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- For other uses, please see Fever (disambiguation).
Fever (also known as pyrexia, or a febrile response from the Latin word febris meaning fever, and archaically known as ague) is a frequent medical symptom that describes an increase in internal body temperature to levels that are above normal (37°C, 98.6°F). Fever is most accurately characterized as a temporary elevation in the body’s thermoregulatory set-point, which is usually by about 1-2°C. Fever differs from hyperthermia, which is an increase in body temperature over the body’s thermoregulatory set-point (due to excessive heat production or insufficient thermoregulation, or both).
The elevation in thermoregulatory set-point means that the previous "normal body temperature" is considered hypothermic, and effector mechanisms kick in. The person who is developing the fever has a cold sensation, and an increase in heart rate, muscle tone and shivering attempt to counteract the perceived hypothermia, thereby reaching the new thermoregulatory set-point.
Measurement
When a patient has or is suspected of having a fever, that person's body temperature is measured using a thermometer. At a first glance, fever is present if:
- rectal temperature (in the anus) is at, or higher than 38 degrees Celsius (100.4 degrees Fahrenheit)
- oral temperature (in the mouth) is at, or higher than 37.5 degrees Celsius (99.5 degrees Fahrenheit)
- axillar temperature (in the armpit) is at, or higher than 37.2 degrees Celsius (99 degrees Fahrenheit)
However, there are many variations in normal body temperature, and this needs to be considered when measuring fever. Body temperature normally fluctuates over the day, with the lowest levels at 4 A.M. and the highest at 6 P.M.. Therefore, an oral temperature of 37.5°C would strictly be a fever in the morning, but not in the afternoon. Normal body temperature may differ as much as 0.4°C (0.7°F) between individuals. In women, temperature differs at various points in the menstrual cycle, and this can be used for family planning (although it is only one of the variables of temperature). Temperature is increased after meals, and psychological factors (like the first day in the hospital) also influence body temperature.
There are different locations where you can measure temperature, and these differ in temperature variability. Tympanic membrane thermometers measure radiant heat energy from the tympanic membrane (=infrared). These may be very convenient, but may also show more variability.
Children develop higher temperatures with activities like playing, but this is not fever because their set-point is normal. Elderly patients may have decreased ability to generate body heat during fever, so even a low-grade fever can have serious underlying causes in geriatrics.
In conclusion, temperature is ideally always measured the same moment of the day, in the same way, after the same amount of activity.
Mechanism
Temperature is regulated in the hypothalamus. Substances that induce fever are called pyrogens. These are both external or exogenous, such as the bacterial substance LPS, and internal or endogenous. The endogenous pyrogens (such as interleukin 1) are a part of the innate immune system, produced by phagocytic cells, and cause the increase in the thermoregulatory set-point in the hypothalamus. The endogenous pyrogens may also come directly from tissue necrosis.
One model for the mechanism of fever is the detection of lipopolysaccharide (LPS), which is a cell wall component of gram-negative bacteria. An immunological protein called Lipopolysaccharide-Binding Protein (LBP) binds to LPS. The LBP-LPS complex then binds to the CD14 receptor of a nearby macrophage. This binding results in the synthesis and release of various cytokine factors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. These cytokine factors are released into general circulation where they migrate to the circumventricular organs of the brain, where the blood-brain barrier is reduced. The cytokine factors bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, they activate the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase (membrane-associated protein involved in eicosanoid and glutathione metabolism, also known as mPEGS-1). These enzymes ultimately mediate the synthesis and release of PGE2.
PGE2 is the ultimate mediator of the febrile response. The set-point temperature of the body will remain elevated until PGE2 is no longer present. PGE2 acts near the ventromedial preoptic area (VMPO) of the anterior hypothalamus and the parvocellular portion of the periventricular nucleus (PVH), where the thermal properties of fever emerge. It is presumed that the elevation in thermoregulatory set-point is mediated by the VMPO, whereas the neuroendocrine effects of fever are mediated by the PVH, pituitary gland, and various endocrine organs.
The brain ultimately orchestrates heat effector mechanisms. These may be
- increased heat production by increased muscle tone, shivering and hormones like epinephrine and thyroid hormones, or,
- prevention of heat loss, such as vasoconstriction or crawling under a blanket.
Types
Pyrexia can be classed as
- low-grade: 38 - 39 °C (99.5 - 102.2 °F)
- moderate: 39 - 40 °C (102.2 - 104 °F)
- high-grade: > 40 °C (> 104 °F)
- Hyperpyrexia: > 42 °C (> 107.6 °F)
Most of the times, fever types can't be used to find the underlying cause. However, there are specific fever patterns that may occasionally hint the diagnosis:
- Pel-Ebstein fever is a specific kind of fever associated with Hodgkin disease, being high for one week and low for the next week and so on. However, there is some debate (*) whether this pattern truly exists.
- Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau.
- In malaria, there may be a fever with a periodicity of 48 hours (tertian fever) or 72 hours (quartan fever, indicating Plasmodium vivax). These patterns may be less clear in travelers.
FebriculaFebricula, definition from Biology-Online.org, consulted June 7, 2006 http://www.biology-online.org/dictionary/Febricula is a mild fever of short duration, of indefinite origin, and without any distinctive pathology.
Causes
Fever is a common symptom of many medical conditions:
- infectious disease, e.g. common cold, HIV, malaria, infectious mononucleosis, gastroenteritis, etc..
- Immunological diseases like lupus erythematosus, sarcoidosis, inflammatory bowel diseases, etc..
- Tissue destruction, which can occur in hemolysis, surgery, infarction, crush syndrome, rhabdomyolysis, cerebral hemorrhage, etc..
- Drug fever
- directly caused be the drug (e.g. progesterone, chemotherapeutics causing tumor necrosis)
- as an adverse reaction to drugs (e.g. antibiotics, sulfa drugs, etc.)
- after drug discontinuation, like with heroin withdrawal
- Cancers such as Hodgkin disease (with Pel-Ebstein fever)
- Metabolic disorders like gout, porphyria, etc..
- Thrombo-embolic processes (i.e. pulmonary embolism, deep venous thrombosis)
Persistent fever which cannot be explained after repeated routine clinical inquiries, is called fever of unknown origin.
Is fever useful?
There are arguments for and against, and the issue is controversialSchaffner A. Fever--useful or noxious symptom that should be treated? Ther Umsch 2006; 63: 185-8. PMID 16613288Soszynski D. The pathogenesis and the adaptive value of fever. Postepy Hig Med Dosw 2003; 57: 531-54. PMID 14737969. There are studies using warm blooded vertebratesSu F, Nguyen ND, Wang Z, Cai Y, Rogiers P, Vincent JL. Fever control in septic shock: beneficial or harmful? Shock 2005; 23: 516-20. PMID 15897803 and humans Schulman CI, Namias N, Doherty J, et al. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect (Larchmt) 2005; 6:369-75. PMID 16433601 in vivo, with some suggesting that they recover more rapidly from infections or critical illness due to fever.
Theoretically, fever has been conserved during evolution because of its advantage for host defenseSchaffner A. Fever--useful or noxious symptom that should be treated? Ther Umsch 2006; 63: 185-8. PMID 16613288. There are certainly some important immunological reactions that are sped up by temperature, and some pathogens with strict temperature preferences could be hinderedFischler MP, Reinhart WH. Fever: friend or enemy? Schweiz Med Wochenschr 1997; 127: 864-70. PMID 9289813. The overall conclusion seems to be that both agressive treatment of feverSchulman CI, Namias N, Doherty J, et al. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect (Larchmt) 2005; 6:369-75. PMID 16433601 and too little fever controlSchaffner A. Fever--useful or noxious symptom that should be treated? Ther Umsch 2006; 63: 185-8. PMID 16613288 can be detrimental. This depends on the clinical situation, so careful assessment is needed.
Treatment
Fever should not necessarily be treated. Fever is an important signal that there's something wrong in the body, and it can be used for follow-up. Fever might help the immune system or hinder specific pathogens, but this is generally considered of little importance. Moreover, not all fevers are of infectious origin.
Most people take medication against fever because it causes discomfort. Fever increases heart rate and metabolism, thus potentially putting an additional strain on elderly patients, patients with heart disease, etc. This may even cause delirium. Therefore, potential benefits (if any) must be weighed against risks in these patients. In any case, fever must be brought under control in instances when fever escalates to hyperpyrexia, and tissue damage is imminent.
Treatment of fever should primarily be based on lowering the setpoint, but facilitating heat loss may contribute. The former is accomplished with antipyretics. Heat loss may be an effect of heat conduction, convection, radiation or evaporation (=sweating, perspiration). This may be particularly important in babies, to whom it is best not to give too many drugs. However, when someone would use water that is too cold, this induces vasoconstriction and prevents adequate heat loss.
References
Articles
Books
- Rhoades, R and Pflanzer, R. Human physiology, third edition, chapter 27 Regulation of body temperature, p. 820 Clinical focus: pathogenesis of fever. ISBN 0030051592
- Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 2005. ISBN 0071391401.
See also
External links
- What to do if your child has a fever from Seattle Children's Hospital
- Fever and Taking Your Child's Temperature
- US National Institute of Health factsheet
- BUPA factsheet
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"Fever"