RESUMEN
BACKGROUND: Whether children with atopic dermatitis have an altered risk of contact allergy than children without atopic dermatitis is frequently debated and studies have been conflicting. Theoretically, the impaired skin barrier in atopic dermatitis (AD) facilitates the penetration of potential allergens and several authors have highlighted the risk of underestimating and overlooking contact allergy in children with atopic dermatitis. OBJECTIVE: To determine the prevalence of contact allergy in Danish children with atopic dermatitis and explore the problem of unacknowledged allergies maintaining or aggravating the skin symptoms. METHODS: In a cross-sectional study, 100 children and adolescents aged 5-17 years with a diagnosis of atopic dermatitis were patch tested with a paediatric series of 31 allergens. RESULTS: Thirty per cent of the children had at least one positive patch test reaction, and 17% had at least one contact allergy that was relevant to the current skin symptoms. The risk of contact allergy was significantly correlated to the severity of atopic dermatitis. Metals and components of topical skincare products were the most frequent sensitizers. CONCLUSION: Patch testing is relevant as a screening tool in the management of children with atopic dermatitis as they may have unacknowledged contact allergies contributing to or maintaining their skin symptoms. Children with atopic dermatitis seem to be at greater risk of sensitization to certain allergens including metals and components of skincare products.
Asunto(s)
Dermatitis Alérgica por Contacto/complicaciones , Dermatitis Alérgica por Contacto/epidemiología , Dermatitis Atópica/complicaciones , Dermatitis Atópica/epidemiología , Adolescente , Niño , Comorbilidad , Estudios Transversales , Dinamarca/epidemiología , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Atópica/diagnóstico , Femenino , Humanos , Masculino , Pruebas del Parche , Prevalencia , Estudios ProspectivosRESUMEN
The importance of contact allergy in children with atopic dermatitis is frequently debated. Previously, patients with atopic dermatitis were believed to have a reduced ability to produce a type IV immunological response. However, this belief has been challenged and authors have highlighted the risk of underestimating and overlooking allergic contact dermatitis in children with atopic dermatitis. Several studies have been published aiming to shed light on this important question but results are contradictory. To provide an overview of the existing knowledge, we systematically reviewed studies that report frequencies of positive patch test reactions in children with atopic dermatitis. We identified 436 manuscripts of which 31 met the inclusion criteria. Although the literature is conflicting, it is evident that contact allergy is a common problem in children with atopic dermatitis.
Asunto(s)
Dermatitis Alérgica por Contacto/complicaciones , Dermatitis Atópica/complicaciones , Adolescente , Alérgenos/efectos adversos , Niño , Preescolar , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Atópica/diagnóstico , Humanos , Pruebas del Parche , Factores de RiesgoAsunto(s)
Fármacos Dermatológicos , Eccema , Dermatosis de la Mano , Infecciones Estafilocócicas , Administración Tópica , Corticoesteroides/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Eccema/tratamiento farmacológico , Dermatosis de la Mano/tratamiento farmacológico , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureusRESUMEN
Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) (OMIM 604129) represents a distinct variant within the DEB clinical spectrum. It is characterized by intense pruritus and distinctive nodular prurigo-like and/or hypertrophic lichenoid lesions mainly localized on the arms, legs and upper shoulders. DEB-Pr is caused by either dominant (DDEB-Pr) or recessive mutations in the COL7A1 gene encoding type VII collagen (COLVII). The full spectrum of COL7A1 mutations in DEB-Pr remains elusive and the genotype-phenotype correlation is largely incomplete. Here, we report and functionally characterize a previously unrecognized translationally silent exonic COL7A1 mutation that results in skipping of exon 87 and is associated with DDEB-Pr phenotypes in several members of three apparently unrelated Danish families. A haplotype segregation study suggested a common ancestor in these kindred. Functional splicing analysis of the mutant exon by a COL7A1 minigene construct and computational prediction for splicing regulatory cis-sequences prove that the mutation alters the activity of an exonic splicing enhancer (ESE) critical for exon inclusion. These findings substantiate for the first time the involvement of an ESE mutation in the pathogenesis of DEB and have implications for genetic counselling of Danish families with DDEB.
