Original article
Safety of Azathioprine Therapy Adjusted to Thiopurine Methyltransferase Activity in the Treatment of Infantile Atopic Dermatitis. Report on 7 Cases
Seguridad de azatioprina según los niveles de tiopurina metiltransferasa en el tratamiento de la dermatitis atópica infantil. Experiencia en 7 casos
R.M. Martel
, P. Melwani, D. Islas, Y. Peñate, L. Borrego
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Servicio de Dermatología, Hospital Universitario Insular de Gran Canaria, Gran Canaria, Spain
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"apellidos" => "Martel" "email" => array:2 [ 0 => "rmartel@aedv.es" 1 => "rosa2martel@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Melwani" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Islas" ] 3 => array:2 [ "nombre" => "Y." "apellidos" => "Peñate" ] 4 => array:2 [ "nombre" => "L." "apellidos" => "Borrego" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Insular de Gran Canaria, Gran Canaria, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Seguridad de azatioprina según los niveles de tiopurina metiltransferasa en el tratamiento de la dermatitis atópica infantil. Experiencia en 7 casos" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2009-07-14" "fechaAceptado" => "2009-12-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec84759" "palabras" => array:3 [ 0 => "Atopic dermatitis" 1 => "Azathioprine" 2 => "Thiopurine methyltransferase" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec84758" "palabras" => array:3 [ 0 => "Dermatitis atópica" 1 => "Azatioprina" 2 => "Tiopurina metiltransferasa" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p class="elsevierStyleSimplePara elsevierViewall">In a small number of cases of childhood atopic dermatitis, topical therapy is ineffective, necessitating prolonged use of systemic immunosuppressants. Over the last few years, a better understanding of the metabolic pathways involved in azathioprine breakdown has enabled us to use this drug more safely. In this study, we evaluated the toxicity of azathioprine treatment adjusted to thiopurine methyltransferase activity in children with severe atopic dermatitis.</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p class="elsevierStyleSimplePara elsevierViewall">We performed a retrospective study of the side effects of azathioprine therapy adjusted to thiopurine methyltransferase activity in children aged under 14 years with atopic dermatitis who were treated in the dermatology department of Hospital Universitario Insular de Gran Canaria in Gran Canaria, Spain. Side effects were evaluated by analysis of leukocyte count and transaminase levels at baseline, after 1 month of treatment, and every 3 months thereafter.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">During the last 4 years, 7 children (mean age, 10 years) with severe atopic dermatitis received azathioprine in our department. Mean duration of treatment was 12 months (range, 1 to 38 months). Only 2 patients presented mild transient leukopenia that did not require treatment to be suspended.