Letter to the Editor
Pneumonitis Induced by Methotrexate in a Patient With Seronegative Rheumatoid Arthritis
Neumonitis inducida por metotrexato en una paciente con artritis reumatoide seronegativa
Meritxell Fernández Matilla
, Nagore Fernández-Llanio Comella, Juan Antonio Castellano Cuesta
Corresponding author
Sección de Reumatología, Hospital Arnau de Vilanova, Valencia, Spain
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(A) Clinical onset. (B) Control.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Methotrexate-induced pneumonitis is a serious (mortality: 13%–20%)<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> but uncommon (0.3%–7.5%)<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2,3</span></a> complication of treatment with this folic acid antagonist in patients with rheumatoid arthritis (RA) and other diseases. The typical onset is characterised by an acute picture of nonproductive cough, dyspnoea, and fever, within the first year of treatment, most commonly during the first months (mean: 36–78 weeks),<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> and irrespective of scheduled dose, patient's smoking habit, and gender. The following risk factors have been identified: advanced age, extra-articular manifestations of rheumatoid arthritis (mainly pulmonary involvement), diabetes, and elevated creatinine levels.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> If this condition is suspected, methotrexate should be immediately discontinued, and respiratory support and systemic steroids at medium-high doses should be initiated; it is also recommended to associate a broad-spectrum antibiotic, with coverage for <span class="elsevierStyleItalic">Pneumocystis jirovecii</span>,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> until the infectious origin is ruled out.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 68-year-old female patient, who in February 2013 was diagnosed with seronegative rheumatoid arthritis in the context of high blood pressure and type II diabetes mellitus with secondary sensorimotor axonal polyneuropathy. We started oral treatment with prednisone 30<span class="elsevierStyleHsp" style=""></span>mg/day and methotrexate 10<span class="elsevierStyleHsp" style=""></span>mg/week. After eight weeks, a partial improvement was observed; for this reason, methotrexate dose was increased to 15<span class="elsevierStyleHsp" style=""></span>mg/week and steroid dose was reduced.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Two months later, the patient presented at the ER of our hospital with 24-h-course dyspnoea, cough, sweating, nausea, fever, and dizziness. Physical examination: BP 92/56<span class="elsevierStyleHsp" style=""></span>mmHg, HR 110<span class="elsevierStyleHsp" style=""></span>bpm, SaO<span class="elsevierStyleInf">2</span> 86%, T 38.4<span class="elsevierStyleHsp" style=""></span>°C, glycaemia 178<span class="elsevierStyleHsp" style=""></span>mg/dL, Glasgow index 15/15, negative meningeal signs, tenderness on abdominal palpation. Of the complementary tests, the most significant data include: ECG: sinus tachycardia 100<span class="elsevierStyleHsp" style=""></span>bpm with isolated ventricular extrasystole; abdominal ultrasound: normal; chest X-ray: bilateral diffuse alveolar consolidation and cardiomegaly (the X-ray performed before treatment start was reported as normal); haemogram: haemoglobin 11.4<span class="elsevierStyleHsp" style=""></span>g/dL, haematocrit 34.4%, MCV 104<span class="elsevierStyleHsp" style=""></span>fL; coagulation: Quick's test 51%, <span class="elsevierStyleSmallCaps">d</span>-dimer: 5109<span class="elsevierStyleHsp" style=""></span>ng/mL; gasometry: lactic acid 5.8<span class="elsevierStyleHsp" style=""></span>mmol/L, pH 7.52; creatinine: 1.8<span class="elsevierStyleHsp" style=""></span>mg/dL (normal values in previous tests); procalcitonin 0.11<span class="elsevierStyleHsp" style=""></span>ng/mL; pro-BNP: 9130<span class="elsevierStyleHsp" style=""></span>pg/mL; urine sediment: normal. The patient was admitted to the Intensive Care Unit, where respiratory support (Mk-reservoir 12<span class="elsevierStyleHsp" style=""></span>lpm and, subsequently, CPAP) and empiric antibiotic therapy with imipenem, along with low doses of noradrenaline and methylprednisolone IV, were initiated; methotrexate was discontinued. Serial blood culture and urine culture were negative, and the echocardiography was normal. Bronchoalveolar lavage was not performed.