Case and Research Letters
Mycobacterium Chelonae Infection in a Patient Being Treated With Adalimumab
Infección por Mycobacterium Chelonae en un paciente en tratamiento con adalimumab
R. Conejero
, M. Ara, M. Lorda, I. Rivera
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Servicio de Dermatología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
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Conejero, M. Ara, M. Lorda, I. Rivera" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Conejero" "email" => array:1 [ 0 => "raquel_conejero@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Ara" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Lorda" ] 3 => array:2 [ "nombre" => "I." "apellidos" => "Rivera" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Infección por <span class="elsevierStyleItalic">Mycobacterium Chelonae</span> en un paciente en tratamiento con adalimumab" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 711 "Ancho" => 948 "Tamanyo" => 255247 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Clusters of Ziehl-positive bacilli between the inflammatory cells (Ziehl stain).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Mycobacterium chelonae</span> is an atypical or nontuberculous mycobacteria belonging to the Runyon group of nonpigmented, rapidly growing mycobacteria. Infection with <span class="elsevierStyleItalic">M chelonae</span> takes the form of either infection of the soft tissue and bones as a result of direct inoculation (the clinical spectrum varies from localized skin abscesses to frank osteomyelitis) or a disseminated infection, usually found in the context of immunodepression. Fever, night sweats, and weight loss are the most common symptoms, and the skin lesions present as diffuse subcutaneous nodules and abscesses.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Adalimumab is a fully human anti-tumor necrosis factor (TNF) α monoclonal antibody. TNF-α plays a very important role in the regulation of immune responses against intracellular pathogens. Consequently, many of the adverse effects that could potentially lead to high morbidity and mortality in patients on anti-TNF therapy are due to lowered resistance to infection. TNF increases the phagocytic capacity of macrophages while promoting the destruction of intracellular pathogens, granuloma formation, and the sequestration of mycobacteria, thereby preventing their spread.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of a 76-year woman with history of type 1 diabetes mellitus, hypertension, hypercholesterolemia, and seropositive rheumatoid arthritis diagnosed 20 years earlier. She had been treated with corticosteroids and methotrexate from 1992 to 2000, corticosteroids and azathioprine from 2000 to 2003, and corticosteroids and adalimumab from 2003 to 2009. Treatment with adalimumab had been suspended from October to December 2008 due to cytomegalovirus infection and reintroduced in January 2009.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In September 2009, she was admitted to the internal medicine department in our hospital for the assessment of an episode of hypoglycemia. When her medical history was being taken, the patient reported inflammation of the right foot, which had started a month earlier, a fistula orifice on the heel, and febrile episodes 3 to 4 times a week in the preceding months. Physical examination on admission revealed firm erythematous-violaceous plaques and nodules localized mainly on the limbs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), and dermatologic evaluation was therefore requested.