Evaluation of the profile of inflammatory cytokines, through immunohistochemistry, in the skin of patients with allergic contact dermatitis to nickel in the acute and chronic phases

Abstract: Background: Allergic contact dermatitis to ion nickel (Ni+2) is an inflammatory dermatosis, common in industrialized countries. It involves the activation of nickel-specific T-cells, followed by proliferation and induction of a mixed profile of both proinflammatory and regulatory cytokines, suggesting that several T-cell subtypes (helper - Th and cytotoxic - Tc) are involved. A broader understanding of the cytokine profile may lead to new therapeutic approaches. Objectives: This study aimed to analyze the cytokines TNF-α, INF-γ, IL-2, IL-4, IL-10, IL-13, IL-17 and IL-23 using the immunohistochemistry technique in order to try to identify their prevalence in chronic and acute eczema of patients with allergic contact dermatitis to Ni+2. Methods: We performed an immunohistochemical study for eight cytokines in 20 patients with Ni+2 allergic contact dermatitis, biopsied at the site of chronic eczema, triggered by the patient's daily contact with Ni+2, and at the site of acute eczema caused by nickel sulfate, 48 hours after applying the contact test. Results: The stained samples showed positive results for the eight cytokines studied. TNF-α, IFN-γ, IL-4, IL-13 and IL-17 had a higher prevalence in chronic eczema, IL-2 and IL-23 in acute eczema, and IL-10 presented a similar prevalence in both acute and chronic eczema. However, these prevalences were statistically significant only for IL-4 and IL-13. Study Limitations: Small sample size. Conclusions: In chronic and acute eczema, we observed the presence of a mixed cytokine profile of the T cell subtypes (Th/Tc), suggesting that the responses are expressed at the same time.

Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis

Abstract: Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.

Nickel allergy: blood and periodontal evaluation after orthodontic treatment / Alergia ao níquel: avaliação periodontal e sanguínea após o tratamento ortodôntico

The aim of this study was to assess periodontal status and bloodparameters in orthodontic patients with nickel allergy one monthafter removal of brackets. Ninety-six randomly selected patientswere initially evaluated. Allergy to nickel was diagnosed using apatch test. After determining the prevalence of subjects allergic tonickel, two groups were formed: 16 allergic (experimental) and 16non-allergic (control) patients. Their periodontal status wasdetermined regularly by a single, blinded, duly calibrated examinerusing the Lõe Index (GI) and their blood was tested (complete bloodtest, including nickel and IgE levels) after nine months oforthodontic treatment and again one month after removing theorthodontic appliances. Statistical analyses included paired andnon-paired t-tests, Mann-Whitney, Wilcoxon, McNemar and lineartrend chi-square tests (p≤0.05). Comparison of the values recordedduring orthodontic treatment and one month after removing theappliances showed that in the allergic group there was significantincrease in eosinophils (p=0.046), basophils (p=0.001) andmonocytes (p=0.002), and decrease in number of bands (p=0.000),while in the control group, there was increase in lymphocytes(p=0.039) and decrease in segmented neutrophils (p=0.030) andIgE levels (p=0.001). In both groups, plasma nickel levels increased(p=0.010; p=0.039) and GI scores decreased. One month afterremoving the brackets, blood and periodontal parameters frompatients with and without nickel allergy were similar.

O objetivo do presente estudo foi avaliar a condição periodontal eos parâmetros sanguíneos em pacientes alérgicos ao níquel, ummês após remoção dos aparelhos. Noventa e seis pacientesselecionados aleatoriamente foram inicialmente avaliadas. Alergiaao níquel foi diagnosticada usando um teste de contato. Após adeterminação da prevalência de alergia ao níquel, formaram-sedois grupos: 16 pacientes alérgicos (experimental) e 16 nãoalérgicos (controle). Condição periodontal foi diagnosticadaatravés do Índice de Lõe (IG). Parâmetros sanguíneos foramdeterminados por meio de um exame de sangue completo,incluindo a quantificação de níquel e níveis de IgE. Avaliações doestado periodontal foram realizados por um único examinador deforma cega, devidamente calibrado e amostras de sangue foramtomadas depois de nove meses de tratamento e um mês após aremoção dos aparelhos ortodônticos. Análise estatística utilizadafoi testes t pareado e não pareado, Mann-Whitney, Wilcoxon,McNemar e qui-quadrado de tendência linear (p≤0,05). Emcomparação com os valores observados durante o tratamento, onúmero de eosinófilos (p=0,046), basófilos (p=0,001) e monócitos(p=0,002) aumentou significativamente depois da remoção dosaparelhos ortodônticos, ao passo que o número de bastões(p=0,000) diminuiu entre os períodos no grupo alérgico. O númerode linfócitos (p=0,039) aumentou no grupo controle e o número desegmentados (p=0,030) diminuiu. A diminuição dos níveis de IgE(p=0,001) entre os períodos ocorreu no grupo de controle. Níveisde níquel no plasma aumentou após a remoção de aparelhosortodônticos em ambos os grupos (p=0,010; p=0,039). O IGdiminuiu em ambos os grupos. Parâmetros periodontais esanguíneos de pacientes com alergia ao níquel foram semelhantesaos não alérgicos um mês após a remoção dos aparelhos.

