Differentials

Group A streptococcal pharyngitis

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Epstein-Barr virus (EBV) pharyngitis may be clinically indistinguishable from streptococcal pharyngitis.

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Throat culture for group A streptococcus is positive. However, 3% to 30% of patients with IM may have positive throat culture for group A streptococcus, and differentiating carrier state from true streptococcal infection in patients with IM can be challenging.[53][54] If EBV is strongly suspected, routine throat culture is not necessary.

Antibiotics should be used only for uncommon cases of true concomitant streptococcal infection, after the throat culture confirmation of group A streptococci. Unnecessary use of ampicillin, amoxicillin, or other beta-lactams frequently results in a rash in patients with IM.[45]

Hepatitis A

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Presents with fever, abdominal pain, jaundice, and malaise.

Hepatomegaly is common.

Eyelid oedema, pharyngitis, adenopathy, splenomegaly, and atypical lymphocytosis are usually absent with hepatitis A.

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Aminotransferases (alanine aminotransferase/aspartate aminotransferase) elevated 10 fold or greater.

Positive hepatitis A serology.

Heterophile antibody negative.

Acute HIV infection

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Early HIV infection can cause an acute illness with fever, malaise, lymphadenopathy, and maculopapular, blanching rash.

Less prominent pharyngitis; more frequent rash; presence of diarrhoea with HIV.

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Plasma viral load test is positive.

Enzyme-linked immunosorbent assay (ELISA) HIV test may be positive. However, often negative in the acute infection, and IM may cause false-positive result.

Adenovirus

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Coryza, cough, pneumonia, conjunctivitis, diarrhoea are typically present in adenovirus infection.

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Nasopharyngeal swab for culture of respiratory viruses is positive for adenovirus.

Human herpes virus-6

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Common febrile illness of early childhood; disease course is characterised by 3 to 5 days of fever followed by a typical exanthem of rose-pink macules and papules that appear with defervescence on the trunk, neck, proximal extremities, and occasionally on the face.

Prolonged febrile mononucleosis syndrome in adults.

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Anti-human herpes virus-6 IgM and IgG positive.

Cytomegalovirus (CMV) infection

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SIGNS / SYMPTOMS

CMV infection in healthy individuals can be asymptomatic or symptoms may resemble mononucleosis syndrome (fever, malaise, pharyngitis).

Physical examination may show lymphadenopathy and splenomegaly.

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Aminotransferases or alkaline phosphatase are frequently elevated.

CMV serology is the most accessible test in the community setting and often sufficient for diagnosis in immunocompetent individuals.

Viral culture, polymerase chain reaction, or pp65 antigen detection may be used if available.

In primary Epstein-Barr virus (EBV) infection in children, dual positivity of EBV viral capsid antigen-IgM (VCA-IgM) and CMV IgM antibodies may occur. This is more common in infants, and less common in adolescents. In one study, nearly all cases of dual positivity represented a false-positive finding, as opposed to co-infection with CMV.[46]

Herpes simplex virus-1

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SIGNS / SYMPTOMS

Exudative pharyngitis, gingivostomatitis, odynophagia.

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Viral throat culture and polymerase chain reaction are positive for herpes simplex virus-1.

Influenza infection

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SIGNS / SYMPTOMS

Influenza season or documented outbreak.

Typically presents with acute onset of symptoms and high fever with myalgia, arthralgia, and cough.

Symptoms typically last <2 weeks.

Absence of characteristic posterior cervical lymphadenopathy.

INVESTIGATIONS

Monospot test is negative for heterophile antibodies.

Serology is negative for Epstein-Barr virus-specific antibodies.

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