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The most notable findings from the workup carried out were an erythrocyte sedimentation rate of 100, a rheumatoid factor of 53.5, and evidence of osteomyelitis of the first metatarsal and the calcaneus of the right foot on the scintigraphic bone scan. The other results of the blood count, biochemistry, coagulation studies, serology, and a thoracoabdominal computed tomography (CT) were normal.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Two skin biopsies were obtained, one for dermatopathology and one for microbiological analysis. Histology revealed an inflammatory mycobacterial granuloma (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), and Ziehl staining showed Ziehl-positive bacilli distributed in groups between the inflammatory cells (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The other sample was smear microscopy-positive for mycobacterium and culture-positive for <span class="elsevierStyleItalic">M chelonae</span>.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">On the basis of these results, a diagnosis of disseminated <span class="elsevierStyleItalic">M chelonae</span> infection was established. Treatment with intravenous imipenem 0.5<span class="elsevierStyleHsp" style=""></span>g/6<span class="elsevierStyleHsp" style=""></span>h and oral clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg/day was initiated and continued for the month the patient remained in the hospital. After discharge, treatment was continued with a regimen of oral levofloxacin 500<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>hours and clarithromycin 500<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>hours for a further 6 months. Fifteen days after the start of antibiotic treatment, lavage and curettage of the lesion on the right foot was performed. The bone was observed to have a granulomatous appearance, and microscopically there was evidence of chronic granulomatous osteomyelitis though staining for acid-alcohol-fast bacilli, smear microscopy, and culture were all negative.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Although the most common mycobacterial infections in patients on anti-TNF therapy are caused by <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>, atypical mycobacterial infections are increasingly being reported. This trend may be due to the fact that such patients are actively screened for <span class="elsevierStyleItalic">M tuberculosis</span> because of the reports of infection in the literature. Also relevant is the fact that the vast majority of the cases of tuberculosis reported have occurred within 3 months of starting anti-TNF therapy, a finding that suggests reactivation of latent infection, something that has not been demonstrated in the case of other mycobacterial infections.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Winthrop et al. reviewed the U.S. Food and Drug Administration MedWatch database for cases of nontuberculous mycobacterial infections in patients receiving anti-TNF therapy.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> They reported that the population affected had a mean age of 62 years and was predominantly female (66.65%). The underlying pathology was rheumatoid arthritis in the majority of these patients (73.70%).</p><p id="par0050" class="elsevierStylePara elsevierViewall">Since 2002, several cases of nontuberculous or atypical mycobacterial infection have been reported in patients receiving anti-TNF therapy.