Case and Research Letter
Good Response to Doxycycline in Hailey-Hailey Disease
Enfermedad de Hailey-Hailey, adecuada respuesta a doxiciclina
M.Á. Flores-Terry
, M.P. Cortina-de la Calle, M. López-Nieto, R. Cruz-Conde de Boom
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Servicio de Dermatología, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
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Flores-Terry, M.P. Cortina-de la Calle, M. López-Nieto, R. Cruz-Conde de Boom" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.Á." "apellidos" => "Flores-Terry" "email" => array:1 [ 0 => "miguelterry85@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M.P." "apellidos" => "Cortina-de la Calle" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "López-Nieto" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Cruz-Conde de Boom" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad de Hailey-Hailey, adecuada respuesta a doxiciclina" ] ] "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" => 578 "Ancho" => 1800 "Tamanyo" => 228430 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A and B, Complete resolution of the lesions in the axillary and inguinal skin folds 16 months after initiating treatment with doxycycline.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hailey-Hailey disease (HHD) or familial benign chronic pemphigus is a rare skin disorder characterized clinically by vesicles and erosions in the intertriginous areas, mainly the axillas and groin.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1–4</span></a> The site of the lesions, the pain, and sometimes their smell have a marked impact on patients’ quality of life<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a>; this has led to the use of numerous medical and surgical treatments, with variable degrees of success. We present a patient with long-standing, extensive HHD who presented an excellent response to doxycycline.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 60-year-old man with no past history of interest was referred from another health area for a recurrent dermatosis that had arisen 20 years earlier and affected the skin folds. He presented crusted, exudative, erosive-vesicular lesions in the skin folds, particularly the axillary and inguinal folds (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), the cubital fossa, neck, and perineum. The lesions were pruritic and painful and became worse during the summer and with exercise. He had previously been treated with corticosteroids and topical antibiotics with little improvement. The patient reported no family history of skin disease, though the youngest of his 4 offspring (2 women and 2 men) presented similar but milder lesions on the neck and in the axillas. Biopsy confirmed the diagnosis of HHD (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Direct immunofluorescence was negative. Routine blood tests were normal and antinuclear antibodies and indirect immunofluorescence for anti-intercellular cement substance and antibasement membrane zone antibodies) were negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Treatment was prescribed with doxycycline at a dose of 100<span class="elsevierStyleHsp" style=""></span>mg/d. This was very well tolerated and led to a rapid improvement that was maintained throughout the summer months. The dose was then reduced to 50<span class="elsevierStyleHsp" style=""></span>mg/d. After 16 months of follow-up on the same dose, the patient remained asymptomatic (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">HHD is a rare chronic genodermatosis of autosomal dominant inheritance. It is caused by mutations in the <span class="elsevierStyleItalic">ATP2C1</span> gene on chromosome 3q21-24. Mutations of this gene, which codes for the secretory pathway Ca<span class="elsevierStyleSup">++</span>/Mn<span class="elsevierStyleSup">++</span>-ATPase (SPCA1) of the Golgi apparatus, cause changes in calcium-dependent intracellular signals, producing a loss of cell adhesion in the epidermis, leading to acantholysis.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1–3</span></a> The exact mechanism of the changes remains unclear.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">HHD has been treated with varying degrees of success using a variety of treatments aimed at mitigating the inflammation or reducing the triggering factors; treatments reported in the literature include topical and systemic corticosteroids, topical antibiotics, oral retinoids, immunosuppressants such as ciclosporin and methotrexate, dapsone, botulinum toxin, oral glycopyrrolate, dermabrasion, various lasers, and photodynamic therapy.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Tetracycline, doxycycline, and minocycline have been used with success in dermatology, exploiting their nonantimicrobial effects as anti-inflammatory agents (inhibition of leucocyte chemotaxis and activation and regulation of inflammatory cytokines in keratinocytes) and their anticollagenase activity via inhibition of the dermal matrix metalloproteinases. Metalloproteinase 9 and its inhibitor have been implicated in HHD and in Darier disease.