RESUMEN
BACKGROUND: 2-Hydroxyethyl methacrylate (HEMA) was added into the European baseline series (EBS) in 2019. There is limited data regarding the frequency, relevance, and sources of exposure to HEMA. OBJECTIVES: To investigate the frequency and clinical relevance of positive reactions to HEMA in the EBS in Israel, and explore sources of exposure. METHODS: Retrospective cohort study that included all patients who underwent patch testing with the EBS in a tertiary center in Israel between 2020 and 2023. Positive reactions to HEMA were stratified by sex, six age groups, and year of study. Sources of exposure to HEMA as well as occupational data were recorded. RESULTS: A total of 1671 consecutive patients underwent HEMA patch testing, with 135 (8.1%) showing positive reactions to HEMA (130 females, 5 males). The prevalence in women (11.0%) was significantly higher compared to men (1.0%) (p < 0.001). Stratification by age and sex revealed the highest frequency of HEMA sensitivity of 16.7% among women younger than 30 years of age, with odds ratio of 2.3 (95%CI: 1.6-3.3, p < 0.001) compared to older women. There was an increase in frequency among women between the years 2022 and 2023 when compared to 2020-2021 (OR 1.7, 95%CI: 1.5-2.1, p < 0.01) attributable to COVID-19 pandemic and social restrictions. Among men the frequency fluctuations over the study period and age categories were nonsignificant. 111 (84%) were judged to be of clinical relevance and nail cosmetics was responsible for 95% of them. Of 111 patients with relevant reaction (110 females, 1 males), 20 (18%) had occupational contact dermatitis (18 nails stylists, 2 dentists). Other culprit products included sanitary pads (n = 4), medical adhesives (n = 3), and paints (n = 2). CONCLUSION: We report the highest frequency of HEMA sensitivity to date of 8.1%, that was most common among young women and in vast majority of cases was attributable to nail cosmetics. Our findings reflect the popularity of nail cosmetics in Israel as well as the global trend of increasing sensitivity to (meth)acrylates.
RESUMEN
BACKGROUND: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States. OBJECTIVES: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. RESULTS: The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.
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Dermatología , Guías como Asunto , Pénfigo , Venereología , Academias e Institutos , Europa (Continente) , Humanos , Pénfigo/diagnóstico , Pénfigo/tratamiento farmacológicoRESUMEN
BACKGROUND: Psychological stress has long been linked with the exacerbation/onset of psoriasis. OBJECTIVES: To determine if antecedent psychological stress is associated with the exacerbation/onset of psoriasis. METHODS: A search of the PubMed, PsycINFO, Cochrane library and ClinicalTrials.gov databases was performed. Surveys evaluating beliefs about stress reactivity were analysed separately. Suitable studies were meta-analysed. RESULTS: Thirty-nine studies (32 537 patients) were included: 19 surveys, seven cross-sectional studies, 12 case-control studies and one cohort study. Forty-six per cent of patients believed their disease was stress reactive and 54% recalled preceding stressful events. Case-control studies evaluating stressful events rates prior to the exacerbation (n = 6) or onset (n = 6) of psoriasis varied in time lag to recollection (≤ 9 months to ≥ 5 years). Pooling five studies evaluating stressful events preceding onset of psoriasis gave an odds ratio (OR) of 3·4 [95% confidence interval (CI) 1·8-6·4; I2 = 87%]; the only study evaluating a documented stress disorder diagnosis reported similar rates between patients and controls (OR 1·2, 95% CI 0·8-1·8). Four studies evaluating stressful events prior to psoriasis exacerbation reported comparable rates with controls, whereas two found more frequent/severe preceding events among patients with psoriasis. A small prospective cohort study reported a modest association between stress levels and exacerbation of psoriasis (r = 0·28, P < 0·05). CONCLUSIONS: The association between preceding stress and exacerbation/onset of psoriasis is based primarily on retrospective studies with many limitations. No convincing evidence exists that preceding stress is strongly associated with exacerbation/onset of psoriasis.