Dermatitis alérgica de contacto por cosméticos en un consultorio alergoinmunologico / Allergic dermatitis of contact by cosmetics in a alego-immunological doctor`s office

La dermatitis de contacto (DC) es una respuesta inflamatoria de la piel, como resultado del contacto de la misma con múltiples factores externos, frecuentemente contenidos en cosméticos. Las pruebas del parche son el pilar diagnostico. Se evaluó la prevalencia de la dermatitis alérgica de contacto por cosméticos, determinando las relaciones epidemiológicas como: edad, sexo, localización, ocupación y sensibilización. El 70% de los pacientes estudiados fueron DAC y el 30% fuerondermatitis irritativas por contacto (DIC). El 57% de las dermatitis alérgicas estaban asociadas a cosméticos,predominando en el sexo femenino.

Contact dermatitis (AD) is an inflammatory response of the skinas a result of contact with multiple external factors, often containedin cosmetics. Patch tests are the diagnostic pillar. Prevalence of allergic contact dermatitis to cosmetics was evaluatedby determining the epidemiological relationships as age, sex, location, occupation and awareness.70% of the patients studied were DAC and 30% were irritant contact dermatitis (ICD).57% of allergic dermatitis were associated with cosmetics, predominantly in females.

Inmunidad innata en dermatitis de contacto alérgica / Innate immunity in allergic contact dermatitis

Dermatitis de contacto alérgica (DCA) es una de las enfermedades cutáneas más comunes. DCA es una respuesta de hipersensibilidad retardada tipo IV que sigue a la exposición tópica a un alérgeno de contacto. Históricamente los linfocitos T en el sistema inmune adaptativo eran vistos como el factor clave en DCA. El reconocimiento de la importancia del sistema inmune innato en DCA ha sido un descubrimiento reciente, de la mano de un significativo avance en el entendimiento de este sistema, incluyendo la identificación de receptores del sistema inmune innato. Estos receptores incluyen receptores toll-like (TLRs), receptores de unión de nucleótidos (NODs) y los receptores de dominios de oligomerizacion (NLRs). TLRs y NLRs son capaces de responder a alérgenos de contacto produciendo citoquinas inflamatorias. Estas citoquinas, referidas como señales de peligro, modulan tanto la fase de sensibilización como la efectora de la DCA. TLRs y NLRs juegan un rol crucial en el desarrollo de DCA. La interferencia de estos receptores o sus vías tiene el potencial de prevenir la DCA. Entender el significado de la inmunidad innata en el desarrollo de la DCA tiene importante implicancia clínica incluyendo avances en potenciales tratamientos y prevención. TLRs y NLRs del sistema inmune innato representan un avance excitante en el estudio de las DCA y enfermedades inflamatorias de la piel.

Allergic contact dermatitis (ACD) is one of the most common skin diseases. ACD is a type IV delayed-type hypersensitivity response following topical exposure to a contact allergen. Historically, T lymphocytes within the adaptive immune system were viewed as the key factor in ACD. Recognition of the importance of the innate immune system in ACD has been a recent development. Significant progress has been made in the understanding of innate immunity, including the identification of receptors within the innate immune system. These receptors include toll-like receptor (TLRs) and nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs). TLRs and NLRs are able to respond to contact allergens by producing inflammatory cytokines. These cytokines, referred to as the danger signals, modulate both the sensitization and elicitation phase of ACD. TLRs and NLRs play a crucial role in ACD development. Interfering with these receptors or their pathways has the potential to prevent ACD. Understanding of the significance of innate immunity in the development of ACD has important clinical implications including advancement in potential preventions and treatments. TLRs and NLRs of the innate immune system represent an exciting advance in the study of ACD and inflammatory skin diseases.

