Schnitzler Syndrome: Diagnostics and Treatment
Authors:
P. Szturz 1; Z. Adam 1; A. Šedivá 2; Z. Fojtík 1; D. Čorbová 3; J. Neubauer 4; J. Prášek 5; R. Hájek 1; J. Mayer 1
Authors‘ workplace:
Interní hematoonkologická klinika, LF MU a FN Brno
1; Ústav imunologie, 2. LF UK a FN Motol
2; Dermatovenerologická klinika, LF MU a FN Brno
3; Radiologická klinika, LF MU a FN Brno
4; Klinika nukleární medicíny, LF MU a FN Brno
5
Published in:
Klin Onkol 2011; 24(4): 271-277
Category:
Reviews
Overview
Backgrounds:
The most important diagnostic criteria for Schnitzler syndrome include chronic urticaria, the presence of monoclonal IgM immunoglobulin, marked inflammation (leukocytosis, elevated CRP and erythrocyte sedimentation rate), subfebrile temperatures or fevers and bone and joint pains. It is a rare idiopathic disease that may lead to potentially life-threatening complications such as development of secondary amyloidosis or transformation into malignant lymphoproliferation. Schnitzler syndrome should be included in differential diagnostics of chronic urticaria and fevers of unknown origin. The diagnostic algorithm is based on clinical presentation and serum and urine electrophoreses to detect monoclonal components. Blockade of interleukin-1 (IL-1), key cytokine in the pathogenesis of the disease, dominates current therapeutic protocols. Anakinra (Kineret™), recombinant human IL-1 receptor antagonist, is the most widely used treatment option. According to literature, disease remission was obtained in all treated patients. Therefore, anakinra represents a significant diagnostic possibility to differentiate Schnitzler syndrome from e. g. monoclonal gammopathy of unknown significance (MGUS) associated with urticaria of different aetiology. Biological therapy with rilonacept (Arcalyst™) and canakinumab (Ilaris™) represents a new treatment alternative for patients, allowing prolonged dosing intervals of 1 and 8 weeks, respectively (compared to 24 hours with anakinra). The review article also presents findings of various imaging methods (conventional radiography, computed tomography, traditional bone scintigraphy) and photographs of patients with Schnitzler syndrome before and after anakinra therapy.
Design:
The aim of the review is to draw attention to the existence of this rare autoinflammatory and potentially pre-malignant condition, present a simple diagnostic algorithm and provide an overview of therapeutic options for the patients.
Conclusions:
Malign potential of Schnitzler syndrome, possible development into systemic amyloidosis and the fact that patients are frequently referred to oncology clinics for differential diagnostics of monoclonal gammopathy, are the main reasons why clinical oncologists should be aware of Schnitzler syndrome.
Key words:
paraproteinemias – multiple myeloma – amyloidosis – interleukins – interleukin 1 receptor antagonist protein
Sources
1. Schnitzler L, Schubert B, Boasson M et al. Urticaire chronique lésions osseuses macroglobulinémie IgM: maladie de Waldenström? Bull Soc Fr Dermatol Syph 1974; 81: 363–366.
2. Besada E, Nossent H. Dramatic response to IL1-RA treatment in longstanding multidrug resistant Schnitzler’s syndrome: a case report and literature review. Clin Rheumatol 2010; 29(5): 567–571.
3. Lipsker D, Veran Y, Grunenberger F et al. The Schnitzler syndrome: four new cases and review of the literature. Medicine (Baltimore) 2001; 80(1): 37–44.
4. de Koning HD, Bodar EJ, van der Meer JW et al. Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum 2007; 37(3): 137–148.
5. Gilson M, Abad S, Larroche C et al. Treatment of Schnitzler’s syndrome with anakinra. Clin Exp Rheumatol 2007; 25(6): 931.
6. Loock J, Lamprecht P, Timmann C et al. Genetic predisposition (NLRP3 V198M mutation) for IL-1-mediated inflammation in a patient with Schnitzler syndrome. J Allergy Clin Immunol 2010; 125(2): 500–502.
7. Eiling E, Schröder JO, Gross WL et al. The Schnitzler syndrome: chronic urticaria and monoclonal gammopathy – an autoinflammatory syndrome? J Dtsch Dermatol Ges 2008; 6(8): 626–631.
8. Kluger N, Bessis D, Guillot B. Tocilizumab as a potential treatment in Schnitzler syndrome. Med Hypotheses 2009; 72(4): 479–480.
9. Adam Z, Krejčí M, Pour L et al. Schnitzlerův syndrom – popis čtrnáctiletého průběhu nemoci a přehled informací o této nemoci. Vnitř Lék 2008; 54(12): 1140–1153.
10. Sanmartín O, Febrer I, Botella R et al. Urticarial lesions and monoclonal IgM gammopathy. Schnitzler’s syndrome. Arch Dermatol 1994; 130(9): 1193–1198.
