Dina Halegoua-De Marzio, MD, is an attending gastroenterologist and transplant hepatologist in practice at Thomas Jefferson University Hospital in Philadelphia, PA. Halegoua-DeMarzio will oversee the Case Conference blog, working with the fellows at Thomas Jefferson for the most interesting and engaging cases of the month.

Disclosure: Halegoua-DeMarzio reports she was an consultant for Intercept Pharma.

BLOG: 54-year-old female with Dengue fever


Dengue is an RNA virus first discovered in 1779 with a genome that encodes ten distinct proteins. The virus belongs to the Flavivirus genus and has four different serotypes. The infectious vector is via mosquito; typically the Aedes aegypti. Worldwide, Dengue fever is the most prevalent mosquito-borne viral illness and is recognized in over 100 different countries with a reported 50 to 100 million cases yearly.

Viremia typically develops 2 to 6 days after exposure and lasts for 3 to 6 days. Viremia is detectable 6 to 18 hours before symptom onset and typically resolves with fever resolution. Antibody response and protective effect is serologic specific with waning immunity to other serotypes. The risk of severe disease is higher in secondary infection than primary which is partly explained by the concept of antibody-dependent enhancement.

Neutralization of virus requires a threshold level of antibodies. Below this threshold cellular uptake of antibody bound virus is paradoxically increased up to 100-fold and can lead to more severe infection. Patients previously exposed to the virus might have a low level of antibodies present at the time of re-infection predisposing them to this phenomenon. Other risk factors for severe disease include: Dengue serotype 2, secondary infections, younger age, better nutritional status, and Caucasian race.

Classic Dengue infection presents as an acute febrile illness with headache, retro-orbital pain, myalgias, and joint pain (which explains the moniker “break bone fever”). The typical course consists of 5-7 days of fever with post-resolution fatigue. Associated symptoms include rash, nausea, vomiting, diarrhea, cough, congestion, and hemorrhage in severe cases.

The World Health Organization criteria defining Dengue Hemorrhagic Fever (DHF) include: increased vascular permeability, marked thrombocytopenia (<100,000), fever lasting two to seven days, and hemorrhagic tendency. Dengue shock syndrome (DSS) consists of the above criteria in addition to systemic shock usually from plasma leakage and carried a 12% mortality.

As in the above case, liver failure and central nervous system dysfunction including seizures can complicate severe DHF, although acute liver failure is uncommon. The mechanism of liver injury is unclear, although the virus can be cultured form hepatocytes which supports the common theory of direct viral damage. There may be a bystander immune injury effect as well. The typical pattern of hepatic injury is hepatocellular and pathology usually shows hepatocellular necrosis and Councilman bodies with little inflammatory infiltrate and steatosis as seen above. Treatment is mostly supportive with aggressive hydration and intensive care when needed as well as avoidance of the disease vector mosquitos.

Acknowledgements: Wei Jiang, MD, Thomas Jefferson University Hospital Pathology Department.


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