Fundamentos sobre o conhecimento dos aditivos químicos presentes nas luvas de borracha / Fundamentals of the knowledge about chemical additives present in rubber gloves

FUNDAMENTOS: Uma das causas mais frequentes de dermatite de contato alérgica, de origem ocupacional, são os aditivos da borracha, presentes nos Equipamentos de Proteção Individual. Os aditivos das luvas natural e sintética mais alergênicos são tiurams, mercaptos e carbamatos. OBJETIVO: levantar o nível de conhecimento em relação aos aditivos químicos utilizados na fabricação das luvas de borracha sintética. MÉTODOS: Foi aplicado um questionário aberto a profissionais que trabalham com fabricação, pesquisa, prescrição e comercialização das luvas. Foi adotado o método de pesquisa qualitativa. RESULTADOS: Foram entrevistadas 30 pessoas: 4 pesquisadores na área de Medicina do Trabalho, 5 médicos do Trabalho, 2 técnicos de segurança do Trabalho, 1 médico do sindicato de trabalhadores da borracha, 1 engenheiro de Segurança do Trabalho, 1 engenheira de Produção do setor de fabricação de luvas de borracha, 4 empresários importadores de luvas, 1 empresário fabricante de luvas, 3 empresários que comercializavam Equipamentos de Proteção Individual, 3 vendedores de lojas de Equipamentos de Proteção Individual, 2 empresários de lojas que comercializavam produtos para alérgicos e 3 dermatologistas. CONCLUSÃO: O conhecimento da composição química das luvas é pequeno. A rotulagem das luvas, com a descrição da composição química, facilitaria a escolha do melhor tipo de luva para cada pessoa. Esta ação, de baixo custo para as empresas, seria um ganho, do ponto de vista da saúde pública, e teria grande repercussão nos usuários de luvas de borracha.

BACKGROUNDS: One of the most frequent causes of allergic contact dermatitis of occupational origin are rubber additives, which are present in Personal Protective Equipment (PPE). The most allergenic additives of natural and synthetic gloves are thiurams, carbamates and mercapto group. OBJECTIVE: To investigate the state of knowledge about the chemical additives used in the manufacture of synthetic rubber gloves. METHODS: This was a qualitative research study in which professionals working in the manufacture, research, prescription and commercialization of gloves answered an open questionnaire. RESULTS: 30 individuals were interviewed: 4 researchers in occupational medicine, 5 occupational physicians, 2 occupational safety technicians, a rubber workers' union physician, an occupational safety engineer, a pro duction engineer of rubber gloves, 4 importers of gloves, a manufacturer of gloves, 3 businessmen who sell PPE, 3 salesclerks working in stores that sell PPE, 2 businessmen who own stores that sell products for allergic indivi duals, and 3 dermatologists. CONCLUSION: Knowledge of the chemical composition of rubber gloves is scant. The labeling of gloves, with the description of their chemical composition, would facilitate choosing the best type of glove for each person. This low-cost action to businesses would be a gain from the standpoint of public health, with huge repercussions for users of rubber gloves.

Imunopatologia da dermatite de contato alérgica / Immunopathology of allergic contact dermatitis

A dermatite de contato alérgica é consequência de uma reação imune mediada por células T contra químicos de baixo peso molecular, denominados haptenos. É uma condição frequente que ocorre em todas as raças e faixas etárias e afeta a qualidade de vida de seus portadores. O mecanismo imunológico desta doença vem sendo revisto nas últimas décadas com significativo avanço no seu entendimento. A metabolização e o caminho dos haptenos, bem como a formação e o mecanismo de ação das células responsáveis tanto pela reação quanto pelo seu término, são discutidos neste artigo.

Allergic contact dermatitis is the consequence of an immune reaction mediated by T cells against low molecular weight chemicals known as haptens. It is a common condition that occurs in all races and age groups and affects the quality of life of those who present it. The immunological mechanism of this disease has been reviewed in recent decades with significant advance in its understanding. The metabolism and pathway of the haptens as well as the activation and mechanism of action of the cells responsible for both the immune reaction and its completion are discussed in this article.

