Mono and Lyme Disease Can Occur Together
Patients can have both mono and Lyme disease at the same time, and misdiagnosis can delay appropriate treatment.
These conditions are often viewed as separate illnesses, with reports suggesting that each can mimic the other. However, a study by Koester and colleagues describes cases where Lyme disease and Epstein-Barr virus (EBV), the cause of mononucleosis, occurred concurrently.
“We describe the clinical presentation of two children with confirmed early Lyme disease and features suggestive of infectious mononucleosis,” writes Koester.
Case 1: Lyme Disease Mistaken for Mono
A 5-year-old boy presented with abdominal pain, fever, fatigue, sore throat, and neck pain. Initial testing revealed a positive heterophile antibody test, leading clinicians to suspect mono.
His positive Lyme IgM immunoblot was dismissed as cross-reactivity. However, two days later, he returned with multiple erythema migrans lesions consistent with early disseminated Lyme disease.
After treatment with amoxicillin, his symptoms resolved rapidly.
This case highlights a key risk: clinicians may dismiss Lyme disease when mono is suspected, especially given known cross-reactivity between EBV and Lyme serologic testing.
Case 2: Mono Overlapping with Lyme Disease
An 8-year-old boy developed fever, sore throat, abdominal pain, and joint symptoms. He was initially diagnosed with Lyme disease based on positive serology.
When symptoms persisted, further evaluation revealed findings consistent with mono, including lymphadenopathy, splenomegaly, and positive EBV antibodies.
Repeat Lyme testing confirmed seroconversion. After completing antibiotic therapy, the patient made a full recovery.
Mono and Lyme Disease Co-Infection: What Clinicians Should Know
Koester and colleagues identified 52 patients with laboratory evidence of both Lyme disease and EBV infection within a short time frame.
Key takeaway: mono testing should not be used to rule out Lyme disease.
Cross-reactivity can lead to false assumptions, delaying diagnosis and treatment. In some cases, patients may truly have both infections simultaneously.
Failure to recognize Lyme disease in this setting can lead to complications, including carditis or neurologic involvement.
Clinical Perspective
Patients presenting with overlapping symptoms—fatigue, fever, sore throat, and joint pain—require careful evaluation.
In Lyme-endemic areas, clinicians should avoid assuming a single diagnosis when multiple infections are possible.
Mono and Lyme disease can coexist. Recognizing this overlap can prevent delays in treatment and improve outcomes.
Related Reading
References
- Koester TM, Meece JK, Fritsche TR, Frost HM. Infectious Mononucleosis and Lyme Disease as Confounding Diagnoses. 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
Bonnie Bennett had some interesting historical remarks about borreliae /ebv testing in her book “Tick Bites & MS…”
also referenced, although regarding viruses more generally in her correspondence with Burgdorfer,
https://contentdm.uvu.edu/cdm/singleitem/collection/Burgdorfer/id/47/rec/51
I’ve had EBV twice, the first time resulted in insomnia of the worst kind, the 2nd time it resulted in the worst CFS like I was in a coma. I’ve never had any Dr even offer help. I struggle through treating myself with illegal stimulants which is far from ideal but without it I would be bedbound once again. I wish someone cared and offered help.
Some patients in my practice thought to have EBV were diagnosed with Lyme disease.
I think this might be my issue. My son was diagnosed with mono about 1 month agobut has since moved out. I started feeling flu like symptoms, vision changes as well as neck pain and then found a tick on the back of my head about 3 weeks ago. Had test results reactive to 4 bands that made lyme dusease equivocal. I am being treated with antibiotics but was not tested for mono. No soar throat but swollen glands and lymphnodes. Mental fog as well and achy all over. Feel horrible.
Hi Dr.Cameron,
I had Lymes disease and mono at the same time as a freshman college. About a year later I had mono again, followed by chronic tonsilitis. I ended up having a tonsillectomy and my health seemed to improve dramatically. However, I recently went to the doctor (less than a year since my tonsillectomy) and they say I have mono again. I’m wondering if the Lymes disease & mono combo just wrecked my immune system. Do you have any medical centers or doctors you recommend that I see? Since I’ve been in college I haven’t been consistently seeing the same doctor, which hasn’t helped.
I find Mono and Lyme disease look alike in my patients. I look a second time at Lyme disease. I also look for other illnesses. I would check with services like Global Lyme Alliance, Lyme disease association and ILADS.
Hi Dr. Cameron,
I had EBV 3 times since 2014. Last April of 2019, I had EBV and Lyme disease concurrently. Treated for Lyme disease for the first time. I got better after 2 months. Yet, in November 2019, my symptoms came back again. Never thought I had both diseases again! Yet, I am just diagnosed with EBV and Lyme disease concurrently again! Extreme fatigue with cardiac symptoms (palpation upon any physical activity). I am just hoping there is some doctor nearby who can truly listen and treat accordingly. Dr. Cameron, do you have any doctor to recommend? I live in Maryland. Is there any support group for people suffering like me? I’d appreciate your help.
You could contact a support group or request assistance from the Global Lyme Alliance, ILADS, or Lyme Disease Association. You can also call my office in New York.