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Schnitzler Syndrome: a Review

  • Orphan Diseases (B Manger, Section Editor)
  • Published:
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Abstract

Purpose of Review

We focus on recent advances in diagnosis and therapeutic strategies, as well as on pathogenesis of Schnitzler syndrome.

Recent Findings

New diagnostic criteria were established, and their external validity was assessed in a retrospective cohort study. The cytokine interleukin-1 (IL-1) plays a crucial role in the pathogenesis of the Schnitzler syndrome, and this explains the spectacular efficiency of IL-1 blocking therapies.

Summary

The Schnitzler syndrome is now considered as a late-onset acquired autoinflammatory syndrome in which the cytokine IL-1 plays a crucial role. IL-1 blocking therapies are efficient on the inflammation-linked symptoms but not on the monoclonal component. Therefore, they probably don’t reduce the risk of the development of lymphoproliferative disorders that remains the main prognostic issue. The link between autoinflammation and the monoclonal component needs to be further elucidated.

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References

Recently published papers of particular interest have been highlighted as: • Of importance •• Of major importance

  1. Schnitzler L. Lésions urticariennes chroniques permanentes (érythème pétaloïde?). Journées Dermatologiques d’Angers. 1972; Cas Clinique. N°46b.

  2. •• Lipsker D. Monoclonal gammopathy of cutaneous significance: review of a relevant concept. J Eur Acad Dermatol Venereol. 2017;31:45–52. This article introduces the concept of monoclonal gammopathy of cutaneous significance and reviews the main entities that fit into it.

    Article  CAS  PubMed  Google Scholar 

  3. De Koning HD, van Gijn ME, Stoffels M, Jongekrijg J, Zeeuwen PLJM, Elferink MG, et al. Myeloid lineage-restricted somatic mosaicism of NLRP3 mutations in patients with variant Schnitzler syndrome. J Allergy Clin Immunol. 2015;135:561–4.

    Article  PubMed  Google Scholar 

  4. Ryan JG, de Koning HD, Beck LA, Booty MG, Kastner DL, Simon A. IL-1 blockade in Schnitzler syndrome: ex vivo findings correlate with clinical remission. J Allergy Clin Immunol. 2008;121:260–2.

    Article  CAS  PubMed  Google Scholar 

  5. De Koning HD, Schalkwijk J, Stoffels M, Jongekrijg J, Jacobs JFM, Verwiel E, et al. The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome. Arthritis Res Ther. 2015;17:187.

    Article  PubMed  PubMed Central  Google Scholar 

  6. De Koning HD, van Vlijmen-Willems IMJJ, Rodijk-Olthuis D, van der Meer JWM, Zeeuwen PLJM, Simon A, et al. Mast-cell interleukin-1beta, neutrophil interleukin-17 and epidermal antimicrobial proteins in the neutrophilic urticarial dermatosis in Schnitzler’s syndrome. Br J Dermatol. 2015;173:448–56.

    Article  PubMed  Google Scholar 

  7. Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M, et al. Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by. Nature. 2012;484:514–8.

    Article  CAS  PubMed  Google Scholar 

  8. Noster R, de Koning HD, Maier E, Prelog M, Lainka E, Zielinski CE. Dysregulation of proinflammatory versus anti-inflammatory human TH17 cell functionalities in the autoinflammatory Schnitzler syndrome. J Allergy Clin Immunol. 2016;138:1161–9.

    Article  CAS  PubMed  Google Scholar 

  9. Mulla E, Neame R. Delayed development of the IgM paraprotein in Schnitzler’s syndrome. Scand J Rheumatol. 2015;44:521–2.

    Article  CAS  PubMed  Google Scholar 

  10. Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. MYD88 L265P somatic mutation in Waldenstrom’s macroglobulinemia. N Engl J Med. 2012;367:826–33.

