Alopecia universalis after discontinuation of pegylated interferon and ribavirin combination therapy for hepatitis C: a case report

array:24 ["pii" => "S1665268119308944" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)30894-4" "estado" => "S300" "fechaPublicacion" => "2014-03-01" "aid" => "70650" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2014" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Ann Hepatol. 2014;13:293-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 116 "formatos" => array:3 [ "EPUB" => 7 "HTML" => 52 "PDF" => 57 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119308956" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)30895-6" "estado" => "S300" "fechaPublicacion" => "2014-03-01" "aid" => "70651" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Ann Hepatol. 2014;13:297-302" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 138 "formatos" => array:3 [ "EPUB" => 12 "HTML" => 97 "PDF" => 29 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Variability of apparent diffusion coefficients in metastatic small cell lung carcinoma: comparisons between-within normal tissue and liver metastases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "297" "paginaFinal" => "302" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 454 "Ancho" => 508 "Tamanyo" => 42898 ] ] "descripcion" => array:1 [ "en" => "Bar graphs depicting the significant variability observed between-tissues (normal tissue vs. metastasis) and with-in lesions (metastatic tissue) in the ADC measurements after a 2-month follow-up evaluation. Normal distribution of data allowed the performance of parametric tests." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ernesto Roldán-Valadez, David Cortez-Conradis, Alejandro Ríos-Hoyo, Óscar Arrieta" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Ernesto" "apellidos" => "Roldán-Valadez" ] 1 => array:2 [ "nombre" => "David" "apellidos" => "Cortez-Conradis" ] 2 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Ríos-Hoyo" ] 3 => array:2 [ "nombre" => "Óscar" "apellidos" => "Arrieta" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308956?idApp=UINPBA00004N" "url" => "/16652681/0000001300000002/v1_201906020852/S1665268119308956/v1_201906020852/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119308932" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)30893-2" "estado" => "S300" "fechaPublicacion" => "2014-03-01" "aid" => "70649" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Ann Hepatol. 2014;13:288-92" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 54 "formatos" => array:3 [ "EPUB" => 5 "HTML" => 25 "PDF" => 24 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "Successful orthotopic liver transplantation and delayed delivery of a healthy newborn in a woman with fulminant hepatic failure during the second trimester of pregnancy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "288" "paginaFinal" => "292" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Manuel Mendizabal, Carlos Rowe, Federico Piñero, Ariel Gonzalez-Campaña, Martín Fauda, Diego Tomás Arufe, María Pía Raffa, Mariano Barreiro, Rodolfo Keller, Fernando Cacheiro, Ernesto Beruti, Oscar Andriani, Marcelo Oscar Silva, Luis Gustavo Podestá" "autores" => array:15 [ 0 => array:2 [ "nombre" => "Manuel" "apellidos" => "Mendizabal" ] 1 => array:2 [ "nombre" => "Carlos" "apellidos" => "Rowe" ] 2 => array:2 [ "nombre" => "Federico" "apellidos" => "Piñero" ] 3 => array:2 [ "nombre" => "Ariel" "apellidos" => "Gonzalez-Campaña" ] 4 => array:2 [ "nombre" => "Martín" "apellidos" => "Fauda" ] 5 => array:2 [ "nombre" => "Diego Tomás" "apellidos" => "Arufe" ] 6 => array:2 [ "nombre" => "Martín" "apellidos" => "Fauda" ] 7 => array:2 [ "nombre" => "María Pía" "apellidos" => "Raffa" ] 8 => array:2 [ "nombre" => "Mariano" "apellidos" => "Barreiro" ] 9 => array:2 [ "nombre" => "Rodolfo" "apellidos" => "Keller" ] 10 => array:2 [ "nombre" => "Fernando" "apellidos" => "Cacheiro" ] 11 => array:2 [ "nombre" => "Ernesto" "apellidos" => "Beruti" ] 12 => array:2 [ "nombre" => "Oscar" "apellidos" => "Andriani" ] 13 => array:2 [ "nombre" => "Marcelo Oscar" "apellidos" => "Silva" ] 14 => array:2 [ "nombre" => "Luis Gustavo" "apellidos" => "Podestá" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308932?idApp=UINPBA00004N" "url" => "/16652681/0000001300000002/v1_201906020852/S1665268119308932/v1_201906020852/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "Alopecia universalis after discontinuation of pegylated interferon and ribavirin combination therapy for hepatitis C: a case report" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "293" "paginaFinal" => "296" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Nesrine Gamal, Lucia Brodosi, Cosimo Misciali, Annalisa Patrizi, Gentiana Vukatana, Nazzarena Malavolta, Mauro Bernardi, Pietro Andreone" "autores" => array:8 [ 0 => array:3 [ "nombre" => "Nesrine" "apellidos" => "Gamal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Lucia" "apellidos" => "Brodosi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Cosimo" "apellidos" => "Misciali" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Annalisa" "apellidos" => "Patrizi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Gentiana" "apellidos" => "Vukatana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "***" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Nazzarena" "apellidos" => "Malavolta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "***" "identificador" => "aff0015" ] ] ] 6 => array:3 [ "nombre" => "Mauro" "apellidos" => "Bernardi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] ] ] 7 => array:4 [ "nombre" => "Pietro" "apellidos" => "Andreone" "email" => array:1 [ 0 => "pietro.andreone@unibo.it" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna and Azienda Ospedaliero Universitaria, Policlinico Sant’Orsola Malpighi di Bologna, Italy" "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna and Azienda Ospedaliero Universitaria, Policlinico Sant’Orsola Malpighi di Bologna, Italy" "etiqueta" => "**" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Dipartimento di Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche, Università di Bologna and Azienda Ospedaliero Universitaria, Policlinico Sant’Orsola Malpighi di Bologna, Italy" "etiqueta" => "***" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 378 "Ancho" => 504 "Tamanyo" => 12718 ] ] "descripcion" => array:1 [ "en" => "Dermoscopy [40x] showing increased number of yellow dots (dotted arrows) and few cadaverized hair (black dots) on the epidermis (solid arrows)." ] ] ] "textoCompleto" => "IntroductionHepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Over the past decade, the current standard-of-care treatment has been the combination of pegylated interferon (Peg-IFN) plus ribavirin (RBV).<a class="elsevierStyleCrossRef" href="#bib0010">2</a> With US Food and Drug Administration approval of boceprevir and telaprevir (two protease inhibitors), the standard-of-care treatment for genotype-1 infection is now Peg-IFN/RBV and a protease inhibitor.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Pegylation is an important technique, which has greatly improved the pharmacologic profile of interferon by reducing the proteins’ sensitivity to proteolysis hence increasing their half-life.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> However, several adverse effects are associated with this treatment, among which the most common are hematological (such as anemia and thrombocytopenia), flu-like syndrome, psychiatric, endocrine, digestive and dermatological.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> The emergence of several types of autoantibodies or even autoimmune diseases has been reported during IFN-alfa treatment.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Alopecia is a dermatologic disorder that means loss of hair. It is commonly believed to be an autoimmune disease, which might be clinically presented as a single patch of hair loss (alopecia areata; AA), complete loss of hair on the scalp (alopecia totalis) or the entire body (alopecia universalis; AU).<a class="elsevierStyleCrossRef" href="#bib0030">6</a> We here report a case of irreversible AU after Peg-IFN α-2b and RBV treatment in a subject with chronic hepatitis C.Case ReportA 49-year-old male patient was diagnosed as having chronic HCV infection proven by positive anti-HCV antibody and detectable HCV-RNA. He was referred to our hepatitis C outpatient clinic in January 2011. His medical history was insignificant except for arthritis of the small joints started in 2007.When he presented to our unit in 2011, he was in good general conditions, yet, obese (BMI 31.3 kg/m<a class="elsevierStyleCrossRef" href="#bib0010">2</a>). Regarding his virological profile, he was HCV-RNA positive (55,000 IU/mL), HCV genotype 3 and serogical tests for HBV and HIV were negative. Transaminases were two times the upper limit of normal. A liver biopsy was performed showing minimal necro-inflammatory activity and fibrosis stage 2 (Ishak score). Immunological blood tests revealed a positive anti-nuclear antibody and a positive anti-thyroid peroxidase antibodies test with normal thyroid stimulating hormone value. Treatment was started with a weekly subcutaneous dose of Peg-IFNα-2b 150 μg, along with a daily oral dose of 1,200 mg of RBV. One week following the first antiviral dose, his HCV-RNA was negative (< 10 IU/mL).No major undesired effects were reported during the treatment course, except for a mild form of pancytopenia at week 8 which required no moderation in his treatment protocol and which was resolved spontaneously by the end of treatment course that lasted for 12 weeks.One month after the completion of the combined antiviral therapy, the patient reported a significant amount of hair loss from his scalp, which progressed to affect his eyebrows, hair on his upper and lower limbs. Hair loss continued to affect the axillary and pubic areas. By the end of the third month following treatment completion, the patient had a total loss of all body hair. The patient was evaluated by a dermatologist who diagnosed his condition as AU and prescribed a topical corticosteroid cream and heliotherapy for 6 months, without improvement.A scalp biopsy was performed 13 months after treatment discontinuation revealing absence of terminal hair follicles with increased number of miniaturized anagen hair follicles (vellus follicles), catagen and telogen germinal units (<a class="elsevierStyleCrossRef" href="#f0005">Figures 1A, 1B</a>). Moderate perifollicular lymphocytic infiltration was also seen with slight fibroplasia. Increased number of yellow dots with few cadaverized hair (black dots) on the epidermis were seen by dermoscopy (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>). The presence of yellow dots differentiates alopecia areata from trichotillomania or telogen effluvium.