Critical Care Medicine-Infections and Immunologic Disease>>>>>Infections in the Immunocompromised Host
Question 4#

A 60-year-old female was admitted to the ICU with acute hypoxic respiratory failure. She endorsed malaise, fevers, and neck swelling for 2 weeks prior to presentation. She received a bilateral lung transplant [cytomegalovirus (CMV) donor negative/recipient negative, Epstein-Barr virus (EBV) donor negative/recipient positive] 4 months ago for idiopathic pulmonary fibrosis and is currently on immunosuppression with azathioprine 200 mg daily and tacrolimus 2 g twice daily. Her antimicrobial prophylaxis includes trimethoprim-sulfamethoxazole one double-strength tablet thrice weekly and itraconazole 200 mg daily. On admission, she was alert and oriented, afebrile, and hemodynamically stable. Cervical lymphadenopathy was present. Her:

Her chest x-ray showed bilateral diffuse infiltrates. Blood cultures showed no growth on culture at 24 hours of collection. Serum EBV quantitative deoxyribonucleic acid (DNA) PCR was 100 000 copies/mL (undetectable on prior measurement 1 month ago). Posttransplant lymphoproliferative disease is suspected.

What is the NEXT BEST step in the management of this patient?

A. Start treatment with rituximab
B. Reduce the current dose of immunosuppressants
C. Start treatment with rituximab and chemotherapy
D. Start treatment with acyclovir
E. Start treatment with valganciclovir

Correct Answer is B


Correct Answer: B

The EBV status and viral load in this solid organ transplant patient point toward a diagnosis of PTLD. Reduction of immunosuppression is a critical step in the management of this condition

PTLD is the most common malignancy complicating solid organ transplantation. Nine out of ten patients with PTLD have evidence of EBV infection by serologic studies or EBV viral load. PTLD occurs as a consequence of the proliferation of infected B cells in the setting of posttransplant immunosuppression. EBV serostatus and the degree of Tcell immunosuppression are the principal risk factors for the development of disease.

In general, the clinical presentation of PTLD is variable. Initially, the disease may present with a mononucleosis-like syndrome, associated with nonspecific constitutional symptoms such as fever, weight loss, and fatigue as well as peripheral lymphadenophathy. It can also present with tissue infiltrative disease or localized lymphomas. Diagnosis is confirmed by histological examination.

The treatment of PTLD must balance the goals of eradicating disease and maintaining a functional graft. Management strategies are based on the category of disease. Early lesions are managed with careful reduction of immunosuppression alone. Other therapies like rituximab are recommended in addition to the reduction of immunosuppression in patients with polymorphic PTLD (CD20+ PTLD). Rituximab alone or in combination with chemotherapy is used in patients with monomorphic PTLD, and chemotherapy with or without radiation is used in patients with classic Hodgkin lymphoma–like PTLD, which is the least common form. 


  1. Finberg RW, Fingeroth JD, Finberg RW, Fingeroth JD, Finberg RW, Fingeroth JD. Infections in transplant recipients. In: Jameson J, Fauci AS, Kasper DL, et al. eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw-Hill. aspx? bookid=2129§ionid=192020844. Accessed November 08, 2018.
  2. Straathof KCM, Savoldo B, Heslop HE, Rooney CM. Immunotherapy for post-transplant lymphoproliferative disease. Br J Haematol. 2002;118(3):728-740.
  3. Heslop HE. How I treat EBV lymphoproliferation. Blood. 2009;114(19):4002-4008.