RESUMEN
The Japanese Dermatological Association established an advisory committee in 1995 to set up severity scoring systems for atopic dermatitis (AD). Its interim report was published in Japanese in the Japanese Journal of Dermatology (108: 1491-1496, 1998) by Chairman Hikotaro Yoshida. Because of the strong demand for an English version, we have decided to publish the report in English. This prospective study was designed to evaluate the status of 259 AD patients using Method 1, which involves a simple global evaluation of disease severity; Method 2, which involves global evaluation by summing severity scores obtained from five body regions (i.e. the head and neck, anterior and posterior trunks, and upper and lower limbs); Method 3, which consists of both assessment of the extent of involved areas at each of the five body regions and that of the severity scores of each eruption component observed in the most severely affected body region; and Method 4, which consists of the evaluation of only subjective components (daytime pruritus and sleep disturbance). Employing the results obtained with Method 1 as a tentative benchmark, we analyzed its correlation with those of Methods 2, 3 and 4 to statistically assess the validity and reliability of these methods. Method 2, Method 3 and the portion of Method 4 involving evaluation of only the subjective symptom of daytime pruritus but not the sleep disturbance were considered useful in evaluating AD severity.
Asunto(s)
Dermatitis Atópica/clasificación , Adolescente , Adulto , Comités Consultivos , Niño , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Femenino , Humanos , Japón , Lenguaje , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prurito/etiología , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Trastornos del Sueño-Vigilia/etiología , Sociedades Médicas , Adulto JovenRESUMEN
The Japanese Dermatological Association established an advisory committee in 1995 to develop a severity scoring system for atopic dermatitis (AD). Its interim and concluding reports were published in Japanese in the Japanese Journal of Dermatology (108: 1491-1496, 1998 and 111: 2023-2033, 2001). Because of the strong demand for an English version, we have decided to publish the reports in English. This manuscript is the English version of the concluding report. The interim report suggested that eruption components such as erythema, papule, erosion, crust, excoriation and lichenification with extent of involved areas in five body regions, including the head and neck, anterior and posterior trunks, and upper and lower limbs, were important items for assessing AD severity. Additionally, it was recommended that streamlining of eruption components was mandatory for improving the statistical validity and reliability. The committee members subsequently concentrated their efforts on this task, and finally proposed an Atopic Dermatitis Severity Classification Criteria of the Japanese Dermatological Association.
Asunto(s)
Dermatitis Atópica/clasificación , Adulto , Comités Consultivos , Anciano , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Femenino , Humanos , Japón , Lenguaje , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prurito/etiología , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Sociedades Médicas , Adulto JovenAsunto(s)
Dermatitis Atópica , Guías de Práctica Clínica como Asunto , Administración Oral , Administración Tópica , Antialérgicos/administración & dosificación , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/epidemiología , Dermatitis Atópica/etiología , Dermatitis Atópica/terapia , Glucocorticoides/administración & dosificación , Antagonistas de los Receptores Histamínicos/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Índice de Severidad de la Enfermedad , Tacrolimus/administración & dosificaciónRESUMEN
BACKGROUND: A simple list of diagnostic criteria for atopic dermatitis for use in epidemiological studies was developed by a U.K. working party. This list served well for both hospital patients with skin diseases and in general population within the U.K. OBJECTIVES: To validate the U.K. diagnostic criteria in Japanese elementary schoolchildren, we collected the questionnaires on regular health checkups, which had been completed by parents of schoolchildren in 2001/2002 and 2004/2005. METHODS: Elementary schoolchildren were examined by dermatologists in eight areas (16,152 children) in 2001/2002 and in three areas (3849 children) in 2004/2005. The questionnaire was distributed to the parents 2 weeks before the skin examination, completed by the parents and collected after the survey. RESULTS: In 2002/2002 comparing the U.K. diagnostic criteria with the findings on clinical examination used as the reference standard, the U.K. criteria (1-year prevalence measure) showed a sensitivity of 71.8%, specificity of 89.3% and positive predictive value of 44.7%. In 2004/2005 we confirmed that the U.K. criteria for a point prevalence measure showed a higher positive predictive value (59.9%) compared with that for 1-year prevalence measure (49.3%). CONCLUSION: Now that we know the sensitivity and specificity of the U.K. criteria in the population examined in this study, we will be able in the near future to estimate the prevalence of atopic dermatitis in a similar population with reverse operation by questionnaires alone using these criteria without examination by dermatologists. Therefore, the validation study of U.K. criteria could be useful for future epidemiologic surveys.
