eMedicine Specialties > Dermatology > Viral Infections

Viral Hemorrhagic Fevers

Author: Arash Michael Saemi, MD, Department of Internal Medicine, Naval Medical Center San Diego
Coauthor(s): Nili N Alai, MD, FAAD, Assistant Clinical Professor, Department of Dermatology, Clinical Faculty and Preceptor, Department of Family Practice, University of California, Irvine; Clinical Faculty and Preceptor, Department of Family Practice Residency Training, Downey Medical Center; Medical Director, The Skin Center at Laguna; Expert Medical Reviewer, Medical Board of California
Contributor Information and Disclosures

Updated: Oct 1, 2008

Introduction

Background

Viral hemorrhagic fevers (VHFs) are a group of etiologically diverse viral diseases unified by common underlying pathophysiology. These febrile diseases result from infection by viruses from 4 viral families: Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae.

The viruses in the 4 families are all RNA viruses. All share the feature of having a lipid envelope. Survival and perpetuation of the viruses is dependent on an animal host known as a natural reservoir; humans are not the natural reservoir. With the exception of a vaccine for yellow fever and ribavirin, which is used as a drug treatment for some arenaviral infections, no cures or drug treatments for viral hemorrhagic fever exist. Only supportive treatment is possible.

Not all viruses in these families cause viral hemorrhagic fever. Viral hemorrhagic fevers share certain clinical manifestations, regardless of the virus that causes the disease. However, different viruses can cause a range of various clinical problems in addition to viral hemorrhagic fever. Common clinical manifestations of viral hemorrhagic fever are increased capillary permeability, leukopenia, and thrombocytopenia. Viral hemorrhagic fever is manifested by sudden onset, fever, headache, generalized myalgia, backache, petechiae, conjunctivitis, and severe prostration. Various hemorrhagic symptoms follow, ultimately resulting in focal inflammatory reaction and necrosis with leukocytosis.

Although the viruses are distributed all over the world, they have a higher occurrence in tropical areas, such as South America, Africa, and the Pacific Islands. They have a higher likelihood of importation because of increased travel and scientific research involving the use of imported tropical animals, which often serve as intermediate hosts. The viruses are transmitted by 2 main categories of natural reservoirs: arthropods and rodents. Arenaviruses and Hantavirus (a Bunyavirus) are primarily rodent-borne, whereas flaviviruses, as well as nairoviruses and phleboviruses (both bunyaviruses), are arthropod-borne.

Transmission occurs mainly by means of contact with the following: natural reservoirs (eg, mosquito bites, rodent bites); reservoir excretions, secretions, or blood; aerosolized particles contaminated by reservoir secretions, excretions, or blood; or intermediate hosts (eg, monkeys, livestock) or their excretions, secretions, or blood. Person-to-person transmission and nosocomial transmission also occur. Nosocomial outbreaks are not uncommon in developing countries, where safe infectious disease practices have not been implemented and supplies are in shortage.

Related resources include the following:

• Medscape Emerging and Reemerging Infectious Diseases Resource Center
• Medscape Disaster Preparedness and Aftermath Resource Center
• eMedicine article CBRNE - Viral Hemorrhagic Fevers
• eMedicine article Viral Hemorrhagic Fevers (Pediatrics version)
• eMedicine article Dermatologic Aspects of Bioterrorism Agents

Pathophysiology

The main common underlying pathophysiologic feature of viral hemorrhagic fevers is that the vascular bed is attacked, with resultant microvascular damage and changes in vascular permeability. However, specific pathophysiologic findings can vary depending on the virus family and the species involved.

In general, an initial febrile illness is followed by hemorrhaging into the skin and the mucous membranes; hemorrhagic rashes; and hemorrhages from body orifices, especially gastrointestinal and genitourinary bleeding. Lassa fever, although fatal, is not characterized by significant bleeding. Other clinical findings include thrombocytopenia and leukocytopenia.

Frequency

United States

Most of the natural reservoirs of these viruses live in tropical areas. Hence, the virus does not typically infect persons in the United States. Random cases of infection occur as a result of the importation of viruses by travelers or the importation of scientific research animal subjects. Several cases of infection resulting in Hantavirus pulmonary syndrome (HPS), however, have been reported across the United States.¹

International

Table 1. Geographic Distribution of Viral Hemorrhagic Fevers

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Mortality/Morbidity

Children can develop dengue hemorrhagic shock syndrome (DHSS), a complication with a mortality rate of 4-12%.

