Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 26-year-old man is evaluated for a 3-day history of fever, lower abdominal pain, tenesmus, hematochezia, and watery diarrhea. Seven months ago, he underwent a cadaveric kidney transplantation. At the time of transplantation, the transplant donor was seropositive for cytomegalovirus, and the patient was seronegative for this virus. Current medications are tacrolimus, mycophenolate mofetil, prednisone, and trimethoprim-sulfamethoxazole. Valganciclovir was discontinued 1 month ago after 6 months of prophylaxis as per standard protocol.

On physical examination, temperature is 38.8 °C (101.8 °F), blood pressure is 100/70 mm Hg, pulse rate is 104/min, and respiration rate is 18/min. BMI is 24. Cardiopulmonary examination is normal. Abdominal examination reveals increased bowel sounds but no tenderness to palpation. There is no organomegaly.

Laboratory studies:

Leukocyte count	2100/µL (2.1 × 109/L)
Alanine aminotransferase	72 units/L
Aspartate aminotransferase	60 units/L
Serum creatinine	1.4 mg/dL (124 µmol/L)

Chest radiograph is normal.

Which of the following is the most likely diagnosis?

A: Clostridium difficile infection
B: Cytomegalovirus infection
C: Mycophenolate mofetil toxicity
D: Tacrolimus toxicity

MKSAP Answer and Critique

The correct answer is B: Cytomegalovirus infection. This item is available to MKSAP 16 subscribers as item 10 in the Nephrology section.

The most likely diagnosis is cytomegalovirus (CMV) infection. Despite advances in immunosuppressive therapy and infection prophylaxis, more than 50% of kidney transplant recipients develop at least one infection during the first year after transplantation. CMV infection is particularly common in these patients. CMV infection is often suspected when patients have leukopenia and fevers during the posttransplant period. Viremia is best detected by polymerase chain reaction (PCR), a fast, sensitive, and reliable technique compared with serology, culture, or early antigen or CMV antigenemia detection. CMV infection can result in CMV disease, with organ involvement manifesting as retinitis, pneumonia, encephalitis, hepatitis, and gastrointestinal tract ulceration.

This patient underwent kidney transplantation 7 months ago and discontinued his CMV prophylaxis therapy 1 month ago as per standard protocol. Kidney transplantation from a donor who is seropositive for CMV to a recipient who is seronegative for this virus places the recipient at high risk for developing this condition. Furthermore, this patient’s fever, leukopenia, and diarrhea are consistent with CMV infection, and his elevated liver chemistry studies raise suspicion for CMV-related hepatitis. Diagnosis of CMV infection is confirmed with a positive serum PCR test for viremia, and disease is confirmed by the presence of mucosal ulcers or erosion and CMV inclusion bodies seen on a biopsy specimen from the wall of the bowel obtained during colonoscopy.

Clostridium difficile infection may cause diarrhea and fever but does not explain this patient’s leukopenia or elevated aminotransferase levels.

Mycophenolate mofetil can cause diarrhea and leukopenia but is rarely associated with elevated liver chemistry studies and does not explain this patient’s fever. In addition, toxicity associated with mycophenolate mofetil usually occurs after a recent dosage change.

Tacrolimus toxicity can cause diarrhea but does not manifest as fever, leukopenia, or abnormal findings on liver chemistry studies.

Key Point

• Cytomegalovirus infection is particularly common in kidney transplant recipients and may manifest as fever, leukopenia, and diarrhea.

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