Assuntos
Síndrome de Bloom/diagnóstico , Síndrome de Bloom/genética , Eritema/diagnóstico , Eritema/genética , Indígenas Norte-Americanos/genética , Síndrome de Bloom/complicações , Criança , Diagnóstico Diferencial , Eritema/complicações , Face/patologia , Humanos , Indígenas Norte-Americanos/etnologia , Masculino , México/etnologiaRESUMO
TRAPS is the most common of the autosomal dominant periodic fever syndromes. It is caused by mutations in the TNFRSF1A gene, which encodes for the type 1 TNF-receptor (TNFR1). We describe here a Brazilian patient with TRAPS associated to a novel TNFRSF1A de novo mutation and the response to anti-TNF therapy. The patient is a 9-year-old girl with recurrent fevers since the age of 3 years, usually lasting 3 to 7 days, and recurring every other week. These episodes are associated with mild abdominal pain, nausea, vomiting and generalized myalgia. Recurrent conjunctivitis and erysipela-like skin lesions in the lower limbs also occur. Laboratory studies show persistent normocytic normochromic anemia, thrombocytosis, elevated erythrocyte sedimentation rate and C-reactive protein. IgD levels are normal. Mutational screening of TNFRSF1A revealed the association of a novel C30F mutation with the common R92Q low-penetrance mutation. The R92Q mutation is seen in 5% of the general population and is associated with an atypical inflammatory phenotype. The patient had a very good response to etanercept, with cessation of fever and normalization of inflammatory markers. Our report expands the spectrum of TNFRSF1A mutations associated with TRAPS, adding further evidence for possible additive effects of a low-penetration R92Q and cysteine residue mutations, and confirms etanercept as an efficacious treatment alternative.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Marcadores Genéticos , Imunoglobulina G/uso terapêutico , Mutação de Sentido Incorreto , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/uso terapêutico , Dor Abdominal/genética , Artralgia/genética , Criança , Conjuntivite/genética , Eritema/genética , Etanercepte , Feminino , Humanos , Náusea/genética , Linhagem , Receptores do Fator de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Resultado do Tratamento , Vômito/genéticaRESUMO
BACKGROUND: Ashy dermatosis, also known as erythema dyschromicum perstans, is an acquired benign disease, characterized by blue-gray pigment patches with erythematous borders. The cause is still unclear, but probably has an immunologic basis. OBJECTIVE: The aim of this study was to determine gene frequencies of the HLA-DR alleles in Mexican patients with ashy dermatosis and compare them with ethnically matched healthy control subjects to reveal the genetic susceptibility to develop ashy dermatosis. METHODS: We included 23 consecutive patients with clinical and histopathologic confirmed diagnosis of erythema dyschromicum perstans. Patients and control subjects received a questionnaire to determine their ethnic origin and a peripheral blood sample was taken for DNA extraction. Finally, Genetic HLA-DRB1 was performed by polymerase chain reaction sequence-specific oligonucleotide reverse dot blot hybridization. RESULTS: Of the 23 patients included in this study, 65% were women and 35% were men. We observed that the disease was located in the trunk in 17 patients (74%) and the upper limbs in 15 patients (65%). The most frequent allele was HLA-DR4 (65%) (pC < 1 x 10(-6), odds ratio = 6.0, 95% confidence interval = 2.8-12.7) whereas in control subjects it was 23%. The most frequent molecular subtype in both patients and healthy control subjects was DRB1( *)0407, being statistically significant after comparing the two groups (pC < 1 x 10(-6), odds ratio = 7.0, 95% confidence interval = 3.1-15.8). LIMITATIONS: Since this is a disease strongly influenced by ethnicity, extrapolation to other ethnic groups is limited. CONCLUSIONS: Many factors influence the ethiopathogenesis of erythema dyschromicum perstans, but it is strongly suggested to have an important genetic susceptibility conferred by genes located within the major histocompatibility complex region.
Assuntos
Predisposição Genética para Doença/epidemiologia , Antígenos HLA-DR/genética , Polimorfismo Genético , Dermatopatias/genética , Dermatopatias/patologia , Adolescente , Adulto , Alelos , Estudos de Coortes , Intervalos de Confiança , Eritema/genética , Eritema/patologia , Etnicidade/genética , Feminino , Regulação da Expressão Gênica , Genótipo , Antígeno HLA-DR4/genética , Humanos , Masculino , México/etnologia , Pessoa de Meia-Idade , Razão de Chances , Probabilidade , Doenças Raras , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
In 1985, Blau reported a family with 11 members in four generations affected by granulomatous arthritis, iritis, skin rash, and periarticular synovial cysts. We report a second family with these abnormalities, thereby confirming this syndrome as a distinct familial entity with transmission compatible with autosomal dominant inheritance. Affected members in our family included a mother and two daughters. Disease onset was at 10 months to 8 years of age. Each had uveitis, symmetric polyarthritis, and synovial cysts overlying the ankle and wrist joints. In addition, both daughters had an intermittent generalized erythematous papular rash that on biopsy revealed noncaseating granulomatous infiltration. All three patients improved during alternate-day steroid therapy. Recognition of this disorder as distinct from other, more common causes of arthritis is important because of the apparent autosomal dominant transmission and because of the excellent responses to low-dose steroid therapy.