Yellow Fever Clinical Presentation

Updated: Jun 26, 2015
  • Author: Mary T Busowski, MD; Chief Editor: Mark R Wallace, MD, FACP, FIDSA  more...
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To arrive at a diagnosis, consider the patient's clinical features and his or her places and dates of travel, including the epidemiologic history of the places visited, immunizations, and activities.

After an incubation period of 3-6 days, most individuals with yellow fever have a mild, self-limiting illness consisting of fever, headache, myalgia, and malaise. More serious illness develops in 15% of cases and presents with the abrupt onset of general malaise, fever, chills, headache, lower back pain, nausea, and dizziness. Physical findings include pulse-fever dissociation (Faget sign), conjunctival injection, and facial flushing.

Significant laboratory findings usually include leukopenia with relative neutropenia. Transaminase levels may rise 48-72 hours after initial symptoms appear. This is followed by a period of remission, with normalization of symptoms and temperature for up to 24 hours. The patient may then either recover or progress to fatal illness (up to half of cases).

Remission followed by the return of symptoms is classified as the period of intoxication. Viremia is reduced, and humoral-mediated reactions are responsible for marked physical illness. [11] This stage is marked by fever, vomiting, abdominal pain, renal failure, and hemorrhage. Petechiae, ecchymoses, epistaxis, and bleeding from gums and venipuncture sites can progress to melena, hematemesis, and metrorrhagia.

Jaundice worsens as the levels of transaminases increase, with serum aspartate aminotransferase (AST) levels typically higher than those of alanine aminotransferase (ALT) owing to direct viral injury to skeletal muscle tissue and myocardium. Progressive liver involvement and humoral-mediated responses can lead to consumption coagulopathy. Prolonged clotting and prothrombin times and reduced levels of fibrinogen and clotting factors II, V, VII, VIII, IX, X occur; also, fibrin split products appear.

Hepatorenal disease carries a mortality rate of 20%-50%; with death occurring 7-10 days after onset of symptoms. The terminal phase is marked by delirium, stupor, and coma due to cerebral edema and microscopic perivascular hemorrhage.


Physical Examination

Physical examination findings for yellow fever include fever, relative bradycardia for the degree of fever (Faget sign), conjunctival injection, and skin flushing.

Other physical findings, such as scleral icterus, jaundice, epigastric tenderness, and hepatomegaly, develop as disease progresses. Early appearance of jaundice indicates a poor prognosis.

Disseminated intravascular coagulation (DIC), induced by liver dysfunction, leads to consumption of platelets and clotting factors. This process clinically presents as a combination of a bleeding diathesis and organ ischemia secondary to fibrin deposition throughout the microcirculation. Petechiae, purpura, mucosal bleeding, and gastrointestinal bleeding (gross or hemoccult) will often be apparent.

Ischemia primarily affects the kidneys and central nervous system leading to altered mental status and/or signs of volume overload (jugular venous distension, presence of rales, and S3 gallop, or edema).

Late stages

In late stages of disease, shock and multiorgan dysfunction syndrome (MODS) dominate the clinical picture. These septic patients present with tachycardia, hypothermia or hyperthermia, and hypotension. Individuals who are severely hypoperfused appear mottled and cyanotic. They are also often obtunded.

Tachypnea and hypoxia with impending respiratory failure may develop as a consequence of sepsis and acute respiratory distress syndrome (ARDS).