Letter to the Editor
Vitamin B12 Deficiency and its Numerous Skin Manifestations
Déficit de vitamina B12 y sus diversas manifestaciones dermatológicas
Leído
28015
Vecesse ha leído el artículo
6082
Total PDF
21933
Total HTML
Compartir estadísticas
array:24 [ "pii" => "S1578219015002528" "issn" => "15782190" "doi" => "10.1016/j.adengl.2015.09.017" "estado" => "S300" "fechaPublicacion" => "2015-11-01" "aid" => "1186" "copyright" => "Elsevier España, S.L.U. and AEDV" "copyrightAnyo" => "2014" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Actas Dermosifiliogr. 2015;106:762-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2097 "formatos" => array:3 [ "EPUB" => 36 "HTML" => 599 "PDF" => 1462 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0001731015002161" "issn" => "00017310" "doi" => "10.1016/j.ad.2015.03.012" "estado" => "S300" "fechaPublicacion" => "2015-11-01" "aid" => "1186" "copyright" => "Elsevier España, S.L.U. y AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2015;106:762-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1597 "formatos" => array:3 [ "EPUB" => 2 "HTML" => 561 "PDF" => 1034 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">CARTA CIENTÍFICO-CLÍNICA</span>" "titulo" => "Déficit de vitamina B12 y sus diversas manifestaciones dermatológicas" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "762" "paginaFinal" => "764" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Vitamin B12 Deficiency and its Numerous Skin Manifestations" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 921 "Ancho" => 1000 "Tamanyo" => 141434 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Hiperpigmentación extensa de distribución flexural con compromiso genital, perineal e inguinal.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Vera-Kellet, R. Andino-Navarrete, L. Navajas-Galimany" "autores" => array:3 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Vera-Kellet" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Andino-Navarrete" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Navajas-Galimany" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219015002528" "doi" => "10.1016/j.adengl.2015.09.017" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219015002528?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731015002161?idApp=UINPBA000044" "url" => "/00017310/0000010600000009/v1_201511040159/S0001731015002161/v1_201511040159/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1578219015002516" "issn" => "15782190" "doi" => "10.1016/j.adengl.2015.09.016" "estado" => "S300" "fechaPublicacion" => "2015-11-01" "aid" => "1188" "copyright" => "Elsevier España, S.L.U. and AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2015;106:764-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 766 "formatos" => array:3 [ "EPUB" => 49 "HTML" => 369 "PDF" => 348 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Census of Centers That Perform Mohs’ Micrographic Surgery in Spain and Description of Their Activity: A Feasibility Study for the Mohs’ Micrographic Surgery Registry of the Foundation of the Spanish Academy of Dermatology and Venereology" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "764" "paginaFinal" => "766" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Censo de los centros que realizan cirugía de Mohs en España y descripción de su actividad: estudio de factibilidad para el registro de cirugía de Mohs de la FAEDV" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "T. Alonso-Alonso, P. Redondo-Bellon, O. Sanmartín-Jiménez, E. de Eusebio-Murillo, I. García-Doval, M.Á. Rodríguez-Prieto" "autores" => array:6 [ 0 => array:2 [ "nombre" => "T." "apellidos" => "Alonso-Alonso" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Redondo-Bellon" ] 2 => array:2 [ "nombre" => "O." "apellidos" => "Sanmartín-Jiménez" ] 3 => array:2 [ "nombre" => "E." "apellidos" => "de Eusebio-Murillo" ] 4 => array:2 [ "nombre" => "I." "apellidos" => "García-Doval" ] 5 => array:2 [ "nombre" => "M.Á." "apellidos" => "Rodríguez-Prieto" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731015002185" "doi" => "10.1016/j.ad.2015.02.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731015002185?