Letter to the Editor
Rituximab in Refractory Autoimmune Hemolytic Anemia in Systemic Lupus Erythematosus
Rituximab en la anemia hemolítica autoinmune refractaria en lupus eritematoso sistémico
María Pavo-Blanco
, Marta Novella-Navarro, Rafael Cáliz-Cáliz, Miguel A. Ferrer-González
Corresponding author
Servicio de Reumatología, Complejo Hospitalario Universitario de Granada, Granada, Spain
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Ferrer-González" "autores" => array:4 [ 0 => array:4 [ "nombre" => "María" "apellidos" => "Pavo-Blanco" "email" => array:1 [ 0 => "mpb.mblanco@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Marta" "apellidos" => "Novella-Navarro" ] 2 => array:2 [ "nombre" => "Rafael" "apellidos" => "Cáliz-Cáliz" ] 3 => array:2 [ "nombre" => "Miguel A." "apellidos" => "Ferrer-González" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Reumatología, Complejo Hospitalario Universitario de Granada, Granada, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Rituximab en la anemia hemolítica autoinmune refractaria en lupus eritematoso sistémico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 911 "Ancho" => 1571 "Tamanyo" => 134119 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes in the hemoglobin levels with rituximab (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/weekly for 4 weeks). Stabilization in week 3 of treatment and tapering of corticosteroids to 5<span class="elsevierStyleHsp" style=""></span>mg/day.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Autoimmune hemolytic anemia (AIHA) is a common manifestation in systemic lupus erythematosus (SLE), and is often refractory to standard treatment. Corticosteroids constitute the first-line treatment, with a rate of initial response of 70%–85%, although the response is maintained 1 year later in less than 20%.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> In cases of refractory AIHA, splenectomy has traditionally been the second-line treatment, with a response rate of 60%–70%, resulting in a considerable increase in the risk of severe infections.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> In cases of refractory disease or in which splenectomy is contraindicated, immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine A and, in recent years, rituximab (anti-[cluster of differentiation] CD20 monoclonal antibody) can be employed with a good response.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> We report two cases of refractory AIHA secondary to SLE treated with rituximab.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Case no. 1: The patient was a 37-year-old woman who had been diagnosed with SLE 10 years ago, and was being treated with hydroxychloroquine (200<span class="elsevierStyleHsp" style=""></span>mg/day). She came to the emergency department with severe weakness, arthralgia and mucocutaneous pallor. Laboratory studies revealed a hemoglobin (Hb) level of 5<span class="elsevierStyleHsp" style=""></span>g/dL and a mean corpuscular volume of 81<span class="elsevierStyleHsp" style=""></span>fL, and thus required a transfusion of packed red cells. We found her total bilirubin (TB) to be 2.3<span class="elsevierStyleHsp" style=""></span>mg/dL at the expense of indirect bilirubin, haptoglobin of 1<span class="elsevierStyleHsp" style=""></span>mg/dL, lactate dehydrogenase (LDH) of 856<span class="elsevierStyleHsp" style=""></span>U/L and positivity on direct and indirect Coombs tests. The patient was diagnosed with AIHA and treatment was begun with corticosteroids (1<span class="elsevierStyleHsp" style=""></span>mg/kg body weight/day) and azathioprine (50<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h). The disease became chronic, with corticosteroid-dependent flares.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Case no. 2: The patient was a 19-year-old woman who had recently been diagnosed with SLE and was being treated with azathioprine (50<span class="elsevierStyleHsp" style=""></span>mg/day) and hydroxychloroquine (200<span class="elsevierStyleHsp" style=""></span>mg/day). She came to the emergency department with a fever of 38.5<span class="elsevierStyleHsp" style=""></span>°C, deterioration of her general health status, polyarthralgia and weakness. Laboratory studies revealed a Hb level of 7.5<span class="elsevierStyleHsp" style=""></span>g/dL, TB of 2.16<span class="elsevierStyleHsp" style=""></span>mg/dL with a predominance of indirect bilirubin and LDH was 678<span class="elsevierStyleHsp" style=""></span>U/L. She was diagnosed with AIHA and was treated with corticosteroids at a dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg body weight/day. She progressed favorably, but subsequently had further hemolytic crises upon corticosteroid tapering.