What are the symptoms, diagnostic tests, and treatment options for infectious mononucleosis (mono)?

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Last updated: June 17, 2025View editorial policy

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From the Guidelines

Infectious mononucleosis (mono) is a viral infection caused by Epstein-Barr virus (EBV) that typically presents with fatigue, sore throat, fever, swollen lymph nodes, and sometimes a rash, and is diagnosed through a combination of clinical evaluation and laboratory tests, with treatment being primarily supportive to manage symptoms and prevent complications. The symptoms of mono can vary widely among individuals but often include fever, sore throat, swollen lymph nodes (especially in the neck), an enlarged spleen, and sometimes a rash 1. Diagnosis involves a combination of clinical evaluation and laboratory tests, including a complete blood count (CBC) which often shows an elevated white blood cell count with atypical lymphocytes, a heterophile antibody test (Monospot), and specific antibody tests for EBV 1.

When considering diagnostic tests, it's essential to note that heterophile antibodies usually become detectable between the sixth and tenth day following symptom onset, and false-negative results are obtained in approximately 10% of patients, especially in children younger than 10 years 1. If rapid Monospot or heterophile test results are negative, additional laboratory testing may be considered to differentiate EBV infection from a mononucleosis-like illness caused by other pathogens, and EBV antibody testing for IgG and IgM to viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA) are recommended 1.

The treatment for mono is primarily supportive since it is a viral and self-limiting illness. This includes:

  • Rest to help the body recover
  • Adequate hydration to prevent dehydration
  • Over-the-counter pain relievers like acetaminophen or ibuprofen (400-600mg every 6-8 hours) to manage fever and sore throat pain
  • Gargling with salt water to relieve throat discomfort
  • Corticosteroids may be prescribed in severe cases with significant throat swelling or complications 1. It's crucial for patients to avoid contact sports and heavy lifting for at least 3-4 weeks to prevent splenic rupture, a rare but serious complication, and alcohol should be avoided during illness and recovery due to the virus's effect on the liver 1. Most people recover completely within 2-4 weeks, though fatigue may persist longer in some cases.

From the Research

Symptoms of Mono

  • Fever, tonsillar pharyngitis, and lymphadenopathy are the characteristic triad of symptoms for infectious mononucleosis 2
  • Fatigue may be profound but tends to resolve within three months 2
  • Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients 2
  • Splenomegaly and hepatomegaly occur in approximately 50% and 10% of cases, respectively 2
  • A skin rash, which is usually widely scattered, erythematous, and maculopapular, occurs in approximately 10 to 45% of cases 2
  • Peripheral blood leukocytosis is observed in most patients; lymphocytes make up at least 50% of the white blood cell differential count 2
  • Atypical lymphocytes constitute more than 10% of the total lymphocyte count 2

Diagnostic Tests for Mono

  • The classic test for infectious mononucleosis is the demonstration of heterophile antibodies 2
  • The monospot test is the most widely used method to detect the serum heterophile antibodies of infectious mononucleosis 2
  • 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 antibodies to viral capsid antigens is recommended 2
  • EBV-specific antibody profiles are the best choice for staging EBV infection 3

Treatment Options for Mono

  • Treatment is mainly supportive 2
  • Reduction of activity and bed rest as tolerated are recommended 2
  • Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present 2
  • Symptomatic treatment, the mainstay of care, includes adequate hydration, analgesics, antipyretics, and adequate rest 4
  • Corticosteroids may benefit patients with respiratory compromise or severe pharyngeal edema 4
  • Patients with infectious mononucleosis should be withdrawn from contact or collision sports for at least four weeks after the onset of symptoms 4

Complications of Mono

  • Infectious mononucleosis is a risk factor for chronic fatigue syndrome 2
  • Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious mononucleosis and is potentially life-threatening 2
  • Rare complications have been reported, including bilateral peritonsillar abscess and splenic infarction 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Infectious Mononucleosis.

Current topics in microbiology and immunology, 2015

Research

Epstein-Barr virus infectious mononucleosis.

American family physician, 2004

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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