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> The definitive diagnosis was alopecia areata universalis in telogen arrest phase. At the time we are writing our report the patient has discontinued the antiviral therapy since 16 months, and AU still shows no improvement. The patient has tolerated this adverse effect well, and refused any systemic medications for the alopecia.<elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="f0010"></elsevierMultimedia>A written informed consent was obtained from the patient to describe this report.DiscussionAA is a disease of the anagen stage hair follicles.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> It is a clinically heterogeneous disease characterized by non-scarring hair loss on the scalp or any hairbearing surface.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> AU is the most severe variant of AA in which all scalp and body hair is lost. AA and AU are commonly believed to have an autoimmune etiology with genetic, environmental and immunological factors involved.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Associations between AA and classical autoimmune disorders, namely, thyroid disease (including Hashimoto’s thyroiditis), myasthenia gravis, systemic lupus erythematosus and vitiligo have been previously reported.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> Combination Peg-IFN/ RBV therapy has been associated with an increased incidence of adverse cutaneous reactions, including injection site reactions, psoriasis, eczematoid drug reaction, sarcoidosis, mixed cryoglobulinemia, cutaneous lupus erythematosus and alopecia.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>,<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Treatment with Peg-IFN has been also associated with several autoimmune disorders such as hypothyroidism, lupus-like syndrome and autoimmune hepatitis.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Recent studies proved that Peg-IFN induces immunologic modulation (shift from Th2 immune-driven response to Th1) and stimulates the synthesis of Th1-cytokines such as IL-1, IL-2 and IFN-γ.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Furthermore, it also increases cytotoxic T-cell activity.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Elevated serum levels of IFN-γ and IL-2 in patients with AU have been reported and these results indicate that immune response in AU is regulated by Th1 cytokines.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> The pathogenetic mechanisms so far known indicate a very complex process leading to an inflammatory reaction that causes hair loss.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> It is a vicious cycle: the keratinocytes release cytokines that activate endothelial cells which, in turn, attract T-cells and macrophages that release more cytokines and so on. Autoantibodies against follicular autoantigens could be found in the serum and skin of AA patients and can occur before clinically detectable hair loss<a class="elsevierStyleCrossRef" href="#bib0095">19</a> but there is no evidence they are pathogenic.<a class="elsevierStyleCrossRef" href="#bib0100">20</a>,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> A concrete hypothesis on the pathogenetic mechanisms of AU in our case is difficult to be formed. Presumably, in genetically predisposed individuals and under the immunemodulatory effect of Peg-IFN/RBV therapy, the hair follicle enters a cycle of autoimmune inhibition of its growth.Although diagnosing alopecia areata might be easy, treating it is not. Our fundamental therapeutic challenge is to reduce the already established inflammatory infiltrates and to prevent further spread to unaffected hair follicles. To date, all therapeutic options do not satisfactorily meet this challenge.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Many treatment modalities have been implicated in the treatment of AA.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Topical corticosteroids and immunotherapy, systemic corticosteroids, systemic immunosuppresants, psoralen plus ultraviolet A photochemotherapy were among treatment options for AA. Alopecia is a physiologically distressing disorder and physicians should provide their patients with realistic advice about treatments and their effectiveness. Several forms of alopecia linked to Peg-IFN/RBV have been reported in the literature ranging from subcutaneous injection site alopecia,<a class="elsevierStyleCrossRef" href="#bib0115">23</a> irreversible AT,<a class="elsevierStyleCrossRef" href="#bib0120">24</a> reversible AU,<a class="elsevierStyleCrossRef" href="#bib0125">25</a>,<a class="elsevierStyleCrossRefs" href="#bib0130">26</a>–<a class="elsevierStyleCrossRef" href="#bib0140">28</a> and one case of irreversible AU.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> Interestingly, unlike all reported cases, our patient experienced hair loss one month after the discontinuation of treatment and this is quiet alarming.To conclude, this case represents an uncommon presentation of a common disease. Physicians must be aware of the potential adverse reactions of an antiviral therapy containing IFN, which might occur even after the discontinuation, and fully inform the patient at the beginning of his treatment course. Ultimately, the advent of interferon-free regimens would represent the fulfillment of an enormous unmet need in interferon-incapable or intolerant patients. We hope that such regimens will utterly supplant interferon-based therapy for most or all HCV patients avoiding the emergence of autoimmune manifestations.DisclosureNo conflict of interest declared." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:3 [ "identificador" => "xres1199011" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1117451" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "s0010" "titulo" => "Case Report" ] 4 => array:2 [ "identificador" => "s0015" "titulo" => "Discussion" ] 5 => array:2 [ "identificador" => "s0020" "titulo" => "Disclosure" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-04-03" "fechaAceptado" => "2013-06-05" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1117451" "palabras" => array:3 [ 0 => "Alopecia" 1 => "Side-effects" 2 => "Antiviral therapy" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "For the last decade, the combination therapy of pegylated interferon (Peg-IFN) plus ribavirin (RBV) has been considered as the standard of care treatment for chronic hepatitis C virus (HCV) infection. However, it has been associated with an increased incidence of many adverse cutaneous reactions and emergence of autoantibodies or even autoimmune diseases. We report a case of irreversible alopecia universalis (AU) with complete hair loss extended to the whole body, which started after discontinuation of Peg-IFN/RBV combination therapy for chronic HCV infection. In conclusion, this case represents an uncommon presentation of a common disease. Physicians must be aware of the potential adverse reactions of an antiviral therapy containing IFN, which might occur even after the discontinuation, and fully inform the patient at the beginning of his treatment course. We hope that interferon-free regimens will utterly supplant interferon-based therapy for most or all HCV patients avoiding the emergence of autoimmune manifestations." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1. A" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 344 "Ancho" => 1013 "Tamanyo" => 68691 ] ] "descripcion" => array:1 [ "en" => "Horizontal section of scalp biopsy taken 13 months following treatment discontinuation showing absence of terminal hair follicles with increased number of miniaturized anagen hair follicles (dotted arrows), catagen and telogen germinal units (solid arrows) [H&E 4x]. B. Magnified follicle unit with miniaturized anagen hair follicle (dotted arrow) and telogen germinal unit (solid arrow) [H&E 20x]." ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 378 "Ancho" => 504 "Tamanyo" => 12718 ] ] "descripcion" => array:1 [ "en" => "Dermoscopy [40x] showing increased number of yellow dots (dotted arrows) and few cadaverized hair (black dots) on the epidermis (solid arrows)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The global burden of hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Lavanchy D." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1478-3231.2008.01934.x" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2009" "volumen" => "29" "paginaInicial" => "74" "paginaFinal" => "81" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19207969" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Pearlman B.L." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1473-3099(12)70060-9" "Revista" => array:6 [ "tituloSerie" => "Lancet Infect Dis" "fecha" => "2012" "volumen" => "12" "paginaInicial" => "717" "paginaFinal" => "728" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22647717" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Reddy K.R." 1 => "Wright T.L." 2 => "Pockros P.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2001.21747" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2001" "volumen" => "33" "paginaInicial" => "433" "paginaFinal" => "438" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11172346" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Review article: the management of side effects during therapy for hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Aspinall R.J." 1 => "Pockros P.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2004.02192.x" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2004" "volumen" => "20" "paginaInicial" => "917" "paginaFinal" => "929" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15521838" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune-mediated side effects of cytokines in humans" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Vial T." 1 => "Descotes J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Toxicology" "fecha" => "1995" "volumen" => "105" "paginaInicial" => "31" "paginaFinal" => "57" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8638283" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Alkhalifah A." 1 => "Alsantali A." 2 => "Wang E." 3 => "McElwee K.J." 4 => "Shapiro J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2009.10.032" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2010" "volumen" => "62" "paginaInicial" => "177" "paginaFinal" => "188" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20115945" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hair Evaluation Methods: Merits and Demerits" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Dhurat Rachita" 1 => "Saraogi Punit" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/0974-7753.58553" "Revista" => array:6 [ "tituloSerie" => "Int J Trichology" "fecha" => "2009" "volumen" => "1" "paginaInicial" => "108" "paginaFinal" => "119" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20927232" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology and genetics of alopecia areata" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "McDonagh A.J." 1 => "Tazi-Ahnini R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2002" "volumen" => "27" "paginaInicial" => "405" "paginaFinal" => "409" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12190641" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alopecia areata: autoimmune basis of hair loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Alexis A.F." 1 => "Dudda-Subramanya R." 2 => "Sinha A.A." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Dermatol" "fecha" => "2004" "volumen" => "14" "paginaInicial" => "364" "paginaFinal" => "370" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15564197" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Profile of alopecia areata: a survey analysis of patient and family" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Shellow W.V." 1 => "Edwards J.E." 2 => "Koo J.Y." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Dermatol" "fecha" => "1992" "volumen" => "31" "paginaInicial" => "186" "paginaFinal" => "189" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1568816" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alopecia areata" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Elder D.E." 1 => "Elenitsas R." 2 => "Johnson B.L." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:7 [ "edicion" => "9" "titulo" => "Lever’s Histopatholgy of the Skin" "fecha" => "2005" "paginaInicial" => "483" "paginaFinal" => "485" "editorial" => "Lippincott Williams and Wilkins" "editorialLocalizacion" => "Philadelphia" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High prevalence of cutaneous reactions to interferon alfa plus ribavirin combination therapy in patients with chronic hepatitis C virus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Sookoian S." 1 => "Neglia V." 2 => "Castano G." 3 => "Frider B." 4 => "Kien M.C." 5 => "Chohuela E." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "1999" "volumen" => "135" "paginaInicial" => "1000" "paginaFinal" => "1001" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10456365" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A review of adverse cutaneous drug reactions resulting from the use of interferon and ribavirin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Mistry N." 1 => "Shapero J." 2 => "Crawford R.I." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Can J Gastroenterol" "fecha" => "2009" "volumen" => "23" "paginaInicial" => "677" "paginaFinal" => "683" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19826642" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Side effects of therapy of hepatitis C and their management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Fried M.W." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Hepatology" "fecha" => "2002" "volumen" => "36" "paginaInicial" => "237" "paginaFinal" => "244" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dermatologic manifestations of hepatitis C infection and the effect of interferon therapy: a literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Jadali Z." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "012151/AIM.0012" "Revista" => array:6 [ "tituloSerie" => "Arch Iran Med" "fecha" => "2012" "volumen" => "15" "paginaInicial" => "43" "paginaFinal" => "48" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22208443" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Maintenance of T1 response as induced during PEG-IFNalpha plus ribavirin therapy controls viral replication in genotype-1 patients with chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:8 [ 0 => "Trapero M." 1 => "Garcia-Buey L." 2 => "Munoz C." 3 => "Viton M." 4 => "Moreno-Monteagudo J.A." 5 => "Borque M.J." 6 => "Quintana N.E." 7 => "Moreno-Otero R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Esp Enferm Dig" "fecha" => "2005" "volumen" => "97" "paginaInicial" => "481" "paginaFinal" => "490" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16262527" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytokines in alopecia areata: contrasting cytokine profiles in localized form and extensive form (alopecia universalis)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Teraki Y." 1 => "Imanishi K." 2 => "Shiohara T." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2340/0001555576421423" "Revista" => array:6 [ "tituloSerie" => "Acta Derm Venereol" "fecha" => "1996" "volumen" => "76" "paginaInicial" => "421" "paginaFinal" => "423" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8982401" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Gregoriou S, Papafragkaki D, Kontochristopoulos G, Rallis E, Kalogeromitros D, Rigopoulos D. Cytokines and other mediators in alopecia areata. Mediators Inflamm 2010. Doi: 10.1155/2010/928030." ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization of hair follicle antigens targeted by the anti-hair follicle immune response" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Tobin D.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.1087-0024.2003.00805.x" "Revista" => array:6 [ "tituloSerie" => "J Investig Dermatol Symp Proc" "fecha" => "2003" "volumen" => "8" "paginaInicial" => "176" "paginaFinal" => "181" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14582669" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Failure of passive transfer of serum from patients with alopecia areata and alopecia universalis to inhibit hair growth in transplants of human scalp skin grafted on to nude mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Gilhar A." 1 => "Pillar T." 2 => "Assy B." 3 => "David M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Br J Dermatol" "fecha" => "1992" "volumen" => "126" "paginaInicial" => "166" "paginaFinal" => "171" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alopecia areata" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Gilhar Amos" 1 => "Etzioni Amos" 2 => "Paus Ralf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra1103442" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "1515" "paginaFinal" => "1525" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22512484" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of alopecia areata" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Harries M.J." 1 => "Sun J." 2 => "Paus R." 3 => "King L.E. Jr" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.c3671" "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2010" "volumen" => "341" "paginaInicial" => "c3671" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20656774" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Localized interferon alfa-2b-induced alopecia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Lang A.M." 1 => "Norland A.M." 2 => "Schuneman R.L." 3 => "Tope W.D." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "1999" "volumen" => "135" "paginaInicial" => "1126" "paginaFinal" => "1128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10490128" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A case of irreversible alopecia associated with ribavirin and peg-interferon therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Shafa S." 1 => "Borum M.L." 2 => "Iglehon E." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MEG.0b013e32832be7a5" "Revista" => array:6 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2010" "volumen" => "22" "paginaInicial" => "122" "paginaFinal" => "123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19959941" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alopecia universalis following interferon alfa-2b and ribavirin treatment for hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Taliani G." 1 => "Biliotti E." 2 => "Capanni M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1179/joc.2005.17.2.212" "Revista" => array:6 [ "tituloSerie" => "J Chemother" "fecha" => "2005" "volumen" => "17" "paginaInicial" => "212" "paginaFinal" => "214" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15920908" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reversible alopecia universalis secondary to PEG-interferon a-2b and ribavirin combination therapy in a patient with chronic hepatitis C virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Kartal E.D." 1 => "Alpat S.N." 2 => "Ozgunes I." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MEG.0b013e32818b27e5" "Revista" => array:6 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2007" "volumen" => "19" "paginaInicial" => "817" "paginaFinal" => "820" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17700271" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alopecia universalis: a rare side effect seen on chronic hepatitis C treatment with peg-IFN and ribavirin" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Demirturk N." 1 => "Aykin N." 2 => "Demirdal T." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Dermatol" "fecha" => "2006" "volumen" => "16" "paginaInicial" => "579" "paginaFinal" => "594" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17101483" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alopecia universalis following interferon Alfa-2b and ribavirin treatment for hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Midian-Singh R." 1 => "Alagugurusamy S." 2 => "Agrawal R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Gastroenterol Hepatol" "fecha" => "2007" "volumen" => "3" "paginaInicial" => "644" "paginaFinal" => "645" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Irreversible alopecia universalis during treatment with pegylated interferon-ribavirin for chronic hepatitis C virus infection: Case report and published work review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Omazzi B." 1 => "Prada A." 2 => "Borroni G." 3 => "Sacrini F." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1872-034X.2012.01036.x" "Revista" => array:6 [ "tituloSerie" => "Hepatol Res" "fecha" => "2012" "volumen" => "42" "paginaInicial" => "1248" "paginaFinal" => "1251" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23181541" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000001300000002/v1_201906020852/S1665268119308944/v1_201906020852/en/main.assets" "Apartado" => array:4 [ "identificador" => "77718" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case Report" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001300000002/v1_201906020852/S1665268119308944/v1_201906020852/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308944?idApp=UINPBA00004N"]

