Dengue Hemorrhagic Fever/Dengue Shock Syndrome

Dengue hemorrhagic fever often begins with abrupt fever and headache and is initially indistinguishable from classic dengue. Warning signs that predict possible progression to severe dengue include:

• Severe abdominal pain and tenderness

• Persistent vomiting

• Hematemesis

• Epistaxis or bleeding from the gums

• Black, tarry stools (melena)

• Edema

• Lethargy, confusion, or restlessness

• Hepatomegaly

• Pleural effusion or ascites

• Marked change in temperature (from fever to hypothermia)

Circulatory collapse and multiorgan failure, called dengue shock syndrome, may develop rapidly 2 to 6 days after symptom onset.

Bleeding diatheses manifest as follows:

• Purpura, petechiae, or ecchymoses at injection sites (usual)

• Hematemesis, melena, or epistaxis

• Subarachnoid hemorrhage (less common)

Bronchopneumonia, with or without bilateral pleural effusion, is common. Myocarditis can occur.

Mortality is usually < 1% in patients managed in centers with experience treating dengue hemorrhagic fever (1), but rates are higher for untreated patients.

• History, physical examination and laboratory criteria

Dengue hemorrhagic fever is suspected in children with World Health Organization–defined clinical criteria for the diagnosis (1):

• Sudden fever that stays high for 2 to 7 days

• Hemorrhagic manifestations

• Hepatomegaly

Hemorrhagic manifestations include at least a positive tourniquet test and petechiae, purpura, ecchymoses, bleeding gums, hematemesis, or melena. The tourniquet test is done by inflating a blood pressure cuff to midway between the systolic and diastolic blood pressure for 15 minutes. The number of petechiae that form within a 2.5-cm diameter circle are counted; > 20 petechiae suggests capillary fragility.

Complete blood count, coagulation tests, urinalysis, liver tests, and dengue serologic tests should be done. Coagulation abnormalities include:

• Thrombocytopenia (≤ 100,000 platelets/mcL [≤ 100 x 10⁹/L])

• A prolonged prothrombin time (PT)

• Prolonged activated partial thromboplastin time (PTT)

• Decreased fibrinogen

• Increased amount of fibrin split products

Other laboratory abnormalities include hypoproteinemia, mild proteinuria, elevated aspartate aminotransferase (AST) levels, and hemoconcentration (hematocrit increased by ≥ 20%).

Serological diagnosis can be made using the IgM capture enzyme-linked immunosorbent assay (MAC-ELISA). Serological testing combined with the dengue virus RNA amplification test is used to provide a diagnosis within the first 1 to 7 days of illness. The plaque reduction neutralization test (PRNT) is specific and sensitive. Titers in acute and convalescent phase serum samples can reliably establish dengue virus infection and may indicate the specific dengue virus type involved. The PRNT requires live dengue viruses for the test and is labor-intensive and expensive. Many laboratories are not able to do the PRNT.

Patients with World Health Organization-defined clinical criteria plus thrombocytopenia or hemoconcentration are presumed to have the disease (2).

• Supportive care

Patients with dengue hemorrhagic fever require intensive treatment to maintain euvolemia. Both hypovolemia (which can cause shock) and overhydration (which can cause acute respiratory distress syndrome) should be avoided. Intravascular volume is monitored by urine output and the degree of hemoconcentration.

Antiviral medications have not been shown to improve outcome.