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Schnitzler Syndrome

  • Heleen D. de Koning
  • Karoline Krause
Chapter

Abstract

Schnitzler syndrome (SchS) is a late-onset autoinflammatory disease characterized by the association of a chronic urticarial rash and monoclonal gammopathy with signs and symptoms of systemic inflammation. Clinical efficacy of IL-1ß blocking drugs revealed the key role of IL-1ß in the pathophysiology of SchS. This was corroborated by in vitro and genetic studies. Anti-IL-1ß treatment abrogates the systemic inflammation, but leaves the monoclonal gammopathy unaffected. The role of the monoclonal gammopathy (cause or consequence) is the major question that remains to be resolved.

Keywords

Schnitzler syndrome Autoinflammatory Urticaria Monoclonal gammopathy Interleukin-1 

Abbreviations

CAPS

Cryopyrin-associated periodic syndrome

CNO

Chronic non-bacterial osteomyelitis

CRP

C-reactive protein

CSU

Chronic spontaneous urticaria

ESR

Erythrocyte sedimentation rate

Ig

Immunoglobulin

IL-1

Interleukin-1

MGUS

Monoclonal gammopathy of unknown significance

MRP

Myeloid-related protein

NUD

Neutrophilic urticarial dermatosis

PBMCs

Peripheral blood mononuclear cells

SchS

Schnitzler syndrome

TLR

Toll-like receptor

References

  1. 1.
    Schnitzler L. Lésions urticariennes chroniques permanentes (erytheme pétaloide?) Journee Dermatologique d’Angers. 1972:Cas cliniques. No. 46B.Google Scholar
  2. 2.
    Schnitzler L, Hurez D, Verret JL. Chronic urticaria—osteo-condensation—macroglobulinemia. Principal case. Study of 20 cases. Ann Dermatol Venereol. 1989;116:547–50.PubMedGoogle Scholar
  3. 3.
    Pizzirani C, Falzoni S, Govoni M, et al. Dysfunctional inflammasome in Schnitzler’s syndrome. Rheumatology. 2009;48:1304–8.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 5.
    Simon A, Asli B, Braun-Falco M, et al. Schnitzler’s syndrome: diagnosis, treatment, and follow-up. Allergy. 2013;68:562–8.CrossRefGoogle Scholar
  6. 6.
    Gusdorf L, Asli B, Barbarot S, et al. Schnitzler syndrome: validation and applicability of diagnostic criteria in real-life patients. Allergy. 2017;72:177–82.CrossRefGoogle Scholar
  7. 7.
    de Koning HD. Schnitzler’s syndrome: lessons from 281 cases. Clin Trans Allergy. 2014;4:41.CrossRefGoogle Scholar
  8. 8.
    Sompuram SR, Bastas G, Vani K, Bogen SA. Accurate identification of paraprotein antigen targets by epitope reconstruction. Blood. 2008;111:302–8.CrossRefGoogle Scholar
  9. 9.
    Grass S, Preuss KD, Ahlgrimm M, et al. Association of a dominantly inherited hyperphosphorylated paraprotein target with sporadic and familial multiple myeloma and monoclonal gammopathy of undetermined significance: a case-control study. Lancet Oncol. 2009;10:950–6.CrossRefGoogle Scholar
  10. 10.
    de Koning HD, Schalkwijk J, Stoffels M, et al. The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome. Arthritis Res Ther. 2015;17:187.CrossRefGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    de Koning HD, Bodar EJ, Simon A, van der Hilst JC, Netea MG, van der Meer JW. Beneficial response to anakinra and thalidomide in Schnitzler’s syndrome. Ann Rheum Dis. 2006;65:542–4.CrossRefGoogle Scholar
  13. 13.
    de Koning HD, Schalkwijk J, van der Ven-Jongekrijg J, Stoffels M, van der Meer JW, 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.CrossRefGoogle Scholar
  14. 14.
    Krause K, Tsianakas A, Wagner N, et al. Efficacy and safety of canakinumab in Schnitzler syndrome: a multicenter randomized placebo-controlled study. J Allergy Clin Immunol. 2017;139:1311–20.CrossRefGoogle Scholar
  15. 15.
    Migliorini P, Del Corso I, Tommasi C, Boraschi D. Free circulating interleukin-18 is increased in Schnitzler syndrome: a new autoinflammatory disease? Eur Cytokine Netw. 2009;20:108–11.PubMedGoogle Scholar
  16. 16.
    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.CrossRefGoogle Scholar
  17. 17.
    Volz T, Wolbing F, Fischer J, et al. Dermal interleukin-1 expression and effective and long-lasting therapy with interleukin-1 receptor antagonist anakinra in Schnitzler syndrome. Acta Derm Venereol. 2012;92:393–4.CrossRefGoogle Scholar
  18. 18.
    de Koning HD, van Vlijmen-Willems IM, Rodijk-Olthuis D, 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.CrossRefGoogle Scholar
  19. 19.
    Bonnekoh H, Scheffel J, Maurer M, Krause K. The use of skin biomarker profiles to distinguish Schnitzler’s syndrome from chronic spontaneous urticaria: results of a pilot study. Br J Dermatol. 2018;178(2):561–2.CrossRefGoogle Scholar
  20. 20.
    Szturz P, Sediva A, Zurek M, et al. Anakinra treatment in Schnitzler syndrome—results of the first retrospective multicenter study in six patients from the Czech Republic. Klin Onkol. 2014;27:111–26.CrossRefGoogle Scholar
  21. 21.
    Loock J, Lamprecht P, Timmann C, Mrowietz U, Csernok E, Gross WL. Genetic predisposition (NLRP3 V198M mutation) for IL-1-mediated inflammation in a patient with Schnitzler syndrome. J Allergy Clin Immunol. 2010;125:500–2.CrossRefGoogle Scholar
  22. 22.
    Rowczenio DM, Trojer H, Russell T, et al. Clinical characteristics in subjects with NLRP3 V198M diagnosed at a single UK center and a review of the literature. Arthritis Res Ther. 2013;15:R30.CrossRefGoogle Scholar
  23. 23.
    de Koning HD, van Gijn ME, Stoffels M, et al. Myeloid lineage-restricted somatic mosaicism of NLRP3 mutations in patients with variant Schnitzler syndrome. J Allergy Clin Immunol. 2015;135:561–4.CrossRefGoogle Scholar
  24. 24.
    Krause K, Grattan CE, Bindslev-Jensen C, et al. How not to miss autoinflammatory diseases masquerading as urticaria. Allergy. 2012;67:1465–74.CrossRefGoogle Scholar
  25. 25.
    Lebbe C, Rybojad M, Klein F, et al. Schnitzler’s syndrome associated with sensorimotor neuropathy. J Am Acad Dermatol. 1994;30(2 Pt 2):316–8.CrossRefGoogle Scholar
  26. 26.
    Klein CJ, Moon JS, Mauermann ML, et al. The neuropathies of Waldenstrom’s macroglobulinemia (WM) and IgM-MGUS. Can J Neurol Sci. 2011;38:289–95.CrossRefGoogle Scholar
  27. 27.
    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.CrossRefGoogle Scholar
  28. 28.
    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.CrossRefGoogle Scholar
  29. 29.
    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.CrossRefGoogle Scholar
  30. 30.
    Krause K, Weller K, Stefaniak R, et al. Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study. Allergy. 2012;67:943–50.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Heleen D. de Koning
    • 1
  • Karoline Krause
    • 2
  1. 1.Mauritskliniek NijmegenNijmegenThe Netherlands
  2. 2.Charité—Universitätsmedizin BerlinBerlinGermany

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