What are the classic symptoms of mononucleosis (mono) besides fatigue?

Classic Symptoms of Mononucleosis Besides Fatigue

The classic triad of mononucleosis consists of fever (often reaching 40°C), tonsillar pharyngitis with sore throat, and cervical lymphadenopathy, with additional hallmark features including hepatosplenomegaly and the presence of atypical lymphocytes on blood smear. 1, 2

Core Clinical Features

Pharyngeal and Lymphatic Manifestations:

• Sore throat with tonsillar pharyngitis is one of the defining symptoms, often severe enough to cause dysphagia 3, 2
• Cervical lymph node enlargement is characteristic, particularly involving posterior cervical or auricular nodes 4
• Palatal petechiae may be visible on examination 4
• Inguinal adenopathy can also occur 4

Fever:

• High-grade fever is typical, potentially reaching 40°C (104°F) 1
• Fever may be persistent and unresponsive to antipyretics in severe cases 1

Hepatosplenic Involvement:

• Hepatosplenomegaly occurs in approximately 50% of cases for splenomegaly and 10% for hepatomegaly 1, 2
• Liver function tests often show mild elevations 1
• Splenic rupture, though rare (0.1-0.5% of cases), is the most feared complication 2

Distinctive Physical Findings

Facial Edema:

• Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients and is a characteristic finding 2

Skin Manifestations:

• A maculopapular rash occurs in 10-45% of cases, usually widely scattered and erythematous 1, 2
• This rash is particularly common in patients treated with antibiotics (especially ampicillin or amoxicillin) 1

Laboratory Abnormalities

Hematologic Changes:

• Peripheral blood leukocytosis with lymphocytes comprising at least 50% of the white blood cell differential 5, 2
• Atypical lymphocytes constituting more than 10% of total lymphocyte count is a hallmark finding 5, 2, 4
• Hematologic complications including anemia, thrombocytopenia, and neutropenia can occur in severe cases 1

Less Common but Important Complications

Neurological Symptoms:

• Headache is common 6
• Rare severe neurological complications can develop 6, 1

Other Systemic Manifestations:

• Myalgia and arthralgia may be present 6
• Interstitial pneumonitis can develop in some cases 6
• Cardiovascular disorders, including coronary aneurysms or valvular disease, have been reported in chronic cases 6
• Digestive tract, pulmonary, ocular, and dermal complications are possible 6

Clinical Pitfalls to Avoid

Duration and Recovery:

• While acute symptoms typically last several weeks, fatigue may persist for several months after the acute infection resolves 3, 4
• Infectious mononucleosis is a recognized risk factor for chronic fatigue syndrome 2

Activity Restrictions:

• Patients must avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly persists due to risk of splenic rupture 2, 4

Diagnostic Considerations:

• The heterophile antibody (Monospot) test has approximately 10% false-negative rate, particularly early in infection and in children under 10 years 5
• When clinical suspicion remains high despite negative heterophile testing, EBV-specific serologic testing should be performed 5