Statistics

Nesrine Gamal*, Lucia Brodosi*, Cosimo Misciali**, Annalisa Patrizi**, Gentiana Vukatana***, Nazzarena Malavolta***, Mauro Bernardi*, Pietro Andreone

Corresponding author

pietro.andreone@unibo.it

Correspondence and reprint request:

* Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna and Azienda Ospedaliero Universitaria, Policlinico Sant’Orsola Malpighi di Bologna, Italy

** Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna and Azienda Ospedaliero Universitaria, Policlinico Sant’Orsola Malpighi di Bologna, Italy

*** Dipartimento di Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche, Università di Bologna and Azienda Ospedaliero Universitaria, Policlinico Sant’Orsola Malpighi di Bologna, Italy

Read

2476

Times
was read the article

608

Total PDF

1868

Total HTML

Share statistics

 array:24 [
  "pii" => "S1665268119308944"
  "issn" => "16652681"
  "doi" => "10.1016/S1665-2681(19)30894-4"
  "estado" => "S300"
  "fechaPublicacion" => "2014-03-01"
  "aid" => "70650"
  "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
  "copyrightAnyo" => "2014"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "crp"
  "cita" => "Ann Hepatol. 2014;13:293-6"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 116
    "formatos" => array:3 [
      "EPUB" => 7
      "HTML" => 52
      "PDF" => 57
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S1665268119308956"
    "issn" => "16652681"
    "doi" => "10.1016/S1665-2681(19)30895-6"
    "estado" => "S300"
    "fechaPublicacion" => "2014-03-01"
    "aid" => "70651"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "crp"
    "cita" => "Ann Hepatol. 2014;13:297-302"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 138
      "formatos" => array:3 [
        "EPUB" => 12
        "HTML" => 97
        "PDF" => 29
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "titulo" => "Variability of apparent diffusion coefficients in metastatic small cell lung carcinoma&#58; comparisons between-within normal tissue and liver metastases"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "297"
          "paginaFinal" => "302"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "f0015"
          "etiqueta" => "Figure 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 454
              "Ancho" => 508
              "Tamanyo" => 42898
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Bar graphs depicting the significant variability observed between-tissues &#40;normal tissue vs&#46; metastasis&#41; and with-in lesions &#40;metastatic tissue&#41; in the ADC measurements after a 2-month follow-up evaluation&#46; Normal distribution of data allowed the performance of parametric tests&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Ernesto Rold&#225;n-Valadez, David Cortez-Conradis, Alejandro R&#237;os-Hoyo, &#211;scar Arrieta"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Ernesto"
              "apellidos" => "Rold&#225;n-Valadez"
            ]
            1 => array:2 [
              "nombre" => "David"
              "apellidos" => "Cortez-Conradis"
            ]
            2 => array:2 [
              "nombre" => "Alejandro"
              "apellidos" => "R&#237;os-Hoyo"
            ]
            3 => array:2 [
              "nombre" => "&#211;scar"
              "apellidos" => "Arrieta"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308956?idApp=UINPBA00004N"
    "url" => "/16652681/0000001300000002/v1_201906020852/S1665268119308956/v1_201906020852/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1665268119308932"
    "issn" => "16652681"
    "doi" => "10.1016/S1665-2681(19)30893-2"
    "estado" => "S300"
    "fechaPublicacion" => "2014-03-01"
    "aid" => "70649"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "crp"
    "cita" => "Ann Hepatol. 2014;13:288-92"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 54
      "formatos" => array:3 [
        "EPUB" => 5
        "HTML" => 25
        "PDF" => 24
      ]
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "titulo" => "Successful orthotopic liver transplantation and delayed delivery of a healthy newborn in a woman with fulminant hepatic failure during the second trimester of pregnancy"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "288"
          "paginaFinal" => "292"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Manuel Mendizabal, Carlos Rowe, Federico Pi&#241;ero, Ariel Gonzalez-Campa&#241;a, Mart&#237;n Fauda, Diego Tom&#225;s Arufe, Mar&#237;a P&#237;a Raffa, Mariano Barreiro, Rodolfo Keller, Fernando Cacheiro, Ernesto Beruti, Oscar Andriani, Marcelo Oscar Silva, Luis Gustavo Podest&#225;"
          "autores" => array:15 [
            0 => array:2 [
              "nombre" => "Manuel"
              "apellidos" => "Mendizabal"
            ]
            1 => array:2 [
              "nombre" => "Carlos"
              "apellidos" => "Rowe"
            ]
            2 => array:2 [
              "nombre" => "Federico"
              "apellidos" => "Pi&#241;ero"
            ]
            3 => array:2 [
              "nombre" => "Ariel"
              "apellidos" => "Gonzalez-Campa&#241;a"
            ]
            4 => array:2 [
              "nombre" => "Mart&#237;n"
              "apellidos" => "Fauda"
            ]
            5 => array:2 [
              "nombre" => "Diego Tom&#225;s"
              "apellidos" => "Arufe"
            ]
            6 => array:2 [
              "nombre" => "Mart&#237;n"
              "apellidos" => "Fauda"
            ]
            7 => array:2 [
              "nombre" => "Mar&#237;a P&#237;a"
              "apellidos" => "Raffa"
            ]
            8 => array:2 [
              "nombre" => "Mariano"
              "apellidos" => "Barreiro"
            ]
            9 => array:2 [
              "nombre" => "Rodolfo"
              "apellidos" => "Keller"
            ]
            10 => array:2 [
              "nombre" => "Fernando"
              "apellidos" => "Cacheiro"
            ]
            11 => array:2 [
              "nombre" => "Ernesto"
              "apellidos" => "Beruti"
            ]
            12 => array:2 [
              "nombre" => "Oscar"
              "apellidos" => "Andriani"
            ]
            13 => array:2 [
              "nombre" => "Marcelo Oscar"
              "apellidos" => "Silva"
            ]
            14 => array:2 [
              "nombre" => "Luis Gustavo"
              "apellidos" => "Podest&#225;"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308932?idApp=UINPBA00004N"
    "url" => "/16652681/0000001300000002/v1_201906020852/S1665268119308932/v1_201906020852/en/main.assets"
  ]
  "en" => array:17 [
    "idiomaDefecto" => true
    "titulo" => "Alopecia universalis after discontinuation of pegylated interferon and ribavirin combination therapy for hepatitis C&#58; a case report"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "293"
        "paginaFinal" => "296"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Nesrine Gamal, Lucia Brodosi, Cosimo Misciali, Annalisa Patrizi, Gentiana Vukatana, Nazzarena Malavolta, Mauro Bernardi, Pietro Andreone"
        "autores" => array:8 [
          0 => array:3 [
            "nombre" => "Nesrine"
            "apellidos" => "Gamal"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Lucia"
            "apellidos" => "Brodosi"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Cosimo"
            "apellidos" => "Misciali"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "&#42;&#42;"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Annalisa"
            "apellidos" => "Patrizi"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "&#42;&#42;"
                "identificador" => "aff0010"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Gentiana"
            "apellidos" => "Vukatana"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "&#42;&#42;&#42;"
                "identificador" => "aff0015"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Nazzarena"
            "apellidos" => "Malavolta"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "&#42;&#42;&#42;"
                "identificador" => "aff0015"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "Mauro"
            "apellidos" => "Bernardi"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "aff0005"
              ]
            ]
          ]
          7 => array:4 [
            "nombre" => "Pietro"
            "apellidos" => "Andreone"
            "email" => array:1 [
              0 => "pietro.andreone@unibo.it"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Dipartimento di Scienze Mediche e Chirurgiche&#44; Universit&#224; di Bologna and Azienda Ospedaliero Universitaria&#44; Policlinico Sant&#8217;Orsola Malpighi di Bologna&#44; Italy"
            "etiqueta" => "&#42;"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Dipartimento di Medicina Specialistica&#44; Diagnostica e Sperimentale&#44; Universit&#224; di Bologna and Azienda Ospedaliero Universitaria&#44; Policlinico Sant&#8217;Orsola Malpighi di Bologna&#44; Italy"
            "etiqueta" => "&#42;&#42;"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Dipartimento di Medicina Interna&#44; dell&#8217;Invecchiamento e Malattie Nefrologiche&#44; Universit&#224; di Bologna and Azienda Ospedaliero Universitaria&#44; Policlinico Sant&#8217;Orsola Malpighi di Bologna&#44; Italy"
            "etiqueta" => "&#42;&#42;&#42;"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#42;"
            "correspondencia" => "Correspondence and reprint request&#58;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "f0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 378
            "Ancho" => 504
            "Tamanyo" => 12718