Comparison of Transepidermal Water Loss, Capacitance and pH Values in the Skin between Intrinsic and Extrinsic Atopic Dermatitis Patients

Atopic dermatitis (AD), with the prevalence rate of around 10 to 15%, is characterized by an intensely pruritic skin lesions with typical distribution and morphology. Recently, AD is divided into extrinsic type (ADe) and intrinsic type (ADi) according to the laboratory findings and associated diseases. ADe is well-known for high IgE level, positive response to food- or aero-allergens, whereas ADi has clinically similar skin lesions and distribution patterns of AD with normal serum IgE levels, negative in vitro test for environmental or food allergens and without associated atopic diseases. To instrumentally evaluate the differences of skin involvement and functions between ADi and ADe, we checked the transepidermal water loss (TEWL), capacitance and pH in both types of childhood AD and age-matched control. The proportion of ADi was around 20% in all AD patients (10/51). Our experiment suggested possible differences between ADi and ADe. Antecubital fossa is a famous involvement site of childhood type of AD, where both types of AD patients showed higher TEWL and decreased capacitance. ADe patients showed increased TEWL in all sites and lower hydration in 4 sites, whereas ADi patients showed no significant differences of TEWL and hydration in forehead, cheek, and back of leg.

Expresión de CCL2 y CS-1 fibronectina en dermatitis alérgica por contacto / Expression of human CCL2 and CS-1 fibronectin in allergic contact dermatitis

Antecedentes: si bien la dermatitis alérgica por contacto (DAC) es una dermatosis humana frecuente, no todos los mecanismos involucrados en su patogenia han sido dilucidados. Objetivo: estudiar la cinética de expresión de CCL2, CS-1 fibronectina y CCL17 en biopsias de reacciones provocadas por pruebas de parches. Diseño: diez pacientes diagnosticados con DAC fueron desafiados en la espalda con antígenos inductores e irrelevantes. A las 2, 10 y 48 horas se observaron las respuestas macroscópicas y se obtuvieron biopsias, las cuales fueron procesadas para realizar estudios histológicos, inmunohistoquímicos y de hibridización in situ. Resultados: todos los individuos presentaron a las 48 horas una respuesta clínica positiva y un infiltrado celular mononuclear perivascular, el cual no fue observado en los controles negativos. ARNm para CCL2 fue encontrado solamente en sitios positivos a las 10 y 48 horas. Los endotelios inflamados expresaron CS-1 fibronectina y CCL17. El número de células CD+ y CD68+ aumentó significativamente con el tiempo en los parches positivos (p<0,0001). En éstos mismos sitios las células infiltrantes CCR5+ y CXCR3+, pero no las CCR3+ también incrementaron significativamente entre las 2 y 10 horas (p<0,03), y a las 48 horas, el porcentaje de células CCR5+ y CXCR3+ a las 10 y 48 horas (rs=0,9; p=0,0007). Conclusión: éste estudio demuestra por primera vez la producción de CCL2 y CS-1 fibronectina en la piel de pacientes con DAC en respuesta al desafío antigénico específico

Dermatosis ocupacionales / Occupational dermatoses

Las dermatosis ocupacionales constituyen un amplio grupo de enfermedades que se presentan con frecuencia en la práctica dermatológica. Este artículo expone las patologías relacionadas con los diferentes ámbitos de la actividad laboral, sus aspectos clínicos más relevantes y los mecanismos etiopatogénicos involucrados

Autoeccematización en un paciente con dermatitis por contacto / Autoeczematization in a patient with contact dermatitis

Se presenta el caso de un paciente con dermatitis por contacto con autoeccematización. Se hace referencia a la inmunopatogenia de esta condición, la cual parece consistir en un fenómeno de autoinmunidad de tipo celular hacia antígenos epidérmicos autólogos

Effects of ranitidine alone and in combination with chlorpheniramine on histamine-induced wheal and flare and psychomotor performance.

Some reports suggest that addition of an H2 antagonist increases the efficacy of H1 antagonist but the influence on the side effect profile of antihistamines are largely unknown. The effects of ranitidine, chlorpheniramine, their combination and placebo on histamine induced wheal and flare, psychomotor performance and subjective symptoms were studied in 6 healthy male volunteers in a double blind randomized and cross-over (Latin square) study. Ranitidine significantly reduced the histamine induced wheal at 4 hrs (P < 0.05). Chlorpheniramine and the combination significantly reduced both histamine induced wheal and flare at 2 hrs and at 4 hrs (P < 0.05). Addition of ranitidine reduced the feeling of sleepiness produced by chlorpheniramine, though other subjective symptoms were not affected. None of the treatment schedules produced any consistent change in the psychomotor performance of the volunteers.