Fever of Unknown Origin in a Kidney Transplant Recipient

Abstract

A 27-year-old African-American man presented with fever for two days and diarrhea for five days. He had end-stage renal disease due to chronic glomerulonephritis and was 18 months post-deceased donor kidney transplant. He received induction therapy with rabbit anti-thymocyte globulin, and his maintenance immunosuppression consisted of mycophenolate mofetil (MMF), tacrolimus (FK) and prednisone at 500 mg twice a day, 3 mg twice a day, and 7.5 mg once a day, respectively. His FK levels ranged from 6-9 ng/ml in the previous six months. His posttransplant course was complicated by mild acute cellular rejection one week posttransplant treated with pulse steroid therapy. He also had cytomegalovirus (CMV) viremia one year posttransplant, at a low level of 600 copies/ml of blood that disappeared with reduction in MMF dose. He also had a prior living related renal transplant that failed after four years due to chronic rejection. He had lived all his life in Cleveland, OH, and was living with his girlfriend. He denied recent travel out of the state of Ohio. His other medications included sulfamethoxazole-trimethoprim. On review of systems, he admitted to having dry cough that resolved spontaneously within a couple of days. On exam, he appeared to be in mild distress. His chest exam was unremarkable, and his abdominal exam did not reveal any tenderness over the allograft. He did not have any peripheral lymphadenopathy. His white blood cell count on admission was mildly decreased at 4000/mm3, with lymphopenia and normal neutrophil count. A chest X-ray on admission was unremarkable. Blood and urine cultures, CMV quantitative PCR in plasma, ultrasound examination of the transplant kidney, upper gastrointestinal endoscopy, and a CT scan of the abdomen and pelvis were unrevealing. Diarrhea resolved within one day of conversion of MMF to azathioprine, and was followed by constipation. We presumed it was from MMF toxicity. The patient remained febrile for at least 7 days after hospitalization. Empiric antibiotics were begun, including ciprofloxacin, metronidazole, and ganciclovir. Three weeks after initial presentation, a PET/CT scan of the chest was performed to evaluate for any lymphoproliferative disorders. It revealed ground-glass bilateral infiltrates and mediastinal lymphadenopathy (Figure 1 and Figure 2). Flexible bronchoscopy was performed, and the pathology of mediastinal lymph node aspirate is shown in Figure 3.Figure 2PET scan showing FDG-avid areas of activity in both lungs and mediastinal lymph nodes. FDG, fluorodeoxyglucoseView Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Small granular structures in the macrophages of the lymph node (Quick-Diff stain).View Large Image Figure ViewerDownload Hi-res image Download (PPT) 1.The term fever of unknown origin (FUO) in transplant patients should be used only for prolonged fevers with no obvious cause after three consecutive outpatient visits or after three days of hospital evaluation, provided that commonly used imaging and microbiologic tests are reported negative by that time. What is the most likely cause of FUO in our case?a.CMV pneumoniab.Tuberculosis pneumoniac.Posttransplant lymphoproliferative disorderd.Histoplasma pneumoniae.Lung cancer2.Based on Figure 3, what would be the most appropriate special stain to identify the organism?a.Acid-fast stainb.Brown–Hopps gram stainc.Grocott’s methenamine silver staind.Warthin–Starry staine.Dieterle method3.Which of the following features of the patient is NOT a risk factor for development of opportunistic infectious pneumonia?a.Episode of rejectionb.CMV viremiac.T cell depletion inductiond.Young age4.The fi ndings of fluorodeoxyglucose (FDG)-avid mediastinal lymphadenopathy in Figure 1 would NOT be seen in:a.Lung cancerb.Mycobacterium tuberculosis infectionc.Histoplasma infectiond.Posttransplant lymphomae.Drug fever5.Which of the following diagnostic tests has the highest sensitivity for the diagnosis of disseminated histoplasmosis?a.Histopathologyb.Culturec.Serum Histoplasma antigend.Serum Histoplasma antibody6.Which of the following is the best initial choice of treatment for disseminated histoplasmosis?a.Amphotericin Bb.Fluconazolec.Ketoconazoled.Itraconazole