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Psoriasis/psicología , Estrés Psicológico/etiología , Adolescente , Adulto , Actitud Frente a la Salud , Niño , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Bullous pemphigoid is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or generalized bullous lesions. In up to 20% of affected patients, bullae may be completely absent, and only excoriations, prurigo-like lesions, eczematous lesions, urticated lesions and/or infiltrated plaques are observed. The disease is significantly associated with neurological disorders. The morbidity of bullous pemphigoid and its impact on quality of life are significant. So far, a limited number of national treatment guidelines have been proposed, but no common European consensus has emerged. Our consensus for the treatment of bullous pemphigoid has been developed under the guidance of the European Dermatology Forum in collaboration with the European Academy of Dermatology and Venereology. It summarizes evidence-based and expert-based recommendations.
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Penfigoide Ampolloso/terapia , Administración Cutánea , Corticoesteroides/administración & dosificación , Técnicas de Laboratorio Clínico/métodos , Consenso , Fármacos Dermatológicos/uso terapéutico , Suplementos Dietéticos , Humanos , Hidroterapia/métodos , Anamnesis/métodos , Grupo de Atención al Paciente , Educación del Paciente como Asunto/métodos , Penfigoide Ampolloso/diagnóstico , Examen Físico/métodos , Grupos de Autoayuda , Esteroides/administración & dosificaciónRESUMEN
BACKGROUND: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, the prognosis of pemphigus was almost fatal. Due to its rarity, only few prospective controlled therapeutic trials are available. OBJECTIVES: For this reason, a group of European dermatologists with a long-standing interest and expertise in basic and clinical pemphigus research has sought to define diagnostic and therapeutic guidelines for the management of patients with pemphigus. RESULTS: This group identified the statements of major agreement or disagreement regarding the diagnostic and therapeutic management of pemphigus. The revised final version of the pemphigus guideline was finally passed on to the European Dermatology Forum (EDF) for a final consensus with the European Academy of Dermatology and Venereology (EADV) and the European Union of Medical Specialists (UEMS).
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Pénfigo/diagnóstico , Pénfigo/terapia , Europa (Continente) , HumanosRESUMEN
Rituximab has recently been reported in retrospective studies to be effective in pemphigus at the dosing schedule used for treating rheumatoid arthritis (RA) of two 1,000 mg infusions 2 weeks apart. While the effect of rituximab on B cells has been well described, its effect on global T cell function has not been assessed. Ten patients who received RA dosage rituximab were prospectively assessed for clinical response. Immunological response including autoantibody titers, CD20+ B cell, and CD4+ T cell counts was assessed pre- and post-treatment. The CD4+ T cell function was determined by a novel assay measuring intracellular ATP levels in response to mitogenic stimulus. At 6 months, 90 % of patients achieved remission. Disease control and remission were achieved at median times of 1 and 3.7 months, respectively. There was a 67 % relapse rate during an average follow-up of 22 months. Global CD4+ T cell numbers and function were preserved 3 months after rituximab. A single cycle of RA dosage rituximab with concomitant immunosuppression is effective in pemphigus. We did not find an effect on total CD4+ T cell numbers or function 3 months after treatment.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Autoanticuerpos/sangre , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Pénfigo/tratamiento farmacológico , Adulto , Anciano , Antígenos CD20/sangre , Antineoplásicos/uso terapéutico , Recuento de Linfocito CD4 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Rituximab , Resultado del TratamientoRESUMEN
Recent evidence that infectious mononucleosis (IM) may be sexually transmitted prompted the present analysis. Infectious mononucleosis is a notifiable disease in the Israel Defense Forces (IDF). For the present study, the archives of the IDF were reviewed for all cases of IM from January 1, 1978 to December 31, 2009, and the rates were calculated. Annual rates decreased from 2.99 cases per 1,000 in 1979 to a low of 0.38 cases per 1,000 young adults in 1987. Between 2002 and 2009, the average annual rate was 0.88 cases per 1,000, just half the average rate of 1.69 observed between 1989 and 2001. Average monthly rates varied from a low of 0.90 cases per 10,000 in February to a high of 1.50 cases per 10,000 in August. The difference in the average rates between winter (1.02 cases per 10,000 soldiers) and summer (1.29 cases per 10,000 soldiers) was significant (p < 0.01). Analysis of the long-term epidemiology of IM shows that the infection rate has varied over time, and that the disease is more prevalent in the warmer months. This seasonality trend was also observed in several STD, raising the possibility of considering this mode of transmission in IM.
