A 33-year-old male student diagnosed with HIV in 2013, with irregular use of ART and prophylaxis, had a CD4 T lymphocyte count of 9 cells/mm and viral load of 137 000 copies of HIV RNA in a milliliter of blood. The patient was hospitalized for investigation of asthenia and dyspnea after low levels of exertion, with 5 days of evolution. These symptoms were accompanied by adynamia, decreased motor force in the left leg, dysphagia, and dysfluency. He also reported weight loss of approximately 8 kg in the 3 months prior to the hospitalization and continuous episodes of forgetfulness.
On physical examination, the patient's general condition was regular, though he was pale, febrile (38.9 C), and had normal cardiac and pulmonary auscultation. Liver and spleen were palpable at 2 cm from the right and left costal margins; however, lymph nodes were not palpable. In the perianal region, the patient presented ulcerated lesions with regular edges, regular and well demarcated edges and no phlogistic signs. The neurological examination revealed normal muscle strength in the upper and lower limbs and preserved tactile sensitivity. The initial blood count showed pancytopenia (hemoglobin: 4.7, leukocytes: 1,670/mm3, lymphocytes: 290/mm3, platelets: 32 000 x 103/mm3) with a slight increase in liver function (aspartate aminotransferase: 102 mug/l, alanine aminotransferase: 86 mug/l), normal renal function, triglycerides of 161 mg/dL, lactate dehydrogenase (LDH) of 588 U/L, and ferritin of 585 microg/mL.
In view of the clinical and laboratory findings, the initial diagnostic hypothesis was disseminated histoplasmosis. Blood cultures of fungi, mycobacteria, aerobes, and investigation of fungi in leukocyte cream were performed. Meanwhile, amphotericin B deoxycholate was empirically prescribed due to his advanced HIV disease. All results were negative. Other additional procedures were red blood cell transfusions, resumption of ART, and secondary prophylaxis. After a blood transfusion, the patient evolved well in relation to the initial complaints. The etiological investigation of pancytopenia continued, and the myeloculture of fungi and mycobacteria was negative.
Abdominal tomography showed moderate hepatosplenomegaly without nodules. Throughout his stay in the hospital, the patient showed partial clinical and laboratory improvement, but 23 days after hospitalization, he developed a febrile episode accompanied by chills and a convulsive crisis. A cranial CT showed no acute findings, and a chest CT showed a budding tree pattern and lesions with bilateral reverse halo signs. Antimicrobial therapy was initiated with piperaziline/tazobactam, which is therapeutic management for suspected pneumocystosis and pulmonary tuberculosis. Corticosteroids were also used, thus completing the vigorous therapy.
The patient was transferred to the intensive unit care and evolved to septic shock and respiratory failure, dying approximately 25 days after the onset of the condition. The patient underwent necropsy. Under gross pathology, the lungs weighed 540 g and presented a diffusely hemorrhagic appearance with consolidation spots, which corresponded to extensive areas of intra-alveolar hemorrhages observed under microscopy, foci of bronchopneumonia, bronchiolitis, and acute edema. Microscopically, the lungs presented diffuse alveolar damage in a proliferative phase, with foci of bronchopneumonia, edema, and intra alveolar hemorrhage.
Hepatosplenomegaly was observed, with the spleen measuring 15 cm and weighing 350 g, the liver was 25 cm in the largest axis and weighed 1900 g. No macroscopic alterations were observed in the liver. When cutting the spleen, numerous white nodules were noted, and these measured approximately 0.5 cm throughout the splenic surface (Figure 1A). The liver presented extensive areas of pallor that had perivascular permeation distribution in peripheral congestion areas and, under microscopy, areas of necrosis of hepatocytes in zones II and III, associated with macrovacuolar steatosis, were observed. In the peripancreatic region, numerous coalescent lymph nodes could be seen, which were concentrated by cavitation containing purulent material (Figure 1B), and microscopy portrayed extensive areas of necrosis, surrounded by a lymphohistiocytic inflammatory infiltrate with a morphological pattern that was consistent with H. capsulatum (Figure 1C). Using Grocott's method, the staining showed the presence of small, uniformly oval, narrow-based budding yeasts with eccentric acorn-like nuclei compatible with Histoplasma sp., which were also found in the liver and spleen (Figure 1D). In the latter, extensive areas of necrosis were observed, from permeation to congestion and, in the subcapsular area, the presence of red blood cells phagocytized by macrophages (Figure 1E). Others findings were hypercellularity with megakaryocytic hyperplasia in bone marrow, and edema in the brain. Data Use was approved by the Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado Ethics Review Board; CAAE 50819121.2.0000.0005.