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219015002516?idApp=UINPBA000044" "url" => "/15782190/0000010600000009/v1_201511040157/S1578219015002516/v1_201511040157/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S157821901500253X" "issn" => "15782190" "doi" => "10.1016/j.adengl.2015.09.018" "estado" => "S300" "fechaPublicacion" => "2015-11-01" "aid" => "1185" "copyright" => "Elsevier España, S.L.U. and AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2015;106:760-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 935 "formatos" => array:3 [ "EPUB" => 52 "HTML" => 464 "PDF" => 419 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Pulmonary and Lymph Node Sarcoidosis Associated With Anti-Tumor Necrosis Factor Therapy in a Patient With Psoriasis: A New Case of This Paradoxical Phenomenon" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "760" "paginaFinal" => "762" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Sarcoidosis pulmonar y ganglionar en un paciente con psoriasis durante terapia anti-TNF alfa: nuevo caso de fenómeno paradójico" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 975 "Ancho" => 975 "Tamanyo" => 142482 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">High resolution computed tomography, axial cuts: Multiple nodules forming masses were observed in the mediastinum, at both hila, and in the left supraclavicular fossa, in addition to nodular pulmonary involvement.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Padilla-España, S. Habicheyn-Hiar, M. de Troya" "autores" => array:3 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Padilla-España" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Habicheyn-Hiar" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "de Troya" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S000173101500215X" "doi" => "10.1016/j.ad.2015.03.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S000173101500215X?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157821901500253X?idApp=UINPBA000044" "url" => "/15782190/0000010600000009/v1_201511040157/S157821901500253X/v1_201511040157/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Vitamin B12 Deficiency and its Numerous Skin Manifestations" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "762" "paginaFinal" => "764" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "C. Vera-Kellet, R. Andino-Navarrete, L. Navajas-Galimany" "autores" => array:3 [ 0 => array:3 [ "nombre" => "C." "apellidos" => "Vera-Kellet" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "R." "apellidos" => "Andino-Navarrete" "email" => array:1 [ 0 => "rominaandino@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "L." "apellidos" => "Navajas-Galimany" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Dermatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Déficit de vitamina B12 y sus diversas manifestaciones dermatológicas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 748 "Ancho" => 1000 "Tamanyo" => 116277 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Multiple hyperpigmented macules on the palm of the left hand.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The patient was a 59-year-old woman with a history of type 2 diabetes mellitus, hypertension, and gout who was receiving treatment with metformin, valsartan, enalapril, and allopurinol. She consulted a dermatologist 1 month after developing hyperpigmented macules. While the lesions appeared initially on the palms of the hands and soles of the feet, the patient subsequently developed widespread cutaneous involvement, predominantly in intertriginous areas (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). Of particular note were hyperpigmented macules on the lips and longitudinal melanonychia on the fingernails (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The differential diagnosis was lichen planus pigmentosus-inversus or an adverse drug reaction of the liquenoide type. Two skin biopsies showed a superficial spongiotic and psoriasiform perivascular dermatitis with eosinophils, consistent with an adverse drug reaction. On follow-up at 6 months, the patient presented mucocutaneous jaundice, asthenia, and dyspnea at rest. A series of tests were ordered and the results revealed severe megaloblastic anemia (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). In the etiologic study, high titers of antibodies to parietal cells and intrinsic factor were found, and upper digestive tract endoscopy showed chronic atrophic inflammation of the gastric mucosa. The results of the following tests were normal: iron, folate, cortisol, thyroid-stimulating hormone, free thyroxine, rapid plasma reagin, and serological assays for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. Treatment with intravenous vitamin B12 was started. The patients progressed satisfactorily, with partial regression of the skin lesions and complete remission of hematologic abnormalities after 5 months of follow-up (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Vitamin B12 plays an important role in the synthesis of DNA and RNA, acting as an enzyme cofactor.