Fever

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This article is about the medical condition. For other uses, see Fever (disambiguation).
Fever
190px
An analog medical thermometer showing a temperature of 38.7 °C or 101.7 °F
ICD-10 R50.
ICD-9 780.6
DiseasesDB 18924
eMedicine med/785
MeSH D005334

Fever (also known as pyrexia or controlled hyperthermia[1]) is a common medical sign characterized by an elevation of temperature above the normal range of 36.5–37.5 °C (97.7–99.5 °F) due to an increase in the body temperature regulatory set-point.[2] This increase in set-point triggers increased muscle tone and shivering.

As a person's temperature increases, there is, in general, a feeling of cold despite an increasing body temperature. Once the new temperature is reached, there is a feeling of warmth. A fever is one of the body's immune responses that attempt to neutralize a bacterial or viral infection. A fever can be caused by many different conditions ranging from benign to potentially serious. With the exception of very high temperatures, treatment to reduce fever is often not necessary; however, antipyretic medications can be effective at lowering the temperature, which may improve the affected person's comfort.

Fever differs from uncontrolled hyperthermia[1], usually just referred to as hyperthermia, in that hyperthermia is an increase in body temperature over the body's thermoregulatory set-point, due to excessive heat production and/or insufficient thermoregulation.

Definition

Temperature Classification
Core (rectal, esophageal, etc.)
Normal 36.5–37.5 °C (97.7–99.5 °F)[3]
Hypothermia <35.0 °C (95.0 °F)[4]
Fever >37.5–38.3 °C (99.5–100.9 °F)[1][5]
Hyperthermia >38.4–39.9 °C (101.1–103.8 °F)[1][5]
Hyperpyrexia >40.0–41.5 °C (104.0–106.7 °F)[6][7]

A wide range for normal temperatures has been found.[5] Fever is generally agreed to be present if:

  • Temperature in the anus (rectum/rectal) is at or over 37.5–38.3 °C (99.5–100.9 °F)[1][5]
  • Temperature in the mouth (oral) is at or over 37.7 °C (99.9 °F)[8]
  • Temperature under the arm (axillary) or in the ear (otic) is at or over 37.2 °C (99.0 °F)

In healthy adult men and women, the range for oral temperature is 33.2–38.2 °C (91.8–100.8 °F), for rectal it is 34.4–37.8 °C (93.9–100.0 °F), for tympanic membrane it is 35.4–37.8 °C (95.7–100.0 °F), and for axillary it is 35.5–37.0 °C (95.9–98.6 °F).[9]

People develop higher temperatures with activities, but this is not considered a fever, as the set-point is normal. Elderly people have a decreased ability to generate body heat, so even a low-grade temperature may represent a serious underlying illness.

Types

The pattern of temperature changes may occasionally hint at the diagnosis:

  • Intermittent fever: Elevated temperature is present only for some hours of the day and becomes normal for remaining hours, e.g., malaria, kala-azar, pyaemia, or septicemia. In malaria, there may be a fever with a periodicity of 24 hours (quotidian), 48 hours (tertian fever), or 72 hours (quartan fever, indicating Plasmodium malariae). These patterns may be less clear in travelers.
  • Pel-Ebstein fever: A specific kind of fever associated with Hodgkin's lymphoma, being high for one week and low for the next week and so on. However, there is some debate as to whether this pattern truly exists.[10]
  • Continuous fever: Temperature remains above normal throughout the day and does not fluctuate more than 1 °C in 24 hours, e.g. lobar pneumonia, typhoid, urinary tract infection, brucellosis, or typhus. Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau.
  • Remittant fever: Temperature remains above normal throughout the day and fluctuates more than 1 °C in 24 hours, e.g., infective endocarditis.

A neutropenic fever, also called febrile neutropenia, is a fever in the absence of normal immune system function. Because of the lack of infection-fighting neutrophils, a bacterial infection can spread rapidly; this fever is, therefore, usually considered a medical emergency. This kind of fever is more commonly seen in people receiving immune-suppressing chemotherapy than in apparently healthy people.

Febricula[11] is a mild fever of short duration, of indefinite origin, and without any distinctive pathology.