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> After 48<span class="elsevierStyleHsp" style=""></span>h, an improvement in her condition and the laboratory values was observed; for this reason, she was transferred to the ward, where two days later she was asymptomatic and oxygen therapy was no longer required. A pulmonary CT was performed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) where the presence of a predominantly peripheral bilateral extensive ground-glass opacity was confirmed, associated with minimum subpleural lung consolidations in the right lower lobe; the preserved lung parenchyma was normal. The patient was discharged with oral steroid treatment (0.5<span class="elsevierStyleHsp" style=""></span>mg/kg) for control at the outpatient offices; oral sulfasalazine was added, and it was discontinued a few weeks later due to hair loss, abdominal pain, and palpable purpura in abdomen and upper part of limbs. Therefore, we continue treatment with oral prednisolone alone in a down-titration schedule up to a maintenance dose of 7.5<span class="elsevierStyleHsp" style=""></span>mg/d. A few weeks later, the patient was completely recovered.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Ten months later, a control high-resolution computed axial tomography scan was performed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B), showing normal lung parenchyma and no ground-glass opacity. Currently, the patient continues in clinical remission of RA and has returned completely to her normal activity.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Since this condition, although rare, is considered to have potential severity, we urge the reader to suspect it when a patient on treatment with methotrexate presents with a clinical picture compatible with respiratory tract infection and/or heart failure.</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: Fernández Matilla M, Fernández-Llanio Comella N, Castellano Cuesta JA. Neumonitis inducida por metotrexato en una paciente con artritis reumatoide seronegativa. Reumatol Clin. 2015;11:190–191.</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" => 520 "Ancho" => 1500 "Tamanyo" => 144592 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Thoracic CT scan. (A) Clinical onset. (B) Control.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Toxicidad pulmonar inducida por metotrexato" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "L. 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Braun" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Scand J Rheumatol" "fecha" => "1993" "volumen" => "22" "paginaInicial" => "225" "paginaFinal" => "228" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8235492" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001100000003/v2_201505050301/S2173574315000428/v2_201505050301/en/main.assets" "Apartado" => array:4 [ "identificador" => "8400" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001100000003/v2_201505050301/S2173574315000428/v2_201505050301/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574315000428?idApp=UINPBA00004M" ]
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| 2021 January | 24 | 33 | 57 |
| 2020 December | 27 | 24 | 51 |
| 2020 November | 35 | 20 | 55 |
| 2020 October | 16 | 17 | 33 |
| 2020 September | 36 | 35 | 71 |
| 2020 August | 19 | 20 | 39 |
| 2020 July | 21 | 22 | 43 |
| 2020 June | 38 | 16 | 54 |
| 2020 May | 23 | 27 | 50 |
| 2020 April | 22 | 16 | 38 |
| 2020 March | 16 | 13 | 29 |
| 2020 February | 1 | 0 | 1 |
| 2018 May | 5 | 0 | 5 |
| 2018 April | 54 | 8 | 62 |
| 2018 March | 70 | 17 | 87 |
| 2018 February | 58 | 9 | 67 |
| 2018 January | 49 | 7 | 56 |
| 2017 December | 59 | 8 | 67 |
| 2017 November | 32 | 9 | 41 |
| 2017 October | 32 | 12 | 44 |
| 2017 September | 34 | 7 | 41 |
| 2017 August | 56 | 9 | 65 |
| 2017 July | 50 | 11 | 61 |
| 2017 June | 65 | 13 | 78 |
| 2017 May | 82 | 23 | 105 |
| 2017 April | 43 | 5 | 48 |
| 2017 March | 54 | 6 | 60 |
| 2017 February | 23 | 10 | 33 |
| 2017 January | 37 | 5 | 42 |
| 2016 December | 64 | 16 | 80 |
| 2016 November | 44 | 7 | 51 |
| 2016 October | 57 | 11 | 68 |
| 2016 September | 67 | 10 | 77 |
| 2016 August | 58 | 7 | 65 |
| 2016 July | 28 | 6 | 34 |
| 2016 January | 1 | 0 | 1 |
| 2015 December | 2 | 0 | 2 |
| 2015 November | 1 | 20 | 21 |
| 2015 October | 1 | 23 | 24 |
| 2015 September | 3 | 0 | 3 |
| 2015 August | 1 | 18 | 19 |
| 2015 July | 30 | 8 | 38 |
| 2015 June | 72 | 20 | 92 |
| 2015 May | 62 | 31 | 93 |
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