Fever

I. Background
Fever is an elevation in the core body temperature above the individual's normal range that occurs in conjunction with an increase in the hypothalamic temperature set point. Fever is defined as a core body temperature of 38°C (100.4°F). Hyperthermia is an elevated body temperature without a change in the hypothalamic setting. Hyperpyrexia, a medical emergency, is defined as a temperature over 41.1°C (106.0°F).
II. Pathophysiology
A. Mechanisms of temperature control
Body temperature is controlled by the hypothalamus, which receives inputs from both the peripheral nerves and from the temperature of the blood supplying the area. Normal body temperature is maintained across environmental variations through the regulation of heat production from metabolic activity (mostly of the muscles and liver) and heat dissipation from the skin and lungs. It is widely held that normal body temperature is 37.0°C (98.6°F), but several studies have shown that average temperatures in healthy adults range from 30.0°C to 37.2°C (86.0°F - 99.0°F) with averages 36.4°C to 36.8°C (97.5°F - 98.2°F) and 99th percentile 37.5°C to 37.7°C (99.5°F - 99.9°F)(1,2).
B. Temperature measurement
How the temperature is taken can affect the result. Rectal temperature is considered the closest approximation to core temperature. Sublingual temperatures are felt to be fairly reliable, and generally measure 0.6°C (1.0°F) lower than rectal temperatures. Axillary and tympanic measurements are less reliable, with axillary temperatures ranging from 0.25°C to 0.85°C (0.4°F - 1.5°F) lower than rectal measurements, and tympanic measurements ranging from 1.3°C (2.3°F) lower than rectal to 0.7°C (1.3°F) higher (3,4).
C. Temperature variation
Normal body temperature varies by an average of 0.5°C (0.9°F) throughout the day, with the lowest temperature early in the morning and peak in the mid afternoon. Other factors that influence normal body temperature include age, race, physical activity, postprandial state, pregnancy or ovulation, endocrine disorders, clothing, and ambient temperature and humidity.
III. Evaluation
A. History
A detailed history is essential to establishing the cause of fever. The history should include the following components:
  • Complete review of systems as well as past medical problems
  • Previous surgeries, with attention to any implanted materials or devices
  • Medications, supplements, and other drugs used
  • Recent and remote travel
  • Exposure to ill individuals
  • Exposure to animals or insects
  • Occupation
  • Ingestion of any questionable foods or substances
  • Family history of unusual illnesses
B. Physical examination
Careful physical examination should be performed.
  • Temperature and other vital signs should be measured accurately. Heart rate, blood pressure, and respiratory rate normally increase in the face of fever. Bradycardia may be a sign of atypical infections. Hypotension may be a sign of systemic sepsis.
  • An examination of all organ systems and body areas should be performed, with emphasis given to the skin, lymphatics, heart, lungs, and nervous system. In addition, genital and rectal examinations should be performed regardless of gender.
C. Testing
Diagnostic testing should be guided by the history and physical examination.
  • When the source of the fever is unclear, helpful laboratory tests include white blood cell count with differential, urinalysis with microscopic examination and culture if results are abnormal, and aerobic and anaerobic blood cultures.
    TABLE 2.6.1 Potential Causes of Fever of Unknown Origin
    Infectious diseases Collagen vascular diseases Malignancies Medications Other
    Tuberculosis Still's disease Lymphoma Carbamazepine Granulomatous diseases
    Occult abscess Temporal arteritis Leukemia Phenytoin Pulmonary embolus
    Osteomyelitis Polyarteritis nodosa Hypernephroma Antihistamines Venous thrombosis
    Endocarditis Rheumatic fever Other solid tumors Methyldopa Endocrine disorders
    Sinusitis Systemic lupus erythematosus Atrial myxoma Allopurinol Factitious fever
    HIV (late stage) Rheumatoid arthritis Colon cancer Sulfonamides Cerebrovascular accident
    Q fever Polymyalgia rheumatica Hepatoma Cephalosporins Alcoholic hepatitis
    Tropheri -- -- Isoniazid Cirrhosis
    Brucella -- -- -- --
    Mycoplasma -- -- -- --
    Chlamydia -- -- -- --
    Histoplasmosis -- -- -- --
    Legionella -- -- --  
    Bartonella -- -- --
    HACEK -- -- --
    Amebic hepatitis -- -- --
    Medical device infections -- -- --
    HACEK, Haemophilus species (H. parainfluenzae, H. aphrophilus, and H. paraphrophilus), Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species.