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Dermoscopy &#91;40x&#93; showing increased number of yellow dots &#40;dotted arrows&#41; and few cadaverized hair &#40;black dots&#41; on the epidermis &#40;solid arrows&#41;&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Hepatitis C virus &#40;HCV&#41; infection is one of the main causes of chronic liver disease worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Over the past decade&#44; the current standard-of-care treatment has been the combination of pegylated interferon &#40;Peg-IFN&#41; plus ribavirin &#40;RBV&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> With US Food and Drug Administration approval of boceprevir and telaprevir &#40;two protease inhibitors&#41;&#44; the standard-of-care treatment for genotype-1 infection is now Peg-IFN&#47;RBV and a protease inhibitor&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Pegylation is an important technique&#44; which has greatly improved the pharmacologic profile of interferon by reducing the proteins&#8217; sensitivity to proteolysis hence increasing their half-life&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> However&#44; several adverse effects are associated with this treatment&#44; among which the most common are hematological &#40;such as anemia and thrombocytopenia&#41;&#44; flu-like syndrome&#44; psychiatric&#44; endocrine&#44; digestive and dermatological&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The emergence of several types of autoantibodies or even autoimmune diseases has been reported during IFN-alfa treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Alopecia is a dermatologic disorder that means loss of hair&#46; It is commonly believed to be an autoimmune disease&#44; which might be clinically presented as a single patch of hair loss &#40;alopecia areata&#59; AA&#41;&#44; complete loss of hair on the scalp &#40;alopecia totalis&#41; or the entire body &#40;alopecia universalis&#59; AU&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> We here report a case of irreversible AU after Peg-IFN &#945;-2b and RBV treatment in a subject with chronic hepatitis C&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Case Report</span><p id="p0010" class="elsevierStylePara elsevierViewall">A 49-year-old male patient was diagnosed as having chronic HCV infection proven by positive anti-HCV antibody and detectable HCV-RNA&#46; He was referred to our hepatitis C outpatient clinic in January 2011&#46; His medical history was insignificant except for arthritis of the small joints started in 2007&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">When he presented to our unit in 2011&#44; he was in good general conditions&#44; yet&#44; obese &#40;BMI 31&#46;3 kg&#47;m<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#41;&#46; Regarding his virological profile&#44; he was HCV-RNA positive &#40;55&#44;000 IU&#47;mL&#41;&#44; HCV genotype 3 and serogical tests for HBV and HIV were negative&#46; Transaminases were two times the upper limit of normal&#46; A liver biopsy was performed showing minimal necro-inflammatory activity and fibrosis stage 2 &#40;Ishak score&#41;&#46; Immunological blood tests revealed a positive anti-nuclear antibody and a positive anti-thyroid peroxidase antibodies test with normal thyroid stimulating hormone value&#46; Treatment was started with a weekly subcutaneous dose of Peg-IFN&#945;-2b 150 <span class="elsevierStyleItalic">&#956;</span>g&#44; along with a daily oral dose of 1&#44;200 mg of RBV&#46; One week following the first antiviral dose&#44; his HCV-RNA was negative &#40;&#60; 10 IU&#47;mL&#41;&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">No major undesired effects were reported during the treatment course&#44; except for a mild form of pancytopenia at week 8 which required no moderation in his treatment protocol and which was resolved spontaneously by the end of treatment course that lasted for 12 weeks&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">One month after the completion of the combined antiviral therapy&#44; the patient reported a significant amount of hair loss from his scalp&#44; which progressed to affect his eyebrows&#44; hair on his upper and lower limbs&#46; Hair loss continued to affect the axillary and pubic areas&#46; By the end of the third month following treatment completion&#44; the patient had a total loss of all body hair&#46; The patient was evaluated by a dermatologist who diagnosed his condition as AU and prescribed a topical corticosteroid cream and heliotherapy for 6 months&#44; without improvement&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">A scalp biopsy was performed 13 months after treatment discontinuation revealing absence of terminal hair follicles with increased number of miniaturized anagen hair follicles &#40;vellus follicles&#41;&#44; catagen and telogen germinal units &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figures 1A&#44; 1B</a>&#41;&#46; Moderate perifollicular lymphocytic infiltration was also seen with slight fibroplasia&#46; Increased number of yellow dots with few cadaverized hair &#40;black dots&#41; on the epidermis were seen by dermoscopy &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>&#41;&#46; The presence of yellow dots differentiates alopecia areata from trichotillomania or telogen effluvium&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The definitive diagnosis was alopecia areata universalis in telogen arrest phase&#46; At the time we are writing our report the patient has discontinued the antiviral therapy since 16 months&#44; and AU still shows no improvement&#46; The patient has tolerated this adverse effect well&#44; and refused any systemic medications for the alopecia&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0035" class="elsevierStylePara elsevierViewall">A written informed consent was obtained from the patient to describe this report&#46;</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Discussion</span><p id="p0040" class="elsevierStylePara elsevierViewall">AA is a disease of the anagen stage hair follicles&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> It is a clinically heterogeneous disease characterized by non-scarring hair loss on the scalp or any hairbearing surface&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> AU is the most severe variant of AA in which all scalp and body hair is lost&#46; AA and AU are commonly believed to have an autoimmune etiology with genetic&#44; environmental and immunological factors involved&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Associations between AA and classical autoimmune disorders&#44; namely&#44; thyroid disease &#40;including Hashimoto&#8217;s thyroiditis&#41;&#44; myasthenia gravis&#44; systemic lupus erythematosus and vitiligo have been previously reported&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Combination Peg-IFN&#47; RBV therapy has been associated with an increased incidence of adverse cutaneous reactions&#44; including injection site reactions&#44; psoriasis&#44; eczematoid drug reaction&#44; sarcoidosis&#44; mixed cryoglobulinemia&#44; cutaneous lupus erythematosus and alopecia&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Treatment with Peg-IFN has been also associated with several autoimmune disorders such as hypothyroidism&#44; lupus-like syndrome and autoimmune hepatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Recent studies proved that Peg-IFN induces immunologic modulation &#40;shift from Th2 immune-driven response to Th1&#41; and stimulates the synthesis of Th1-cytokines such as IL-1&#44; IL-2 and IFN-&#947;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Furthermore&#44; it also increases cytotoxic T-cell activity&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Elevated serum levels of IFN-&#947; and IL-2 in patients with AU have been reported and these results indicate that immune response in AU is regulated by Th1 cytokines&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The pathogenetic mechanisms so far known indicate a very complex process leading to an inflammatory reaction that causes hair loss&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> It is a vicious cycle&#58; the keratinocytes release cytokines that activate endothelial cells which&#44; in turn&#44; attract T-cells and macrophages that release more cytokines and so on&#46; Autoantibodies against follicular autoantigens could be found in the serum and skin of AA patients and can occur before clinically detectable hair loss<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> but there is no evidence they are pathogenic&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> A concrete hypothesis on the pathogenetic mechanisms of AU in our case is difficult to be formed&#46; Presumably&#44; in genetically predisposed individuals and under the immunemodulatory effect of Peg-IFN&#47;RBV therapy&#44; the hair follicle enters a cycle of autoimmune inhibition of its growth&#46;</p><p id="p0045" class="elsevierStylePara elsevierViewall">Although diagnosing alopecia areata might be easy&#44; treating it is not&#46; Our fundamental therapeutic challenge is to reduce the already established inflammatory infiltrates and to prevent further spread to unaffected hair follicles&#46; To date&#44; all therapeutic options do not satisfactorily meet this challenge&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Many treatment modalities have been implicated in the treatment of AA&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Topical corticosteroids and immunotherapy&#44; systemic corticosteroids&#44; systemic immunosuppresants&#44; psoralen plus ultraviolet A photochemotherapy were among treatment options for AA&#46; Alopecia is a physiologically distressing disorder and physicians should provide their patients with realistic advice about treatments and their effectiveness&#46; Several forms of alopecia linked to Peg-IFN&#47;RBV have been reported in the literature ranging from subcutaneous injection site alopecia&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> irreversible AT&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> reversible AU&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and one case of irreversible AU&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Interestingly&#44; unlike all reported cases&#44; our patient experienced hair loss one month after the discontinuation of treatment and this is quiet alarming&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">To conclude&#44; this case represents an uncommon presentation of a common disease&#46; Physicians must be aware of the potential adverse reactions of an antiviral therapy containing IFN&#44; which might occur even after the discontinuation&#44; and fully inform the patient at the beginning of his treatment course&#46; Ultimately&#44; the advent of interferon-free regimens would represent the fulfillment of an enormous unmet need in interferon-incapable or intolerant patients&#46; We hope that such regimens will utterly supplant interferon-based therapy for most or all HCV patients avoiding the emergence of autoimmune manifestations&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Disclosure</span><p id="p0055" class="elsevierStylePara elsevierViewall">No conflict of interest declared&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:7 [
        0 => array:3 [
          "identificador" => "xres1199011"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abs0010"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1117451"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "s0005"
          "titulo" => "Introduction"
        ]
        3 => array:2 [
          "identificador" => "s0010"