Hyperpyrexia

Hyperpyrexia is a fever with an extreme elevation of body temperature greater than or equal to 41.5 °C (106.7 °F).[12] Such a high temperature is considered a medical emergency as it may indicate a serious underlying condition or lead to significant side effects.[13] The most common cause is an intracranial hemorrhage.[12] Other possible causes include sepsis, Kawasaki syndrome,[14] neuroleptic malignant syndrome, drug effects, serotonin syndrome, and thyroid storm.[13] Infections are the most common cause of fevers, however as the temperature rises other causes become more common.[13] Infections commonly associated with hyperpyrexia include: roseola, rubeola and enteroviral infections.[15] Immediate aggressive cooling to less than 38.9 °C (102.0 °F) has been found to improve survival.[13] Hyperpyrexia differs from hyperthermia in that in hyperpyrexia the body's temperature regulation mechanism sets the body temperature above the normal temperature, then generates heat to achieve this temperature, while in hyperthermia the body temperature rises above its set point.[12]

Hyperthermia

Hyperthermia occurs from a number of causes including heatstroke, neuroleptic malignant syndrome, malignant hyperthermia, stimulants such as amphetamines and cocaine, idiosyncratic drug reactions, and serotonin syndrome.

Signs and symptoms

File:Michael Ancher 001.jpg
Ancher, Michael, "The Sick Girl", 1882, Statens Museum for Kunst

A fever is usually accompanied by sickness behavior, which consists of lethargy, depression, anorexia, sleepiness, hyperalgesia, and the inability to concentrate.[16][17][18]

Differential diagnosis

Fever is a common symptom of many medical conditions:

Persistent fever that cannot be explained after repeated routine clinical inquiries is called fever of unknown origin.

Pathophysiology

File:Fever-conceptual.svg
Hyperthermia: Characterized on the left. Normal body temperature (thermoregulatory set-point) is shown in green, while the hyperthermic temperature is shown in red. As can be seen, hyperthermia can be conceptualized as an increase above the thermoregulatory set-point.
Hypothermia: Characterized in the center: Normal body temperature is shown in green, while the hypothermic temperature is shown in blue. As can be seen, hypothermia can be conceptualized as a decrease below the thermoregulatory set-point.
Fever: Characterized on the right: Normal body temperature is shown in green. It reads "New Normal" because the thermoregulatory set-point has risen. This has caused what was the normal body temperature (in blue) to be considered hypothermic.

Temperature is ultimately regulated in the hypothalamus. A trigger of the fever, called a pyrogen, causes a release of prostaglandin E2 (PGE2). PGE2 then in turn acts on the hypothalamus, which generates a systemic response back to the rest of the body, causing heat-creating effects to match a new temperature level.

In many respects, the hypothalamus works like a thermostat.[19] When the set point is raised, the body increases its temperature through both active generation of heat and retaining heat. Vasoconstriction both reduces heat loss through the skin and causes the person to feel cold. The liver produces extra heat. If these measures are insufficient to make the blood temperature in the brain match the new setting in the hypothalamus, then shivering begins in order to use muscle movements to produce more heat. When the fever stops, and the hypothalamic setting is set lower; the reverse of these processes (vasodilation, end of shivering and nonshivering heat production) and sweating are used to cool the body to the new, lower setting.

This contrasts with hyperthermia, in which the normal setting remains, and the body overheats through undesirable retention of excess heat or over-production of heat.[19] Hyperthermia is usually the result of an excessively hot environment (heat stroke) or an adverse reaction to drugs. Fever can be differentiated from hyperthermia by the circumstances surrounding it and its response to anti-pyretic medications.

Pyrogens

A pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous) to the body. The bacterial substance lipopolysaccharide (LPS), present in the cell wall of some bacteria, is an example of an exogenous pyrogen. Pyrogenicity can vary: In extreme examples, some bacterial pyrogens known as superantigens can cause rapid and dangerous fevers. Depyrogenation may be achieved through filtration, distillation, chromatography, or inactivation.

Endogenous

In essence, all endogenous pyrogens are cytokines, molecules that are a part of the innate immune system. They are produced by phagocytic cells and cause the increase in the thermoregulatory set-point in the hypothalamus. Major endogenous pyrogens are interleukin 1 (α and β) [20], interleukin 6 (IL-6) and tumor necrosis factor-alpha. Minor endogenous pyrogens include interleukin-8, tumor necrosis factor-α, tumor necrosis factor-β, macrophage inflammatory protein-α and macrophage inflammatory protein-β as well as interferon-α, interferon-β, and interferon-γ.[20]

These cytokine factors are released into general circulation, where they migrate to the circumventricular organs of the brain due to easier absorption caused by the blood-brain barrier's reduced filtration action there. The cytokine factors then bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, the arachidonic acid pathway is then activated.

Exogenous

One model for the mechanism of fever caused by exogenous pyrogens includes 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 endogenous cytokine factors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. In other words, exogenous factors cause release of endogenous factors, which, in turn, activate the arachidonic acid pathway.

PGE2 release

PGE2 release comes from 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. 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 on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3). EP3-expressing neurons in the POA innervate the dorsomedial hypothalamus (DMH), the rostral raphe pallidus nucleus in the medulla oblongata (rRPa), and the paraventricular nucleus (PVN) of the hypothalamus . Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which evokes non-shivering thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface. It is presumed that the innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs.

Hypothalamus

The brain ultimately orchestrates heat effector mechanisms via the autonomic nervous system. These may be:

The autonomic nervous system may also activate brown adipose tissue to produce heat (non-exercise-associated thermogenesis, also known as non-shivering thermogenesis), but this seems important mostly for babies. Increased heart rate and vasoconstriction contribute to increased blood pressure in fever.

Usefulness

There are arguments for and against the usefulness of fever, and the issue is controversial.[21][22] There are studies using warm-blooded vertebrates[23] and humans[24] in vivo, with some suggesting that they recover more rapidly from infections or critical illness due to fever. A Finnish study suggested reduced mortality in bacterial infections when fever was present.[25]

In theory, fever can aid in host defense.[21] There are certainly some important immunological reactions that are sped up by temperature, and some pathogens with strict temperature preferences could be hindered.[26] Fevers may be useful to some extent since they allow the body to reach high temperatures, causing an unbearable environment for some pathogens. White blood cells also rapidly proliferate due to the suitable environment and can also help fight off the harmful pathogens and microbes that invaded the body.[citation needed]

Research[27] has demonstrated that fever has several important functions in the healing process:

Management

Fever should not necessarily be treated.[29] Most people recover without specific medical attention.[30] In general, people are advised to keep adequately hydrated. Oral rehydration solutions or water are generally used for this purpose. Excessive water may lead however to hyponatremia. Some limited evidence supports the use of tepid sponging.[31] If the temperature reaches the level of hyperpyrexia aggressive cooling is required.[13]

Medications

The antipyretic ibuprofen is effective in treating a fever.[32] It is more effective than acetaminophen / paracetamol in children however both may be used together,[33] safely.[34] The effectiveness of acetaminophen by itself is questionable.[35] Ibuprofen is also superior to aspirin,[36] which is not usually recommended in children due to the risk of Reye's syndrome.

Etymology

File:Yoshitoshi The Fever.jpg
The print depicts Kiyomori, suffering from fever, as he confronts Enma, the king of hell, and the ghosts of Kiyomori's victims.

Pyrexia is from the Greek pyretos meaning fire. Febrile is from the Latin word febris, meaning fever, and archaically known as ague.

In other animals

Fever is an important feature for the diagnosis of disease in domestic animals. The body temperature of animals, which is taken rectally, is different from one species to another. For example, a horse is said to have a fever above 101.0 °F (38.3 °C). [37]

In species that allow the body to have a wide range of "normal" temperatures, such as camels,[38] it is sometimes difficult to determine a febrile stage.


References

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Further reading

  • Rhoades, R. and Pflanzer, R. Human physiology, third edition, chapter 27 Regulation of body temperature, p. 820 Clinical focus: pathogenesis of fever. ISBN 0-03-005159-2

External links

Temperature
Aches/Pains
Malaise and fatigue
Miscellaneous
ar:حمى

arc:ܐܫܬܐ (ܐܣܝܘܬܐ) bn:জ্বর bg:Треска (болест) ca:Febre cs:Horečka cy:Y dwymyn da:Feber de:Fieber el:Πυρετός es:Fiebre eo:Febro eu:Sukar fa:تب fr:Fièvre gl:Febre gu:તાવ ko:발열 hi:ज्वर io:Febro id:Demam is:Hitasótt it:Febbre he:חום (תסמין) kn:ಜ್ವರ sw:Homa ht:Lafyèv la:Febris lv:Drudzis lt:Karščiavimas ln:Fɛ́fɛlɛ hu:Láz ml:പനി ms:Demam nl:Koorts new:ज्वर ja:発熱 no:Feber nn:Feber pnb:تاپ ps:تبه pl:Gorączka pt:Febre ro:Febră qu:Ruphariy ru:Лихорадка sq:Ethet scn:Frevi si:උණ simple:Fever sk:Horúčka sl:Vročina ckb:تا (نیشانەی نەخۆشی) fi:Kuume sv:Feber tl:Lagnat ta:காய்ச்சல் te:జ్వరం th:ไข้ tr:Ateş (tıp) uk:Лихоманка vec:Fevra vi:Sốt wa:Five yi:פיבער

zh:发热
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  2. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  3. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  4. ↑ Marx, John (2006). Rosen's emergency medicine: concepts and clinical practice. Mosby/Elsevier. p. 2239. ISBN 9780323028455. 
  5. ↑ 5.0 5.1 5.2 5.3 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  6. ↑ Manson's Tropical Diseases: Expert Consult. Saunders Ltd. 2008. p. 1229. ISBN 1-4160-4470-1. 
  7. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  8. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  9. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  10. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.. They cite Richard Asher's lecture Making Sense (Lancet, 1959, 2, 359)
  11. ↑ Febricula, definition from Biology-Online.org, consulted June 7, 2006 http://www.biology-online.org/dictionary/Febricula
  12. ↑ 12.0 12.1 12.2 Loscalzo, Joseph; Fauci, Anthony S.; Braunwald, Eugene; Dennis L. Kasper; Hauser, Stephen L; Longo, Dan L. (2008). Harrison's principles of internal medicine. McGraw-Hill Medical. pp. Chapter 17, Fever versus hyperthermia. ISBN 0-07-146633-9. 
  13. ↑ 13.0 13.1 13.2 13.3 13.4 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  14. ↑ Marx, John (2006). Rosen's emergency medicine: concepts and clinical practice. Mosby/Elsevier. p. 2506. ISBN 9780323028455. 
  15. ↑ Marx, John (2006). Rosen's emergency medicine: concepts and clinical practice. Mosby/Elsevier. p. 2506. ISBN 9780323028455. 
  16. ↑ Hart, B. L. (1988) "Biological basis of the behavior of sick animals". Neurosci Biobehav Rev. 12: 123-137.PubMed
  17. ↑ Johnson, R. (2002) "The concept of sickness behavior: a brief chronological account of four key discoveries". Veterinary Immunology and Immunopathology. 87: 443-450 PubMed
  18. ↑ Kelley, K. W., Bluthe, R. M., Dantzer, R., Zhou, J. H., Shen, W. H., Johnson, R. W. Broussard, S. R. (2003) "Cytokine-induced sickness behavior". Brain Behav Immun. 17 Suppl 1: S112-118 PubMed
  19. ↑ 19.0 19.1 Fauci, Anthony; et al. (2008). Harrison's Principles of Internal Medicine (17 ed.). McGraw-Hill Professional. pp. 117–121. ISBN 9780071466332. 
  20. ↑ 20.0 20.1 Chapter 58 in: Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3. 
  21. ↑ 21.0 21.1 Schaffner A. Fever—useful or noxious symptom that should be treated? Ther Umsch 2006; 63: 185-8. PMID 16613288
  22. ↑ Soszynski D. The pathogenesis and the adaptive value of fever. Postepy Hig Med Dosw 2003; 57: 531-54. PMID 14737969
  23. ↑ Su, F.; Nguyen, N.D.; Wang, Z.; Cai, Y.; Rogiers, P.; Vincent, J.L. Fever control in septic shock: beneficial or harmful? Shock 2005; 23: 516-20. PMID 15897803
  24. ↑ Schulman, C.I.; 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
  25. ↑ Rantala S, Vuopio-Varkila J, Vuento R, Huhtala H, Syrjänen J. Predictors of mortality in beta-hemolytic streptococcal bacteremia: A population-based study. J Infect. March 2, 2009. PMID 19261333
  26. ↑ Fischler, M.P.; Reinhart, W.H. Fever: friend or enemy? Schweiz Med Wochenschr 1997; 127: 864-70. PMID 9289813
  27. ↑ Craven, R and Hirnle, C. (2006). Fundamentals of nursing: Human health and function. Fourth edition. p. 1044
  28. ↑ 28.0 28.1 Lewis, SM, Heitkemper, MM, and Dirksen, SR. (2007). Medical-surgical nursing: Assessment and management of clinical problems. sixth edition. p. 212
  29. ↑ "Fever". Medline Plus Medical Encyclopedia. U.S. National Library of Medicine. Retrieved 20 May 2009. 
  30. ↑ "What To Do If You Get Sick: 2009 H1N1 and Seasonal Flu". Centers for Disease Control and Prevention. 2009-05-07. Retrieved 2009-11-01. 
  31. ↑ Meremikwu M, Oyo-Ita A (2003). "Physical methods for treating fever in children". Cochrane Database Syst Rev (2): CD004264. doi:10.1002/14651858.CD004264. PMID 12804512. 
  32. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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  34. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  35. ↑ Meremikwu M, Oyo-Ita A (2002). "Paracetamol for treating fever in children". Cochrane Database Syst Rev (2): CD003676. doi:10.1002/14651858.CD003676. PMID 12076499. 
  36. ↑ Autret E, Reboul-Marty J, Henry-Launois B; et al. (1997). "Evaluation of ibuprofen versus aspirin and paracetamol on efficacy and comfort in children with fever". Eur. J. Clin. Pharmacol. 51 (5): 367–71. doi:10.1007/s002280050215. PMID 9049576. 
  37. ↑ "Equusite Vital Signs". www.equusite.com. Retrieved 2010-03-22. 
  38. ↑ "Body Temperature of the Camel and Its Relation to Water Economy". ajplegacy.physiology.org. Retrieved 2010-03-22. 
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