Transformation of IgM-MGUS into Waldenström´s macroglobulinemia in two of six patients treated for Schnitzler´s syndrome

Česká verzia

Authors: Zdeněk Adam ¹; Miroslav Tomíška ¹; Zdeněk Řehák ²; Renata Koukalová ²; Marta Krejčí ¹; Zdeněk Král ¹; Zuzana Adamová ⁴; Sabina Ševčíková ³; Luděk Pour ¹; Martin Štork ¹; Martin Krejčí ¹; Viera Sandecká ¹
Authors place of work: Interní hematologická a onkologická klinika LF MU a FN Brno ¹; Oddělení nukleární medicíny Masarykův onkologický ústav Brno ²; Ústav patologické fyziologie LF MU a FN Brno ³; Chirurgické oddělení nemocnice Vsetín ⁴
Published in the journal: Vnitř Lék 2021; 67(E-3): 15-23
Category: Review Articles

Summary

Transformation of IgM-MGUS into Waldenström´s macroglobulinemia in two of six patients treated for Schnitzler´s syndrome Schnitzler´s syndrome is a very rare, adult-onset, apparently acquired autoinflammatory disease. Chronic urticarial rash and symptoms of systemic inflammation including fever, arthralgia and bone pain with the presence of monoclonal immunoglobulin M (IgM), rarely IgG, are among hallmarks of the disease. We performed a retrospective study of 6 patients (5 men, 1 woman) diagnosed with Schnitzler´s syndrome fulfilling the Strasbourg criteria who had been treated at our centre in the University Hospital Brno from 2007 to 2021. Median age at diagnosis was 54 (45–67) years, median follow up was 8 (3–14) years. All 6 patients had IgM κ monoclonal gammopathy, increased CRP and/or erythrocyte sedimentation rate and arthralgia or bone pain, 4 patients suffered from fever, three had leucocytosis ≥ 10 × 109/L and lymphadenopathy was found in one patient. 18FDG-PET/CT scan with low-dose total body CT became a part of the initial baseline assessment in 5 patients with suspected Schnitzler´s syndrome, while Na18F-PET/CT was used in one patient to confirm the presence of osteosclerotic leasions as a criterion of the disease. All patients had osteosclerotic or hyperostotic bone lesions detected by low-dose CT examination, with increased 18FDG uptake in illiac and femoral bone marrow. The patient with Na18F-PET/CT scan revealed intensive abnormal tracer uptake with Na18F-PET/CT being more sensitive for detection of osteosclerotic lesions in Schnitzler´s syndrome than 18FDG-PET/CT. All patients were treated with daily subcutaneous anakinra without any adverse events, with excellent clinical results. We observed complete disappearance of urticaria and other symptoms persisting during years of anakinra administration.

IgM-MGUS transformed into Waldenström´s macroglobulinemia in two of six patients, but only one patient developed symptoms requiring RBD (Rituximab, Bendamustin, and Dexamethasone) treatment, which induced almost complete remission of the disease. Successful RBD therapy enabled to prolong intervals of maintenance anakinra from 24 to 48 hours with almost complete control of urticarial rash and other symptoms. We suggest close monitoring of patients with Schnitzler´s syndrome to early capture potential transformation into Waldenström´s macroglobulinemia with succesful treatment of both conditions.

Keywords:

Schnitzler´s syndrome – 18FDG-PET/CT – Na18F-PET/CT – anakinra – Waldenström´s disease

Zdroje

1. de Koning HD. Schnitzler’s syndrome: lessons from 281 cases. Clin Transl Allergy 2014; 4: 41–45.

2. Mulla E, Neame R. Delayed development of the IgM paraprotein in Schnitzler’s syndrome. Scand J Rheumatol 2015; 44: 521–522.

3. Willekens I, Walgraeve N, Goethals L et al. Correlative bone imaging in a case of Schnitzler’s syndrome and brief review of the literature. Hell J Nucl Med 2015; 18: 71–73.

4. Hrodek O. Schnitzler syndrome: an under-diagnosed clinical entity Transfuze a hematologie dnes. 2013; 19(4): 214–215.

5. Janíková-Obořilová, Adam Z. Schnitzlerův syndrom Vnitřní lék 1998; 44 (7): 423–4274.

6. Lipsker D, Veran Y, Grunenberger F et al. The Schnitzler syndrome. Four new cases and review of the literature. Medicine (Baltimore) 2001; 80: 37–44.

7. Simon A, Asli B, Braun-Falco M et al. Schnitzler’s syndrome: diagnosis, treatment, and follow-up. Allergy 2013; 68: 562–568.

8. Kacar M, Pathak S, Savic S. Hereditary systemic autoinflammatory diseases and Schnitzler’s syndrome Rheumatology (Oxford) 2019; 58(Suppl 6): 31–43.

