A 6-year-old girl is admitted to the hospital due to a week of fever. The patient has a history of fulminant viral myocarditis for which she received a cardiac transplant 8 months ago. Viral studies prior to transplantation were negative for Epstein-Barr virus (EBV) and cytomegalovirus (CMV). She is taking maintenance immunosuppression medications. Temperature is 38.1 C (100.6 F), blood pressure is 102/74 mm Hg, pulse is 76/min, and respirations are 22/min. Heart examination reveals normal S1 and S2 with no S3 or S4 and no murmurs. Pulses are 2+ in all extremities. The lungs are clear to auscultation. There are several enlarged anterior cervical lymph nodes bilaterally. Laboratory results are as follows: Echocardiogram shows normal heart structure and function. A CT scan of the chest reveals scattered bilateral atelectasis and several highly enlarged mediastinal lymph nodes. Which of the following is the most likely cause of this patient's symptoms?

Question

A 6-year-old girl is admitted to the hospital due to a week of fever.  The patient has a history of fulminant viral myocarditis for which she received a cardiac transplant 8 months ago.  Viral studies prior to transplantation were negative for Epstein-Barr virus (EBV) and cytomegalovirus (CMV).  She is taking maintenance immunosuppression medications.  Temperature is 38.1 C (100.6 F), blood pressure is 102/74 mm Hg, pulse is 76/min, and respirations are 22/min.  Heart examination reveals normal S1 and S2 with no S3 or S4 and no murmurs.  Pulses are 2+ in all extremities.  The lungs are clear to auscultation.  There are several enlarged anterior cervical lymph nodes bilaterally.  Laboratory results are as follows:  Echocardiogram shows normal heart structure and function.  A CT scan of the chest reveals scattered bilateral atelectasis and several highly enlarged mediastinal lymph nodes.  Which of the following is the most likely cause of this patient's symptoms?

Quizplus · Accepted Answer

11ec25c8_d61b_1a7e_bc81_1f27a0f92171_MD0003_00 This patient developed a febrile illness with lymphadenopathy and leukopenia while taking immunosuppressive medications following solid-organ transplantation. Although many pathogens can cause febrile illness in the setting of immunocompromise, the presence of an elevated Epstein-Barr virus (EBV) titer suggests posttransplantation lymphoproliferative disorder (PTLD). PTLD is a plasmocytic or lymphoid proliferation that occurs in the weeks or months following solid-organ or hematopoietic stem cell transplantation. It is triggered by the use of immunosuppressive medications that impair cytotoxic T-cell immunosurveillance, which leads to the unchecked replication of oncogenic viral pathogens in transplanted donor tissue or host cells. Most cases (>95%) are caused by the reactivation of EBV, a human herpesvirus that establishes life-long latent infection in B and T lymphocytes following initial infection. EBV is an oncogenic virus because it produces proteins (eg, latent membrane protein) that lead to B-cell proliferation and generates prosurvival nuclear transcription factors (EBNA) that lead to B-cell immortalization. Subsequent cell spread through the reticuloendothelial system results in lymphadenopathy, hepatosplenomegaly, bone marrow infiltration (eg, leukopenia, anemia), and/or B-symptoms. Diagnosis is often suspected due to a markedly elevated EBV titer, but biopsy may be required for confirmation. (Choice A) Graft versus host disease occurs in patients who undergo hematopoietic stem cell transplantation, not solid-organ transplantation. It occurs when donor cells attack host tissue because they do not recognize the human leukocyte antigens on the host cell surface. Patients often develop skin, biliary tract, and gastrointestinal disease. Lymphadenopathy is not typical. (Choice B) Pneumocystis pneumonia is common in patients with deficits in cell-mediated immunity due to immunosuppressive medications. Patients typically have progressive respiratory failure with bilateral reticulonodular pulmonary infiltrates and profound hypoxia. Although lactate dehydrogenase levels are often elevated, lymphadenopathy is not common. (Choice D) Viral myocarditis often causes chest pain, arrhythmia, or heart failure; a second episode of viral myocarditis is uncommon, may cause heart abnormalities (eg, wall dysfunction, pericardial effusion) that could be identified on echocardiogram, and is unlikely to explain cervical and mediastinal lymphadenopathy. (Choice E) Heart transplant rejection is generally marked by significant echocardiogram abnormalities (eg, reduced left ventricular ejection); lymphadenopathy is atypical. Educational objective: Posttransplantation lymphoproliferative disorder is a plasmocytic or lymphoid proliferation that occurs in those on high-dose immunosuppressive medications following transplantation. Most cases are due to Epstein-Barr virus (EBV) and are marked by reticuloendothelial manifestations (eg, lymphadenopathy, hepatosplenomegaly, cytopenias) and elevated EBV titers.

A 6-Year-Old Girl Is Admitted to the Hospital Due to a Week