    Article  CAS  PubMed  Google Scholar 

  11. • De Koning HD. Schnitzler’s syndrome: lessons from 281 cases. Clin Transl Allergy. 2014;4:41. This study summarizes the clinical, biological, histological, and morphological data of all the patients with a Schnitzler syndrome reported to date.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Akimoto R, Yoshida M, Matsuda R, Miyasaka K, Itoh M. Schnitzler’s syndrome with IgG kappa gammopathy. J Dermatol. 2002;29:735–8.

    Article  PubMed  Google Scholar 

  13. Welsh B, Tate B. Schnitzler’s syndrome: report of a case with progression to Waldenstrom’s macroglobulinaemia. Australas J Dermatol. 1999;40:201–3.

    Article  CAS  PubMed  Google Scholar 

  14. 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;80:37–44.

    Article  CAS  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. •• Gusdorf L, Asli B, Barbarot S, Neel A, Masseau A, Puechal X, et al. Schnitzler syndrome: validation and applicability of diagnostic criteria in real-life patients. Allergy. 2017;72:177–82. This study confirms the applicability and the validity of the existing diagnostic criteria in real-life patients.

    Article  CAS  PubMed  Google Scholar 

  17. Kieffer C, Cribier B, Lipsker D. Neutrophilic urticarial dermatosis: a variant of neutrophilic urticaria strongly associated with systemic disease. Report of 9 new cases and review of the literature. Medicine (Baltimore). 2009;88:23–31.

    Article  Google Scholar 

  18. Broekaert SMC, Boer-Auer A, Kerl K, Herrgott I, Schulz X, Bonsmann G, et al. Neutrophilic epitheliotropism is a histopathological clue to neutrophilic urticarial dermatosis. Am J Dermatopathol. 2016;38:39–49.

    Article  PubMed  Google Scholar 

  19. Gusdorf L, Bessis D, Lipsker D. Lupus erythematosus and neutrophilic urticarial dermatosis: a retrospective study of 7 patients. Medicine (Baltimore). 2014;93:e351.

    Article  CAS  Google Scholar 

  20. Lipsker D. The Schnitzler syndrome. Orphanet J Rare Dis. 2010;5:38.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sokumbi O, Drage LA, Peters MS. Clinical and histopathologic review of Schnitzler syndrome: the Mayo Clinic experience (1972-2011). J Am Acad Dermatol. 2012;67:1289–95.

    Article  PubMed  Google Scholar 

  22. Carlesimo M, Abruzzese C, Narcisi A, La Verde G, De Marco G, Verga E, et al. Chronic vasculitis urticaria associated to a monoclonal gammopathy of IgM and IgA type, a Schnitzler syndrome? Eur J Dermatol. 2010;20:838–9.

    PubMed  Google Scholar 

  23. Ricci M, Bettazzi LG, Varenna M, Marchesoni A. Atypical bone sclerosis. Arthritis Rheumatol Hoboken NJ. 2016;68:816.

    Article  CAS  Google Scholar 

  24. Niederhauser BD, Dingli D, Kyle RA, Ringler MD. Imaging findings in 22 cases of Schnitzler syndrome: characteristic para-articular osteosclerosis, and the “hot knees” sign differential diagnosis. Skelet Radiol. 2014;43:905–15.

    Article  Google Scholar 

  25. Willekens I, Walgraeve N, Goethals L, De Geeter F. Correlative bone imaging in a case of Schnitzler’s syndrome and brief review of the literature. Hell J Nucl Med. 2015;18:71–3.

    PubMed  Google Scholar 

  26. Ferrando FJ, Pujol J, Hortells JL, Navarro M, Pinol J, Carapeto FJ. Schnitzler’s syndrome: report of a case with bone osteolysis. J Investig Allergol Clin Immunol. 1994;4:203–5.

    CAS  PubMed  Google Scholar 

  27. Terpos E, Asli B, Christoulas D, Brouet J-C, Kastritis E, Rybojad M, et al. Increased angiogenesis and enhanced bone formation in patients with IgM monoclonal gammopathy and urticarial skin rash: new insight into the biology of Schnitzler syndrome. Haematologica. 2012;97:1699–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Martinez-Taboada VM, Fontalba A, Blanco R, Fernandez-Luna JL. Successful treatment of refractory Schnitzler syndrome with anakinra: comment on the article by Hawkins et al. Arthritis Rheum. 2005;52:2226–7.

