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Schnitzler's syndrome associated with pancreatitis: a disease of IL-1 dysregulation

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Abstract

Schnitzler's syndrome (SS) is a rare inflammatory disease of unknown origin characterized by chronic urticaria and monoclonal gammopathy (usually IgM) associated with at least two of the following components: fever, arthralgia or arthritis, bone pain, hepato- and/or splenomegaly, lymphadenopathy, elevated erythrocyte sedimentation rate, leukocytosis, and/or abnormal findings on bone morphological investigations. To date, about 100 cases have been described with only 4 being reported in the USA. The mean time to diagnosis from the onset of disease is 5.4 years, given the varied symptoms with which patients may present. The pathogenesis of SS remains unknown but likely involves dysregulation of the IL-1 pathway. 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. She also had a history of chronic pancreatitis as well as a family history of recurrent pancreatitis. The diagnosis of Schnitzler's syndrome was made, and she was successfully treated with the IL-1 receptor antagonist, anakinra.

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References

  1. Lipsker D, Veran Y, Grunenberger F, Cribier B, Heid E, Grosshans E (2001) The Schnitzler syndrome. Four new cases and review of the literature. Medicine (Baltimore) 80:37–44

    Article  CAS  Google Scholar 

  2. de Koning HD, Bodar EJ, van der Meer JW, Simon A, Schnitzler Syndrome Study Group (2007) Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum 37:137–148

    Article  PubMed  Google Scholar 

  3. Dinarello CA (2009) Interleukin-1beta and the autoinflammatory diseases. N Engl J Med 360:2467–2470

    Article  PubMed  CAS  Google Scholar 

  4. Gabay C, Lamacchia C, Palmer G (2010) IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol 6:232–241

    Article  PubMed  CAS  Google Scholar 

  5. Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A et al (2009) An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med 360:2426–2437

    Article  PubMed  CAS  Google Scholar 

  6. Saurat JH, Schifferli J, Steiger G, Dayer JM, Didierjean L (1991) Antiinterleukin-1 alpha autoantibodies in humans: characterization, isotype distribution and receptor-binding inhibition-higher frequency in Schnitzler's syndrome (urticaria and macroglobulinemia). J Allergy Clin Immunol 88:244–256

    Article  PubMed  CAS  Google Scholar 

  7. Ryan JG, de Koning HD, Beck LA, Booty MG, Kastner DL, Simon A (2008) IL-1 blockade in Schnitzler syndrome: ex vivo findings correlate with clinical remission. J Allergy Clin Immunol 121:260–262

    Article  PubMed  CAS  Google Scholar 

  8. de Kleijn EM, Telgt D, Laan R (1997) Schnitzler's syndrome presenting as fever of unknown origin (FUO). The role of cytokines in its systemic features. Neth J Med 51:140–142

    Article  PubMed  Google Scholar 

  9. Migliorini P, Corso ID, Tommasi C, Boraschi D (2009) Free circulating interleukin-18 is increased in Schnitzler syndrome: a new autoinflammatory disease? Eur Cytokine Netw 20:108–111

    PubMed  CAS  Google Scholar 

  10. Pizzirani C, Falzoni S, Govoni M, La Corte R, Donadei S, Di Virgilio F et al (2009) Dysfunctional inflammasome in Schnitzler's syndrome. Rheumatology 48:1304–1308

    Article  PubMed  CAS  Google Scholar 

  11. Loock J, Lamprecht P, Timmann C, Mrowietz U, Csernok E, Gross WL (2010) Genetic predisposition (NLRP3 V198M mutation) for IL-1-mediated inflammation in a patient with Schnitzler syndrome. J All Clin Immunol 125:500–502

    Article  CAS  Google Scholar 

  12. Lipsker D, Spehner D, Drillien R, Schmitt P, Cribier B, Heid E et al (2000) Schnitzler syndrome: heterogeneous immunopathological findings involving IgM-skin interactions. Br J Dermatol 142:954–959

    Article  PubMed  CAS  Google Scholar 

  13. Nashan D, Sunderkötter C, Bonsmann G, Luger T, Goerdt S (1995) Chronic urticaria, arthralgia, raised erythrocyte sedimentation rate and IgG paraproteinaemia: a variant of Schnitzler's syndrome? Br J Dermatol 133:132–134

    Article  PubMed  CAS  Google Scholar 

  14. Rizzi R, Curci P, Rinaldi E, Rinaldi F, Cimmino A, Ricco R et al (2008) Schnitzler's syndrome: monoclonal gammopathy associated with chronic urticaria. Acta Haematol 120(1):1–4

    Article  PubMed  Google Scholar 

  15. Tanneberger O, Büchner S, Zimmerli LU (2007) Schnitzler's syndrome with urticaria vasculitis. Internist (Berl) 48:1432–1435

