Letter to the Editor
Macrophage Activation Syndrome: Experience in the Questioned Role of Etoposide
Síndrome de activación macrofágica: experiencia sobre el cuestionado papel del etopósido
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Conde, Karla P. Aedo, Tatiana Miraval-Niño de Guzmán" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Leslye F." "apellidos" => "Conde" "email" => array:1 [ 0 => "leslyecondeb@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Karla P." "apellidos" => "Aedo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Tatiana" "apellidos" => "Miraval-Niño de Guzmán" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima, Peru" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Enfermedades Sistémicas, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de activación macrofágica: experiencia sobre el cuestionado papel del etopósido" ] ] "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" => 682 "Ancho" => 1546 "Tamanyo" => 99637 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Bone marrow aspiration. The cytopathology of this tissue shows active hemophagocytosis on the part of macrophages (hematoxylin-eosin staining, 1000×).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Reactive hemophagocytic lymphohistiocytosis (HLH), or macrophage activation syndrome (MAS), is an unusual complication of systemic inflammatory diseases.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Its association with juvenile idiopathic arthritis (JIA) is rare and treatment must be immediate. We report the case of a girl in whom we detected this association and treated it successfully with a drug that is not first-line therapy because of its potential adverse effects.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 9-year-old girl who had recently been diagnosed as having JIA. She was admitted to the hospital after a 3-day history of persistent fever (40<span class="elsevierStyleHsp" style=""></span>°C) and generalized facial edema, presumably associated with methotrexate she was taking, a treatment that was interrupted. At admission, she was pale, had painful hepatosplenomegaly and an increase in the volume of several joints. Laboratory tests showed pancytopenia (hemoglobin 6.4<span class="elsevierStyleHsp" style=""></span>g/dL; 132,000 platelets/mm<span class="elsevierStyleSup">3</span> and 1080 neutrophils/mm<span class="elsevierStyleSup">3</span>), prothrombin time and partial thromboplastin time were increased (16.8″ and 59.2″, respectively) and fibrinogen was decreased (164.7<span class="elsevierStyleHsp" style=""></span>mg/dL).</p><p id="par0015" class="elsevierStylePara elsevierViewall">Treatment was begun with methylprednisolone and paracetamol, but the fever persisted. The suspicion of MAS led to tests that revealed hypertriglyceridemia (291<span class="elsevierStyleHsp" style=""></span>mg/dL) and elevated ferritin (9579<span class="elsevierStyleHsp" style=""></span>mg/mL). Myelogram disclosed bone marrow with spicules, activated macrophages with cytophagocytosis of cell debris and erythroblast nuclei (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Bacterial cultures of urine, blood and bone marrow were negative. It was decided to begin treatment with methylprednisolone pulses (1000<span class="elsevierStyleHsp" style=""></span>mg/day for 3 days) plus cyclosporine A (2<span class="elsevierStyleHsp" style=""></span>mg/kg body weight [bw]/day). The general status of the patient improved and the fever disappeared; however, the biochemical profile showed no changes. Thus, we started to administer intravenous etoposide (150<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/day), the dose of cyclosporine A was increased (4<span class="elsevierStyleHsp" style=""></span>mg/kg bw/day) and prednisone therapy was maintained (1<span class="elsevierStyleHsp" style=""></span>mg/kg bw/day). The patient had a favorable clinical and biochemical course. Twelve days after receiving etoposide, she was asymptomatic and was discharged. Thereafter, we continued monitoring the patient for clinical and biochemical follow-up, which corroborated her improvement through the laboratory results (acute-phase reactants at normal levels).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Macrophage activation syndrome is associated with a high mortality rate (22%).<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">2,3</span></a> For this reason, early diagnosis and proper treatment are essential to ensure the best possible prognosis. Etoposide, also referred to as VP-16, has an accelerated cellular mitosis and induces apoptosis. The cytotoxicity it generates causes alopecia, constipation, nausea, myelosuppression and secondary malignancy (leukemia); these effects are potentiated with the simultaneous use of cyclosporine A. For refractory HLH, it is recommended that there be an initial induction phase (2 weeks) with etoposide, cyclosporine A and dexamethasone,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">4,5</span></a> to be followed by 6 weeks of etoposide, if necessary.