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In both cases, given the persistence of relapses despite corticosteroid and immunosuppressive therapy, it was proposed to initiate treatment with rituximab at a weekly dose of 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> for 4 weeks, and the outcome was favorable and rapid. The treatment maintained Hb levels over 12.5<span class="elsevierStyleHsp" style=""></span>g/dL after 10 and 12 months, respectively (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In the first patient, we administered a second course of rituximab 1 year later; however, the second patient achieved a response that she continues to maintain.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The efficacy of rituximab in autoimmune hematologic disorders is probably due not only to the elimination of the pathogenic autoantibody, but to B-cell depletion as antigen-presenting cells and their conversion to producers of cytokines.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Although the impact of rituximab as the first-line treatment of patients with AIHA is still unknown, it has been found to be effective as second-line therapy in prospective and retrospective studies,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6–8</span></a> with rates of relapse-free survival that range from 64% to 100% at 36 months. Moreover, the rate of response to therapy with a combination of rituximab and corticosteroids is significantly higher than that of corticosteroid monotherapy.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Autoimmune hemolytic anemia is a serious pathological condition. Thus, an early diagnosis is important, as is intensive treatment to detain the hemolytic process. In our experience, the use of rituximab resulted in a rapid and durable response that continued over time in two patients of similar characteristics. We consider, in this respect, and according to the literature reviewed, that the initiation of this drug should not be delayed.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7,10</span></a> Given the safety and tolerability of rituximab,<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a> its use as the second-line of treatment should be recommended, instead of the utilization of immunosuppressive agents that have a greater toxicity or rather than splenectomy.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pavo-Blanco M, Novella-Navarro M, Cáliz-Cáliz R, Ferrer-González MA. Rituximab en la anemia hemolítica autoinmune refractaria en lupus eritematoso sistémico. Reumatol Clín. 2018;14:248–249.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 911 "Ancho" => 1571 "Tamanyo" => 134119 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes in the hemoglobin levels with rituximab (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/weekly for 4 weeks). Stabilization in week 3 of treatment and tapering of corticosteroids to 5<span class="elsevierStyleHsp" style=""></span>mg/day.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of rituximab in adults with warm antibody autoimmune hemolytic anaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Dierickx" 1 => "A. Kentos" 2 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 13 | 3 | 16 |
| 2024 October | 169 | 45 | 214 |
| 2024 September | 233 | 57 | 290 |
| 2024 August | 187 | 52 | 239 |
| 2024 July | 237 | 51 | 288 |
| 2024 June | 192 | 49 | 241 |
| 2024 May | 162 | 54 | 216 |
| 2024 April | 167 | 37 | 204 |
| 2024 March | 127 | 38 | 165 |
| 2024 February | 120 | 33 | 153 |
| 2024 January | 137 | 33 | 170 |
| 2023 December | 100 | 33 | 133 |
| 2023 November | 153 | 83 | 236 |
| 2023 October | 167 | 65 | 232 |
| 2023 September | 183 | 64 | 247 |
| 2023 August | 120 | 28 | 148 |
| 2023 July | 135 | 40 | 175 |
| 2023 June | 130 | 31 | 161 |
| 2023 May | 117 | 42 | 159 |
| 2023 April | 111 | 26 | 137 |
| 2023 March | 138 | 51 | 189 |
| 2023 February | 120 | 36 | 156 |
| 2023 January | 127 | 25 | 152 |
| 2022 December | 126 | 43 | 169 |
| 2022 November | 144 | 37 | 181 |
| 2022 October | 150 | 48 | 198 |
| 2022 September | 131 | 66 | 197 |
| 2022 August | 129 | 56 | 185 |
| 2022 July | 148 | 47 | 195 |
| 2022 June | 159 | 64 | 223 |
| 2022 May | 167 | 39 | 206 |
| 2022 April | 204 | 59 | 263 |
| 2022 March | 245 | 58 | 303 |
| 2022 February | 229 | 59 | 288 |
| 2022 January | 158 | 73 | 231 |
| 2021 December | 134 | 53 | 187 |
| 2021 November | 127 | 51 | 178 |
| 2021 October | 166 | 57 | 223 |
| 2021 September | 118 | 58 | 176 |
| 2021 August | 113 | 43 | 156 |
| 2021 July | 114 | 28 | 142 |
| 2021 June | 118 | 37 | 155 |
| 2021 May | 153 | 50 | 203 |
| 2021 April | 276 | 99 | 375 |
| 2021 March | 163 | 27 | 190 |
| 2021 February | 121 | 34 | 155 |
| 2021 January | 122 | 39 | 161 |
| 2020 December | 217 | 27 | 244 |
| 2020 November | 92 | 34 | 126 |
| 2020 October | 67 | 20 | 87 |
| 2020 September | 54 | 33 | 87 |
| 2020 August | 35 | 19 | 54 |
| 2020 July | 32 | 17 | 49 |
| 2020 June | 53 | 19 | 72 |
| 2020 May | 32 | 22 | 54 |
| 2020 April | 17 | 20 | 37 |
| 2020 March | 20 | 4 | 24 |
| 2019 March | 1 | 2 | 3 |
| 2018 November | 0 | 1 | 1 |
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