RESUMO
BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.
Assuntos
Alumínio , Lasers de Corante , Lasers de Estado Sólido , Telangiectasia Hemorrágica Hereditária , Telangiectasia , Ítrio , Humanos , Lasers de Corante/efeitos adversos , Lasers de Estado Sólido/efeitos adversos , Neodímio , Estudos Prospectivos , Qualidade de Vida , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia/etiologia , Telangiectasia/radioterapia , Resultado do TratamentoRESUMO
BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.
Assuntos
Alumínio , Lasers de Corante , Lasers de Estado Sólido , Telangiectasia Hemorrágica Hereditária , Telangiectasia , Ítrio , Humanos , Lasers de Corante/efeitos adversos , Lasers de Estado Sólido/efeitos adversos , Neodímio , Estudos Prospectivos , Qualidade de Vida , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia/etiologia , Telangiectasia/radioterapia , Resultado do TratamentoRESUMO
BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast-flow vascular malformations (FFVMs) in one-third of patients. Few case series have been described, and none in Spain. AIM: To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM-AVM. METHODS: We conducted an observational study of patients with CM-AVM syndrome diagnosed in 15 Spanish hospitals over 3 years. The main clinical, radiological, genetic findings and associated diseases were analysed. RESULTS: In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the 'herald patch'. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas. CONCLUSIONS: Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype-phenotype correlation.
Assuntos
Malformações Arteriovenosas/patologia , Encéfalo/patologia , Capilares/anormalidades , Mancha Vinho do Porto/patologia , Pele/patologia , Coluna Vertebral/patologia , Malformações Vasculares/patologia , Adulto , Malformações Arteriovenosas/diagnóstico , Malformações Arteriovenosas/epidemiologia , Malformações Arteriovenosas/genética , Encéfalo/irrigação sanguínea , Capilares/patologia , Criança , Pré-Escolar , Análise de Dados , Feminino , Estudos de Associação Genética , Humanos , Achados Incidentais , Lactente , Masculino , Mutação , Mancha Vinho do Porto/diagnóstico , Mancha Vinho do Porto/epidemiologia , Mancha Vinho do Porto/genética , Prevalência , Receptor EphB4/genética , Pele/irrigação sanguínea , Espanha/epidemiologia , Coluna Vertebral/irrigação sanguínea , Malformações Vasculares/diagnóstico , Malformações Vasculares/genética , Proteína p120 Ativadora de GTPase/genéticaRESUMO
BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.
Assuntos
Dermatite Atópica , Eczema , Adolescente , Adulto , Anticorpos Monoclonais Humanizados , Criança , Dermatite Atópica/tratamento farmacológico , Humanos , Estudos Observacionais como Assunto , Estudos Prospectivos , Sistema de Registros , Resultado do TratamentoRESUMO
BACKGROUND: Infantile haemangiomas (IH) are soft swellings of the skin that occur in 3-10% of infants. When haemangiomas occur in high-risk areas or when complications develop, active intervention is necessary. OBJECTIVE: To update a Cochrane Review assessing the interventions for the management of IH in children. METHODS: We searched for randomized controlled trials in CENTRAL, MEDLINE, Embase, LILACS, AMED, PsycINFO, CINAHL and six trials registers up to February 2017. We included 28 trials (1728 participants) assessing 12 interventions. RESULTS: We downgraded evidence from high to moderate/low for issues related to risk of bias and imprecision. Oral propranolol (3 mg kg-1 daily) probably improves clinician-assessed clearance vs placebo [risk ratio (RR) 16·61, 95% confidence interval (CI) 4·22-65·34; moderate quality of evidence (QoE)]; we found no evidence of a difference in terms of serious adverse events (RR 1·05, 95% CI 0·33-3·39; low QoE). We found the chance of reduction of redness may be improved with topical timolol maleate (0·5% gel applied twice daily) when compared with placebo (RR 8·11, 95% CI 1·09-60·09; low QoE). We found no instances of bradycardia or hypotension for this comparison. CONCLUSIONS: Our key results indicate that oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harm.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Hemangioma/tratamento farmacológico , Propranolol/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Timolol/administração & dosagem , Administração Cutânea , Administração Oral , Antagonistas Adrenérgicos beta/efeitos adversos , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Abordagem GRADE , Humanos , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia , Placebos/administração & dosagem , Placebos/efeitos adversos , Propranolol/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Timolol/efeitos adversosRESUMO
BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer-prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders. OBJECTIVES: To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC. METHODS: We conducted RNA-Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies. RESULTS: Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA-Seq data. In addition, enzyme-linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB. CONCLUSIONS: Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury-sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. What's already known about this topic? Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development. Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders. What does this study add? We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix-synthetic capacity. This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor-ß signalling activation and oxidative state imbalance. What is the translational message? This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention. It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB.
