Letter to the Editor
Severe rifampicin-induced thrombocytopenia in a patient with miliary tuberculosis
J. Maurícioa,
, B. Flor-de-Limab, P. Pachecoc
Corresponding author
joana.mauricio@hff.min-saude.pt
Corresponding author at: Hospital Prof. Doutor Fernando Fonseca, IC 19, 2720-276, Amadora, Portugal.
Corresponding author at: Hospital Prof. Doutor Fernando Fonseca, IC 19, 2720-276, Amadora, Portugal.
a Internal Medicine Resident, Internal Medicine Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
b Specialist at Infectious Diseases Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
c Headmaster of Infectious Diseases Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
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Unenhanced chest computed tomography with axial (B), coronal (C) and sagittal (D and E) maximum-intensity projection imaging demonstrated areas of ground glass opacity, many with round and oval morphologies, in both lungs. Not also in B inter- and intralobular septal thickening with a crazy-paving pattern (arrows).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "W. Schmitt, E. Marchiori" "autores" => array:2 [ 0 => array:2 [ "nombre" => "W." "apellidos" => "Schmitt" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Marchiori" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531043720300830?idApp=UINPBA00004E" "url" => "/25310437/0000002600000004/v2_202009030742/S2531043720300830/v2_202009030742/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Severe rifampicin-induced thrombocytopenia in a patient with miliary tuberculosis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "247" "paginaFinal" => "249" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J. Maurício, B. Flor-de-Lima, P. Pacheco" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Maurício" "email" => array:1 [ 0 => "joana.mauricio@hff.min-saude.pt" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "B." "apellidos" => "Flor-de-Lima" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "P." "apellidos" => "Pacheco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Internal Medicine Resident, Internal Medicine Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Specialist at Infectious Diseases Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Headmaster of Infectious Diseases Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Hospital Prof. Doutor Fernando Fonseca, IC 19, 2720-276, Amadora, Portugal." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Tuberculosis is a potentially treatable infectious disease caused by <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> Complex. Pulmonary presentation is the most frequent, with non-pulmonary forms being more commonly observed in children and immunocompromised patients. Tuberculosis remains a major public health problem in Portugal, although its incidence has been decreasing (15,6 cases/100,000 inhabitants, according to the Portuguese National Statistical Institute, 2017). Newly diagnosed tuberculosis patients are empirically treated with a combination of four drugs: isoniazid, rifampicin, pyrazinamide and ethambutol.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> No antituberculous drug is free of risk, and the World Health Organization (WHO) recommends monitoring and reporting suspected or confirmed adverse drug reactions (ADR) caused by antituberculous drugs.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Most ADR are benign, result from inherent toxicity to the drug and can be minimized by dosage adjustment, exposure duration reduction or by vitamin supplementation.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Less frequently, ADRs are immune-mediated and can present as cutaneous, hematological or systemic manifestations. These are rarer and more unpredictable, imposing both diagnostic and therapeutic challenges.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Rifampicin, one of the most important antituberculous agents, is a well-tolerated and effective drug. Most frequent adverse reactions to rifampicin (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) include gastrointestinal effects, cutaneous reactions, hepatotoxicity and flu-like syndrome. Immunological reactions, such as hemolytic anemia, agranulocytosis and thrombocytopenia, are less frequent.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Immune-mediated thrombocytopenia induced by rifampicin, first described in 1970, is a potentially fatal ADR. It is characterized by rapid platelet destruction following drug administration in susceptible individuals and occurs more frequently in situations of intermittent administration or reintroduction after a period of discontinuation.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">The authors report a clinical case of a 60-year-old male patient with ulcerative colitis who maintained active disease, even after corticosteroid and azathioprine therapy. Biological therapy with an anti-TNF-α was started, after exclusion of latent tuberculosis. Approximately 4 months later he presented anorexia, night sweats and weight loss. Laboratory results showed hemoglobin 10,4 g/dL, lymphocytes 300/μL, sodium 132 mEq/L, lactate dehydrogenase 426 U/L, C-reactive protein 153 mg/L, negative IGRA test and HIV serology. CT-scan showed scattered micronodules in the pulmonary parenchyma, a necrotic mediastinal adenopathic conglomerate, a necrotic hilar adenopathy and homogenous hepatosplenomegaly. As the patient presented no cough, a bronchoalveolar lavage was collected, which was positive for acid-fast bacilli. The nucleic acid amplification test detected the presence of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> Complex and a definitive diagnosis of miliary tuberculosis was established. First-line antituberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) were initiated, with good tolerance. On the 15th day of therapy, laboratorial findings showed increased transaminases (AST 329 U/L, ALT 270 U/L) and hyperbilirubinemia (total bilirubin 2,15 mg/dL), which determined the temporary suspension of the antituberculous agents. After normalization, antituberculous drugs were sequentially reintroduced according to the following scheme: amikacin, levofloxacin and pyrazinamide; subsequently introduced ethambutol, with