Infectious Mononucleosis: An Updated Review
Authors: Leung Alexander K.C. , Lam Joseph M. , Barankin Benjamin 
Published: August 2023

Background:
Infectious mononucleosis is common among adolescents and young adults.
Although the majority of cases resolve spontaneously, life-threatening manifestations, and compli-
cations have been recognised.

Objective:
The purpose of this article is to familiarize clinicians with the clinical manifestations,
evaluation, diagnosis, and management of infectious mononucleosis.

Methods:
A search was conducted in October 2022 in PubMed Clinical Queries using the key terms
"infectious mononucleosis" OR “Epstein-Barr virus” OR “EBV”. The search strategy included all
clinical trials, observational studies, and reviews published within the past 10 years. Only papers
published in the English literature were included in this review. The information retrieved from the
aforementioned search was used in the compilation of the present article.

Results:
Infectious mononucleosis, caused by Epstein-Barr virus, most commonly affects adoles-
cents and adults aged 15 to 24 years. Epstein-Barr virus is transmitted primarily in saliva. Infectious
mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy. Fa-
tigue may be profound but tends to resolve within three months. Periorbital and/or palpebral edema,
typically bilateral, occurs in one-third of patients. Splenomegaly and hepatomegaly occur in approx-
imately 50% and 10% of cases, respectively. A skin rash, which is usually widely scattered, ery-
thematous, and maculopapular, occurs in approximately 10 to 45% of cases. Peripheral blood leu-
kocytosis is observed in most patients; lymphocytes make up at least 50% of the white blood cell
differential count. Atypical lymphocytes constitute more than 10% of the total lymphocyte count.
The classic test for infectious mononucleosis is the demonstration of heterophile antibodies. The monospot test is the most widely used method to detect the serum heterophile antibodies of infectious mononucleosis. When confirmation of the diagnosis of infectious mononucleosis is required in
patients with mononucleosis-like illness and a negative mono-spot test, serologic testing for anti-
bodies to viral capsid antigens is recommended. Infectious mononucleosis is a risk factor for chronic fatigue syndrome. Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious
mononucleosis and is potentially life-threatening. Treatment is mainly supportive. Reduction of activity and bed rest as tolerated are recommended. Patients should be advised to avoid contact sports
or strenuous exercise for 8 weeks or while splenomegaly is still present. Most patients have an uneventful recovery.

Conclusion:
Infectious mononucleosis is generally a benign and self-limited disease. Prompt diag-
nosis is essential to avoid unnecessary investigations and treatments and to minimize complications.
Splenic rupture is the most feared complication. As avoiding exposure to EBV is almost impossible,
the most effective way to prevent EBV infection and infectious mononucleosis is the development
of an effective, safe, and affordable EBV vaccine that can confer life-long immunity.