The systemic pathology of Venezuelan equine encephalitis virus infection in humans.

The histopathology of fatal Venezuelan equine encephalitis (VEE) in humans has not been well documented. To evaluate the spectrum of disease in man, the histologic slides of the 21 autopsied patients who died with documented VEE infection during the 1962-63 VEE epidemic in Zulia, Venezuela were reviewed. The main histopathologic lesion observed in multiple organs and tissues, especially the brain, gastrointestinal tract, and lungs, was moderate to marked diffuse congestion and edema with hemorrhage. In the central nervous system (CNS), mild or focal mixed inflammatory cell infiltrates were present in the leptomeninges and perivascular spaces (65%). Meningoencephalitis associated with intense necrotizing vasculitis was observed in 2 patients (10%), and cerebritis was observed in 5 cases (25%). There was a striking depletion of lymphocytes with vascular thrombosis and necrosis of follicles in lymph nodes (77%), spleen (69%), and the gastrointestinal tract (90%). Widespread hepatocellular degeneration and individual cell necrosis was observed in 61% of the cases. Most patients (90%) had interstitial pneumonia, frequently complicated by acute bronchopneumonia (33%). Overall, the lesions observed in the CNS and reticuloendothelial tissues are comparable to what is observed in experimental animals; however, extensive hepatocellular degeneration and interstitial pneumonia are not prominent pathologic features of VEE in animals. The findings are consistent with the hypothesis that lymphoid and reticuloendothelial tissues are the targets in VEE virus infection in humans, and that many of the histopathologic changes are attributable to primary lymphoid and endothelial cell injury.

Hypertensive pulmonary vascular disease in Down syndrome.

Clinical studies have suggested that patients with Down syndrome have precocious development of pulmonary hypertension, even in the absence of congenital heart disease. To examine the pathologic basis of this impression, we studied 82 patients with Down syndrome autopsied at The Johns Hopkins Hospital from 1913 to present. The patients ranged in age from 26 hours to 25 years; 41 (50%) were female. Atrioventricular canal defect was present in 40 patients, nine of whom also had pulmonary stenosis. Eight had isolated ventricular septal defect and seven had other malformations. Histologic sections of the lung from each patient were studied and the degree of hypertensive pulmonary vascular disease graded. Age and sex-matched controls without cardiovascular manifestations, all other autopsied patients with atrioventricular canal defect not associated with Down syndrome, and age-matched patients with ventricular septal defect or other malformations were similarly studied for pulmonary vascular changes. Comparison of the 27 patients with Down syndrome and no cardiovascular malformations with normal controls showed no differences, with one notable exception: an 8-month-old child with Down syndrome had severe HPVD secondary to idiopathic pulmonary hypertension. HPVD in patients with the various cardiovascular malformations was similar for those groups with Down syndrome and those without, when HPVD was considered as a function of the patients' age and the type of malformation. We conclude that, in general, patients with Down syndrome have no predisposition to develop severe or precocious hypertensive pulmonary vascular disease.