Disseminated Aspergillosis Following Infliximab Therapy in an Immunosuppressed Patient With Crohn's Disease and Chronic Hepatitis C: A Case Study and Review of the Literature

Joel W. Alderson, DO; Thomas G. Van Dinter, Jr., MD; Michael J. Opatowsky, MD; Elizabeth C. Burton, MD


September 21, 2005

Methods and Results

Organ and central nervous system tissues were formalin-fixed and paraffin-embedded. Postmortem heart blood was obtained for aerobic and anaerobic cultures, and fresh lung tissue was obtained for bacterial, mycobacterial, fungal, and viral cultures. Histologic sections were stained with hematoxylin and eosin and selected sections with Grocott's methenamine silver or cytomegalovirus immunohistochemical stains.

Postmortem external examination revealed an intact infected stoma (Figure 3). Internal examination was significant for a surgically absent large bowel and an 8-in segment of incarcerated small bowel (Figure 3) within a ventral hernia just distal to the stoma. A small, perforated fungal ulcer and transmural necrosis were found in this segment of small bowel, and there was evidence of fecal peritonitis. Multiple gray and tan, plaquelike lesions were present on the pleural surfaces and tracheal and bronchial mucosa that histologically contained acute inflammation and multiple fungal septate hyphae with dichotomous 45° angle branching. Multiple abscesses were present in the lungs and heart (Figure 3). Histologic sections from both lungs revealed necrotizing fungal pneumonia), multiple abscesses, infarcts, and vascular invasion with fungal hyphae (Figure 4). Postmortem lung tissue cultures were positive for Aspergillus fumigatus. There was also evidence of cytomegalovirus pneumonia, which was confirmed by immunohistochemical stains and postmortem culture. Histologic examination of the heart found fungal pancarditis with multiple abscesses involving the pericardium, epicardium, myocardium, and endocardium. Both kidneys contained multiple, predominantly cortical fungal abscesses, and microscopically Aspergillus was seen within the interstitium and invading the glomeruli and blood vessel walls. Multiple brain abscesses were also present involving the cerebral cortex (Figure 4) and cerebellum. There was acute fungal leptomeningitis with vascular invasion and mycotic thrombi (Figure 4). The liver was cirrhotic with an intact, patent metal vascular stent, and there was evidence of pancreatitis. Microscopic examination of other organs, including the stomach, pituitary gland, and thyroid gland, also found fungal microabscesses.

(A) Macroscopic images of the ileostomy stoma site. (B) Portion of small bowel with perforation and serosal exudates. (C) Right lung cavitary abscess and multiple miliary-type abscesses. (D) Heart with multiple epicardial abscesses.

(A) Hematoxylin- and eosin-stained microscopic section demonstrates necrotizing fungal pneumonia. (B) Aspergillus fungal hyphae within the right lung. (C) Grocott's methenamine silver-stained section from the lung demonstrates Aspergillus fungi with septate hyphae and acute-angle branching. (D) Macroscopic image demonstrates right frontal cortex fungal abscess. (E) Microscopic section demonstrates vascular wall invasion by Aspergillus fungi and mycotic embolism within Virchow-Robin spaces of leptomeninges. Original magnification for (A) is 10x and for (B), (C), and (E) is 40x.


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