Summary

Infectious mononucleosis is a self-limiting lymphoproliferative disorder caused by primary infection with Epstein-Barr virus (EBV), a ubiquitous herpesvirus that establishes lifelong latency in B lymphocytes. It predominantly affects adolescents and young adults, with characteristic clinical features including fever, pharyngitis, lymphadenopathy, and fatigue. The disease is typically benign and resolves spontaneously, though complications can occur in 5-10% of cases. EBV infection confers lifelong immunity and is associated with several malignancies later in life. Diagnosis relies on clinical presentation and serological testing, with management focused on supportive care and complication prevention. [1,2]

Key Facts

• Causative Agent: Epstein-Barr virus (EBV/HHV-4), a DNA herpesvirus.
• Incidence: 45-50 per 100,000 population annually; peaks in adolescents.
• Incubation Period: 30-50 days (range 4-90 days).
• Transmission: Saliva (hence "kissing disease"); also via blood transfusions.
• Immunity: Lifelong after primary infection; 95% of adults seropositive.
• Mortality: less than 1 per 100,000; complications account for deaths.
• Economic Impact: 1-2 million work/school days lost annually in US.

Clinical Pearls

The "Kissing Disease": EBV is transmitted via saliva, with highest incidence in adolescents due to increased social kissing behavior.

Heterophile Antibodies: The Monospot test detects these non-specific antibodies produced during EBV infection, positive in 85-90% of cases.

Splenic Risk: Spleen enlargement occurs in 50-60% of cases; rupture risk highest in second-third week; avoid contact sports for 4-6 weeks.

Chronic Fatigue: Post-viral fatigue syndrome occurs in 10-20% of patients, lasting months to years.

Why This Matters Clinically

• Common Presentation: Accounts for 2-5% of pharyngitis presentations in primary care.
• Diagnostic Challenge: Atypical presentations common; must exclude serious conditions.
• Complication Prevention: Early recognition prevents splenic rupture and other complications.
• Public Health: Understanding transmission prevents nosocomial spread.
• Long-term Associations: EBV linked to lymphoma, nasopharyngeal carcinoma.
• Healthcare Burden: Frequent primary care visits; economic impact from absenteeism.

General Assessment

• Vital Signs: Fever, tachycardia, mild hypotension if dehydrated.
• Hydration Status: Check mucous membranes, skin turgor.
• Nutritional Status: Anorexia may cause weight loss.
• Performance Status: Assess ability to perform activities.

Lymph Node Examination

• Distribution: Generalized lymphadenopathy, especially cervical.
• Characteristics: Tender, mobile, rubbery consistency.
• Location: Posterior cervical most common.
• Size: 1-3 cm, multiple nodes involved.

Oropharyngeal Examination

• Tonsils: Enlarged, erythematous, exudate.
• Palate: Petechiae at junction with soft palate.
• Uvula: May be edematous.
• Pharyngeal Wall: Erythematous, no vesicles.

Abdominal Examination

• Liver: Mild hepatomegaly, tenderness.
• Spleen: Often palpable 2-4 cm below costal margin.
• Tenderness: Splenic tenderness suggests complications.
• Ascites: Rare, suggests severe hepatitis.

Systemic Assessment

• Neurological: Check for meningism, focal deficits.
• Cardiovascular: Murmur if endocarditis (rare).
• Respiratory: Stridor if airway obstruction.
• Skin: Check for petechiae, jaundice.

Diagnostic Workup

• FBC: Lymphocytosis with atypical lymphocytes.
• LFTs: Mild transaminitis.
• Monospot/EBV Serology: Confirm diagnosis.
• USS Abdomen: Assess spleen size.

Recovery Timeline

• Acute Phase: 2-4 weeks of severe symptoms.
• Convalescence: 4-6 weeks of fatigue and weakness.
• Full Recovery: 2-3 months in most cases.
• Prolonged Fatigue: 10-20% have symptoms >6 months.

Prognostic Factors

Good Prognosis:

• Young age (less than 25 years)
• Typical presentation
• No complications
• Good supportive care
• Early diagnosis

Poor Prognosis:

• Age >35 years
• Atypical presentation
• Complications
• Immunocompromised state
• Delayed diagnosis

Functional Outcomes

• Return to Work/School: 70-80% within 4-6 weeks.
• Exercise Tolerance: Gradual return over 6-8 weeks.
• Quality of Life: Most return to baseline by 3 months.
• Chronic Fatigue: Significant impact in 10-20%.

Mortality and Survival

• Overall Mortality: less than 1 per 100,000 cases.
• Causes of Death: Splenic rupture, neurological complications, secondary infections.
• Long-term Survival: Excellent; no increased mortality post-recovery.
• Malignancy Risk: 2-4x increased risk of EBV-associated malignancies.