Asunto(s)
Colágeno Tipo VII/genética , Epidermólisis Ampollosa Distrófica/genética , Exones/genética , Mutación/genética , Empalme del ARN/genética , Adolescente , Adulto , Femenino , Efecto Fundador , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal disorder, caused by heterozygous missense mutation in GJB2, encoding the gap junction protein connexin 26. The commonest mutation is the p.Asp50Asn mutation, and only a few other mutations have been described to date. AIM: To report the fatal clinical course and characterize the genetic background of a premature male neonate with the clinical and histological features of KID syndrome. METHODS: Genomic DNA was extracted from peripheral blood and used for PCR amplification of the GJB2 gene. Direct sequencing was used for mutation analysis. RESULTS: The clinical features included hearing impairment, ichthyosiform erythroderma with hyperkeratotic plaques, palmoplantar keratoderma, alopecia of the scalp and eyelashes, and a thick vernix caseosa-like covering of the scalp. On histological analysis, features characteristic of KID syndrome, such as acanthosis and papillomatosis of the epidermis with basket-weave hyperkeratosis, were seen. The skin symptoms were treated successfully with acitretin 0.5 mg/kg. The boy developed intraventricular and intracerebral haemorrhage, leading to hydrocephalus. His condition was further complicated by septicaemia and meningitis caused by infection with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Severe respiratory failure followed, and the child died at 46 weeks of gestational age (13 weeks postnatally). Sequencing of the GJB2 gene showed that the child was heterozygous for a novel nucleotide change, c.263C>T, in exon 2, leading to a substitution of alanine for valine at position 88 (p.Ala88Val). CONCLUSIONS: This study has identified a new heterozygous de novo mutation in the Cx26 gene (c.263C>T; p.Ala88Val) leading to KID syndrome.
Asunto(s)
Conexinas/genética , Enfermedades del Prematuro/genética , Mutación , Animales , Biopsia , Conexina 26 , Sordera/tratamiento farmacológico , Sordera/genética , Sordera/patología , Fármacos Dermatológicos/uso terapéutico , Resultado Fatal , Humanos , Ictiosis/tratamiento farmacológico , Ictiosis/genética , Ictiosis/patología , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/patología , Queratitis/tratamiento farmacológico , Queratitis/genética , Queratitis/patología , Masculino , Piel/patologíaRESUMEN
BACKGROUND: Hand eczema (HE) is a frequent, long-lasting disease with both personal and societal repercussions. Consequently, more information is needed on factors that maintain symptoms. OBJECTIVES: In this study, patients with HE were followed for 6 months from the first visit to a dermatologist to identify factors associated with severe disease and a poor prognosis. METHODS: Study participants were 799 patients with HE from nine dermatological clinics in Denmark. Severity assessment of the HE was done at baseline and at the 6-month follow-up using the Hand Eczema Severity Index (HECSI) and by patients using a self-administered photographic guide. Additional information was obtained from a baseline questionnaire. RESULTS: At baseline, 60.3% assessed their HE as moderate to very severe using the self-administered photographic guide compared with 36.1% at follow-up. The mean HECSI value decreased from 19.9 points at baseline to 11.2 points at follow-up (P < 0.001). In a multivariable logistic regression analysis, statistically significant associations with severe HE at baseline were older age (P < 0.001), atopic dermatitis (P = 0.01) and > or = 1 positive patch test (P < 0.001). Being an unskilled worker was a predictor for a poor prognosis at follow-up (P = 0.04), and the presence of frequent symptoms during the previous 12 months was associated with severe initial disease (P = 0.02) and a poor prognosis (P = 0.04). CONCLUSIONS: Overall, the disease had improved 6 months after the dermatological examination: nevertheless, many patients continued to have significant symptoms. Dermatologists should pay special attention to patients with frequent eruptions and to unskilled workers.
Asunto(s)
Eccema/diagnóstico , Dermatosis de la Mano/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Eccema/psicología , Femenino , Estudios de Seguimiento , Dermatosis de la Mano/psicología , Humanos , Masculino , Persona de Mediana Edad , Fotograbar , Pronóstico , Estudios Prospectivos , Análisis de Regresión , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Since tropical spastic paraparesis in 1985 was found to be associated with HTLV-I infection, it has been suggested that a retrovirus might be involved in multiple sclerosis (MS). Our group has studied long-term cultures of cerebrospinal fluid cells and peripheral blood mononuclear cells from MS patients and controls with the purpose of elucidating the possible involvement of a retrovirus in MS. For an extended period electron microscopical analysis (EM) of T-cell lines, derived from MS patients and controls and cultured for 4 weeks was performed. In two cultures obtained 8 months apart from a patient with progressive MS, retrovirus-like particles were observed in 1-2% of the cells examined. Recently a B-lymphoblastoid cell line (LCL) producing retrovirus-like particles and EBV was established from a 30-year-old male patient with a chronic progressive myelopathy, clinically resembling multiple sclerosis. Similar cell lines have now been established from two MS patients. The retrovirus-like particles produced by the LCL have been purified by gradient ultracentrifugation. In the purified material reverse transcriptase assays are clearly positive in the gradients where EM shows retrovirus-like particles. Antigen characterization, nucleic acid sequence analysis and antibody studies are now being performed. The retrovirus found is definitively different from other known human retroviruses. It has previously been found that 100% of patients with MS have antibodies against EBV, in contrast to controls where only 86-95% have antibodies against this virus. Previous epidemiological studies have pointed toward a post-pubertal primary EBV infection as an important event in the induction of MS disease. These studies have now been substantiated by our group. Though it is still unknown whether EBV infection is a prerequisite for development of MS or whether the 100% EBV seropositivity is a consequence of the MS disease, we have put forward the hypothesis that the etiological agent for development of MS and MS-like diseases is a new hitherto uncharacterized retrovirus, whereas development of neurologic disease is related to or even dependent on a delayed infection with a virus from the herpes group, most likely EBV. This dual infection hypothesis has been analyzed and was found to be in accordance with the most consistent epidemiological characteristics of MS. We have previously, also from epidemiological data, negated retroviruses, behaving as the known human retroviruses, as an independent cause of MS.
