Relapsing Evans syndrome and systemic lupus erythematosus with antiphospholipid syndrome treated with Bortezomib in combination with plasma exchange

doi:10.1016/j.clim.2018.12.010

Clinical Immunology

Volume 199, February 2019, Pages 44-46

https://doi.org/10.1016/j.clim.2018.12.010 Get rights and content

Abstract

Relapsing Evans syndrome (ES) and systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome (APS) is very rare association. Coexistence of these syndromes is potentially fatal and require high-dose combined immunosuppressive therapy. We describe a case of successful use of Bortezomib and plasma exchange in a patient with ES and APS refractory to standard therapy. Thirty-two-year-old male who presented episodes of relapsing hemolytic anemia, pancytopenia and multiple thrombosis with positive direct and indirect antiglobulin test result, lupus anticoagulant and medium titer of anti-beta-2-glycoprotein 1 and anti-cardiolipin antibodies was diagnosed with ES and SLE with secondary APS. High-dose therapy by steroids and Cyclosporin A were started with temporary improvement. There was also no stable improvement with Rituximab and Cyclophosphamide. Bortezomib in combination with cyclosporine A and plasma exchange was introduced. He had stable improvement in hematological parameters with no evidence of relapse of hemolytic crisis or thrombosis during a follow-up for 1 year.

Introduction

The presence of autoimmune hemolytic anemia (AIHA) in conjunction with immune-mediated thrombocytopenia characterizes Evans syndrome (ES). Although anemia and thrombocytopenia are common features of systemic lupus erythematosus (SLE), ES is a rare manifestation in systemic lupus SLE. Coexistence of antiphospholipid syndrome (APS) with AIHA and APS with ES displays a frequency of 4% and 10%, respectively [1,2]. As the first-line therapy for ES glucocorticosteroids (GC) and intravenous immunoglobulin (IVIG) are typically used. The second-line therapy includes immunosuppressive agents, the monoclonal antibody Rituximab, or chemotherapy (vincristine). In 2008 Rückert et al. reported a case of APS with ES successfully treated with a combination of rituximab and cyclophosphamide [3]. Here, we present a clinical history of refractory ES and SLE with APS successfully treated with Bortezomib (BTZ) that led to steady clinical and serological improvement for both syndromes.

Section snippets

Clinical case

A 32-year-old man with history of recurrent deep vein thrombosis was admitted to our institution with fever, dyspnea and episode of nasal bleeding, life-threatening hemolytic anemia (Hb = 68 g/L) and pancytopenia (RBC = 2,29 ∗ 109/L, WBC = 1,75 ∗ 10^9/L, PP = 4800/μL). Laboratory signs of hemolysis were found (lactate dehydrogenase (LDH) was 655 U/L, reticulocytes were 5%, direct and indirect antiglobulin test were positive). The enzyme-linked immunosorbent assay (ELISA kits, Orgentec

Discussion

We present a case report of a stable remission of relapsing ES and SLE- APS treated with Bortezomib and plasma exchange after non responsiveness to a combination therapy with medium/high dose GC, Cyclosporine A, Rituximab and Cyclophosphamide.

Considering the presence of oral mucosal ulceration, no-erosive arthritis, serositis (pleuritis and pericarditis), hematologic syndrome (leucopenia, thrombocytopenia, hemolytic anemia), immunologic syndrome (aPL, low level of complement), CNS disorder

Conclusion

Unfortunately, we did not observe stable decrease of anti-beta-2-glycoprotein 1 and anti-cardiolipin during BTZ therapy. Still is not clear the pharmacological mechanism of action of PIs in these autoantibody-mediated disorders, since BTZ inhibited the production of the anti-erythrocyte antibodies but this was not the case for antiphospholipid antibodies. A combination of plasma exchange followed by BTZ, low GC doses and cyclosporine A may be a rescue therapy in resistant cases of SLE with APS

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acknowledgments

The authors would like to thank Professor P.L. Meroni for critical review of the manuscript.

Funding

This work is supported in part by the grant of the Government of the Russian Federation for the state support of scientific research carried out under the supervision of leading scientists, agreement 14.W03.31.0009, on the basis of SPbU projects 15.34.3.2017 and 15.64.785.2017.

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Brief CommunicationRelapsing Evans syndrome and systemic lupus erythematosus with antiphospholipid syndrome treated with Bortezomib in combination with plasma exchange

Abstract

Introduction

Section snippets

Clinical case

Discussion

Conclusion

Declaration of conflicting interests

Acknowledgments

Funding

Blood

Rheumatology (Oxford)

Blood Rev.

The “primary” antiphospholipid syndrome: major clinical and serological features

Medicine (Baltimore)

Primary antiphospholipid syndrome: features of patients with raised anticardiolipin antibodies and no other disorder

Ann. Rheum. Dis.

Brief Communication
Relapsing Evans syndrome and systemic lupus erythematosus with antiphospholipid syndrome treated with Bortezomib in combination with plasma exchange