    Article  PubMed  Google Scholar 

  29. Lipsker D, Lenormand C. Management of Schnitzler’s syndrome. Expert Opin Orphan Drugs. 2014;2:947–55.

    Article  CAS  Google Scholar 

  30. Neel A, Henry B, Barbarot S, Masseau A, Perrin F, Bernier C, et al. Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler’s syndrome: a French multicenter study. Autoimmun Rev. 2014;13:1035–41.

    Article  CAS  PubMed  Google Scholar 

  31. Perrin F, Neel A, Graveleau J, Ruellan A-L, Masseau A, Hamidou M. Two cases of anakinra-induced neutropenia during auto-inflammatory diseases: drug reintroduction can be successful. Presse Med. 2014;43:319–21.

    Article  PubMed  Google Scholar 

  32. De Koning HD, Schalkwijk J, van der Ven-Jongekrijg J, Stoffels M, van der Meer JWM, Simon A. Sustained efficacy of the monoclonal anti-interleukin-1 beta antibody canakinumab in a 9-month trial in Schnitzler’s syndrome. Ann Rheum Dis. 2013;72:1634–8.

    Article  PubMed  Google Scholar 

  33. Vanderschueren S, Knockaert D. Canakinumab in Schnitzler syndrome. Semin Arthritis Rheum. 2013;42:413–6.

    Article  CAS  PubMed  Google Scholar 

  34. Pesek R, Fox R. Successful treatment of Schnitzler syndrome with canakinumab. Cutis. 2014;94:E11–2.

    PubMed  Google Scholar 

  35. Krause K, Tsianakas A, Wagner N, Fischer J, Weller K, Metz M, et al. Efficacy and safety of canakinumab in Schnitzler syndrome: a multicenter randomized placebo-controlled study. J Allergy Clin Immunol. 2017;139:1311–20.

    Article  CAS  PubMed  Google Scholar 

  36. Krause K, Weller K, Stefaniak R, Wittkowski H, Altrichter S, Siebenhaar F, et al. Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study. Allergy. 2012;67:943–50.

    Article  CAS  PubMed  Google Scholar 

  37. Krause K, Feist E, Fiene M, Kallinich T, Maurer M. Complete remission in 3 of 3 anti-IL-6-treated patients with Schnitzler syndrome. J Allergy Clin Immunol. 2012;129:848–50.

    Article  PubMed  Google Scholar 

  38. Asli B, Brouet JC, Fermand JP. Spontaneous remission of Schnitzler syndrome. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2011;107:87–8.

    Article  Google Scholar 

  39. Conlon NP, Hayden P, Barnes L, Doran M, O’Shea F, Feighery C. Schnitzler’s syndrome: a case highlighting the complications of long-standing acquired autoinflammation. Eur J Dermatol. 2014;24:405–6.

    PubMed  Google Scholar 

  40. Gameiro A, Gouveia M, Pereira M, Tellechea O, Goncalo M. Clinical characterization and long-term follow-up of Schnitzler syndrome. Clin Exp Dermatol. 2016;41:461–7.

    Article  CAS  PubMed  Google Scholar 

  41. Margerin F, Gottenberg JE, Lipsker D. Occurrence of rheumatoid arthritis in a patient treated with anakinra for Schnitzler syndrome: a case report. J Rheumatol. 2016;43:1447.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Faculté de Médecine, Université de Strasbourg et Clinique Dermatologique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    L. Gusdorf & D. Lipsker

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  1. L. Gusdorf
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  2. D. Lipsker
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Correspondence to D. Lipsker.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Gusdorf, L., Lipsker, D. Schnitzler Syndrome: a Review. Curr Rheumatol Rep 19, 46 (2017). https://doi.org/10.1007/s11926-017-0673-5

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  • DOI: https://doi.org/10.1007/s11926-017-0673-5

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