Causes of a Positive Heterophile Mono Screen
The primary cause of a positive heterophile mono screen is acute Epstein-Barr virus (EBV) infection, which is the most common etiology of infectious mononucleosis. 1
Primary Cause
- Epstein-Barr virus (EBV) infection is the predominant cause of a positive heterophile antibody test, with heterophile antibodies typically appearing between the sixth and tenth day following symptom onset 1
- These heterophile antibodies peak during the second or third week of illness and may persist for a year or longer 1
False Positive Causes
Several conditions can cause false-positive heterophile antibody test results:
- Leukemia 1
- Pancreatic carcinoma 1
- Viral hepatitis 1
- Cytomegalovirus (CMV) infection 1
- Other conditions with activated immune systems 1
False Negative Results
- False-negative results occur in approximately 10% of patients with EBV infection 1
- Children younger than 10 years of age are especially prone to false-negative results 1
- False-negative results are relatively common early in the course of infection (first week) 2
Diagnostic Considerations
When heterophile antibody tests are negative but clinical suspicion for mononucleosis remains high:
- Consider other infections that can cause mononucleosis-like illness: CMV, adenovirus, HIV, Toxoplasma gondii 1
- EBV-specific antibody testing is recommended, including IgG and IgM to viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA) 1
- The presence of VCA IgM (with or without VCA IgG) antibodies in the absence of EBNA antibodies indicates recent primary EBV infection 1
- EBNA antibodies typically develop 1-2 months after primary infection and indicate past infection 1
Clinical Context
- A positive heterophile test in the appropriate clinical context (fever, pharyngitis, lymphadenopathy) has 71-90% accuracy for diagnosing infectious mononucleosis 3
- Atypical lymphocytosis of at least 10% plus lymphocytosis of at least 50% strongly supports the diagnosis of infectious mononucleosis 2
- Infectious mononucleosis is most common in adolescents and young adults aged 15-24 years 4
Clinical Pitfalls to Avoid
- Don't rely solely on heterophile antibody testing in children under 10 years of age due to high false-negative rates 1
- Don't dismiss the possibility of EBV infection with a negative heterophile test in the first week of illness 2
- Don't forget to consider other causes of mononucleosis-like illness when heterophile tests are negative 1
- Don't overlook the need for EBV-specific serologic testing when clinical suspicion is high but heterophile testing is negative 1