Review
Allergic contact dermatitis: Immune system involvement and distinctive clinical cases
S. Imbesi
, P.L. Minciullo, S. Isola, S. Gangemi
Corresponding author
School and Division of Allergy and Clinical Immunology, University of Messina, Messina, Italy
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Spinach extract in solid phase. Lane 1: Patient serum; Lane 2: Patient serum previously incubated with spinach extract; Lane 3: Patient serum previously incubated with chard extract; Lane 4: Patient serum previously incubated with beet extract; Lane 5: Patient serum previously incubated with mushroom extract; Lane 6: Patient serum previously incubated with lamb extract M: Molecular mass marker.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Ferrer, B. Redón, B. Bartolomé, A. Michavila" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Ferrer" ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Redón" ] 2 => array:2 [ "nombre" => "B." "apellidos" => "Bartolomé" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Michavila" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054610002880?idApp=UINPBA00004N" "url" => "/03010546/0000003900000006/v1_201304101057/S0301054610002880/v1_201304101057/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0301054611002679" "issn" => "03010546" "doi" => "10.1016/j.aller.2011.07.007" "estado" => "S300" "fechaPublicacion" => "2011-11-01" "aid" => "335" "copyright" => "SEICAP" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Allergol Immunopathol (Madr). 2011;39:362-73" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3388 "formatos" => array:3 [ "EPUB" => 14 "HTML" => 2465 "PDF" => 909 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Series: Basic Statistics For Busy Clinicians (VII)</span>" "titulo" => "Survival analysis and Cox regression" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "362" "paginaFinal" => "373" ] ] "contieneResumen" => array:1 [ "en" => true ] "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" => 757 "Ancho" => 1431 "Tamanyo" => 54413 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Graphic representation of the survival times corresponding to the patients in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "N. Benítez-Parejo, M.M. Rodríguez del Águila, S. Pérez-Vicente" "autores" => array:3 [ 0 => array:2 [ "nombre" => "N." "apellidos" => "Benítez-Parejo" ] 1 => array:2 [ "nombre" => "M.M." "apellidos" => "Rodríguez del Águila" ] 2 => array:2 [ "nombre" => "S." "apellidos" => "Pérez-Vicente" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054611002679?idApp=UINPBA00004N" "url" => "/03010546/0000003900000006/v1_201304101057/S0301054611002679/v1_201304101057/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Allergic contact dermatitis: Immune system involvement and distinctive clinical cases" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "374" "paginaFinal" => "377" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "S. Imbesi, P.L. Minciullo, S. Isola, S. Gangemi" "autores" => array:4 [ 0 => array:4 [ "nombre" => "S." "apellidos" => "Imbesi" "email" => array:1 [ 0 => "sele19pf@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "P.L." "apellidos" => "Minciullo" ] 2 => array:2 [ "nombre" => "S." "apellidos" => "Isola" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Gangemi" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "School and Division of Allergy and Clinical Immunology, University of Messina, Messina, Italy" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Contact dermatitis is an inflammatory skin condition induced by exposure to an environmental agent.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Two main types of contact dermatitis may be distinguished: irritant contact dermatitis, due to pro-inflammatory and toxic factors able to activate the skin innate immunity; and allergic contact dermatitis, which is a T-cell-mediated hypersensitivity reaction.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Contact dermatitis is usually characterised by itching with erythema, vesicles and bullae in acute phase and by lichen with cracks and fissures in chronic phase.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Epidemiology</span><p id="par0020" class="elsevierStylePara elsevierViewall">Contact dermatitis is a highly frequent disease with a significant influence on the quality of life of the affected patients and a relevant socioeconomic impact.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The occurrence of allergic contact dermatitis increases with age; prevalence rates of 13.3–24.5% have been reported, but the highest sensitisation rate has been found in children aged 0–3 years.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">However, many cases may pass unnoticed, so it is not simple to establish the frequency of this affection.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Age and sex do not represent risk factors, whereas the occupational activity is the main condition implicated in the onset of allergic contact dermatitis.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Pathogenesis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Chemically reactive small molecular compounds penetrating into the skin may determine a hapten-specific immune response that involves T cells, invariant Natural Killer T cells, Natural Killer, T regulatory cells, epidermal Langerhans cells and keratinocytes.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Most of the T-regulatory cells involved in this process are the IL-10-producing T cells, namely Tr1, and the CD4+CD25+ T-regulatory lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Two temporally and spatially spaced phases are usually necessary to achieve a contact hypersensitivity reaction: the sensitisation and the elicitation phase.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In the sensitisation phase, which occurs at the first contact of the skin with the hapten, the innate immunity induces inflammation and consequently the recruitment of dendritic cells, especially Langerhans cells, and leukocytes. Cutaneous haptens are processed by dendritic cells and are expressed in the groove of MHC classes I and II molecules on the cell surface. Hapten-bearing dendritic cells migrate to the draining lymph nodes; here they present the antigenic peptides to specific effector and regulatory T cells. Activated specific T cells leave the lymph nodes and circulate in blood, tissues, and secondary lymphatic organs. The sensitisation step lasts 10–15 days. This first step has no clinical consequence in the majority of cases. However a “primary allergic contact dermatitis” has been described; it is characterised by a hapten-specific skin inflammation 5–15 days after the initial skin contact. The persistence of the hapten in the skin for a long period of time allows the recruitment and activation in the skin of CD8+ T cells, which have been primed in the lymphoid organs a few days before.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Re-exposure of sensitised individuals with the same hapten induces the activation of specific T lymphocytes in the dermis and the epidermis and triggers the inflammatory process responsible for the appearance of cutaneous lesions within 24/72<span class="elsevierStyleHsp" style=""></span>h. The inflammatory reaction, determined by type 1 or type 17 cytokines, persists for only a few days; its rate decreases through the clearance of hapten from the skin and the activation of regulatory T cells.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Human hapten-specific CD8+ T cells show a type 1 cytokine profile, whereas the cytokine released by CD4+ T cells are more variable, with a predominance of Th1 cells and a lower number of Th2 cells. Tr1 lymphocytes represent 7–10% of nickel-specific T-cell clones isolated from the affected skin or the blood of allergic individuals. These Tr1 cells, depending on IL-10, block the maturation of dendritic cells and release IL-12 to impair the activation of hapten-specific Th1 effector lymphocytes.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The involvement of Th17 cells has been observed in some recent studies. For example, in patients with nickel contact dermatitis, our group reported an increase in serum levels of IL-22; one of the cytokines produced.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Another study of ours showed an alteration of the redox homeostasis occurring in nickel allergic contact dermatitis and particularly in “systemic nickel allergy syndrome” (SNAS) through the measurement of serum levels of specific biomarkers of oxidative stress, such as protein carbonyl groups and nitrosylated proteins.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Increased IL-18 serum levels have been found in patients with allergic contact dermatitis. This pro-inflammatory cytokine is involved in the Th1 response and immune cell infiltration into the tissues, so it probably has a role in the induction of contact dermatitis, together with IL-12 and IFN-gamma.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Common and particular causes of allergic contact dermatitis: our experience</span><p id="par0080" class="elsevierStylePara elsevierViewall">Allergic contact dermatitis may be caused by metals, cosmetics, skin care products, drugs, or plants.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Nickel is the most common cause in women in almost all countries because of the frequent exposure to high-nickel content jewellery. Hand eczema is often of the dyshidrotic type.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Potassium dichromate is the most common contact allergen in men exposed to cement.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Regarding cosmetics, allergic contact dermatitis is caused by preservatives, perfumes, active or category-specific ingredients, excipients /emulsifiers, and sunscreens.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Contact dermatitis to clothes is usually related to formaldehyde; disperse dyes<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>; accelerators; and antioxidants used in the production of synthetic rubber. It is often located in the axillae because of the action of sweat and friction.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Topical drugs, through their active principle, the vehicle or the preservatives, have been reported as responsible for allergic contact dermatitis. We described the case of a 26-year-old woman who presented an itchy erythematous reaction and oedema localised to the face after a topical acne treatment with a gel containing benzoyl peroxide.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The most frequent allergic contact dermatitis caused by plants is related to sesquiterpene lactones found in plants belonging to Compositae family. A particular kind of finger dermatitis may be determined by the contact with plants from the Liliaceae and Alstroemeriaceae families. Moreover, we reported a particular case of allergic contact dermatitis due to <span class="elsevierStyleItalic">Zantedeschia aethiopica</span>. “A 30-year-old non-atopic woman developed itching, redness, and swelling on her hands after cutting calla lily in her garden”. The manifestations appeared 2–3<span class="elsevierStyleHsp" style=""></span>h after the contact with the plant. We performed a Patch test with a piece of calla lily stem, which resulted positive after readings on Day 2 and Day 4.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Another report by our group concerns a case of contact dermatitis that occurred in a 28-year-old man after prolonged contact with a carbon-fibre fishing rod.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Protein contact dermatitis is a chronic or recurrent eczema caused by proteins deriving from fruits, vegetables, spices, plants, woods, animal proteins, grains and enzymes.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> We reported protein contact dermatitis caused by <span class="elsevierStyleItalic">Anisakis simplex</span> in a 54-year-old woman, who worked in the fish industry. Prick test with the extract of <span class="elsevierStyleItalic">A. simplex</span> and Patch test with the larvae, prepared according to the method reported by Conde-Salazar et al., showed the sensitisation.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21,22</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Substances usually responsible for contact dermatitis have been related to other manifestations. For example, alginate paste used for dental impressions has been reported as a cause of fatal anaphylactic shock<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and cadmium sulphate used in a denture wearer engendered a burning mouth syndrome.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Diagnosis</span><p id="par0130" class="elsevierStylePara elsevierViewall">Epicutaneous patch testing is the best method to diagnose an allergic contact dermatitis, reproducing its pathogenetic mechanism. The classic positive patch test reaction is a miniature form of the same dermatitis: erythema, oedema, and small, closely set vesicles, which often extend beyond the borders of the patch.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Different patch test units are now commercially available, such as the Finn Chambers or van der Bend square chambers.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Patients should be informed about avoiding excessive exercise, showers, etc. to keep the test system dry. The most frequently encountered contact allergens have been included in standard patch test series.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">27</span></a> Most commercially available allergens supplied in syringes are incorporated in petrolatum.</p><p id="par0140" class="elsevierStylePara elsevierViewall">The patch test system, applied on the upper half of the back, is usually removed after 48<span class="elsevierStyleHsp" style=""></span>h, as recommended by the International Contact Dermatitis Research Group,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> and readings should be taken 20<span class="elsevierStyleHsp" style=""></span>min after removal of the strips, and after 72 or 96<span class="elsevierStyleHsp" style=""></span>h. For some test series it could be necessary to read the tests once more after 7 days, to avoid missing the late reactions.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Occasionally some severe reactions can cause itching and burning, so the patch test can be prematurely removed.</p><p id="par0150" class="elsevierStylePara elsevierViewall">The interpretation method recommended by the International Contact Dermatitis Research group (ICDG<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>) is:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><p id="par0155" class="elsevierStylePara elsevierViewall">−: negative reaction</p></li><li class="elsevierStyleListItem" id="lsti0010"><p id="par0160" class="elsevierStylePara elsevierViewall">?+: faint erythema only: doubtful reaction</p></li><li class="elsevierStyleListItem" id="lsti0015"><p id="par0165" class="elsevierStylePara elsevierViewall">1+: nonvascular erythema, infiltration, possibly papules: weak positive reaction</p></li><li class="elsevierStyleListItem" id="lsti0020"><p id="par0170" class="elsevierStylePara elsevierViewall">2+: vesicular erythema, infiltration, papules: strong positive reaction</p></li><li class="elsevierStyleListItem" id="lsti0025"><p id="par0175" class="elsevierStylePara elsevierViewall">3+: intense erythema and infiltration, coalescing vesicles, bullous reaction: extreme positive reaction</p></li><li class="elsevierStyleListItem" id="lsti0030"><p id="par0180" class="elsevierStylePara elsevierViewall">IR: irritant reaction of different types</p></li></ul></p><p id="par0185" class="elsevierStylePara elsevierViewall">Irritant reactions are characterised by fine wrinkling, erythema and papules in follicular distribution, petechiae, pustules, bullae or even necrosis and with minimal infiltration.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,30</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Sometimes, other tests may be useful to diagnose an allergic contact dermatitis. For example, “open tests” are used for testing poorly defined or unknown substances (gels, liquids or creams), brought by the patient and potential cause of irritant reactions if occluded. Cosmetics such as perfumes, aftershave lotions and hairsprays are tested in this manner. It is applied undiluted to the normal skin twice a day for at least two days. The test is read after 15–30<span class="elsevierStyleHsp" style=""></span>min to detect contact urticaria. A negative open test indicates that an occlusive patch test can be performed with the substance without expecting severe irritant reactions.</p><p id="par0195" class="elsevierStylePara elsevierViewall">The “provocative use tests” are performed to confirm positive patch test reactions.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">“Photopatch testing” should be used to investigate patients with clinically suspected photoallergic contact dermatitis, which is caused by photochemical conversion of a certain agent into a contact allergen, mainly induced by UVA. Plant derivatives, fragrances, antiseptics and sunscreen agents are known for photosensitisation.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Treatment</span><p id="par0205" class="elsevierStylePara elsevierViewall">Identifying the aetiological agent is necessary in order to avoid the possible sources of reactions in patients with diagnosed allergic contact dermatitis. The elimination of contact allergen is the best preventive measure. In presence of the cutaneous manifestations, topical steroids are used in the acute stage and are gradually replaced by ointments and cold creams.</p><p id="par0210" class="elsevierStylePara elsevierViewall">In the event of widespread and severe allergic contact dermatitis, systemic corticosteroids may be used for a short period of time.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Antihistamines may be used to alleviate itching.</p><p id="par0215" class="elsevierStylePara elsevierViewall">Conventional immunosuppressive treatment is not appropriate but new immunomodulating macrolactams have been successfully tested in clinical trials.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33,34</span></a> New classes of immunosuppressors, inhibitors of cellular metabolic activity, and inhibitors of cell adhesion molecules targeted skin application of regulatory cytokines and neutralisation of pro-inflammatory cytokines (antisense oligonucleotides, anticytokine antibodies, soluble cytokine receptors) have been considered as future approaches.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0220" class="elsevierStylePara elsevierViewall">The conspicuous variety of clinical pictures requires more and more attention on the part of physicians, especially allergists and dermatologists, in order to better diagnose, prevent, and treat allergic contact dermatitis.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres86040" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec74211" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Pathogenesis" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Common and particular causes of allergic contact dermatitis: our experience" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Diagnosis" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Treatment" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-04-15" "fechaAceptado" => "2011-05-27" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec74211" "palabras" => array:5 [ 0 => "Allergic contact dermatitis" 1 => "Th1 cells" 2 => "Th2 cells" 3 => "Th17 cells" 4 => "Regulatory T cells" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim of this review is drawing the attention to the contact dermatitis, an inflammatory skin condition due to pro-inflammatory and toxic factors able to activate the skin innate immunity (irritant contact dermatitis) or caused by a T-cell- mediated hypersensitivity reaction (allergic contact dermatitis).</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The immune system involvement and a variety of clinical pictures are described in order to better diagnose, prevent and treat allergic contact dermatitis.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Allergic contact dermatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 22 | 0 | 22 |
| 2024 October | 184 | 19 | 203 |
| 2024 September | 249 | 35 | 284 |
| 2024 August | 193 | 21 | 214 |
| 2024 July | 237 | 18 | 255 |
| 2024 June | 169 | 16 | 185 |
| 2024 May | 219 | 13 | 232 |
| 2024 April | 167 | 29 | 196 |
| 2024 March | 231 | 16 | 247 |
| 2024 February | 273 | 15 | 288 |
| 2024 January | 738 | 17 | 755 |
| 2023 December | 248 | 26 | 274 |
| 2023 November | 340 | 30 | 370 |
| 2023 October | 306 | 42 | 348 |
| 2023 September | 201 | 28 | 229 |
| 2023 August | 132 | 18 | 150 |
| 2023 July | 131 | 16 | 147 |
| 2023 June | 180 | 9 | 189 |
| 2023 May | 139 | 12 | 151 |
| 2023 April | 111 | 4 | 115 |
| 2023 March | 126 | 9 | 135 |
| 2023 February | 76 | 3 | 79 |
| 2023 January | 78 | 20 | 98 |
| 2022 December | 77 | 15 | 92 |
| 2022 November | 85 | 18 | 103 |
| 2022 October | 48 | 20 | 68 |
| 2022 September | 83 | 20 | 103 |
| 2022 August | 74 | 22 | 96 |
| 2022 July | 68 | 19 | 87 |
| 2022 June | 75 | 12 | 87 |
| 2022 May | 78 | 16 | 94 |
| 2022 April | 76 | 20 | 96 |
| 2022 March | 84 | 12 | 96 |
| 2022 February | 75 | 8 | 83 |
| 2022 January | 97 | 13 | 110 |
| 2021 December | 56 | 19 | 75 |
| 2021 November | 72 | 15 | 87 |
| 2021 October | 60 | 30 | 90 |
| 2021 September | 37 | 17 | 54 |
| 2021 August | 30 | 7 | 37 |
| 2021 July | 26 | 7 | 33 |
| 2021 June | 37 | 33 | 70 |
| 2021 May | 47 | 24 | 71 |
| 2021 April | 113 | 28 | 141 |
| 2021 March | 47 | 24 | 71 |
| 2021 February | 25 | 12 | 37 |
| 2021 January | 15 | 15 | 30 |
| 2020 December | 0 | 2 | 2 |
| 2020 October | 0 | 1 | 1 |
| 2020 July | 0 | 1 | 1 |
| 2020 May | 0 | 2 | 2 |
| 2020 April | 0 | 3 | 3 |
| 2020 February | 0 | 6 | 6 |
| 2020 January | 0 | 12 | 12 |
| 2019 December | 0 | 2 | 2 |
| 2019 July | 0 | 5 | 5 |
| 2019 June | 0 | 26 | 26 |
| 2019 May | 0 | 17 | 17 |
| 2019 April | 0 | 3 | 3 |
| 2019 February | 0 | 4 | 4 |
| 2018 March | 20 | 1 | 21 |
| 2018 February | 50 | 2 | 52 |
| 2018 January | 3 | 2 | 5 |
| 2017 December | 103 | 1 | 104 |
| 2017 November | 8 | 6 | 14 |
| 2017 October | 11 | 3 | 14 |
| 2017 September | 11 | 6 | 17 |
| 2017 August | 16 | 14 | 30 |
| 2017 July | 11 | 10 | 21 |
| 2017 June | 18 | 13 | 31 |
| 2017 May | 9 | 20 | 29 |
| 2017 April | 9 | 17 | 26 |
| 2017 March | 10 | 5 | 15 |
| 2017 February | 12 | 14 | 26 |
| 2017 January | 9 | 10 | 19 |
| 2016 December | 17 | 7 | 24 |
| 2016 November | 13 | 21 | 34 |
| 2016 October | 23 | 17 | 40 |
| 2016 September | 28 | 13 | 41 |
| 2016 August | 23 | 11 | 34 |
| 2016 July | 15 | 8 | 23 |
| 2016 June | 16 | 15 | 31 |
| 2016 May | 10 | 15 | 25 |
| 2016 April | 25 | 24 | 49 |
| 2016 March | 14 | 24 | 38 |
| 2016 February | 20 | 23 | 43 |
| 2016 January | 14 | 26 | 40 |
| 2015 December | 14 | 15 | 29 |
| 2015 November | 17 | 22 | 39 |
| 2015 October | 27 | 18 | 45 |
| 2015 September | 23 | 25 | 48 |
| 2015 August | 19 | 6 | 25 |
| 2015 July | 15 | 8 | 23 |
| 2015 June | 18 | 6 | 24 |
| 2015 May | 14 | 15 | 29 |
| 2015 April | 16 | 23 | 39 |
| 2015 March | 42 | 14 | 56 |
| 2015 February | 14 | 10 | 24 |
| 2015 January | 25 | 2 | 27 |
| 2014 December | 41 | 7 | 48 |
| 2014 November | 33 | 7 | 40 |
| 2014 October | 47 | 10 | 57 |
| 2014 September | 35 | 4 | 39 |
| 2014 August | 6 | 3 | 9 |
| 2014 July | 11 | 4 | 15 |
| 2014 June | 4 | 3 | 7 |
| 2014 May | 12 | 4 | 16 |
| 2014 April | 16 | 5 | 21 |
| 2014 March | 71 | 19 | 90 |
| 2014 February | 73 | 13 | 86 |
| 2014 January | 51 | 8 | 59 |
| 2013 December | 75 | 10 | 85 |
| 2013 November | 53 | 6 | 59 |
| 2013 October | 69 | 15 | 84 |
| 2013 September | 57 | 10 | 67 |
| 2013 August | 61 | 15 | 76 |
| 2013 July | 49 | 12 | 61 |
| 2013 June | 33 | 5 | 38 |
| 2013 May | 31 | 8 | 39 |
| 2013 April | 26 | 11 | 37 |
| 2013 March | 19 | 5 | 24 |
| 2013 February | 20 | 5 | 25 |
| 2013 January | 3 | 3 | 6 |
| 2012 December | 3 | 2 | 5 |
| 2012 November | 0 | 2 | 2 |
| 2012 October | 2 | 2 | 4 |
| 2011 November | 1466 | 0 | 1466 |
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