Schnitzler Syndrome 

  • Author: Joel G DeKoven, MD, FRCPC; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jan 11, 2012
 

Background

Schnitzler syndrome (SS), first reported in 1972,[1] is characterized by chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis, and a monoclonal immunoglobulin M (IgM) gammopathy in a concentration that is usually less than 10 g/L. Since 1972, approximately 100 cases of Schnitzler syndrome have been reported.[2, 3, 4, 5]

Next

Pathophysiology

The exact pathogenesis of Schnitzler syndrome is unclear. Some hypothesize that the deposition of the IgM paraprotein, leading to the formation of immune complexes and the activation of the complement cascade, is responsible for the cutaneous manifestations of Schnitzler syndrome. Another proposed mechanism involves the uncontrolled activation of interleukin 1-alpha (IL-1alpha).

Previous
Next

Epidemiology

Frequency

United States

Only a few cases of Schnitzler syndrome have been reported from the United States.

International

Schnitzler syndrome is rare, with approximately 100 cases reported in the literature. The original case was from France, with the greatest number of cases originating from the same country. The vast majority of cases come from Western Europe.

Mortality/Morbidity

Most Schnitzler syndrome patients have a chronic benign course. Spontaneous remissions have not been reported. Approximately 10-15% of patients eventually develop a lymphoproliferative disorder, including lymphoplasmacytic lymphoma, Waldenström macroglobulinemia, or IgM myeloma. Schnitzler's original patient died at age 88 years, with a diffuse lymphoplasmacytic infiltration of his liver and bone marrow. Thus, the initial workup of a Schnitzler syndrome patient should include an examination of the bone marrow, immunoelectrophoresis of serum, and a urinary protein level. A lymph node biopsy should be performed if the nodes are enlarged.

Race

The majority of Schnitzler syndrome cases are in white western Europeans.

Sex

Males have a slight predominance.

Age

Patients with Schnitzler syndrome have ranged from age 13-71 years at the time of diagnosis. The average age of onset is approximately 52 years,[2, 3] although the average delay to diagnosis is more than 5 years.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Joel G DeKoven, MD, FRCPC  Associate Professor, Division of Dermatology, Department of Medicine, University of Toronto, Sunnybrook Health Sciences Centre and St Michael's Hospital, Canada

Joel G DeKoven, MD, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Contact Dermatitis Society, Canadian Dermatology Association, Canadian Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Coauthor(s)

Kucy Pon, MD, FRCPC  Assistant Professor, Division of Dermatology, Department of Medicine, University of Toronto Faculty of Medicine

Kucy Pon, MD, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, Canadian Medical Association, and Canadian Medical Protective Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Jean-Hilaire Saurat, MD  Chair, Professor, Department of Dermatology, University of Geneva, Switzerland

Jean-Hilaire Saurat, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey Meffert, MD  Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

References

  1. Schnitzler L, Schubert B, Boasson M. Urticaire chronique, lons osseuses, macroglobuline IgM: maladie de Waldenstrom. Bull Soc Franc Derm Syph. 1974;81:363.

  2. de Koning HD, Bodar EJ, van der Meer JW, Simon A,. Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum. Dec 2007;37(3):137-48. [Medline].

  3. Asli B, Bievenu B, Cardoliani F, et al. Chronic Urticaria and Monoclonal IgM gammopathy (Schnitzler Syndrome). Report of 11 cases treated with Pefloxacin. Arch Dermatol. 2007;143:1046-1050.

  4. Kurian A, Lee JK, Vadas P. Schnitzler syndrome with cold-induced urticaria. J Dermatol Case Rep. Dec 31 2010;4(4):50-3. [Medline]. [Full Text].

  5. Tinazzi E, Puccetti A, Patuzzo G, Sorleto M, Barbieri A, Lunardi C. Schnitzler syndrome, an autoimmune-autoinflammatory syndrome: report of two new cases and review of the literature. Autoimmun Rev. May 2011;10(7):404-9. [Medline].

  6. 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). Jan 2001;80(1):37-44. [Medline].

