Contributed by Arnob K. Mukherjee, MD,1 Orestes E. Solis, MD,4 Noriko Salamon, MD,2 Rupal I. Mehta, MD3
1Department of Psychiatry and Biobehavioral Sciences, 2 Department of Radiological Sciences 3 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, 4Department of Neurology and Psychiatry, University of Santo Tomas (Manila, Philippines)
CLINICAL HISTORY AND IMAGING
A 49-year-old man presented with fever and altered mental status. He had a complex prior medical history notable for type I diabetes mellitus with end-stage renal disease and peripheral vascular disease. Eight years prior to admission he underwent pancreatic and renal transplantation secondary to diabetes. The renal transplantation procedure was initially complicated by intra-operative myocardial infarction, and subsequently by acute and chronic allograft rejection. Consequently, the patient had been on long-term immunosuppressive therapy. He also suffered from chronic atrial fibrillation requiring warfarin and had undergone cardiac valve replacement one year earlier.
Upon admission for new onset of low-grade fever, chills and disorientation, the patient was noted to have positive CMV IgG titers. His screening tests were negative for toxoplasmosis, HIV and HSV. Lumbar puncture revealed elevated leukocyte count (>600 with 89% neutrophils; 1% lymphocytes; 10% monocytes). Concurrently, a chest CT showed pulmonary edema with a right pleural effusion. Brain MRI and cultures were negative. The patient was empirically treated for meningitis and possible pneumonia with multiple broad-spectrum antibiotics. However, pulmonary edema and dyspnea progressed over the course of his hospitalization, requiring increasing oxygen support.
Over the next few weeks, the patient exhibited worsening lethargy and developed a diffuse pustular rash on his extremities. Doxycycline was added to his regimen for concerns of possible rickettsial disease. Subsequent brain MRI with and without gadolinium revealed multiple small foci of abnormal enhancement scattered in the bilateral cerebral hemispheres, cerebellum and brainstem. These increased in number on serial studies (Figure 1) despite persistently negative blood, cerebrospinal fluid (CSF), and sputum cultures.
Ultimately, a large abscess developed on the patient's left calf; surgical drainage and culture recovered Gram-positive rods. Full body CT scan also revealed a pancreatic cyst which yielded Enterococcus species, coagulase negative Staphylococcus, and Candida glabrata on evacuation. Continued intensive antibiotic therapy (including trimethoprim-sulfamethoxazole and third-generation cephalosporins) and ventilator assistance were administered, but the patient's respiratory failure did not remit. Approximately two months after initial presentation, his pupils were found to be pinpoint in size and non-reactive to light, raising concern for a cerebrovascular accident. Given the patient's prognosis following these events, the family elected to withdraw life support and the patient died.
GENERAL POST-MORTEM EXAMINATION
At autopsy, the lungs were heavy and diffusely firm with prominent consolidation of the right lower and right middle lobes. Bilateral pleural effusions were noted; microscopic studies showed diffuse alveolar damage although there was no evidence of an infectious process within the heart or lungs. Hemorrhagic pancreatitis, cardiomegaly, and hepatosplenomegaly were identified. Diffusely scattered purulent micronodules were present on cut sections of hepatic parenchyma. Multiple cutaneous ulcers (0.3-3.0 cm in diameter) with tan-yellow purulent exudate were also identified on the lower extremities.
Examination of the brain showed symmetrical gyral pattern with leptomeningeal opacities overlying the bilateral frontal areas (Figure 2). The basal vasculature showed no abnormalities. There was no evidence of uncal or cerebellar tonsillar herniation. Coronal sections of the fixed cerebral hemispheres displayed sharply demarcated cortical-white matter junction. Scattered tan-yellow micronodules were seen diffusely on gross examination of the cerebral and cerebellar hemispheres, basal ganglia and brainstem (Figures 3 and 4).
On microscopic examination the disseminated nodules corresponded to granulomata composed predominantly of lymphocytes and foamy macrophages (Figures 5 and 6). Special studies with Gram, Periodic acid-Schiff, Acid-Fast, and Fite stains were all negative. However, Grocott's Methenamine Silver (GMS) stain highlighted aggregates of beaded, filamentous organisms (~1 Ám in diameter) with 90-degree branching pattern (Figures 7 and 8). Sulphur granules were not appreciated.