          "titulo" => "Case Report"
        ]
        4 => array:2 [
          "identificador" => "s0015"
          "titulo" => "Discussion"
        ]
        5 => array:2 [
          "identificador" => "s0020"
          "titulo" => "Disclosure"
        ]
        6 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-04-03"
    "fechaAceptado" => "2013-06-05"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1117451"
          "palabras" => array:3 [
            0 => "Alopecia"
            1 => "Side-effects"
            2 => "Antiviral therapy"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">For the last decade&#44; the combination therapy of pegylated interferon &#40;Peg-IFN&#41; plus ribavirin &#40;RBV&#41; has been considered as the standard of care treatment for chronic hepatitis C virus &#40;HCV&#41; infection&#46; However&#44; it has been associated with an increased incidence of many adverse cutaneous reactions and emergence of autoantibodies or even autoimmune diseases&#46; We report a case of irreversible alopecia universalis &#40;AU&#41; with complete hair loss extended to the whole body&#44; which started after discontinuation of Peg-IFN&#47;RBV combination therapy for chronic HCV infection&#46; In conclusion&#44; this case represents an uncommon presentation of a common disease&#46; Physicians must be aware of the potential adverse reactions of an antiviral therapy containing IFN&#44; which might occur even after the discontinuation&#44; and fully inform the patient at the beginning of his treatment course&#46; We hope that interferon-free regimens will utterly supplant interferon-based therapy for most or all HCV patients avoiding the emergence of autoimmune manifestations&#46;</p></span>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:7 [
        "identificador" => "f0005"
        "etiqueta" => "Figure 1&#46; A"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 344
            "Ancho" => 1013
            "Tamanyo" => 68691
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Horizontal section of scalp biopsy taken 13 months following treatment discontinuation showing absence of terminal hair follicles with increased number of miniaturized anagen hair follicles &#40;dotted arrows&#41;&#44; catagen and telogen germinal units &#40;solid arrows&#41; &#91;H&#38;E 4x&#93;&#46; B&#46; Magnified follicle unit with miniaturized anagen hair follicle &#40;dotted arrow&#41; and telogen germinal unit &#40;solid arrow&#41; &#91;H&#38;E 20x&#93;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "f0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 378
            "Ancho" => 504
            "Tamanyo" => 12718
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Dermoscopy &#91;40x&#93; showing increased number of yellow dots &#40;dotted arrows&#41; and few cadaverized hair &#40;black dots&#41; on the epidermis &#40;solid arrows&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bs0010"
          "bibliografiaReferencia" => array:29 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The global burden of hepatitis C"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Lavanchy D&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1478-3231.2008.01934.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Liver Int"
                        "fecha" => "2009"
                        "volumen" => "29"
                        "paginaInicial" => "74"
                        "paginaFinal" => "81"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19207969"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection&#58; the new standard of care"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Pearlman B&#46;L&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1473-3099(12)70060-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Infect Dis"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "717"
                        "paginaFinal" => "728"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22647717"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy and safety of pegylated &#40;40-kd&#41; interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Reddy K&#46;R&#46;"
                            1 => "Wright T&#46;L&#46;"
                            2 => "Pockros P&#46;J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/jhep.2001.21747"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2001"
                        "volumen" => "33"
                        "paginaInicial" => "433"
                        "paginaFinal" => "438"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11172346"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Review article&#58; the management of side effects during therapy for hepatitis C"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Aspinall R&#46;J&#46;"
                            1 => "Pockros P&#46;J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2036.2004.02192.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Aliment Pharmacol Ther"
                        "fecha" => "2004"
                        "volumen" => "20"
                        "paginaInicial" => "917"
                        "paginaFinal" => "929"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15521838"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immune-mediated side effects of cytokines in humans"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Vial T&#46;"
                            1 => "Descotes J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Toxicology"
                        "fecha" => "1995"
                        "volumen" => "105"
                        "paginaInicial" => "31"
                        "paginaFinal" => "57"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8638283"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia areata update&#58; part I&#46; Clinical picture&#44; histopathology&#44; and pathogenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Alkhalifah A&#46;"
                            1 => "Alsantali A&#46;"
                            2 => "Wang E&#46;"
                            3 => "McElwee K&#46;J&#46;"
                            4 => "Shapiro J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2009.10.032"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2010"
                        "volumen" => "62"
                        "paginaInicial" => "177"
                        "paginaFinal" => "188"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20115945"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hair Evaluation Methods&#58; Merits and Demerits"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Dhurat Rachita"
                            1 => "Saraogi Punit"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4103/0974-7753.58553"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Trichology"
                        "fecha" => "2009"
                        "volumen" => "1"
                        "paginaInicial" => "108"
                        "paginaFinal" => "119"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20927232"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology and genetics of alopecia areata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "McDonagh A&#46;J&#46;"
                            1 => "Tazi-Ahnini R&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Dermatol"
                        "fecha" => "2002"
                        "volumen" => "27"
                        "paginaInicial" => "405"
                        "paginaFinal" => "409"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12190641"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia areata&#58; autoimmune basis of hair loss"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Alexis A&#46;F&#46;"
                            1 => "Dudda-Subramanya R&#46;"
                            2 => "Sinha A&#46;A&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Dermatol"
                        "fecha" => "2004"
                        "volumen" => "14"
                        "paginaInicial" => "364"
                        "paginaFinal" => "370"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15564197"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Profile of alopecia areata&#58; a survey analysis of patient and family"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Shellow W&#46;V&#46;"
                            1 => "Edwards J&#46;E&#46;"
                            2 => "Koo J&#46;Y&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Dermatol"
                        "fecha" => "1992"
                        "volumen" => "31"
                        "paginaInicial" => "186"
                        "paginaFinal" => "189"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1568816"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia areata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Elder D&#46;E&#46;"
                            1 => "Elenitsas R&#46;"
                            2 => "Johnson B&#46;L&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:7 [
                        "edicion" => "9"
                        "titulo" => "Lever&#8217;s Histopatholgy of the Skin"
                        "fecha" => "2005"
                        "paginaInicial" => "483"
                        "paginaFinal" => "485"
                        "editorial" => "Lippincott Williams and Wilkins"
                        "editorialLocalizacion" => "Philadelphia"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High prevalence of cutaneous reactions to interferon alfa plus ribavirin combination therapy in patients with chronic hepatitis C virus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Sookoian S&#46;"
                            1 => "Neglia V&#46;"
                            2 => "Castano G&#46;"
                            3 => "Frider B&#46;"
                            4 => "Kien M&#46;C&#46;"
                            5 => "Chohuela E&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dermatol"
                        "fecha" => "1999"
                        "volumen" => "135"
                        "paginaInicial" => "1000"
                        "paginaFinal" => "1001"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10456365"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A review of adverse cutaneous drug reactions resulting from the use of interferon and ribavirin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Mistry N&#46;"
                            1 => "Shapero J&#46;"
                            2 => "Crawford R&#46;I&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Can J Gastroenterol"
                        "fecha" => "2009"
                        "volumen" => "23"