Asunto(s)
Herpesvirus Humano 4/fisiología , Esclerosis Múltiple/microbiología , Retroviridae/aislamiento & purificación , Adulto , Línea Celular , Humanos , Masculino , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , ADN Polimerasa Dirigida por ARN/metabolismo , Retroviridae/patogenicidad , Retroviridae/ultraestructuraRESUMEN
Multiple sclerosis is a disease characterized by neurologic dysfunction due to focal CNS lesions with demyelination. The cause of the disease is unknown; but it may be due to a virus and/or autoimmune reactions. The latter cause is suspected on account of family- and ethnical studies, the first on account of locally produced antibodies in the cerebrospinal fluid, and also epidemiologic investigations. The newly discovered human retroviruses, especially HTLV-I which is the cause of tropical spastic paraparesis, has been suspected as a possible cause; but this has been disproved by multiple antibody- and PCR-studies. An uncharacterized exogenous or an endogenous retrovirus is still considered to be a possible cause or possibly partial cause of the disease which could be multifactorial.
Asunto(s)
Esclerosis Múltiple/microbiología , Infecciones por Retroviridae/complicaciones , Enfermedades Autoinmunes , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/inmunología , Humanos , Esclerosis Múltiple/etiología , Esclerosis Múltiple/inmunología , Paraparesia Espástica Tropical/inmunología , Paraparesia Espástica Tropical/microbiología , Infecciones por Retroviridae/inmunologíaRESUMEN
The intrafamilial epidemiology of multiple sclerosis was compared with the known intrafamilial epidemiology of infections with HTLV-I. Infections with this retrovirus most often have a subclinical course, but can cause leukemia or a neurological disease resembling multiple sclerosis. Through the Danish Multiple Sclerosis Registry, information was obtained on 79 parent-child cases of multiple sclerosis, and in 55 cases further information was obtained through questionnaires. The study did not reveal any common intrafamilial pattern of MS and HTLV-I infections. It can be concluded that if multiple sclerosis is associated with a specific 'MS virus', it is hardly one with the same epidemiology as HTLV-I, maybe because MS could be a multifactorial disease only developing if various factors coincide in the same person.
Asunto(s)
Infecciones por HTLV-I/epidemiología , Esclerosis Múltiple/epidemiología , Infecciones por Retroviridae/epidemiología , Dinamarca , Familia , Femenino , Humanos , Masculino , Esclerosis Múltiple/microbiología , Sistema de RegistrosRESUMEN
The influence of infection by herpes simplex virus type 2 (HSV-2) on the respiratory burst capacity of mouse macrophages was studied by luminol-dependent chemiluminescence with phorbol myristate acetate (PMA) as trigger. Peritoneal cells from virus-infected mice were strongly primed for a respiratory burst during the acute phase of the infection. By 12 h after infection the response had increased 40-fold over control values. Most of the response was elicited by mononuclear phagocytes. When resting peritoneal macrophages were infected with HSV-2 in vitro a maximal priming effect was seen with 2 x 10(6) p.f.u./ml of virus after 8 h, but a significant response was obtained after 4 h of infection; after 12 h incubation with virus the response declined to reach background levels at 24 h. Peritoneal cells from C57BL/6 mice which are relatively resistant to HSV-2 showed a higher respiratory burst capacity after infection than cells from more susceptible BALB/c mice. Incubation of macrophages with crude niurine interferon (IFN)-alpha/beta produced by macrophages or purified murine IFN-alpha, in concentrations comparable to those obtained early (2 to 5 h) after infection of macrophage cultures with HSV-2 also augmented the respiratory burst. Addition of an IFN-alpha/beta-specific antiserum to HSV-2-infected cultures almost completely removed the response. We therefore conclude that HSV-2 induces an early and genetically determined activation of macrophages, mediated in an autocrine manner by IFN-alpha/beta secreted by the macrophages early during infection.
