RESUMO
BACKGROUND: The Eczema Area and Severity Index (EASI) is an investigator-assessed instrument measuring the severity of clinical signs in atopic dermatitis (AD). The EASI was identified as one of the best-validated outcome measures for AD; however, no previous studies address how to interpret the EASI score for clinical use. OBJECTIVES: To evaluate the interpretability and the ease of use of the EASI. METHODS: A retrospective analysis of paediatric and adult patients with AD was performed. Interpretability was evaluated by stratifying the EASI scores according to the Investigator's Global Assessment. The severity strata displaying the highest kappa coefficient of agreement were then selected as the recommended EASI band. The time to administer the EASI was recorded in a subgroup of patients. RESULTS: The suggested severity strata for the EASI are as follows: 0 = clear; 0·1-1·0 = almost clear; 1·1-7·0 = mild; 7·1-21·0 = moderate; 21·1-50·0 = severe; 50·1-72·0 = very severe (κ = 0·75). The EASI was also found to be acceptable in terms of ease of use, with assessments by trained investigators taking approximately 6 min. CONCLUSIONS: Our study provides the first guide for interpreting the EASI score. It enables translation of the EASI numerical output into an AD global severity state that should be more meaningful to providers and patients. Along with a short administration time, the EASI demonstrates adequate feasibility, further supporting its use in clinical trials.
Assuntos
Dermatite Atópica/diagnóstico , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Criança , Estudos de Viabilidade , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure.
Assuntos
Ensaios Clínicos como Assunto , Dermatite Atópica/terapia , Humanos , Assistência de Longa Duração , Avaliação de Resultados da Assistência ao Paciente , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Subjects with atopic dermatitis (AD) have defects in antimicrobial peptide (AMP) production possibly contributing to an increased risk of infections. In laboratory models, vitamin D can alter innate immunity by increasing AMP production. OBJECTIVE: To determine if AD severity correlates with baseline vitamin D levels, and to test whether supplementation with oral vitamin D alters AMP production in AD skin. METHODS: This was a multi-centre, placebo-controlled, double-blind study in 30 subjects with AD, 30 non-atopic subjects, and 16 subjects with psoriasis. Subjects were randomized to receive either 4000 IU of cholecalciferol or placebo for 21 days. At baseline and day 21, levels of 25-hydroxyvitamin D (25OHD), cathelicidin, HBD-3, IL-13, and Eczema Area and Severity Index (EASI) and Rajka-Langeland scores were obtained. RESULTS: At baseline, 20% of AD subjects had serum 25OHD below 20 ng/mL. Low serum 25OHD correlated with increased Fitzpatrick Skin Type and elevated BMI, but not AD severity. After 21 days of oral cholecalciferol, mean serum 25OHD increased, but there was no significant change in skin cathelicidin, HBD-3, IL-13 or EASI scores. CONCLUSIONS: This study illustrated that darker skin types and elevated BMI are important risk factors for vitamin D deficiency in subjects with AD, and highlighted the possibility that seasonality and locale may be potent contributors to cathelicidin induction through their effect on steady state 25OHD levels. Given the molecular links between vitamin D and immune function, further study of vitamin D supplementation in subjects with AD is warranted.
Assuntos
Colecalciferol/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Suplementos Nutricionais , Vitaminas/uso terapêutico , Adulto , Dermatite Atópica/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
BACKGROUND: The increased susceptibility of patients with atopic dermatitis (AD) to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood. OBJECTIVES: The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. MATERIALS AND METHODS: In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n = 24) compared with AD without a history of viral infections (ADEH-) (n = 20) before and after treatment with herpes simplex virus (HSV). RESULTS: We found that interferon (IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen (HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). CONCLUSIONS: These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Dermatite Atópica/imunologia , Antígeno HLA-B7/imunologia , Imunidade Celular/fisiologia , Interferon gama/biossíntese , Erupção Variceliforme de Kaposi/imunologia , Linfócitos T CD8-Positivos/metabolismo , Estudos de Casos e Controles , Dermatite Atópica/complicações , Frequência do Gene , Antígeno HLA-B7/genética , Humanos , Erupção Variceliforme de Kaposi/complicações , Leucócitos Mononucleares/imunologia , FenótipoAssuntos
Dermatite Atópica/microbiologia , Lipídeos/química , Infecções Cutâneas Estafilocócicas/metabolismo , Staphylococcus aureus , Adulto , Idoso , Dermatite Atópica/metabolismo , Regulação para Baixo/fisiologia , Epiderme/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Dermatite Atópica/induzido quimicamente , Imunidade Celular/efeitos dos fármacos , Pele/patologia , Ustekinumab/efeitos adversos , Administração Tópica , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Interleucina-17/imunologia , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Pele/efeitos dos fármacos , Células Th1/imunologia , Células Th17/imunologia , Ustekinumab/administração & dosagem , Adulto JovemRESUMO
PPD-sensitized monocytes and macrophages from tuberculin-positive subjects are both capable of inducing blastogenic transformation of autologous lymphocytes. Incorporation of thymidine-(3)H and morphological transformation were always greater in lymphocyte cultures containing macrophages than in those containing monocytes. More lymphocytes entered the first detectable S phase in cultures containing macrophages. Lymphocyte DNA synthesis occurred as early as 40 hr of culture and always in cells in contact with mononuclear phagocytes. By 120-144 hr, many transformed lymphocytes were free in suspension; at the same time, the "immunological cluster" had increased greatly in size and contained transformed and untransformed lymphocytes. The greater effectiveness of macrophages at induction of lymphocyte transformation may be related to the efficiency of this cell type at trapping antigen and its effectiveness at making contact with and binding lymphocytes.