Asunto(s)
Dermatitis Atópica/diagnóstico , Dermatitis Atópica/epidemiología , Niño , Servicios de Salud Comunitaria , Dermatología/métodos , Humanos , Japón , Valor Predictivo de las Pruebas , Prevalencia , Estándares de Referencia , Instituciones Académicas , Sensibilidad y Especificidad , Encuestas y Cuestionarios , Reino UnidoRESUMEN
Substance P (SP) selectively activates mast cells that reside in connective tissues. We studied the reactions of bone marrow-derived mast cells (BMMC) of three mouse strains, cultured with or without fibroblasts. BMMC co-cultured with fibroblasts, but not those cultured alone, increased intracellular Ca(2+), released LTB(4) and histamine in response to SP. PD098059 significantly inhibited the release of LTB(4), but not histamine in all strains. SB203580 failed to reduce or slightly impaired the release of LTB(4). These results suggest that mast cells undergo maturation under the influence of fibroblasts, acquiring the responsiveness to SP with Ca(2+) signals and predominantly ERK-MAP kinase.
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Leucotrieno B4/metabolismo , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Sustancia P/inmunología , Sustancia P/farmacología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Calcio/metabolismo , Señalización del Calcio/inmunología , Técnicas de Cocultivo , Inhibidores Enzimáticos/farmacología , Fibroblastos/citología , Flavonoides/farmacología , Liberación de Histamina/efectos de los fármacos , Imidazoles/farmacología , Masculino , Mastocitos/citología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Células 3T3 NIH , Piridinas/farmacología , Especificidad de la Especie , Sustancia P/metabolismoRESUMEN
The increase of serum IgE levels is closely associated with atopic dermatitis. We have previously revealed that cellular extract of PAM212 cells (PAM-extract), BALB/c mouse keratinocyte cell line, induced a remarkable increase of serum IgE levels, in vivo, when subcutaneously injected into BALB/c mice. However, precise mechanism of IgE-increasing activity was unclear. To elucidate the mechanism of IgE-increase in sera of BALB/c mice induced by PAM-extract, we explored the direct influence of PAM-extract on immunoglobulin production and class-switching in the culture of splenic lymphocytes and purified B-cells, in vitro. Splenic lymphocytes or purified B-cells obtained from BALB/c mice were cultured with various combinations of IL-4, anti-CD40 antibody, and PAM-extract for 7 days. IgE and IgG concentrations of culture supernatants were measured by ELISA. Epsilon germ-line transcriptions were assessed by RT-PCR from the cultured cells. IgE and IgG concentrations in culture supernatant of splenic lymphocytes were increased by an addition of PAM-extract in the presence of both IL-4 and anti-CD40 antibody. Epsilon germ-line transcript was also induced in parallel to the increase of IgE production. Similar results were obtained when purified B-cells were employed in stead of whole splenic lymphocytes. The enhancement of IgE production in vitro was also observed, when splenic lymphocytes of CBAj mouse were cultured with cellular extract of KCMH-1 cells, CBAj mouse keratinocyte cell line. The cellular extract of keratinocyte promotes immunoglobulin class-switching to IgE and IgE production from mouse splenic B-cells in an IL-4- and CD40-stimuli-dependent manner. Such enhancement may account for the increase of serum IgE in patients with dermatitis in association with a Th2 microenvironment.
Asunto(s)
Linfocitos B/inmunología , Extractos Celulares/inmunología , Inmunoglobulina E/biosíntesis , Queratinocitos/inmunología , Animales , Anticuerpos/inmunología , Antígenos CD40/inmunología , Línea Celular , Células Cultivadas , Dinoprostona/farmacología , Ensayo de Inmunoadsorción Enzimática , Cambio de Clase de Inmunoglobulina , Inmunoglobulina G/análisis , Inmunoglobulina G/metabolismo , Interleucina-4/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Bazo/citologíaRESUMEN
Sweating aggravates itch in atopic dermatitis, but the mechanism is unclear. In this study, we examined the involvement of type I hypersensitivity in the aggravation of atopic dermatitis by sweating. Skin tests with autologous sweat were positive in 56 of 66 patients (84.4%) with atopic dermatitis, but only in 3 of 27 healthy volunteers (11.1%). Sweat samples from both patients and healthy volunteers induced varying degrees of histamine release from basophils of patients with atopic dermatitis. However, the histamine release was impaired by removal of IgE on the basophils. Incubation of basophils with myeloma IgE before sensitization with serum of patients blocked the ability to release histamine-induced sweat. IgE antibody against antigen(s) in sweat may be present in serum of patients with atopic dermatitis. Key words:
Asunto(s)
Anticuerpos Antiidiotipos/análisis , Dermatitis Atópica/inmunología , Histamina/metabolismo , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/análisis , Sudor/inmunología , Adolescente , Adulto , Análisis de Varianza , Autoantígenos/análisis , Basófilos/inmunología , Basófilos/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Estudios de Cohortes , Dermatitis Atópica/fisiopatología , Desensibilización Inmunológica , Femenino , Histamina/análisis , Humanos , Hipersensibilidad Inmediata/fisiopatología , Masculino , Probabilidad , Valores de Referencia , Sensibilidad y Especificidad , Pruebas CutáneasRESUMEN
BACKGROUND: Defects in immune responses have been reported in patients with Behçet's disease (BD). To further characterize the immune dysfunction and its contribution to the pathogenesis, we have studied Fas ligand (FasL) expression in peripheral blood lymphocytes (PBL) and mononuclear cells in the skin lesions in patients with BD. METHODS: FasL expression in PBL was studied with RT-PCR and immunoblotting with rabbit anti-human FasL antibody. We studied the expression of FasL in cryostat sections of biopsy specimens of erythema nodosum lesions from 4 patients with BD and of a genital ulcer lesion in another patient using immunohistochemical staining. Apoptotic cell death was detected with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. RESULTS: We found that FasL mRNA and FasL protein expression was detected marginally in the unstimulated PBL, and was induced upon activation in normal individuals. PBL from patients with BD exhibited an enhanced expression of FasL mRNA and FasL protein without in vitro stimulation. Moreover, mitogen stimulation failed to augment FasL expression of their lymphocytes, suggesting a dysregulation of FasL expression of PBL in patients with BD. The skin biopsy specimens revealed that cells infiltrating into skin lesions expressed FasL and there were several TUNEL staining-positive cells in the lesions, suggesting that Fas/FasL-mediated apoptosis is involved in the development of the skin lesion and thus may be associated with the pathogenesis. CONCLUSIONS: We found an excessive expression of FasL in circulating as well as skin-infiltrating lymphocytes and the presence of apoptotic cells in the skin lesions, suggesting that lymphocytes expressing FasL aberrantly may play a role in the development and pathogenesis of BD.
