Mono vs Lyme Disease: Symptoms, Testing, and Differences
Mono and Lyme disease share overlapping symptoms
Both illnesses may occur at the same time
Diagnosis may be challenging in children
Welcome to another Inside Lyme Podcast. I am your host Dr. Daniel Cameron. I find that the best way to understand Lyme disease is through reviewing actual cases. In this episode, I review two pediatric cases involving children diagnosed with both Lyme disease and mononucleosis.
Koester and colleagues first described these cases in 2018.
Parents and clinicians often ask whether mono can be mistaken for Lyme disease or whether both infections can occur together.
Mono and Lyme disease share symptoms including fatigue, fever, sore throat, headache, muscle aches, abdominal pain, and swollen lymph nodes. Because of this overlap, diagnosis may become challenging.
Diagnostic uncertainty is discussed further in Lyme disease misdiagnosis.
Mono vs Lyme disease: What are the differences?
Mono and Lyme disease overlap considerably, but differences in rash patterns, exposure history, testing, and symptom progression may help distinguish the two conditions.
Mononucleosis is commonly caused by Epstein-Barr virus (EBV), which may further complicate evaluation when symptoms overlap with Lyme disease.
Symptoms more commonly associated with mono include sore throat, swollen lymph nodes, and splenomegaly.
Symptoms more commonly associated with Lyme disease include erythema migrans rash, neurologic symptoms, joint pain, and tick exposure history.
How are mono and Lyme disease tested?
Testing strategies differ between the two illnesses.
Mono testing often includes heterophile antibody testing or Epstein-Barr virus testing.
Lyme disease testing frequently includes enzyme immunoassay screening followed by immunoblot testing when appropriate.
Testing limitations are discussed further in Lyme test accuracy.
Case 1: Positive mono test initially overshadowed Lyme disease
A 5-year-old boy developed abdominal pain, intermittent fevers, neck pain, fatigue, and sore throat. He had no known tick bite or rash.
The physicians ordered testing for both mono and Lyme disease.
After mono testing returned positive, clinicians dismissed Lyme disease despite a positive IgM immunoblot (bands 23, 39, and 41 kDa), assuming the results represented false positive findings.
Two days later, however, the child developed multiple erythema migrans lesions consistent with early disseminated Lyme disease.
He was prescribed 14 days of amoxicillin. Within four days, symptoms improved substantially.
More on rash presentations can be found in erythema migrans rash.
Case 2: Persistent symptoms despite treatment
An 8-year-old boy developed fevers, headache, sore throat, abdominal pain, fatigue, myalgia, and joint pain. There was no history of rash or tick bite.
Initial testing for Group A Streptococcus and mononucleosis was negative.
Lyme disease testing was positive by enzyme immunoassay screening and IgM Western blot.
Despite treatment with amoxicillin, he continued having fevers and worsening abdominal and joint pain.
“Exam and abdominal ultrasound confirmed splenomegaly and lymphadenopathy, but no hepatomegaly,” the authors reported.
Repeat testing later supported both Lyme disease and mononucleosis diagnoses.
After 21 days of amoxicillin, symptoms resolved completely.
Notably, he did not develop the rash sometimes observed when amoxicillin is given during mononucleosis.
Can mono and Lyme disease occur together?
Yes. These cases suggest mono and Lyme disease may coexist.
Koester and colleagues also referenced a study in which 52 patients tested positive for both Lyme disease and mononucleosis.
Persistent symptoms after one diagnosis should not automatically exclude another explanation.
Overlap syndromes are discussed further in persistent Lyme disease symptoms.
Should a positive IgM Lyme test be dismissed?
Some clinicians remain cautious when interpreting isolated positive IgM Western blot findings.
However, these cases illustrate why positive Lyme testing should be interpreted alongside symptoms, examination findings, and exposure history rather than dismissed automatically.
Frequently Asked Questions
Can mono and Lyme disease happen at the same time?
Yes. Published pediatric cases describe patients diagnosed with both illnesses simultaneously.
Can mono be mistaken for Lyme disease?
Yes. Similar symptoms and nonspecific presentations may complicate diagnosis, particularly early in illness.
Can mono cause a false positive Lyme test?
Interpretation of testing can be challenging, which is why laboratory results are often interpreted alongside symptoms, examination findings, and exposure history.
Should a positive mono test rule out Lyme disease?
No. A positive mono test should not automatically exclude Lyme disease if symptoms remain concerning.
Clinical Takeaway
Mono and Lyme disease share enough overlapping symptoms that diagnosis may become challenging, particularly in children.
Testing for one infection should not automatically exclude the possibility of another when symptoms evolve or persist.
Children with prolonged fatigue, fever, or evolving symptoms may require broader diagnostic consideration rather than reliance on a single explanation.
Related Articles
Epstein Barr virus and Lyme disease
Why Lyme tests miss disease
Coinfections and Lyme disease
Pediatric Lyme disease
References
- Koester TM, Meece JK, Fritsche TR, Frost HM. Infectious Mononucleosis and Lyme Disease as Confounding Diagnoses: A Report of 2 Cases. Clin Med Res. 2018.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
Atteinte de la maladie de lyme depuis 2006 avec virus et bactéries que faire ?
translated from French as “Lyme disease since 2006 with viruses and bacteria what to do?” The problems of access to care for a doctor with experience treating tick borne illness can be a problem in other countries.