Case and Research Letter
Metastatic Crohn Disease
Enfermedad de Crohn metastásica
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Ruiz-Villaverde, D. Sánchez-Cano, I. Perez-Lopez, J. Aneiros-Fernández" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Ruiz-Villaverde" "email" => array:1 [ 0 => "ismenios@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "D." "apellidos" => "Sánchez-Cano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "Perez-Lopez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "J." "apellidos" => "Aneiros-Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Dermatología Médico-Quirúrgica y Venereología, Complejo Hospitalario de Granada, Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Medicina Interna, Complejo Hospitalario de Granada, Granada, España" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Complejo Hospitalario de Granada, Granada, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad de Crohn metastásica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1778 "Ancho" => 1167 "Tamanyo" => 521026 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Eczematous plaques with an atrophic center and no ulceration on the anterior aspect of both thighs.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Skin involvement in Crohn disease (CD) occurs in up to 44% of the patients affected by this disease, depending on the series.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> From a pathophysiologic point of view, mucocutaneous lesions can be divided into specific lesions, caused by the same pathophysiologic mechanism as CD, reactive lesions, histologically different from the former and caused by cross-antigenicity between the skin and the digestive tract, and associated lesions, whose mechanism is not well understood.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Metastatic CD presents with specific lesions. It was first described in 1965 and is the least common specific manifestation of CD. We present a case recently diagnosed in our unit.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 35-year-old man with a 9-year history of CD, well controlled on infliximab at a dose of 5<span class="elsevierStyleHsp" style=""></span>mg/kg every 8 weeks. He was referred from gastroenterology outpatients for an 8-week history of eczema on the anterior aspect of both thighs. The lesions had not responded to 5 weeks of topical therapy with clobetasol cream under an occlusive dressing.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Physical examination revealed the presence of eczematous plaques of up to 5<span class="elsevierStyleHsp" style=""></span>cm in diameter on the anterior aspect of both thighs. The lesions had a pale atrophic center with no ulceration and a slightly indurated erythematous border covered by a serous crust. There were no palpable locoregional lymph nodes (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). Additional tests (complete blood count, routine biochemistry, erythrocyte sedimentation rate, C-reactive protein, autoantibodies, circulating immune complexes, angiotensin converting enzyme, and 24-hour urinary calcium) were within normal limits and no abnormalities were observed on chest x-ray.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Histology revealed the presence of a chronic granulomatous inflammatory infiltrate in the dermis, with intense epithelial hyperplasia and foci of ulceration (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>A). Noncaseating granulomas with multinucleated giant cells were visible at higher magnification, some with a perivascular distribution (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>B). Stains (Ziehl-Neelsen and Grocott) performed to exclude mycobacterial and mycotic infections were negative.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Infliximab levels were normal (4<span class="elsevierStyleHsp" style=""></span>μg/ml; normal target range, 3-10<span class="elsevierStyleHsp" style=""></span>μg/ml) and antidrug antibody (ADA) levels were elevated (ADA, 15<span class="elsevierStyleHsp" style=""></span>arbitrary units [AU]/ml; a value greater than 10<span class="elsevierStyleHsp" style=""></span>AU/ml is considered positive).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Based on these findings, we made a diagnosis of metastatic CD. Treatment was started with prednisone at a dose of 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/d, achieving moderate control of the cutaneous alterations. Changing the treatment of the patient's underlying disease to adalimumab at therapeutic doses for CD was suggested, and this led to the definitive resolution of the plaques for which the patient had consulted.</p><p id="par0035" class="elsevierStylePara elsevierViewall">CD is currently considered to be 1 of the immune-mediated systemic diseases able to affect organs outside the digestive tract, such as the skin. Although there is no reliably demonstrated hypothesis, the presence of perivascular granulomas and circulating immune complexes points to phenomena of a vasculitic nature.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The global prevalence of metastatic CD is below 0.7%, with a slight female predominance, and it can affect the population with pediatric-onset CD.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> The clinical heterogeneity of the condition may be a cause of incorrect diagnosis or underdiagnosis.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Clinically, it presents as indurated erythematous plaques or nodules that may or may not be pigmented and that are sometimes ulcerated; there is no continuity between these lesions and the intestinal disease. The sites most frequently affected are the genital region,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> the skin folds (submammary, retroauricular, inguinal, and abdominal), and the lower limbs, though isolated or multiple lesions can arise anywhere on the skin. No relationship with activity of the intestinal disease is observed, though skin lesions appear to be more common among patients with involvement of the colon.