Asunto(s)
Síndrome de Behçet/inmunología , Linfocitos/metabolismo , Glicoproteínas de Membrana/biosíntesis , Adulto , Apoptosis/inmunología , Síndrome de Behçet/sangre , Síndrome de Behçet/metabolismo , Síndrome de Behçet/patología , Proteína Ligando Fas , Humanos , Immunoblotting , Etiquetado Corte-Fin in Situ , Linfocitos/inmunología , Glicoproteínas de Membrana/sangre , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Persona de Mediana Edad , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Increased serum IgE levels are found in atopic diseases, especially atopic dermatitis. It is generally accepted that the high serum IgE levels are increased by exposure to exogenous antigens. However, exposure to antigens in the absence of proper adjuvants does not usually increase serum IgE. Here, we studied the involvement of skin factor(s) in increasing serum IgE. The soluble fractions were obtained from two keratinocyte cell lines, PAM 212 and KCMH-1, derived from BALB/c and CBA/J mice, respectively. These were injected subcutaneously into parental mice strains at 2-week intervals. The levels of serum immunoglobulins and the release of IgE in vitro from spleen cells were measured by ELISA. The biological activity of the increased serum IgE was assessed by sensitization of RBL-2H3 mast cells with serum. Six injections of PAM 212-derived fraction (PAM extract) consistently increased the serum levels of IgE, IgG1 and IgG2b, but not those of IgM, IgG2a, IgG3 or IgA in BALB/c mice. The high serum levels of IgE were sustained for at least 10 weeks after one or two injections of PAM extract. When RBL-2H3 cells were sensitized with the serum from mice injected with PAM extract, they released histamine in response to anti-IgE. Moreover, spleen cells of these mice produced significantly higher amounts of IgE than those of uninjected mice in the presence of IL-4 and anti-CD40 antibody. On the other hand, no significant increase in immunoglobulins was observed following injection of the soluble fraction from KCMH-1 cells in CBA/J mice. These results suggest that the release of the soluble fraction of keratinocytes and its exposure to immunologically competent cells may induce an increase in serum IgE levels by a Th2-dominant mechanism.
Asunto(s)
Inmunoglobulina E/sangre , Queratinocitos/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/aislamiento & purificación , Animales , Línea Celular , Dermatitis Atópica/etiología , Dermatitis Atópica/inmunología , Relación Dosis-Respuesta Inmunológica , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Especificidad de la EspecieRESUMEN
Surface plasmon resonance (SPR)-based sensors have been used to detect the binding between interactive molecules. We applied the SPR technology to the analysis of interactions between living cells and molecules reactive to the cells, using mast cells and mast cell-reactive antigens. The exposure of dinitrophenol-human serum albumin (DNP-HSA), an antigen that stimulates mast cells, to IgE-sensitized mast cells induced a robust and long-lasting SPR signal in a dose-dependent manner. The maximal increase in SPR signal induced by 100 ng/ml DNP-HSA was 0.200 +/- 0.120 angle (mean +/- SD, n = 37), about 1000 times larger than the theoretically expected increase for the simple binding of DNP-HSA to Fc(epsilon)RI, the high-affinity IgE receptor. A small, but similarly prolonged signal was observed when the cells were stimulated by an agonist of the adenosine A3 receptor. The signal induced by DNP-HSA was abolished by genistein, and partially inhibited by phorbol 12-myristate 13-acetate and wortmannin. Interestingly, the signal induced by DNP-HSA was only weakly inhibited by DNP-lysine, suggesting that DNP-lysine manifests its action not by inhibiting, but by modulating the crosslinking of Fc(epsilon)RI. We concluded that SPR sensors can detect biologically significant signals in a real-time manner from the interactions between cells and molecules reactive to the cells.