II. Definitions

  1. Fever
    1. Standard criteria
      1. Temperature >38 C (100.4 F)
    2. Criteria in adults over age 65 years
      1. Fever: Temperature rise of 1.1 C (2 F) over baseline
      2. High fever suggesting severe infection: 38.3 C (101 F)
  2. Remittent Fever
    1. Daily elevated Temperature (>38 C or 100.4 F)
    2. Returns to baseline but not to normal
  3. Intermittent Fever (Periodic Fever, Relapsing Fever)
    1. Intermittently elevated Temperature (>38 C, 100.4 F)
    2. Return to baseline and to normal
    3. Examples
      1. PFAPA Syndrome: Fever every 3-4 weeks
        1. Most common cause in children age <5 years
      2. Relapsing Fever (Borrelia species): Every 2-3 weeks
      3. Malaria
        1. Plasmodium Vivax: fever at 48 hour intervals (Tertian Fever)
        2. Plasmodium Malariae: fever at 72 hour intervals (Quartan Fever)
      4. Rat Bite Fever: Fever every 3 to 5 days
      5. Hodgkin's Disease: Pel-Ebstein Fever
      6. Cyclic Neutropenia: Fever every 3 weeks
        1. Associated with Mucosal Ulcer
  4. Fever Peak Timing
    1. Fever typically peaks in the evening
    2. Morning fever peak
      1. Polyarteritis Nodosa
      2. Typhoid Fever
      3. Whipple Disease
    3. Twice daily fever peak
      1. Malaria
      2. Miliary Tuberculosis
      3. Still Disease
      4. Visceral Leishmaniasis
  5. Hectic Fever
    1. Daily elevated Temperature (>38 C or 100.4 F)
    2. Either remittent or intermittent pattern
    3. Temperature excursion >1.4 C (2.5 F)
    4. Examples
      1. Intermittent bacteremia (dental abscess, UTI)
      2. Epstein-Barr Virus
      3. Familial Mediterranean Fever
      4. Crohn's Disease
      5. Still's Disease (Juvenile Rheumatoid Arthritis)
  6. Sustained or Continuous Fever
    1. Daily elevated Temperature (>38 C or 100.4 F)
    2. Fluctuation of elevated Temperature < 0.3 C (0.5 F)
    3. Associated conditions
      1. Drug Fever
      2. Salmonella
  7. Pulse-Temperature Dissociation
    1. Pulse slower than normal for fever degree (pulse fails to increase with fever spike)
    2. Associated conditions
      1. Typhoid Fever
      2. Rickettsial infection
  8. Fever with Bradycardia (Facet Sign)
    1. See Pulse-Temperature Dissociation as above
    2. Associated conditions
      1. Central Nervous System Malignancy
      2. Lymphoma
      3. Typhoid Fever
      4. Yellow Fever

III. Pathophysiology

  1. Fever is an inflammatory response
    1. Endogenous pyrogens (inflammatory Cytokines) trigger the Hypothalamus to increase Body Temperature
    2. Fever is not synonymous with infection, as fever can be triggered by any systemic inflammatory response
  2. Fever is a host adaptive response to invading infection
    1. Increased Body Temperature increases immune function
    2. Increased Body Temperature decreases viral and Bacterial replication
  3. Fever during pregnancy
    1. Fever (esp prolonged >3 days) in first trimester in pregnancy has been associated with congenital disorders
    2. Associations include congenital neurodevelopmental disorders (e.g. Autism)
    3. Risk does not appear to be reduced by antipyretics
    4. Antoun (2021) Mol Autism 12(1): 60 [PubMed]

IV. Classification

  1. Fever Without Focus
    1. Age <36 months
    2. Higher risk in younger infants
    3. Fever without localizing signs
    4. Acute onset of fever persisting <1 week
    5. Assess for Occult Bacteremia
  2. Fever of Unknown Origin (FUO)
    1. Fever exceeding 1 week duration
    2. Fever documented in the hospital
    3. All possible investigations performed during the week

V. Causes: Common Non-Infectious Causes of Low Grade Fever

  1. Over-dressing
  2. Recent Exercise
  3. Hot weather
  4. Warm foods
  5. Recent Immunization
    1. DTP Vaccine within 24 hours
    2. MMR Vaccine within 7 to 10 days

VI. Management

  1. See Fever Symptomatic Treatment
  2. See Fever Without Focus
  3. Fever is not harmful in critically ill patients (HEAT Trial)
    1. Lowering fever does not affect outcomes (including days admitted to ICU)
    2. Young (2015) N Engl J Med 373:2215-24 [PubMed]

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