Letter to the Editor
Antineutrophil cytoplasmic antibodies associated vasculitis in patient with Crohn's disease treated with adalimumab
Vasculitis asociada a anticuerpo anticitoplasma de neutrófilo en paciente con enfermedad de Crohn en tratamiento con adalimumab
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"tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "560" "paginaFinal" => "561" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Carmen Martín Varas, Manuel Heras, Ana Saiz, Raquel Coloma, Leonardo Calle, Ramiro Callejas, Álvaro Molina, María Astrid Rodríguez, María José Fernández-Reyes Luis" "autores" => array:9 [ 0 => array:3 [ "nombre" => "Carmen" "apellidos" => "Martín Varas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Manuel" "apellidos" => "Heras" "email" => array:1 [ 0 => "mherasb@saludcastillayleon.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Ana" "apellidos" => "Saiz" 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=> array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "María José" "apellidos" => "Fernández-Reyes Luis" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital General de Segovia, Segovia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Ramón y Cajal, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Farmacia, Hospital General de Segovia, Segovia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Vasculitis asociada a anticuerpo anticitoplasma de neutrófilo en paciente con enfermedad de Crohn en tratamiento con adalimumab" ] ] "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" => 999 "Ancho" => 995 "Tamanyo" => 106497 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Image of high-resolution chest CT scan revealing an alveolar pattern compatible with pulmonary haemorrhage.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Tumour necrosis factor-alpha (TNF-alpha) is a cytokine involved in kidney damage, which mediates glomerular inflammation and T cell-mediated tissue damage.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Inhibition of TNF-alpha is an effective therapy for the treatment of autoimmune diseases, with a positive effect on antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 54-year-old male, with Crohn's disease (CD) diagnosed in 2003, and undergoing chronic treatment with 40<span class="elsevierStyleHsp" style=""></span>mg of subcutaneous adalimumab every 15 days since 2014. He subsequently developed inflammatory arthropathy, motor-sensory polyneuropathy and optic neuritis. The patient came to the Emergency Room because of fever which had lasted for more than one month, general malaise, asthenia and mild oedema in the lower limbs. By physical examination, he appeared to be in a good general condition, blood pressure of 135/60<span class="elsevierStyleHsp" style=""></span>mmHg, a heart rate of 65 beats per minute, pitting oedema and signs of chronic venous insufficiency in the lower limbs. The rest of the physical examination was not relevant. The blood test obtained at the emergency room showed haemoglobin 9<span class="elsevierStyleHsp" style=""></span>g/dl, haematocrit 27.1%, creatinine 3.6<span class="elsevierStyleHsp" style=""></span>mg/dl (the previous measurement was 0.8<span class="elsevierStyleHsp" style=""></span>mg/dl), C-reactive protein 7.9<span class="elsevierStyleHsp" style=""></span>mg/dl, pH 7.40, bicarbonate 19.2<span class="elsevierStyleHsp" style=""></span>mmol/l and pCO<span class="elsevierStyleInf">2</span> 31<span class="elsevierStyleHsp" style=""></span>mmHg. Positive ANCA (positive anti-PR3, negative anti-MPO) was detected in the delayed immunological study. The rest was normal. The urine test showed: sodium 74<span class="elsevierStyleHsp" style=""></span>mmol/l, potassium 36<span class="elsevierStyleHsp" style=""></span>mmol/l, osmolality 437<span class="elsevierStyleHsp" style=""></span>mOsm/kg; systematic: proteins ++, blood +++ and sediment with more than 50 red blood cells per field, 10–15 leukocytes per field and granular casts. The quantification of proteins in 24-h urine was 1.2<span class="elsevierStyleHsp" style=""></span>g/day. The chest X-ray showed parenchymal consolidation in the right hemithorax and left-sided pleural effusion. Hyperechogenic kidneys were found on the abdominal ultrasound, with no signs of pyelocalyceal dilation.