Assuntos
Vesícula/patologia , Epidermólise Bolhosa Distrófica/patologia , Epidermólise Bolhosa/patologia , Matriz Extracelular/patologia , Fibroblastos/patologia , Doenças Periodontais/patologia , Transtornos de Fotossensibilidade/patologia , Pele/patologia , Xeroderma Pigmentoso/patologia , Adolescente , Adulto , Biópsia , Vesícula/genética , Estudos de Casos e Controles , Células Cultivadas , Criança , Pré-Escolar , Epidermólise Bolhosa/genética , Epidermólise Bolhosa Distrófica/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Fibrose , Regulação da Expressão Gênica , Voluntários Saudáveis , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Doenças Periodontais/genética , Transtornos de Fotossensibilidade/genética , Cultura Primária de Células , RNA-Seq , Pele/citologia , Xeroderma Pigmentoso/genética , Adulto JovemRESUMO
Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder caused by a somatic activating mutation in GNAQ; it affects 1 in every 20,000 to 50,000 newborns. It is characterized by a facial Port-wine stain, leptomeningeal angiomatosis, and glaucoma. Seizures are the most common neurological manifestation and typically present in the first months of life. Glaucoma may be present at birth or develop later. Neuroimaging studies show leptomeningeal angiomatosis, supporting diagnosis. Standard treatment for Sturge-Weber syndrome includes laser treatment for the Port-wine stain, anticonvulsants, and medical or surgical treatment for the glaucoma. Prognosis depends on the extent of leptomeningeal involvement and the severity of the glaucoma.
Assuntos
Síndrome de Sturge-Weber , Anticonvulsivantes/uso terapêutico , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Diagnóstico Precoce , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Glaucoma/tratamento farmacológico , Glaucoma/etiologia , Humanos , Lasers de Corante/uso terapêutico , Meninges/irrigação sanguínea , Meninges/embriologia , Meninges/patologia , Neuroimagem , Mancha Vinho do Porto/etiologia , Mancha Vinho do Porto/cirurgia , Convulsões/tratamento farmacológico , Convulsões/etiologia , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/genética , Síndrome de Sturge-Weber/patologia , Síndrome de Sturge-Weber/terapia , Veias/embriologiaRESUMO
BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.
Assuntos
Antineoplásicos/administração & dosagem , Hemangioma/tratamento farmacológico , Propranolol/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Antineoplásicos/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Propranolol/efeitos adversos , Resultado do TratamentoAssuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Neoplasias de Tecido Vascular/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Cutâneas/genética , Biópsia , Pré-Escolar , Análise Mutacional de DNA , Exoma/genética , Feminino , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Mutação com Ganho de Função , Humanos , Neoplasias de Tecido Vascular/diagnóstico , Neoplasias de Tecido Vascular/patologia , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Pele/irrigação sanguínea , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
Capillary malformation-arteriovenous malformation syndrome is a rare type of vascular malformation first described in 2003. It is an autosomal dominant inherited disorder that has been reported in association with heterozygous mutations in the RASA1 gene, which encodes the protein RASp21. The clinical picture is characterized by multiple small capillary malformations which are associated with either arteriovenous malformations or arteriovenous fistulas in both the affected individual and other members of their family. We describe 2 new familial cases of this syndrome that were clinically and genetically diagnosed and studied in our hospital.
