Man, 25, With Sinus Pain, Sore Throat, and Rash

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A 25-year-old white man presents to urgent care with a nine-day history of increasing sinus pressure, mild sore throat, dry cough, and low-grade fever. Physical exam of the ears, nose, throat, and chest is unremarkable, but the patient does display mild maxillary sinus tenderness. Sinus pain (and symptom duration) is the primary complaint. The patient was recently exposed to influenza B, but a rapid flu test is negative. A five-day course of amoxicillin-clavulanate is prescribed for a presumed diagnosis of bacterial sinusitis.

A diffuse morbiliform rash covers the patient's chest.

One week later, the patient returns with worsening sore throat and a morbilliform rash (see Figures 1 and 2), which covers the trunk, upper arms, and thighs. He has no known allergies to drugs, foods, or other environmental triggers. Examination reveals slightly tender, mobile anterior and posterior cervical lymphadenopathy, as well as bilateral tonsillar erythema and exudates, which were not present at the initial visit.

Diffuse morbiliform rash on the patient's back.

The rest of the exam is normal, and the patient’s sinus symptoms have resolved. Heterophile antibody testing yields positive results, suggesting infection with Epstein-Barr virus (EBV).


EBV is a pervasive herpesvirus that infects approximately 95% of adults worldwide.1 More than 90% of adults are seropositive for EBV antibodies by the age of 30.2 Although affected individuals are often asymptomatic, some patients develop symptoms of infectious mononucleosis (IM).2 An aminopenicillin rash can occur in patients with IM who are treated with amoxicillin or ampicillin, as was the case with this patient.

Incidence and pathophysiology

Infection with EBV most commonly occurs between the ages of 15 and 24.1,2 Infection before the age of 1 is rarely seen due to circulating maternal antibodies; incidence of IM in those younger than 1 or older than 30 is < 1 per 1,000 cases annually.2 The average annual incidence of infection is 0.5% in young adults (ages 15 and 24) but has been reported as high as 4.8%.2 About 10% to 20% of people who never knowingly come into contact with the virus will become infected annually; of those, up to 50% will develop IM.2 There are no known correlations in incidence based on sex or seasonal changes.2

Like all herpesviridae, EBV causes a latent infection that persists for a lifetime, specifically in replicating B lymphocytes.1 Saliva is the most common mode of EBV transmission, as viral shedding occurs in the throat and mouth.1,3 While the viral load in saliva is the highest during the first six months of infection, there are no clear data determining the risk for transmission throughout the course of asymptomatic shedding.4 There is a 30-to-50–day incubation period of EBV infection before a patient experiences symptoms of IM.1 During this period, B lymphocytes and epithelial cells (specifically in the tonsillar crypts) are believed to be the source of viral replication.1,3

Clinical presentation of IM

Common symptoms of IM include sore throat, fever, and fatigue. Approximately one in 13 patients ages 16 to 20 who pre­sent with a fever and sore throat will be diagnosed with IM.6 However, symptomatology alone is more sensitive than specific and is not sufficient to diagnose IM.6 Combined fatigue and pharyngitis is sensitive (81%-83%) but not specific, and posterior cervical lymphadenopathy increases the likelihood of IM (specificity, 87%).6

Continue to: The classic triad associated with IM includes...


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