Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 19-year-old man is evaluated for a sore throat, daily fever, frontal headache, myalgia, and arthralgia of 5 days’ duration. He also has severe discomfort in the lower spine and a rash on his trunk and extremities. He returned from a 7-day trip to the Caribbean 8 days ago. The remainder of the history is noncontributory.

On physical examination, temperature is 38.3 °C (100.9 °F), blood pressure is 104/72 mm Hg, pulse rate is 102/min, and respiration rate is 16/min. His posterior pharynx is notably injected but without exudate. He has a maculopapular rash on his chest, arms, and legs that spares the palms and soles. There is no palpable lymphadenopathy. The remainder of the examination, including cardiopulmonary and abdominal examinations, is normal.

Laboratory studies:

Leukocyte count	3100/µL (3.1 x 109/L)
Platelet count	85,500/µL (85.5 x 109/L)
Hemoglobin	13.9 g/dL (139 g/L)
Alanine aminotransferase	114 units/L
Aspartate aminotransferase	154 units/L
Total bilirubin	1.2 mg/dL (20.5 µmol/L)

Which of the following is the most likely diagnosis?

A: Dengue fever
B: Leptospirosis
C: Malaria
D: Syphilis
E: Yellow fever

MKSAP Answer and Critique

The correct answer is A: Dengue fever.

Dengue fever, a flavivirus infection transmitted by the bite of the Aedes aegyptimosquito, is the most prevalent mosquito-borne viral illness in the world. Dengue is endemic to many parts of the world, especially Southeast Asia and tropical geographic areas. A significant rise in the incidence of dengue has occurred recently in the Caribbean islands and Latin America, resulting from the reestablishment of the A. aegypti vector in these areas. On several occasions, domestically acquired (autochthonous) cases in the United States, generally limited to the southern states, have been reported. Classic manifestations in symptomatic persons present after an incubation period of 4 to 7 days. Typically, patients experience abrupt fever with chills, severe frontal headache, retro-orbital pain, and musculoskeletal pain, characteristically severe in the lumbar spine, earning dengue the name “break-bone fever.” A nonspecific macular or maculopapular rash, sparing the palms and soles, often develops within 3 to 4 days of onset of illness, tending to coincide with the resolution of fever. Referred to as a “saddle-back” pattern, a second episode of fever and symptoms may occur in some patients. Abnormal laboratory findings include leukopenia, neutropenia, thrombocytopenia, and mildly elevated liver aminotransferase concentrations, with the serum aspartate aminotransferase level often higher than the serum alanine aminotransferase level. The febrile illness may be followed by a prolonged episode of fatigue. Full recovery is expected in all infected persons. The diagnosis of dengue fever remains mainly clinical. During the early phase of illness, real-time reverse transcriptase polymerase chain reaction can be useful in detecting virus in the blood. However, acute and convalescent serologic testing is commonly used to confirm a diagnosis in returning travelers. Treatment of dengue fever involves symptomatic relief. Currently, no vaccine is clinically available to protect against infection.

Leptospirosis, caused by infection with pathogenic spirochetes belonging to the genus Leptospira, is endemic throughout the world. Infection occurs through direct or indirect contact with urine or tissues of infected animals, most often rodents and other small mammals. In most infected patients, a self-limited illness characterized by high fever, myalgia, abdominal pain, and conjunctival suffusion occurs, with a rash developing infrequently.

Malaria does not cause a rash and is not endemic to the Caribbean islands except for the Dominican Republic and Haiti.

Yellow fever, another flavivirus infection contracted through the bite of the A. aegypti mosquito, occurs mostly in areas of sub-Saharan Africa and South America, but is not endemic to the Caribbean islands.

Key Point

• Classic manifestations of dengue infection in symptomatic persons include fever with chills, severe frontal headache, retro-orbital pain, and musculoskeletal pain that is characteristically severe in the lumbar spine, as well as a nonspecific macular or maculopapular rash sparing the palms and soles.

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