RESUMO
Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.
Assuntos
Granuloma/imunologia , Inflamação/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Vírus da Rubéola/fisiologia , Rubéola (Sarampo Alemão)/imunologia , Idoso , Antígenos Virais/metabolismo , Estudos de Coortes , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Doenças Genéticas Inatas , Transplante de Células-Tronco Hematopoéticas , Humanos , Imuno-Histoquímica , Síndromes de Imunodeficiência , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-1/antagonistas & inibidores , Rubéola (Sarampo Alemão)/complicações , Células Th2/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
We collected sputum samples and cough plates from 15 cystic fibrosis patients in the Netherlands who were colonized with Aspergillus fumigatus; we recovered A. fumigatus of the same genotype in cough aerosols and sputum samples from 2 patients. The belief that transmission of A. fumigatus from cystic fibrosis patients does not occur should be reconsidered.
Assuntos
Aspergilose/etiologia , Aspergilose/transmissão , Aspergillus fumigatus , Fibrose Cística/complicações , Exposição por Inalação/efeitos adversos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/epidemiologia , Aspergillus fumigatus/classificação , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Fibrose Cística/epidemiologia , Genótipo , Humanos , Tipagem Molecular , Países Baixos/epidemiologia , Vigilância em Saúde Pública , Escarro/microbiologiaRESUMO
A healthy 7-year-old boy presented with bilateral symmetrical lacrimal gland enlargement; a week later salivary gland enlargement was also noted. Clinical investigations suggested no diagnosis, and surgical biopsy was considered. Valproic acid (sodium valproate), which he was taking for absence seizures, has been reported to cause salivary gland swelling in adults. Suspecting that a similar mechanism could be causal, the drug was discontinued. Complete resolution of the lacrimal and salivary gland enlargement rapidly ensued. This is the first report of lacrimal gland enlargement caused by valproic acid.