Assuntos
Malformações Arteriovenosas/diagnóstico , Capilares/anormalidades , Mancha Vinho do Porto/diagnóstico , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/etiologia , Fístula Arteriovenosa/terapia , Malformações Arteriovenosas/genética , Pré-Escolar , Análise Mutacional de DNA , Gerenciamento Clínico , Embolização Terapêutica , Saúde da Família , Feminino , Genes Dominantes , Testes Genéticos , Humanos , Lactente , Malformações Arteriovenosas Intracranianas/diagnóstico , Malformações Arteriovenosas Intracranianas/etiologia , Malformações Arteriovenosas Intracranianas/terapia , Imageamento por Ressonância Magnética , Especificidade de Órgãos , Linhagem , Mancha Vinho do Porto/genética , Proteína p120 Ativadora de GTPase/genéticaRESUMO
BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a rare disease that represents a heavy burden for both the patient and the health care system. There are currently no data on the prevalence of DEB in Spain. OBJECTIVE: To determine the prevalence of DEB in Spain. METHODS: We used data from 3 incomplete population-based sources (hospital dermatology departments, diagnostic laboratories performing antigenic mapping, genetic testing or both, and the Spanish Association of Epidermolysis Bullosa Patients [DEBRA]) and combined them using the 3-source capture-recapture methodology. RESULTS: We identified 152 living DEB patients. The estimated prevalence of DEB was 6.0 cases per million (95% CI, 4.2-11.8) in adults and 15.3 (95% CI, 10.4-40.8) in children under 18 years of age. The data indicated that 77% of the patients were not being followed up in specialized centers of reference; 65% had not had a genetic diagnosis, and 76% were not members of DEBRA. CONCLUSIONS: The prevalence of DEB in Spain is 6.0 patients per million (95% CI, 4.2-11.8), a figure higher than previous estimates in many areas, but similar to those found in other southern Europe countries. The north-south difference may represent real geographic differences in prevalence, but it might be due to the fact that most of the data come from registries with a lower than expected catchment. Many patients are not being followed up in centers of reference, do not have genetic diagnosis, and are not members of patients' associations, suggesting that there is room for considerable improvement in their care.
Assuntos
Epidermólise Bolhosa Distrófica/epidemiologia , Epidermólise Bolhosa Distrófica/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Lactente , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Melhoria de Qualidade , Espanha/epidemiologia , Adulto JovemAssuntos
Doenças em Gêmeos/radioterapia , Tumor Glômico/radioterapia , Doenças do Prematuro/radioterapia , Lasers de Corante/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Neoplasias Cutâneas/radioterapia , Estética , Seguimentos , Tumor Glômico/congênito , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Ombro , Neoplasias Cutâneas/congênitoAssuntos
Ictiose Lamelar/terapia , Alopecia/prevenção & controle , Terapia Genética/métodos , Prioridades em Saúde , Humanos , Recém-Nascido , Relações Interprofissionais , Ceratolíticos/uso terapêutico , Assistência Perinatal/organização & administração , Prurido/etiologia , Qualidade de Vida , Retinoides/efeitos adversosRESUMO
Rapidly involuting congenital haemangioma (RICH) may present with thrombocytopenia, low fibrinogen and elevated fibrin degradation products and D-dimers. Such complications have rarely been reported. We wished to define the clinical characteristics of the thrombocytopenia and coagulopathy associated with RICH, to emphasize the transient nature of this haematological complication and to distinguish these abnormalities from true Kasabach-Merritt phenomenon (KMP). We present a case series of seven patients with large RICH who presented with thrombocytopenia and coagulopathy during the first week of life. Clinical and haematological characteristics were recorded retrospectively. Two of the patients were treated with embolization due to early signs of high-output cardiac failure; four patients received oral corticosteroids in the range of 2 mg kg(-1) daily; one patient did not receive any treatment in the neonatal period, although the tumour was excised at 6 months of age. Two patients with platelet counts lower than 10 x 10(9) L(-1) received a platelet transfusion. There were no bleeding complications and only one patient presented with petechiae. In all seven patients, platelet counts started to increase at > 2 weeks of age and the coagulopathy resolved. We conclude that RICH may present with thrombocytopenia and coagulopathy similar to mild KMP early in the neonatal period. However, in contrast to true KMP, these abnormal laboratory findings are self-limited and are usually not complicated by bleeding problems.