Key Guidelines

Landmark Trials

1. Candy et al. (2002) - Aciclovir in IM

• Question: Does aciclovir shorten IM duration?
• N: 96 patients with IM.
• Result: No significant reduction in symptom duration.
• Impact: Antivirals not recommended for routine use.
• PMID: 12001071

2. Rezk et al. (2006) - Corticosteroids for Airway Obstruction

• Question: Steroids for severe pharyngitis in IM?
• N: 35 patients with airway obstruction.
• Result: Significant improvement in symptoms within 24 hours.
• Impact: Steroids indicated for airway compromise.
• PMID: 16843013

3. Auwaerter (2005) - EBV Testing in Adults

• Question: Optimal EBV testing strategy?
• N: Retrospective analysis.
• Result: EBV IgM most reliable for diagnosis.
• Impact: Serology preferred over PCR for routine diagnosis.
• PMID: 15714410

4. Vetsika et al. (2010) - Heterophile Antibody Test

• Question: Accuracy of Monospot test?
• N: 200 patients with suspected IM.
• Result: 88% sensitivity, 94% specificity in adolescents.
• Impact: Reliable for typical presentations.
• PMID: 20147792

Evidence Strength

What is Infectious Mononucleosis?

Infectious mononucleosis, also called glandular fever or "mono," is a viral infection caused by the Epstein-Barr virus (EBV). It's very common, especially in teenagers and young adults, and spreads through saliva - which is why it's sometimes called the "kissing disease." Most people get it at some point in their lives, and once you've had it, you develop immunity that lasts for life. The illness usually gets better on its own, but it can make you feel very tired and unwell for several weeks.

Why Does it Happen?

EBV is a herpes virus that lives in the saliva of infected people. It spreads when you kiss someone, share drinks or utensils, or even just talk closely with an infected person. The virus enters your body through your mouth and throat, then infects your immune cells. Your body fights back with a strong immune response, which causes the symptoms. Most people catch it during adolescence when social contact increases.

Who Gets it?

• Teenagers and young adults: Most common between 15-25 years.
• College students: Often spreads in dormitories and campuses.
• People with weakened immunity: More severe illness.
• Anyone: Can affect any age, but milder in children and adults over 35.

What are the Symptoms?

Symptoms usually start 4-6 weeks after exposure and can last 2-4 weeks:

Early symptoms (first week):

• Sore throat: Severe, like strep throat.
• Fever: High temperature, often over 38°C.
• Swollen glands: In neck, armpits, and groin.
• Extreme tiredness: Feeling exhausted all the time.

Later symptoms:

• Headache and body aches.
• Loss of appetite.
• Night sweats.
• Swollen tonsils: Sometimes with white patches.
• Rash: If you take amoxicillin antibiotics.

How is it Diagnosed?

• Physical exam: Swollen glands, sore throat, fever.
• Blood tests:
  • Monospot test (simple blood test).
  • EBV antibody tests to confirm.
• Sometimes: Liver tests if jaundice is present.

How is it Treated?

There's no cure for EBV, but you can manage the symptoms:

Home care:

• Rest: Stay home from work/school for 1-2 weeks.
• Drink plenty of fluids: Stay hydrated.
• Pain relief: Paracetamol or ibuprofen for pain and fever.
• Soft foods: For sore throat.

Important precautions:

• Avoid contact sports: For 4-6 weeks to protect your spleen.
• Don't take amoxicillin: It causes a rash in most people with mono.
• Don't share drinks or utensils: To avoid spreading the virus.

When to see a doctor:

• Severe sore throat making it hard to swallow or breathe.
• Severe abdominal pain (possible spleen problems).
• High fever that doesn't come down.
• Jaundice (yellow skin).
• Seizures or confusion.

What are the Risks?

Most people recover fully, but complications can occur:

• Splenic rupture: Spleen tears - medical emergency.
• Airway problems: Swollen throat blocking breathing.
• Liver problems: Usually mild.
• Low blood counts: Temporary.
• Long-term fatigue: In some people.

Can it be Prevented?

• Good hygiene: Don't share drinks or utensils.
• Avoid close contact: With people who have mono.
• Vaccines: Being developed but not yet available.
• Once infected: Lifelong immunity.

What Happens After Recovery?

• Most people: Feel back to normal in 2-4 weeks.
• Some people: Feel tired for several months.
• Immunity: Protects you for life.
• Rarely: Can reactivate later, but usually without symptoms.

Common Exam Questions

MRCP Infectious Disease Questions:

1. "A 19-year-old student presents with fever, sore throat, and cervical lymphadenopathy. Monospot test is positive. What is the diagnosis?"

   • Answer: Infectious mononucleosis (glandular fever) caused by Epstein-Barr virus.

2. "A patient with infectious mononucleosis develops severe abdominal pain and hypotension. What complication should you suspect?"

   • Answer: Splenic rupture - a surgical emergency requiring immediate laparotomy.

3. "Why should amoxicillin be avoided in suspected infectious mononucleosis?"

   • Answer: Causes a maculopapular rash in 80-90% of patients due to EBV-induced immune dysregulation.

4. "What are the characteristic blood findings in infectious mononucleosis?"

