RESUMO
OBJECTIVES: Interferon regulatory factor 5 (IRF5) is a major regulator of type I interferon induction and is also critical to produce pro-inflammatory cytokines. An influence of IRF5 genetic variants on the increased risk of immune-mediated diseases has been described. Accordingly, we aimed to evaluate the implication of IRF5 in the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular pathology. METHODS: Three tag genetic variants (rs2004640, rs2070197 and rs10954213), representative of 3 different haplotype blocks within IRF5, were genotyped in 372 Caucasian patients with IgAV and 876 sex and ethnically matched healthy controls by TaqMan assays. RESULTS: No significant differences in the genotype and allele frequencies between patients with IgAV and healthy controls were observed when each IRF5 polymorphism was evaluated independently. Likewise, no significant differences between patients with IgAV and healthy controls were found when we assessed the three IRF5 polymorphisms combined, conforming haplotypes. In addition, there were no significant differences in genotype, allele and haplotype frequencies of IRF5 when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. CONCLUSIONS: Our results do not support an influence of IRF5 on the pathogenesis of IgAV.
Assuntos
Predisposição Genética para Doença , Imunoglobulina A , Fatores Reguladores de Interferon/genética , Vasculite/genética , Estudos de Casos e Controles , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: Cytokines signaling pathway genes represent a key component of the genetic network implicated in the pathogenesis of immunoglobulin-A vasculitis (IgAV), an inflammatory vascular pathology. Interleukin (IL)17A is described as a genetic risk locus for some autoimmune diseases, such as giant cell arteritis and spondyloarthritis. Accordingly, we aimed to determine the potential influence of IL17A on the pathogenesis of IgAV. METHODS: Five IL17A tag polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), which cover the major variability of this gene, were genotyped in 360 Caucasian patients with IgAV and 1,003 sex and ethnically matched healthy controls using TaqMan probes. RESULTS: No statistically significant differences between patients with IgAV and healthy controls were observed when each IL17A genetic variant was analysed independently. Similarly, no statistically significant differences between patients with IgAV and healthy controls were found when the five IL17A polymorphisms were evaluated combined conforming haplotypes. In addition, there were no statistically significant differences in genotype, allele and haplotype frequencies of IL17A when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. CONCLUSIONS: Our results do not support an influence of IL17A on the pathogenesis of IgAV.
Assuntos
Predisposição Genética para Doença , Imunoglobulina A , Interleucina-17/genética , Vasculite/genética , Estudos de Casos e Controles , Redes Reguladoras de Genes , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , Vasculite/patologiaAssuntos
Antivirais/efeitos adversos , Tratamento Farmacológico da COVID-19 , Exantema/induzido quimicamente , Idoso , Azitromicina/efeitos adversos , Cloroquina/efeitos adversos , Toxidermias , Exantema/tratamento farmacológico , Exantema/patologia , Feminino , Humanos , Hidroxicloroquina/efeitos adversosAssuntos
Varicela , Infecções por Coronavirus , Exantema , Herpes Simples , Herpes Zoster , Pandemias , Pneumonia Viral , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Dermatite Fototóxica/etiologia , Piridonas/efeitos adversos , Idoso , Dermatite Fototóxica/patologia , Eritema/etiologia , Feminino , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Prurido/etiologia , Luz Solar/efeitos adversosRESUMO
Erythropoietic protoporphyria arises from an inherited disorder of porphyrin metabolism which leads to an accumulation of protoporphyrin IX in the erythropoietic system and other tissues. It is characterized by cutaneous photosensitivity, usually difficult to keep under control. Among the scant therapeutic options proposed to reduce photosensitivity in erythropoietic protoporphyria, narrow-band UVB phototherapy has occasionally been used to induce sunlight tolerance. We report an adult case of erythropoietic protoporphyria with a severe photosensitivity treated with narrow-band UVB that developed an appropriate sunlight phototolerance, without adverse events during phototherapy.
Assuntos
Transtornos de Fotossensibilidade/radioterapia , Porfiria Eritropoética/radioterapia , Raios Ultravioleta , Terapia Ultravioleta , Adulto , Humanos , Masculino , Transtornos de Fotossensibilidade/etiologia , Transtornos de Fotossensibilidade/metabolismo , Porfiria Eritropoética/complicações , Porfiria Eritropoética/metabolismo , Protoporfirinas/metabolismo , Luz Solar/efeitos adversosRESUMO
CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV.
RESUMO
We report a 13-year-old girl with severe pustular psoriasis who had an excellent response to treatment with adalimumab after failure with methotrexate, acitretin, cyclosporin, phototherapy, and biologic drugs including etanercept and infliximab.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/patologia , Adalimumab , Adolescente , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.
Assuntos
Doenças Autoimunes , Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/genética , Imunoglobulina A/imunologia , Polimorfismo de Nucleotídeo Único , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Vasculite , Adulto , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Fator Ativador de Células B/imunologia , Receptor do Fator Ativador de Células B/imunologia , Feminino , Humanos , Masculino , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologia , Vasculite/genética , Vasculite/imunologiaRESUMO
Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.