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Onset of vitamin B12 deficiency is usually subacute, starting when the body's reserves are exhausted. The deficiency can be caused by a range of nutritional problems, including a lack of intrinsic factor, achlorhydria, ileal disease, malnutrition, and malabsorption syndromes.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Diagnosis and treatment are of great clinical importance, mainly because of the progressive hematologic and neurologic involvement.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The following cutaneous manifestations have been described: generalized hyperpigmentation, glossitis, nail abnormalities, and premature graying. Hyperpigmentation is often more pronounced on the limbs, primarily on the dorsum of the hands and feet, in flexural areas, and occasionally on the nails, tongue, and oral mucous membranes.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Since hyperpigmentation is a nonspecific symptom, a broad range of differential diagnoses should be considered in such cases: diabetes mellitus, Addison disease, Cushing syndrome, post-inflammatory lesions, amyloidosis, melanosis of the skin, heavy metal deposition, thyroid disease, tumors, drug reactions, and porphyria cutanea tarda, among others.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The pathophysiology of hyperpigmentation is still a matter of debate. The first hypothesis was proposed by Gilliam and Cox,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> who reported that patients with vitamin B12 deficiency had decreased levels of reduced glutathione (GSH). It is known that GSH inhibits tyrosinase activity and consequently melanogenesis. Low levels of GSH permit increased tyrosinase activity, and thereby favor an increase in melanogenesis. Griepp<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> proposed a hypothesis involving biopterin, a substance essential to the hydroxylation of phenylalanine. Given the role of phenylalanine in the synthesis of melanin, high levels of this amino acid could explain hyperpigmentation. Marks<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> hypothesized that a change in the location and distribution of melanin might be involved, observing that megaloblastic anemia is associated with a defect in the transport of melanin and its incorporation into keratinocytes.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Accurate recognition of the cutaneous manifestations and eventual systemic involvement is essential in establishing a diagnosis. Blood tests may reveal macrocytosis, immature nuclei, and hypersegmented granulocytes. There may be an increase in levels of serum bilirubin and lactate dehydrogenase, as occurred in the present case. The sensitivity of low serum vitamin B12 concentrations (< 200<span class="elsevierStyleHsp" style=""></span>(g/mL) ranges from 65% to 95%,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> making it necessary to complement this finding with other tests having greater sensitivity. Levels of methylmalonic acid higher than 400<span class="elsevierStyleHsp" style=""></span>nmol/L and homocysteine above 21<span class="elsevierStyleHsp" style=""></span>μmol/L have a sensitivity of 98% and 96%, respectively.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Once the diagnosis is confirmed, the cause of the deficiency should be investigated. In severe cases, it should be remembered that the most common cause of vitamin B12 deficiency is autoimmune gastritis.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In our patient, further tests and explorations revealed high titers of antibodies against parietal cells and intrinsic factor and chronic atrophic inflammation of the gastric mucosa. These findings supported a diagnosis of autoimmune gastritis. However, it should be noted that the patient was receiving treatment with metformin, a drug that has been associated with decreased serum levels of vitamin B12. A recent meta-analysis found treatment with metformin to be significantly associated with an increased incidence of vitamin B12 deficiency and reduced serum levels.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> It is therefore possible that the etiology in this case may have been twofold.