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Mononucleosis Infecciosa/epidemiología , Adolescente , Adulto , Femenino , Humanos , Incidencia , Israel/epidemiología , Masculino , Persona de Mediana Edad , Estaciones del Año , Adulto JovenRESUMEN
BACKGROUND: Atopic dermatitis (AD) has been associated with sensory hypersensitivity in children. OBJECTIVE: To examine the sensory profile of adults with AD using a standardized questionnaire that measures sensory processing and related behaviours in daily living. METHODS: Thirty-two patients aged 18-53 years with AD and 32 healthy, sex- and age-matched control subjects completed the Adolescent/Adult Sensory Profile (AASP). Severity of AD was assessed by the Severity Scoring of Atopic Dermatitis (SCORAD). RESULTS: Patients with AD showed higher sensory sensitivity and avoidance than the controls, mainly in the tactile, vestibular, visual and auditory modalities. CONCLUSIONS: Adults with AD may suffer from sensory hypersensitivity. Additional studies should examine the influence of the peripheral and the central nervous system on sensory hypersensitivity. Better understanding of the sensory impairment of patients with AD may help improving treatment strategies for the disease.
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Dermatitis Atópica/fisiopatología , Sensación/fisiología , Umbral Sensorial/fisiología , Actividades Cotidianas/psicología , Adolescente , Adulto , Estudios de Casos y Controles , Sistema Nervioso Central/fisiología , Dermatitis Atópica/psicología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Sistema Nervioso Periférico/fisiología , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Pemphigus vulgaris is a rare life-threatening autoimmune bullous disease caused by immunoglobulin G (IgG) autoantibodies directed against desmogleins 1 and 3. Previously, we showed that intravenous immunoglobulin (IVIG) ameliorates anti-desmoglein-induced experimental pemphigus vulgaris in newborn naive mice. The aim of this study was to examine the efficacy of anti-anti-desmoglein-specific IVIG in a similar model. Pemphigus-vulgaris-specific IVIG (PV-sIVIG) was affinity-purified from IVIG on a column of single-chain variable fragment (scFv) anti-desmogleins 1 and 3. The anti-idiotypic activity of PV-sIVIG was confirmed by enzyme-linked immunosorbent assay, inhibition assay. After induction of pemphigus by injection of anti-desmogleins 1 and 3 scFv to newborn mice, the animals were treated with PV-sIVIG, IVIG (low or high dose) or IgG from a healthy donor (n = 10 each). The skin was examined 24-48 h later, and samples of affected areas were analysed by histology and immunofluorescence. In vitro study showed that PV-sIVIG significantly inhibited anti-desmogleins 1 and 3 scFv binding to recombinant desmoglein-3 in a dose-dependent manner. Specificity was confirmed by inhibition assay. In vivo analysis revealed cutaneous lesions of pemphigus vulgaris in mice injected with normal IgG (nine of 10 mice) or low-dose IVIG (nine of 10 mice), but not in mice treated with PV-sIVIG (none of 10) or high-dose IVIG (none of 10). On immunopathological study, PV-sIVIG and regular IVIG prevented the formation of acantholysis and deposition of IgG in intercellular spaces. In conclusion, the PV-sIVIG preparation is more effective than native IVIG in inhibiting anti-desmoglein-induced pemphigus vulgaris in mice and might serve as a future therapy in patients with the clinical disease.
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Anticuerpos Antiidiotipos/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Pénfigo/tratamiento farmacológico , Anticuerpos de Cadena Única/metabolismo , Piel/efectos de los fármacos , Acantólisis/prevención & control , Animales , Animales Recién Nacidos , Anticuerpos Antiidiotipos/efectos adversos , Anticuerpos Antiidiotipos/inmunología , Anticuerpos Antiidiotipos/aislamiento & purificación , Autoanticuerpos/administración & dosificación , Autoanticuerpos/inmunología , Autoanticuerpos/metabolismo , Desmogleína 1/inmunología , Desmogleína 3/inmunología , Modelos Animales de Enfermedad , Epítopos , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Inmunoglobulinas Intravenosas/inmunología , Inmunoglobulinas Intravenosas/aislamiento & purificación , Ratones , Ratones Endogámicos C57BL , Pénfigo/inmunología , Pénfigo/fisiopatología , Ingeniería de Proteínas , Anticuerpos de Cadena Única/administración & dosificación , Anticuerpos de Cadena Única/genética , Piel/inmunología , Piel/metabolismo , Piel/patologíaRESUMEN
Recent reports of increased rates of gonorrhea initiated an analysis of secular trends of gonorrhea in a young adult population. Gonorrhea is a notifiable disease in the Israel Defense Forces. The diagnosis is based on the typical clinical presentation, relevant epidemiologic data, and positive bacteriological culture. For the present study, the archives of the Epidemiology Department were reviewed for all documented cases of gonorrhea from January 1, 1978 to December 31, 2008, and the annual and seasonal incidence rates were calculated. Annual gonorrhea rates decreased from 2.3 cases per 1,000 soldiers in 1978 to an all-time low of 0.07 cases per 1,000 soldiers in 2008, representing a 97% decline. Multi-year average monthly rates varied from a low of 5.83 cases per 100,000 population in February to a high of 8.97 cases per 100,000 in August. The difference in the person-time incidence (PTI) rates for winter (5.9 cases per 100,000 person-years) and summer (6.8 cases per 100,000 person-years) was statistically significant (p < 0.01). Analyzing the long-term epidemiology of gonorrhea has shown that the infection rate is continuously decreasing and that it appears to be more prevalent in the warmer months.