  • A chest radiograph and abdominal imaging (computed tomography or ultrasound) may be helpful if the history and physical examination suggest a pulmonary or abdominal infection.
  • If the source of the fever remains undetermined after these common tests have been performed, other tests to consider include the human immunodeficiency virus serology, rapid plasma reagin, rheumatoid factor, antinuclear antibody, sedimentation rate or C-reactive protein, serum chemistries and enzymes, tuberculosis skin testing, examination of the spinal fluid, and technetium-labeled bone scan.
IV. Diagnosis
A. Acute febrile illness
In the outpatient setting, most fevers are associated with an acute illness and are caused by self-limited viral infections, such as upper respiratory tract infections or acute gastroenteritis. These infections usually resolve in 7 to 10 days and require only supportive and symptomatic therapy. Common bacterial infections requiring antibiotic therapy include streptococcal pharyngitis, cellulitis, tract infections, pneumonia, acute exacerbation of chronic bronchitis, and bacterial sinusitis. A careful history and physical examination, supported by selected diagnostic tests should lead to a specific diagnosis in almost all of these cases.
Figure 2.6.1. Approach to the evaluation of fever. FUO, fever of unknown origin.
B. Fever in the elderly
Infections in the elderly often do not result in the same signs and symptoms as in younger patients. While some elderly patients may fail to mount a febrile response to some infections, febrile elders are more likely to have a bacterial illness than are their younger counterparts. A careful search for an infection should be undertaken for older individuals with fever, signs or symptoms of an infection (e.g., cough, urinary frequency), or a change in their appetite, behaviors, physical abilities, or mental status. Common sites of infections in the elderly include the skin, lungs, and the urinary system.
C. Postoperative fever
Common causes of fever in the postoperative period can be categorized by how soon after surgery the fever develops. Fever in the first 2 days after surgery is often caused by atelectasis of the lungs. Urinary tract infections, pneumonia, and infections of intravascular access sites commonly present on postoperative days 3 through 5. Fevers beyond the fifth day after surgery should lead one to consider wound infections or abscesses.
D. Fever of unknown origin (FUO)
Numerous definitions of FUO exist, but most include a fever documented on several different days over 2 or 3 weeks, with no diagnosis found following repeated physical examinations and routine diagnostic tests. Diseases that may cause FUO are listed in Table 2.6.1. One approach to evaluating the patient with FUO is shown in Figure 2.6.1. The underlying etiology is eventually found in over 90% of FUO cases. Historically, the most common cause of FUO was infection, followed by malignancies, and then rheumatologic diseases. In more recent studies, rheumatologic causes have surpassed malignancies as the second most common cause of FUO. FUO is much more likely to be caused by an unusual presentation of a common disease than a common presentation of an unusual disease (5).
References
1. Mackowiak PA, Wasserman SS, Levine MM. A critical appraisal of 98.6 degrees F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA 1992;268:1578 - 1580.
2. Leckie T. Normal temperature in the elderly. Last modified 22 June 2004. Accessed at BestBETs: Best Evidence Topics (www.bestbets.org/cgi-bin/bets.pl?record=00774) on 15 May 2005.
3. Ridell A, Eppich W. Should tympanic temperature measurement be trusted? Last modified 19 February 2003. Accessed at BestBETs: Best Evidence Topics (www.bestbets.org/cgi-bin/bets.pl?record=00340) on 15 May 2005.
4. Craig JV, Lancaster GA, Williamson PR, et al. Temperature measured at the axilla compared with rectum in children and young people: systemic review. BMJ 2000;320:1174 - 1178.
5. Mourad O, Palda V, Detsky AS. A comprehensive evidence-based approach to fever of unknown origin. Arch Intern Med 2003;163:545 - 551.