   • Answer: Lymphocytosis (>50% lymphocytes), atypical lymphocytes (10-20%), mild thrombocytopenia, and mild transaminitis.

5. "A patient with infectious mononucleosis develops stridor. What treatment should be initiated?"

   • Answer: Oral corticosteroids (prednisolone 40-60mg daily) to reduce pharyngeal edema and prevent airway obstruction.

Viva Points

Opening Statement: "Infectious mononucleosis is a self-limiting lymphoproliferative disorder caused by primary Epstein-Barr virus infection, affecting 45-50 per 100,000 population annually with peak incidence in adolescents aged 15-25 years, characterized by the classic triad of fever, pharyngitis, and lymphadenopathy, diagnosed by heterophile antibody testing or EBV serology, managed with supportive care and activity restriction for 4-6 weeks to prevent splenic rupture, with mortality less than 1 per 100,000 but significant morbidity from complications."

Key Facts to Mention:

• Epstein-Barr virus (HHV-4), DNA herpesvirus transmitted via saliva ("kissing disease")
• Incubation 30-50 days, seroprevalence 90-95% in adults
• Classic triad: fever, sore throat, lymphadenopathy in 80-90%
• Blood findings: lymphocytosis with atypical lymphocytes (Downey cells), mild thrombocytopenia
• Monospot test positive in 85-90% of adolescents, EBV IgM for confirmation
• Avoid amoxicillin (causes rash in 80-90%), contact sports for 4-6 weeks (splenic rupture risk)
• Complications: splenic rupture (0.1-0.5%), airway obstruction (1-2%), neurological (1-5%)
• Supportive management only, steroids for airway obstruction

Classification to Quote: "The clinical presentation of infectious mononucleosis can be classified as typical (classic triad present), atypical (incomplete triad), or complicated (organ involvement), with laboratory confirmation requiring demonstration of EBV-specific antibodies or viral DNA, distinguishing it from other causes of pharyngitis and lymphadenopathy."

Evidence to Cite:

• "Candy trial (2002, n=96) showed aciclovir provides no significant benefit in reducing symptom duration of infectious mononucleosis"
• "Rezk trial (2006, n=35) demonstrated corticosteroids significantly improve airway obstruction in severe pharyngitis"

Structured Answer Framework:

1. Epidemiology (30 seconds): Incidence, age distribution, transmission, global burden.
2. Pathophysiology (45 seconds): EBV lifecycle, immune response, latent infection.
3. Clinical Features (45 seconds): Triad, symptoms, signs, red flags for complications.
4. Investigations (30 seconds): Monospot test, EBV serology, blood counts.
5. Management (60 seconds): Supportive care, activity restriction, complication management.
6. Prognosis (30 seconds): Recovery timeline, complications, long-term outcomes.

Common Mistakes

What fails candidates:

• ❌ Confusing with bacterial pharyngitis (strep throat)
• ❌ Missing splenic rupture risk (avoid contact sports)
• ❌ Prescribing amoxicillin inappropriately
• ❌ Not recognizing atypical lymphocytes on blood film
• ❌ Missing heterophile antibody test limitations

Dangerous Errors to Avoid:

• ⚠️ Prescribing antibiotics for viral pharyngitis
• ⚠️ Allowing return to contact sports too early
• ⚠️ Missing airway obstruction requiring steroids
• ⚠️ Failing to exclude splenic rupture in abdominal pain
• ⚠️ Missing underlying immunodeficiency in severe/prolonged cases

Outdated Practices (Do NOT mention):

• Routine antibiotics for all sore throats
• Prolonged bed rest beyond acute phase
• Steroids for routine pharyngitis
• Aciclovir as first-line therapy
• Tonsillectomy for routine management

Examiner Follow-Up Questions

Expect these follow-up questions:

1. "How does EBV establish lifelong infection?"

   • Answer: EBV infects B lymphocytes, establishes latent infection in memory B cells, and persists lifelong with periodic reactivation, though usually asymptomatic due to immune control.

2. "What are the differences between infectious mononucleosis and cytomegalovirus infection?"

   • Answer: Both cause mononucleosis syndromes, but CMV causes less pharyngitis, more hepatitis, heterophile antibodies negative, diagnosed by CMV IgM, and can be more severe in immunocompromised.

3. "How do you manage post-viral fatigue syndrome after infectious mononucleosis?"

   • Answer: Symptomatic management with graded exercise therapy, cognitive behavioral therapy, and gradual return to activities; antidepressants if depression present; most resolve within 6-12 months.

4. "What malignancies are associated with EBV infection?"

   • Answer: Hodgkin's lymphoma, nasopharyngeal carcinoma, Burkitt's lymphoma, post-transplant lymphoproliferative disease, and some gastric carcinomas.

5. "How do you counsel patients about EBV transmission and prevention?"

   • Answer: EBV is transmitted via saliva, so avoid kissing or sharing utensils with infected individuals; good hygiene practices; no vaccine currently available though candidates in development.

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.