Use of eculizumab in a systemic lupus erythemathosus patient presenting thrombotic microangiopathy and heterozygous deletion in CFHR1-CFHR3. A case report and systematic review

Abstract

The association of thrombotic microangiopathy (TMA) with systemic lupus erythematosus (SLE) has been described in 0.5 to 10% of cases, and patients present worse outcome. TMA is described as the association of microangiopathic hemolytic anemia, thrombocytopenia, and an organ injury, frequently the kidney. This study describes a successful case of use of eculizumab in a patient with SLE and TMA refractory to standard therapy, and provides a literature review. Case description and search in PubMed and MEDLINE using systemic lupus erythemathous and/or antiphospholipid syndrome (APS) and eculizumab retrieved 15 case reports. Eighteen-year-old female presented acute renal failure and TMA and was diagnosed with SLE. Steroids and IV cyclophosphamide were started together with plasma exchange. After 55 days, she still persisted with microangiopathic anemia, thrombocytopenia, and anuria, and eculizumab was introduced. She had rapid improvement in hematological parameters, and dialysis was discontinued 25 days after the first dose. Genetic analysis showed large heterozygous deletion encompassing the entire CFHR1 and CFHR3, a finding previously associated with patients presenting atypical hemolytic-uremic syndrome (aHUS). Twenty patients who received eculizumab with SLE and/or APS have been published to date: 11 were female and mean age at presentation was 31 years. Seven out of the 20 patients presented only SLE, 5 patients only APS and 8 patients both SLE and APS. Eighteen patients underwent plasma exchange, with a mean of 20 (4-120) sessions per patient. Thirteen patients received rituximab. Hematological response was evident in 100% and kidney recovery in 85% of patients. The terminal complement blockade with eculizumab is an optional treatment for patients with SLE and/or APS presenting TMA and refractory to current immunosuppression therapies. Genetic testing may help recognize patients with aHUS and SLE/APS and therefore help to determine length of treatment with eculizumab.

Renal microvascular lesions in lupus nephritis

“…A recent study reviewed 20 patients who received eculizumab with SLE and/or APS until 2017, where a hematological response was evident in 100% of the patients, and kidney recovery was evident in 85% of the patients. This study suggested that eculizumab might be a potential alternative treatment for patients with SLE and/or APS presenting with TMA and who were refractory to current immunosuppression therapies [57].…”

A systematic review of the role of eculizumab in systemic lupus erythematosus-associated thrombotic microangiopathy

“…Six further articles were excluded at this stage (involving 7 patients): two involved the same patient cases duplicated between published journals and published conference abstracts, one study reported a patient with SLE who was excluded before the end of the study, one study looked at four patients, two of whom had lupus but the results were not stratified by diagnosis and so were uninterpretable, one study reported a patient with SLE who was given eculizumab to treat an episode of aHUS caused by Dengue fever [25], and one study reported a patient with inactive SLE who was given eculizumab to treat Degos disease [26]. Therefore, 14 papers were included in the systematic literature review [21,[27][28][29][30][31][32][33][34][35][36][37][38][39] (Fig. 1).…”

Management and treatment of glomerular diseases (part 2): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

“…136,137 Anticomplement therapies may be considered in catastrophic APS, thrombocytopenic purpura, complement-mediated TMA, and recurrent TMA in an allograft. [138][139][140][141] Anticoagulation remains the standard of care when APS is present. 142 However, the impact of anticoagulation on renal lesions is unclear, and many patients experience a decline in kidney function despite therapeutic anticoagulation.…”