Hemorrhagic Fever With Renal Failure Syndrome Clinical Presentation

Updated: Oct 04, 2018
  • Author: Rajendra Bhimma, MBChB, MD, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal); Chief Editor: Craig B Langman, MD  more...
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Presentation

History

The clinical features in hemorrhagic fever with renal failure syndrome (HFRS) consist of a triad of fever, hemorrhage, and renal insufficiency. Other common symptoms during the initial phase of the illness include headache, myalgia, abdominal and back pain, nausea, vomiting, and diarrhea. Other symptoms include chills, dizziness, increased thirst, costovertebral tenderness, and flank pain. The incubation period is 12-16 days. The disease may range from mild to severe. Subclinical infections are especially common in children. The average incubation period varies from 4-42 days. The disease is characterized by fever, hemorrhagic manifestations, and (if severe) hypovolemic shock.

Recently, hemorrhagic fever with renal failure syndrome associated with acute pancreatitis has been described in an adult male, but there have been no similar reports in children. [4] In another case report, hemorrhagic fever with renal failure syndrome from Dobrava virus infection with and atypical presentation of orchitis was described in a 25-year-old man. [5]

The disease has 5 progressive stages: febrile, hypotensive, oliguric, diuretic, and convalescent. Only a third of patients follow a typical clinical course. Physicians should be aware of the various presentations during each stage. Individual patients can completely skip stages.

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Physical

Physical examination of the patient is based on the stage of the illness.

  • The febrile stage occurs in all patients and lasts about 3-7 days. The disease is characterized by an abrupt onset of fever with a temperature in the range of 40°C.

    • Patients may complain of headache, chills, abdominal pain, malaise, blurred vision, and lower back pain.

    • Flushing of the face, neck, and chest due to probable vascular dysregulation may be observed.

    • Petechia may occur in the axilla and soft palate.

    • Subconjunctival hemorrhage is noted in one third of patients.

    • Absolute bradycardia may be noted.

    • A normal or mildly elevated hematocrit level caused by hemoconcentration may be observed. Leucocytosis with atypical lymphocytes. The disease is characterized by thrombocytopenia [6] , which also defines prognosis and severity of renal failure.

    • The onset of proteinuria and microhematuria can be observed. [7] Proteinuria due to Hantavirus nephritis is transient and usually resolves within 2 weeks.

  • The hypotensive stage lasts approximately a few hours to 2 days. It occurs in 11% of patients and coincides with defervescence. This phase is characterized by low blood pressure and kidney failure.

    • Patients may have tachycardia, which may indicate impending shock.

    • Patients may have acute abdomen caused by a paralytic ileus.

    • Patients may have convulsions or purposeless movements.

    • The coagulation profile may reveal a prolonged bleeding time, prothrombin time (PT), and activated partial thromboplastin time (aPTT).

  • The oliguric stage occurs in 65% of the patients and lasts about 3-6 days.

    • Acute kidney injury characterized by oliguria, hypertension, bleeding tendency (caused by uremia), and edema are characteristic of this stage. During this phase, blood urea and serum creatinine reach their highest levels.

    • Patients may develop pulmonary edema.

    • Thrombocytopenia usually resolves in the oliguric stage.

  • The diuretic stage lasts 2-3 weeks.

    • Diuresis in the range of 3-6 L/d occurs after symptoms from the previous stage disappear. Responsiveness of the collecting duct to vasopressin is reduced.

    • Rapid signs of dehydration and severe shock can occur during this stage if fluid replacement is inadequate. The patient's volume status should be closely monitored.

  • The convalescent stage may last for as long as 3-6 months.

    • Clinical recovery usually begins in the middle of the second week, with a gradual resolution of symptoms and azotemia.

    • The concentrating capacity of the renal tubules recovers over many months.

    • Patients may still have lack of stamina and complain often of muscular pain. Some may have an intention tremor.

    • During convalescence, patients begin to gain weight.

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Causes

The viruses of the genus Hantavirus (family Bunyaviridae) cause different forms of hemorrhagic fever with renal failure syndrome. The severity of the illness depends on the infecting virus and on the geographic distribution. The Hantaviruses associated with HFRS include inter alia: Hantaan virus (HTNV), Dobrava/Belgrade virus (DOBV), Seoul virus (SEOV), Puumala virus (PUUV), and Saaremaa virus (SAAV), while HPS is caused by Sin Nombre (SNV) and related viruses.

  • Korean hemorrhagic fever, a severe type of hemorrhagic fever with renal failure syndrome observed in Asia, is caused by a Hantavirus and is transmitted by the infected A agrarius mouse (striped field mouse). [8]

  • Balkan hemorrhagic fever, a severe type of hemorrhagic fever with renal failure syndrome observed in Balkan countries, is caused by the Dobrava virus and is transmitted by the infected A flavicollis mouse (yellow-necked field mouse).

  • A mild-to-moderate form of hemorrhagic fever with renal failure syndrome is caused by the Seoul virus and is transmitted by the infected Rattusrattus rat (black rat) or the Rattusnovergicus rat (urban rat).

  • Nephropathiaepidemica, a mild form of hemorrhagic fever with renal failure syndrome observed in Europe, is caused by the Puumala virus and is transmitted by the infected Clethrionomysglariolus vole (European bank vole).

  • The virus is usually transmitted to humans through inhalation of infected animal excreta (ie, urine, feces, saliva). Transmission by bite occurs among rodents and may also result in human infection. There has been no documentation to date of transmission between humans. Epidemiological investigations have linked viral exposure to activities such as heavy farm work, threshing, sleeping on the ground, military exercises, and lower socioeconomic status.

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