Table 2. Viral Hemorrhagic Fever – related Mortality Rates

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Race

No race is known to be more vulnerable than another to RNA viral infection. Geography is a determining factor.

Sex

Neither sex is known to be more or less vulnerable to RNA viral infection.

Age

Age plays a role in increasing the vulnerability to infection in only 2 circumstances, as follows:

• First, young and elderly persons are more susceptible because of their weaker immune systems.
• Second, adults are more susceptible if they work in settings in which the exposure risk is increased (eg, clinics or hospitals, agrarian settings).

Clinical

History

Not all individuals who are infected have viral hemorrhagic fever. The target organ is the vascular bed. As a result, the dominant clinical manifestations are due to microvascular damage and changes in vascular permeability.

Viral hemorrhagic fever should be suspected in patients who live in or who have returned from locations of viral occurrence if they have severe fever and evidence of vascular involvement (eg, subnormal blood pressure, postural hypotension, petechiae, easy bleeding, flushing, nondependent edema).

• The severity of symptoms varies. Common symptoms include the following:
  • Myalgia
  • Fever
  • Prostration
  • Vomiting
  • Headache
  • Petechial hemorrhages
  • Hypotension
  • Flushing of the head and the chest
  • Edema
  • Malaise
  • Diarrhea
• Severe viral hemorrhagic fever evolves to shock and generalized mucous membrane hemorrhage.
  • Viral hemorrhagic fever is often accompanied by neurologic, hematopoietic, or pulmonary involvement.
  • Hepatic damage is also common among viral hemorrhagic fevers, but hepatic failure, as indicated by jaundice and other evidence, is seen in some cases of Rift Valley fever (RVF), Congo-Crimean hemorrhagic fever (CCHF), Marburg fever, Ebola fever, and yellow fever.
  • Neurologic symptoms and thrombocytopenia are common in Argentinian and Bolivian hemorrhagic fevers.
  • Kyasanur Forest disease and Omsk fever are known for their pulmonary involvement and a biphasic illness with central nervous system (CNS) manifestations.
  • Hantavirus pulmonary syndrome (HPS) is known for its pulmonary involvement leading to noncardiogenic pulmonary edema.¹