    Article  CAS  Google Scholar 

  16. Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al (2003) Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood 102:3759–3764

    Article  PubMed  CAS  Google Scholar 

  17. Verret JL, Leclech C, Rousselet MC, Hurez D, Schnitzler L (1993) Schnitzler syndrome and Waldenström disease. Fatal outcome of the original case. Ann Dermatol Venereol 120:459–460

    PubMed  CAS  Google Scholar 

  18. Blaise S (2003) Sensitive chonic inflammatory demyelinating polyradiculoneuropathy in Schnitzler's syndrome. Ann Dermatol Venereol 130:348–351

    PubMed  CAS  Google Scholar 

  19. Lebbe C, Rybojad M, Klein F, Oksenhendler E, Catala M, Danon F et al (1994) Schnitzler syndrome associated with sensorimotor neuropathy. J Am Acad Dermatol 30:316–318

    Article  PubMed  CAS  Google Scholar 

  20. Worm M, Kolde G (2003) Schnitzler's syndrome: successful treatment of two patients using thalidomide. Br J Dermatol 148:601–602

    Article  PubMed  CAS  Google Scholar 

  21. Ramadan KM, Eswedi HA, El-Agnaf MR (2007) Schnitzler syndrome: a case report of successful treatment using the anti-CD20 monoclonal antibody rituximab. Br J Dermatol 156:1072e4

    Article  Google Scholar 

  22. Murota H, Shoda Y, Ishibashi T, Sugahara H, Matsumura I, Katayama I (2009) Improvement of recurrent urticaria in a patient with Schnitzler syndrome associated with B-cell lymphoma with combination rituximab and radiotherapy. J Am Acad Derm 61:1070–1075

    Article  PubMed  Google Scholar 

  23. Besada E, Nossent H (2010) Dramatic response to IL1-RA treatment in longstanding multidrug resistant Schnitzler's syndrome: a case report and literature review. Clin Rheumatol 29:567–571

    Article  PubMed  Google Scholar 

  24. Mertens M, Singh JA (2009) Anakinra for rheumatoid arthritis. Cochrane Database Syst Rev 1:CD005121

    PubMed  Google Scholar 

  25. Sediva A, Polouckova A, Podrazil M, Fronkova E, Kalina T (2010) Characterization of the B-cell compartment in a patient with Schnitzler syndrome. Scand J Rheumatol 0:1–3

    Google Scholar 

  26. Lust JA, Lacy M, Zeldenrust SR, Dispenzieri A, Gertz M, Witzig TE et al (2009) Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1β-induced interleukin-6 production and the myeloma proliferative component. Mayo Clin Proc 84:114–122

    Article  PubMed  CAS  Google Scholar 

  27. Dinarello C (2009) Targeting the pathogenic role of interleukin 1β in the progression of smoldering/indolent myeloma to active disease. Mayo Clin Proc 84:105–107

    Article  PubMed  Google Scholar 

  28. Nishida A, Andoh A, Imaeda H, Inatomi O, Shiomi H, Fujiyama Y (2010) Expression of interleukin 1-like cytokine interleukin 33 and its receptor complex (ST2L and IL1RAcP) in human pancreatic myofibroblasts. Gut 59:531–541

    Article  PubMed  CAS  Google Scholar 

  29. Smithies AM, Sargen K, Demaine AG, Kingsnorth AN (2000) Investigation of the interleukin 1 gene cluster and its association with acute pancreatitis. Pancreas 20:234–240

    Article  PubMed  CAS  Google Scholar 

  30. Norman J (1995) Interleukin-1 receptor antagonist decreases severity of experimental acute pancreatitis. Surgery 117:648–655

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Cecilia A. Larocca, John W. McEvoy, Todd Kolb & Brian T. Garibaldi

  2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Carla L. Ellis

  3. Division of Dermatopathology and Oral Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jacqueline Junkins-Hopkins

  4. Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Alan N. Baer

  5. Division of Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, 5501 Hopkins Bayview Circle, Baltimore, MD, 21224, USA

    Todd Kolb & Brian T. Garibaldi

Authors
  1. Cecilia A. Larocca
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  2. John W. McEvoy
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  3. Carla L. Ellis
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  4. Jacqueline Junkins-Hopkins
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  5. Todd Kolb
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  6. Alan N. Baer
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  7. Brian T. Garibaldi
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Correspondence to Brian T. Garibaldi.

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Larocca, C.A., McEvoy, J.W., Ellis, C.L. et al. Schnitzler's syndrome associated with pancreatitis: a disease of IL-1 dysregulation. Clin Rheumatol 31, 169–174 (2012). https://doi.org/10.1007/s10067-011-1804-4

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  • DOI: https://doi.org/10.1007/s10067-011-1804-4

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