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Gonorrea/epidemiología , Adolescente , Adulto , Humanos , Incidencia , Israel/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estaciones del Año , Adulto JovenRESUMEN
BACKGROUND: Pemphigus vulgaris is a chronic autoimmune mucocutaneous blistering disease. In the last 20 years, immunomodulatory agents have been added to the therapeutic armamentarium. Only few recent studies have evaluated the long-term outcome of pemphigus and possible prognostic parameters in a large group of patients. The aim of this study was to evaluate and analyse the course and prognostic factors of pemphigus in patients followed from 1976 to 2004. PATIENTS AND METHODS: The study group consisted of 155 patients attending the pemphigus clinic of a major tertiary-care medical centre. Background, clinical and treatment data were derived from the patient files and telephone contact. Statistical analysis was performed with Pearson correlation, Fisher exact test, and univariate and multivariate logistic regression models. RESULTS: Age < 40 years at disease onset, Sephardic Jewish origin, and mucosal involvement at diagnosis and high number of relapses were found to be independent prognostic factors of poor outcome. A long (> 1 year) primary remission was a good prognostic factor. During the 26-year study period, 16 patients died. None of the deaths was directly related to either the disease or a complication of treatment. CONCLUSIONS: The course and outcome of pemphigus are worse in patients who are young at diagnosis (< 40 years) or of Sephardic Jewish origin. Mucosal involvement at diagnosis and poor response to treatment also predict poor outcome. The mortality rate of pemphigus is apparently lower than reported in the literature, perhaps because of the contemporary use of adjuvant immunomodulatory therapeutic agents.
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Pénfigo/diagnóstico , Pénfigo/mortalidad , Corticoesteroides/uso terapéutico , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Inmunomodulación , Judíos/etnología , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pénfigo/etnología , Pronóstico , Recurrencia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Tick-borne relapsing fever (TBRF) is endemic to Israel. Since 2004, the Israel Defence Forces (IDF) has mandated the prophylaxis of tick-bitten subjects with a five-day doxycycline course. We examined the safety and effectiveness of this policy in preventing TBRF. We analyzed the records from January 2004 to January 2007, and identified all reported events of tick bites or TBRF cases. Data were available on 27 events in which 816 soldiers have undergone physical examination following exposure, and seven TBRF cases were recorded in this group-an attack rate of 0.86% compared with the expected rate of 5.34% from previous army data (relative risk [RR] = 0.16). Of those screened, 128 (15.7%) had tick-bite and were intended for prophylaxis, of which four TBRF cases occurred-3.13% attack rate compared with an expected rate of 38.4% in these bitten individuals without prophylaxis (RR = 0.08, number needed to treat = 3). In all cases in which screening and prophylaxis were provided within 48 h of tick bite, complete prevention of TBRF was achieved. No cases of Jarisch-Herxheimer reaction (JHR) was recorded. Tick-bite screening and prophylactic treatment with doxycycline in endemic areas is a practical, safe, and highly effective policy for preventing TBRF.
