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Doxycycline, a Well-Tolerated, Economic, and Effective Alternative for the First-Line Treatment of Bullous Pemphigoid
Doxiciclina, una alternativa efectiva, bien tolerada y de bajo coste como tratamiento de primera línea del penfigoide ampolloso
D. Morgado-Carrasco, C. Riquelme-Mc Loughlin, X. Fustà-Novell, P. Iranzo
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Dermatology Department, Hospital Clínic de Barcelona, Barcelona, España
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Morgado-Carrasco, C. Riquelme-Mc Loughlin, X. Fustà-Novell, P. Iranzo" "autores" => array:4 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Riquelme-Mc Loughlin" ] 2 => array:2 [ "nombre" => "X." "apellidos" => "Fustà-Novell" ] 3 => array:4 [ "nombre" => "P." "apellidos" => "Iranzo" "email" => array:1 [ 0 => "piranzo@clinic.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Dermatology Department, Hospital Clínic de Barcelona, Barcelona, España" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Doxiciclina, una alternativa efectiva, bien tolerada y de bajo coste como tratamiento de primera línea del penfigoide ampolloso" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Bullous pemphigoid is the most common autoimmune blistering disease and one that is associated with high morbidity and mortality. Treatment can be complicated by advanced age, comorbidities, and cognitive and/or physical limitations of the patients. Traditionally, oral corticosteroids have been used at doses of 0.5-1.5<span class="elsevierStyleHsp" style=""></span>mg/kg, but it has been shown that high-potency topical corticosteroids (HPTCs) applied over the entire body have a similar effectiveness with fewer side effects,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> and so these are recommended as first-line treatment of bullous pemphigoid.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> However, use of these agents can be difficult due to lack of therapeutic adherence given the patient characteristics, logistic constraints, and adverse effects associated with systemic absorption. Among other treatment alternatives, tetracyclines have been widely used for treatment of bullous pemphigoid, thanks to their anti-inflammatory effect (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), low cost, and good tolerability; however, robust evidence of their efficacy has not been available.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Recently, Williams et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> published the results of a randomized noninferiority clinical trial (defining an effectiveness margin of 37% as acceptable) comparing doxycycline (200<span class="elsevierStyleHsp" style=""></span>mg/day, 132 patients) with prednisolone (0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day, 121 patients). Both groups were allowed to apply HPTCs to cutaneous lesions only, without exceeding 30<span class="elsevierStyleHsp" style=""></span>g/week, for the first 3 weeks. The mean age of the patients was 77 years and 68% had moderate or severe bullous pemphigoid. The main outcome measures were effectiveness at 6 weeks, where effectiveness was defined as having <span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>3 blisters, and safety, determined by severe adverse effects at 52 weeks. In the doxycycline group, 74% achieved total control of bullous pemphigoid at 6 weeks compared with 91% in the prednisolone group (adjusted difference of 18.6% [90% CI: 11.1%-26.1%]), enabling the conclusion to be drawn that doxycycline was not inferior to prednisolone. Severe adverse effects were reported in 18% of the doxycycline group and 36% of the prednisolone group, including 3 and 11 treatment-related deaths, respectively. The recurrence rate was similar in both groups, as well as the decrease in Dermatology Quality of Life Index. Both treatments were less effective in patients with severe disease, and the use of topical corticosteroids was greater in the doxycycline group.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Despite doubts about whether the 37% limit for noninferiority of doxycycline treatment is acceptable (this limit was based on a survey of dermatologists in the United Kingdom, in which the specialists responded that they would accept up to a 25% reduction in the effectiveness of treatment provided it was accompanied by a reduction in adverse effects<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a>), the study shows that doxycycline is highly effective, and allows adequate disease control with fewer side effects and deaths than with oral corticosteroids. Moreover, in the cost-effectiveness analysis of this study, no significant differences were found between the cost of treatment with doxycycline and with prednisolone.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In view of the above results, we consider a reasonable therapeutic alternative is to initiate treatment for bullous pemphigoid with doxycycline and HPTC limited to cutaneous lesions, and initiate oral corticosteroids in the event of therapeutic failure.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1014553" "palabras" => array:5 [ 0 => "Bullous pemphigoid" 1 => "Blistering diseases" 2 => "Tetracyclines" 3 => "Doxycycline" 4 => "Therapy" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Morgado-Carrasco D, Riquelme-Mc Loughlin C, Fustà-Novell X, Iranzo P. Doxiciclina, una alternativa efectiva, bien tolerada y de bajo coste como tratamiento de primera línea del penfigoide ampolloso. Actas Dermosifiliogr. 