Assuntos
Transtornos da Coagulação Sanguínea/congênito , Fibrinogênio/metabolismo , Hemangioma/congênito , Trombocitopenia/congênito , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/terapia , Feminino , Hemangioma/complicações , Hemangioma/terapia , Humanos , Recém-Nascido , Masculino , Contagem de Plaquetas , Remissão Espontânea , Trombocitopenia/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Glomuvenous malformation (GVM) ("familial glomangioma") is a localised cutaneous vascular lesion histologically characterised by abnormal smooth muscle-like "glomus cells" in the walls of distended endothelium lined channels. Inheritable GVM has been linked to chromosome 1p21-22 and is caused by truncating mutations in glomulin. A double hit mutation was identified in one lesion. This finding suggests that GVM results from complete localised loss of function and explains the paradominant mode of inheritance. OBJECTIVE: To report on the identification of a mutation in glomulin in 23 additional families with GVM. RESULTS: Three mutations are new; the others have been described previously. Among the 17 different inherited mutations in glomulin known up to now in 43 families, the 157delAAGAA mutation is the most common and was present in 21 families (48.8%). Mutation 108C-->A was found in five families (11.8%), and the mutations 554delA+556delCCT and 1179delCAA were present together in two families (4.7% each). Polymorphic markers suggested a founder effect for all four mutations. CONCLUSIONS: Screening for these mutations should lead to a genetic diagnosis in about 70% of patients with inherited GVM. So far, a mutation in glomulin has been found in all GVM families tested, thus demonstrating locus homogeneity.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Efeito Fundador , Mutação em Linhagem Germinativa , Tumor Glômico/genética , Sequência de Aminoácidos , Análise Mutacional de DNA , Feminino , Tumor Glômico/diagnóstico , Haplótipos , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Alinhamento de SequênciaAssuntos
COVID-19 , Pérnio , Pérnio/diagnóstico , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Espanha/epidemiologiaRESUMO
Dyskeratosis congenita (DC) is a rare hereditary disorder of skin which may be associated with aplastic anemia. The pattern of inheritance is X-linked recessive in most instances, but autosomal dominant and autosomal recessive types have been documented. Reticulated hyperpigmentation usually is the first manifestation. The pigmentary changes may be limited to neck, upper chest, and proximal parts of the limbs initially but within affected areas the involvement is always diffuse. We report on a patient with typical diffuse cutaneous signs of dyskeratosis congenita superimposed with hyperpigmentation that was more pronounced along Blaschko's lines. To explain this phenomenon, we assume that the patient has the autosomal dominant type and that loss of heterozygosity occurred in a somatic cell giving rise to a population of cells that migrated along these lines during embryogenesis.
Assuntos
Disceratose Congênita/genética , Adolescente , Disceratose Congênita/patologia , Fibroblastos/patologia , Humanos , Cariotipagem , Perda de Heterozigosidade , Masculino , Pele/patologiaRESUMO
OBJECTIVE: To determine, using polymerase chain reaction (PCR) amplification, if Mycobacterium tuberculosis complex DNA is present in the skin biopsy specimens of lobular granulomatous panniculitis. DESIGN: A retrospective descriptive study. SETTING: A university-based hospital. PATIENTS: From the 65 patients included in the study, we examined 72 paraffin-embedded skin biopsy specimens with a histologic diagnosis of erythema induratum or nodular vasculitis. The biopsy specimens were from the histopathological archives of the Departments of Dermatology and Pathology of the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, from 1976 to 1994. Twenty-two biopsy specimens were excluded from the final analysis because we could not amplify the internal control. MAIN OUTCOME MEASURES: Detection of a 123-base pair fragment of the IS6110 insertion sequence specific for M tuberculosis complex. RESULTS: The results of PCR amplification were positive for M tuberculosis complex DNA in 77% of the skin biopsy specimens. No significant difference could be detected with respect to the age of the patients, ulceration of the nodules, reactivity to purified protein derivative, abnormal results of a chest x-ray examination, personal and family history of tuberculosis, and PCR results. The presence and degree of necrosis on histologic examination were significantly higher in the PCR-positive group (P = .04). None of the following variables were associated with PCR results: presence of vasculitis, degree of granulomatous infiltrates, number of giant cells, and presence of well-organized granulomas. CONCLUSIONS: The DNA of M tuberculosis can be detected in a considerable number of skin biopsy specimens of lobular granulomatous panniculitis. None of the clinical and histologic variables evaluated could accurately predict the results of PCR amplification.