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Personal Militar , Ornithodoros , Profilaxis Posexposición/métodos , Fiebre Recurrente/prevención & control , Enfermedades por Picaduras de Garrapatas/prevención & control , Adolescente , Animales , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Enfermedades Endémicas , Femenino , Humanos , Mordeduras y Picaduras de Insectos/epidemiología , Israel/epidemiología , Masculino , Fiebre Recurrente/tratamiento farmacológico , Fiebre Recurrente/epidemiología , Enfermedades por Picaduras de Garrapatas/tratamiento farmacológico , Enfermedades por Picaduras de Garrapatas/epidemiologíaRESUMEN
BACKGROUND: Although pemphigus is a rare autoimmune blistering disease, it attracts the attention of physicians of many disciplines. OBJECTIVE: This study aims to assess the number of articles on pemphigus that have been published over 15 years in dermatology vs. non-dermatology medical journals, and to evaluate the quality of available evidence. METHODS: PubMed was searched for articles on pemphigus published between 1 January 1993 to 31 December 2007 using the search word pemphigus. Articles were characterized by publication type and journal type per year. Regression analysis was used to determine the effect of year of publication on number of publications of each type. RESULTS: The search yielded 2032 publications on pemphigus during the evaluation period. Sixty-one per cent were published in dermatology journals. Overall, the number of publications increased linearly with time. Most of this increase was accounted for by publications in non-dermatology journals. There was an increase in clinical trials over the course of the study period. The number of certain publications with lower quality of evidence, mainly case reports and letters to the editor, increased significantly in the last few years. There was no increase in publications with high quality of evidence. CONCLUSIONS: The increase on data from non-dermatology disciplines is a welcome contribution. Nevertheless, high-quality evidence on pemphigus is still lacking. We trust that the current trend towards evidence-based dermatology will impact future research on this severe disease.
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Pénfigo , Medicina Basada en la Evidencia , Humanos , Factor de Impacto de la Revista , Pénfigo/diagnóstico , Pénfigo/patología , Pénfigo/terapiaRESUMEN
In the past few decades, great progress has been made in psoriasis research, culminating with the development of new, biological treatments. We designed this study to test the hypothesis that there is a linear increase in psoriasis publications over time. We evaluated all PubMed articles from 1 January 1993 to 31 December 2007. We categorized the search into basic science, traditional therapy and new biological treatments. We used regression analysis to determine the effect of year of publication upon number of publications of each type. There was a significant quadratic increase in the number of all types of psoriasis publications, with basic science-related publications being greatest, followed by relevant clinical publications. We conclude that better understanding of psoriasis immunopathology has led to a significant yearly increase in clinical studies, contributing approximately 60% of studies in the entire field of dermatology reports.
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Bibliometría , Investigación Biomédica/tendencias , Dermatología/tendencias , Psoriasis/tratamiento farmacológico , Humanos , Publicaciones Periódicas como Asunto/tendencias , Edición/tendencias , Estudios RetrospectivosRESUMEN
BACKGROUND: Pemphigus vulgaris is a chronic autoimmune mucocutaneous blistering disease. Only a few studies have evaluated the epidemiological and aetiological parameters of pemphigus vulgaris in a large group of patients over the long term. METHODS: The sample included 155 patients with a diagnosis of pemphigus who attended the pemphigus clinic of a major tertiary medical centre from 1976 to 2004. Data were obtained from the patient files and entered into an ad hoc form; patients were contacted by telephone for missing information. RESULTS: The female-to-male ratio was 1.5 : 1. Non-Ashkenazi Jews accounted for 37% of the sample. In only 10% of the patients was a potential aetiologic or precipitating factor identified. CONCLUSIONS: Pemphigus vulgaris is characterized by a female predominance, consistent with other autoimmune disease. The gender, age and ethnic distribution of affected patients have not changed in the last 40 years. In the vast majority of cases, the aetiologic or precipitating factor is unknown, although drugs appear to be very rare.
