Life threatening steroid-resistant autoimmune anemia successfully treated with rituximab: a case report.

To the Editor: A 17-year-old woman was admitted for asthenia and increasing dyspnea. She had had an immune thrombocytopenia treated with intravenous immunoglobulins and corticosteroids but she had no treatment for 5 years. The examination revealed only pallor and dyspnea to minor exercise. Laboratory investigations showed auto-immune hemolytic anemia, with: hemoglobin 50 g/L, reticulocytes 130 G/L, increased lactate deshydrogenase (1526 U/L) and unconjugated bilirubinemia (195 mmol/L), and low haptoglobin level (0.09 g/L). The direct antiglobulin test was positive (anti-IgGþþþ, anti-C3dþþ). Platelets level was 190 G/L, leukocytes 5.5 G/L. C reactive protein was 26 g/L. Bacteriological tests and virus serologies were negative. Antinuclear antibodies were 1/80. She received three pulses of intravenous methylprednisolone (1 g/day then 1.5 mg/kg/day), and red blood cell (RBC) transfusions, but the hemoglobin level fell to 30 g/L (Fig. 1). Simultaneously, she had several lypothymias, electric signs of myocardial suffering and increased level of troponin I level (0.18 mg/L, N < 0.05) which led to transfer in intensive care unit. Despite methylprednisolone increased to 2 mg/kg/day, associated with massive (17) RBC transfusions, hemoglobin level stayed low around 50 G/L. Platelet count fell to 70 G/L, without hemorrhagic syndrome nor consommation coagulopathy. Bone marrow aspirate demonstrated the peripheral origin of the cytopenias. Splenectomy was proposed but the patient refused. Mycophenolate mofetil (MMF) was added 7 days after hospital admission but because of the long action delay of MMF, rituximab was added, at the dose of 375 mg/m weekly. The treatment was well tolerated. Hemoglobin level rose up and reached 120 G/L at the fourth course of rituximab, with normalization of platelet count and hemolysis parameters (Fig. 1). No need of RBC was noted after the second perfusion. Corticosteroids were rapidly tapered, as the AIHA was considered to be corticosteroid-resistant and MMF was maintained 1 year but the patient stopped it deliberately. Two years after the onset, the patient is well with no treatment. The first-line therapy in AIHA is usually corticosteroids, but relapses are common. Immunosuppressive agents (ciclosporin, MMF, azathioprine), or immunoglobulins have been used in refractory cases but splenectomy remains the most effective alternative therapy for chronic refractory autoimmune cytopenia or emergency situation [1]. Rituximab is a chimeric monoclonal antibody targeting CD20 antigen on the surface of B lymphocytes, successfully used in malignant lymphoproliferative disorders and autoimmune diseases. The main side effects are infusion-related toxicities. Its efficacy in refractory immune thrombocytopenia has been reported [2], but data in warm AIHA are limited [3,4] and focus on chronic refractory AIHA. To our knowledge, life-saving use of anti-CD20 monoclonal antibody has been described in only one case of systemic lupus erythematosus with severe warm AIHA, refractory to various treatments [5]. In this case, we used rituximab because of the worsening of the patient’s condition despite corticosteroids, the disapproval about splenectomy, the action delay of MMF, and the life threatening situation. Rituximab seemed to be the treatment with the shortest action delay. Rituximab should be considered as a life saving therapy, in corticosteroid resistant AIHA.