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Histology may reveal epidermal thinning, vacuolar changes and nuclear elongation of keratinocytes, increases in the number of melanocytes in basal layers, and the presence of numerous melanophages in the papillary dermis.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3,9</span></a> Electron microscopy will show intracytoplasmic desmosomes, numerous aggregated bundles of tonofilaments in the cytoplasm of keratinocytes, and highly condensed keratohyalin granules.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> In the present case, the results of the 2 histological studies carried out were not consistent with the findings described above and were, rather, indicative of an adverse drug reaction. The possible complementary role in the etiology of 1 of this patient's medications could explain these findings, and the histological changes associated with the drug reaction may have masked those more often found in cases of vitamin B12 deficiency.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Recommended treatment is based on the administration of vitamin B12 either orally, intravenously, or intramuscularly; a number of management protocols exist. In a randomized clinical trial comparing oral and parenteral therapy, both groups showed similar reductions in mean corpuscular volume and increases in hematocrit at 4 months.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The present case highlights the causal relationship between vitamin B12 deficiency and generalized skin hyperpigmentation, an association that presents a wide variety of dermatological manifestations. Clinical suspicion plays a fundamental role in the diagnostic process, and is higher in patients at higher risk, including vegetarians, malnourished patients, older people, and patients who have malabsorption syndromes or have undergone gastrectomy or bariatric surgery.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Vera-Kellet C, Andino-Navarrete R, Navajas-Galimany L. Déficit de vitamina B12 y sus diversas manifestaciones dermatológicas. Actas Dermosifiliogr. 2015;106:762–764.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 748 "Ancho" => 1000 "Tamanyo" => 116277 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Multiple hyperpigmented macules on the palm of the left hand.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 921 "Ancho" => 1000 "Tamanyo" => 138344 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Extensive hyperpigmentation in intertriginous areas with genital, perineal and inguinal involvement.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 922 "Ancho" => 1300 "Tamanyo" => 198706 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A, Hyperpigmented macules on the face and upper and lower lip. B, Dermoscopic image of melanonychia affecting the fingernail.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pretreatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Aftercare \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Normal Range \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Erythrocyte count (x10<span class="elsevierStyleSup">6</span>/mm<span class="elsevierStyleSup">3</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.0–5.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hemoglobin (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12–16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hematocrit (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36–46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean corpuscular volume (fL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">114.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80–100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Reticulocytes (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5–1.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Serum B12 levels (pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">105 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">559 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">200–900 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Blood film \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Anisocytosis, polychromasia, macrocytosis, dacrocyte, hypersegmented neutrophils \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypochromia, polychromasia, microcytosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab940655.