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

Case Report

A 55-year-old white woman with a history of inflammatory bowel disease presented to an outside hospital with shortness of breath and diffuse bilateral infiltrates on chest x-ray 11 days after receiving a single 450-mg dose of infliximab. Her current medical regimen included prednisone 30 mg twice daily for 3 months and azathioprine 50 mg daily for 4 weeks. The patient had a 25- to 30-year history of inflammatory bowel disease, initially diagnosed as ulcerative colitis, and had undergone total abdominoperineal proctocolectomy with an ileostomy 25 years prior. She also had 2 prior ileostomy revisions due to recurrent stoma breakdown and peristomal bleeding. Biopsies of the distal 5-10 cm of ileum later revealed histopathologic changes consistent with Crohn's disease. She was recently diagnosed with pyoderma gangrenosum affecting the ileostomy site. In order to avoid repeat stomal revision or relocation, infliximab was administered. The patient had acquired hepatitis C virus presumably from a blood transfusion in the early 1980s. She had developed cirrhosis and was treated with interferon and ribavirin 5 years previously. She had also undergone a transjugular intrahepatic portosystemic shunt (TIPS) procedure 10 years prior and was currently undergoing liver transplant evaluation, with a model end-stage liver disease (MELD) score[5] of 15 (United Network for Organ Sharing [UNOS]). Child class[6] status was unknown.

At the time of admission, her azathioprine was discontinued; methylprednisolone was increased to 40 mg twice daily; and intravenous antibiotics were started. Shortly after admission, her respiratory status deteriorated and she was placed on full mechanical ventilatory support. On hospital day 3, a sputum culture test revealed Candida species, and the patient was started on intravenous fluconazole. She had persistent low-grade fevers. Serial chest x-ray results showed modest improvement; however, attempts to wean the patient from ventilatory support were unsuccessful, and the patient remained in critical condition. Repeat sputum culture tests revealed light growth of Aspergillus species on 2 occasions, and intravenous amphotericin B was started. Sputum culture tests for mycobacteria were negative. Multiple blood culture tests were negative.

On hospital day 23, the patient was transferred to our facility at which time her white blood cell count was 9.8 K/mcL with a marked left shift (50% bands and 41% segmented neutrophils). Her ileostomy site was draining brown fluid that was guaiac-positive. Intravenous voriconazole was started. An electrocardiogram showed diffuse ST elevation and PR interval depression suggestive of pericarditis. Troponin I testing revealed markedly elevated levels (peak, 34.2 ng/mL). A 2-dimensional transthoracic echocardiogram did not reveal any significant pericardial effusion, evidence of myocardial abscesses, or wall motion abnormalities to suggest an acute myocardial infarction, and her left ventricular ejection fraction was within normal range. A portable bedside chest x-ray revealed right greater than left mixed but predominantly alveolar opacities without any large pleural effusion, discrete mass, or nodules (Figure 1). Pulmonary ventilation pressures were markedly elevated (peak airway pressure, 55 cm H20; plateau pressure, 50 cm H20) with a peak flow of 93. The patient progressed to coma (Glasgow Coma Score, 8). An unenhanced cranial computed tomographic (CT) scan showed a low-density nonhemorrhagic, noncalcified mass in the subcortical left frontal lobe and an ill-defined area of diminished density in the left cerebellum and ipsilateral cerebellar peduncle that was suggestive of ischemic injury (Figure 2). Despite intensive medical therapy and ventilatory support, she progressed to multiorgan failure. Therapy was withdrawn on hospital day 24, and the patient died.

Portable chest x-ray demonstrates right greater than left mixed but predominantly alveolar opacities without detectable cavitation or large layering pleural effusion.

Unenhanced cranial computed tomographic scan reveals a low-density nonhemorrhagic mass in the subcortical aspect of the left frontal lobe with little discernible mass effect and no midline shift. Other slices (not shown) showed several vaguely defined lesions within the cerebellum.


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