</p> <span class="elsevierStyleSectionTitle">Discussion</span><p class="elsevierStyleSimplePara elsevierViewall">Our experience shows that, when adjusted to thiopurine methyltransferase activity, azathioprine is a safe drug for the treatment of children with severe atopic dermatitis. However, clinical trials should be performed to compare the risk-benefit ratios of the different immunosuppressants used to treat these patients.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Introducción</span><p class="elsevierStyleSimplePara elsevierViewall">Existe un pequeño número de casos de dermatitis atópica (DA) infantil donde la terapia tópica es insuficiente para el control de la enfermedad y es necesario el uso prolongado de agentes inmunosupresores sistémicos. En los últimos años el mejor conocimiento de las vías metabólicas implicadas en la catabolización de la azatioprina (AZT) parece ofrecernos un uso más seguro de este fármaco. Hemos evaluado la toxicidad de la AZT según los niveles de tiopurina metiltransferasa (TPMT) en niños con DA grave.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de los efectos secundarios de la AZT ajustada a los niveles de TPMT en menores de 14 años con DA que han sido tratados en el Servicio de Dermatología del Hospital Universitario Insular de Gran Canaria. La evaluación de los efectos secundarios se realizó mediante controles analíticos con recuento leucocitario y de transaminasemia en la visita basal, al mes y cada tres meses durante el tratamiento.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">En los últimos 4 años, 7 niños (media de 10 años) con DA grave han recibido AZT en nuestro Servicio. La duración media del tratamiento fue de 12 meses (rango 1–38); sólo dos pacientes presentaron una leucopenia leve transitoria que no requirió la suspensión del tratamiento.</p> <span class="elsevierStyleSectionTitle">Discusión</span><p class="elsevierStyleSimplePara elsevierViewall">Según nuestra experiencia la AZT, ajustada a los niveles de TPMT, se muestra como un fármaco seguro en el tratamiento de niños con DA grave, aunque son precisos ensayos clínicos que comparen la relación riesgo/beneficio entre los inmunosupresores empleados en estos pacientes.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dermatitis atópica infantil: revisión y actualización" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 6 | 10 | 16 |
| 2024 Octubre | 54 | 42 | 96 |
| 2024 Septiembre | 52 | 25 | 77 |
| 2024 Agosto | 66 | 54 | 120 |
| 2024 Julio | 64 | 26 | 90 |
| 2024 Junio | 58 | 34 | 92 |
| 2024 Mayo | 56 | 30 | 86 |
| 2024 Abril | 39 | 19 | 58 |
| 2024 Marzo | 59 | 29 | 88 |
| 2024 Febrero | 41 | 34 | 75 |
| 2024 Enero | 35 | 29 | 64 |
| 2023 Diciembre | 35 | 19 | 54 |
| 2023 Noviembre | 45 | 45 | 90 |
| 2023 Octubre | 43 | 42 | 85 |
| 2023 Septiembre | 49 | 26 | 75 |
| 2023 Agosto | 31 | 24 | 55 |
| 2023 Julio | 51 | 45 | 96 |
| 2023 Junio | 37 | 23 | 60 |
| 2023 Mayo | 39 | 26 | 65 |
| 2023 Abril | 38 | 19 | 57 |
| 2023 Marzo | 29 | 19 | 48 |
| 2023 Febrero | 28 | 23 | 51 |
| 2023 Enero | 27 | 25 | 52 |
| 2022 Diciembre | 37 | 25 | 62 |
| 2022 Noviembre | 17 | 35 | 52 |
| 2022 Octubre | 19 | 26 | 45 |
| 2022 Septiembre | 16 | 38 | 54 |
| 2022 Agosto | 18 | 38 | 56 |
