eMedicine Specialties > Dermatology > Allergy & Immunology

Schnitzler Syndrome: Treatment & Medication

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
Coauthor(s): Kucy Pon, MD, FRCPC, Assistant Professor, Division of Dermatology, Department of Medicine, University of Toronto Faculty of Medicine
Contributor Information and Disclosures

Updated: Jun 30, 2009

Treatment

Medical Care

Up until about 2005, the urticarial eruption of Schnitzler syndrome was typically resistant to treatment. No treatment was consistently effective.

Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive agents have been reported to provide variable relief from the symptoms of bone pain and arthralgias associated with Schnitzler syndrome.

Skin and extracutaneous manifestations respond poorly to H1 and H2 antihistamines. Colchicine and dapsone have been tried with variable success in different patients. A few patients were responsive to treatment with thalidomide but the occurrence of peripheral neuropathy limits its use.10,11 Rituximab, an anti-CD20 monoclonal antibody, was reported to be effective in one patient12 but unsuccessful in another.13  Reports of using chloroquine, chlorambucil, cyclophosphamide, azathioprine, plasmapheresis, and high-dose intravenous immunoglobulin have indicated no response. Psoralen plus UV light (PUVA) may reduce the intensity of the rash in some patients.

NSAIDs have proved to be of some benefit for the bone pain and fever, but not for the urticaria. Systemic steroids may be somewhat effective at controlling the cutaneous eruption, but usually at doses that can cause significant long-term adverse effects.

Pefloxacin mesylate administered at a dose of 800 mg/d may be a therapeutic option. In a case series of 11 patients, it was shown to significantly reduce the intensity and frequency of many of the manifestations in a majority of the group, and it provided a steroid-sparing effect for some patients being treated with systemic corticosteroids.3 It was less active on the osteoarticular component of Schnitzler syndrome. 

Anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, has emerged as the treatment of choice. Its mechanism of action involves competitive inhibition of binding of IL-1alpha and IL-1beta to the IL-1 receptor type 1. Complete remissions have been reported in at least 10 patients with this therapy at a daily subcutaneous dose of 100 mg.2,10,13,14 Some patients have experienced a recurrence of signs and symptoms within 1 day of stopping treatment; anakinra likely must be given on a continuous basis. Localized painful erythematous injection site reactions have been described with this therapy.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Interleukin-1 Receptor Antagonist


Anakinra (Kineret)

Competitively and selectively inhibits IL-1 binding to type I receptor.

Adult

100 mg SC qd

Pediatric

Not established

None reported; higher rate of serious infections and neutropenia are possible when coadministered with TNF blocking agents (eg, etanercept, infliximab, adalimumab); may decrease response to live virus vaccines

Documented hypersensitivity to product or E coli derived products; active infections

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Serious infections may occur (discontinue treatment if serious infection develops); neutropenia may occur (especially if administered concomitantly with TNF blocking agents); most common adverse effect is local reaction at site of injection; caution if administered to nursing women

More on Schnitzler Syndrome

Overview: Schnitzler Syndrome
Differential Diagnoses & Workup: Schnitzler Syndrome
Treatment & Medication: Schnitzler Syndrome
Follow-up: Schnitzler Syndrome
References
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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. 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].

  5. 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].

  6. 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].

  7. 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].

  8. 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.

  9. 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].

  10. 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].

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

  12. 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.

  13. 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].

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

  20. 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].

  21. 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].

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Further Reading

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Keywords

Schnitzler syndrome, Schnitzler's syndrome, chronic urticaria, nonpruritic urticaria, monoclonal immunoglobulin M gammopathy, monoclonal IgM gammopathy

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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 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.

Medical Editor

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.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
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.

Managing Editor

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-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.

CME Editor

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 None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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