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MKSAP quiz: Intermittent fever, sweats, fatigue

A 35-year-old woman is evaluated for intermittent fever, sweats, fatigue, and dull midchest pain of 2 weeks' duration. Medical history is significant for liver transplantation 6 months ago for primary biliary cirrhosis; she was seronegative for cytomegalovirus and Epstein-Barr virus, and her donor was positive for both. Results of pretransplant testing for tuberculosis were negative. Following a physical exam, lab studies, and chest radiograph, what is the most likely cause of her clinical findings?


A 35-year-old woman is evaluated for intermittent fever, sweats, fatigue, and dull midchest pain of 2 weeks' duration. Medical history is significant for liver transplantation 6 months ago for primary biliary cirrhosis; she was seronegative for cytomegalovirus and Epstein-Barr virus, and her donor was positive for both. Results of pretransplant testing for tuberculosis were negative. She received valganciclovir prophylaxis for 3 months after transplantation. Medications are tacrolimus, prednisone, mycophenolate mofetil, and trimethoprim-sulfamethoxazole.

On physical examination, temperature is 37.7 °C (99.9 °F), blood pressure is 142/88 mm Hg, pulse rate is 92/min, and respiration rate is 14/min. Oropharynx has whitish plaques on the palate and buccal mucosa. No enlarged lymph nodes are palpable. Cardiopulmonary examination is normal. Abdomen is soft and nontender without hepatosplenomegaly. Extremities are without edema. No skin lesions are noted.

Laboratory studies are significant for a leukocyte count of 5200/µL (5.2 × 109/L) and hematocrit of 33%. Liver and kidney function are normal. Bacterial and fungal blood cultures show no growth.

Chest radiograph shows clear lung fields but left hilar enlargement. Chest CT confirms an enlarged, 3-cm left hilar lymph node; the liver and spleen are unremarkable.

Which of the following is the most likely cause of her clinical findings?

A. Cytomegalovirus infection
B. Invasive candidal infection
C. Posttransplant lymphoproliferative disease
D. Reactivation tuberculosis

Reveal the Answer

MKSAP Answer and Critique

The correct answer is C. Posttransplant lymphoproliferative disease. This item is available to MKSAP 17 subscribers as item 55 in the Infectious Disease section. More information on MKSAP 17 is available online.

This patient most likely has posttransplant lymphoproliferative disease (PTLD). She is at increased risk for PTLD because she was seronegative for Epstein-Barr virus (EBV) and the organ donor was seropositive. PTLD is related to B-cell proliferation induced by infection with EBV in the setting of chronic immunosuppression and resulting decreased T-cell immune surveillance. She presents within a typical timeframe (first few months to 1 year after transplantation) with lymphadenopathy found on CT scan and systemic symptoms consistent with PTLD. In addition to PTLD, EBV after transplantation can cause a mononucleosis syndrome, leukopenia and thrombocytopenia, and hepatitis or pneumonitis. Quantitative serum polymerase chain reaction for EBV can suggest a diagnosis of PTLD, which is confirmed by biopsy and histopathologic evaluation of the swollen lymph nodes or extranodal mass. Management consists of reduction in immunosuppression, if possible, and may require chemotherapy, which often includes rituximab.

Cytomegalovirus infection is common after transplantation, especially in seronegative recipients with seropositive donors, and can manifest as a nonspecific febrile syndrome. However, cytomegalovirus would be unlikely to cause a single, significantly enlarged lymph node; this presentation makes PTLD more likely.

Although this patient has whitish plaques in her oropharynx consistent with oral thrush, and disseminated fungal infections may cause systemic symptoms such as this patient is experiencing, an invasive Candida infection would not cause her isolated lymphadenopathy and is not supported by her negative fungal blood cultures.

Tuberculosis reactivation increases in incidence after solid organ transplantation and is more likely to have extrapulmonary findings. It could present with lymphadenopathy and fever but clear lungs, as in this patient. However, she had a negative result on a test for latent tuberculosis before transplantation, which makes reactivation of tuberculosis unlikely.

Key Point

  • Patients are at high risk for posttransplant lymphoproliferative disease if they received an organ from a donor seropositive for Epstein-Barr virus when they are seronegative.