Successful Treatment of Catastrophic Antiphospholipid Syndrome Using Rituximab: Case Report and Review of the Literature

Abstract

Background: Kidney involvement is a frequent complication of systemic lupus erythematosus (SLE) and kidney biopsy is essential in differentiating lupus nephritis (LN) from thrombotic microangiopathy (TMA) secondary to antiphospholipid autoantibodies (aPL). Association between antiphospholipid syndrome (APS) and acquired hemophilia due to inhibitors was very rarely described in SLE patients. Case presentation: We present the case of a 61-year-old male diagnosed with SLE who acquired deficiency of clotting factor VIII due to circulating inhibitors, admitted for acute kidney injury (AKI), microangiopathic hemolytic anemia, thrombocytopenia, and diplopia. Kidney biopsy showed TMA due to APS, but no signs of LN. Head computed tomography identified low dense areas in the white matter, suggesting small blood vessels’ involvement. A diagnosis of probable catastrophic antiphospholipid syndrome (CAPS) was established and treatment with low molecular weight heparin, intravenous methylprednisolone, plasmapheresis, and rituximab was initiated, followed by resolution of AKI, diplopia, and TMA with complete depletion of CD19+B-lymphocytes (CD19+B-Ly) after one month. We further review the current knowledge regarding pathogenesis and management of CAPS in SLE patients. Conclusions: Targeted therapy was possible after kidney biopsy, improving renal and general prognosis. CD19+B-Ly repopulation preceded biological relapse, so monitoring of CD19+B-Ly may serve as a tool to predict relapses and guide rituximab therapy.

Eculizumab therapy and complement regulation in a case of resistant catastrophic antiphospholipid syndrome

“…Management options for resistant CAPS include escalation of immunosuppression, with cyclophosphamide, rituximab or eculizumab 12 13. Cyclophosphamide may be chosen where CAPS is secondary to SLE, alongside other disease-specific therapies including hydroxychloroquine 13 14. Cyclophosphamide was initiated in our patient while her diagnostic work-up was in progress, with an initial suspicion for underlying SLE although serology was later negative.…”

“…Management options for resistant CAPS include escalation of immunosuppression, with cyclophosphamide, rituximab or eculizumab 12 13. Cyclophosphamide may be chosen where CAPS is secondary to SLE, alongside other disease-specific therapies including hydroxychloroquine 13 14.…”

“…Rituximab is an anti-CD20 monoclonal antibody resulting in B-cell depletion and possibly increasing regulatory B-cell proportion, to decrease the pathogenic immune spiral 12 13. However, this process can take weeks for peak clinical effect, as opposed to eculizumab 18.…”

Corticosteroids, Plasmapheresis, Argatroban, Rituximab, and Sirolimus Provided Clinical Benefit for Catastrophic Antiphospholipid Syndrome in a Patient with a History of Heparin-Induced Thrombocytopenia

“…While some studies show no substantial change in autoantibody levels after rituximab, some of the features of CAPS may be due to high levels of acute phase reactants and cytokines [11]. Tus, by reducing the number of circulating B cells and normalizing their distribution, rituximab may lower the levels of these cytokines [11]. In other words, antibody titers alone may not tell the whole story.…”

“…Moreover, there are no randomized, prospective, or controlled clinical trials that have studied plasmapheresis (or TPE, therapeutic plasma exchange) for CAPS [4]. In addition, only a few dozen total patients who have received rituximab for either CAPS or APS have been reported [9][10][11]. Tus, the evidence is relatively sparse overall and especially for patients who have received both plasmapheresis and rituximab.…”