Fever, Adult

Fever, Adult is a topic covered in the 5-Minute Emergency Consult.

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  • Fever is an elevation of core body temperature caused by an increase in the body's thermoregulatory set point.
  • Prostaglandin E2 (PGE2) synthesis in the anterior hypothalamus controls the thermostat, and is the target of antipyretics.
  • Core temperature is regulated to 37°C ± 2°C.
  • Autonomic discharge from hypothalamus can raise core temperature through shivering and dermal vasoconstriction.
  • Normal circadian variation in core temperature occurs with nadir in early morning and peaks in late afternoon.
  • Fever is not synonymous with hyperthermia or hyperpyrexia.
  • Hyperthermia is an elevated temperature with normal thermostat set point; caused by excessive endogenous heat production or endogenous production (e.g., malignant hyperthermia or heat stroke).
  • Hyperpyrexia is extreme fever >41.5°C usually from CNS hemorrhages.
  • Both exogenous and endogenous factors can raise the body's set thermoregulatory point:
    • Endogenous pyrogens include PGE2, IL-1, IL-6, TNF, IFN-γ.
    • Exogenous pyrogens include lipopolysaccharide (LPS) endotoxin and other TLR ligands, and toxic shock syndrome toxin (TSST-1) and other MHC II ligands.
  • Patients on anticytokine medications or glucocorticoids have impaired fever response.
  • Fever of unknown origin (FUO):
    • Fever >38.3°C for at least 3 wk as an outpatient and 3 days of inpatient evaluation or 3 outpatient visits without determining etiology.


  • Infectious processes:
    • CNS, chest and lung, gastrointestinal, genitourinary, skin, soft tissue and bone, vascular and endocardial
    • Iatrogenic: Catheters, implants, hardware, recent surgical sites.
  • 1° CNS processes such as CVA, trauma, seizures
  • Neoplastic fevers
  • Drug fever:
    • Most drugs can cause elevated temperatures by a wide variety of mechanisms
    • Toxidromes (e.g., adrenergic, anticholinergic, dopaminergic, salicylate overdose, serotonin toxicity)
    • Hypersensitivity:
      • Allergic reaction
      • Serum sickness
    • Jarisch–Herxheimer reaction
    • Local phlebitis from irritant drugs
  • Severe withdrawal:
    • Alcohol
    • Benzodiazepines
  • Systemic rheumatologic and inflammatory diseases (e.g., familial Mediterranean fever, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, temporal arteritis)
  • Endocrine:
    • Hyperthyroidism, pheochromocytoma
  • Miscellaneous:
    • Alcoholic cirrhosis
    • Acute inhalation exposures (e.g., metal fume fever)
    • Cotton fever:
      • Febrile reaction from an injected contaminant when IV drug abusers strain drug through cotton
    • Sickle cell disease
    • Hemolytic anemia
    • Pulmonary embolus
  • Common causes of FUO:
    • Infectious:
      • Abdominal and pelvic abscesses
      • Cardiac (endocarditis, pericarditis)
      • Cat scratch disease
      • Cytomegalovirus
      • Epstein–Barr virus
      • TB (miliary, renal, or meningitic)
      • Typhoid enteric fevers
      • Visceral leishmaniasis
    • Neoplastic:
      • Colon adenocarcinoma
      • Hepatocellular carcinoma and metastases
      • Myeloproliferative disorders
      • Leukemia and lymphoma
      • Renal cell carcinoma

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