RESUMO
We have investigated 8 patients from 7 unrelated families with lamellar ichthyosis (LI) for defects in the keratinocyte transglutaminase (TGK) gene. We have characterized three novel homozygous mutations and a previously reported splice acceptor site mutation. One patient showed a C-to-T change in the binding site for the transcription factor Sp1 within the promoter region. Another patient had a Gly 143-to-Glu mutation in exon 3 and a third patient, affected with a particular form of LI sparing the four limbs, demonstrated a Val382-to-Met mutation within exon 7. These three patients exhibited drastically reduced transglutaminase activity and an absence of detectable TGK polypeptide, as assessed by immunofluorescence and immunoblotting. Northern blot analysis showed that the Sp1 site mutation was associated with profound reduction of TGK transcript levels whereas normal transcript levels were observed for the two missense mutations. We hypothesize that the Sp1 site mutation impairs transcription of the TGK gene, whereas the two missense mutations induce structural changes leading to protein instability. Linkage to TGK was excluded in another family and no evidence for TGK defect was found in 3 other patients. These results further support the involvement of TGK in some patients with LI. They identify a TGK mutation as a cause for non-generalized LI and further delineate the molecular mechanisms underlying TGK deficiency in LI.
Assuntos
Ictiose Lamelar/genética , Mutação Puntual , Transglutaminases/genética , Adulto , Northern Blotting , Criança , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Ligação Genética , Humanos , Ictiose Lamelar/enzimologia , Immunoblotting , Masculino , Linhagem , RNA Mensageiro/metabolismo , Coloração e Rotulagem , Transglutaminases/análiseRESUMO
OBJECTIVE: To determine the frequency of the various underlying causes of erythroderma in newborns or infants, as well as which clinical or laboratory findings were relevant for the etiological diagnosis. PATIENTS: Fifty-one patients who presented with exfoliative erythroderma during their first year of life were included in this retrospective study. SETTING: Department of Pediatric Dermatology at a university hospital. RESULTS: On average, the etiological diagnosis was established 11 months after the onset of erythroderma. The underlying causes observed included immunodeficiency (30%), simple or complex ichthyosis (24%), Netherton syndrome (18%), and eczematous or papulosquamous dermatitis (20%). Five patients (10%) had erythroderma of unknown origin. The following parameters were of value in determining the underlying cause of erythroderma: congenital onset, skin induration and the presence of large scaling plaques, alopecia with or without hair dysplasia, evolution, response to topical corticosteroid therapy, presence of infections, and failure to thrive. Histological analysis confirmed the diagnosis in only 19 (45%) of 42 cases. However, it proved of great value for the detection of significant lymphocyte infiltration or keratinocyte necrosis indicating a diagnosis of Omenn syndrome or immunodeficiency. The prognosis was poor in this series: the mortality rate was 16%, and severe dermatosis persisted in 29 (67%) of the survivors. CONCLUSIONS: The etiological diagnosis of neonatal erythroderma is difficult to make; some clinical features may be helpful, but no one feature is characteristic of a cause. An immunodeficiency must be suspected in cases of severe erythroderma with skin induration, severe alopecia, failure to thrive, infectious complications, or evocative histological findings. The prognosis is poor, with a high rate of mortality in immunodeficiency disorders and severe chronic disease in Netherton syndrome and psoriasis.
Assuntos
Dermatite Esfoliativa , Dermatite Esfoliativa/congênito , Dermatite Esfoliativa/diagnóstico , Dermatite Esfoliativa/etiologia , Dermatite Esfoliativa/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
There are three components in the treatment of atopic dermatitis: 1) a general treatment (mainly antibiotherapy directed towards Staphylococcus aureus during acute phases), 2) local treatment (local antiseptics, local steroids, emollients), 3) practical advice. In addition, it is of great importance that clear and complete information on the illness should be given to the parents.
Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/terapia , Administração Tópica , Antibacterianos/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Criança , Dermatite Atópica/tratamento farmacológico , Emolientes/uso terapêutico , Glucocorticoides , HumanosRESUMO
BACKGROUND: Dermatitis herpetiformis (DH) is a chronic papulovesicular immune-mediated disorder associated with gluten-sensitive enteropathy. We report eight cases in which DH appeared many years after celiac disease (CD) in child. PATIENTS AND METHODS: The diagnosis of CD was based on histological features of total or subtotal villous atrophy, full remission after withdrawal of gluten from the diet, and eventually circulating antibodies (IgA gliadin, antireticulin and antiendomysium) at the time of diagnosis and their disappearance under gluten-free diet. The diagnosis of DH was made from clinical findings, histological examination of the involved skin and direct immunofluorescence microscopy of normal or perilesional skin. HLA class II typing was performed in five patients. DRB1, DQA1, DQB1 and DBP1 alleles were studied. RESULTS: DH appeared between 3 and 22 years after the initial diagnosis of CD. Five patients did not show at that time any digestive symptoms. In three cases, a break in the gluten-free diet or a recent revival of the normal diet preceded the rash. In only one case, DH appeared while the patient was under gluten-free diet. In three patients, the rash appeared many years after the gluten-free diet had been stopped. Phenotype DR3 and/or DR7 of the celiac disease could be found in four of the five patients studied; three of them were found to bear DQW2. The DR2 allele was not found in any of the five tested patients. DISCUSSION: These eight cases illustrate the absence of precise nosological barrier between gluten-sensitive enteropathy of the DH and that observed in CD. The presence of the DR7 allele, and especially the absence of the DR2 allele, could explain the particularly severe and symptomatic course of the enteropathy in these patients. The delay in the appearance of DH, after a very variable period of normal diet, could correspond to the necessary time for progressive accumulation of IgA (or immune complex IgA-gluten) in the skin after a digestive sensitization to gluten. The preventive role of gluten-free diet is thus probable. CONCLUSION: CD and DH likely correspond to two different stages of the same disease, thus requiring a prolonged follow-up of both digestive and skin tissues. Long-term eviction of gluten to prevent eventual DH must be balanced with the demand and the cost of such a diet.
Assuntos
Doença Celíaca/complicações , Dermatite Herpetiforme/complicações , Doença Celíaca/dietoterapia , Doença Celíaca/genética , Criança , Pré-Escolar , Dermatite Herpetiforme/genética , Glutens/uso terapêutico , Humanos , Lactente , Assistência de Longa Duração , Estudos Retrospectivos , TempoRESUMO
Twenty experts, members of a French medical network devoted to neurofibromatosis 1 have elaborated recommendations for the management of the disease. Bibliography was obtained through a Medline of articles from 1966 to 1999 for the terms neurofibromatosis, NF1, neurofibroma and from textbooks. A consensual document was written taking into account extracted data. An annual careful clinical examination is recommended except in cases with complications. Screening investigations are not recommended due to the rarity of complications, generally symptomatic and easily detected during the clinical follow-up. The only controversial exception might be magnetic resonance imaging for early detection of optic pathway gliomas in young children. A co-ordinated follow-up in specialised multidisciplinary centres, providing patients with a rational management, is recommended.
Assuntos
Neurofibromatose 1/diagnóstico , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico por imagem , Neurofibromatose 1/terapia , Prognóstico , Radiografia , Fatores de TempoRESUMO
INTRODUCTION: Blue nevi are small acquired melanocytic tumors. Two clinical forms are described, a fibrous form and a cellular form. Giant nevi are exceptional. CASE REPORT: We describe a patient with a giant blue nevus of the scalp. In addition to this congenital, noninvasive tumor the patient presented numerous cutaneous melanocytic nevi. The main lesion was removed by surgical exeresis followed later with reconstruction plasty. The histological examination of the surgical specimen showed an infiltrating blue cell nevi. After a 4-year follow-up, there has been no recurrence and no metastasis. DISCUSSION: There have been 11 cases of giant blue nevi reported in the literature. All were congenital lesions with polymorphous clinical and histological aspects. Fibrous forms are noninvasive and cellular forms have a potential for local invasion, whether shortly after birth or later with invasion of muscles, bone and meninges without intracerebral extension. Congenital blue nevi require early surgical exeresis.
Assuntos
Neoplasias Primárias Múltiplas , Nevo Azul/congênito , Couro Cabeludo , Neoplasias Cutâneas/congênito , Pré-Escolar , Feminino , Seguimentos , Humanos , Nevo Azul/cirurgia , Nevo Pigmentado/congênito , Neoplasias Cutâneas/cirurgia , Transplante de Pele , Expansão de TecidoRESUMO
INTRODUCTION: Cutaneous granulomatous lesions rarely occur in primary immunodeficiency syndromes. CASES REPORTS: We observed chronic granulomatous lesions on the skin of 5 children with inborn immunodeficiency syndromes. The deficiency was of the mixed type in all 5 cases and included major hypogammaglobulinaemia in 4. Erythemato-squamous infiltrated plaques were found in 4 children and erythematous nodules in the fifth. Extra-cutaneous lesions (cavum and rectocolon) occurred in 2 children. Search for an infectious cause was negative. Anti-tuberculosis drugs were tried in 3 children as a test regimen and were ineffective. Systemic corticosteroids gave major clinical improvement in 2 children. DISCUSSION: Several pathogenic processes have been hypothesized to explain the development of granulomatous lesions in immunodeficiency syndromes. The action of an unknown infectious agent has been suspected. An intrinsic anomaly in immune function regulation, particularly in a disequilibrium in the complex cytokine network controlling the formation of granulomas could also be involved. Systemic corticosteroid therapy appears to be effective but must be given with caution in these patients with immune deficiency.
