Infectious Mononucleosis in Middle Age

CASE PRESENTATION A previously healthy 42-year-old man developed temperatures to 38.8°C, muscle and joint aches, fatigue, and loss of appetite. Within several days, he also had diarrhea and emesis. On the fourth day of his illness, he saw his physician, who made a diagnosis of gastroenteritis. When the fever and fatigue had continued for 2 weeks, the patient went to an urgent care center. By this time, his enteric symptoms had ceased. He had no complaints of headache, sore throat, or rash. He was described as looking tired. He had a temperature of 38.2°C, blood pressure of 126/70 mm Hg, pulse of 94/ min, and respirations of 18/min. He had no icterus. His oropharynx showed no injection or exudate. The examining physician did not report lymphadenopathy and judged his liver and spleen to be of normal size. There were no other notable findings. The patient again left with a diagnosis of gastroenteritis. The next day, however, his laboratory test results came back documenting a hematocrit value of 0.37, hemoglobin level of 130 g/L, and white blood cell count of 10.0 3 10/L, with an automated differential showing 0.24 segmented neutrophils, 0.74 lymphocytes, and 0.02 monocytes. The chemistry panel showed a total bilirubin level of 29.07 μmol/L (1.71 mg/ dL), conjugated bilirubin of 17.10 μmol/L (1 mg/dL), aspartate aminotransferase of 412 U/L, alanine aminotransferase of 811 U/L, and alkaline phosphatase of 524 U/L. His renal function, cholesterol, total protein, albumin, and glucose levels were normal. Urinalysis showed bilirubin by dipstick. Blood, urine, and stool cultures were negative. A chest radiograph was interpreted as showing a possible left lower lobe infiltrate. Oral clarithromycin was prescribed, and the patient was asked to return to the center for further evaluation of his hepatitis. Test results were negative for antihepatitis A IgM, hepatitis B surface antigen, and antihepatitis C antibody (thirdgeneration test). A test for hepatitis C virus RNA by polymerase chain reaction was also negative. An antihepatitis B surface antibody test was positive, consistent with the patient’s history of immunization for hepatitis B. His past medical history is notable only for surgical repair of strabismus in childhood and correction of a deviated nasal septum. His only medication was occasional acetaminophen in an attempt to control his fever. He reported no history of significant alcohol use, no tobacco or other drug use, and no blood transfusion. He is single and heterosexual, identifying no risk factors for human immunodeficiency virus (HIV). He works at a hospital, where he has some contact with patients. He has traveled to the Caribbean, Central America, Europe, India, and Australia, but did not leave the United States during the year before his illness. There is no family history of liver disease. During his third week of illness, the patient returned to the urgent care center because of continued temperatures to 38.5°C. On physical examination, he had a temperature of 37.6°C, mild oropharyngeal erythema, and enlarged tonsils. Crackles were heard at the left lung base. The physician who saw him noted unspecified hepatomegaly but could not feel a splenic edge. Rapid mononucleosis and streptococcal screens were negative. The erythrocyte sedimentation rate was 18 mm/h. The patient continued taking clarithromycin but did not improve. More than 21 days into his illness, he made a fourth visit to the urgent care center because of persisting fevers and slight hoarseness without sore throat. His temperature was 37.7°C. His throat was again described as red with enlarged tonsils, and now was covered by a white exudate. Careful examination failed to detect significant peripheral lymphadenopathy. His breath sounds were entirely normal. His liver was felt 3 finger breadths below the costal margin; the spleen was still not palpable. Repeated tests showed a hematocrit value of 0.37, hemoglobin level of 127 g/L, and white blood cell count of 9.7 3 10/L. This time a manual differential was requested; it showed 0.35 segmented neutrophils, 0.52 lymphocytes, 0.10 atypical lymphocytes, and 0.03 monocytes. A repeat chemistry panel revealed levels of total bilirubin of 15.39 μmol/L (0.9 mg/ dL), aspartate aminotransferase of 143 U/L, alanine aminotransferase of 508 U/L, and alkaline phosphatase of 407 U/L. Mononucleosis was suspected and confirmed by a positive test result for Epstein-Barr virus (EBV) viral capsid antigen (VCA) IgM and negative test result for cytomegalovirus (CMV) IgM. After a full month, the fevers disappeared. Six weeks after his illness be-