RESUMO
BACKGROUND: Imatinibmesylate (imatinib) is a small molecule tyrosine kinase inhibitor administered to patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. Although imatinib-associated interstitial lung disease is uncommon, a few cases have been reported so far. However, in all these cases interstitial lung disease developed during the use of imatinib. The present case is the first report of imatinib-induced interstitial lung disease developing after discontinuation of the drug. CASE PRESENTATION: A 51-year-old woman was administered oral imatinib for gastrointestinal stromal tumor. Ten weeks later, imatinib was discontinued because of facial edema. On this occasion, chest radiography showed no abnormal findings. However, 2 weeks after discontinuation of imatinib, she developed fever, dry cough, and dyspnea. Chest radiography and computed tomography showed diffuse interstitial infiltrates in both lungs. Examination of bronchoalveolar lavage fluid showed an increased proportion of lymphocytes. Imatinib-induced interstitial lung disease was suspected, because no other cause was evident. After administration of corticosteroids, her clinical condition and chest radiographic findings improved. CONCLUSION: We report a unique case of imatinib-induced interstitial lung disease that developed 2 weeks after discontinuation of the drug. Physicians should consider occurrence of imatinib-induced interstitial lung disease even after discontinuation of the drug.
RESUMO
For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.
Assuntos
Cirrose Hepática Biliar/genética , Transativadores/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Linfócitos B , Estudos de Casos e Controles , Diferenciação Celular/genética , Feminino , Loci Gênicos/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/genética , Polimorfismo Genético , Fator de Transcrição STAT4/genética , Fator de Necrose Tumoral alfa/genética , População Branca/genética , Adulto JovemRESUMO
Three cases of organizing pneumonia (OP) that occurred after planned radiation therapy for postoperative breast cancer are reported. All patients received tangential radiation therapy and adjuvant tamoxifen (TAM) for postoperative breast cancer. Two patients developed fever and cough; one was asymptomatic. Chest radiography and computed tomography demonstrated peripheral alveolar opacities outside the radiation field. Bronchoalveolar lavage showed an elevated total cell count with a high percentage of lymphocytes, as well as elevated eosinophil levels in two cases. Transbronchial lung biopsy revealed a histologic pattern consistent with organizing pneumonia. For the two symptomatic cases, treatment with corticosteroids reduced clinical symptoms promptly and improved imaging findings. The single asymptomatic case improved without treatment. The number of such reported cases has increased in recent years, but the etiology is unclear. In the three cases presented, TAM combined with radiation therapy may have been the cause of the OP.