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–7</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">On reviewing the literature, we found the following 3 cases relating specifically to <span class="elsevierStyleItalic">M chelonae</span>: 1 reported in 2006 by Sicot et al<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> in a patient treated with infliximab; another in 2008 in which Diaz et al<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> described a patient treated with adalimumab for rheumatoid arthritis whose lesions developed 2 months after the start of biologic treatment; and the third reported by Adenis-Lamarre et al<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> in 2009 in a patient with rheumatoid arthritis receiving adalimumab who developed skin lesions and was subsequently diagnosed with <span class="elsevierStyleItalic">M chelonae</span> infection.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Our case differs from those described above in the duration of treatment of the patient with adalimumab (6 years) because in the other cases reported, the infection developed within a few months of the start of treatment. We are also of the opinion that our patient's osteomyelitis may also have been caused by the <span class="elsevierStyleItalic">M chelonae</span> infection, although this hypothesis could not be confirmed by histology or microbiology because the patient had already been receiving appropriate antibiotic therapy for 15 days when samples were obtained.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion, anti-TNF therapy has been associated with opportunistic infections and patients receiving such therapy should be considered to be immunosuppressed. The risk level for infection due to nontuberculous mycobacteria in these patients is not yet known. However, the frequent presence of additional risk factors, such as concomitant treatment with other immunosuppressants (corticosteroids, methotrexate) and the underlying disease itself, make it difficult to estimate the specific weight of these new drugs in the process.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Conejero R, Ara M, Lorda M, Rivera I. Infección por <span class="elsevierStyleItalic">Mycobacterium chelonae</span> en paciente en tratamiento con adalimumab. Actas Dermosifliogr. 2012;103:70-71.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 712 "Ancho" => 948 "Tamanyo" => 85931 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Firm plaques and nodules on the legs.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 710 "Ancho" => 948 "Tamanyo" => 181398 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Suppurative granuloma due to mycobacterial infection.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 711 "Ancho" => 948 "Tamanyo" => 255247 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Clusters of Ziehl-positive bacilli between the inflammatory cells (Ziehl stain).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nontuberculous mycobacterial infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.A. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 1 | 1 | 2 |
| 2024 Octubre | 78 | 38 | 116 |
| 2024 Septiembre | 123 | 19 | 142 |
| 2024 Agosto | 132 | 51 | 183 |
| 2024 Julio | 88 | 50 | 138 |
| 2024 Junio | 114 | 30 | 144 |
| 2024 Mayo | 90 | 39 | 129 |
| 2024 Abril | 77 | 25 | 102 |
| 2024 Marzo | 86 | 21 | 107 |
| 2024 Febrero | 91 | 25 | 116 |
| 2024 Enero | 68 | 32 | 100 |
| 2023 Diciembre | 100 | 29 | 129 |
| 2023 Noviembre | 118 | 30 | 148 |
| 2023 Octubre | 62 | 30 | 92 |
| 2023 Septiembre | 75 | 36 | 111 |
| 2023 Agosto | 48 | 25 | 73 |
| 2023 Julio | 67 | 29 | 96 |
| 2023 Junio | 86 | 18 | 104 |
| 2023 Mayo | 54 | 23 | 77 |
| 2023 Abril | 57 | 15 | 72 |
| 2023 Marzo | 38 | 19 | 57 |
| 2023 Febrero | 49 | 24 | 73 |
| 2023 Enero | 58 | 36 | 94 |
| 2022 Diciembre | 54 | 50 | 104 |
| 2022 Noviembre | 21 | 26 | 47 |
