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• Sjögren’s syndrome with cryoglobulinemic vasculitis – successful treatment with rituximab
  Shweta S Bhagat
  Published on: 12 March 2008

• Published on: 12 March 2008

  Sjögren’s syndrome with cryoglobulinemic vasculitis – successful treatment with rituximab

  • Shweta S Bhagat, Specialist Registrar
  • Other Contributors:
    • Sumeet Agrawal, Bhaskar Dasgupta

  Dear Editor,

  We read with interest the review on anti CD-20 monoclonal antibody treatment for cryoglobulinemic vasculitis by Cacoub et al. We share our experience with two cases of cryoglobulinemic vasculitis associated with Sjogren’s syndrome which were treated successfully with Rituximab. An 80-year-old man with Sjogren’s syndrome (SS) for 15 years, (anti-Ro/La positive, with peripheral neuropathy and immune thr...

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  Dear Editor,

  We read with interest the review on anti CD-20 monoclonal antibody treatment for cryoglobulinemic vasculitis by Cacoub et al. We share our experience with two cases of cryoglobulinemic vasculitis associated with Sjogren’s syndrome which were treated successfully with Rituximab. An 80-year-old man with Sjogren’s syndrome (SS) for 15 years, (anti-Ro/La positive, with peripheral neuropathy and immune thrombocytopenia), was on treatment with azathioprine and corticosteroids. He presented with multiple, rapidly progressive, painful, non-healing, necrotic ulcers on both shins, severe Raynaud’s, petechial rash on the legs, fatigue and worsening neuropathy. Blood and protein was present in his urine. He had raised CRP, impaired renal function, very low complement, Rheumatoid factor (RF) >1000, and positive ANA (1:80 titre). Cryoglobulins Type I-IgM kappa, were positive - 5.4 g/l. Investigations for hepatitis C, lymphoproliferative disorders, malignancies and other causes of cryoglobulinemia were negative. He was treated with high dose intravenous corticosteroids and iloprost for SS associated cryoglobulinemic vasculitis. He did not improve substantially and was treated with Rituximab (2 doses of 1000mg each at 2-week interval). His renal function,fatigue, rash and neuropathy improved significantly. His ulcers started healing rapidly. At 6 months follow up, his ulcers have healed and he has mild residual weakness of hand grip. The second case is a 48-year-old lady with primary SS who presented with a painful, blotchy rash on her legs. Investigations revealed elevated globulins, RF and presence of mixed cryoglobulins (type II). After initial plasmapheresis she was switched to prednisolone and azathioprine. Her painful rash and sialadenitis recurred, cryoglobulinemia persisted. Following a course of rituximab (2 doses of 1000mg each at 2-week interval) she remained symptom free for 8 months. A relapse warranted a second course-she is now asymptomatic for over 2 years.

  Cryoglobulins are present in upto 20% of patients with SS. Systemic features are more common in patients of SS with cryogloulinemia. Their 5-year survival is reduced as compared to those without, (1, 2) making it important to recognize and treat this complication of SS, to reduce morbidity and mortality. Rituximab has been used safely and effectively in cryoglobulinemias due to various causes, particularly HCV related. (3, 4) It is used successfully in primary Non-Hodgkin’s lymphomas, and those associated with SS (5). Very few cases of cryoglobulinemia associated with SS, treated successfully with rituximab, have been reported. Pijpe et al suggested that rituximab was effective in the treatment of primary SS. (6) Another study of 16 patients with systemic complications of primary SS, of which 5 had cryoglobulinemia, showed rituximab to be efficacious, well tolerated and allowed for marked reduction in corticosteroid use (7). B-cell activation is a consistent immunoregulatory abnormality in SS. Oligoclonal B-cell expansion in the form of monoclonal light chains or immunoglobulins in the serum and urine are found in 80-100% patients of SS with systemic involvement and 25-40% of those with glandular disease. (8). Controlled trials are needed to gather enough evidence for the successful treatment of cryoglobulinemia with rituximab (B-cell depletion therapy) as demonstrated by our cases.

  References

  1. Vasilev VI, Khodarev NV et. al. Cryoglobulinemia in Sjogren’s syndrome. Ter Arkh 1990;62(5):66-70.

  2. Ramos-Casals M, Cervera R, Yagüe J, García-Carrasco M, Trejo O, Jiménez S, Morlà RM, Font J, Ingelmo M. Cryoglobulinemia in primary Sjögren's syndrome: prevalence and clinical characteristics in a series of 115 patients. Semin Arthritis Rheum 1998;28:200-5.

  3. Zaja F, De Vita S, Mazzaro C, Sacco S, Damiani D, De Marchi G, Michelutti A, Baccarani M, Fanin R, Ferraccioli . Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood 2003;101(10):3827-34.

  4. Bryce AH, Dispenzieri A et. al. Response to rituximab in patients with type II cryoglobulinemia. Clin Lymphoma Myeloma 2006;7(2):140-4.

  5. Voulgarelis M, Giannouli S, Anagnostou D, Tzioufas AG. Combined therapy with rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) for Sjögren's syndrome-associated B-cell aggressive non-Hodgkin's lymphomas. Rheumatology (Oxford) 2004;43:1050-3. Epub 2004 Jun 8

  6. Pijpe J, van Imhoff GW, Spijkervet FK, Roodenburg JL, Wolbink GJ, Mansour K, Vissink A, Kallenberg CG, Bootsma H. Rituximab treatment in patients with primary Sjogren’s syndrome: an open-label phase II study. Arthritis Rheum 2005;52:2740-50.

  7. Seror R, Sordet C, Guillevin L, Hachulla E, Masson C, Ittah M, Candon S, Le Guern V, Aouba A, Sibilia J, Gottenberg JE, Mariette X. Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjögren’s syndrome. Ann Rheum Dis 2007;66:351-7.

  8. Manoussakis MN, Moutsopoulos HM. Sjogren’s syndrome: autoimmune epithelitis. Baillieres Best Pract Res Clin Rheumatol 2000;14:73-95.

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  Conflict of Interest:
  None declared.

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