Pediatric Mononucleosis and Epstein-Barr Virus Infection Clinical Presentation

Updated: Dec 05, 2018
  • Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor: Russell W Steele, MD  more...
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Acute infectious mononucleosis presents with a history of 1-2 weeks of fatigue and malaise; however, onset may be abrupt.

The incubation period in adolescents is 30-50 days; however, it is shorter in young children.

Symptoms include sore throat, headache, fever, myalgias, nausea, and abdominal pain. Sore throat is the most frequent presenting symptom. Gradually worsening over the first week, it may be the most severe sore throat the patient has experienced. Headache usually occurs during the first week and may be retro-orbital.

Left upper quadrant pain may be due to splenic enlargement. Abdominal pain should prompt suspicion of splenic rupture.

Symptoms usually persist for 2-3 weeks, but fatigue is often more prolonged.

Infants and young children with primary infection are usually asymptomatic.



Infectious mononucleosis is characterized by pharyngitis, generalized lymphadenopathy, and hepatosplenomegaly. Most clinical symptoms are due to T-cell proliferation and organ infiltration. Children younger than 4 years frequently have splenomegaly or hepatomegaly, rash, and symptoms of an upper respiratory tract infection.


Pharyngitis is exudative in one third of patients and is the most consistent physical finding.

Petechiae are present at the junction of the hard and soft palates in 25-60% of patients.

Tonsillar enlargement can be massive and occasionally causes airway obstruction. The enlargement can be associated with dehydration due to difficulty in swallowing.


Lymphadenopathy is prominent and most commonly affects the posterior cervical lymph nodes. Anterior cervical and submandibular nodal involvement is common, and axillary and inguinal nodes are also affected.

Enlarged epitrochlear nodes are highly suggestive of infectious mononucleosis.

Nodal enlargement is usually symmetric.

Nodes are mildly tender to palpation and are freely moveable.


Although hepatomegaly is common, jaundice is rare. Percussion tenderness over the liver is common.


Splenomegaly is common. The spleen is often palpable 2-3 cm below the left costal margin and may be tender.

The spleen rapidly enlarges over the first week of symptoms, usually decreasing in size over the next 7-10 days.

The spleen can rupture from relatively minor trauma or even spontaneously.


More than 90% of patients develop fever, which is most severe in the afternoon, typically peaking at 38-39°C, but it may reach 40°C. Fever resolves over 10-14 days. Despite fever, the pulse is usually normal or relatively low, and tachycardia is unusual.

Maculopapular rash

A usually faint, widely scattered, and erythematous maculopapular rash occurs in 3-15% of patients and is more common in young children.

Treatment with amoxicillin or ampicillin is associated with rash in approximately 80% of patients. This is often encountered when primary Epstein-Barr virus (EBV) infection is initially misdiagnosed as strep throat and is treated as such.

Circulating immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to ampicillin are observed.

Eyelid edema

This may be present, especially in the first week of illness.

Genital ulcers

Genital ulcers have been described in girls and may be confused with genital herpes. [16]



Epstein-Barr virus is the etiologic agent in approximately 90% of acute infectious mononucleosis cases.

Cytomegalovirus (CMV), another herpesvirus, is most commonly associated with Epstein-Barr virus–negative infectious mononucleosis syndrome.

Other viruses associated with a similar acute illness include adenovirus; hepatitis A, hepatitis B, or hepatitis C; herpes simplex 1 and herpes simplex 2; human herpesvirus 6; rubella; and primary HIV in adolescents or young adults.

The etiology of most Epstein-Barr virus–negative infectious mononucleosis cases remains unknown.