What are the clinical findings of infectious mononucleosis (mono)?

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From the Guidelines

Infectious mononucleosis (mono) typically presents with a triad of fever, sore throat, and lymphadenopathy, as well as extreme fatigue, which can last for weeks to months, and is often accompanied by a maculopapular rash, hepatomegaly, and mild liver function abnormalities 1. The clinical findings of mono can be divided into several categories, including:

  • Common symptoms:
    • Fever
    • Sore throat
    • Lymphadenopathy
    • Extreme fatigue
    • Maculopapular rash
  • Less common manifestations:
    • Jaundice
    • Neurological complications like Guillain-Barré syndrome or encephalitis
    • Hematologic abnormalities such as hemolytic anemia or thrombocytopenia
  • Laboratory findings:
    • Lymphocytosis with atypical lymphocytes
    • Elevated liver enzymes
    • Positive heterophile antibody tests (monospot) The diagnosis of mono can be confirmed by the detection of IgM and IgG directed against the EBV viral capsid antigen (VCA) with negative EBNA1 IgG 1. It is essential to differentiate infectious mononucleosis from lymphoproliferative disease, non-Hodgkin's lymphoma, and Hodgkin's disease through biopsy diagnosis and classification by a specialist haematopathologist, including EBER in situ hybridisation to detect the presence of EBV 1. The management of mono should focus on relieving symptoms, as the infection is usually self-limiting, and monitoring for potential complications, such as splenic rupture or neurological involvement 1.

From the Research

Clinical Findings of Mono

The clinical findings of mono, also known as infectious mononucleosis, can be summarized as follows:

  • Fever, tonsillar pharyngitis, and lymphadenopathy are the classic triad of symptoms, with fatigue being a common accompanying symptom 2, 3, 4
  • 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, with lymphocytes making 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

The diagnostic tests for mono include:

  • Demonstration of heterophile antibodies, with the monospot test being the most widely used method 2, 5
  • Serologic testing for antibodies to viral capsid antigens, which is recommended when confirmation of the diagnosis is required in patients with a negative mono-spot test 2
  • EBV-specific antibody profiles, which are the best choice for staging EBV infection 3

Complications

The complications of mono can include:

  • Spontaneous splenic rupture, which occurs in 0.1 to 0.5% of patients and is potentially life-threatening 2
  • Chronic fatigue syndrome, which is a risk factor for patients with mono 2
  • Certain cancers and autoimmune diseases, which can occur as long-term consequences of EBV infection 3

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

Infectious Mononucleosis: diagnosis and clinical interpretation.

British journal of biomedical science, 2021

Research

Epstein-Barr virus infectious mononucleosis.

Clinical otolaryngology and allied sciences, 2001

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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