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"documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2015;145:505-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Fever induced by hydroxycarbamide" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "505" "paginaFinal" => "506" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fiebre por hidroxiurea" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Eva Lizarralde Palacios, Alfonso Gutiérrez Macías, Mayte Rámiz Martínez, Mikel Escalante Boleas" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Eva" "apellidos" => "Lizarralde Palacios" ] 1 => array:2 [ "nombre" => "Alfonso" "apellidos" => "Gutiérrez Macías" ] 2 => array:2 [ "nombre" => "Mayte" "apellidos" => "Rámiz Martínez" ] 3 => array:2 [ "nombre" => "Mikel" "apellidos" => "Escalante Boleas" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S002577531500086X" "doi" => "10.1016/j.medcli.2015.01.022" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577531500086X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616300365?idApp=UINPBA00004N" "url" => "/23870206/0000014500000011/v1_201604300039/S2387020616300365/v1_201604300039/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Recurrent diffuse alveolar hemorrhage in systemic lupus erythematosus treated with rituximab and immunoglobulins" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "507" "paginaFinal" => "508" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Águeda Prior-Español, Melania Martínez-Morillo, Anne Riveros-Frutos, Alejandro Olivé" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Águeda" "apellidos" => "Prior-Español" "email" => array:1 [ 0 => "agueda_88@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Melania" "apellidos" => "Martínez-Morillo" ] 2 => array:2 [ "nombre" => "Anne" "apellidos" => "Riveros-Frutos" ] 3 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Olivé" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Reumatología, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento con rituximab e inmunoglobulinas en la hemorragia alveolar difusa recurrente en lupus eritematoso sistémico" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Diffuse alveolar hemorrhage (DAH) is a rare but potentially severe systemic lupus erythematosus (SLE) complication. Classically, the treatment is performed with methylprednisolone and cyclophosphamide pulses. More recently, plasmapheresis and immunoglobulins have been used successfully, and, lastly, rituximab.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Recurrence of the disease is uncommon and represents a therapeutic challenge. We present the case of a patient with SLE and recurrent DAH who did not respond to conventional treatment, and subsequently received immunoglobulins and rituximab successfully.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This is a 23-year-old male with a history of migraine and epilepsy during childhood who attended consultation for haemoptysis. In the case history, the patient referred to recurrent aphtosis and persistent chronic anaemia that did not correct after oral iron therapy. Chest radiography and computed tomography (CT) were performed, showing bilateral alveolar infiltrates compatible with DAH. Traces of blood were observed in the bronchoscopy, and the microbiological study was negative. Laboratory tests revealed a haemolytic anaemia with positive Coombs test, lymphopenia (500<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span><span class="elsevierStyleHsp" style=""></span>lymphocytes/l), hypocomplementemia, 1/160 ANA fine speckled pattern and positive anti-La and Ro52 antibodies. After excluding other causes of DAH and considering the analytical data and recurrent aphtosis, the diagnostic approach was DAH secondary to SLE.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Treatment was initiated with 3 pulses of intravenous (IV) methylprednisolone 500<span class="elsevierStyleHsp" style=""></span>mg followed by prednisone at a mg/kg/day dose, along with hydroxychloroquine, showing clinical and laboratory improvement. After 40 days, he was readmitted for a new episode of DAH confirmed by CT and bronchoscopy. A new cycle of 3 pulses of methylprednisolone 500<span class="elsevierStyleHsp" style=""></span>mg IV was administered, adding to the treatment cyclophosphamide 500<span class="elsevierStyleHsp" style=""></span>mg IV. After an initial clinical and radiological improvement, the lab tests prior to the 5th dose of cyclophosphamide showed a 9% decrease in the haematocrit count. The patient was asymptomatic except for a persistent sinus tachycardia. Haemolysis was ruled out and a new X-ray and CT scan were performed, which confirmed the reappearance of multiple infiltrates, more extensive, indicative of DAH recurrence. Given the recurrent DAH, compassionate-use treatment was prescribed with rituximab 1000<span class="elsevierStyleHsp" style=""></span>mg IV in 2 doses, 15 days apart, and IV immunoglobulins at doses of 0.5<span class="elsevierStyleHsp" style=""></span>g/kg/day during 4 days, as well as IV iron therapy. After 30 days of treatment the patient showed normalization of haematocrit and disappearance of alveolar infiltrates on chest radiograph. At 3 months of the administration of rituximab remains in remission.10 cases of SLE patients treated with rituximab and DAH<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3–10</span></a> are described in Anglo-Saxon medical literature (PubMed: <span class="elsevierStyleItalic">alveolar hemorrhage and systemic lupus erythematosus</span> 1969–2014). 90% were women, with an average age of 30.4 years (range: 18–52 years). The onset type of SLE was DAH in just one case. The average progression time from diagnosis was 5 years (range: 1–12 years). All cases were resistant to conventional DAH treatment and had received other immunosuppressants prior to rituximab: methylprednisolone 100%, cyclophosphamide 80%, mycophenolate 30%, plasmapheresis 30%, immunoglobulins 20% and azathioprine 10%. All patients had good response after administration, without subsequent recurrence, except one patient who died at 4 months from an infectious cause. The effect duration is described in 80% of cases, lasting for a minimum of 6 months. Response to rituximab results from B cell depletion, which involves a decrease in autoantibodies that mediate the immune response; but also increases the number and the function of regulatory T cells, which are typically low in periods of SLE activity. These actions need weeks to occur and could explain the efficacy of rituximab in preventing recurrences. The exact mechanism of action by which rituximab produces a rapid effect upon administration is not known; it has been postulated to be due to inhibiting the cooperation between T and B lymphocytes, besides inhibiting the synthesis of cytokines by these cells.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6–9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Given the low incidence of this complication in patients with SLE, there are no randomized studies on the use of rituximab alone or in combination with other immunosuppressants. On the other hand, there is a publication bias of the cases that respond to treatment. However, we believe that both rituximab as well as immunoglobulins should be considered in cases of DAH in connectivopathies resistant to conventional treatment.</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: Prior-Español Á, Martínez-Morillo M, Riveros-Frutos A, Olivé A. Tratamiento con rituximab e inmunoglobulinas en la hemorragia alveolar difusa recurrente en lupus eritematoso sistémico. Med Clin (Barc). 2015;145:507–508.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemorragia alveolar difusa en pacientes con lupus eritematoso sistémico. 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Letter to the Editor
Recurrent diffuse alveolar hemorrhage in systemic lupus erythematosus treated with rituximab and immunoglobulins
Tratamiento con rituximab e inmunoglobulinas en la hemorragia alveolar difusa recurrente en lupus eritematoso sistémico
Águeda Prior-Español
, Melania Martínez-Morillo, Anne Riveros-Frutos, Alejandro Olivé
Corresponding author
Servicio de Reumatología, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain