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1.
Presse Med ; 49(4): 104047, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32768611

RESUMO

Allergic reactions in tattoos and permanent make-up are rare but they could be problematic. The clinical presentation and the histopathology are diverse and often confusing. Symptomatic treatment is frequently unsuccessful and invasive techniques can be required. Patch testing to identify the causative allergen is disappointing. The composition of the inks is complex; organic and inorganic colorants, auxiliary components and by-products must be considered. Physical factors such as ultraviolet and laser irradiation could play a role in haptenization of colorants in the skin. Clinical observation and advanced diagnostic methods can be helpful in the diagnosis. Preventive systematic skin testing with tattoo inks, apart from being time-consuming and expensive, is useless.


Assuntos
Alérgenos/isolamento & purificação , Hipersensibilidade/etiologia , Tatuagem/efeitos adversos , Alérgenos/análise , Alérgenos/imunologia , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/imunologia , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Tinta , Pele/imunologia , Pele/patologia
2.
Pediatrics ; 145(5)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32341178

RESUMO

Nickel is a ubiquitous metal added to jewelry and metallic substances for its hardening properties and because it is inexpensive. Estimates suggest that at least 1.1 million children in the United States are sensitized to nickel. Nickel allergic contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type hypersensitivity reaction worldwide. The incidence among children tested has almost quadrupled over the past 3 decades. The associated morbidities include itch, discomfort, school absence, and reduced quality of life. In adulthood, individuals with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD in children has been postulated to result from early and frequent exposure to metals with high amounts of nickel release (eg, as occurs with ear piercing or with products used daily in childhood such as toys, belt buckles, and electronics).To reduce exposure to metal sources with high nickel release by prolonged and direct contact with human skin, Denmark and the European Union legislated a directive several decades ago with the goal of reducing high nickel release and the incidence of Ni-ACD. Since then, there has been a global reduction in incidence of Ni-ACD in population-based studies of adults and studies of children and young adults being tested for allergic contact dermatitis. These data point to nickel exposure as a trigger for elicitation of Ni-ACD and, further, provide evidence that legislation can have a favorable effect on the economic and medical health of a population.This policy statement reviews the epidemiology, history, and appearances of Ni-ACD. Examples of sources of high nickel release are discussed to highlight how difficult it is to avoid this metal in modern daily lives. Treatments are outlined, and avoidance strategies are presented. Long-term epidemiological interventions are addressed. Advocacy for smarter nickel use is reviewed. The American Academy of Pediatrics supports US legislation that advances safety standards (as modeled by the European Union) that protect children from early and prolonged skin exposure to high-nickel-releasing items. Our final aim for this article is to aid the pediatric community in developing nickel-avoidance strategies on both individual and global levels.


Assuntos
Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/terapia , Exposição Ambiental/efeitos adversos , Níquel/efeitos adversos , Administração Tópica , Anti-Inflamatórios/administração & dosagem , Dermatite Alérgica de Contato/imunologia , Exposição Ambiental/prevenção & controle , Humanos , Níquel/imunologia , Testes do Emplastro/métodos , Resultado do Tratamento
3.
Clin Rev Allergy Immunol ; 59(1): 101-108, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32323145

RESUMO

Contact dermatitis linked to cosmetic products is a very common reason for visits to the dermatologist, and in more than half the cases, it is due to an allergic reaction. Fragrances are most often the culprit. The aim of the study was to describe the common fragrance allergens in different categories of cosmetic products available on the European market. We wanted to assess the influence of cosmetic type and distribution channel on the presence of fragrance allergens. There are the allergens whose concentration exceeds 0.001% in leave-on products and 0.01% in rinse-off products. A total of 2044 commercial hygiene, care, and makeup cosmetic products were analyzed to specifically study regulated fragrance allergens. The influence that the product category and its distribution channel (retail stores and specialized stores such as beauty institutes or hairdressers and pharmacy) have on the prevalence of these allergens was evaluated. The Kruskal-Wallis test has been used for statistical data analysis. There is a wide range of fragrance allergens, the most common being limonene (found in about 30% of products tested), linalool (just over a quarter of the products tested), and benzyl alcohol (approximately 16% of the products tested). The average number of allergens found and their nature varies depending on the type of product in question (maximum number for shampoos and oral care with about 70 allergens and minimum number for nail polish and makeup for eyes with fewer than 10 allergens). In the area of hygiene, deodorants and oral hygiene products are particularly noteworthy, the former for their significantly high number of allergens and the latter for their low number. There is also a significant difference between the number of allergens found in eye makeup and foundations. Our results indicate that the number of regulated fragrance allergens is particularly influenced by the type of products.


Assuntos
Alérgenos/análise , Cosméticos/química , Dermatite Alérgica de Contato/imunologia , Perfumes/química , Monoterpenos Acíclicos/análise , Monoterpenos Acíclicos/imunologia , Animais , Álcool Benzílico/análise , Álcool Benzílico/imunologia , Feminino , Humanos , Limoneno/análise , Limoneno/imunologia , Masculino , Odorantes
4.
PLoS One ; 15(1): e0217192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945067

RESUMO

BACKGROUND: Dermatological services in Laos, South East Asia are limited to the capital and patch testing is currently not available, so no data exists regarding the common cutaneous allergens in this population. OBJECTIVES: The aim of this study was to document positive patch tests in medical students without evidence of contact dermatitis in Laos. PATIENTS/MATERIALS/METHODS: One hundred and fifty medical students were patch tested using TRUE Test® panels 1 to 3 (35 allergens). Readings were taken at Days 2 and 4. RESULTS: Thirty-eight students (25.3%) had a positive reaction to at least one allergen, accounting for 52 reactions in total. The proportion of the students with positive patch test reading was significantly higher in the female [33/96 (34%)] than in the male [5/54 (9%)], p<0.001. The most common allergens were: nickel (10%), gold (6.6%), thiomersal (6.6%), cobalt dichloride (2%) and p-tert-Butylphenol formaldehyde resin (2%). Balsam of Peru (0.66%), black rubber mix (0.66%), Cl+Me-Isothiazolinone (0.66%), fragrance mix 1 (0.66%), quinolone mix (0.66%), methyldibromo glutaronitrile (0.66%), mercapto mix (0.66%), epoxy resin (0.66%), paraben mix (0.66%), thiuram (0.66%) and wool alcohols (0.66%) accounted for all of the other positive reactions. CONCLUSION: This study represents the first documented patch test results in Lao medical students and in the adult Lao population. The results of this study will inform any future research into contact allergy in Laos and give an insight into the background level of contact sensitivity in this population.


Assuntos
Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Testes do Emplastro , 2-Naftilamina/efeitos adversos , 2-Naftilamina/análogos & derivados , Adolescente , Adulto , Alérgenos/imunologia , Bálsamos/efeitos adversos , Cobalto/efeitos adversos , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/patologia , Resinas Epóxi/efeitos adversos , Feminino , Ouro/efeitos adversos , Humanos , Laos , Masculino , Pessoa de Meia-Idade , Níquel/efeitos adversos , Fenilenodiaminas/efeitos adversos , Resinas Sintéticas/efeitos adversos , Estudantes de Medicina , Timerosal/efeitos adversos
5.
Int J Mol Sci ; 21(2)2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31940843

RESUMO

Contact hypersensitivity (CHS) is an established animal model for allergic contact dermatitis. Dendritic cells (DCs) play an important role in the sensitization phase of CHS by initiating T cell responses to topically applied haptens. The cannabinoid receptors 1 (CB1) and 2 (CB2) modulate DC functions and inflammatory skin responses, but their influence on the capacity of haptenized DCs to induce CHS is still unknown. We found lower CHS responses to 2,4-dinitro-1-fluorobenzene (DNFB) in wild type (WT) mice after adoptive transfer of haptenized Cnr2-/- and Cnr1-/-/Cnr2-/- bone marrow (BM) DCs as compared to transfer of WT DCs. In contrast, induction of CHS was not affected in WT recipients after transfer of Cnr1-/- DCs. In vitro stimulated Cnr2-/- DCs showed lower CCR7 and CXCR4 expression when compared to WT cells, while in vitro migration towards the chemokine ligands was not affected by CB2. Upregulation of MHC class II and co-stimulatory molecules was also reduced in Cnr2-/- DCs. This study demonstrates that CB2 modulates the maturation phenotype of DCs but not their chemotactic capacities in vitro. These findings and the fact that CHS responses mediated by Cnr2-/- DCs are reduced suggest that CB2 is a promising target for the treatment of inflammatory skin conditions.


Assuntos
Células Dendríticas/imunologia , Dermatite Alérgica de Contato/imunologia , Receptor CB2 de Canabinoide/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Quimiotaxia , Células Dendríticas/citologia , Dermatite Alérgica de Contato/genética , Dinitrofluorbenzeno/toxicidade , Antígenos de Histocompatibilidade/genética , Antígenos de Histocompatibilidade/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/genética , Receptores CCR4/genética , Receptores CCR4/metabolismo , Receptores CCR7/genética , Receptores CCR7/metabolismo
6.
Sci Immunol ; 5(43)2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31901073

RESUMO

During industrialization, humans have been exposed to increasing numbers of foreign chemicals. Failure of the immune system to tolerate drugs, cosmetics, and other skin products causes allergic contact dermatitis, a T cell-mediated disease with rising prevalence. Models of αß T cell response emphasize T cell receptor (TCR) contact with peptide-MHC complexes, but this model cannot readily explain activation by most contact dermatitis allergens, which are nonpeptidic molecules. We tested whether CD1a, an abundant MHC I-like protein in human skin, mediates contact allergen recognition. Using CD1a-autoreactive human αß T cell clones to screen clinically important allergens present in skin patch testing kits, we identified responses to balsam of Peru, a tree oil widely used in cosmetics and toothpaste. Additional purification identified benzyl benzoate and benzyl cinnamate as antigenic compounds within balsam of Peru. Screening of structurally related compounds revealed additional stimulants of CD1a-restricted T cells, including farnesol and coenzyme Q2. Certain general chemical features controlled response: small size, extreme hydrophobicity, and chemical constraint from rings and unsaturations. Unlike lipid antigens that protrude to form epitopes and contact TCRs, the small size of farnesol allows sequestration deeply within CD1a, where it displaces self-lipids and unmasks the CD1a surface. These studies identify molecular connections between CD1a and hypersensitivity to consumer products, defining a mechanism that could plausibly explain the many known T cell responses to oily substances.


Assuntos
Alérgenos/imunologia , Antígenos CD1/imunologia , Antígenos de Plantas/imunologia , Bálsamos , Linfócitos T/imunologia , Linhagem Celular , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/imunologia , Humanos , Testes do Emplastro , Extratos Vegetais/efeitos adversos , Receptores de Antígenos de Linfócitos T/imunologia , Higiene da Pele
7.
Toxicol Lett ; 322: 50-57, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31958493

RESUMO

Allergic contact dermatitis (ACD) is an important occupational and environmental disease caused by topical exposure to chemical allergens. In the EU, it has been calculated that 4 % of animals are used in toxicity test for the assessment of skin sensitization (Peiser et al., 2012). To come a complete replacement of animals, evaluation of relative skin sensitization potency is necessary. The identification of mechanisms influencing allergen potency requires a better understanding of molecular events that trigger cell activation. Therefore, (i) the effects of selected allergens on surface markers expression and cytokines release in contact allergen-induced cell activation were assessed, and (ii) the role of Protein Kinase C (PKC) beta activation in contact allergen-induced cell activation was investigated. The human pro-myelocytic cell line THP-1 was used as experimental model surrogate of dendritic cells. Cells were exposed to select contact allergens of different potency and cell surface marker expression (CD80, CD86, HLA-DR) was determined by flow cytometry analysis. Cytokines production (IL-6, IL-8, IL-10, IL-12p40, IL-18) was evaluated with specific sandwich ELISA. The effective contribution of PKC beta in chemical allergen-induced cell activation was assessed by Western Blot analysis (PKC beta activation) and using a specific PKC beta inhibitor (PKC beta pseudosubstrate). In addition, to investigate if contact allergens are able to induce indeed dendritic cells (DCs) maturation, THP-1 cells were differentiated to immature DC and then exposed to contact allergen of different potency. Overall, our finding provides insights into the process of sensitization and strength of cell activation associated with allergens of different potency. Results obtained suggest that contact allergens of different potency are able to induce a different degree of activation of dendritic cells maturation involved in the process of ACD.


Assuntos
Alérgenos/classificação , Alternativas aos Testes com Animais , Células Dendríticas/efeitos dos fármacos , Dermatite Alérgica de Contato , Pele/efeitos dos fármacos , Xenobióticos/classificação , Alérgenos/toxicidade , Antígenos de Superfície/biossíntese , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Células Dendríticas/enzimologia , Células Dendríticas/imunologia , Dermatite Alérgica de Contato/enzimologia , Dermatite Alérgica de Contato/imunologia , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Humanos , Proteína Quinase C beta/metabolismo , Pele/enzimologia , Pele/imunologia , Xenobióticos/toxicidade
8.
Food Chem Toxicol ; 137: 111137, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31982450

RESUMO

Skin contact or exposure to sensitizers often occurs as a consequence of occupational exposures (e.g. poison ivy in forestry), wearing jewelry (e.g. nickel), or use of cosmetics (e.g. fragrances). However, many of the known skin sensitizers or their chemical variants are also consumed orally through foods or other sources. Since oral exposure to antigenic substances can lead to tolerance, consumption of sensitizers may impact the development and potency of skin sensitization, especially if the sensitizer is consumed early in life, prior to the first skin contact. To address this issue, we have reviewed human clinical and epidemiological literature relevant to this subject and evaluated whether early oral exposures to relevant sensitizers, or their chemical variants, are associated with reduced prevalence of skin sensitization to three main allergic sensitizers - nickel, urushiols of poison ivy, and sesquiterpene lactones of chrysanthemum and other plants.


Assuntos
Dermatite Alérgica de Contato/imunologia , Lactonas/toxicidade , Níquel/toxicidade , Extratos Vegetais/toxicidade , Sesquiterpenos/toxicidade , Pele/imunologia , Toxicodendron/toxicidade , Dermatite Alérgica de Contato/etiologia , Dieta , Humanos , Pele/efeitos dos fármacos , Toxicodendron/imunologia
9.
JAMA Dermatol ; 156(1): 85-91, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774454

RESUMO

Importance: Contact dermatitis in the anogenital area is associated with sleep disturbance and dyspareunia and can profoundly affect quality of life. The literature on anogenital contact dermatitis and culprit allergens is limited. The last large-scale study on common, relevant allergens in patients with anogenital dermatitis was published in 2008. Objectives: To characterize patients with anogenital dermatitis referred for patch testing by the North American Contact Dermatitis Group, to identify common allergens, and to explore sex-associated differences between anogenital dermatitis and allergens. Design, Setting, and Participants: A retrospective, cross-sectional analysis was conducted of the North American Contact Dermatitis Group database among 28 481 patients who underwent patch testing from January 1, 2005, to December 31, 2016, at outpatient referral clinics in the United States and Canada. Exposure: Patch testing for allergens. Main Outcomes and Measures: Currently relevant allergic patch test reactions in patients with anogenital dermatitis. Results: Of 28 481 patients tested during the study period, 832 patients (336 men and 496 women; mean [SD] age, 50.1 [26.5] years) had anogenital involvement and 449 patients (177 men and 272 women; mean [SD] age, 49.6 [17.4] years) had anogenital dermatitis only. Compared with those without anogenital involvement, there were significantly more male patients in the group with anogenital dermatitis (177 [39.4%] vs 8857 of 27 649 [32.0%]; relative risk, 1.37; 95% CI, 1.14-1.66; P < .001). In the group with anogenital involvement, female patients were significantly less likely than male patients to have allergic contact dermatitis as a final diagnosis (130 [47.8%] vs 107 [60.5%]; relative risk, 0.78; 95% CI, 0.64-0.94; P = .01), whereas a final diagnosis of other dermatoses (eg, lichen planus, lichen sclerosus, or lichen simplex chronicus) was more frequent for female patients than for male patients (67 [24.6%] vs 28 [15.8%]; relative risk, 1.54; 95% CI, 1.02-2.31; P = .03). Of the 449 patients in the group with anogenital involvement only, 227 (50.6%) had 1 or more relevant reaction with patch testing. Allergens that were statistically significantly more common in patients with anogenital involvement compared with those without anogenital involvement included medicaments such as dibucaine (10 of 250 patients tested [4.0%] vs 32 of 17 494 patients tested [0.2%]; relative risk, 22.74; 95% CI, 11.05-46.78; P < .001) and preservatives such as methylchloroisothiazolinone and methylisothiazolinone (30 of 449 patients tested [6.7%] vs 1143 of 27 599 patients tested [4.1%]; relative risk, 1.61; 95% CI, 1.14-2.41; P = .008). A total of 152 patients met the definition for anogenital allergic contact dermatitis, which is defined as anogenital involvement only, allergic contact dermatitis as the only diagnosis, and 1 or more positive reaction of current clinical relevance. Conclusions and Relevance: For patients with anogenital involvement only who were referred for patch testing, male patients were more likely to have allergic contact dermatitis, whereas female patients were more likely to have other dermatoses. Common allergens or sources consisted of those likely to contact the anogenital area. For individuals with anogenital involvement suspected of having allergic contact dermatitis, reactions to preservatives, fragrances, medications (particularly topical anesthetics), and topical corticosteroids should be tested.


Assuntos
Alérgenos/imunologia , Doenças do Ânus/diagnóstico , Dermatite Alérgica de Contato/diagnóstico , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Masculinos/diagnóstico , Testes do Emplastro/estatística & dados numéricos , Administração Cutânea , Adulto , Idoso , Anestésicos/efeitos adversos , Doenças do Ânus/epidemiologia , Doenças do Ânus/imunologia , Cosméticos/efeitos adversos , Estudos Transversais , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/imunologia , Feminino , Doenças dos Genitais Femininos/epidemiologia , Doenças dos Genitais Femininos/imunologia , Doenças dos Genitais Masculinos/epidemiologia , Doenças dos Genitais Masculinos/imunologia , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Qualidade de Vida , Estudos Retrospectivos , Adulto Jovem
10.
JAMA Dermatol ; 156(1): 79-84, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774459

RESUMO

Importance: Facial dermatitis in women is well characterized. However, recent shifts in the men's grooming industry may have important implications for male facial dermatitis. Objective: To characterize male patients with facial dermatitis. Design, Setting, and Participants: A 22-year retrospective cross-sectional analysis (1994-2016) of North American Contact Dermatitis Group (NACDG) data, including 50 507 patients who underwent patch testing by a group of dermatology board-certified patch test experts at multiple centers was carried out. Facial dermatitis was defined as involvement of the eyes, eyelids, lips, nose, or face (not otherwise specified). Main Outcomes and Measures: The main outcome was to compare characteristics (including demographics and allergens) between male patients with facial dermatitis (MFD) and those without facial dermatitis (MNoFD) using statistical analysis (relative risk, CIs). Secondary outcomes included sources of allergic and irritant contact dermatitis and, for occupationally related cases, specific occupations and industries in MFD. Results: Overall, 1332 male patients (8.0%) were included in the MFD group and 13 732 male patients (82.0%) were included in MNoFD. The mean (SD) age of participants was 47 (17.2) years in the MFD group and 50 (17.6) years in the MNoFD group. The most common facial sites were face (not otherwise specified, 817 [48.9%]), eyelids (392 [23.5%]), and lips (210 [12.6%]). Participants in the MFD group were significantly younger than MNoFD (mean age, 47 vs 50 years; P < .001). Those in the MFD group were less likely to be white (relative risk [RR], 0.92; 95% CI, -0.90 to 0.95) or have occupationally related skin disease (RR, 0.49; 95% CI, -0.42 to 0.58; P < .001) than MNoFD. The most common allergens that were associated with clinically relevant reactions among MFD included methylisothiazolinone (n = 113; 9.9%), fragrance mix I (n = 27; 8.5%), and balsam of Peru (n = 90; 6.8%). Compared with MNoFD, MFD were more likely to react to use of dimethylaminopropylamine (RR, 2.49; 95% CI, -1.42 to 4.37]) and paraphenylenediamine (RR, 1.43; 95% CI, -1.00 to 2.04; P < .001). Overall, 60.5% of NACDG allergen sources were personal care products. Conclusions and Relevance: Although many allergens were similar in both groups, MFD were more likely to react to use of dimethylaminopropylamine and paraphenylenediamine, presumably owing to their higher prevalence in hair products. Most sources of allergic and irritant contact dermatitis in MFD were personal care products. This study provides insight into the risks and exposures of the increasing number of grooming products used by male dermatology patients. This will enable clinicians to better identify male patients who would benefit from patch testing and treat those with facial dermatitis.


Assuntos
Alérgenos/imunologia , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatoses Faciais/diagnóstico , Testes do Emplastro/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/imunologia , Dermatoses Faciais/epidemiologia , Dermatoses Faciais/imunologia , Humanos , Masculino , Metaloporfirinas , Pessoa de Meia-Idade , América do Norte/epidemiologia , Estudos Retrospectivos
11.
Int Immunopharmacol ; 78: 106061, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31821937

RESUMO

Xanthone is a phenolic compound found in a few higher plant families; it has a variety of biological activities, including antioxidant, anti-inflammatory, and anticancer properties. However, the molecular and cellular mechanisms underlying the activity of xanthone in allergic contact dermatitis (ACD) remain to be explored. Therefore, this study aimed to investigate the regulatory effects of xanthone in ACD in human keratinocytes (HaCaT cell), and human mast cell line (HMC-1 cell) in vitro and in an experimental murine model. The results demonstrated that treatment with xanthone reduced the production of pro-inflammatory cytokines and chemokines including interleukin (IL)-1ß, IL-6, IL-8, and expression of chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT cells. Xanthone also suppressed the production of pro-inflammatory cytokines, chemokines, and allergic mediators in phorbol myristate acetate/A23187 calcium ionophore (PMACI)-stimulated HMC-1 cells. Xanthone significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) and activation of caspase-1 signaling pathway in vitro model. Additionally, xanthone administration alleviated 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis like-skin lesion by reducing the serum levels of immunoglobulin E (IgE), histamine, and pro-inflammatory cytokines and suppressing MAPKs phosphorylation. Xanthone administration also inhibited mortality due to compound 48/80-induced anaphylactic shock and suppressed the passive cutaneous anaphylaxis (PCA) reaction mediated by IgE. Collectively, these results suggest that xanthone has a potential for use in the treatment of allergic inflammatory diseases.


Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/farmacologia , Dermatite Alérgica de Contato/tratamento farmacológico , Pele/efeitos dos fármacos , Xantonas/farmacologia , Administração Oral , Anafilaxia/induzido quimicamente , Anafilaxia/imunologia , Animais , Antialérgicos/uso terapêutico , Calcimicina/administração & dosagem , Calcimicina/imunologia , Linhagem Celular , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/patologia , Dinitrofluorbenzeno/administração & dosagem , Dinitrofluorbenzeno/imunologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Mediadores da Inflamação/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/patologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/imunologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/imunologia , Pele/imunologia , Pele/patologia , Acetato de Tetradecanoilforbol/administração & dosagem , Acetato de Tetradecanoilforbol/imunologia , Xantonas/uso terapêutico , p-Metoxi-N-metilfenetilamina/imunologia , p-Metoxi-N-metilfenetilamina/toxicidade
12.
J Invest Dermatol ; 140(4): 806-815.e5, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31518559

RESUMO

The skin is our interface with the outside world, and consequently it is exposed to a wide range of microbes and allergens. Recent studies have indicated that allergen-specific skin-resident memory T (TRM) cells play a role in allergic contact dermatitis (ACD). However, the composition and dynamics of the epidermal T-cell subsets during ACD are not known. Here we show that exposure of the skin to the experimental contact allergen DNFB results in a displacement of the normally occurring dendritic epidermal T cells (DETC) concomitant with an accumulation of epidermal CD8+CD69+CD103+ TRM cells in mice. By studying knockout mice, we provide evidence that CD8+ T cells are required for the displacement of the DETC and that DETC are not required for recruitment of CD8+ TRM cells to the epidermis following allergen exposure. We demonstrate that the magnitude of the allergic reaction correlates with the number of CD8+ epidermal TRM cells, which again correlates with allergen dose and number of allergen exposures. Finally, in an attempt to elucidate why CD8+ epidermal TRM cells persist in the epidermis, we show that CD8+ epidermal TRM cells have a higher proliferative capability and are bioenergetically more stable, displaying a higher spare respiratory capacity than DETC.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Dermatite Alérgica de Contato/imunologia , Memória Imunológica , Animais , Linfócitos T CD8-Positivos/patologia , Células Dendríticas/patologia , Dermatite Alérgica de Contato/patologia , Modelos Animais de Doenças , Epiderme/patologia , Camundongos , Camundongos Knockout
14.
J Invest Dermatol ; 140(1): 21-28, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31101475

RESUMO

The role of the innate immune system in allergic contact dermatitis (ACD) has traditionally been confined to the initial antigen sensitization phase. However, more recent findings have shown the role of innate immunity in additional aspects of ACD, including the effector phase of the classic type IV hypersensitivity reaction. As a result, the precise immunologic mechanisms mediating ACD are more complex than previously believed. The aim of this review is to provide insight into recent advances in understanding the role of the innate immune system in the pathogenesis of ACD, including novel mechanistic roles for macrophages, innate lymphoid cells, natural killer cells, innate γδ T cells, and other signaling molecules. These insights provide new opportunities for therapeutic intervention in ACD.


Assuntos
Dermatite Alérgica de Contato/imunologia , Células Matadoras Naturais/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Linfócitos T/imunologia , Humanos , Hipersensibilidade Tardia , Imunidade Inata , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Transdução de Sinais
15.
J Cosmet Dermatol ; 19(1): 173-179, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31106952

RESUMO

BACKGROUND: Previous studies have documented the cosmetic allergic contact dermatitis due to common cosmetic allergens in standard series and various cosmetic products used in rosacea patients; however, the prevalence of contact sensitization to other cosmetic allergens other than those in standard series is largely unknown. AIMS: To assess the prevalence of contact sensitization to a European cosmetic series of allergens (Chemotechnique Diagnostics AB, Malmö, Sweden) in rosacea patients and to compare this with the prevalence observed in general population. METHODS: In this prospective monocenter study, 103 patients with rosacea and 104 control subjects were investigated for contact sensitizations via patch testing the cosmetic series including 49 allergens. RESULTS: At least one positive allergic reaction was observed in 62 (60.2%) rosacea patients, and in 25 (24.0%) control subjects. Compared with control subjects, rosacea patients were statistically more likely to have positive patch tests. The most common allergens giving positive results were octyl gallate (10.68%), dodecyl gallate (8.74%), tert-Butylhydroquinone (7.77%), thimerosal (6.80%), euxyl K400 (6.80%), cocamidopropyl betaine (5.83%), and 2,6-Di-tert-butyl-4-cresol (4.85%). CONCLUSIONS: This study shows that rosacea patients show a strikingly high prevalence of contact sensitization to cosmetic allergens. We recommend the additional use of cosmetic series for patch testing, and the careful use of cosmetics in rosacea patients if cosmetic contact sensitivity is suspected.


Assuntos
Alérgenos/imunologia , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/epidemiologia , Rosácea/complicações , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Rosácea/imunologia , Adulto Jovem
17.
Toxicol In Vitro ; 62: 104691, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31648045

RESUMO

There is a complex interplay between numerous cell types that act at different steps of the mechanism leading to allergic contact dermatitis. The validated in vitro methods for skin sensitisation assessment provide good statistical correspondence to local lymph node assay (LLNA) or to human data but, for the most part, poorly represent the actual in vivo situation as they generally involve single cell type culture in 2D. Significant progress has been made over the past decades to develop new technologies of data generation concurrently with novel approaches to improve the models especially by the use of co-culture. The importance of heterotypic cell-cell interactions in the in vitro assessment of skin sensitisation should not be overlooked. This review addresses the technical aspects to take into consideration when co-culturing depending on the desired objective and describes the different keratinocytes and dendritic cells co-cultures developed in 2D and 3D. To date, from a regulatory point of view, no alternative method to animal testing for skin sensitisation potential assessment using a keratinocytes and dendritic cells co-culture model is yet proposed. This review also presents several directions of further development.


