Can Mononucleosis Cause Oral Ulcers?
Yes, infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) can cause oral ulcers, though this is not a typical or common manifestation of the disease. The classic presentation involves tonsillar pharyngitis, fever, and lymphadenopathy—not true ulceration 1, 2.
Clinical Context and Frequency
The typical oral manifestations of infectious mononucleosis include:
- Tonsillar pharyngitis with exudates (not ulcers) is the hallmark oral finding 1, 2
- Sore throat occurs as a primary symptom in the classic triad 3, 1
- True oral ulcers are rarely described in the medical literature for EBV infection 4
When ulcers do occur with EBV infection, they represent an atypical presentation. One case series documented only 13 instances of genital ulceration in females attributable to EBV, highlighting how uncommon mucosal ulceration is with this virus 4.
Diagnostic Approach When Oral Ulcers Are Present
If a patient presents with oral ulcers and suspected mononucleosis:
First-line laboratory testing should include:
- Full blood count (looking for lymphocytosis with >50% lymphocytes and >10% atypical lymphocytes) 5, 2
- Heterophile antibody test (monospot test) for IM diagnosis 2
- HIV antibody and syphilis serology to exclude other viral causes 5, 6
- Fasting blood glucose 5
If monospot is negative but clinical suspicion remains:
- EBV-specific antibody profiles (viral capsid antigen antibodies) are the best choice for staging EBV infection 1, 2
For persistent ulcers beyond 2 weeks:
- Biopsy is mandatory to exclude malignancy and other serious conditions 5, 7
- Multiple biopsies if ulcers have different morphological characteristics 5
Critical Pitfalls to Avoid
- Do not assume oral ulcers are from mononucleosis without considering more common causes like recurrent aphthous stomatitis, traumatic ulceration, or herpes simplex virus 6, 8
- Do not delay biopsy beyond 2 weeks for persistent ulcers, as malignancy and serious systemic diseases must be excluded 5, 7
- Do not rely solely on clinical appearance without appropriate serologic testing when IM is suspected 2
Bottom Line for Clinical Practice
While EBV can theoretically cause oral ulcers, this is exceedingly rare. When evaluating a patient with both oral ulcers and suspected mononucleosis, consider them as potentially separate issues requiring independent diagnostic workup. The oral ulcers likely represent a different etiology (aphthous ulcers, HSV, trauma) occurring coincidentally with IM 6, 8. Proceed with standard diagnostic algorithms for both conditions rather than attributing the ulcers to EBV without strong evidence 5, 7.