9. Basile C, Rossi L, Casucci F et al. Kidney involvement in the Schnitzler syndrome, a rare disease. Clin Kidney J. 2017; 10(6): 723–727. doi: 10.1093/ckj/sfx077.

10. Jain T, Offord CP, Kyle RA, Dingli D. Schnitzler syndrome: an under-diagnosed clinical entity. Haematologica. 2013; 98(10): 1581–1585. doi: 10.3324/haematol.2013.084830.

11. Terpos E, Asli B, Christoulas D, Brouet J-C, Kastritis E, Rybojad M et al. Increased angiogenesis and enhanced bone formation in patients with IgM monoclonal gammopathy and urticarial skin rash: new insight into the biology of Schnitzler syndrome. Haematologica. 2012; 97(11): 1699–1703.

12. 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. Skeletal Radiol. 2014; 43(7): 905–915.

13. Darrieutort-Laffite C, Ansquer C, Aubert H et al.Rheumatic involvement and bone scan features in Schnitzler syndrome: initial and follow-up data from a single-center cohort of 25 patients. Arthritis Res Ther. 2020; 22(1): 272. doi: 10.1186/s13075-020-02318-5.

14. Alix L, Néel A, Cador B et al. Diagnostic value of 18-F fluorodeoxyglucose PET/CT and bone scan in Schnitzler syndrome. Autoimmunity. 2019; 52(7–8): 264–271.doi: 10.1080/08916934.2019.1680649.

15. Bursztejn AC, Imperiale A, Lipsker D. Aortitis: A new feature of Schnitzler syndrome. JAAD Case Rep. 2017; 3(5): 454–456. doi: 10.1016/j.jdcr.2017.06.016. PMID: 28971133; PMCID: PMC5602823.

16. Kyle RA, Therneau TM, Rajkumar SV et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood. 2003; 102(10): 3759–3764.

17. Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al. Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol. 2003; 30(2): 110–115.

18. Elba S, Castellino A, Soriasio R et al. Immunoglobulin M (IgM) multiple myeloma versus Waldenström macroglobulinemia: diagnostic challenges and therapeutic options: two case reports. J Med Case Rep. 2020; 14(1): 75. doi: 10.1186/s13256-020-02380-2. PMID: 32564775; PMCID: PMC7310052.

19. Gerz MA: Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management. Amer J Hematol. 2021; 96(2): 258–269.

20. Gavriatopoulou M, Musto P, Caers J et al. European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias. Leukemia. 2018 Sep;32(9):1883-1898. doi: 10.1038/s41375-018-0209-7. Epub 2018 Jul 23. PMID: 30038381.

21. Kastritis E, Leblond V, Dimopoulos MA, ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4): iv41–iv50. doi: 10.1093/annonc/mdy146.

22. Aouba A, Pressiat C, Pricopi M et al. Complete remission of Schnitzler syndrome and Waldenström macroglobulinemia under rituximab-cyclophosphamide-dexamethasone. Dermatology 2015; 230(1): 18–22.

23. Cascavilla N, Bisceglia M, D’Arena G. Successful treatment of Schnitzler’s syndrome with anakinra after failure of rituximab trial. Int J Immunopathol Pharmacol 2010; 23(2): 633–636.

24. Murota H, Shoda Y, Ishibashi T et al. Improvement of recurrent urticaria in a patient with Schnitzler syndrome associated with B-cell lymphoma with combination rituximab and radiotherapy. J Am Acad Dermatol 2009; 61(6): 1070–1075.

25. 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.

26. Ramadan KM, Eswedi HA, El-Agnaf MR. Schnitzler syndrome: a case report of successful treatment using the anti-CD20 monoclonal antibody rituximab. Br J Dermatol 2007; 156(5): 1072–1074.

27. Husak R, Nestoris S, Goerdt S et al. Severe course of chronic urticaria, arthralgia, fever and elevation of erythrocyte sedimentation rate: Schnitzler’s syndrome without monoclonal gammopathy? Br J Dermatol 2000; 142: 581–582.

28. Cristina T, Varella N, Nishimura MY et al. Schnitzler’s syndrome without monoclonal gammopathy. Acta Derm Venereol 2005; 85: 272–273.

29. Jani P, Vissing MB, Ahmed S et al. Ibrutinib for the Management of Schnitzler Syndrome: A Novel Therapy for a Rare Condition. J Oncol Pract. 2018; 14(6): 387–388. doi: 10.1200/ JOP.18.00050. Epub 2018 Mar 20.

30. Doležalová P. Nové indikace léčby anakinrou Farmakoterapie (Praha, Print) 2019; 15(3): 333–337.

31. Šedivá, A, Slíva J, Doležalová P et al. Anakinra Farmakoterapie (Praha, Print) 2011; 7(6): 621–629.