Assuntos
Eritema/etiologia , Doença Granulomatosa Crônica/etiologia , Síndromes de Imunodeficiência/congênito , Criança , Pré-Escolar , Eritema/imunologia , Eritema/terapia , Feminino , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/terapia , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Lactente , MasculinoRESUMO
INTRODUCTION: There are two hereditary forms of primary telangiectasia with a totally opposite prognosis. In Rendu-Osler disease, also called hereditary haemorrhagic telangiectasia, there is a major risk of severe haemorrhage in adults. In benign hereditary telangiectasia there is no such risk. CASE REPORT: We report two brothers who were diagnosed as having Rendu-Osler disease. Under standard electron microscopy, a biopsy of a telangiectasia taken from the right arm pit showed that the vessels of the superficial reticular derma were dilated with thick walls but no dehiscences as in Rendu-Osler disease. DISCUSSION: This ultrastructure explains why there had been no haemorrhages in our two cases and favoured a diagnosis of hereditary benign telangiectasia.
Assuntos
Pele/ultraestrutura , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia/genética , Criança , Pré-Escolar , Diagnóstico Diferencial , Humanos , Masculino , Microscopia Eletrônica , Prognóstico , Telangiectasia/diagnóstico , Telangiectasia/patologiaRESUMO
INTRODUCTION: Rothmund-Thomson syndrome is a genodermatosis associated with early poikilodermal lesions. The condition usually occurs in children. Features include skeletal deformations and increased risk of malignancy. CASE REPORT: A 3 and a half year-old girl with poikilodermal lesions predominating in photoexposed areas presented a rash after exposure to sun. The first manifestations occurred during the first months of life. Examination of DNA repair on a culture of UV irradiated fibroblasts showed reduced DNA repair capacity. DISCUSSION: Other childhood photodermatoses were eliminated by the clinical signs. It would be important to know whether there is a correlation between DNA repair and development of neoplasia in Rothmund-Thomson syndrome.
Assuntos
Reparo do DNA , Transtornos de Fotossensibilidade/etiologia , Síndrome de Rothmund-Thomson/genética , Pré-Escolar , Feminino , Humanos , Síndrome de Rothmund-Thomson/patologiaAssuntos
Dermatopatias/etiologia , Doenças da Vulva/etiologia , Fatores Etários , Criança , Pré-Escolar , Condiloma Acuminado/complicações , Feminino , Hemangioma/diagnóstico , Histiocitose de Células de Langerhans/complicações , Humanos , Lactente , Erupções Liquenoides/complicações , Linfangioma/diagnóstico , Infecções Estreptocócicas/complicações , Vulva/anormalidades , Neoplasias Vulvares/diagnósticoAssuntos
Neurofibromatose 1/diagnóstico , Neurofibromatose 1/terapia , Guias de Prática Clínica como Assunto , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idade de Início , Criança , Pré-Escolar , Diagnóstico Diferencial , França/epidemiologia , Humanos , Incidência , Neurofibromatose 1/complicações , Neurofibromatose 1/epidemiologia , Neurofibromatose 1/genética , Sistema de RegistrosAssuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Transtornos Cromossômicos , Dermatopatias/genética , Anormalidades Múltiplas/imunologia , Feminino , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/genética , Lactente , Dermatopatias/complicações , SíndromeRESUMO
Spontaneous resolution of deformities after excision of facial skin lesions has been known and used for a long time by plastic surgeons. The resorption mechanism of deformity is based on natural skin expansion, and seems to be directly related to the action of the muscles of facial expression and their skin relations. Natural expansion has been shown to be effective in children. Between 1990 and 1994 excision of skin lesions, including congenital nevi, leading to postoperative deformity of the cheek, labial commissure, nose, eyelid and forehead, was performed on 35 patients, aged from 3 month to 12 years. The average follow-up is 24 months. For 26 patients (74%), natural resorption was observed 4 or 6 weeks later with good aesthetic results. For 6 patients (17%), the deformity persisted 3 or 6 months later, but did not require any further surgery. For 3 patients (9%), a second operation was necessary. Using the skins natural capacity for expansion in the treatment of facial skin defects in children is a method of reconstruction which has already been used for excision in enforced position. The platysma and muscles of facial expression by their action on skin mobilisation, allow natural expansion. A better knowledge of cutaneous biomechanical properties enables plastic surgeons to find an alternative to other classical methods.
Assuntos
Face/cirurgia , Dermatopatias/cirurgia , Cirurgia Plástica/métodos , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Hemangiomas are frequent in childhood, but those associated to dysmorphic anomalies are rare. We report a young girl with hemangiomas of the face, neck, and upper trunk, severe laryngeal dyspnea, and sternal atrophic skin without sternal nonunion, probably corresponding to a minor form of PHACES syndrome.