Eculizumab Responsive Atypical Hemolytic Uremic Syndrome Triggered by a Multisystem Lupus Flare
- Trainee Case Reports - V
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1202 Glomerular Diseases: Immunology and Inflammation
- Syed, Bushra, Cleveland Clinic, Cleveland, Ohio, United States
- Rincon-Choles, Hernan, Cleveland Clinic, Cleveland, Ohio, United States
- Calle, Juan C., Cleveland Clinic, Cleveland, Ohio, United States
Uninhibited alternative complement pathway activation leads to complement mediated hemolytic uremic syndrome. Infections, pregnancy, drugs or ongoing lupus activity can trigger this cascade. Concurrent occurrence of aHUS with lupus is rare. We present a case of aHUS with hematological and renal responsiveness to eculizumab
A 25-year-old Caucasian female with HTN, IgA deficiency and class III A + V lupus nephritis on maintenance prednisone, mycophenolate and hydroxychloroquine, presented with abdominal pain and encephalopathy.
Workup showed Hb of 7.9g/dl,thrombocytopenia,schistocytes, low haptoglobin and elevated LDH. TTP and autoimmune hemolysis were ruled out.Hypocomplementemia and positive dsDNA and ANA were noted.Soluble membrane attack complex level was elevated and membrane cofactor protein was low. Factors H , I , B were within normal limits. Factor H autoantibody, antiphospholipid antibody panel and scleroderma antibodies were negative. Creatinine peaked at 5 mg/dl (baseline1.2mg/dl )and she had nephrotic range proteinuria -6g.
Hemorrhagic pancreatitis and cerebritis seen on imaging. Infectious etiologies were ruled out. Renal biopsy showed Class III and V Lupus with moderate activity , thrombotic microangiopathy and diffuse ATN.
Despite initiation of pulse dose steroids, cyclophosphamide she developed multisystem organ failure requiring mechanical ventilation, renal replacement therapy and multiple transfusions. Plasma exchange was deferred due to IgA deficiency. Subsequently initiated on eculizumab with improvement in hematological parameters after 2 doses. Renal recovery with discontniuation of dialysis occurred after 4 doses. She remains in remission on prednisone, MMF, hydroxychloroquine and eculizumab at 9 month follow up with a Cr of 0.7 and proteinuria of 0.5g.
Active Lupus serves as a driver for aHUS. Thrombotic microangiopathy is an independent risk factor for poor outcome in lupus nephritis with mortality rates of over 30% despite the use of multimodal treatment strategies. Terminal complement inhibitors can effectively induce hematological and renal response and there should be a low clinical threshold to initiate eculizumab in the setting of refractory disease. Data regarding the optimal dosing schedule, monitoring and treatment end points is lacking and needs additional studies.