11. 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(1): 23–31.
12. Berdy SS, Bloch KJ. Schnitzler’s syndrome: a broader clinical spectrum. J Allergy Clin Immunol 1991; 87(4): 849–854.
13. Borradori L, Rybojad M, Puissant A et al. Urticarial vasculitis associated with a monoclonal IgM gammopathy: Schnitzler’s syndrome. Br J Dermatol 1990; 123(1): 113–118.
14. Janier M, Bonvalet D, Blanc MF et al. Chronic urticaria and macroglobulinemia (Schnitzler’s syndrome): report of two cases. J Am Acad Dermatol 1989; 20(2 Pt 1): 206–211.
15. Olsen E, Førre O, Lea T et al. 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): 379–384.
16. Lecompte M, Blais G, Bisson G et al. Schnitzler’s syndrome. Skeletal Radiol 1998; 27(5): 294–296.
17. De Waele S, Lecouvet FE, Malghem J et al. Schnitzler’s syndrome: an unusual cause of bone pain with suggestive imaging features. AJR Am J Roentgenol 2000; 175(5): 1325–1327.
18. Flórez AF, Gallardo-Agromayor E, García-Barredo R et al. Radiological aid to clinical diagnosis of Schnitzler’s syndrome: multimodality imaging approach. Clin Rheumatol 2008; 27(1): 107–110.
19. Krejčí M, Adam Z, Hájek R. Mnohočetný myelom. Klin Onkol 2008; 21 (Suppl 1): 187–189.
20. Pujol RM, Barnadas MA, Brunet S et al. Urticarial dermatosis associated with Waldenström’s macroglobulinemia. J Am Acad Dermatol 1989; 20(5 Pt 1): 855–857.
21. Lipsker D, Cribier B, Maloisel F et al. Chronic urticaria and IgA myeloma. Acta Derm Venereol 1998; 78(5): 395.
22. Karakelides M, Monson KL, Volcheck GW et al. Monoclonal gammopathies and malignancies in patients with chronic urticaria. Int J Dermatol 2006; 45(9): 1032–1038.
23. Ščudla V, Budíková M, Petrová P et al. Analýza sérových hladin vybraných biologických ukazatelů u monoklonální gamapatie nejistého významu a mnohočetného myelomu. Klin Onkol 2010; 23(3): 171–181.
24. Fojtík Z, Adam Z, Krejčí M et al. Diferenciální diagnostika syndromu Schnitzlerové a dalších chorob způsobujících urtiku, kostní bolesti a subfebrilie. In: Rovenský J, Pavelka K, Plank L et al (eds). Vybrané kazuistiky v reumatológii. Bratislava: SAP 2009: 81–101.
25. Šedivá A. Poruchy regulace zánětu a periodické horečky. Alergie 2006; 8(1): 36–41.
26. Claes K, Bammens B, Delforge M et al. Another devastating complication of the Schnitzler’s syndrome: AA amyloidosis. Br J Dermatol 2008; 158(1): 182–184.
27. Martinez-Taboada VM, Fontalba A, Blanco R et al. Successful treatment of refractory Schnitzler syndrome with anakinra: comment on the article by Hawkins et al. Arthritis Rheum 2005; 52(7): 2226–2227.
28. Šedivá A, Poloučková A, Podrazil M et al. Characterization of the B-cell compartment in a patient with Schnitzler syndrome. Scand J Rheumatol 2010; 40(2): 158–160.
29. Lebbe C, Rybojad M, Klein F et al. Schnitzler’s syndrome associated with sensorimotor neuropathy. J Am Acad Dermatol 1994; 30(2 Pt 2): 316–318.
30. Eiling E, Möller M, Kreiselmaier I et al. Schnitzler syndrome: treatment failure to rituximab but response to anakinra. J Am Acad Dermatol 2007; 57(2): 361–364.
31. Thonhoffer R, Uitz E, Graninger W. Schnitzler’s syndrome-exacerbation after anti-TNF treatment. Rheumatology 2007; 46(6): 1041–1042.
32. de Koning HD, Bodar EJ, Simon A et al. Beneficial response to anakinra and thalidomide in Schnitzler’s syndrome. Ann Rheum Dis 2006; 65(4): 542–544.
33. Obořilová A, Adam Z. Schnitzler’s syndrome. Vnitř Lék 1998; 44(7): 423–427.
34. Stahl N, Radin A, Mellis S. Rilonacept-CAPS and beyond. Ann N Y Acad Sci 2009; 1182: 124–134.
35. Church LD, McDermott MF. Canakinumab: a human anti-IL-1β monoclonal antibody for the treatment of cryopyrin-associated periodic syndromes. Expert Rev Clin Immunol 2010; 6(6): 831–841.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2011 Issue 4
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