What are the potential complications of mononucleosis (mono) in adolescents and young adults?

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Potential Complications of Mononucleosis

The most critical complication of infectious mononucleosis is spontaneous splenic rupture, occurring in 0.1-0.5% of cases and representing a potentially life-threatening emergency, while other significant complications include airway obstruction from tonsillar enlargement, hepatitis, neurologic manifestations, and hematologic abnormalities. 1, 2

Life-Threatening Complications

Splenic Rupture

  • Splenic rupture is the most feared complication, with a mortality rate of 9% when it occurs 2
  • The average time from symptom onset to splenic rupture is 14 days, but cases have been reported up to 8 weeks after illness onset 2
  • Men under 30 years of age within the first 4 weeks of symptom onset are at highest risk 2
  • Abdominal pain is the presenting complaint in 88% of splenic rupture cases 2
  • Importantly, 86% of splenic ruptures occur without any preceding trauma history, making this a truly spontaneous complication 2
  • Only 73.8% of splenic injuries occur within the traditional 21-day activity restriction period, with 90.5% occurring within 31 days 3

Airway Obstruction

  • Severe tonsillar enlargement can lead to upper airway obstruction requiring urgent intervention 1
  • This represents an acute emergency requiring immediate recognition and management 1

Hematologic Complications

Blood Cell Abnormalities

  • Hemolytic anemia can develop, though typically mild and self-limited 1
  • Thrombocytopenia occurs in some patients and may contribute to bleeding risk 1
  • Granulocytopenia can develop, potentially increasing infection susceptibility 1

Hepatic Complications

  • Hepatomegaly occurs in approximately 10% of cases 1
  • Mild hepatitis with elevated transaminases is common, though typically asymptomatic 1
  • Severe hepatic dysfunction is rare but can occur 1

Neurologic Complications

Central Nervous System Involvement

  • Encephalitis or meningoencephalitis can develop, though uncommon 1
  • Guillain-Barré syndrome has been reported as a rare complication 4
  • Seizures may occur in severe cases with CNS involvement 1
  • Bell's palsy and other cranial nerve palsies can develop 1

Peripheral Nervous System

  • Peripheral neuropathies may occur rarely 1
  • Transverse myelitis has been documented as a rare complication 4

Cardiac Complications

  • Myocarditis and pericarditis are occasionally encountered, though typically mild 4
  • ECG abnormalities including ST segment changes and T wave abnormalities can occur even without clinical cardiac symptoms 4

Chronic Sequelae

Post-Infectious Fatigue

  • Infectious mononucleosis is a recognized risk factor for chronic fatigue syndrome 1
  • Fatigue may be profound initially but typically resolves within 3 months in uncomplicated cases 1
  • A subset of patients develops persistent fatigue lasting beyond the acute illness 1

Immunologic Complications

Lymphoproliferative Disorders

  • In immunocompromised patients, EBV infection carries increased risk of severe disease and lymphoproliferative disorders 5
  • Hemophagocytic lymphohistiocytosis (hemophagocytic syndrome) can develop, particularly in patients on immunosuppressive therapy 4
  • Post-transplant lymphoproliferative disorder is a concern in transplant recipients 4

Important Clinical Caveats

Risk Stratification

  • Young males (particularly under age 30) require heightened vigilance during the first month of illness due to elevated splenic rupture risk 2
  • Patients should be counseled that splenic rupture can occur without trauma and to seek immediate care for abdominal pain 2, 3

Activity Restrictions

  • Given that substantial splenic injuries occur between 21-31 days after symptom onset, activity restriction should extend to at least 8 weeks rather than the traditional 3-4 weeks 2, 3
  • Contact sports, heavy lifting, and vigorous activity should be avoided during this period 1, 2
  • If return to high-risk activities is desired before 8 weeks, ultrasound should confirm resolution of splenomegaly 2

Special Populations

  • Children under 10 years may have atypical presentations and require EBV-specific antibody testing rather than heterophile antibody testing 6
  • Immunocompromised patients require more extensive monitoring and consideration of EBV viral load testing 6

References

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Primary Transmission of Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Diagnostic Approach for Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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