Assuntos
Linfócitos/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Técnicas de Cultura , DNA/biossíntese , Humanos , Isótopos de Iodo , Ativação Linfocitária , Timidina/metabolismo , Fatores de Tempo , TrítioRESUMO
BACKGROUND: Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. OBJECTIVES: To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. METHODS: This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. RESULTS: An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. CONCLUSIONS: In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.
Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Imunossupressores/administração & dosagem , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Tacrolimo/análogos & derivados , Administração Cutânea , Adolescente , Adulto , Criança , Pré-Escolar , Dermatite Atópica/microbiologia , Método Duplo-Cego , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veículos Farmacêuticos/administração & dosagem , Infecções Cutâneas Estafilocócicas/imunologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/imunologia , Superantígenos/imunologia , Tacrolimo/administração & dosagem , Adulto JovemRESUMO
An evaluation and review of a structurally related group of fragrance materials.
Assuntos
Acetatos/química , Acetatos/toxicidade , Perfumes/química , Perfumes/toxicidade , Acetatos/farmacocinética , Animais , Humanos , Hidrocarbonetos Cíclicos/química , Hidrocarbonetos Cíclicos/farmacocinética , Hidrocarbonetos Cíclicos/toxicidade , Perfumes/farmacocinéticaRESUMO
In the current study, we investigated whether Staphylococcus aureus grown from affected skin of atopic dermatitis (AD) patients secreted identifiable toxins that could act as allergens to induce IgE-mediated basophil histamine release. The secreted toxins of S. aureus grown from AD patients were identified by ELISA using antibodies specific for staphylococcal enterotoxin (SE) exfoliative toxin (ET), or toxic shock syndrome toxin (TSST-1). S. aureus isolates from 24 of 42 AD patients secreted identifiable toxins with SEA, SEB, and TSST accounting for 92% of the isolates. 32 of 56 AD sera (57%) tested contained significant levels of IgE primarily to SEA, SEB, and/or TSST. In contrast, although SEA, SEB, or TSST secreting S. aureus could be recovered from the skin of psoriasis patients, their sera did not contain IgE antitoxins. Freshly isolated basophils from 10 AD patients released 5-59% of total histamine in response to SEA, SEB, or TSST-1 but only with toxins to which patients had specific IgE. Basophils from eight other AD patients and six normal controls who had no IgE antitoxin failed to demonstrate toxin-induced basophil histamine release. Stripped basophils sensitized with three AD sera containing IgE to toxin released 15-41% of total basophil histamine only when exposed to the relevant toxin, but not to other toxins. Sensitization of basophils with AD sera lacking IgE antitoxin did not result in release of histamine to any of the toxins tested. These data indicate that a subset of patients with AD mount an IgE response to SEs that can be grown from their skin. These toxins may exacerbate AD by activating mast cells, basophils, and/or other Fc epsilon-receptor bearing cells armed with the relevant IgE antitoxin.
Assuntos
Alérgenos/imunologia , Anticorpos Antibacterianos/imunologia , Toxinas Bacterianas/imunologia , Dermatite Atópica/imunologia , Exotoxinas/imunologia , Imunoglobulina E/imunologia , Staphylococcus aureus/imunologia , Basófilos/imunologia , Liberação de Histamina , Humanos , Hipergamaglobulinemia/imunologiaRESUMO
AD is a complex, multifactorial, cutaneous manifestation of the atopic diathesis. Observations from bone marrow transplantation cases have shown transmission of the disease from atopic donors [30] and indicate that the basic defect is carried in immune and inflammatory cells which infiltrate skin lesions. Mast cells appear to be important in the initiation of inflammatory events and eosinophils may have an important role in perpetuating the response. New evidence suggests that IL-4 may be a crucial factor controlling mast cells as well as IgE production in allergic disease. The significance of the Fc&RII/CD23 in regulating IgE synthesis and its role in Langerhans' cell/antigen interactions in atopic dermatitis represents an intriguing area in need of further study.
