Assuntos
Adenosina Desaminase/deficiência , Adenosina Desaminase/genética , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Peptídeos e Proteínas de Sinalização Intercelular/genética , Úlcera da Perna/genética , Dermatopatias Genéticas/diagnóstico , Adulto , Doença Crônica , Consanguinidade , Humanos , Úlcera da Perna/patologia , Masculino , Linhagem , Dermatopatias Genéticas/genéticaAssuntos
Carcinoma de Células Escamosas/complicações , Líquen Plano/complicações , Neoplasias Cutâneas/complicações , Úlcera Cutânea/complicações , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Doenças do Pé/complicações , Mãos , Humanos , Masculino , Neoplasias Cutâneas/patologiaAssuntos
Fibrossarcoma/etiologia , Joias/toxicidade , Neoplasias Induzidas por Radiação/patologia , Neoplasias de Tecidos Moles/etiologia , Tórax/patologia , Idoso de 80 Anos ou mais , Evolução Fatal , Fibrossarcoma/patologia , Humanos , Masculino , Metástase Neoplásica , Esclerose/etiologia , Neoplasias de Tecidos Moles/patologia , Tório/toxicidade , Urânio/toxicidadeRESUMO
OBJECTIVES: The broader and prolonged use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) could expose patients to an increased risk of adverse reactions, including dermatological complications. We assessed the cumulative incidence of anti-TNF-induced cutaneous adverse reactions in IBD patients, their risk factors, their dermatological management, and their outcome in a large cohort of IBD patients. METHODS: In a single-center observational retrospective study, including all consecutive adult IBD patients treated with an anti-TNF agent between 2001 and 2014, all patients with dermatological complications under anti-TNF therapy were identified in a well-defined cohort of IBD patients. We conducted a survival analysis to determine the cumulative incidence of dermatological complications and risk factors for developing any dermatological complications, cutaneous infections, and psoriasiform lesions. Survival curves were estimated by the Kaplan-Meier method, and we used a Cox proportional hazards model to test the association between parameters and time to each event: any dermatological complication, cutaneous infections, and psoriasis lesions. RESULTS: Among 583 IBD patients, 176 dermatological complications occurred, involving 20.5% of patients. Median duration of follow-up was 38.2 months (range: 1-179). Psoriasiform lesions (10.1%; 59/583) and cutaneous infections (11.6%, 68/583) were the most frequently observed, with a cumulative incidence of, respectively, 28.9% and 17.6% at 10 years. They led to anti-TNF discontinuation, respectively, in 18.6% and 2.9% of patients. In case of switching to another anti-TNF agent for psoriasiform lesions, recurrence occurred in 57% of patients. Ulcerative colitis was associated with a lower risk of developing cutaneous infections than Crohn's disease (hazard ratio (HR)=0.25; 95% confidence interval (CI)=0.09-0.68; P=0.007). Higher dosing of anti-TNF agent was associated with a higher risk of developing cutaneous infections (HR=1.99; 95% CI=1.09-3.64; P=0.025). A younger age at time of anti-TNF initiation was associated with a higher risk of dermatological complications (HR=2.25; 95% CI=1.39-3.62; P<0.001). CONCLUSIONS: Dermatological complications involve one of five patients treated with anti-TNF therapy after a 14-year follow-up. Association of cutaneous infections with higher anti-TNF dosing suggests a dose-dependent effect. Discontinuation of anti-TNF therapy due to dermatological complications is required in one out of five patients with psoriasiform lesions, but specific dermatological treatment allows to continue anti-TNF therapy in half of them.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Toxidermias/epidemiologia , Psoríase/epidemiologia , Dermatopatias Infecciosas/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Relação Dose-Resposta a Droga , Toxidermias/etiologia , Toxidermias/patologia , Feminino , Humanos , Incidência , Infliximab , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Dermatopatias Infecciosas/induzido quimicamente , Dermatopatias Infecciosas/tratamento farmacológico , Adulto JovemAssuntos
Blefarite/etiologia , Neoplasias da Mama/secundário , Neoplasias da Túnica Conjuntiva/secundário , Conjuntivite/etiologia , Neoplasias Palpebrais/diagnóstico , Idoso , Biópsia , Blefarite/diagnóstico , Neoplasias da Mama/diagnóstico , Neoplasias da Túnica Conjuntiva/diagnóstico , Conjuntivite/diagnóstico , Diagnóstico Diferencial , Neoplasias Palpebrais/complicações , Feminino , HumanosAssuntos
Granuloma Anular/diagnóstico , Doenças do Pênis/diagnóstico , Administração Tópica , Idoso de 80 Anos ou mais , Anti-Inflamatórios/administração & dosagem , Clobetasol/administração & dosagem , Diagnóstico Diferencial , Granuloma Anular/tratamento farmacológico , Humanos , Masculino , Doenças do Pênis/tratamento farmacológicoRESUMO
Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.