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The recent publication of 6 cases of HHD with a dramatic response to doxycycline,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> with ease of access and management, low cost, and few side effects, led us to use this drug. The treatment achieved an excellent response never before experienced by our patient either spontaneously or with other topical treatments (dermal corticosteroids and fusidic acid).</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Flores-Terry MÁ, Cortina-de la Calle MP, López-Nieto M, Cruz-Conde de Boom R. Enfermedad de Hailey-Hailey, adecuada respuesta a doxiciclina. Actas Dermosifiliogr. 2016;107:537–539.</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" => 574 "Ancho" => 1800 "Tamanyo" => 232266 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A and B, Erosive, erythematous plaques in the axillary and inguinal skin folds.</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" => 857 "Ancho" => 1300 "Tamanyo" => 386644 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Suprabasal acantholysis with a dilapidated brick wall appearance. Hematoxylin and eosin (H&E), original magnification<span class="elsevierStyleHsp" style=""></span>×20). Inset: detail of the acantholysis; H&E, original magnification<span class="elsevierStyleHsp" style=""></span>×40.</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" => 578 "Ancho" => 1800 "Tamanyo" => 228430 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A and B, Complete resolution of the lesions in the axillary and inguinal skin folds 16 months after initiating treatment with doxycycline.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Z. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 4 | 6 | 10 |
| 2024 Octubre | 98 | 68 | 166 |
| 2024 Septiembre | 109 | 37 | 146 |
| 2024 Agosto | 133 | 57 | 190 |
| 2024 Julio | 109 | 39 | 148 |
| 2024 Junio | 145 | 48 | 193 |
| 2024 Mayo | 104 | 35 | 139 |
| 2024 Abril | 113 | 37 | 150 |
| 2024 Marzo | 88 | 29 | 117 |
| 2024 Febrero | 98 | 43 | 141 |
| 2024 Enero | 89 | 35 | 124 |
| 2023 Diciembre | 77 | 20 | 97 |
| 2023 Noviembre | 77 | 29 | 106 |
| 2023 Octubre | 89 | 33 | 122 |
| 2023 Septiembre | 91 | 29 | 120 |
| 2023 Agosto | 93 | 26 | 119 |
| 2023 Julio | 112 | 38 | 150 |
| 2023 Junio | 126 | 23 | 149 |
| 2023 Mayo | 112 | 29 | 141 |
| 2023 Abril | 99 | 19 | 118 |
| 2023 Marzo | 84 | 32 | 116 |
| 2023 Febrero | 119 | 32 | 151 |
| 2023 Enero | 91 | 36 | 127 |
| 2022 Diciembre | 99 | 31 | 130 |
| 2022 Noviembre | 75 | 28 | 103 |
| 2022 Octubre | 79 | 27 | 106 |
| 2022 Septiembre | 57 | 38 | 95 |
| 2022 Agosto | 37 | 30 | 67 |
| 2022 Julio | 85 | 47 | 132 |
| 2022 Junio | 65 | 34 | 99 |
| 2022 Mayo | 152 | 28 | 180 |
| 2022 Abril | 181 | 41 | 222 |
| 2022 Marzo | 137 | 46 | 183 |
| 2022 Febrero | 148 | 31 | 179 |
| 2022 Enero | 210 | 51 | 261 |
| 2021 Diciembre | 123 | 55 | 178 |
| 2021 Noviembre | 141 | 43 | 184 |
| 2021 Octubre | 157 | 59 | 216 |
| 2021 Septiembre | 118 | 48 | 166 |
| 2021 Agosto | 134 | 43 | 177 |
| 2021 Julio | 157 | 39 | 196 |
| 2021 Junio | 167 | 40 | 207 |
| 2021 Mayo | 117 | 42 | 159 |
| 2021 Abril | 366 | 84 | 450 |
| 2021 Marzo | 191 | 23 | 214 |
| 2021 Febrero | 143 | 14 | 157 |
| 2021 Enero | 91 | 13 | 104 |
| 2020 Diciembre | 85 | 15 | 100 |
| 2020 Noviembre | 86 | 11 | 97 |
| 2020 Octubre | 49 | 15 | 64 |
| 2020 Septiembre | 85 | 16 | 101 |
| 2020 Agosto | 57 | 25 | 82 |
| 2020 Julio | 68 | 19 | 87 |
| 2020 Junio | 46 | 32 | 78 |
| 2020 Mayo | 59 | 24 | 83 |
| 2020 Abril | 38 | 21 | 59 |
| 2020 Marzo | 35 | 12 | 47 |
| 2020 Febrero | 4 | 0 | 4 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Octubre | 1 | 0 | 1 |
| 2019 Septiembre | 1 | 0 | 1 |
| 2019 Agosto | 8 | 0 | 8 |
| 2019 Julio | 6 | 0 | 6 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 6 | 0 | 6 |
| 2019 Abril | 15 | 0 | 15 |
| 2019 Marzo | 4 | 5 | 9 |
| 2019 Febrero | 1 | 0 | 1 |
| 2019 Enero | 5 | 0 | 5 |
| 2018 Diciembre | 2 | 0 | 2 |
| 2018 Noviembre | 1 | 0 | 1 |
| 2018 Octubre | 4 | 0 | 4 |
| 2018 Septiembre | 6 | 0 | 6 |
| 2018 Febrero | 56 | 2 | 58 |
| 2018 Enero | 116 | 7 | 123 |
| 2017 Diciembre | 129 | 2 | 131 |
| 2017 Noviembre | 38 | 4 | 42 |
| 2017 Octubre | 42 | 7 | 49 |
| 2017 Septiembre | 40 | 10 | 50 |
| 2017 Agosto | 57 | 8 | 65 |
| 2017 Julio | 48 | 6 | 54 |
| 2017 Junio | 54 | 13 | 67 |
| 2017 Mayo | 40 | 11 | 51 |
| 2017 Abril | 26 | 22 | 48 |
| 2017 Marzo | 25 | 10 | 35 |
| 2017 Febrero | 36 | 6 | 42 |
| 2017 Enero | 23 | 9 | 32 |
| 2016 Diciembre | 33 | 20 | 53 |
| 2016 Noviembre | 26 | 23 | 49 |
| 2016 Octubre | 36 | 19 | 55 |
| 2016 Septiembre | 0 | 1 | 1 |
| 2016 Agosto | 2 | 2 | 4 |
| 2016 Julio | 4 | 4 | 8 |
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