What is the course and treatment of infectious mononucleosis (Mono)?

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Last updated: March 27, 2025View editorial policy

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From the Guidelines

The primary treatment for infectious mononucleosis (Mono) is supportive care, focusing on rest, hydration, and symptom management, as there is no specific antiviral therapy effective against Epstein-Barr virus (EBV) 1. The course of the disease typically begins with a prodromal phase of fatigue, malaise, and headache, followed by the classic triad of fever, sore throat, and swollen lymph nodes, particularly in the neck. Key aspects of management include:

  • Rest, especially during the acute phase, with gradual return to normal activities as symptoms improve
  • Adequate hydration
  • Over-the-counter pain relievers such as acetaminophen (500-1000 mg every 6 hours) or ibuprofen (400-600 mg every 6-8 hours) to manage fever and sore throat pain
  • Gargling with warm salt water for additional throat relief
  • Avoidance of contact sports and heavy lifting for at least 4 weeks due to the risk of splenic rupture from an enlarged spleen
  • Avoidance of alcohol during recovery to prevent additional liver stress, as mild liver inflammation is common In cases of severe throat inflammation or complications like airway obstruction, corticosteroids like prednisone (40-60 mg daily for 5-7 days) may be prescribed 1. It's essential to note that while acyclovir inhibits replication of EBV in vitro, a meta-analysis of 5 clinical trials did not show benefit in the treatment of infectious mononucleosis 1, making it not recommended for routine use. Most patients recover completely within 2-4 weeks, though fatigue may persist longer in some cases.

From the Research

Course of Infectious Mononucleosis

  • Infectious mononucleosis usually runs a mild self-limiting course 2
  • The disease is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy 3
  • Fatigue may be profound but tends to resolve within three months 3
  • Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients 3
  • Splenomegaly and hepatomegaly occur in approximately 50% and 10% of cases, respectively 3

Treatment of Infectious Mononucleosis

  • Treatment is mainly supportive, with reduction of activity and bed rest as tolerated 3
  • Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present 3
  • Corticosteroids may be beneficial for the treatment of several complications associated with Epstein-Barr virus 2, 4
  • Antiviral medications have been used to treat infectious mononucleosis, but their use is controversial 2, 5
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) may quickly resolve symptoms associated with EBV-induced infectious mononucleosis in patients with atopic predispositions 6

Complications of Infectious Mononucleosis

  • Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious mononucleosis and is potentially life-threatening 3
  • Infectious mononucleosis is a risk factor for chronic fatigue syndrome 3
  • Other complications include hepatitis, peripheral nervous system involvement, and CNS involvement 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Antiviral treatment for severe EBV infections in apparently immunocompetent patients.

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2010

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Antiviral agents for infectious mononucleosis (glandular fever).

The Cochrane database of systematic reviews, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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