Histopathology of Severe Dengue in Lungs of Human Fatal Cases

Context: Severe dengue fever includes dengue hemorrhagic fever (DHF) and dengue shock syndrome. Previously, the Ministry of Health of Brazil categorized dengue with complications (DCC) when the patient died without changes in hemostasis. Design: One hundred twenty-four autopsy cases with fatal dengue, performed between 2011 and 2013 in Ceara, Brazil, were analyzed. Standard staining, immunohistochemistry for dengue antigen, and polymerase chain reaction assay for viral RNA were performed. Results: Twenty-seven cases were classified as DHF (21.8%), while 97 were DCC (78.2%). The median age was 36.9 years (1-84 years); 65% of patients were men. Most patients died within 1 to 5 days after the onset of dengue symptoms. Underlying diseases were hypertension (39.7%) and diabetes (19.3%). The main symptoms were fever (85%), dyspnea (70%), cough (53%), abdominal pain (57%), and hemorrhagic phenomenon (48%). Histologically, intraalveolar edema, congestion and/or hemorrhage, interstitial or intraalveolar inflammatory cell infiltration, and hyaline membranes were observed in all cases in different degrees of severity. Severity was scored according to the area of the lung involved, defining 3 categories: absent (0); mild, up to 50% (1%-50%) of pulmonary parenchyma compromised; and severe, 51% to 100% of lung parenchyma compromised. According to severity score, intraalveolar edema, pulmonary cell infiltration, and hemorrhage were significantly more severe in the DHF group than DCC group (P < .01). Patients with severe score for interstitial inflammatory cell infiltration had a risk of 13.12 (2.54-67.64) of dying from changes in hemostasis and vascular permeability (P < .01), whereas for those with mild score for edema and hemorrhage, the risk was 3.12 (1.07-9.17) and 4.04 (1.39-11.71), respectively. Conclusions: Patients with signs of vascular leakage should be monitored for warning signs in order to avoid a fatal outcome.