Differentials
Infectious mononucleosis
SIGNS / SYMPTOMS
May see pharyngitis, splenomegaly, hepatomegaly, jaundice, rash, and myalgia.
INVESTIGATIONS
CBC typically shows at least 50% lymphocytes, of which 10% or more are atypical.
Confirmation of the diagnosis is based on a positive serum agglutination test (such as Monospot) or serologic test for detection of Epstein-Barr virus (EBV)-specific antibodies directed against the viral antigens, such as viral capsid antigen and EBV nuclear antigen.
Toxoplasmosis
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
INVESTIGATIONS
Positive serologic tests for antibodies to Toxoplasma gondii. Rising antibody titers 2-4 weeks after initial infection, or positive IgM tests, show recent infection.
Viral hepatitis
SIGNS / SYMPTOMS
Right upper quadrant abdominal pain, jaundice.
INVESTIGATIONS
Aminotransferases (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) elevated.
Hepatitis serology positive.
HIV test negative.
Morbilliform drug eruption
SIGNS / SYMPTOMS
Typically presents as a maculopapular rash that develops within 2 weeks of starting treatment, but can appear up to 14 days after stopping the drug. The rash may become confluent and spares the palms and soles.
INVESTIGATIONS
Diagnosis is usually clinical. However, CBC with differential may show leukopenia, thrombocytopenia, and eosinophilia. Serum IgE levels may be elevated. Biopsy of the skin lesion may show eosinophils, edema, and inflammation.
Viral exanthems (enterovirus)
SIGNS / SYMPTOMS
May see acute febrile illness and rash. Diagnosis is usually clinical, based on the specific features of the prodromal period, rash, and associated symptoms.
INVESTIGATIONS
Tests are usually not necessary, as diagnosis is clinical. HIV tests will be negative unless the patient has concomitant HIV infection.
Parvovirus B19
SIGNS / SYMPTOMS
Patients are typically asymptomatic.
May present with "slapped cheek" rash on the face and a lacy red rash on the limbs and trunk.
Associated pain and swelling of the joints of the hands, wrists, and knees may be present.
Infection in pregnancy can cause first-trimester abortion, or hemolysis in the older fetus, resulting in fetal anemia, hypoxia, heart failure, and edema.
INVESTIGATIONS
Serum parvovirus B19 IgM and IgG titers are positive in recent infection.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Residence in/travel to a country/area or territory with local transmission, or close contact with a confirmed or probable case of COVID-19, in the 14 days prior to symptom onset.
The situation is evolving rapidly; see our COVID-19 topic for further information.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
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