Asunto(s)
Pénfigo/epidemiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pénfigo/patología , Pénfigo/terapia , PronósticoRESUMEN
Pemphigus vulgaris (PV) is fascinating to dermatologists, epithelial biologists and immunologists alike, as its pathogenesis has been clarified to a much greater extent than that of most other organ-specific autoimmune diseases, and as it has provided abundant novel insights into desmoglein biology and pathology along the way. Historically, the most influential PV pathogenesis concept is that of Stanley and Amagai. This concept holds that autoantibodies against desmogleins are both essential and sufficient for epidermal blister formation (acantholysis) by impeding the normal functioning of these major adhesion proteins. However, as with most good theories, this landmark concept has left a number of intriguing and important questions open (or at least has not managed to answer these to everyone's satisfaction). Moreover, selected dissenting voices in the literature have increasingly called attention to what may or may not be construed as inconsistencies in this dominant PV pathogenesis paradigm of the recent past. The present debate feature therefore bravely rises to the challenge of re-examining the entire currently available evidence, as rationally and as undogmatically as possible, by provocatively asking a carefully selected congregation of experts (who have never before jointly published on this controversial topic!) to discuss how essential anti-desmoglein autoantibodies really are in the immunopathogenesis of PV. Not surprisingly, some of our expert "witnesses" in this animated debate propose diametrically opposed answers to this question. While doing so, incisive additional questions are raised that relate to the central one posed, and our attention is called to facts that may deserve more careful consideration than they have received so far. Together with the intriguing (often still very speculative) complementary or alternative pathogenesis scenarios proposed in the following pages, this offers welcome "food for thought" as well as very specific suggestions for important future research directions--within and beyond the camp of PV aficionados. The editors trust that this attempt at a rational public debate of the full evidence that is currently at hand will constructively contribute to further dissecting the exciting--and clinically very relevant!--immunopathogenesis of PV in all its complexity.
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Autoanticuerpos/inmunología , Desmogleína 1/inmunología , Desmogleína 3/inmunología , Pénfigo/inmunología , Animales , Autoanticuerpos/fisiología , Desmogleína 1/fisiología , Desmogleína 3/fisiología , Desmosomas/fisiología , Modelos Animales de Enfermedad , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Queratinocitos/inmunología , Queratinocitos/patología , Ratones , Pénfigo/patología , Pénfigo/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. To determine whether MF is linked to HTLV-1. METHODS: Blood samples were collected from 60 patients, 15 family relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test. DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real-time PCR using primers sk43 and sk44 together with a tax-specific fluorescent probe. RESULTS: In Western blot, antibodies against three to four HTLV-1 antigens were detected in 52% of patients with MF. All of the patients with HAM/TSP were positive, while only 7% of the MFRs and none of the 20 healthy controls reacted with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15 MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV-1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus from the blood of the PCR-positive MFR by seminested PCR. A positive result was also obtained in this test. Phylogenetic tree analyses revealed a high homology of this sequence with other HTLV-1 sequences from the Middle East. The above PCR-positive MFR was the brother of a PCR-negative patient with MF. CONCLUSIONS: These findings demonstrate that HTLV-1 is probably not the aetiological agent of MF. However, it may play a role in immunosuppression and in the spreading of the disease.
Asunto(s)
Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Micosis Fungoide/virología , Provirus/aislamiento & purificación , Neoplasias Cutáneas/virología , Adulto , Anciano , ADN Viral/sangre , Femenino , Anticuerpos Anti-HTLV-I/sangre , Virus Linfotrópico T Tipo 1 Humano/clasificación , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa/métodos , Provirus/genética , Neoplasias Cutáneas/genéticaRESUMEN
The skin is a common target of cellular and/or antibody mediated pathological immune responses. Pemphigoids, pemphigus vulgaris and dermatitis herpetiformis are bullous disease due to autoantibodies targeting specific proteins of the skin. The pemphigoid autoantigens are the BP180 and the BP230 antigens, two components of the epithelial basement membrane zone. Additional antigenic targets reported in a portion of patients are laminin 5, the alpha6 subunit of the hemidesmosomal integrin alpha6beta4 and a glycoprotein termed p200. The epidermal and mucosal epithelial cells detachment (acantholysis) characteristic of pemphigus vulgaris is induced by autoantibodies directed against the desmoglein 3 and 1. The desmogleins are desmosomal cadherins, which play a major role in the cell-to-cell adhesion. Dermatitis herpetiformis is regarded as cutaneous phenotype of coeliac disease. A novel autoimmune hypothesis of coeliac disease links wheat gliadin and tissue transglutaminase (TG2) in the gut, which leads to T cell response and IgA autoantibody formation. In dermatitis herpetiformis skin the target for IgA deposition seems to be epidermal TG3. Urticaria is a complex syndrome caused by both immune and non-immune mechanisms. In a subsets of patients with chronic urticaria mast cell degranulation is induced by autoantibodies directed against the a-subunit of the high-affinity IgE receptor, and/or the IgE.