Assuntos
Vasculite por IgA/genética , Vasculite por IgA/imunologia , Imunoglobulina A/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Interleucina-33/genética , Interleucina-33/imunologia , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Redes Reguladoras de Genes , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Vasculite por IgA/etiologia , Masculino , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Adulto JovemAssuntos
Antivirais/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Inibidores de Proteases/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Quimioterapia Combinada , Hepatite C Crônica/complicações , Humanos , Interferons/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Inibidores de Proteases/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêuticoRESUMO
BACKGROUND: Extracorporeal photochemotherapy (ECP), also known as photopheresis, is a generally well-tolerated therapeutic, immunomodulatory approach successfully used in cutaneous T-cell lymphoma and other diseases produced by T-lymphocytes such as graft vs host disease. OBSERVATIONS: On 2 separate occasions, a 54-year-old white man with Sézary syndrome developed cutaneous phototoxic reactions and chorioretinitis after being treated with ECP. A pharmacokinetic study showed therapeutic blood levels of 8-methoxypsoralen as long as 18 weeks after therapy had been terminated. However, the analysis of mutations in genes involved in the drug's disposition could not explain these abnormal levels. CONCLUSIONS: To our knowledge, there has been no previous description of ECP-related retinal toxic effects. This adverse effect was probably linked to impaired drug elimination. Further studies would be needed to determine the underlying mechanism.
Assuntos
Coriorretinite/etiologia , Fotoferese/efeitos adversos , Síndrome de Sézary/terapia , Neoplasias Cutâneas/terapia , Coriorretinite/sangue , Humanos , Masculino , Metoxaleno/farmacocinética , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/farmacocinética , Síndrome de Sézary/sangue , Neoplasias Cutâneas/sangueRESUMO
The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46-0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease.
Assuntos
Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos de Histocompatibilidade Classe II/genética , Imunoglobulina A/imunologia , Vasculite/genética , Vasculite/imunologia , Humanos , Modelos LogísticosRESUMO
BACKGROUND: Eccrine porocarcinoma (EPC) is an uncommon malignant neoplasm that originates in the intraepidermal portion of the eccrine sweat duct. Although porocarcinoma is a slow-growing tumor, up to 20% of cases can metastasize to regional lymph nodes, thus increasing mortality. METHODS: We describe the clinical and histopathological features and clinical course of three cases of extensive metastatic EPC diagnosed in our department over the last 10 years. RESULTS: All three patients were women aged 89-96 years. They had numerous skin tumors on the left leg that were histologically and immunohistochemically diagnosed as metastatic EPC. Only one patient had a history of primary porocarcinoma, which had been excised 6 years earlier. The remaining two patients had a previous lesion diagnosed as squamous cell carcinoma. We treated the patients with palliative radiotherapy and/or chemotherapy. Only one patient is currently alive. CONCLUSIONS: The cases of cutaneous and regional metastatic EPC we present occurred in elderly women with major involvement of the left leg. The third case is noteworthy, as the patient presented a long latency period before metastases appeared. Difficulties in the clinical diagnosis--and occasionally histological diagnosis--of primary EPC could delay more aggressive treatment, although optimal treatment does not always guarantee a good prognosis.
Assuntos
Porocarcinoma Écrino/secundário , Cuidados Paliativos , Neoplasias das Glândulas Sudoríparas/patologia , Idoso de 80 Anos ou mais , Quimiorradioterapia , Porocarcinoma Écrino/tratamento farmacológico , Porocarcinoma Écrino/radioterapia , Feminino , Humanos , Metástase Linfática , Neoplasias das Glândulas Sudoríparas/tratamento farmacológico , Neoplasias das Glândulas Sudoríparas/radioterapiaRESUMO
We describe the case of a 32-year-old male patient who had presented from birth with generalized ichthyosiform dermatosis, palmoplantar keratoderma with constrictive bands around the fingers and keratotic plaques in a linear arrangement, located in the large skin folds. The dermatopathological examination showed orthokeratotic hyperkeratosis and epidermal hyperplasia with hypergranulosis. No other members of the patient's family were affected. With these clinical and histological findings, the diagnosis was keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK syndrome). The patient rejected treatment with oral retinoids and was treated with emollients and 30 % urea creams, with little clinical response.
Assuntos
Ictiose/patologia , Ceratose/patologia , Esclerodermia Localizada/patologia , Adulto , Humanos , Masculino , SíndromeRESUMO
Colloid milium is a degenerative process that is characterized clinically by the development of translucent, yellow, 1-2 mm papules located in photoexposed areas. Histologically, deposits of a colloid substance are seen in the papillary dermis. We present two cases of this infrequent pathology in two male patients, who had been subjected to intense sun exposure because of their work. We initiated treatment with photoprotective creams and topical tretinoin, with little clinical improvement.