suspension of amikacin; subsequently added rifampicin. About 6 days after rifampicin reintroduction, an abrupt drop of platelet count from 241 × 10<span class="elsevierStyleSup">3</span>/μL to 2 × 10<span class="elsevierStyleSup">3</span>/μL occurred, with associated epistaxis. The antiplatelet antibody test was negative and other possible causes of thrombocytopenia were excluded. Severe thrombocytopenia induced by rifampicin was assumed and the drug was discontinued. After platelet transfusion and methylprednisolone pulses, the platelet count returned to normal values. The patient was discharged to the Center for Pneumological Diagnosis, medicated with levofloxacin, ethambutol, pyrazinamide and isoniazid. After that, <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> Complex isolated from the sputum cultural exam showed resistance to isoniazid and pyrazinamide, and the therapeutic regimen was changed to levofloxacin, ethambutol, cycloserine and clofazimine, for 12 months.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Immunocompromised patients and intermittent treatment, as was the case of this patient, are predisposing factors for hypersensitivity reactions to antituberculous agents.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The mechanisms responsible for it are not yet fully identified, but it is known that they are based on an immunological mechanism: rifampicin is thought to bind non-covalently to the platelet membrane glycoproteins, causing conformational changes in the glycoprotein Ib/IX complex, and increasing the affinity of pre-existing natural antibodies (present in low concentrations and with low affinity in the absence of this drug), with consequent platelet destruction.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The mechanism of hypersensitivity is type II (cytotoxic hypersensitivity, antibody-dependent) according to the classification of Gell and Coombs.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There is no definitive diagnostic method to confirm the responsibility of rifampicin in this type of hypersensitivity. In the absence of laboratory confirmation, the diagnosis can be corroborated by the normalization of the platelet count after suspension of the drug in question. Although it is a diagnosis of exclusion, a high degree of suspicion is necessary for a rapid diagnosis.</p><p id="par0020" class="elsevierStylePara elsevierViewall">This case is highlighted by its rarity and severity, with the occurrence of multiple adverse reactions to the antituberculous drugs in an immunocompromised patient with miliary tuberculosis. The WHO recently published the initial results of a pilot study about the surveillance of antituberculous agents’ adverse events, named aDSM (active tuberculosis Drug Safety Monitoring and management), which demonstrates monitoring is feasible.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The authors also wish to emphasize that, although uncommon, the occurrence of rifampicin-induced thrombocytopenia is a potentially serious and fatal ADR, which imposes its suspension and contraindicates its reintroduction.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0025" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Ethical disclosures</span><p id="par0030" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><p id="par0035" class="elsevierStylePara elsevierViewall">Protection of human and animal subjects: The authors declare that no experiments were performed on humans or animals for this study.</p></li><li class="elsevierStyleListItem" id="lsti0010"><p id="par0040" class="elsevierStylePara elsevierViewall">Confidentiality of data: The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received enough information and gave their written informed consent to participate in the study.</p></li><li class="elsevierStyleListItem" id="lsti0015"><p id="par0045" class="elsevierStylePara elsevierViewall">Right to privacy and informed consent: The authors declare that no patient data appear in this article.</p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Ethical disclosures" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-06-27" "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">System organ class \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Frequency \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adverse events \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pseudomembranous colitis; Influenza \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blood system disorders</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1% and <10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥0,1% and <1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leukopenia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disseminated intravascular coagulation; Eosinophilia; Agranulocytosis; Hemolytic anemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Immune system disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anaphylactic reaction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nervous system disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1% and <10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Headache; Dizziness \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eye disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tear discoloration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vascular disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shock; Flushing; Vasculitis; Bleeding \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Respiratory disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dyspnea; Wheezing; Sputum discolored \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastrointestinal disorders</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥1% and <10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nausea, vomiting \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥0,1% and <1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diarrhea \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatobiliary disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatitis; Hyperbilirubinemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Skin and subcutaneous tissue disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema multiforme; Stevens-Johnson syndrome; Toxic epidermal necrolysis; Drug reaction with eosinophilia and systemic symptoms; Pruritus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Musculoskeletal disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myopathy; Bone pain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal and urinary disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unknown \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute kidney injury \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2371330.