Warm AIHA is usually caused by IgG antibodies. Cases of AIHA caused by other autoantibodies, such as warm-reactive IgM or IgA, have rarely been reported in the literature [
5]. In these patients, often, warm IgM autoantibodies and warm IgA autoantibodies are found either alone or in combination with IgG autoantibodies [
5]. AIHA caused by both warm-reactive IgM and IgA autoantibodies is exceedingly rare [
5]. Branstetter
et al. [
5] reported the first case of severe AIHA caused by warm-reactive IgM and IgA autoantibodies in an otherwise healthy 3-month-old child. In our case, we highlight an unusual combination of autoantibodies causing AIHA in a pediatric patient. In fact, the DAT showed the presence of multiple warm-reactive autoantibodies composed of IgM, IgG, IgA, and C3d autoantibodies. The presence of warm IgM antibodies could explain the severity of our case and especially the resistance to steroids [
5‐
7]. In fact, unlike typical warm-reactive IgG-mediated AIHA, warm-reactive IgM-mediated AIHA is often steroid refractory and unresponsive to IVIG [
5]. Splenectomy and rituximab are the only second-line treatments that could be used in these cases with a proven short-term efficacy [
4]. However, splenectomy is associated with surgical and infective complications. Rituximab is a humanized chimeric anti-CD20 monoclonal antibody, directed against CD20, which rapidly depletes B cells from the blood, lymph nodes, and bone marrow [
8]. Its
in vivo mechanism of action includes complement-mediated cytotoxicity, antibody-dependent cytotoxicity, apoptosis, and inhibition of B cell proliferation [
8,
9]. The dosage used is 375 mg/m
2 administered weekly for 4 weeks in total. This drug was first developed for the treatment of hematological malignancies, such as aggressive non-Hodgkin lymphoma and chronic lymphocytic leukemia. The efficacy of rituximab in the treatment of pediatric patients with AIHA has been proved in a few studies [
9‐
11]. The largest series of AIHA treated by rituximab in children was described by Zecca
et al. [
10]. In this study 15 children with refractory AIHA were treated with rituximab. Of these 15 children, 13 (87%) responded, whereas 2 patients did not show any improvement. Two months after treatment, the median Hb level of patients had increased from 7.7 g/dL to 11.8 g/dL and the median absolute reticulocyte count had decreased from 236 to 109 × 10
9/L. The interval from diagnosis to treatment ranged from 2.1 to 98.5 months and the interval from treatment to response varied from 5 to 72 days. All children received two or more courses of immunosuppressive treatment, and a splenectomy was performed on two patients in order to control the hemolysis. Only three responder patients relapsed and received a second course of rituximab, achieving a disease remission. Quartier
et al. [
9] evaluated the efficacy of rituximab in a group of six children with AIHA. The duration of AIHA before the use of rituximab varied from 3 to 10 months. All patients achieved sustained remission after rituximab. In these two studies, patients had no severe hemolysis that could threaten their life. The type of anemia was warm-reactive IgG-mediated AIHA in the majority of cases, except one of them who had cold-reactive IgM-mediated AIHA. Our observation is particular because her anemia was very severe and poorly tolerated. The severity of the hemolysis in this case could be explained by the presence of warm IgM autoantibodies. The child required immediate treatment with multiple packed RBCs transfusions (at least one transfusion/day), IVIG, and corticosteroids. However, all of these treatments failed. Plasmapheresis may be considered in such severe forms. However, it has a short-term profit, a high rate of morbidity, and mortality. Thus, we decided to treat our patient with rituximab. This drug is effective in acute AIHA with profound hemolysis refractory to conventional therapies. Moreover, it may spare the patient from plasmapheresis in such a critical situation with a sustained remission in most cases.