Assuntos
Dermatite Atópica , Antígenos de Diferenciação de Linfócitos B/imunologia , Basófilos/patologia , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Liberação de Histamina , Humanos , Imunidade Celular , Imunoglobulina E/imunologia , Células de Langerhans/patologia , Receptores Fc/imunologia , Receptores de IgERESUMO
An evaluation and review of a structurally related group of fragrance materials.
Assuntos
Norisoprenoides/toxicidade , Perfumes/toxicidade , Pele/efeitos dos fármacos , Administração Cutânea , Administração Oral , Alérgenos/classificação , Alérgenos/farmacocinética , Alérgenos/toxicidade , Animais , Qualidade de Produtos para o Consumidor , Relação Dose-Resposta a Droga , Prova Pericial , Feminino , Humanos , Masculino , Norisoprenoides/química , Norisoprenoides/farmacocinética , Noxas/classificação , Noxas/farmacocinética , Noxas/toxicidade , Perfumes/classificação , Perfumes/farmacocinética , Medição de Risco , Pele/metabolismo , Pele/patologia , Absorção Cutânea , Testes de Irritação da Pele , Testes de ToxicidadeRESUMO
An evaluation and review of a structurally related group of fragrance materials.
Assuntos
Inibidores de Ciclo-Oxigenase/toxicidade , Noxas/toxicidade , Perfumes/toxicidade , Salicilatos/toxicidade , Pele/efeitos dos fármacos , Alérgenos/classificação , Alérgenos/farmacocinética , Alérgenos/toxicidade , Animais , Qualidade de Produtos para o Consumidor , Inibidores de Ciclo-Oxigenase/classificação , Inibidores de Ciclo-Oxigenase/farmacocinética , Relação Dose-Resposta a Droga , Prova Pericial , Humanos , Noxas/classificação , Noxas/farmacocinética , Perfumes/farmacocinética , Medição de Risco , Salicilatos/classificação , Salicilatos/farmacocinética , Pele/metabolismo , Absorção Cutânea , Testes de Irritação da Pele , Testes Cutâneos , Testes de ToxicidadeRESUMO
An evaluation and review of a structurally related group of fragrance materials.
Assuntos
Cinamatos/toxicidade , Perfumes/toxicidade , Propanóis/toxicidade , Pele/efeitos dos fármacos , Administração Cutânea , Alérgenos/classificação , Alérgenos/farmacocinética , Alérgenos/toxicidade , Animais , Cinamatos/classificação , Cinamatos/farmacocinética , Qualidade de Produtos para o Consumidor , Ésteres , Humanos , Noxas/classificação , Noxas/farmacocinética , Noxas/toxicidade , Perfumes/classificação , Perfumes/farmacocinética , Propanóis/classificação , Propanóis/farmacocinética , Medição de Risco , Pele/metabolismo , Absorção Cutânea , Testes de Irritação da Pele , Testes Cutâneos , Testes de ToxicidadeRESUMO
Peripheral blood lymphocytes obtained at various intervals from normal individuals and from a patient with mycosis fungoides (MF) were cultured with phytohemagglutinin (PHA) for 3 days to activate suppressor cells. After being cultured, the PHA-treated cells were irradiated, washed, and then transferred to fresh medium with PHA. The PHA responsiveness of the cells from normal individuals was suppressed approximately 90% by autologous or normal allogeneic lymphocytes activated for 3 days with PHA, whereas the cells activated for 3 days with PHA from the patient with MF lacked the capacity to inhibit the mitogenic response of autologous or allogeneic lymphocytes. These data suggest that this patient lacked suppressor T-cells that have a specificity for helper T-cells.
Assuntos
Micose Fungoide/imunologia , Reticulócitos/patologia , Linfócitos T/imunologia , Idoso , Dermatite Esfoliativa/imunologia , Feminino , Humanos , Lectinas/farmacologia , Doenças Linfáticas/imunologia , Micose Fungoide/sangue , SíndromeRESUMO
The immunologic aberrations associated with atopic dermatitis include the paradox of reduced cell-mediated immune responses in the setting of increased cell-mediated immunity features that resemble allergic contact dermatitis. In this review, we present evidence that abnormalities in monocytes and Langerhans cells alter the function of T-helper-cell subpopulations to cause the immunologic defects associated with atopic dermatitis. Increased monocyte prostaglandin E2 production inhibits Th1 responses, accentuating interleukin (IL)-4 secretion by Th2 cells. Elevated prostaglandin E2 secretion correlates with abnormally increased cyclic adenosine monophosphate-phosphodiesterase activity in monocytes and this, along with other defective inflammatory cell responses, can be normalized in vitro by phosphodiesterase inhibitors. It appears that in addition to prostaglandin E2, IL-10 acts to regulate the balance between Th1 and Th2 functional responses accounting for many atopic features, including increased IL-4, IL-5, and IL-6 production by T cells; increased IgE synthesis; decreased interferon-gamma production; and impaired cell-mediated immune responses. All of these abnormalities can be related to increased phosphodiesterase activity in atopic monocytes, and inhibition of this key enzyme appears to reverse atopic dermatitis inflammatory abnormalities in vitro and in vivo.
