Fatal Complication of Recent Liver Transplant.

A 62-year-old man with alcoholic cirrhosis and hepatocellular carcinoma underwent an uneventful liver transplant. The donor was a 19-year-old man: zero-antigen HLA match, lymphocyte crossmatch negative, and donor/recipient cytomegalovirus (CMV) seronegative. Induction immunosuppression was basiliximab; maintenance was tacrolimus and mycophenolate mofetil (MMF). He was discharged to home on postoperation day (POD) 8 and was seen on a routine follow-up clinic visit within a week. His only complaint was acute-onset diarrhea within 24 h of presentation. Stool cultures returned negative. On POD 19, he presented to the emergency department with worsening diarrhea and 102°F temperature. Blood cultures, bacterial stool cultures, Clostridium difficile polymerase chain reaction (PCR) and stool parasite antigen screen were negative. Plasma Epstein–Barr virus (EBV)- and CMV-PCR were undetectable. The diarrhea resolved without therapy; however, on POD 22, he became leukopenic (1 K/μL), prompting discontinuation of MMF and trimethoprim–sulfamethoxazole. He received three doses of filgrastim with improvement in leukopenia (2.7 K/μL) and was discharged to home on tacrolimus monotherapy. He was readmitted on POD 27 with recurrent diarrhea, syncope, fever, worsening leukopenia, and new-onset rash (Figure 1). Repeat blood cultures, bacterial stool cultures, Clostridium difficile PCR, stool parasite antigen screen, EBV- and CMV-PCR were negative. After a skin biopsy (Figure 2), appropriate therapy was initiated with resolution of the rash and diarrhea, but the patient had persistent pancytopenia, prompting a bone marrow biopsy (Figure 3). On POD 47, the patient developed acute respiratory distress; he refused intubation and subsequently died. Postmortem analysis demonstrated small intestinal invasive candidiasis; no fungal elements or infection was noted in the lungs.Figure 2Skin biopsy. Hematoxylin and eosin stain demonstrating mild interface dermatitis with a necrotic keratinocyte (arrow).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Bone marrow biopsy demonstrating aplasia. Gomori’s methenamine silver stain was performed and was negative for fungal elements (image not shown).View Large Image Figure ViewerDownload Hi-res image Download (PPT) 1.Which of the following is the most likely diagnosis in this patient?a.Cytomegalovirus infectionb.Clostridium difficile colitisc.Graft-versus-host disease (GVHD)d.Ehrlichiosis2.What would be most helpful in the work-up of this patient?a.CT chestb.CT abdomen and pelvis to establish infectious sourcec.Biopsies of the GI tract and/or skin rashd.Repeat stool cultures3.What histologic findings on skin biopsy would establish the diagnosis?a.Interface dermatitis with the presence of four necrotic keratinocytes in the epidermis/mm of biopsy diameterb.Inflammatory changes with viral inclusions having a distinct “owl’s eye” appearancec.Mixed perivascular inflammatory infiltrate with subepidermal sloughing and necrotic keratinocyted.Multinucleated giant cells with nuclei of infected cells demonstrating “steel-gray” changes and nuclear molding4.What tests would you obtain to confirm the diagnosis?a.Repeat blood culturesb.Chimeric studies on tissue biopsy and/or whole bloodc.CT–PET scand.MRI abdomen5.How would you treat this patient?a.Ganciclovir and maintenance immunosuppressionb.Intravenous metronidazole and oral vancomycinc.Cefepime and antimicrobial prophylaxisd.Steroids, TNF-α inhibitor, immunosuppression, and antimicrobial prophylaxis