| 2022 Octubre | 20 | 19 | 39 |
| 2022 Septiembre | 20 | 37 | 57 |
| 2022 Agosto | 24 | 30 | 54 |
| 2022 Julio | 27 | 35 | 62 |
| 2022 Junio | 24 | 26 | 50 |
| 2022 Mayo | 43 | 28 | 71 |
| 2022 Abril | 69 | 40 | 109 |
| 2022 Marzo | 50 | 46 | 96 |
| 2022 Febrero | 61 | 32 | 93 |
| 2022 Enero | 54 | 32 | 86 |
| 2021 Diciembre | 46 | 38 | 84 |
| 2021 Noviembre | 70 | 37 | 107 |
| 2021 Octubre | 68 | 46 | 114 |
| 2021 Septiembre | 35 | 37 | 72 |
| 2021 Agosto | 46 | 35 | 81 |
| 2021 Julio | 33 | 26 | 59 |
| 2021 Junio | 39 | 26 | 65 |
| 2021 Mayo | 50 | 56 | 106 |
| 2021 Abril | 72 | 14 | 86 |
| 2021 Marzo | 73 | 29 | 102 |
| 2021 Febrero | 84 | 24 | 108 |
| 2021 Enero | 51 | 20 | 71 |
| 2020 Diciembre | 61 | 17 | 78 |
| 2020 Noviembre | 40 | 28 | 68 |
| 2020 Octubre | 29 | 18 | 47 |
| 2020 Septiembre | 38 | 11 | 49 |
| 2020 Agosto | 25 | 21 | 46 |
| 2020 Julio | 24 | 26 | 50 |
| 2020 Junio | 53 | 20 | 73 |
| 2020 Mayo | 29 | 17 | 46 |
| 2020 Abril | 49 | 18 | 67 |
| 2020 Marzo | 39 | 17 | 56 |
| 2020 Febrero | 3 | 2 | 5 |
| 2020 Enero | 6 | 3 | 9 |
| 2019 Diciembre | 8 | 2 | 10 |
| 2019 Noviembre | 4 | 2 | 6 |
| 2019 Octubre | 0 | 1 | 1 |
| 2019 Septiembre | 4 | 0 | 4 |
| 2019 Agosto | 4 | 4 | 8 |
| 2019 Julio | 4 | 3 | 7 |
| 2019 Junio | 6 | 5 | 11 |
| 2019 Mayo | 5 | 11 | 16 |
| 2019 Abril | 2 | 6 | 8 |
| 2019 Marzo | 4 | 6 | 10 |
| 2019 Enero | 3 | 4 | 7 |
| 2018 Diciembre | 2 | 0 | 2 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 4 | 0 | 4 |
| 2018 Septiembre | 1 | 0 | 1 |
| 2018 Abril | 0 | 1 | 1 |
| 2018 Marzo | 1 | 0 | 1 |
| 2018 Febrero | 100 | 5 | 105 |
| 2018 Enero | 80 | 10 | 90 |
| 2017 Diciembre | 111 | 14 | 125 |
| 2017 Noviembre | 87 | 10 | 97 |
| 2017 Octubre | 64 | 7 | 71 |
| 2017 Septiembre | 67 | 6 | 73 |
| 2017 Agosto | 113 | 14 | 127 |
| 2017 Julio | 66 | 6 | 72 |
| 2017 Junio | 84 | 25 | 109 |
| 2017 Mayo | 82 | 10 | 92 |
| 2017 Abril | 76 | 16 | 92 |
| 2017 Marzo | 102 | 55 | 157 |
| 2017 Febrero | 95 | 10 | 105 |
| 2017 Enero | 65 | 9 | 74 |
| 2016 Diciembre | 90 | 13 | 103 |
| 2016 Noviembre | 101 | 5 | 106 |
| 2016 Octubre | 101 | 16 | 117 |
| 2016 Septiembre | 122 | 15 | 137 |
| 2016 Agosto | 92 | 7 | 99 |
| 2016 Julio | 80 | 12 | 92 |
| 2016 Junio | 14 | 16 | 30 |
| 2016 Mayo | 6 | 16 | 22 |
| 2016 Abril | 9 | 3 | 12 |
| 2016 Marzo | 20 | 3 | 23 |
| 2016 Febrero | 7 | 3 | 10 |
| 2016 Enero | 14 | 13 | 27 |
| 2015 Diciembre | 10 | 6 | 16 |
| 2015 Noviembre | 35 | 11 | 46 |
| 2015 Octubre | 18 | 1 | 19 |
| 2015 Septiembre | 8 | 2 | 10 |
| 2015 Agosto | 18 | 1 | 19 |
| 2015 Julio | 87 | 14 | 101 |
| 2015 Junio | 77 | 11 | 88 |
| 2015 Mayo | 123 | 18 | 141 |
| 2015 Abril | 80 | 15 | 95 |
| 2015 Marzo | 99 | 10 | 109 |
| 2015 Febrero | 56 | 10 | 66 |
| 2015 Enero | 96 | 16 | 112 |
| 2014 Diciembre | 99 | 7 | 106 |
| 2014 Noviembre | 53 | 8 | 61 |
| 2014 Octubre | 71 | 19 | 90 |
| 2014 Septiembre | 69 | 12 | 81 |
| 2014 Agosto | 90 | 14 | 104 |
| 2014 Julio | 96 | 15 | 111 |
| 2014 Junio | 134 | 15 | 149 |
| 2014 Mayo | 139 | 14 | 153 |
| 2014 Abril | 101 | 9 | 110 |
| 2014 Marzo | 103 | 22 | 125 |
| 2014 Febrero | 123 | 16 | 139 |
| 2014 Enero | 109 | 11 | 120 |
| 2013 Diciembre | 39 | 10 | 49 |
| 2013 Noviembre | 29 | 13 | 42 |
| 2013 Octubre | 29 | 7 | 36 |
| 2013 Septiembre | 22 | 8 | 30 |
| 2013 Agosto | 19 | 6 | 25 |
| 2013 Julio | 15 | 10 | 25 |
| 2013 Junio | 12 | 17 | 29 |
| 2013 Mayo | 11 | 8 | 19 |
| 2013 Abril | 16 | 14 | 30 |
| 2013 Marzo | 18 | 12 | 30 |
| 2013 Febrero | 51 | 3 | 54 |
| 2013 Enero | 40 | 8 | 48 |
| 2012 Diciembre | 24 | 4 | 28 |
| 2012 Noviembre | 3 | 5 | 8 |
| 2012 Octubre | 0 | 1 | 1 |
| 2012 Agosto | 1 | 0 | 1 |
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