Assuntos
Dermatite Atópica/fisiopatologia , Linfócitos/fisiologia , Monócitos/enzimologia , Diester Fosfórico Hidrolases/metabolismo , Animais , Dermatite Atópica/patologia , Dinoprostona/metabolismo , Humanos , Nucleotídeos Cíclicos/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Linfócitos T/fisiologiaRESUMO
Peripheral blood mononuclear leukocytes (MNL) from patients with atopic dermatitis spontaneously produce large amounts of IgE in vitro. These cells also show markedly elevated levels of cAMP phosphodiesterase (PDE) which may be responsible for the observed abnormal cAMP responsiveness. Treatment of atopic dermatitis MNL with varying concentrations of the cAMP PDE inhibitor Ro 20-1724 resulted in progressively decreasing amounts of IgE synthesis, statistically significant at the 10(-4) M and 10(-5) M concentrations. There was a close correlation between PDE inhibition and inhibition of IgE synthesis, r = 0.93, p less than 0.05. To define the cellular target of the drug, we used monoclonal antibodies directed toward MNL subsets (Lyt 3, OKT8, OKT4, monocyte-myeloid) in a modified "panning" method to perform experiments with purified subsets. With untreated subsets, removal of OKT4-positive cells significantly reduced IgE synthesis; readdition of OKT4-positive cells enhanced IgE synthesis. OKT8 cells and monocytes did not affect IgE synthesis. Pretreatment of T cell-depleted MNL with Ro 20-1724 resulted in significantly more inhibition of IgE synthesis than did pretreatment of T enriched cells prior to recombination with the reciprocal untreated subset and subsequent culture. Similarly, pretreatment of monocyte-depleted cells resulted in significantly more inhibition of IgE synthesis than pretreatment of monocyte-enriched cells prior to recombination and culture. The majority of the effect appeared to be mediated by a direct effect on the B cells. However, some inhibition of IgE synthesis was also achieved through pretreatment of T enriched cells. Since pretreatment of isolated suppressor/cytotoxic or helper/inducer T-cell subsets did not give the same degree of inhibition as with unfractionated T cells, a T-T interaction may be involved in this aspect. The imidazolidinone derivative, Ro 20-1724, significantly and consistently inhibited both the elevated cAMP phosphodiesterase activity and the elevated spontaneous IgE synthesis of MNL from patients with atopic dermatitis. These findings demonstrate a previously undescribed link between cAMP PDE levels and in vitro IgE synthesis.
Assuntos
4-(3-Butoxi-4-metoxibenzil)-2-imidazolidinona/farmacologia , Dermatite Atópica/patologia , Imidazóis/farmacologia , Imunoglobulina E/biossíntese , Adolescente , Adulto , Separação Celular , Depressão Química , Dermatite Atópica/metabolismo , Humanos , Leucócitos/classificação , Pessoa de Meia-IdadeRESUMO
The atopic conditions, atopic dermatitis, asthma, and allergic rhinitis, may arise as a result of infiltrating bone marrow-derived cells into skin or respiratory mucosae. Release of inflammatory factors from these cells could account for cutaneous vascular instability and pruritus in atopic dermatitis. Erythema and itch have been induced by experimental stress interviews and by blind food challenges. In the latter, increased plasma histamine was detected and correlated with cutaneous reactions. Basophils from patients with atopic dermatitis have increased histamine release after exposure to immunologic or nonimmunologic lectin stimuli. This increased releasability may relate to inadequate cyclic AMP regulation of cell function. We have found that leukocytes of patients with atopic dermatitis have elevated phosphodiesterase activity and consequently reduced intracellular cyclic AMP. Exposure of the cells to a phosphodiesterase inhibitor caused considerable reduction in histamine release. Similarly, exposure of atopic B lymphocytes to a phosphodiesterase inhibitor greatly reduced the high spontaneous IgE synthesis in mononuclear leukocyte cultures. Elevated leukocyte phosphodiesterase activity may also serve as a marker for the atopic diathesis. We have found elevated enzyme activity in umbilical cord blood from newborns with atopic parents, suggesting that this defect may relate to a genetically determined defect. These studies have provided insight into basic abnormalities associated with atopic dermatitis and the atopic diathesis. Defects of regulatory mechanisms in immune and inflammatory cells may help explain the seemingly disparate disorders of physiologic, pharmacologic, and immunologic systems in atopy.