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Frequency of the adverse events to rifampicin (Adapted).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculosis treatment and management of some problems related to the medication" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R. Duarte" 1 => "A. Carvalho" 2 => "D. Ferreira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0873-2159(15)30052-0" "Revista" => array:7 [ "tituloSerie" => "Rev Port Pneumol" "fecha" => "2010" "volumen" => "16" "numero" => "4" "paginaInicial" => "559" "paginaFinal" => "572" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20700555" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "O. Akkerman" 1 => "A. Aleksa" 2 => "J. Alffenaar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijid.2019.03.036" "Revista" => array:6 [ "tituloSerie" => "Int J Infect Dis" "fecha" => "2019" "volumen" => "83" "paginaInicial" => "72" "paginaFinal" => "76" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30953827" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antituberculosis drugs: Drugs interactions, adverse effects, and use in special situations. Part 1: First- line drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.A. Arbex" 1 => "M.C. Varella" 2 => "H.R. Siqueira" 3 => "F.A. Mello" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1590/S1806-37132010000500016" "Revista" => array:7 [ "tituloSerie" => "J Bras Pneumol" "fecha" => "2010" "volumen" => "36" "numero" => "5" "paginaInicial" => "626" "paginaFinal" => "640" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21085830" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypersensitivity reactions to antituberculosis therapy: epidemiology, mechanism and patient management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Bouchentouf" 1 => "Z. Yasser" 2 => "A. Benjelloune" 3 => "M.A. Aitbenasser" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Fran Viet Pneu" "fecha" => "2011" "volumen" => "2" "numero" => "5" "paginaInicial" => "4" "paginaFinal" => "8" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rifampicin-induced thrombocytopenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.K. Verma" 1 => "A. Singh" 2 => "A. Chandra" 3 => "S. Kumar" 4 => "R.K. Gupta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/0253-7613.68432" "Revista" => array:6 [ "tituloSerie" => "Indian J Pharmacol" "fecha" => "2010" "volumen" => "42" "paginaInicial" => "240" "paginaFinal" => "242" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20927251" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glycoprotein Ib/IX complex is the target in rifampicin-induced immune thrombocytopenia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Pereira" 1 => "P. Hidalgo" 2 => "M. Ocqueteau" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.1365-2141.2000.02299.x" "Revista" => array:5 [ "tituloSerie" => "Br J Haematol" "fecha" => "2000" "volumen" => "1" "paginaInicial" => "907" "paginaFinal" => "910" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Rifadin 300mg Capsules - Summary of Product Characteristics (SmPC) - (eMC)., Electronic Medicines Compendium. <a target="_blank" href="https://www.medicines.org.uk/emc/product/6384/smpc#UNDESIRABLE_EFFECTS">https://www.medicines.org.uk/emc/product/6384/smpc#UNDESIRABLE_EFFECTS</a>. Accessed July 23, 2019." ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/25310437/0000002600000004/v2_202009030742/S2531043719301758/v2_202009030742/en/main.assets" "Apartado" => array:4 [ "identificador" => "72880" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/25310437/0000002600000004/v2_202009030742/S2531043719301758/v2_202009030742/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531043719301758?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 12 | 7 | 19 |
| 2024 October | 86 | 41 | 127 |
| 2024 September | 105 | 32 | 137 |
| 2024 August | 134 | 39 | 173 |
| 2024 July | 162 | 41 | 203 |
| 2024 June | 102 | 47 | 149 |
| 2024 May | 98 | 43 | 141 |
| 2024 April | 73 | 39 | 112 |
| 2024 March | 106 | 38 | 144 |
| 2024 February | 79 | 35 | 114 |
| 2024 January | 82 | 28 | 110 |
| 2023 December | 65 | 31 | 96 |
| 2023 November | 86 | 63 | 149 |
| 2023 October | 96 | 44 | 140 |
| 2023 September | 78 | 31 | 109 |
| 2023 August | 84 | 22 | 106 |
| 2023 July | 67 | 37 | 104 |
| 2023 June | 56 | 20 | 76 |
| 2023 May | 63 | 31 | 94 |
| 2023 April | 58 | 18 | 76 |
| 2023 March | 80 | 28 | 108 |
| 2023 February | 51 | 29 | 80 |
| 2023 January | 41 | 22 | 63 |
| 2022 December | 76 | 35 | 111 |
| 2022 November | 94 | 40 | 134 |
| 2022 October | 96 | 56 | 152 |
| 2022 September | 59 | 40 | 99 |
| 2022 August | 76 | 41 | 117 |
| 2022 July | 77 | 60 | 137 |
| 2022 June | 64 | 34 | 98 |
| 2022 May | 94 | 47 | 141 |
| 2022 April | 87 | 44 | 131 |
| 2022 March | 106 | 48 | 154 |
| 2022 February | 86 | 40 | 126 |
| 2022 January | 125 | 59 | 184 |
| 2021 December | 91 | 42 | 133 |
| 2021 November | 97 | 45 | 142 |
| 2021 October | 103 | 76 | 179 |
| 2021 September | 83 | 52 | 135 |
| 2021 August | 78 | 49 | 127 |
| 2021 July | 57 | 19 | 76 |
| 2021 June | 86 | 37 | 123 |
| 2021 May | 104 | 44 | 148 |
| 2021 April | 244 | 96 | 340 |
| 2021 March | 230 | 62 | 292 |
| 2021 February | 115 | 43 | 158 |
| 2021 January | 99 | 33 | 132 |
| 2020 December | 123 | 38 | 161 |
| 2020 November | 92 | 32 | 124 |
| 2020 October | 109 | 50 | 159 |
| 2020 September | 115 | 60 | 175 |
| 2020 August | 203 | 67 | 270 |
| 2020 July | 255 | 120 | 375 |
| 2020 June | 67 | 33 | 100 |
| 2020 May | 69 | 31 | 100 |
| 2020 April | 65 | 12 | 77 |
| 2020 March | 55 | 21 | 76 |
| 2020 February | 51 | 18 | 69 |
| 2020 January | 47 | 26 | 73 |
| 2019 December | 42 | 41 | 83 |
| 2019 November | 24 | 25 | 49 |
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