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

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Infectious Mononucleosis: Symptoms and Treatment

Primary Symptoms

Infectious mononucleosis presents with a classic triad of fever, tonsillar pharyngitis, and lymphadenopathy, with profound fatigue that typically resolves within three months. 1

Cardinal Features

  • Fever: Often reaches 40°C (104°F), though may be mild or absent in some patients 2
  • Sore throat with tonsillar pharyngitis: One of the most prominent presenting symptoms 1
  • Cervical lymphadenopathy: Particularly posterior cervical or auricular nodes are characteristic 3
  • Profound fatigue: The hallmark symptom that may persist for several months after acute infection resolves 3

Common Physical Findings

  • Splenomegaly: Occurs in approximately 50% of cases 1
  • Hepatomegaly: Present in approximately 10% of cases 1
  • Periorbital/palpebral edema: Bilateral eyelid swelling occurs in one-third of patients 1
  • Palatal petechiae: Supportive diagnostic finding 3

Skin Manifestations

  • Maculopapular rash: Occurs in 10-45% of cases, widely scattered and erythematous 1
  • Antibiotic-associated rash: Particularly common when ampicillin or amoxicillin is administered (a key pitfall to avoid) 2

Laboratory Findings

Hematologic Abnormalities

  • Peripheral blood leukocytosis: Present in most patients with lymphocytes comprising at least 50% of the differential 1
  • Atypical lymphocytosis: More than 10% of total lymphocyte count 1
  • Atypical lymphocytosis ≥20% OR atypical lymphocytosis ≥10% plus lymphocytosis ≥50% strongly supports the diagnosis 3

Other Laboratory Findings

  • Elevated liver function tests: Mild transaminase elevations are common 2, 4
  • Hematologic complications: Anemia, thrombocytopenia, and neutropenia can occur in severe cases 2

Diagnostic Testing

Heterophile Antibody Testing

  • Monospot test: The most widely used method and typically sufficient with classic clinical presentation 1
  • Important caveat: False-negative results are relatively common early in infection 3

EBV-Specific Serology

  • When to use: Required when mononucleosis-like illness presents with negative monospot test 1
  • VCA IgM with or without VCA IgG, in the absence of EBNA antibodies: Indicates recent primary infection 2

Severe Complications Requiring Immediate Attention

Life-Threatening Complications

  • Splenic rupture: Occurs in 0.1-0.5% of patients and is potentially fatal 1
  • Respiratory compromise or severe pharyngeal edema: May require corticosteroid intervention 3
  • Persistent high fever unresponsive to antipyretics: Warrants medical evaluation 2

Less Common Severe Manifestations

  • Neurological complications: Headache and rare severe neurological symptoms 2
  • Interstitial pneumonitis: Can develop in some cases 2

Treatment Approach

Supportive Care (Mainstay of Treatment)

Treatment is primarily supportive, as infectious mononucleosis is generally benign and self-limited. 1

  • Adequate hydration, analgesics, and antipyretics: Core symptomatic management 3
  • Activity modification: Reduction of activity and bed rest as tolerated, guided by patient's energy level rather than enforced bed rest 3
  • Adequate rest: Essential but should not be rigidly enforced 3

Activity Restrictions

Patients must avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is present to prevent splenic rupture 1

Medications NOT Routinely Recommended

  • Corticosteroids: Not recommended for routine treatment 3
    • Exception: May benefit patients with respiratory compromise or severe pharyngeal edema 3
  • Acyclovir: Not recommended for routine treatment 3
  • Antihistamines: Not recommended for routine treatment 3

Critical Pitfall to Avoid

Never prescribe ampicillin or amoxicillin for suspected streptococcal pharyngitis without ruling out mononucleosis first, as this causes a characteristic rash in the majority of mono patients 2

Clinical Course and Prognosis

  • Acute symptoms: Most symptoms, signs, and laboratory abnormalities return to normal by 1 month 4
  • Protracted symptoms: Fatigue, cervical lymphadenopathy, and pharyngitis may improve more slowly 4
  • Long-term fatigue: May persist for several months but typically resolves within three months 1, 3
  • Chronic fatigue syndrome: Infectious mononucleosis is a recognized risk factor 1
  • Overall prognosis: Most patients have an uneventful recovery 1

References

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Guideline

Mononucleosis Diagnosis and Symptoms

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Epstein-Barr virus infectious mononucleosis.

American family physician, 2004

Research

Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus.

The Journal of the American Board of Family Practice, 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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