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On the first day of admission, the patient presented with isolated bloody sputum, which, along with anaemia and parenchymal condensation, led to a suspected pulmonary haemorrhage, confirmed in a high-resolution chest CT scan (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In light of suspected pulmonary-renal syndrome, treatment was started for the pulmonary haemorrhage with 500-mg pulses of 6-methylprednisolone for two days and a kidney biopsy was performed which demonstrated the suspected pauci-immune extracapillary glomerulonephritis. Being positive for ANCAs, the dose of 6-methylprednisolone was increased to 1<span class="elsevierStyleHsp" style=""></span>g, in two additional pulses, followed by 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day of oral prednisone. An intravenous pulse of 1.2<span class="elsevierStyleHsp" style=""></span>g of cyclophosphamide was also administered. With these measures the patient had clinical improvement.. The bloody sputum remitted and he was discharged with a creatinine level of 3.2<span class="elsevierStyleHsp" style=""></span>mg/dl. In our outpatient clinic, a regimen of 1<span class="elsevierStyleHsp" style=""></span>mg/kg of oral prednisone, with another two pulses of 1.2<span class="elsevierStyleHsp" style=""></span>g of cyclophosphamide per month was maintained. The patient presented with a creatinine level of 1.7<span class="elsevierStyleHsp" style=""></span>mg/dl and negative ANCAs (anti-PR3) in the last blood test. To assess whether vasculitis was a side effect of adalimumab, levels were requested. These values were negative (the patient had already received a pulse of cyclophosphamide); the antibodies versus adalimumab were also negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">We report the case of a patient with CD, undergoing chronic active treatment with an anti-TNF agent, whose condition became complicated years later with ANCA-positive vasculitis with pulmonary and renal involvement, which could be a <span class="elsevierStyleItalic">de novo</span> process or a <span class="elsevierStyleItalic">side effect</span> of the treatment with adalimumab.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Anti-TNF alpha agents have been studied extensively in recent years, and their positive effect in the treatment of ANCA-associated systemic vasculitis (infliximab and etanercept), based on the blocking of the TNF involved in kidney damage, has been demonstrated.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–4</span></a> The usefulness of adalimumab for the treatment of these vasculitides has recently been reported.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> However, these drugs are not devoid of side effects. In fact, cutaneous vasculitis<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> and autoimmune diseases related to anti-TNF agents<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a> are frequently reported in the literature. Regarding adalimumab, Simms et al. reported the first case of ANCA-associated necrotising glomerulonephritis in a woman with rheumatoid arthritis treated with this drug.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> We report a case of vasculitis that developed in a patient with CD undergoing chronic treatment with adalimumab. It was difficult to discern if the vasculitis of our patient was <span class="elsevierStyleItalic">de novo</span> or, a side effect of the anti-TNF agent, thus a complication of treatment with adalimumab. Therefore it was decided to administer steroids and cyclophosphamide – the standard treatment for vasculitis. There was good clinical response, the ANCAs became negative and there was no data of activity on his CD.