2018;109:549–550.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Source: Monk et al..<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p>" "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Possible mechanism of action</span></td><td class="td" title="table-entry " align="left" valign="top">Inhibition of chemiotaxis and neutrophil migration, and indirect inhibition of neutrophil elastase \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Decrease in T-cell, mast cell, and eosinophil activation and proliferation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inhibition of phospholipase A<span class="elsevierStyleInf">2</span> and proinflammatory cytokines \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inhibition of metalloproteinases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Increased collagen production (proanabolic effect) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Precautions</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cutaneous adverse effects \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dose-dependent phototoxicity, onycholysis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Special populations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not recommended in pregnancy (FDA category D)<br>Do not use in children under 8 years of age, it can cause permanent tooth decoloration \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1819404.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tetracyclines in the Treatment of Bullous Pemphigoid.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparison of oral and topical corticosteroids in patients with bullous pemphigoid" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. 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Siegel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.phrs.2010.10.007" "Revista" => array:6 [ "tituloSerie" => "Pharmacol Res" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "130" "paginaFinal" => "145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20937386" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: A pragmatic, non-inferiority, randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.C. Williams" 1 => "F. Wojnarowska" 2 => "G. Kirtschig" 3 => "J. Mason" 4 => "T.R. Godec" 5 => "E. Schmidt" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet Lond Engl" "fecha" => "2017" "volumen" => "389" "numero" => "10079" "paginaInicial" => "1630" "paginaFinal" => "1638" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomised controlled trial to compare the safety, effectiveness and cost-effectiveness of doxycycline (200mg/day) with that of oral prednisolone (0.5mg/kg/day) for initial treatment of bullous pemphigoid: the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.R. Chalmers" 1 => "F. Wojnarowska" 2 => "G. Kirtschig" 3 => "J. Mason" 4 => "M. Childs" 5 => "D. Whitham" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3310/hta21810" "Revista" => array:6 [ "tituloSerie" => "Health Technol Assess" "fecha" => "2017" "volumen" => "21" "paginaInicial" => "1" "paginaFinal" => "90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29280434" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010900000006/v1_201808010420/S1578219018301665/v1_201808010420/en/main.assets" "Apartado" => array:4 [ "identificador" => "34945" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Resident's Forum" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010900000006/v1_201808010420/S1578219018301665/v1_201808010420/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219018301665?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 26 | 13 | 39 |
| 2024 Octubre | 166 | 50 | 216 |
| 2024 Septiembre | 180 | 50 | 230 |
| 2024 Agosto | 257 | 90 | 347 |
| 2024 Julio | 247 | 47 | 294 |
| 2024 Junio | 157 | 43 | 200 |
| 2024 Mayo | 155 | 39 | 194 |
| 2024 Abril | 130 | 32 | 162 |
| 2024 Marzo | 172 | 31 | 203 |
| 2024 Febrero | 128 | 28 | 156 |
| 2024 Enero | 116 | 27 | 143 |
| 2023 Diciembre | 122 | 27 | 149 |
| 2023 Noviembre | 125 | 30 | 155 |
| 2023 Octubre | 164 | 23 | 187 |
| 2023 Septiembre | 118 | 32 | 150 |
| 2023 Agosto | 83 | 19 | 102 |
| 2023 Julio | 97 | 41 | 138 |
| 2023 Junio | 86 | 28 | 114 |
| 2023 Mayo | 80 | 28 | 108 |
| 2023 Abril | 82 | 27 | 109 |
| 2023 Marzo | 86 | 30 | 116 |
| 2023 Febrero | 65 | 33 | 98 |
| 2023 Enero | 126 | 32 | 158 |
| 2022 Diciembre | 67 | 48 | 115 |
| 2022 Noviembre | 59 | 50 | 109 |
| 2022 Octubre | 47 | 28 | 75 |
| 2022 Septiembre | 39 | 35 | 74 |
| 2022 Agosto | 40 | 44 | 84 |
| 2022 Julio | 26 | 38 | 64 |
| 2022 Junio | 21 | 35 | 56 |
| 2022 Mayo | 75 | 38 | 113 |
| 2022 Abril | 72 | 51 | 123 |
| 2022 Marzo | 78 | 47 | 125 |
| 2022 Febrero | 85 | 32 | 117 |
| 2022 Enero | 72 | 52 | 124 |
| 2021 Diciembre | 59 | 48 | 107 |
| 2021 Noviembre | 81 | 50 | 131 |
| 2021 Octubre | 59 | 65 | 124 |
| 2021 Septiembre | 76 | 55 | 131 |
| 2021 Agosto | 66 | 51 | 117 |
| 2021 Julio | 99 | 43 | 142 |
| 2021 Junio | 82 | 50 | 132 |
| 2021 Mayo | 76 | 62 | 138 |
| 2021 Abril | 153 | 135 | 288 |
| 2021 Marzo | 95 | 45 | 140 |
| 2021 Febrero | 99 | 54 | 153 |
| 2021 Enero | 65 | 40 | 105 |
| 2020 Diciembre | 69 | 52 | 121 |
| 2020 Noviembre | 42 | 39 | 81 |
| 2020 Octubre | 32 | 25 | 57 |
| 2020 Septiembre | 45 | 30 | 75 |
| 2020 Agosto | 41 | 36 | 77 |
| 2020 Julio | 28 | 27 | 55 |
| 2020 Junio | 42 | 47 | 89 |
| 2020 Mayo | 25 | 17 | 42 |
| 2020 Abril | 19 | 16 | 35 |
| 2020 Marzo | 49 | 24 | 73 |
| 2020 Febrero | 2 | 0 | 2 |
| 2020 Enero | 3 | 0 | 3 |
| 2019 Mayo | 1 | 0 | 1 |
| 2018 Agosto | 0 | 1 | 1 |
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