Physical

• Arenaviruses²
  • Lassa, Argentinian, and Bolivian viral hemorrhagic fevers
    • The first signs are nonspecific and include fever, headache, and sore throat.
    • The second stage is characterized by an exacerbation of symptoms and rashes on the face or the neck.
    • Gastrointestinal and urogenital tract bleeding and shock may follow during the second week.
    • Neurologic sequelae are a main feature, especially in Lassa hemorrhagic fever.
  • Argentinian viral hemorrhagic fever
    • Early symptoms include high fever, malaise, headache, retro-orbital pain, anorexia, and nausea.
    • Signs are erythematous rash of the face, the neck, and the thorax, and hemorrhages into the skin and the mucous membranes.
    • CNS involvement appears around day 7 in fatal cases. It is an important indicator of severity and is a better indicator than hemorrhage.
  • Bolivian viral hemorrhagic fever
    • Bolivian hemorrhagic fever has an insidious onset, leading to high temperature, severe myalgia, headache, vomiting, retrobulbar pain, conjunctival hyperemia, leukopenia, and mild thrombocytopenia.
    • Petechiae of the skin and the oral mucous membranes usually appear around day 4.
    • Epistaxis, gingival bleeding, hematemesis, melena, and metrorrhagia may follow.
    • Hypotension and/or neurologic abnormalities, including tremors, delirium, and seizures, develop between days 6 and 10.
    • Circulatory collapse eventually results in death.
  • Lassa fever
    • Lassa fever can vary from a long-lasting acute fever to a fatal disease.
    • Its clinical manifestations include headache, fever, weakness, myalgia, ulcerative pharyngitis, dysphagia, anorexia, nausea, vomiting, cough, and constipation.
    • The aforementioned findings can be followed by diarrhea, melena, dysuria, cutaneous petechiae and ecchymoses, erythema of the face and the thorax, facial and cervical edema, rales, rhonchi, stridor, wheezing, hypotension, hepatic tenderness, pleural effusions, cloudy sensorium, and seizures.
• Bunyaviruses
  • Rift Valley fever³
    • RVF is an influenzalike disease.
    • Its onset involves chills, fever, headache, retro-orbital pain, myalgia, anorexia, vomiting, and diarrhea.
    • Physical signs include fever, facial erythema, and conjunctival suffusion.
    • A small percentage of patients present with retinal lesions, which may result in permanent blindness, hemorrhagic diathesis, and encephalitis.
    • RVF may progress to a hemorrhagic fever stage. Clinical manifestations of this stage may include hematemesis, melena, petechial and ecchymotic cutaneous lesions, gingival bleeding, hematuria, epistaxis, and jaundice.
  • Congo-Crimean hemorrhagic fever
    • Early symptoms of CCHF include those previously mentioned for RVF.
    • Patients may present with erythema of the pharynx, the conjunctivae, the face, and the neck; a petechial rash on the trunk and the limbs; and hemorrhages of the uvula and the soft palate.
    • CCHF is a severe disease. On days 3-7, patients may have hematemesis; melena; cutaneous purpura; epistaxis; hematuria; hemoptysis; and bleeding from gingival, oral, uterine, and venipuncture sites.
  • Korean hemorrhagic fever⁴
    • This infection is a subgroup of hemorrhagic fever with renal syndrome (HFRS).
    • Disease progression is severe and is characterized by fever, hemorrhage, and renal failure.
  • Hantavirus pulmonary syndrome
    • The illness has 5 distinct phases and is marked by deterioration of breathing during the cardiopulmonary phase.
    • Capillary leakage results in noncardiogenic pulmonary edema and may progress to shock.
    • As in HFRS, disease progression is rapid with a high rate of mortality.
• Filoviruses
  • Ebola and Marburg viruses are pantropic, that is, they infect and cause lesions in many organs, especially the liver and the spleen.
    • Both organs become enlarged and dark while undergoing severe degeneration.
    • Disseminated intravascular coagulation may be a feature of late disease.
    • Damage to endothelial cells increases vascular permeability, followed by hemorrhage and shock; these are central features of the infections, which have high mortality rates.
  • Ebola fever
    • Early symptoms of Ebola-induced viral hemorrhagic fever are high temperature, headache, myalgia, stomach pain, rashes, sore throat, and red and itchy eyes.
    • Within 1 week of disease onset, chest pain, hemorrhaging from body orifices, blindness, and death occur.
  • Marburg fever⁵
    • Disease onset is marked by fever, chills, headache, and myalgia.
    • Approximately 5 days after disease onset, a maculopapular rash may appear, with greatest prominence on the trunk.
    • Patients present with jaundice, inflammation of the pancreas, weight loss, delirium, shock, liver failure, and multiorgan dysfunction.
• Flaviviruses
  • Omsk hemorrhagic fever
    • Physical findings include congested conjunctivae, papulovesicular eruptions on the soft palate (an important diagnostic sign), severe pain in the back and the limbs, fever, headache, diarrhea, and vomiting.
    • The illness is biphasic, with meningismus or meningoencephalitis occurring in the second phase.
    • The disease is also characterized by hyperemia of the face and the upper body.
    • Bleeding gums, epistaxis, hemoptysis, uterine hemorrhage, hematemesis, melena, and other hemorrhaging may occur.
  • Yellow fever
    • Yellow fever is characterized by jaundice, a result of midzone necrosis of the liver (by about the third day), flushing of the face, congested conjunctivae, and reddening edges of the tongue.
    • The heart and the kidney are damaged.
    • Hemorrhagic symptoms may appear early, with swelling and bleeding of the gums and epistaxis. Hemorrhaging from the gastrointestinal mucosa may cause black vomit and melena.
  • Dengue fever^6,7
    • Patients present with maculopapular rashes and fever, severe joint and muscle pains, lymphadenopathy, and altered or diminishing gustation.
    • Dengue fever, like yellow fever, may progress from a febrile illness to a hemorrhagic one.
    • Minor hemorrhagic symptoms, such as epistaxis, petechiae, or bleeding gums, may accompany other febrile symptoms early in the disease.
    • An enlarged liver can be palpated during the later stages of the disease.
    • Children may develop DHSS, a complication with a mortality rate of 4-12%.

Causes

Causes of viral hemorrhagic fevers are the specific RNA viruses mentioned above.

• Infection by different viruses results in hemorrhagic fever with different complications, symptoms, and severity, as previously discussed.
• Viruses are usually transmitted by mosquitoes, ticks, or rodents. Some species of bats may also prove to be virus carriers.⁸
• The strong immunologic response to the viruses may be central to the pathophysiology of plasma leakage associated with these diseases.⁹

• Search for CME/CE on This Topic »

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