Mono vs Lyme Disease: How to Tell the Difference
MONO OR LYME?
WHY SYMPTOMS OVERLAP
AND DIAGNOSIS MAY BE MISSED
Mono vs Lyme disease can be difficult to distinguish because both cause fatigue, fever, and sore throat—leading to missed or delayed diagnosis.
Key difference: Mono is caused by a virus, while Lyme disease is a bacterial infection that may require antibiotic treatment.
In some cases, patients may have both infections at the same time, which can complicate diagnosis and delay treatment.
Understanding the differences—and when to test for both—is critical, especially in areas where Lyme disease is common.
Mono vs Lyme Disease: Why They Are Confused
Mononucleosis (often caused by Epstein-Barr virus) and Lyme disease frequently present with overlapping symptoms:
- Fatigue
- Fever
- Sore throat
- Muscle and joint pain
- Headache
This overlap can lead to misdiagnosis, particularly when only one condition is considered.
Learn more in the Lyme disease symptoms guide.
Can You Have Mono and Lyme Disease at the Same Time?
Yes—patients can have both mono and Lyme disease simultaneously.
Koester and colleagues described cases where children were diagnosed with both conditions, highlighting how one diagnosis may overshadow the other.
In one case, a child tested positive for mono, leading clinicians to dismiss a positive Lyme test as a false positive. However, the child later developed multiple erythema migrans rashes, confirming Lyme disease.
This delay in recognizing Lyme disease could have led to worse outcomes without appropriate treatment.
Key Differences Between Mono and Lyme Disease
- Mono: Often includes sore throat, swollen lymph nodes, and splenomegaly
- Lyme disease: May include joint pain, neurologic symptoms, or erythema migrans rash
- Mono: Caused by Epstein-Barr virus (viral infection)
- Lyme disease: Caused by Borrelia burgdorferi (bacterial infection)
Despite these differences, early symptoms may look nearly identical.
Why Lyme Disease May Be Missed When Mono Is Diagnosed
A diagnosis of mono may lead clinicians to overlook Lyme disease, particularly if Lyme test results are unclear or dismissed.
In the reported cases, positive IgM Western blot results were initially considered false positives.
However, follow-up findings confirmed Lyme disease, emphasizing the importance of not dismissing early test results.
Learn more about Lyme test accuracy.
Why Testing for Both Conditions Matters
Testing for both mono and Lyme disease may be important in patients with persistent or unexplained symptoms.
Failure to recognize co-infection or overlapping conditions may delay treatment and prolong illness.
This is particularly relevant in Lyme-endemic regions.
Some patients with overlapping symptoms may also develop ongoing issues, as seen in persistent Lyme disease symptoms.
What Should You Do If Symptoms Overlap?
Patients with symptoms consistent with both mono and Lyme disease may benefit from evaluation for both conditions, particularly in endemic areas.
Careful clinical assessment and appropriate testing can help avoid delays in diagnosis and treatment.
Clinical Perspective
Mono vs Lyme disease is not always a simple distinction.
Clinicians may consider evaluating for both conditions when symptoms overlap or when recovery does not follow the expected course.
In some cases, treating Lyme disease appropriately leads to rapid improvement—even when mono is also present.
Clinical Takeaway
Mono vs Lyme disease should be considered together when symptoms overlap, as misdiagnosis may delay appropriate treatment.
Recognizing when both conditions may coexist can improve outcomes and reduce prolonged illness.
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.