Asunto(s)
Interferón Tipo I/farmacología , Macrófagos/metabolismo , Consumo de Oxígeno , Simplexvirus/fisiología , Animales , Células Cultivadas , Herpes Simple/genética , Herpes Simple/metabolismo , Mediciones Luminiscentes , Activación de Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Consumo de Oxígeno/efectos de los fármacos , Simplexvirus/genética , Acetato de Tetradecanoilforbol/farmacología , Factores de TiempoRESUMEN
Herpes simplex virus primes mouse macrophages for a genetically determined respiratory burst mediated in an autocrine manner by interferon (IFN)-alpha/beta. We have analysed the effect of IFN-alpha/beta on the respiratory burst capacity of mouse peritoneal macrophages by luminol-dependent chemiluminescence using phorbol myristate acetate as trigger. Crude macrophage-produced IFN-alpha/beta as well as purified IFN-alpha and -beta regularly augmented the respiratory burst capacity of peritoneal cells in a concentration-dependent manner. The augmented response was exclusively mediated by macrophages and was manifest after 4 h incubation with IFN-alpha/beta, peaked after 8 h and gradually declined to near background levels after 24 h. The effect of macrophage-produced IFN-alpha/beta was completely abolished by preincubation of IFN with antiserum to IFN-alpha/beta. The data obtained with this antiserum indicated that endogenous IFN, undetectable by a standard cytopathic effect-inhibition assay, was sometimes spontaneously produced by the peritoneal cells. Furthermore, the crude macrophage preparation seemed to contain a macrophage deactivating factor counteracting the effect of IFN-alpha/beta. Genetic analysis of the sensitivity of macrophages for the respiratory burst-priming effect of IFN-alpha/beta revealed that the trait is inherited as a co-dominant autosomal feature. Macrophages from herpes simplex virus-resistant C57BL/6 mice were more sensitive than macrophages from virus-susceptible BALB/c mice and cells from mice of the reciprocal crosses showed an equal sensitivity intermediate between those of the parental strains. A physiological role of differential IFN sensitivity in the context of resistance to virus infections is suggested.
Asunto(s)
Herpes Simple/genética , Interferón Tipo I/farmacología , Mediciones Luminiscentes , Macrófagos/microbiología , Consumo de Oxígeno/efectos de los fármacos , Animales , Susceptibilidad a Enfermedades , Femenino , Herpes Simple/inmunología , Herpes Simple/metabolismo , Inmunidad Innata , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Cavidad PeritonealRESUMEN
A B-lymphoblastoid cell line (LCL) of polyclonal origin was isolated from a 30-year-old male patient with a chronic progressive myelopathy clinically resembling multiple sclerosis (MS). The LCL expresses Epstein-Barr virus (EBV) encoded proteins and on transmission electron microscopy (EM) the LCL was shown to produce both EBV particles and retrovirus-like particles spontaneously. The LCL was negative for human retrovirus (HIV-I and HTLV-I) sequences by polymerase chain reaction (PCR). Furthermore the patient was seronegative to these retroviruses including HTLV-II and HIV-II. We, therefore, suggest that the LCL is double-infected with EBV and a hitherto uncharacterized human retrovirus. The possible implications of these two viruses on development of diseases are discussed.
Asunto(s)
Herpesvirus Humano 4/ultraestructura , Cuerpos de Inclusión Viral/ultraestructura , Esclerosis Múltiple/microbiología , Paraparesia Espástica Tropical/microbiología , Retroviridae/ultraestructura , Adulto , Antígenos CD/análisis , Línea Celular Transformada/microbiología , Línea Celular Transformada/patología , Diagnóstico Diferencial , Técnica del Anticuerpo Fluorescente , VIH-1/ultraestructura , Virus Linfotrópico T Tipo 1 Humano/ultraestructura , Humanos , Masculino , Microscopía Electrónica , Esclerosis Múltiple/patología , Paraparesia Espástica Tropical/patología , Reacción en Cadena de la PolimerasaRESUMEN
Although the etiology of multiple sclerosis is as yet unknown, epidemiological observations strongly point toward one or more infectious agent(s) being involved in the disease. In recent years some studies have indicated involvement of retrovirus in multiple sclerosis (MS). However, an intrafamilial epidemiological study revealed that MS and the known human retroviruses had a divergent epidemiology. Some studies have shown the association of Epstein-Barr virus (EBV) with MS and one recent study revealed dual infection by retrovirus and EBV in a cell line established from a patient with an MS-like disease. Our hypothesis for the development of MS and MS-like diseases is that a hitherto uncharacterized retrovirus is the etiological agent, but development of neurologic disease is related to or even dependent on a delayed EBV infection. The dual infection hypothesis is analyzed and found to be consistent with the epidemiological characteristics of MS.