  7. Olsen E, Forre O, Lea T, Langeland T. Unique antigenic determinants (idiotypes) used as markers in a patient with macroglobulinemia and urticaria. Similar idiotypes demonstrated in the skin and on peripheral blood lymphocytes. Acta Med Scand. 1980;207(5):379-84. [Medline].

  8. Saurat JH, Schifferli J, Steiger G, Dayer JM, Didierjean L. Anti-interleukin-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. Aug 1991;88(2):244-56. [Medline].

  9. Vandenhende MA, Bentaberry F, Morlat P, Bonnet F. Anakinra: An effective treatment in the Schnitzler syndrome. Joint Bone Spine. Dec 2011;78(6):636-7. [Medline].

  10. Morita A, Sakakibara S, Yokota M, Tsuji T. A case of urticarial vasculitis associated with macroglobulinemia (Schnitzler's syndrome). J Dermatol. Jan 1995;22(1):32-5. [Medline].

  11. Simon A, van der Meer JWM, Drenth JPH. Familial auto-inflammatory syndromes. In: Harris ED, Budd RC, Firestein GS. Kelley's textbook of Rheumatology. 7th. Philadelphia: Saunders; 2004:Chapter 112 pp1773-88.

  12. Akimoto R, Yoshida M, Matsuda R, Miyasaka K, Itoh M. Schnitzler's syndrome with IgG kappa gammopathy. J Dermatol. Nov 2002;29(11):735-8. [Medline].

  13. 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. Apr 2006;65(4):542-4. [Medline].

  14. Worm M, Kolde G. Schnitzler's syndrome: successful treatment of two patients using thalidomide. Br J Dermatol. Mar 2003;148(3):601-2. [Medline].

  15. Ramadan KM, Eswedi HA, El-Agnaf MR. Schnitzler syndrome: A case report of successful treatment using the anti-CD20 momoclonal antibody rituximab. Br J Dermatol. 2007;156:1072-74.

  16. Eiling E, Moller M, Kreiselmaier I, Brasch J, Schwarz T. Schnitzler syndrome: treatment failure to rituximab but response to anakinra. J Am Acad Dermatol. Aug 2007;57(2):361-4. [Medline].

  17. 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. Jul 2005;52(7):2226-7. [Medline].

  18. Bonnetblanc JM, Drouet M, Laplaud P, Bedane C, Bernard P. Urticaria with macroglobulinaemia. Disease activity associated alterations in immunoglobulins profile and bone marrow hypodiploidy. Dermatologica. 1990;181(1):41-3. [Medline].

  19. Borradori L, Rybojad M, Puissant A, Dallot A, Verola O, Morel P. Urticarial vasculitis associated with a monoclonal IgM gammopathy: Schnitzler's syndrome. Br J Dermatol. Jul 1990;123(1):113-8. [Medline].

  20. Harati A, Brockmeyer NH, Altmeyer P, Kreuter A. Skin disorders in association with monoclonal gammopathies. Eur J Med Res. Mar 29 2005;10(3):93-104. [Medline].

  21. Machet L, Vaillant L, Machet MC, Reisenleiter M, Goupille P, Lorette G. Schnitzler's syndrome (urticaria and macroglobulinemia): evolution to Waldenström's disease is not uncommon. Acta Derm Venereol. Sep 1996;76(5):413. [Medline].

  22. Nashan D, Sunderkotter C, Bonsmann G, Luger T, Goerdt S. Chronic urticaria, arthralgia, raised erythrocyte sedimentation rate and IgG paraproteinaemia: a variant of Schnitzler's syndrome?. Br J Dermatol. Jul 1995;133(1):132-4. [Medline].

  23. Puddu P, Cianchini G, Girardelli CR, Colonna L, Gatti S, de Pita O. Schnitzler's syndrome: report of a new case and a review of the literature. Clin Exp Rheumatol. Jan-Feb 1997;15(1):91-5. [Medline].

  24. Sanmartín O, Febrer I, Botella R, Grau M, de la Cuadra J, Aliaga A. Urticarial lesions and monoclonal IgM gammopathy. Schnitzler's syndrome. Arch Dermatol. Sep 1994;130(9):1195, 1198. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.