Letters to the Editor  |   November 2004
Common Problems With Uncommon Presentations
Author Affiliations
  • John R. Manzella, DO, FACOI, FACOP
    Jim Thorpe, Pennsylvania
Article Information
Ophthalmology and Otolaryngology / Pediatrics
Letters to the Editor   |   November 2004
Common Problems With Uncommon Presentations
The Journal of the American Osteopathic Association, November 2004, Vol. 104, 455-456. doi:
The Journal of the American Osteopathic Association, November 2004, Vol. 104, 455-456. doi:
To the Editor:  
As clinical director of the Eastcentral PA Allied Health Education Center, Lehighton, Pa, I have had the opportunity to provide rural rotations for medical students and residents in a rural primary care setting. Diseases present differently at different ages. As a board-certified physician in both internal medicine and pediatrics, I would like to submit a series of educational papers in a board-style format to help educate our future clinicians. 
Background: The purpose of this series is to present a classic case in a board-style examination question format. The scenarios will then be changed to test the clinician's ability to discern differences between common problems in not-so-common age groups. Study Objective: To increase student and physician awareness of clinical presentations based on the age of the patients in question. 
Method: A variety of cases sampled from a private internal medicine and pediatric practice in rural Pennsylvania, as well as multiple morning reports, grand rounds and teaching rounds at the Children's Hospital of New Jersey at Newark Beth Israel Medical Center and St Michael's Medical Center, both located in Newark, New Jersey. 
  1. A 16-year-old girl is seen with fatigue, fever, pharyngitis, and lymphadenopathy. All of the following are consistent with a diagnosis of acute infectious mononucleosis in an adolescent except:
    • elevated liver enzymes
    • mild leukocytosis with lymphocytes
    • heterophile antibody test positive within 24 and 72 hours
    • positive EBV IgM test result
    • Monospot test negative within 24 and 72 hours
  2. A 4-year-old boy is seen with fatigue, fever, pharyngitis, and lymphadenopathy. All of the following are consistent with the diagnosis of acute infectious mononucleosis in a child, except:
    • negative heterophile antibody test
    • negative EBV IgM test result
    • splenomegaly
    • thrombocytopenia
    • chest x-ray film positive for interstitial infiltrates
  3. A 41-year-old man is seen with fatigue, fever, pharyngitis, and lymphadenopathy. All of the following are consistent with a diagnosis of acute infectious mononucleosis in an adult, except:
    • jaundice
    • microcytic anemia
    • atypical lymphocytes on peripheral smear
    • Guillain-Barré syndrome
    • encephalitis
Infectious mononucleosis is popular at all levels of testing. Adolescents and young adults are the most commonly infected age groups, but adults and children may be infected by the Epstein-Barr virus (EBV), a member of the Herpesviridae family that accounts for 90% of infectious mononucleosis cases. Physicians may consider other causes of infectious mononucleosis (eg, cytomegalovirus, adenovirus, toxoplasmosis) in patients with persistently EBV-negative titers. This syndrome may be seen in all age groups. 
Question 1 is the classic case students and interns will encounter on part 2 and part 3 of the board examinations. Liver enzymes often rise to between two and three times normal levels and return to baseline within 1 month. When such a patient undergoes a complete blood cell count, a mild leukocytosis with a relative lymphocytosis is the classic finding. The EBV IgM test is positive within a short time after acute exposure. The EBV IgG titers will persist for life and have little clinical value in the acute setting. 
The correct answer to question 1 is “c.” Heterophil antibodies will often be negative within the first week of infection, warranting repeating the test in 1 or 2 weeks to confirm the diagnosis. 
Examination pearl: A negative mononucleosis spot test (Monospot) result does not rule out infectious mononucleosis. Know your time lines! 
Question 2 tests students' and interns' ability to discern laboratory values in the young child. In adolescents and adults, results of the heterophile antibody test, or mononucleosis spot test (Monospot) are nearly always positive after 1 week, whereas in children younger than 5 years, results are rarely positive. 
The correct answer is “b.” If necessary for confirmation of disease presence (ie, elevated liver enzymes of unknown etiology), the EBV-IgM (and/or CMV-IgM) test is the “gold standard.” “Mono” in any age group is a great masquerader and may present with a variety of chest x-ray findings including interstitial infiltrates. Thrombocytopenia is often found along with a lymphocytosis on a complete blood cell count. Examination pearl: The results of the monospot are usually negative in young children. 
Question 3 demonstrates that adults may suffer from acute infectious mononucleosis. The patient generally has jaundice, intense headaches (possibly even encephalitis), as well as myriad other systemic complaints. Board examinations focus heavily on central nervous system pathology, such as Guillain-Barré syndrome. Results of the mononucleosis spot test (Monospot) are usually positive, with atypical lymphocytes present on a peripheral blood smear. 
The correct answer to question 3 is “b.” Hemolytic anemia may be present with infectious mononucleosis but never in a patient with microcytic anemia in the acute setting. Microcytic anemias are usually found with iron deficiency, lead exposure, sideroblastosis, and chronic disease. Examination pearl: In adults with jaundice and no signs of sepsis, hepatitis, or malignancy, think of infectious mononucleosis. 
Cohen JI. Epstein-Barr virus infection. N Engl J Med. 2000;343:481-492.
Cohen JL. Epstein-Barr virus and the immune system. Hide and seek. JAMA. 1997;278:510-513.
Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL, eds. Harrison's Principles of Internal Medicine. 13th ed. New York, NY: McGraw-Hill, Inc Health Professions Division;1995 .
Nelson WE, Behrman RE, Kliegman R, Arvin AM. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders;1996 .
Outlines in Clinical Medicine on Physicians” Online; Epstein-Barr Virus, pages 1-6. Updated on May 19, 2003.