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, the standard treatment with steroids and cyclophosphamide may be favourable to treat those cases of ANCA-positive vasculitis that may arise within autoimmune diseases treated with anti-TNF agents, in which there are reasonable doubts as to whether it is a <span class="elsevierStyleItalic">de novo</span> process or a side effect of the anti-TNF therapy.</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: Martín Varas C, Heras M, Saiz A, Coloma R, Calle L, Callejas R, et al. Vasculitis asociada a anticuerpo anticitoplasma de neutrófilo en paciente con enfermedad de Crohn en tratamiento con adalimumab. Nefrologia. 2017;37:560–561.</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" => 999 "Ancho" => 995 "Tamanyo" => 106497 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Image of high-resolution chest CT scan revealing an alveolar pattern compatible with pulmonary haemorrhage.</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" => "Vasculitis induced by tumor necrosis factor-targeted therapies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 4 | 8 |
| 2024 October | 59 | 37 | 96 |
| 2024 September | 49 | 39 | 88 |
| 2024 August | 67 | 67 | 134 |
| 2024 July | 44 | 36 | 80 |
| 2024 June | 53 | 41 | 94 |
| 2024 May | 78 | 34 | 112 |
| 2024 April | 71 | 42 | 113 |
| 2024 March | 58 | 25 | 83 |
| 2024 February | 42 | 34 | 76 |
| 2024 January | 32 | 26 | 58 |
| 2023 December | 25 | 33 | 58 |
| 2023 November | 36 | 29 | 65 |
| 2023 October | 42 | 20 | 62 |
| 2023 September | 43 | 31 | 74 |
| 2023 August | 39 | 25 | 64 |
| 2023 July | 47 | 22 | 69 |
| 2023 June | 44 | 25 | 69 |
| 2023 May | 54 | 25 | 79 |
| 2023 April | 40 | 23 | 63 |
| 2023 March | 51 | 22 | 73 |
| 2023 February | 40 | 22 | 62 |
| 2023 January | 43 | 19 | 62 |
| 2022 December | 73 | 24 | 97 |
| 2022 November | 66 | 29 | 95 |
| 2022 October | 64 | 44 | 108 |
| 2022 September | 54 | 25 | 79 |
| 2022 August | 92 | 47 | 139 |
| 2022 July | 66 | 45 | 111 |
| 2022 June | 49 | 38 | 87 |
| 2022 May | 69 | 31 | 100 |
| 2022 April | 109 | 47 | 156 |
| 2022 March | 66 | 64 | 130 |
| 2022 February | 64 | 50 | 114 |
| 2022 January | 95 | 32 | 127 |
| 2021 December | 85 | 47 | 132 |
| 2021 November | 64 | 27 | 91 |
| 2021 October | 117 | 45 | 162 |
| 2021 September | 72 | 34 | 106 |
| 2021 August | 87 | 37 | 124 |
| 2021 July | 74 | 29 | 103 |
| 2021 June | 60 | 23 | 83 |
| 2021 May | 56 | 45 | 101 |
| 2021 April | 113 | 38 | 151 |
| 2021 March | 75 | 41 | 116 |
| 2021 February | 86 | 29 | 115 |
| 2021 January | 60 | 16 | 76 |
| 2020 December | 51 | 14 | 65 |
| 2020 November | 46 | 24 | 70 |
| 2020 October | 39 | 9 | 48 |
| 2020 September | 47 | 21 | 68 |
| 2020 August | 47 | 15 | 62 |
| 2020 July | 47 | 15 | 62 |
| 2020 June | 49 | 21 | 70 |
| 2020 May | 63 | 16 | 79 |
| 2020 April | 37 | 17 | 54 |
| 2020 March | 45 | 14 | 59 |
| 2020 February | 52 | 22 | 74 |
| 2020 January | 57 | 21 | 78 |
| 2019 December | 73 | 25 | 98 |
| 2019 November | 118 | 18 | 136 |
| 2019 October | 52 | 9 | 61 |
| 2019 September | 89 | 22 | 111 |
| 2019 August | 45 | 12 | 57 |
| 2019 July | 40 | 18 | 58 |
| 2019 June | 48 | 22 | 70 |
| 2019 May | 53 | 20 | 73 |
| 2019 April | 83 | 18 | 101 |
| 2019 March | 54 | 28 | 82 |
| 2019 February | 43 | 29 | 72 |
| 2019 January | 27 | 20 | 47 |
| 2018 December | 122 | 41 | 163 |
| 2018 November | 158 | 17 | 175 |
| 2018 October | 106 | 11 | 117 |
| 2018 September | 67 | 18 | 85 |
| 2018 August | 47 | 11 | 58 |
| 2018 July | 48 | 9 | 57 |
| 2018 June | 54 | 12 | 66 |
| 2018 May | 81 | 18 | 99 |
| 2018 April | 72 | 7 | 79 |
| 2018 March | 90 | 12 | 102 |
| 2018 February | 53 | 2 | 55 |
| 2018 January | 51 | 7 | 58 |
| 2017 December | 50 | 8 | 58 |
| 2017 November | 37 | 7 | 44 |
| 2017 October | 56 | 12 | 68 |
| 2017 September | 2 | 1 | 3 |
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