                        "paginaInicial" => "677"
                        "paginaFinal" => "683"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19826642"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Side effects of therapy of hepatitis C and their management"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Fried M&#46;W&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2002"
                        "volumen" => "36"
                        "paginaInicial" => "237"
                        "paginaFinal" => "244"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dermatologic manifestations of hepatitis C infection and the effect of interferon therapy&#58; a literature review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Jadali Z&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "012151/AIM.0012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Iran Med"
                        "fecha" => "2012"
                        "volumen" => "15"
                        "paginaInicial" => "43"
                        "paginaFinal" => "48"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22208443"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maintenance of T1 response as induced during PEG-IFNalpha plus ribavirin therapy controls viral replication in genotype-1 patients with chronic hepatitis C"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:8 [
                            0 => "Trapero M&#46;"
                            1 => "Garcia-Buey L&#46;"
                            2 => "Munoz C&#46;"
                            3 => "Viton M&#46;"
                            4 => "Moreno-Monteagudo J&#46;A&#46;"
                            5 => "Borque M&#46;J&#46;"
                            6 => "Quintana N&#46;E&#46;"
                            7 => "Moreno-Otero R&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Esp Enferm Dig"
                        "fecha" => "2005"
                        "volumen" => "97"
                        "paginaInicial" => "481"
                        "paginaFinal" => "490"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16262527"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytokines in alopecia areata&#58; contrasting cytokine profiles in localized form and extensive form &#40;alopecia universalis&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Teraki Y&#46;"
                            1 => "Imanishi K&#46;"
                            2 => "Shiohara T&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2340/0001555576421423"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Derm Venereol"
                        "fecha" => "1996"
                        "volumen" => "76"
                        "paginaInicial" => "421"
                        "paginaFinal" => "423"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8982401"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Gregoriou S&#44; Papafragkaki D&#44; Kontochristopoulos G&#44; Rallis E&#44; Kalogeromitros D&#44; Rigopoulos D&#46; Cytokines and other mediators in alopecia areata&#46; <span class="elsevierStyleItalic">Mediators Inflamm</span> 2010&#46; Doi&#58; 10&#46;1155&#47;2010&#47;928030&#46;"
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characterization of hair follicle antigens targeted by the anti-hair follicle immune response"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Tobin D&#46;J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1087-0024.2003.00805.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Investig Dermatol Symp Proc"
                        "fecha" => "2003"
                        "volumen" => "8"
                        "paginaInicial" => "176"
                        "paginaFinal" => "181"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14582669"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Failure of passive transfer of serum from patients with alopecia areata and alopecia universalis to inhibit hair growth in transplants of human scalp skin grafted on to nude mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Gilhar A&#46;"
                            1 => "Pillar T&#46;"
                            2 => "Assy B&#46;"
                            3 => "David M&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Br J Dermatol"
                        "fecha" => "1992"
                        "volumen" => "126"
                        "paginaInicial" => "166"
                        "paginaFinal" => "171"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia areata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Gilhar Amos"
                            1 => "Etzioni Amos"
                            2 => "Paus Ralf"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra1103442"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "366"
                        "paginaInicial" => "1515"
                        "paginaFinal" => "1525"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22512484"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of alopecia areata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Harries M&#46;J&#46;"
                            1 => "Sun J&#46;"
                            2 => "Paus R&#46;"
                            3 => "King L&#46;E&#46; Jr"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.c3671"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "2010"
                        "volumen" => "341"
                        "paginaInicial" => "c3671"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20656774"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Localized interferon alfa-2b-induced alopecia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Lang A&#46;M&#46;"
                            1 => "Norland A&#46;M&#46;"
                            2 => "Schuneman R&#46;L&#46;"
                            3 => "Tope W&#46;D&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dermatol"
                        "fecha" => "1999"
                        "volumen" => "135"
                        "paginaInicial" => "1126"
                        "paginaFinal" => "1128"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10490128"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A case of irreversible alopecia associated with ribavirin and peg-interferon therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Shafa S&#46;"
                            1 => "Borum M&#46;L&#46;"
                            2 => "Iglehon E&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MEG.0b013e32832be7a5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Gastroenterol Hepatol"
                        "fecha" => "2010"
                        "volumen" => "22"
                        "paginaInicial" => "122"
                        "paginaFinal" => "123"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19959941"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia universalis following interferon alfa-2b and ribavirin treatment for hepatitis C"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Taliani G&#46;"
                            1 => "Biliotti E&#46;"
                            2 => "Capanni M&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1179/joc.2005.17.2.212"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Chemother"
                        "fecha" => "2005"
                        "volumen" => "17"
                        "paginaInicial" => "212"
                        "paginaFinal" => "214"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15920908"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reversible alopecia universalis secondary to PEG-interferon a-2b and ribavirin combination therapy in a patient with chronic hepatitis C virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Kartal E&#46;D&#46;"
                            1 => "Alpat S&#46;N&#46;"
                            2 => "Ozgunes I&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MEG.0b013e32818b27e5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Gastroenterol Hepatol"
                        "fecha" => "2007"
                        "volumen" => "19"
                        "paginaInicial" => "817"
                        "paginaFinal" => "820"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17700271"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia universalis&#58; a rare side effect seen on chronic hepatitis C treatment with peg-IFN and ribavirin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "Demirturk N&#46;"
                            1 => "Aykin N&#46;"
                            2 => "Demirdal T&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Dermatol"
                        "fecha" => "2006"
                        "volumen" => "16"
                        "paginaInicial" => "579"
                        "paginaFinal" => "594"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17101483"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alopecia universalis following interferon Alfa-2b and ribavirin treatment for hepatitis C"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Midian-Singh R&#46;"
                            1 => "Alagugurusamy S&#46;"
                            2 => "Agrawal R&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Gastroenterol Hepatol"
                        "fecha" => "2007"
                        "volumen" => "3"
                        "paginaInicial" => "644"
                        "paginaFinal" => "645"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Irreversible alopecia universalis during treatment with pegylated interferon-ribavirin for chronic hepatitis C virus infection&#58; Case report and published work review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Omazzi B&#46;"
                            1 => "Prada A&#46;"
                            2 => "Borroni G&#46;"
                            3 => "Sacrini F&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1872-034X.2012.01036.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatol Res"
                        "fecha" => "2012"
                        "volumen" => "42"
                        "paginaInicial" => "1248"
                        "paginaFinal" => "1251"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23181541"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/16652681/0000001300000002/v1_201906020852/S1665268119308944/v1_201906020852/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "77718"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Case Report"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001300000002/v1_201906020852/S1665268119308944/v1_201906020852/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308944?idApp=UINPBA00004N"
]