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Summary of Laboratory Test Results on Diagnosis and 5 Months Posttreatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin B12 deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. Stabler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMcp1113996" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2013" "volumen" => "368" "paginaInicial" => "149" "paginaFinal" => "160" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23301732" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0065" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nutritional diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E.M. Fathman" 1 => "E.B. Geisel" 2 => "A. Salmo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "titulo" => "Andrews’ diseases of the skin: clinical dermatology." "paginaInicial" => "606" "paginaFinal" => "615" "edicion" => "9th ed." "serieFecha" => "2000" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0070" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperpigmentation in megaloblastic anemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V.J. Marks" 1 => "R.A. Briggaman" 2 => "C.E.JJr. Wheeler" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol." "fecha" => "1985" "volumen" => "12" "paginaInicial" => "914" "paginaFinal" => "917" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3998224" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0075" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin B12 deficiency: a case report of ongoing cutaneous hyperpigmentation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.F. Hoffman" 1 => "D.M. Palmer" 2 => "D. Papadopoulos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cutis." "fecha" => "2003" "volumen" => "71" "paginaInicial" => "127" "paginaFinal" => "130" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12635892" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0080" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidermal changes in vitamin B12 deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.N. Gilliam" 1 => "A.J. Cox" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol." "fecha" => "1973" "volumen" => "107" "paginaInicial" => "231" "paginaFinal" => "236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4685579" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0085" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperpigmentation syndromes (diffuse hypermelanosis)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.R. Griepp" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med." "fecha" => "1978" "volumen" => "138" "paginaInicial" => "356" "paginaFinal" => "357" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/629627" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0090" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutting edge issues in autoimmune gastritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B.H. Toh" 1 => "J. Chan" 2 => "T. Kyaw" 3 => "F. Alderuccio" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12016-010-8218-y" "Revista" => array:6 [ "tituloSerie" => "Clin Rev Allergy Immunol" "fecha" => "2012" "volumen" => "42" "paginaInicial" => "269" "paginaFinal" => "278" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21174235" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0095" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of metformin on vitamin B12 deficiency: a meta-analysis review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Niafar" 1 => "F. Hai" 2 => "J. Porhomayon" 3 => "N.D. Nader" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11739-014-1157-5" "Revista" => array:6 [ "tituloSerie" => "Intern Emerg Med." "fecha" => "2015" "volumen" => "10" "paginaInicial" => "93" "paginaFinal" => "102" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25502588" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0100" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reversible hyperpigmentation of skin and nails with white hair due to vitamin B12 deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N. Noppakun" 1 => "D. Swasdikul" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol." "fecha" => "1986" "volumen" => "122" "paginaInicial" => "896" "paginaFinal" => "899" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3740873" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0105" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperpigmentation in megaloblastic anemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.H. Lee" 1 => "W.S. Lee" 2 => "K.C. Whang" 3 => "S.J. Lee" 4 => "J.B. Chung" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int J Dermatol." "fecha" => "1988" "volumen" => "27" "paginaInicial" => "571" "paginaFinal" => "575" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3209318" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0110" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effective treatment of cobalamin deficiency with oral cobalamin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.M. Kuzminski" 1 => "E.J. del Giacco" 2 => "R.H. Allen" 3 => "S.P. Stabler" 4 => "J. Lindenbaum" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "1998" "volumen" => "92" "paginaInicial" => "1191" "paginaFinal" => "1198" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9694707" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010600000009/v1_201511040157/S1578219015002528/v1_201511040157/en/main.assets" "Apartado" => array:4 [ "identificador" => "6157" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010600000009/v1_201511040157/S1578219015002528/v1_201511040157/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219015002528?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 102 | 20 | 122 |
| 2024 Octubre | 833 | 65 | 898 |
| 2024 Septiembre | 801 | 69 | 870 |
| 2024 Agosto | 733 | 108 | 841 |
| 2024 Julio | 596 | 96 | 692 |
| 2024 Junio | 543 | 109 | 652 |
| 2024 Mayo | 540 | 88 | 628 |
| 2024 Abril | 442 | 71 | 513 |
| 2024 Marzo | 620 | 73 | 693 |
| 2024 Febrero | 948 | 58 | 1006 |
| 2024 Enero | 1020 | 76 | 1096 |
| 2023 Diciembre | 833 | 70 | 903 |
| 2023 Noviembre | 588 | 82 | 670 |
| 2023 Octubre | 476 | 66 | 542 |
| 2023 Septiembre | 512 | 77 | 589 |
| 2023 Agosto | 429 | 47 | 476 |
| 2023 Julio | 403 | 95 | 498 |
| 2023 Junio | 533 | 67 | 600 |
| 2023 Mayo | 431 | 82 | 513 |
| 2023 Abril | 329 | 54 | 383 |
| 2023 Marzo | 254 | 67 | 321 |
| 2023 Febrero | 253 | 48 | 301 |
| 2023 Enero | 328 | 60 | 388 |
| 2022 Diciembre | 236 | 80 | 316 |
| 2022 Noviembre | 192 | 58 | 250 |
| 2022 Octubre | 215 | 49 | 264 |
| 2022 Septiembre | 154 | 75 | 229 |
| 2022 Agosto | 114 | 71 | 185 |
| 2022 Julio | 176 | 85 | 261 |
| 2022 Junio | 156 | 63 | 219 |
| 2022 Mayo | 377 | 76 | 453 |
| 2022 Abril | 476 | 68 | 544 |
| 2022 Marzo | 519 | 79 | 598 |
| 2022 Febrero | 449 | 66 | 515 |
| 2022 Enero | 533 | 80 | 613 |
| 2021 Diciembre | 370 | 80 | 450 |
| 2021 Noviembre | 330 | 85 | 415 |
| 2021 Octubre | 414 | 78 | 492 |
| 2021 Septiembre | 340 | 82 | 422 |
| 2021 Agosto | 532 | 92 | 624 |
| 2021 Julio | 396 | 72 | 468 |
| 2021 Junio | 444 | 75 | 519 |
| 2021 Mayo | 322 | 90 | 412 |
| 2021 Abril | 636 | 247 | 883 |
| 2021 Marzo | 338 | 127 | 465 |
| 2021 Febrero | 198 | 99 | 297 |
| 2021 Enero | 212 | 97 | 309 |
| 2020 Diciembre | 125 | 102 | 227 |
| 2020 Noviembre | 100 | 70 | 170 |
| 2020 Octubre | 86 | 101 | 187 |
| 2020 Septiembre | 70 | 64 | 134 |
| 2020 Agosto | 62 | 96 | 158 |
| 2020 Julio | 83 | 76 | 159 |
| 2020 Junio | 40 | 89 | 129 |
| 2020 Mayo | 33 | 89 | 122 |
| 2020 Abril | 32 | 91 | 123 |
| 2020 Marzo | 23 | 84 | 107 |
| 2020 Febrero | 6 | 77 | 83 |
| 2020 Enero | 0 | 69 | 69 |
| 2019 Diciembre | 4 | 41 | 45 |
| 2019 Noviembre | 0 | 43 | 43 |
| 2019 Octubre | 0 | 33 | 33 |
| 2019 Septiembre | 4 | 54 | 58 |
| 2019 Agosto | 0 | 44 | 44 |
| 2019 Julio | 0 | 44 | 44 |
| 2019 Junio | 2 | 46 | 48 |
| 2019 Mayo | 1 | 149 | 150 |
| 2019 Abril | 0 | 94 | 94 |
| 2019 Marzo | 2 | 49 | 51 |
| 2019 Febrero | 3 | 28 | 31 |
| 2019 Enero | 3 | 15 | 18 |
| 2018 Diciembre | 4 | 11 | 15 |
| 2018 Noviembre | 1 | 4 | 5 |
| 2018 Octubre | 7 | 0 | 7 |
| 2018 Septiembre | 3 | 19 | 22 |
| 2018 Agosto | 0 | 48 | 48 |
| 2018 Julio | 0 | 30 | 30 |
| 2018 Junio | 0 | 18 | 18 |
| 2018 Mayo | 0 | 24 | 24 |
| 2018 Abril | 0 | 27 | 27 |
| 2018 Marzo | 0 | 19 | 19 |
| 2018 Febrero | 56 | 26 | 82 |
| 2018 Enero | 47 | 31 | 78 |
| 2017 Diciembre | 42 | 16 | 58 |
| 2017 Noviembre | 40 | 26 | 66 |
| 2017 Octubre | 25 | 19 | 44 |
| 2017 Septiembre | 35 | 33 | 68 |
| 2017 Agosto | 43 | 35 | 78 |
| 2017 Julio | 37 | 52 | 89 |
| 2017 Junio | 40 | 41 | 81 |
| 2017 Mayo | 43 | 36 | 79 |
| 2017 Abril | 23 | 19 | 42 |
| 2017 Marzo | 23 | 42 | 65 |
| 2017 Febrero | 20 | 17 | 37 |
| 2017 Enero | 14 | 17 | 31 |
| 2016 Diciembre | 18 | 17 | 35 |
| 2016 Noviembre | 29 | 23 | 52 |
| 2016 Octubre | 25 | 18 | 43 |
| 2016 Septiembre | 0 | 3 | 3 |
| 2016 Agosto | 0 | 10 | 10 |
| 2016 Julio | 0 | 1 | 1 |
| 2016 Junio | 1 | 5 | 6 |
| 2016 Mayo | 2 | 4 | 6 |
| 2016 Enero | 0 | 3 | 3 |
| 2015 Diciembre | 0 | 2 | 2 |
| 2015 Noviembre | 0 | 16 | 16 |
Mostrar todo
