; 52(7): 2226-7. [Crossref]  [PubMed]
  33. Krause K, Bonnekoh H, Ellrich A, Tsianakas A, Wagner N, Fischer J, et al. Long-term efficacy of canakinumab in the treatment of Schnitzler syndrome. J Allergy Clin Immunol.2020;145(6): 1681-1686. [Crossref]  [PubMed]
  34. Claves F, Siest R, Lefebvre C, Valmary-Degano S, and Syl vain Carras. Dramatic Efficacy of Ibrutinib in a Schnitzler Syndrome Case with Indolent Lymphoma. Journal of Clinical Immunology. 2021;41:1380-1383. [Crossref]  [PubMed]
  35. Huang Y, Wang Y, Yu F, et al. Case report: therapeutic use of Ibrutinib in a patient with Schnitzler syndrome. Front Immunol. 2022;13:894464. [Crossref]  [PubMed]  [PMC]