32. Néel A, Henry B, Barbarot S et al. Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler’s syndrome: A French multicenter study. Autoimmun Rev 2014; 13: 1035–1041.

33. Rowczenio DM, Pathak S, Arostegui JI et al. Molecular genetic investigation, clinical features, and response to treatment in 21 patients with Schnitzler syndrome. Blood. 2018; 131(9): 974–981. doi:10.1182/blood-2017-10-810366.

34. Vanderschueren S, van der Veen A. The Schnitzler syndrome: chronic urticaria in disguise: a single-centre report of 11 cases and a critical reappraisal of the literature. Clin Exp Rheumatol. 2017; 35(1): 69–73.

35. Giurgea I, Grateau G, Georgin-Lavialle S; French Network of Dysimmune Disorders Associated with Hemopathies. Monoclonal Gammopathy, Arthralgias, and Recurrent Fever Syndrome: A New Autoinflammatory Syndrome? J Rheumatol. 2019; 46(11): 1535–1539. doi: 10.3899/jrheum.181204.

36. Soudet S, Fajgenbaum D, Delattre C et al. Schnitzler syndrome co-occurring with idiopathic multicentric Castleman disease that responds to anti-IL-1 therapy: A case report and clue to pathophysiology. Curr Res Transl Med. 2018; 66(3): 83–86. doi: 10.1016/j. retram.2018.06.001.

37. Gorodetskiy VR, Salugina SO, Fedorov ES. Increasing the Interval of Canakinumab Administration Effectively Supports the Remission of Schnitzler’s Syndrome. Case Rep Rheumatol. 2018;2018:5416907. doi: 10.1155/2018/5416907. PMID: 29850358; PMCID: PMC5925130.

38. Fujita Y, Asano T, Sakai A et al. A case of Schnitzler’s syndrome without monoclonal gammopathy successfully treated with canakinumab. BMC Musculoskelet Disord. 2021;22(1):257. doi: 10.1186/s12891-021-04120-z. Betrains A, Staels F, Vanderschueren S. Efficacy and safety of canakinumab treatment in schnitzler syndrome: A systematic literature review. Semin Arthritis Rheum. 2020; 50(4): 636–642. doi: 10.1016/j.semarthrit.2020.05.002.

39. 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(4): 1311–1320.

40. Krause K, Bonnekoh H, Ellrich A et al. Long-term efficacy of canakinumab in the treatment of Schnitzler syndrome. J Allergy Clin Immunol. 2020; 145(6): 1681–1686.e5. doi:10.1016/j.jaci.2019.12.909.

41. Betrains A, Staels F, Vanderschueren S. Efficacy and safety of canakinumab treatment in schnitzler syndrome: A systematic literature review. Semin Arthritis Rheum. 2020; 50(4): 636–642. doi: 10.1016/j.semarthrit.2020.05.002.

42. Krause K, Feist E, Fiene M et al. Complete remission in 3 of 3 anti-IL-6-treated patients with Schnitzler syndrome. J Allergy Clin Immunol 2012; 129: 848–850.

43. Claus J, Vanderschueren S. Variable Responses to Tocilizumab in Four Patients with Schnitzler Syndrome. J Clin Immunol 2019; 39(4): 370–372.

44. Yan R, Cao W, Liu X, Li F, Shen M. A Chinese case series of Schnitzler syndrome and complete remission in one tocilizumab-treated patient. Clin Rheumatol. 2020; 39(12): 3847–3852.

45. Kluger N, Bessis D, Guillot B. Tocilizumab as a potential treatment in Schnitzler syndrome. Med Hypotheses 2009; 72(4): 479–480.

46. Więsik-Szewczyk E, Felis-Giemza A et al. Schnitzler Syndrome in a 27-Year-Old Man: Diagnostic and Therapeutic Dilemma in Adult Auto-Inflammatory Syndromes A Case Report and Literature Review. Int J Gen Med. 2020; 13: 713–719. doi: 10.2147/IJGM.S265482

47. Bonnekoh H, Frischbutter S, Roll S et al. Tocilizumab treatment in patients with Schnitzler syndrome: An open-label study. J Allergy Clin Immunol Pract. 2021; S2213–2198(21)00152- 5. doi: 10.1016/j.jaip.2021.01.024.

48. Castillo JJ, Advani RH, Branagan AR et al. Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia. Lancet Haematol. 2020; 7(11): e827–e837. doi:10.1016/S2352-3026(20)30224-6.

49. Castillo JJ, Garcia-Sanz R, Hatjiharissi E, Kyle RA et al. Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström Macroglobulinaemia. Br J Haematol. 2016; 175(1): 77–86. doi: 10.1111/bjh.14196.