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Histologically the lesions are characterized by the presence of noncaseating granulomas of epithelioid histiocytes and multinucleated cells in the papillary and reticular dermis, though no evidence has been found of concordance between the presence of granulomas on intestinal biopsy and their appearance in the skin. A perivascular lymphocytic inflammatory infiltrate is characteristic. Histology can be indistinguishable from cutaneous sarcoidosis.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In our case, due to the site of the lesions, the differential diagnosis included cellulitis, allergic contact dermatitis, pyoderma gangrenosum, and Wegener granulomatosis. From a pathologic viewpoint, the differential diagnosis included sarcoidosis, mycobacteriosis, and the deep mycoses.</p><p id="par0060" class="elsevierStylePara elsevierViewall">No well-established action protocols have been drawn up and treatment is therefore prescribed in accordance with the patient's preference, the side effects, and the need for monitoring.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The number of lesions and their site may allow us to use first-line topical therapies (corticosteroids or calcineurin inhibitors). If no response is achieved, systemic corticosteroids (prednisone, 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg), oral metronidazole (800-1500<span class="elsevierStyleHsp" style=""></span>mg/d), conventional immunosuppressants (methotrexate, azathioprine, ciclosporin), or even biologics (infliximab, certolizumab, or adalimumab) may be required.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5,6</span></a> Recently, case series have been published describing patients with pediatric-onset CD successfully treated with adalimumab after failure of initial therapy with infliximab, with follow-up for over a year, as occurred in the case we have presented.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></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: Ruiz-Villaverde R, Sánchez-Cano D, Perez-Lopez I, Aneiros-Fernández J. Enfermedad de Crohn metastásica. Actas Dermosifiliogr. 2017;108:171–172.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1778 "Ancho" => 1167 "Tamanyo" => 521026 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Eczematous plaques with an atrophic center and no ulceration on the anterior aspect of both thighs.</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" => 1286 "Ancho" => 2500 "Tamanyo" => 1126131 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>, Chronic granulomatous inflammatory infiltrate in the mid dermis. Hematoxylin and eosin (H&E), original magnification ×1. <span class="elsevierStyleBold">B</span>, Noncaseating granulomas with multinucleated giant cells. H&E, original magnification ×20.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metastatic cutaneous Crohn's disease of the face: A case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Albuquerque" 1 => "F. Magro" 2 => "S. Rodrigues" 3 => "J. Lopes" 4 => "S. Lopes" 5 => "J.M. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 15 | 9 | 24 |
| 2024 Octubre | 84 | 47 | 131 |
| 2024 Septiembre | 95 | 37 | 132 |
| 2024 Agosto | 131 | 74 | 205 |
| 2024 Julio | 127 | 32 | 159 |
| 2024 Junio | 92 | 38 | 130 |
| 2024 Mayo | 67 | 30 | 97 |
| 2024 Abril | 68 | 26 | 94 |
| 2024 Marzo | 69 | 30 | 99 |
| 2024 Febrero | 96 | 32 | 128 |
| 2024 Enero | 58 | 38 | 96 |
| 2023 Diciembre | 67 | 21 | 88 |
| 2023 Noviembre | 82 | 20 | 102 |
| 2023 Octubre | 78 | 38 | 116 |
| 2023 Septiembre | 71 | 25 | 96 |
| 2023 Agosto | 51 | 18 | 69 |
| 2023 Julio | 75 | 29 | 104 |
| 2023 Junio | 66 | 23 | 89 |
| 2023 Mayo | 70 | 21 | 91 |
| 2023 Abril | 91 | 21 | 112 |
| 2023 Marzo | 57 | 25 | 82 |
| 2023 Febrero | 53 | 29 | 82 |
| 2023 Enero | 52 | 30 | 82 |
| 2022 Diciembre | 63 | 41 | 104 |
| 2022 Noviembre | 46 | 33 | 79 |
| 2022 Octubre | 43 | 19 | 62 |
| 2022 Septiembre | 46 | 29 | 75 |
| 2022 Agosto | 39 | 27 | 66 |
| 2022 Julio | 39 | 39 | 78 |
| 2022 Junio | 37 | 29 | 66 |
| 2022 Mayo | 76 | 37 | 113 |
| 2022 Abril | 56 | 28 | 84 |
| 2022 Marzo | 40 | 38 | 78 |
| 2022 Febrero | 74 | 31 | 105 |
| 2022 Enero | 72 | 46 | 118 |
| 2021 Diciembre | 47 | 42 | 89 |
| 2021 Noviembre | 62 | 39 | 101 |
| 2021 Octubre | 70 | 56 | 126 |
| 2021 Septiembre | 41 | 43 | 84 |
| 2021 Agosto | 48 | 40 | 88 |
| 2021 Julio | 45 | 31 | 76 |
| 2021 Junio | 27 | 35 | 62 |
| 2021 Mayo | 47 | 53 | 100 |
| 2021 Abril | 114 | 112 | 226 |
| 2021 Marzo | 73 | 40 | 113 |
| 2021 Febrero | 63 | 57 | 120 |
| 2021 Enero | 48 | 21 | 69 |
| 2020 Diciembre | 72 | 24 | 96 |
| 2020 Noviembre | 22 | 21 | 43 |
| 2020 Octubre | 30 | 14 | 44 |
| 2020 Septiembre | 46 | 33 | 79 |
| 2020 Agosto | 29 | 22 | 51 |
| 2020 Julio | 27 | 27 | 54 |
| 2020 Junio | 38 | 38 | 76 |
| 2020 Mayo | 31 | 10 | 41 |
| 2020 Abril | 21 | 22 | 43 |
| 2020 Marzo | 22 | 13 | 35 |
| 2020 Febrero | 3 | 0 | 3 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Septiembre | 4 | 0 | 4 |
| 2019 Agosto | 7 | 0 | 7 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 6 | 0 | 6 |
| 2019 Abril | 3 | 4 | 7 |
| 2019 Febrero | 2 | 0 | 2 |
| 2018 Diciembre | 5 | 0 | 5 |
| 2018 Octubre | 1 | 0 | 1 |
| 2018 Septiembre | 5 | 0 | 5 |
| 2018 Febrero | 16 | 3 | 19 |
| 2018 Enero | 26 | 3 | 29 |
| 2017 Diciembre | 29 | 6 | 35 |
| 2017 Noviembre | 24 | 8 | 32 |
| 2017 Octubre | 24 | 3 | 27 |
| 2017 Septiembre | 20 | 2 | 22 |
| 2017 Agosto | 27 | 13 | 40 |
| 2017 Julio | 20 | 7 | 27 |
| 2017 Junio | 34 | 6 | 40 |
| 2017 Mayo | 32 | 13 | 45 |
| 2017 Abril | 30 | 16 | 46 |
| 2017 Marzo | 65 | 50 | 115 |
| 2017 Febrero | 21 | 25 | 46 |
| 2017 Enero | 3 | 9 | 12 |
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