Assuntos
Técnicas de Cocultura/métodos , Dermatite Alérgica de Contato/imunologia , Imunização , Imunocompetência/imunologia , Humanos , Modelos Biológicos , Valor Preditivo dos Testes
18.
Toxicol In Vitro ; 62: 104697, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31669365

RESUMO

The potential risk of skin sensitisation, associated with the development of allergic contact dermatitis (ACD), is a consideration in the safety assessment of new ingredients for use in personal care products. Protein haptenation in skin by sensitising chemicals is the molecular initiating event causative of skin sensitisation. Current methods for monitoring skin sensitisation rely on limited reactivity assays, motivating interest in the development of proteomic approaches to characterise the skin haptenome. Increasing our mechanistic understanding of skin sensitisation and ACD using proteomics presents an opportunity to develop non-animal predictive methods and/or risk assessment approaches. Previously, we have used a novel stable isotope labelling approach combined with data independent mass spectrometry (HDMSE) to characterise the haptenome for a number of well-known sensitisers. We have now extended this work by characterising the haptenome of the sensitisers Diphenylcyclopropenone (DPCP) and Ethyl Acrylate (EA) with the model protein Human Serum Albumin (HSA) and the complex lysates of the skin keratinocyte, HaCaT cell line. We show that haptenation in complex nucleophilic models is not random, but a specific, low level and reproducible event. Proteomic analysis extends our understanding of sensitiser reactivity beyond simple reactivity assays and offers a route to monitoring haptenation in living cells.


Assuntos
Dermatite Alérgica de Contato/patologia , Haptenos/química , Imunização , Proteínas/química , Proteômica/métodos , Pele/efeitos dos fármacos , Acrilatos/toxicidade , Linhagem Celular , Ciclopropanos/toxicidade , Dermatite Alérgica de Contato/imunologia , Humanos , Espectrometria de Massas , Modelos Moleculares , Albumina Sérica/química
20.
PLoS One ; 14(11): e0224448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31693680

RESUMO

BACKGROUND: The mechanisms explaining multimorbidity between asthma, dermatitis and rhinitis (allergic multimorbidity) are not well known. We investigated these mechanisms and their specificity in distinct cell types by means of an interactome-based analysis of expression data. METHODS: Genes associated to the diseases were identified using data mining approaches, and their multimorbidity mechanisms in distinct cell types were characterized by means of an in silico analysis of the topology of the human interactome. RESULTS: We characterized specific pathomechanisms for multimorbidities between asthma, dermatitis and rhinitis for distinct emergent non-eosinophilic cell types. We observed differential roles for cytokine signaling, TLR-mediated signaling and metabolic pathways for multimorbidities across distinct cell types. Furthermore, we also identified individual genes potentially associated to multimorbidity mechanisms. CONCLUSIONS: Our results support the existence of differentiated multimorbidity mechanisms between asthma, dermatitis and rhinitis at cell type level, as well as mechanisms common to distinct cell types. These results will help understanding the biology underlying allergic multimorbidity, assisting in the design of new clinical studies.


Assuntos
Asma/imunologia , Dermatite Alérgica de Contato/imunologia , Dermatite Atópica/imunologia , Mapas de Interação de Proteínas/imunologia , Rinite Alérgica/imunologia , Asma/epidemiologia , Asma/genética , Células Sanguíneas/imunologia , Células Sanguíneas/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Conjuntos de Dados como Assunto , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/genética , Dermatite Atópica/epidemiologia , Dermatite Atópica/genética , Perfilação da Expressão Gênica , Humanos , Imunidade Celular/genética , Multimorbidade , Mapas de Interação de Proteínas/genética , Rinite Alérgica/epidemiologia , Rinite Alérgica/genética
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