Infections in Oncology: Fulminant Hepatic Failure Due to Disseminated Adenovirus Infection in a Patient With Chronic Lymphocytic Leukemia

Eric B. Haura, MD, Mark A.Winden, PA, Alan D. Proia, MD, PhD, and James F. Trotter, MD

Disclosures

Cancer Control. 2002;9(3) 

In This Article

Case Report

A 56-year-old man developed pneumonia in 1996 and was treated with antibiotics. He was noted to be hypogammaglobulinemic, and intravenous immunoglobulin (Ig) was prescribed. During his first infusion in 1996, he had an unspecified reaction and no further administrations were given. In March 1998, he presented with recurrent pneumonia and was diagnosed with CLL by peripheral blood immunophenotyping. A chest radiograph showed bilateral infiltrates, and a computed tomography scan of the chest demonstrated bilateral air space disease with periaortic and mesenteric lymphadenopathy. Sputum cultures grew Proteus mirabilis, and he was treated with intravenous antibiotics and discharged home. One month later he was readmitted for increasing dyspnea and productive cough. He was treated with intravenous antibiotics and transferred to Duke University Medical Center on April 19, 1998.

The patient was from West Virginia, worked as a mechanic, and had no significant chemical exposure. He was married, did not smoke, and had no significant history of alcohol intake and no risk factor for acquisition of HIV. On examination his temperature was 39.4°C, blood pressure 109/55 mm Hg, pulse 109 beats per minute, and respiratory rate 22. He was alert and oriented. He had no lymphadenopathy. His chest examination showed bibasilar rales and diffuse rhonchi. His cardiovascular examination was normal, and his abdomen was unremarkable without evidence of ascites or hepatosplenomegaly.

Laboratory studies on admission disclosed the following values: hemoglobin, 10.3 g/dL; hematocrit, 31%, white blood cell count, 2,200/mm3; 32% lymphocytes; platelet count, 167,000/mm3; lactate dehydrogenase, 544 IU/L; aspartate aminotransferase (AST), 25 IU/L; alanine aminotransferase (ALT), 40 IU/L; IgG, 74 mg/dL (normal 588-1,573); IgM, 0 mg/dL (57-237); and IgA, 21 mg/dL (46-287). A bone marrow biopsy showed hypercellular marrow and patchy involvement by small lymphocytes consistent with CLL. Approximately 50% of the lymphocytes were abnormal and stained with multiple B-cell lineage antigens as well as CD5, CD23, and lambda light chain. No granulomata were seen, and cultures for bacteria, mycobacteria, and fungi were negative. Adenovirus grew slowly from the bone marrow culture, and identification of this agent occurred 2 1/2 weeks following the patent's death.

The patient developed worsening pancytopenia over the next 72 hours. The platelet count fell to 10,000, the white blood cell count fell to 600/mm3, and hematocrit fell to 22%. He was given granulocyte colony-stimulating factor (G-CSF) and packed red blood cell transfusions. On April 24, 1998, his liver function tests became elevated, with AST 3,680 IU/L and ALT 1,320 IU/L. Hepatitis B core antibody was positive, while hepatitis C antibody, hepatitis A IgM, cytomegalovirus IgM, and HIV enzyme-linked immunosorbent assay (ELISA) were all negative. Forty-eight hours later, his AST had risen to 11,984 IU/L, the ALT was 1,961 IU/L, total bilirubin level was 6.1 mg/dL, and prothrombin time was 18.3 seconds. His chest radiograph showed normal heart, mediastinum, and hila with heterogeneous opacities in the bases as well as bilateral basilar bronchiectasis.

He was transferred to the intensive care unit because of altered mental status and hypoxia. An hepatic Doppler ultrasound showed normal hepatic parenchyma and patent hepatic and portal veins. The patient became hemodynamically unstable and required intravenous dopamine and endotracheal intubation. He developed grand mal seizures and suffered cardiopulmonary arrest. He died of multiorgan system failure on April 27, 1998.

At autopsy, cultures of the consolidated lung tissue were positive for adenovirus and cytomegalovirus. Bone marrow cultures were positive for adenovirus, serotype 4. Liver histology showed subtotal hepatic necrosis and immunostains for adenovirus were positive (Figs 1 and 2). Immunostains of the liver tissue were negative for herpes simplex virus, cytomegalovirus, hepatitis B surface, and hepatitis B core antigen. The only other site of adenoviral infection at autopsy was a cecal ulcer. Other evidence for immune dysfunction included Strongyloides stercoralis infection of the jejunum and superficially invasive candidiasis at the gastroesophageal junction. B-cell CLL involved the bone marrow, thoracic and abdominal lymph nodes, the interstitium around airways of the right and left lungs, and the submucosa of the small and large intestines.

"Smudge cell" inclusions of adenovirus are present within hepatocytes (arrows). These are intranuclear, basophilic inclusions without a halo that at times may encompass the entire cell. Separate intracytoplasmic inclusions are not present.

Immunohistochemical stain for adenovirus shows localization of viral-specific antigen in the infected hepatocyte cell (arrows).

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