| 2022 Julio | 21 | 42 | 63 |
| 2022 Junio | 16 | 37 | 53 |
| 2022 Mayo | 19 | 35 | 54 |
| 2022 Abril | 28 | 37 | 65 |
| 2022 Marzo | 27 | 50 | 77 |
| 2022 Febrero | 22 | 27 | 49 |
| 2022 Enero | 19 | 40 | 59 |
| 2021 Diciembre | 20 | 40 | 60 |
| 2021 Noviembre | 24 | 45 | 69 |
| 2021 Octubre | 29 | 54 | 83 |
| 2021 Septiembre | 22 | 44 | 66 |
| 2021 Agosto | 15 | 39 | 54 |
| 2021 Julio | 13 | 33 | 46 |
| 2021 Junio | 44 | 35 | 79 |
| 2021 Mayo | 30 | 22 | 52 |
| 2021 Abril | 65 | 44 | 109 |
| 2021 Marzo | 61 | 31 | 92 |
| 2021 Febrero | 72 | 30 | 102 |
| 2021 Enero | 34 | 22 | 56 |
| 2020 Diciembre | 30 | 19 | 49 |
| 2020 Noviembre | 22 | 23 | 45 |
| 2020 Octubre | 17 | 12 | 29 |
| 2020 Septiembre | 29 | 19 | 48 |
| 2020 Agosto | 55 | 19 | 74 |
| 2020 Julio | 34 | 13 | 47 |
| 2020 Junio | 21 | 30 | 51 |
| 2020 Mayo | 29 | 21 | 50 |
| 2020 Abril | 23 | 23 | 46 |
| 2020 Marzo | 16 | 20 | 36 |
| 2020 Febrero | 4 | 0 | 4 |
| 2020 Enero | 0 | 13 | 13 |
| 2019 Diciembre | 0 | 9 | 9 |
| 2019 Noviembre | 0 | 3 | 3 |
| 2019 Octubre | 0 | 5 | 5 |
| 2019 Agosto | 0 | 2 | 2 |
| 2019 Julio | 0 | 9 | 9 |
| 2019 Junio | 0 | 10 | 10 |
| 2019 Mayo | 2 | 35 | 37 |
| 2019 Marzo | 0 | 11 | 11 |
| 2019 Febrero | 0 | 5 | 5 |
| 2018 Marzo | 6 | 2 | 8 |
| 2018 Febrero | 11 | 3 | 14 |
| 2018 Enero | 7 | 5 | 12 |
| 2017 Diciembre | 21 | 8 | 29 |
| 2017 Noviembre | 8 | 5 | 13 |
| 2017 Octubre | 12 | 8 | 20 |
| 2017 Septiembre | 22 | 4 | 26 |
| 2017 Agosto | 35 | 8 | 43 |
| 2017 Julio | 37 | 0 | 37 |
| 2017 Junio | 32 | 7 | 39 |
| 2017 Mayo | 34 | 10 | 44 |
| 2017 Abril | 29 | 10 | 39 |
| 2017 Marzo | 33 | 24 | 57 |
| 2017 Febrero | 24 | 5 | 29 |
| 2017 Enero | 15 | 6 | 21 |
| 2016 Diciembre | 30 | 5 | 35 |
| 2016 Noviembre | 21 | 3 | 24 |
| 2016 Octubre | 18 | 18 | 36 |
| 2016 Septiembre | 29 | 8 | 37 |
| 2016 Agosto | 28 | 6 | 34 |
| 2016 Julio | 32 | 7 | 39 |
| 2016 Junio | 7 | 9 | 16 |
| 2016 Mayo | 9 | 0 | 9 |
| 2016 Abril | 10 | 1 | 11 |
| 2016 Marzo | 5 | 0 | 5 |
| 2016 Febrero | 5 | 2 | 7 |
| 2016 Enero | 8 | 0 | 8 |
| 2015 Diciembre | 10 | 1 | 11 |
| 2015 Noviembre | 7 | 3 | 10 |
| 2015 Octubre | 8 | 4 | 12 |
| 2015 Septiembre | 10 | 3 | 13 |
| 2015 Agosto | 19 | 5 | 24 |
| 2015 Julio | 15 | 4 | 19 |
| 2015 Junio | 21 | 6 | 27 |
| 2015 Mayo | 49 | 13 | 62 |
| 2015 Abril | 28 | 8 | 36 |
| 2015 Marzo | 39 | 13 | 52 |
| 2015 Febrero | 26 | 20 | 46 |
| 2015 Enero | 21 | 14 | 35 |
| 2014 Diciembre | 28 | 20 | 48 |
| 2014 Noviembre | 18 | 12 | 30 |
| 2014 Octubre | 22 | 20 | 42 |
| 2014 Septiembre | 32 | 11 | 43 |
| 2014 Agosto | 28 | 17 | 45 |
| 2014 Julio | 35 | 13 | 48 |
| 2014 Junio | 32 | 11 | 43 |
| 2014 Mayo | 33 | 10 | 43 |
| 2014 Abril | 31 | 6 | 37 |
| 2014 Marzo | 40 | 14 | 54 |
| 2014 Febrero | 24 | 13 | 37 |
| 2014 Enero | 32 | 9 | 41 |
| 2013 Diciembre | 27 | 11 | 38 |
| 2013 Noviembre | 19 | 12 | 31 |
| 2013 Octubre | 29 | 17 | 46 |
| 2013 Septiembre | 31 | 23 | 54 |
| 2013 Agosto | 16 | 15 | 31 |
| 2013 Julio | 19 | 41 | 60 |
| 2013 Junio | 19 | 11 | 30 |
| 2013 Mayo | 12 | 12 | 24 |
| 2013 Abril | 23 | 23 | 46 |
| 2013 Marzo | 22 | 17 | 39 |
| 2013 Febrero | 11 | 11 | 22 |
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