Overview
Definition:
Infectious mononucleosis (IM) is a clinical syndrome characterized by fever, pharyngitis, and lymphadenopathy, most commonly caused by Epstein-Barr virus (EBV)
Cytomegalovirus (CMV) is another herpesvirus that can cause a similar syndrome, termed CMV mononucleosis, which is particularly relevant in immunocompetent adolescents and young adults, presenting a diagnostic challenge due to overlapping symptoms with EBV IM.
Epidemiology:
EBV is ubiquitous, with seroconversion typically occurring in childhood or adolescence
CMV is also widespread, with primary infection often occurring in early childhood
However, symptomatic mononucleosis due to CMV is less common than EBV-associated IM in immunocompetent individuals, though it can be a significant cause of heterophile-negative mononucleosis, particularly in older adolescents and young adults
Prevalence of primary CMV infection increases with age.
Clinical Significance:
Distinguishing between CMV and EBV mononucleosis is crucial for appropriate patient counseling and management, especially regarding potential complications and recovery timelines
While both are generally self-limiting in immunocompetent adolescents, CMV infection has implications in immunocompromised individuals and pregnant women
Understanding the differences aids in accurate diagnosis and effective management, vital for DNB and NEET SS preparation.
Clinical Presentation
Symptoms:
Fever, typically prolonged
Sore throat, often severe and exudative
Fatigue and malaise, profound and persistent
Headache
Myalgias
Nausea or abdominal discomfort
Rash, particularly maculopapular or petechial, may occur, especially if ampicillin or amoxicillin is administered.
Signs:
Pharyngeal edema and tonsillar exudates, often mimicking strep pharyngitis
Posterior cervical lymphadenopathy (more common in EBV), but generalized lymphadenopathy can occur
Splenomegaly, usually mild to moderate
Hepatomegaly and mild jaundice can be present
Periorbital edema (Hoagland sign) is more characteristic of EBV but can be seen in CMV
Palatal petechiae are common in EBV but less so in CMV.
Diagnostic Criteria:
Diagnosis of mononucleosis is primarily clinical, supported by laboratory findings
Definitive diagnosis requires serological testing to identify the causative agent (EBV or CMV)
For EBV, the presence of heterophile antibodies (Monospot test) is highly suggestive, though false negatives can occur early in infection
For CMV, specific IgM and IgG antibodies against CMV are required
Atypical lymphocytes on peripheral blood smear are characteristic of both.
Diagnostic Approach
History Taking:
Detailed history focusing on onset and duration of fever, sore throat severity, fatigue levels, and exposure to individuals with similar symptoms
Inquire about medications, especially antibiotics
Ask about sexual activity in adolescents due to potential transmission routes for both viruses
Any history of immunocompromise or underlying medical conditions.
Physical Examination:
Thorough examination including vital signs, assessment of pharyngeal congestion and exudates, palpation of cervical, axillary, and inguinal lymph nodes for size and tenderness, abdominal palpation for hepatosplenomegaly, and examination for any rash.
Investigations:
Complete Blood Count (CBC) with differential: Leukocytosis with a predominance of atypical lymphocytes (over 10% is common)
Heterophile antibody test (Monospot test): Positive in most EBV cases, may be negative early
EBV-specific serology: VCA IgM, VCA IgG, EBNA antibodies to determine acute, past, or reactivated infection
CMV-specific serology: CMV IgM, CMV IgG, CMV IgG avidity to confirm acute infection
Liver function tests (LFTs): May show mild elevation of transaminases
Throat swab for bacterial culture: To rule out Group A Streptococcus
Polymerase Chain Reaction (PCR): Can detect viral DNA in blood or other body fluids, useful in specific situations.
Differential Diagnosis:
Streptococcal pharyngitis, acute HIV infection, viral hepatitis, toxoplasmosis, primary herpetic gingivostomatitis, other viral infections (e.g., adenovirus, influenza), drug reactions, and lymphoid malignancies.
Management
Initial Management:
Supportive care is the mainstay of treatment for both CMV and EBV mononucleosis in immunocompetent adolescents
Rest is paramount
Adequate hydration is essential
Pain and fever management with analgesics like acetaminophen or ibuprofen.
Medical Management:
Antiviral therapy is generally not indicated for uncomplicated CMV or EBV mononucleosis in immunocompetent individuals
Ganciclovir or valganciclovir may be considered in immunocompromised patients with severe CMV disease
Corticosteroids are typically reserved for severe cases with airway compromise or significant organ involvement, and their routine use is controversial and not recommended for uncomplicated IM.
Surgical Management:
Surgical intervention is not typically required for uncomplicated CMV or EBV mononucleosis
Splenectomy may be considered in rare cases of splenic rupture, a life-threatening complication.
Supportive Care:
Adequate fluid intake is critical, especially with fever and pharyngitis
Soft, bland diet for sore throat
Monitoring for signs of complications such as airway obstruction, splenic rupture, or neurological involvement
Advice regarding avoiding strenuous physical activity and contact sports for at least 4-6 weeks post-resolution of symptoms to prevent splenic rupture.
Complications
Early Complications:
Splenic rupture (rare but life-threatening), airway obstruction due to severe pharyngeal edema, meningoencephalitis, Guillain-Barré syndrome, hepatitis, hemolytic anemia, thrombocytopenia, myocarditis, and pneumonitis.
Late Complications:
Post-viral fatigue syndrome, which can be prolonged
Reactivation of EBV or CMV can occur, especially in immunocompromised individuals
Chronic active EBV infection is a rare but serious entity.
Prevention Strategies:
Prevention of primary infection is difficult due to ubiquitous nature of viruses
Good hygiene practices are essential
In immunocompromised individuals, prophylaxis with antivirals may be considered
Avoiding close contact during the infectious period and ensuring adequate vaccination status for other preventable diseases that can mimic mononucleosis.
Prognosis
Factors Affecting Prognosis:
The prognosis for CMV and EBV mononucleosis in immunocompetent adolescents is generally excellent, with most individuals recovering fully within weeks to a few months
Factors that may influence prognosis include the presence of complications, underlying immunocompromise, and the specific strain of virus involved.
Outcomes:
Most patients experience resolution of acute symptoms within 2-4 weeks, although fatigue can persist for several months
Long-term sequelae are uncommon in immunocompetent individuals
Reactivation of CMV can lead to significant morbidity in immunocompromised patients.
Follow Up:
Follow-up is typically not required for uncomplicated cases once symptoms have resolved
Patients should be advised to seek medical attention if new or worsening symptoms develop, or if signs of complications arise
For individuals with immunocompromise or significant complications, long-term monitoring may be necessary.
Key Points
Exam Focus:
Differentiate CMV from EBV mononucleosis based on serology and clinical nuances
Recognize heterophile-negative mononucleosis
Understand indications for antiviral therapy and corticosteroids
Remember risks associated with splenic rupture.
Clinical Pearls:
Posterior cervical lymphadenopathy and palatal petechiae are more suggestive of EBV
Heterophile antibody test (Monospot) is useful but has limitations early in infection
Atypical lymphocytes on peripheral smear are a key hematological finding for both.
Common Mistakes:
Over-reliance on the Monospot test without confirmatory serology, especially in early disease
Prescribing antibiotics unnecessarily for viral pharyngitis
Inappropriately using corticosteroids for uncomplicated mononucleosis
Underestimating the risk of splenic rupture in athletes.