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> The utilization of this medication is still controversial, and there is a lack of consensus as to fully recommending its use because of paradoxical effects involving myelosuppression. This alternative is recommended only in refractory cases.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5,6</span></a> Etoposide has been previously utilized in 8 patients with MAS and induced a favorable and rapid response in each case, with no adverse effects.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">7–9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In this instance, etoposide was added because the patient showed resistance to standard therapy. She received only 3 doses because of its high toxicity and the development of pancytopenia. The strategy we employed was successful; however, it proposes a strict control of the etoposide combined with the suggested treatment.</p><p id="par0030" class="elsevierStylePara elsevierViewall">We presented MAS, a condition that is not very common, that was refractory to standard treatment. Thus, we opted for the use of etoposide. The patient we report progressed favorably. Nevertheless, as it is just a single case, we do not recommend generalizing this approach. The outcome can be taken into account in future studies that attempt to establish a complete scheme for the treatment of refractory reactive HLH.</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: Conde LF, Aedo KP, Miraval-Niño de Guzmán T. Síndrome de activación macrofágica: experiencia sobre el cuestionado papel del etopósido. Reumatol Clín. 2017;13:239–240.</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" => 682 "Ancho" => 1546 "Tamanyo" => 99637 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Bone marrow aspiration. The cytopathology of this tissue shows active hemophagocytosis on the part of macrophages (hematoxylin-eosin staining, 1000×).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Síndrome de activación de macrófago como manifestación inicial de lupus eritematoso sistémico severo de inicio juvenil. Respuesta favorable a ciclofosfamida" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Torres" 1 => "E. Solís" 2 => "M. Zeferino" 3 => "C. Céspedes" 4 => "B. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 16 | 24 |
| 2024 October | 58 | 32 | 90 |
| 2024 September | 67 | 21 | 88 |
| 2024 August | 73 | 34 | 107 |
| 2024 July | 54 | 29 | 83 |
| 2024 June | 51 | 33 | 84 |
| 2024 May | 53 | 41 | 94 |
| 2024 April | 67 | 21 | 88 |
| 2024 March | 51 | 34 | 85 |
| 2024 February | 41 | 28 | 69 |
| 2024 January | 50 | 25 | 75 |
| 2023 December | 36 | 22 | 58 |
| 2023 November | 38 | 22 | 60 |
| 2023 October | 59 | 33 | 92 |
| 2023 September | 73 | 37 | 110 |
| 2023 August | 49 | 14 | 63 |
| 2023 July | 51 | 23 | 74 |
| 2023 June | 35 | 24 | 59 |
| 2023 May | 50 | 36 | 86 |
| 2023 April | 43 | 5 | 48 |
| 2023 March | 76 | 29 | 105 |
| 2023 February | 65 | 28 | 93 |
| 2023 January | 45 | 6 | 51 |
| 2022 December | 60 | 42 | 102 |
| 2022 November | 73 | 28 | 101 |
| 2022 October | 79 | 30 | 109 |
| 2022 September | 59 | 39 | 98 |
| 2022 August | 48 | 42 | 90 |
| 2022 July | 49 | 36 | 85 |
| 2022 June | 50 | 26 | 76 |
| 2022 May | 71 | 36 | 107 |
| 2022 April | 60 | 44 | 104 |
| 2022 March | 65 | 47 | 112 |
| 2022 February | 73 | 35 | 108 |
| 2022 January | 66 | 42 | 108 |
| 2021 December | 44 | 38 | 82 |
| 2021 November | 43 | 43 | 86 |
| 2021 October | 94 | 60 | 154 |
| 2021 September | 63 | 38 | 101 |
| 2021 August | 52 | 43 | 95 |
| 2021 July | 46 | 22 | 68 |
| 2021 June | 60 | 24 | 84 |
| 2021 May | 88 | 60 | 148 |
| 2021 April | 174 | 79 | 253 |
| 2021 March | 130 | 18 | 148 |
| 2021 February | 89 | 30 | 119 |
| 2021 January | 63 | 14 | 77 |
| 2020 December | 79 | 14 | 93 |
| 2020 November | 51 | 17 | 68 |
| 2020 October | 24 | 10 | 34 |
| 2020 September | 73 | 27 | 100 |
| 2020 August | 80 | 21 | 101 |
| 2020 July | 46 | 19 | 65 |
| 2020 June | 32 | 22 | 54 |
| 2020 May | 28 | 17 | 45 |
| 2020 April | 19 | 12 | 31 |
| 2020 March | 18 | 4 | 22 |
| 2020 February | 1 | 0 | 1 |
| 2018 May | 4 | 1 | 5 |
| 2018 April | 54 | 12 | 66 |
| 2018 March | 83 | 7 | 90 |
| 2018 February | 21 | 5 | 26 |
| 2018 January | 17 | 3 | 20 |
| 2017 December | 33 | 13 | 46 |
| 2017 November | 28 | 17 | 45 |
| 2017 October | 24 | 15 | 39 |
| 2017 September | 20 | 13 | 33 |
| 2017 August | 40 | 27 | 67 |
| 2017 July | 42 | 33 | 75 |
| 2017 June | 5 | 9 | 14 |
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