Article information

ISSN: 16652681
Original language: English

DOI:10.1016/S1665-2681(19)30894-4

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 October	26	7	33
2024 September	78	12	90
2024 August	68	17	85
2024 July	61	11	72
2024 June	52	7	59
2024 May	43	7	50
2024 April	49	6	55
2024 March	50	2	52
2024 February	59	3	62
2024 January	79	7	86
2023 December	64	24	88
2023 November	39	24	63
2023 October	57	37	94
2023 September	46	13	59
2023 August	56	11	67
2023 July	37	7	44
2023 June	51	7	58
2023 May	84	7	91
2023 April	74	2	76
2023 March	39	6	45
2023 February	25	7	32
2023 January	28	19	47
2022 December	27	13	40
2022 November	25	19	44
2022 October	27	16	43
2022 September	29	15	44
2022 August	39	8	47
2022 July	27	7	34
2022 June	14	7	21
2022 May	12	7	19
2022 April	26	5	31
2022 March	38	11	49
2022 February	21	5	26
2022 January	37	12	49
2021 December	21	9	30
2021 November	28	6	34
2021 October	30	10	40
2021 September	28	10	38
2021 August	24	6	30
2021 July	19	8	27
2021 June	12	8	20
2021 May	12	8	20
2021 April	28	9	37
2021 March	26	11	37
2021 February	10	7	17
2021 January	9	10	19
2020 December	12	8	20
2020 November	3	9	12
2020 October	5	4	9
2020 September	13	8	21
2020 August	13	11	24
2020 July	7	7	14
2020 June	8	5	13
2020 May	10	10	20
2020 April	4	5	9
2020 March	4	9	13
2020 February	9	10	19
2020 January	8	16	24
2019 December	10	14	24
2019 November	9	2	11
2019 October	1	2	3
2019 September	5	3	8
2019 August	1	1	2
2019 July	1	3	4
2019 June	11	11	22

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter