View source for Fever

{{Short description|Raised body temperature cause by disease}}
{{Hatnote group|
{{Distinguish|hyperthermia}}
{{Other uses}}
}}
{{Use dmy dates|date=February 2020}}
{{Infobox medical condition
| name          = Fever
| synonyms      = Pyrexia, febrile response, febrile<ref name=NC08/>
| image         = Symptoms-fever.jpg
| caption       = Person with fever
| field         = [[Infectious disease (medical specialty)|Infectious disease]], [[pediatrics]]
| symptoms      = '''Initially''': [[shivering]], feeling [[cold]], [[chills]]<ref name=Peds2011/><br />'''Later''': [[flushed]], [[sweat]]ing<ref name=Sue2014/>
| complications = [[Febrile seizure]]<ref name=CDC2010/>
| onset         =
| duration      =
| types         =
| causes        = [[Virus]], [[bacteria]], increase in the body's temperature [[Human body temperature#Fever|set point]]<ref name=Kl2015/><ref name=Gar2012p375/>
| risks         =
| diagnosis     = Temperature higher than the normal range of {{convert|37.2|and|38.3|C|F|1}}<ref name=NC08/><ref name=Harrisons20th/><ref name=CC09/><!-- defined by template:HumanTemperature -->
| differential  = [[Hyperthermia]]<ref name=NC08/>
| prevention    =
| treatment     = Based on underlying cause, not required for fever itself<ref name=Peds2011/><ref name=Ric2015/>
| medication    = [[Ibuprofen]], [[paracetamol]] (acetaminophen)<ref name=Ric2015/><ref name=Gar2012/>
| prognosis     =
| frequency     = Common<ref name=Peds2011/><ref name=Ki2013/>
| deaths        =
| alt           =
}}

'''Fever''' or '''pyrexia''' in humans is a symptom of an anti-infection defense mechanism that appears with [[Human body temperature|body temperature]] exceeding the normal range caused by an increase in the body's temperature [[Human body temperature#Fever|set point]] in the [[hypothalamus]].<ref name=Kl2015>{{cite book|last=Kluger|first=Matthew J. | name-list-style = vanc |title=Fever: Its Biology, Evolution, and Function|date=2015|publisher=Princeton University Press|isbn=978-1400869831|page=57|url=https://books.google.com/books?id=gIF9BgAAQBAJ&pg=PA57}}</ref><ref name=Gar2012p375>{{cite book|veditors = Garmel GM, Mahadevan SV|title=An introduction to clinical emergency medicine|chapter=Fever in adults|date=2012|publisher=Cambridge University Press|location=Cambridge|isbn=978-0521747769|page=375|edition=2nd|chapter-url=https://books.google.com/books?id=pyAlcOfBhjIC&q=An%20Introduction%20to%20Clinical%20Emergency%20Medicine&pg=PA375}}</ref><ref name=Harrisons20th>{{cite book | author = Dinarello CA, Porat R | date = 2018 | chapter = Chapter 15: Fever | title = Harrison's Principles of Internal Medicine | edition = 20th | volume = 1–2 |veditors= Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo, J |location=New York | publisher=McGraw-Hill | isbn=9781259644030 | url =  https://books.google.com/books?id=XGQntQEACAAJ&q=9781259644030 | access-date = 31 March 2020}}</ref><ref>{{Cite journal |last=Franjić |first=Siniša |date=2019-03-31 |title=Fever Can Be A Symptom of Many Diseases |journal=Journal of Medicine and HealthCare |pages=1–3 |doi=10.47363/jmhc/2021(3)146|s2cid=243837498 |doi-access=free }}</ref> There is no single agreed-upon upper limit for normal temperature: sources use values ranging between {{convert|37.2|and|38.3|C|F|1}} in humans.<ref name=NC08/><ref name=Harrisons20th/><ref name=CC09/><!-- defined by template:HumanTemperature -->

The increase in set point triggers increased [[muscle tone|muscle contraction]]s and causes a feeling of [[cold]] or [[chills]].<ref name="Peds2011" /> This results in greater heat production and efforts to conserve heat.<ref name="Sue2014" /> When the set point temperature returns to normal, a person feels hot, becomes [[Flushing (physiology)|flushed]], and may begin to [[Perspiration|sweat]].<ref name="Sue2014">{{cite book|author1=Huether, Sue E. |title=Pathophysiology: The Biologic Basis for Disease in Adults and Children|date=2014|publisher=Elsevier Health Sciences|isbn=978-0323293754|page=498|edition=7th|url=https://books.google.com/books?id=l9XsAwAAQBAJ&pg=PA498}}</ref> Rarely a fever may trigger a [[febrile seizure]], with this being more common in young children.<ref name="CDC2010">{{cite web| author = CDC Staff | date = 31 March 2020 | title=Taking Care of Someone Who is Sick: Caring for Someone Sick at Home|url=https://www.cdc.gov/flu/homecare/treatfever.htm|access-date=8 May 2015|archive-url=https://web.archive.org/web/20150324084355/http://www.cdc.gov/flu/homecare/treatfever.htm |archive-date=24 March 2015 }}</ref> Fevers do not typically go higher than {{convert|41|to|42|C|F|0}}.<ref name="Gar2012p375" />

A fever can be caused by many [[medical conditions]] ranging from non-serious to [[life-threatening]].<ref name=Gar2012p5/> This includes [[viral infection|viral]], [[bacterial infection|bacterial]], and [[parasitic infections]]—such as [[influenza]], the [[common cold]], [[meningitis]], [[urinary tract infections]], [[appendicitis]], [[Lassa fever]], [[COVID-19]], and [[malaria]].<ref name="Gar2012p5" /><ref name="Rod2020">{{cite journal | vauthors = Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, Alvarado-Arnez LE, Bonilla-Aldana DK, Franco-Paredes C | title = Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis | journal = Travel Medicine and Infectious Disease | volume =  34| pages =  101623| date = 13 March 2020 | pmid =  32179124| doi = 10.1016/j.tmaid.2020.101623 | pmc = 7102608 }}</ref> Non-infectious causes include [[vasculitis]], [[deep vein thrombosis]], [[connective tissue disease]], side effects of medication or vaccination, and [[cancer]].<ref name=Gar2012p5>{{cite book|veditors = Garmel GM, Mahadevan SV|title=An introduction to clinical emergency medicine|date=2012|publisher=Cambridge University Press|location=Cambridge|isbn=978-0521747769|page=5|edition=2nd}}</ref><ref>{{cite journal | vauthors = Dayal R, Agarwal D | s2cid = 34481402 | title = Fever in Children and Fever of Unknown Origin | journal = Indian Journal of Pediatrics | volume = 83 | issue = 1 | pages = 38–43 | date = January 2016 | pmid = 25724501 | doi = 10.1007/s12098-015-1724-4 }}</ref> It differs from [[hyperthermia]], in that hyperthermia is an increase in body temperature over the temperature set point, due to either too much heat production or not enough [[thermoregulation|heat loss]].<ref name=NC08/>

Treatment to reduce fever is generally not required.<ref name=Peds2011/><ref name=Ric2015/> Treatment of associated pain and inflammation, however, may be useful and help a person rest.<ref name=Ric2015>{{cite journal | vauthors = Richardson M, Purssell E | s2cid = 206857750 | title = Who's afraid of fever? | journal = Archives of Disease in Childhood | volume = 100 | issue = 9 | pages = 818–820 | date = September 2015 | pmid = 25977564 | doi = 10.1136/archdischild-2014-307483 }}</ref> Medications such as [[ibuprofen]] or [[paracetamol]] (acetaminophen) may help with this as well as lower temperature.<ref name=Ric2015/><ref name=Gar2012>{{cite book|veditors = Garmel GM, Mahadevan SV|title=An introduction to clinical emergency medicine|date=2012|publisher=Cambridge University Press|location=Cambridge|isbn=978-0521747769|page=401|edition=2nd}}</ref> Children younger than three months require medical attention, as might people with serious medical problems such as a [[compromised immune system]] or people with other symptoms.<ref>{{Cite web|url = https://www.nlm.nih.gov/medlineplus/ency/article/003090.htm|title = Fever|date = 30 August 2014|website = MedlinePlus|url-status = live|archive-url = https://web.archive.org/web/20090511181606/http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm|archive-date = 11 May 2009|df = dmy-all}}</ref> [[Hyperthermia]] requires treatment.<ref name=Peds2011/>

Fever is one of the most common [[medical signs]].<ref name=Peds2011/> It is part of about 30% of healthcare visits by children<ref name=Peds2011>{{cite journal | vauthors = Sullivan JE, Farrar HC | title = Fever and antipyretic use in children | journal = Pediatrics | volume = 127 | issue = 3 | pages = 580–587 | date = March 2011 | pmid = 21357332 | doi = 10.1542/peds.2010-3852 | doi-access = free }}</ref> and occurs in up to 75% of adults who are seriously sick.<ref name=Ki2013>{{cite journal | vauthors = Kiekkas P, Aretha D, Bakalis N, Karpouhtsi I, Marneras C, Baltopoulos GI | title = Fever effects and treatment in critical care: literature review | journal = Australian Critical Care | volume = 26 | issue = 3 | pages = 130–135 | date = August 2013 | pmid = 23199670 | doi = 10.1016/j.aucc.2012.10.004 }}</ref> While fever evolved as a defense mechanism, [[Antipyretic|treating a fever]] does not appear to improve or worsen outcomes.<ref name=Sch2006>{{cite journal | vauthors = Schaffner A | title = Fieber – nützliches oder schädliches, zu behandelndes Symptom? | trans-title = Fever–useful or noxious symptom that should be treated? | journal = Therapeutische Umschau | volume = 63 | issue = 3 | pages = 185–188 | date = March 2006 | pmid = 16613288 | doi = 10.1024/0040-5930.63.3.185 | language = de }} Abstract alone is in German and in English.</ref><ref name="Antipyretic therapy in febrile crit">{{cite journal | vauthors = Niven DJ, Stelfox HT, Laupland KB | title = Antipyretic therapy in febrile critically ill adults: A systematic review and meta-analysis | journal = Journal of Critical Care | volume = 28 | issue = 3 | pages = 303–310 | date = June 2013 | pmid = 23159136 | doi = 10.1016/j.jcrc.2012.09.009 }}</ref><ref name=":0">{{Cite journal |last=Ray |first=Juliet J. |date=December 2015 |title=Fever: suppress or let it ride? |journal=Journal of Thoracic Disease |volume=7 |issue=12 |pages=E633–E636 |doi=10.3978/j.issn.2072-1439.2015.12.28 |pmid=26793378 |pmc=4703655 }}</ref> Fever is often viewed with greater concern by parents and healthcare professionals than is usually deserved, a phenomenon known as "fever phobia."<ref name=Peds2011/><ref>{{cite journal | vauthors = Crocetti M, Moghbeli N, Serwint J | title = Fever Phobia Revisited: Have Parental Misconceptions About Fever Changed in 20 Years? | journal = Pediatrics | volume = 107 | issue = 6 | pages = 1241–1246 | date = June 2001 | pmid = 11389237| doi = 10.1542/peds.107.6.1241  }}</ref>
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==Associated symptoms==
A fever is usually accompanied by [[sickness behavior]], which consists of [[lethargy]], [[Depression (mood)|depression]], [[Anorexia (symptom)|loss of appetite]], [[sleepiness]], [[hyperalgesia]], [[dehydration]],<ref>{{Cite web |date=2020-05-05 |title=Fever: Symptoms, treatments, types, and causes |url=https://www.medicalnewstoday.com/articles/168266 |access-date=2022-04-22 |website=www.medicalnewstoday.com }}</ref><ref>{{Cite journal |last1=Harden |first1=L. M. |last2=Kent |first2=S. |last3=Pittman |first3=Q. J. |last4=Roth |first4=J. |date=2015-11-01 |title=Fever and sickness behavior: Friend or foe? |url=https://www.sciencedirect.com/science/article/pii/S0889159115004079 |journal=Brain, Behavior, and Immunity |volume=50 |pages=322–333 |doi=10.1016/j.bbi.2015.07.012 |pmid=26187566 |s2cid=19396134 |issn=0889-1591|url-access=subscription }}</ref> and the inability to concentrate. Sleeping with a fever can often cause intense or confusing [[nightmare]]s, commonly called "fever dreams".<ref>{{cite journal | vauthors = Kelley KW, Bluthé RM, Dantzer R, Zhou JH, Shen WH, Johnson RW, Broussard SR | s2cid = 25400611 | title = Cytokine-induced sickness behavior | journal = Brain, Behavior, and Immunity | volume = 17 Suppl 1 | issue = 1 | pages = S112–S118 | date = February 2003 | pmid = 12615196 | doi = 10.1016/S0889-1591(02)00077-6 }}</ref><!--<ref name="Hart">{{cite journal | vauthors = Hart BL | title = Biological basis of the behavior of sick animals | journal = Neuroscience and Biobehavioral Reviews | volume = 12 | issue = 2 | pages = 123–137 | year = 1988 | pmid = 3050629 | doi = 10.1016/S0149-7634(88)80004-6 }}</ref><ref>{{cite journal | vauthors = Johnson RW | title = The concept of sickness behavior: a brief chronological account of four key discoveries | journal = Veterinary Immunology and Immunopathology | volume = 87 | issue = 3–4 | pages = 443–450 | date = September 2002 | pmid = 12072271 | doi = 10.1016/S0165-2427(02)00069-7 }}</ref>  SHOULD VERTERINARY SOURCES APPEAR IN THIS ARTICLE? ONLY THE VERY LAST SECTION OF THE ARTICLE IS VETERNIARY IN FOCUS.--> Mild to severe [[delirium]] (which can also cause [[hallucinations]]) may also present itself during high fevers.<ref>{{cite journal | vauthors = Adamis D, Treloar A, Martin FC, Macdonald AJ | title = A brief review of the history of delirium as a mental disorder | journal = History of Psychiatry | volume = 18 | issue = 72 Pt 4 | pages = 459–469 | date = December 2007 | pmid = 18590023 | doi = 10.1177/0957154X07076467 | s2cid = 24424207 | url = https://hal.archives-ouvertes.fr/hal-00570887/document| hdl = 2262/51619 | hdl-access = free }}</ref>

== Differential diagnosis ==

===Hyperthermia===
[[Hyperthermia]] is an elevation of body temperature over the temperature set point, due to either too much heat production or not enough [[thermoregulation|heat loss]].<ref name="NC08" /><ref name="Harrisons20th" /> Hyperthermia is thus not considered fever.<ref name="Harrisons20th" />{{rp|103}}<ref>{{Cite journal |last1=Beard |first1=Robin M. |last2=Day |first2=Michael W. |date=June 2008 |title=Fever and Hyperthermia |journal=Nursing2022 |volume=38 |issue=6 |pages=28–31 |doi=10.1097/01.NURSE.0000320353.79079.a5 |issn=0360-4039 |pmid=18497656 |doi-access=free}}</ref> Hyperthermia should not be confused with [[hyperpyrexia]] (which is a very high fever).<ref name="Harrisons20th" />{{rp|102}}

Clinically, it is important to distinguish between fever and hyperthermia as hyperthermia may quickly lead to death and does not respond to antipyretic medications. The distinction may however be difficult to make in an emergency setting, and is often established by identifying possible causes.<ref name="Harrisons20th" />{{rp|103}}

==Mechanism==
{{See also|Thermoregulation in humans}}

===Hypothalamus===
Temperature is regulated in the [[hypothalamus]]. The trigger of a fever, called a pyrogen, results in the release of [[prostaglandin E2]] (PGE2). PGE2 in turn acts on the hypothalamus, which creates a systemic response in the body, causing heat-generating effects to match a new higher temperature set point. There are four receptors in which PGE2 can bind (EP1-4), with a previous study showing the EP3 subtype is what mediates the fever response.<ref>{{cite journal |vauthors=Ushikubi F et al. |date=September 1998 |title=Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3 |journal=Nature |volume=395 |issue=6699 |pages=281–284 |bibcode=1998Natur.395..281U |doi=10.1038/26233 |pmid=9751056 |s2cid=4420632}}</ref> Hence, the hypothalamus can be seen as working like a [[thermostat]].<ref name="Harrisons20th" /> When the set point is raised, the body increases its temperature through both active generation of heat and retention of heat. Peripheral [[vasoconstriction]] both reduces heat loss through the skin and causes the person to feel cold. [[Norepinephrine]] increases [[thermogenesis]] in [[brown adipose tissue]], and muscle contraction through shivering raises the [[Basal metabolic rate|metabolic rate]].<ref name="pmid25976513">{{cite journal |vauthors=Evans SS, Repasky EA, Fisher DT |date=June 2015 |title=Fever and the thermal regulation of immunity: the immune system feels the heat |journal=Nature Reviews. Immunology |volume=15 |issue=6 |pages=335–349 |doi=10.1038/nri3843 |pmc=4786079 |pmid=25976513}}</ref>

If these measures are insufficient to make the blood temperature in the brain match the new set point in the hypothalamus, the brain orchestrates heat effector mechanisms via the [[autonomic nervous system]] or primary motor center for shivering. These may be:<ref>{{Cite journal |last=Nakamura |first=Kazuhiro |date=November 2011 |title=Central circuitries for body temperature regulation and fever |url=https://www.physiology.org/doi/10.1152/ajpregu.00109.2011 |journal=American Journal of Physiology-Regulatory, Integrative and Comparative Physiology |language=en |volume=301 |issue=5 |pages=R1207–R1228 |doi=10.1152/ajpregu.00109.2011 |pmid=21900642 |issn=0363-6119|url-access=subscription }}</ref><ref>{{Cite journal |last1=Morrison |first1=S.F. |last2=Nakamura |first2=K. |date=2019-02-10 |title=Central Mechanisms for Thermoregulation |url=https://www.annualreviews.org/doi/10.1146/annurev-physiol-020518-114546 |journal=Annual Review of Physiology |language=en |volume=81 |issue=1 |pages=285–308 |doi=10.1146/annurev-physiol-020518-114546 |pmid=30256726 |issn=0066-4278|url-access=subscription }}</ref><ref>{{Cite journal |last1=Nakamura |first1=Kazuhiro |last2=Nakamura |first2=Yoshiko |last3=Kataoka |first3=Naoya |date=January 2022 |title=A hypothalamomedullary network for physiological responses to environmental stresses |url=https://www.nature.com/articles/s41583-021-00532-x |journal=Nature Reviews Neuroscience |language=en |volume=23 |issue=1 |pages=35–52 |doi=10.1038/s41583-021-00532-x |pmid=34728833 |issn=1471-003X|url-access=subscription }}</ref>
* Increased heat production by increased [[muscle tone]], [[shivering]] (muscle movements to produce heat) and release of hormones like [[epinephrine]]; and
* Prevention of heat loss, e.g., through [[vasoconstriction]].
When the hypothalamic set point moves back to baseline—either spontaneously or via medication—normal functions such as sweating, and the reverse of the foregoing processes (e.g., vasodilation, end of shivering, and nonshivering heat production) are used to cool the body to the new, lower setting.{{citation needed|date=April 2020}}

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. 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.<ref name="Harrisons20th" />{{verify source|date=April 2020}}

In infants, the autonomic nervous system may also activate [[brown adipose tissue]] to produce heat (non-shivering thermogenesis).<ref>{{Cite journal |last1=Nowack |first1=Julia |last2=Giroud |first2=Sylvain |last3=Arnold |first3=Walter |last4=Ruf |first4=Thomas |date=2017-11-09 |title=Muscle Non-shivering Thermogenesis and Its Role in the Evolution of Endothermy |journal=Frontiers in Physiology |volume=8 |page=889 |doi=10.3389/fphys.2017.00889 |issn=1664-042X |pmc=5684175 |pmid=29170642 |doi-access=free}}</ref>

Increased heart rate and vasoconstriction contribute to increased [[blood pressure]] in fever.<ref>{{Cite journal |last=Deussen |first=A. |date=September 2007 |title=[Hyperthermia and hypothermia. Effects on the cardiovascular system] |url=https://pubmed.ncbi.nlm.nih.gov/17554514/ |journal=Der Anaesthesist |volume=56 |issue=9 |pages=907–911 |doi=10.1007/s00101-007-1219-4 |issn=0003-2417 |pmid=17554514}}</ref>

===Pyrogens===
<!--WHERE SHOULD THIS GO?   The highly toxic [[metabolism]]-boosting supplement [[2,4-Dinitrophenol|2,4-dinitrophenol]] induces [[hyperthermia|high body temperature]] via the inhibition of [[Adenosine triphosphate|ATP]] production by [[mitochondria]], resulting in impairment of [[cellular respiration]]. Instead of producing ATP, the energy of the [[proton gradient]] is lost as heat.<ref name="pmid22351299">{{cite journal | vauthors = Yen M, Ewald MB | title = Toxicity of weight loss agents | journal = Journal of Medical Toxicology | volume = 8 | issue = 2 | pages = 145–152 | date = June 2012 | pmid = 22351299 | pmc = 3550246 | doi = 10.1007/s13181-012-0213-7 }}</ref>-->
A pyrogen is a substance that induces fever.<ref>{{cite book |last1=Hagel |first1=Lars |url=https://archive.org/details/handbookprocessc00hage |title=Handbook of Process Chromatography |last2=Jagschies |first2=Günter |last3=Sofer |first3=Gail |date=2008-01-01 |publisher=Academic Press |isbn=978-0-12-374023-6 |edition=2nd |pages=[https://archive.org/details/handbookprocessc00hage/page/n145 127]–145 |chapter=5 – Analysis |doi=10.1016/b978-012374023-6.50007-5 |url-access=limited |name-list-style=vanc}}</ref> In the presence of an infectious agent, such as bacteria, viruses, viroids, ''etc''., the immune response of the body is to inhibit their growth and eliminate them. The most common pyrogens are endotoxins, which are [[lipopolysaccharide]]s (LPS) produced by [[Gram-negative bacteria]] such as ''[[Escherichia coli|E. coli]].'' But pyrogens include non-endotoxic substances (derived from microorganisms other than gram-negative-bacteria or from chemical substances) as well.<ref>{{cite book |url=https://archive.org/details/biocompatibility00bout |title=Biocompatibility and Performance of Medical Devices |vauthors=Kojima K |date=2012-01-01 |publisher=Woodhead Publishing |isbn=978-0-85709-070-6 |editor-last=Boutrand |editor-first=Jean-Pierre |series=Woodhead Publishing Series in Biomaterials |pages=[https://archive.org/details/biocompatibility00bout/page/n434 404]–448 |chapter=17 – Biological evaluation and regulation of medical devices in Japan |doi=10.1533/9780857096456.4.404 |url-access=limited |s2cid=107630997}}</ref> The types of pyrogens include internal (endogenous) and external (exogenous) to the body.<ref>{{Citation |last=El-Radhi |first=A. Sahib |title=Pathogenesis of Fever |date=2018 |journal=Clinical Manual of Fever in Children |pages=53–68 |editor-last=El-Radhi |editor-first=A. Sahib |url=https://doi.org/10.1007/978-3-319-92336-9_3 |access-date=2024-06-26 |place=Cham |publisher=Springer International Publishing |doi=10.1007/978-3-319-92336-9_3 |isbn=978-3-319-92336-9 |pmc=7122269}}</ref>

The "pyrogenicity" of given pyrogens varies: in extreme cases, bacterial pyrogens can act as [[superantigens]] and cause rapid and dangerous fevers.<ref>{{Cite journal |last=Affairs |first=Office of Regulatory |date=2018-11-03 |title=Pyrogens, Still a Danger |url=https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/pyrogens-still-danger |archive-url=https://web.archive.org/web/20190502165201/https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/pyrogens-still-danger |url-status=dead |archive-date=2 May 2019 |journal=FDA}}</ref> <!--[[Depyrogenation]]--><!--OF WHAT? PATIENTS? PLASMA? SENTENCE NONSENSICAL AS IT STANDS--><!-- may be achieved through [[filtration]], [[distillation]], [[chromatography]], or inactivation.-->

====Endogenous====
Endogenous pyrogens are [[cytokine]]s released from [[monocyte]]s (which are part of the [[immune system]]).<ref>{{cite book |title=Veterinary Medicine |date=2017-01-01 |publisher=W.B. Saunders |isbn=978-0-7020-5246-0 |editor-last=Constable |editor-first=Peter D. |edition=11th |pages=43–112 |chapter=4 – General Systemic States |doi=10.1016/b978-0-7020-5246-0.00004-8 |pmc=7195945 |editor2-last=Hinchcliff |editor2-first=Kenneth W. |editor3-last=Done |editor3-first=Stanley H. |editor4-last=Grünberg |editor4-first=Walter |name-list-style=vanc |s2cid=214758182}}</ref> In general, they stimulate chemical responses, often in the presence of an [[antigen]], leading to a fever. Whilst they can be a product of external factors like exogenous pyrogens, they can also be induced by internal factors like [[damage associated molecular pattern]]s such as cases like [[rheumatoid arthritis]] or lupus.<ref>{{cite journal |vauthors=Dinarello CA |date=2015-03-31 |title=The history of fever, leukocytic pyrogen and interleukin-1 |journal=Temperature |volume=2 |issue=1 |pages=8–16 |doi=10.1080/23328940.2015.1017086 |pmc=4843879 |pmid=27226996}}</ref>

Major endogenous pyrogens are [[interleukin 1]] (α and β)<ref name="boron-58">{{cite book |author=Stitt, John |url=https://books.google.com/books?id=unBlQgAACAAJ |title=Medical Physiology: A Cellular and Molecular Approach |publisher=Elsevier Saunders |year=2008 |isbn=9781416031154 |veditors=Boron WF, Boulpaep, EL |edition=2nd |location=Philadelphia |chapter=Chapter 59: Regulation of Body Temperature |access-date=2 April 2020 |url-access=subscription}}</ref>{{rp|1237–1248}} and [[interleukin 6]] (IL-6).<ref>{{Cite book |last=Murphy, Kenneth (Kenneth M.) |title=Janeway's immunobiology |others=Weaver, Casey |year=2017 |isbn=978-0-8153-4505-3 |edition=9th |location=New York |pages=118–119 |oclc=933586700}}</ref> Minor endogenous pyrogens include [[interleukin-8]], [[Lymphotoxin alpha|tumor necrosis factor-β]], [[macrophage inflammatory protein]]-α and macrophage inflammatory protein-β as well as [[interferon-α]], [[IFN-β|interferon-β]], and [[Interferon-gamma|interferon-γ]].<ref name="boron-58" />{{rp|1237–1248}} [[Tumor necrosis factor-α]] (TNF) also acts as a pyrogen, mediated by [[interleukin 1]] (IL-1) release.<ref>{{cite journal |vauthors=Stefferl A, Hopkins SJ, Rothwell NJ, Luheshi GN |date=August 1996 |title=The role of TNF-alpha in fever: opposing actions of human and murine TNF-alpha and interactions with IL-beta in the rat |journal=British Journal of Pharmacology |volume=118 |issue=8 |pages=1919–1924 |doi=10.1111/j.1476-5381.1996.tb15625.x |pmc=1909906 |pmid=8864524}}</ref> These cytokine factors are released into general circulation, where they migrate to the brain's [[circumventricular organ]]s where they are more easily absorbed than in areas protected by the [[blood–brain barrier]].<ref>{{Citation |last1=Kennedy |first1=Rachel H. |title=Neuroimmune Signaling: Cytokines and the CNS |date=2016 |work=Neuroscience in the 21st Century |pages=1–41 |editor-last=Pfaff |editor-first=Donald W. |url=https://doi.org/10.1007/978-1-4614-6434-1_174-1 |access-date=2024-06-26 |place=New York |publisher=Springer |doi=10.1007/978-1-4614-6434-1_174-1 |isbn=978-1-4614-6434-1 |last2=Silver |first2=Rae |editor2-last=Volkow |editor2-first=Nora D.|url-access=subscription }}</ref> The cytokines then bind to [[endothelium|endothelial receptor]]s on vessel walls to receptors on [[microglial cell]]s, resulting in activation of the [[arachidonic acid pathway]].<ref>{{Cite book |last=Eskilsson |first=Anna |title=Inflammatory Signaling Across the Blood-Brain Barrier and the Generation of Fever |date=2020 |publisher=Linköping University, Department of Biomedical and Clinical Sciences |isbn=978-91-7929-936-1 |location=Linköping}}</ref>

Of these, IL-1β, TNF, and IL-6 are able to raise the temperature setpoint of an organism and cause fever. These proteins produce a [[cyclooxygenase]] which induces the hypothalamic production of PGE2 which then stimulates the release of neurotransmitters such as [[cyclic adenosine monophosphate]] and increases body temperature.<ref>{{cite book |last1=Srinivasan |first1=Lakshmi |title=Fetal and Neonatal Physiology |last2=Harris |first2=Mary Catherine |last3=Kilpatrick |first3=Laurie E. |date=2017-01-01 |publisher=Elsevier |isbn=978-0-323-35214-7 |editor-last=Polin |editor-first=Richard A. |edition=5th |pages=1241–1254.e4 |chapter=128 – Cytokines and Inflammatory Response in the Fetus and Neonate |doi=10.1016/b978-0-323-35214-7.00128-1 |editor2-last=Abman |editor2-first=Steven H. |editor3-last=Rowitch |editor3-first=David H. |editor4-last=Benitz |editor4-first=William E. |name-list-style=vanc}}</ref>

==== Exogenous ====
Exogenous pyrogens are external to the body and are of microbial origin. In general, these pyrogens, including bacterial cell wall products, may act on Toll-like receptors in the hypothalamus and elevate the thermoregulatory setpoint.<ref>{{cite book |last1=Wilson |first1=Mary E. |title=Tropical Infectious Diseases: Principles, Pathogens and Practice |last2=Boggild |first2=Andrea K. |date=2011-01-01 |publisher=W.B. Saunders |isbn=978-0-7020-3935-5 |editor-last=Guerrant |editor-first=Richard L. |edition=3rd |pages=925–938 |chapter=130 – Fever and Systemic Symptoms |doi=10.1016/b978-0-7020-3935-5.00130-0 |editor2-last=Walker |editor2-first=David H. |editor3-last=Weller |editor3-first=Peter F. |name-list-style=vanc}}</ref>

An example of a class of exogenous pyrogens are bacterial [[lipopolysaccharide]]s (LPS) present in the cell wall of [[gram-negative bacteria]]. According to one mechanism of pyrogen action, an immune system protein, [[lipopolysaccharide-binding protein]] (LBP), binds to LPS, and the LBP–LPS complex then binds to a [[CD14]] receptor on a [[macrophage]]. The LBP-LPS binding to CD14 results in cellular synthesis and release of various endogenous [[cytokine]]s, e.g., interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNFα). A further downstream event is activation of the [[arachidonic acid pathway]].<ref>{{cite journal |vauthors=Roth J, Blatteis CM |date=October 2014 |title=Mechanisms of fever production and lysis: Lessons from experimental LPS fever |journal=Comprehensive Physiology |volume=4 |issue=4 |pages=1563–1604 |doi=10.1002/cphy.c130033 |isbn=9780470650714 |pmid=25428854}}</ref>

===Neural circuit mechanism with PGE2 action===
PGE2 release comes from the [[arachidonic acid]] pathway. This pathway (as it relates to fever), is mediated by the [[enzyme]]s [[phospholipase|phospholipase A2]] (PLA2), [[cyclooxygenase|cyclooxygenase-2]] (COX-2), and [[prostaglandin E2 synthase]]. These enzymes ultimately mediate the synthesis and release of PGE2.<ref>{{Cite journal |last1=Samuelsson |first1=Bengt |last2=Morgenstern |first2=Ralf |last3=Jakobsson |first3=Per-Johan |date=September 2007 |title=Membrane Prostaglandin E Synthase-1: A Novel Therapeutic Target |url=https://linkinghub.elsevier.com/retrieve/pii/S0031699724117267 |journal=Pharmacological Reviews |language=en |volume=59 |issue=3 |pages=207–224 |doi=10.1124/pr.59.3.1|pmid=17878511 |url-access=subscription }}</ref>

PGE2 is the ultimate mediator of the febrile response. The setpoint 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).<ref>{{Cite journal |last1=Nakamura |first1=Kazuhiro |last2=Kaneko |first2=Takeshi |last3=Yamashita |first3=Yoko |last4=Hasegawa |first4=Hiroshi |last5=Katoh |first5=Hironori |last6=Ichikawa |first6=Atsushi |last7=Negishi |first7=Manabu |date=1999-01-29 |title=Immunocytochemical localization of prostaglandin EP3 receptor in the rat hypothalamus |url=https://linkinghub.elsevier.com/retrieve/pii/S0304394098009628 |journal=Neuroscience Letters |language=en |volume=260 |issue=2 |pages=117–120 |doi=10.1016/S0304-3940(98)00962-8|pmid=10025713 |url-access=subscription }}</ref><ref name=":1">{{Cite journal |last1=Nakamura |first1=Kazuhiro |last2=Matsumura |first2=Kiyoshi |last3=Kaneko |first3=Takeshi |last4=Kobayashi |first4=Shigeo |last5=Katoh |first5=Hironori |last6=Negishi |first6=Manabu |date=2002-06-01 |title=The Rostral Raphe Pallidus Nucleus Mediates Pyrogenic Transmission from the Preoptic Area |journal=The Journal of Neuroscience |language=en |volume=22 |issue=11 |pages=4600–4610 |doi=10.1523/JNEUROSCI.22-11-04600.2002 |issn=0270-6474 |pmc=6758794 |pmid=12040067}}</ref><ref>{{Cite journal |last1=Lazarus |first1=Michael |last2=Yoshida |first2=Kyoko |last3=Coppari |first3=Roberto |last4=Bass |first4=Caroline E |last5=Mochizuki |first5=Takatoshi |last6=Lowell |first6=Bradford B |last7=Saper |first7=Clifford B |date=September 2007 |title=EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses |url=https://www.nature.com/articles/nn1949 |journal=Nature Neuroscience |language=en |volume=10 |issue=9 |pages=1131–1133 |doi=10.1038/nn1949 |pmid=17676060 |issn=1097-6256|url-access=subscription }}</ref><ref name=":2">{{Cite journal |last1=Nakamura |first1=Yoshiko |last2=Yahiro |first2=Takaki |last3=Fukushima |first3=Akihiro |last4=Kataoka |first4=Naoya |last5=Hioki |first5=Hiroyuki |last6=Nakamura |first6=Kazuhiro |date=2022-12-23 |title=Prostaglandin EP3 receptor–expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling |journal=Science Advances |language=en |volume=8 |issue=51 |pages=eadd5463 |doi=10.1126/sciadv.add5463 |issn=2375-2548 |pmc=9788766 |pmid=36563142|bibcode=2022SciA....8D5463N }}</ref> EP3-expressing neurons in the POA innervate the [[dorsomedial hypothalamus]] (DMH),<ref>{{Cite journal |last1=Nakamura |first1=Yoshiko |last2=Nakamura |first2=Kazuhiro |last3=Matsumura |first3=Kiyoshi |last4=Kobayashi |first4=Shigeo |last5=Kaneko |first5=Takeshi |last6=Morrison |first6=Shaun F. |date=December 2005 |title=Direct pyrogenic input from prostaglandin EP3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus |journal=European Journal of Neuroscience |language=en |volume=22 |issue=12 |pages=3137–3146 |doi=10.1111/j.1460-9568.2005.04515.x |issn=0953-816X |pmc=2441892 |pmid=16367780}}</ref><ref name=":3">{{Cite journal |last1=Nakamura |first1=Y. |last2=Nakamura |first2=K. |last3=Morrison |first3=S.F. |date=2009-06-30 |title=Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions |journal=Neuroscience |language=en |volume=161 |issue=2 |pages=614–620 |doi=10.1016/j.neuroscience.2009.03.041 |pmc=2857774 |pmid=19327390}}</ref> the rostral [[raphe]] pallidus nucleus in the [[medulla oblongata]] (rRPa),<ref name=":1" /><ref name=":3" /> and the [[paraventricular nucleus]] (PVN) of the [[hypothalamus]].<ref>{{Cite journal |last1=Zhang |first1=Zhi-Hua |last2=Yu |first2=Yang |last3=Wei |first3=Shun-Guang |last4=Nakamura |first4=Yoshiko |last5=Nakamura |first5=Kazuhiro |last6=Felder |first6=Robert B. |date=October 2011 |title=EP3 receptors mediate PGE2-induced hypothalamic paraventricular nucleus excitation and sympathetic activation |journal=American Journal of Physiology-Heart and Circulatory Physiology |language=en |volume=301 |issue=4 |pages=H1559–H1569 |doi=10.1152/ajpheart.00262.2011 |issn=0363-6135 |pmc=3197370 |pmid=21803943}}</ref> Under normal conditions, EP3-expressing neurons in the POA are important [[Thermoregulation|thermoregulatory]] neurons, which provide continuous inhibitory signals with the transmitter [[GABA]] to control [[Sympathetic nervous system|sympathetic]] output neurons in the DMH and rRPa, thereby performing bidirectional regulation of basal body temperature.<ref name=":2" /> During infection, PGE2 produced in the brain inhibits the activity of EP3-expressing neurons in the POA to attenuate the inhibition of sympathetic output, and thereby activates the sympathetic output system, which evokes non-shivering thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface, leading to fever.<ref name=":2" /> 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]].

==Diagnosis==
{{HumanTemperature}}
A range for [[Normal human body temperature|normal temperatures]] has been found.<ref name=CC09 /><!-- defined by template:HumanTemperature --> Central temperatures, such as rectal temperatures, are more accurate than peripheral temperatures.<ref name = Niven2015>{{cite journal | vauthors = Niven DJ, Gaudet JE, Laupland KB, Mrklas KJ, Roberts DJ, Stelfox HT | s2cid = 4004360 | title = Accuracy of peripheral thermometers for estimating temperature: a systematic review and meta-analysis | journal = Annals of Internal Medicine | volume = 163 | issue = 10 | pages = 768–777 | date = November 2015 | pmid = 26571241 | doi = 10.7326/M15-1150 }}</ref>
Fever is generally agreed to be present if the elevated temperature<ref>{{Cite web |title=Fever - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/fever/symptoms-causes/syc-20352759 |access-date=2022-04-23 |website=Mayo Clinic }}</ref> is caused by a raised set point and:
* Temperature in the [[Human anus|anus]] (rectum/rectal) is at or over {{convert|37.5|–|38.3|C|F|1}}.<ref name=NC08/><ref name="CC09"/><!-- defined by template:HumanTemperature --> An [[ear]] (tympanic) or [[forehead]] (temporal) temperature may also be used.<ref>{{cite web |title=Measuring a Baby's Temperature |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/measuring-a-babys-temperature |website=www.hopkinsmedicine.org |access-date=10 September 2019 |archive-url=https://web.archive.org/web/20191103102816/https://www.hopkinsmedicine.org/health/conditions-and-diseases/measuring-a-babys-temperature |archive-date=3 November 2019 |url-status=dead }}</ref><ref>{{cite web |title=Tips for taking your child's temperature |url=https://www.mayoclinic.org/healthy-lifestyle/infant-and-toddler-health/in-depth/thermometer/art-20047410 |website=Mayo Clinic |access-date=10 September 2019 }}</ref>
* Temperature in the mouth (oral) is at or over {{convert|37.2|C|F}} in the morning or over {{convert|37.7|C|F}} in the afternoon<ref name=Harrisons20th/><ref name=Reiew09>{{cite journal | vauthors = Barone JE | title = Fever: Fact and fiction | journal = The Journal of Trauma | volume = 67 | issue = 2 | pages = 406–409 | date = August 2009 | pmid = 19667898 | doi = 10.1097/TA.0b013e3181a5f335 }}</ref>
* Temperature under the arm (axillary) is usually about {{convert|0.6|C-change|F-change}} below core body temperature.<ref name="Pecoraro Petri Costantino Squizzato pp. 1071–1083">{{cite journal | last1=Pecoraro | first1=Valentina | last2=Petri | first2=Davide | last3=Costantino | first3=Giorgio | last4=Squizzato | first4=Alessandro | last5=Moja | first5=Lorenzo | last6=Virgili | first6=Gianni | last7=Lucenteforte | first7=Ersilia | title=The diagnostic accuracy of digital, infrared and mercury-in-glass thermometers in measuring body temperature: a systematic review and network meta-analysis | journal=Internal and Emergency Medicine | publisher=Springer Science and Business Media LLC | volume=16 | issue=4 | date=2020-11-25 | issn=1828-0447 | doi=10.1007/s11739-020-02556-0 | pages=1071–1083| pmid=33237494 | pmc=7686821 }}</ref>

In adults, the [[Normal human body temperature|normal range]] of temperatures in healthy individuals is {{convert|36.32|–|37.76|C|F|1}} (rectal), {{convert|35.76|–|37.52|C|F|1}} ([[tympanic membrane|ear]]), {{convert|35.61|–|37.61|C|F|1}} (urine), {{convert|35.73|–|37.41|C|F|1}} (oral), and {{convert|35.01|–|36.93|C|F|1}} (axillary), with no significant gender differences.<ref name="geneva2019">{{cite journal |doi=10.1093/ofid/ofz032 |title=Normal Body Temperature: A Systematic Review |date=2019 |last1=Geneva |first1=Ivayla I. |last2=Cuzzo |first2=Brian |last3=Fazili |first3=Tasaduq |last4=Javaid |first4=Waleed |journal=Open Forum Infectious Diseases |volume=6 |issue=4 |pages=ofz032 |pmid=30976605 |pmc=6456186 }}</ref>

Normal body temperatures vary depending on many factors, including age, sex, time of day, ambient temperature, activity level, and more.<ref name="Garami">{{Cite journal|last1=Garami|first1=András|last2=Székely|first2=Miklós|date=2014-05-06|title=Body temperature|journal=Temperature: Multidisciplinary Biomedical Journal|volume=1|issue=1|pages=28–29|doi=10.4161/temp.29060|issn=2332-8940|pmc=4972507|pmid=27583277}}</ref><ref>{{Cite web|url=https://www.medicalnewstoday.com/articles/327458|title=Body temperature: What is the new normal?|website=www.medicalnewstoday.com|date=12 January 2020|access-date=2020-04-07}}</ref>  Normal daily temperature variation has been described as 0.5&nbsp;°C (0.9&nbsp;°F).<ref name=Harrisons20th/>{{rp|4012}}  A raised temperature is not always a fever.<ref name="Garami" />  For example, the temperature rises in healthy people when they exercise, but this is not considered a fever, as the set point is normal.<ref name="Garami" /> On the other hand, a "normal" temperature may be a fever, if it is unusually high for that person; for example, [[medically frail]] elderly people have a decreased ability to generate body heat, so a "normal" temperature of {{convert|37.3|C|F}} may represent a clinically significant fever.<ref name="Garami" /><ref>{{cite journal |last1=Alsalamah |first1=M |last2=Alrehaili |first2=B |last3=Almoamary |first3=A |last4=Al-Juad |first4=A |last5=Badri |first5=M |last6=El-Metwally |first6=A |title=The optimal oral body temperature cutoff and other factors predictive of sepsis diagnosis in elderly patients. |journal=Annals of Thoracic Medicine |date=July 2022 |volume=17 |issue=3 |pages=159–165 |doi=10.4103/atm.atm_52_22 |pmid=35968398|pmc=9374123 |doi-access=free }}</ref>

=== Associated conditions ===
Fever is a common [[symptom]] of many medical conditions:

* [[Infectious disease]], e.g., [[COVID-19]],<ref name="Rod2020" /> [[dengue]], [[Ebola virus disease|Ebola]], [[gastroenteritis]], [[HIV]], [[influenza]], [[Lyme disease]], [[rocky mountain spotted fever]], [[Syphilis#Secondary|secondary syphilis]], [[malaria]], [[infectious mononucleosis|mononucleosis]], as well as infections of the skin, e.g., [[abscess]]es and [[boils]].<ref>{{Cite journal |last1=Raoult |first1=Didier |last2=Levy |first2=Pierre-Yves |last3=Dupont |first3=Hervé Tissot |last4=Chicheportiche |first4=Colette |last5=Tamalet |first5=Catherine |last6=Gastaut |first6=Jean-Albert |last7=Salducci |first7=Jacques |date=January 1993 |title=Q fever and HIV infection |url=http://journals.lww.com/00002030-199301000-00012 |journal=AIDS |volume=7 |issue=1 |pages=81–86 |doi=10.1097/00002030-199301000-00012 |issn=0269-9370 |pmid=8442921|url-access=subscription }}</ref><ref>{{Cite journal |last1=French |first1=Neil |last2=Nakiyingi |first2=Jessica |last3=Lugada |first3=Eric |last4=Watera |first4=Christine |last5=Whitworth |first5=James A. G. |last6=Gilks |first6=Charles F. |date=May 2001 |title=Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults |url=https://journals.lww.com/aidsonline/Fulltext/2001/05040/Increasing_rates_of_malarial_fever_with.10.aspx |url-status=live |journal=AIDS |volume=15 |issue=7 |pages=899–906 |doi=10.1097/00002030-200105040-00010 |issn=0269-9370 |pmid=11399962 |s2cid=25470703 |archive-url=https://web.archive.org/web/20220222192422/https://journals.lww.com/aidsonline/Fulltext/2001/05040/Increasing_rates_of_malarial_fever_with.10.aspx |archive-date=2022-02-22|url-access=subscription }}</ref><ref>{{Cite journal |last1=Heymann |first1=D. L. |last2=Weisfeld |first2=J. S. |last3=Webb |first3=P. A. |last4=Johnson |first4=K. M. |last5=Cairns |first5=T. |last6=Berquist |first6=H. |date=1980-09-01 |title=Ebola Hemorrhagic Fever: Tandala, Zaire, 1977–1978 |journal=Journal of Infectious Diseases |volume=142 |issue=3 |pages=372–376 |doi=10.1093/infdis/142.3.372 |issn=0022-1899 |pmid=7441008}}</ref><ref>{{Cite journal |last1=Feldmann |first1=Heinz |last2=Geisbert |first2=Thomas W |date=March 2011 |title=Ebola haemorrhagic fever |journal=The Lancet |volume=377 |issue=9768 |pages=849–862 |doi=10.1016/s0140-6736(10)60667-8 |issn=0140-6736 |pmc=3406178 |pmid=21084112}}</ref><ref>{{Cite journal |last1=Oakley |first1=Miranda S. |last2=Gerald |first2=Noel |last3=McCutchan |first3=Thomas F. |last4=Aravind |first4=L. |last5=Kumar |first5=Sanjai |date=October 2011 |title=Clinical and molecular aspects of malaria fever |journal=Trends in Parasitology |volume=27 |issue=10 |pages=442–449 |doi=10.1016/j.pt.2011.06.004 |issn=1471-4922 |pmid=21795115}}</ref><ref>{{Cite journal |last1=Colunga-Salas |first1=Pablo |last2=Sánchez-Montes |first2=Sokani |last3=Volkow |first3=Patricia |last4=Ruíz-Remigio |first4=Adriana |last5=Becker |first5=Ingeborg |date=2020-09-17 |title=Lyme disease and relapsing fever in Mexico: An overview of human and wildlife infections |journal=PLOS ONE |volume=15 |issue=9 |pages=e0238496 |bibcode=2020PLoSO..1538496C |doi=10.1371/journal.pone.0238496 |issn=1932-6203 |pmc=7497999 |pmid=32941463 |doi-access=free}}</ref>
* [[Immunology|Immunological]] diseases, e.g., [[relapsing polychondritis]],<ref name="Puechal 2014">{{cite journal |vauthors=Puéchal X, Terrier B, Mouthon L, Costedoat-Chalumeau N, Guillevin L, Le Jeunne C |date=March 2014 |title=Relapsing polychondritis |journal=Joint, Bone, Spine |volume=81 |issue=2 |pages=118–124 |doi=10.1016/j.jbspin.2014.01.001 |pmid=24556284 |s2cid=205754989}}</ref> [[autoimmune hepatitis]], [[granulomatosis with polyangiitis]], [[Horton disease]], [[inflammatory bowel disease]]s, [[Kawasaki disease]], [[lupus erythematosus]], [[sarcoidosis]], [[Adult-onset Still's disease|Still's disease]], [[rheumatoid arthritis]], [[lymphoproliferative disorders]] and [[psoriasis]];{{citation needed|date=April 2020}}
* Tissue destruction, as a result of [[cerebral hemorrhage|cerebral bleeding]], [[crush syndrome]], [[hemolysis]], [[infarction]], [[rhabdomyolysis]], [[surgery]], etc.;<ref>{{Citation |last=Arnhold |first=Jürgen |title=Cell and Tissue Destruction in Selected Disorders |date=2020 |work=Cell and Tissue Destruction |pages=249–287 |url=http://dx.doi.org/10.1016/b978-0-12-816388-7.00009-7 |access-date=2022-04-22 |publisher=Elsevier |doi=10.1016/b978-0-12-816388-7.00009-7 |isbn=9780128163887 |s2cid=209284148|url-access=subscription }}</ref><ref>{{Cite book |author=Arnhold, Jürgen |title=Cell and tissue destruction: mechanisms, protection, disorders |publisher=Elsevier Science |year=2019 |isbn=978-0-12-816388-7 |oclc=1120070914}}</ref>
* [[Cancer]]s, particularly blood cancers such as [[leukemia]] and [[lymphoma]]s;<ref>{{Cite web |title=Signs and Symptoms of Cancer {{!}} Do I Have Cancer? |url=https://www.cancer.org/cancer/cancer-basics/signs-and-symptoms-of-cancer.html |access-date=2020-06-20 |website=www.cancer.org}}</ref>
* [[Metabolic disorder]]s, e.g., [[gout]], and [[porphyria]];<ref>{{Cite book |author=Centerwall, Willard R. |title=Phenylketonuria: an inherited metabolic disorder associated with mental retardation |date=1965 |publisher=U.S. Department of Health, Education, and Welfare, Welfare Administration, Children's Bureau |oclc=392284}}</ref> and<ref>{{Citation |title=Metabolic Disorder |date=2020-02-07 |work=Definitions |publisher=Qeios |doi=10.32388/7344b1 |s2cid=42063856|doi-access=free }}</ref>
* Inherited metabolic disorder, e.g., [[Fabry disease]].<ref name="Harrisons20th" />
Adult and pediatric manifestations for the same disease may differ; for instance, in [[COVID-19]], one metastudy describes 92.8% of adults versus 43.9% of children presenting with fever.<ref name="Rod2020" />

In addition, fever can result from a reaction to an incompatible blood product.<ref>{{cite book |last1=Dean |first1=Laura |url=https://www.ncbi.nlm.nih.gov/books/NBK2265/ |title=Blood transfusions and the immune system |date=2005 |publisher=National Center for Biotechnology Information (US)}}</ref>

==Types==
[[File:Fever Patterns v1.2.svg|thumb|upright=1.8|Different fever patterns observed in ''Plasmodium'' infections]]Various patterns of measured patient temperatures have been observed, some of which may be indicative of a particular [[medical diagnosis]]:
* [[Continuous fever]], where temperature remains above normal and does not fluctuate more than {{val|1|u=°C}} in 24 hours<ref>{{cite journal | vauthors = Ogoina D | title = Fever, fever patterns and diseases called 'fever' – a review | journal = Journal of Infection and Public Health | volume = 4 | issue = 3 | pages = 108–124 | date = August 2011 | pmid = 21843857 | doi = 10.1016/j.jiph.2011.05.002 | doi-access = free }}</ref> (e.g. in [[bacterial pneumonia]], [[typhoid fever]], [[infective endocarditis]], [[tuberculosis]], or [[typhus]]).<ref>Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau (drops due to fever-reducing drugs are excluded).{{citation needed|date=April 2020}}</ref><ref>{{cite book |last1=Dall |first1=Lawrence |last2=Stanford |first2=James F. |editor1-last=Walker |editor1-first=H. Kenneth |editor2-last=Hall |editor2-first=W. Dallas |editor3-last=Hurst |editor3-first=J. Willis |title=Clinical Methods: The History, Physical, and Laboratory Examinations |date=1990 |publisher=Butterworths |location=Boston |isbn=0-409-90077-X |edition=3rd |url=https://www.ncbi.nlm.nih.gov/books/NBK324/ |chapter=Fever, Chills, and Night Sweats|pmid=21250166 }}</ref>
* [[Intermittent fever]] is present only for a certain period, later cycling back to normal (e.g., in [[malaria]], [[Visceral leishmaniasis|leishmaniasis]], [[pyemia]], [[sepsis]],<ref>{{cite book |first1=Muhammad |last1=Inayatullah |first2=Shabbir Ahmed |last2=Nasir |year=2016 |title=Bedside Techniques: Methods of Clinical Examination |publisher=Paramount Books (Pvt.) Limited |edition=4th |isbn=978-969-494-920-8 }}{{page needed|date=January 2018}}</ref> or [[African trypanosomiasis]]).<ref>{{Cite web|date=2020-04-28|title= African Trypanosomiasis – Disease|url=https://www.cdc.gov/parasites/sleepingsickness/disease.html|access-date=2021-07-18 |website=CDC |url-status=live |archive-url=https://web.archive.org/web/20210718232904/https://www.cdc.gov/parasites/sleepingsickness/disease.html |archive-date= 2021-07-18 }}</ref>
* [[Remittent fever]], where the temperature remains above normal throughout the day and fluctuates more than {{val|1|u=°C}} in 24 hours (e.g., in [[infective endocarditis]] or [[brucellosis]]).<ref>{{cite web |url=https://www.lecturio.com/concepts/brucellosis/| title=Brucella/Brucellosis
|website=The Lecturio Medical Concept Library |access-date= 19 July 2021}}</ref>
* [[Pel–Ebstein fever]] is a cyclic fever that is rarely seen in patients with [[Hodgkin's lymphoma]].{{Citation needed|date=March 2025}}
* Undulant fever, seen in [[brucellosis]].{{Citation needed|date=March 2025}}
* [[Typhoid fever]] is a [[continuous fever]] showing a characteristic ''step-ladder pattern,'' a step-wise increase in temperature with a high plateau.<ref>{{cite web |url=https://www.lecturio.com/concepts/enteric-fever-typhoid-fever/| title=Enteric Fever (Typhoid Fever)|website=The Lecturio Medical Concept Library | date=27 August 2020|access-date= 19 July 2021}}</ref>

Among the types of intermittent fever are ones specific to cases of malaria caused by different pathogens. These are:<ref name="Ferri 2009">{{Cite book |author=Ferri FF |chapter=Chapter 332. Protozoal infections |title=Ferri's Color Atlas and Text of Clinical Medicine |year=2009 |publisher=Elsevier Health Sciences |isbn=9781416049197 |pages=1159ff |chapter-url=https://books.google.com/books?id=ZbisJsvDEegC&pg=PA1159 |url-status=live |archive-url=https://web.archive.org/web/20160603093438/https://books.google.com/books?id=ZbisJsvDEegC&pg=PA1159 |archive-date=3 June 2016 | access-date = 31 March 2020}}</ref><ref>{{cite book | vauthors = Muhammad I, Nasir, SA |title= Bedside Techniques: Methods of Clinical Examination | location = [[Multan, Pakistan]] | publisher= Saira Publishers/Salamat Iqbal Press  |date=2009 }}{{page needed|date=April 2020}}{{better source needed|date=April 2020}}</ref>
* Quotidian fever, with a 24-hour periodicity, typical of [[malaria]] caused by ''[[Plasmodium knowlesi]]'' (''P. knowlesi'');<ref>{{cite journal |last1=Singh |first1=B. |last2=Daneshvar |first2=C. |title=Human Infections and Detection of Plasmodium knowlesi |journal=Clinical Microbiology Reviews |date=1 April 2013 |volume=26 |issue=2 |pages=165–184 |doi=10.1128/CMR.00079-12|pmid=23554413 |pmc=3623376 |doi-access=free }}</ref><ref>{{cite journal |last1=Chin |first1=W. |last2=Contacos |first2=P. G. |last3=Coatney |first3=G. R. |last4=Kimball |first4=H. R. |title=A Naturally Acquired Quotidian-Type Malaria in Man Transferable to Monkeys |journal=Science |date=20 August 1965 |volume=149 |issue=3686 |page=865 |doi=10.1126/science.149.3686.865|pmid=14332847 |bibcode=1965Sci...149..865C |s2cid=27841173 }}</ref>
* [[Tertian fever]], with a 48-hour periodicity, typical of later course [[malaria]] caused by ''[[Plasmodium falciparum|P. falciparum]]'', ''[[Plasmodium vivax|P. vivax]]'', or ''[[Plasmodium ovale|P. ovale]]'';<ref name="Ferri 2009" />
* [[Quartan fever]], with a 72-hour periodicity, typical of later course [[malaria]] caused by ''[[Plasmodium malariae|P. malariae]]''.<ref name="Ferri 2009" />

In addition, there is disagreement regarding whether a specific fever pattern is associated with [[Hodgkin's lymphoma]]—the [[Pel–Ebstein fever]], with patients argued to present high temperature for one week, followed by low for the next week, and so on, where the generality of this pattern is debated.<ref>{{Cite web |date=2021-11-09 |title=Hodgkin Lymphoma: Practice Essentials, Background, Pathophysiology |url=https://emedicine.medscape.com/article/201886-clinical |website=Medscape}}</ref><ref>{{cite journal | vauthors = Hilson AJ | title = Pel-Ebstein fever | journal = The New England Journal of Medicine | volume = 333 | issue = 1 | pages = 66–67 | date = July 1995 | pmid = 7777006 | doi = 10.1056/NEJM199507063330118 }}, which cites [[Richard Asher]]'s lecture, "Making Sense" [''Lancet'' (1959) '''2''': 359].</ref>

Persistent fever that cannot be explained after repeated routine clinical inquiries is called [[fever of unknown origin]].<ref name="Harrisons20th" /><ref>{{Cite journal |last1=Magrath |first1=Melissa |last2=Pearlman |first2=Michelle |last3=Peng |first3=Lan |last4=Lee |first4=William |date=2018-06-30 |title=Granulomatous Hepatitis and Persistent Fever of Unknown Origin: A Case Report |journal=Gastroenterology, Hepatology & Digestive Disorders |volume=1 |issue=2 |pages=1–2 |doi=10.33425/2639-9334.1009 |s2cid=86786427 |issn=2639-9334|doi-access=free }}</ref> A [[neutropenic fever]], also called febrile neutropenia, is a fever in the absence of normal immune system function.<ref name="Klastersky 2014 13–26">{{Citation |last=Klastersky |first=Jean A. |title=Prevention of Febrile Neutropenia |date=2014 |url=http://dx.doi.org/10.1007/978-1-907673-70-2_2 |work=Febrile Neutropenia |pages=13–26 |place=Tarporley |publisher=Springer Healthcare Ltd. |doi=10.1007/978-1-907673-70-2_2 |isbn=978-1-907673-69-6 |access-date=2022-04-22|url-access=subscription }}</ref> Because of the lack of infection-fighting [[neutrophil]]s, a bacterial infection can spread rapidly; this fever is, therefore, usually considered to require urgent medical attention.<ref>{{Cite journal|last1=White|first1=Lindsey|last2=Ybarra|first2=Michael|date=2017-12-01|title=Neutropenic Fever|url=https://linkinghub.elsevier.com/retrieve/pii/S0889858817301284|journal=Hematology/Oncology Clinics of North America|volume=31|issue=6|pages=981–993|doi=10.1016/j.hoc.2017.08.004|pmid=29078933|via=ClinicalKey|url-access=subscription}}</ref> This kind of fever is more commonly seen in people receiving immune-suppressing [[chemotherapy]] than in apparently healthy people.<ref name="Klastersky 2014 13–26" /><ref>{{Cite book |editor=Rolston, Kenneth VI |editor2=Rubenstein, Edward B. |title=Textbook of febrile neutropenia |date=2001 |publisher=Martin Dunitz |isbn=978-1-84184-033-8 |oclc=48195937}}</ref>

=== Hyperpyrexia ===
Hyperpyrexia is an extreme elevation of [[body temperature]] which, depending upon the source, is classified as a [[core body temperature]] greater than or equal to {{convert|40|or|41|C|F|0}}; the range of hyperpyrexia includes cases considered severe (≥ 40&nbsp;°C) and extreme (≥ 42&nbsp;°C).<ref name="Harrisons20th" /><ref name="MDMA-Hyperpyrexia systematic review">{{cite journal | vauthors = Grunau BE, Wiens MO, Brubacher JR | title = Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review | journal = Canadian Journal of Emergency Medicine | volume = 12 | issue = 5 | pages = 435–442 | date = September 2010 | pmid = 20880437 | doi = 10.1017/s1481803500012598 | quote = Dantrolene may also be associated with improved survival and reduced complications, especially in patients with extreme (≥ 42&nbsp;°C) or severe (≥ 40&nbsp;°C) hyperpyrexia | doi-access = free }}</ref><ref name="Neurobiology of hyperthermia">{{cite book | editor=Sharma HS | title=Neurobiology of Hyperthermia | date=2007 | publisher=Elsevier | isbn=978-0080549996 | pages=175–177, 485 | edition=1st | url=https://books.google.com/books?id=Vk1UTlmEwrQC&pg=485 | access-date=19 November 2016 | quote=Despite the myriad of complications associated with heat illness, an elevation of core temperature above 41.0&nbsp;°C (often referred to as fever or hyperpyrexia) is the most widely recognized symptom of this syndrome. | url-status=live | archive-url=https://web.archive.org/web/20170908174330/https://books.google.com/books?id=Vk1UTlmEwrQC&pg=485#v=onepage&q=hyperpyrexia%20core%20temperature&f=false | archive-date=8 September 2017  }}</ref> It differs from [[hyperthermia]] in that one's [[Human thermoregulation#Control system|thermoregulatory system's set point]] for body temperature is set above normal, then heat is generated to achieve it. In contrast, hyperthermia involves body temperature rising above its set point due to outside factors.<ref name="Harrisons20th" /><ref>See section in Chapter 15 therein, the section on "Fever versus hyperthermia".</ref> The high temperatures of hyperpyrexia are considered [[medical emergency|medical emergencies]], as they may indicate a serious underlying condition or lead to severe morbidity (including permanent [[brain damage]]), or to death.<ref name="EM01" /> A common cause of hyperpyrexia is an [[intracranial hemorrhage]].<ref name="Harrisons20th" /> Other causes in emergency room settings include Malignant Catatonia, [[sepsis]], [[Kawasaki syndrome]],<ref name="Marx 2006 2506">Marx (2006), p. 2506.</ref> [[neuroleptic malignant syndrome]], [[drug overdose]], [[serotonin syndrome]], and [[thyroid storm]].<ref name="EM01">{{cite journal | vauthors = McGugan EA | title = Hyperpyrexia in the emergency department | journal = Emergency Medicine | volume = 13 | issue = 1 | pages = 116–120 | date = March 2001 | pmid = 11476402 | doi = 10.1046/j.1442-2026.2001.00189.x }}</ref>

==Function==
[[Image:fever-conceptual.svg|thumb|upright=1.6|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.<br />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.<br />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.]]

=== Immune function ===
Fever is thought to contribute to host defense,<ref name="Sch2006" /> as the reproduction of [[pathogen]]s with strict temperature requirements can be hindered, and the rates of some important immunological reactions are increased by temperature.<ref name="Fischler">{{cite journal | vauthors = Fischler MP, Reinhart WH | title = [Fever: friend or enemy?] | language = de | journal = Schweizerische Medizinische Wochenschrift | volume = 127 | issue = 20 | pages = 864–870 | date = May 1997 | pmid = 9289813 }}</ref> Fever has been described in teaching texts as assisting the healing process in various ways, including:
:* increased mobility of [[leukocytes]];<ref name = Craven2003>{{cite book |vauthors=Craven RF, Hirnle CJ | year = 2003 | title = Fundamentals of Nursing: Human Health and Function | edition = 4th | location = Philadelphia, PA | publisher = Lippincott Williams & Wilkins | isbn = 9780781758185 | url = https://archive.org/details/fundamentalsofnu0000unse_c8z5 | url-access = registration |  access-date = 2 April 2020 }}</ref>{{rp|1044}}
:* enhanced leukocyte [[phagocytosis]];<ref name = Craven2003/>{{rp|1030}}
:* decreased [[endotoxin]] effects;<ref name = Craven2003/>{{rp|1029}} and
:* increased [[Cell proliferation|proliferation]] of [[T cells]].<ref name = Craven2003/>{{rp|1030}}<ref name=LewisDirksenHeitkemper2005>{{cite book |vauthors=Lewis SM, Dirksen SR, Heitkemper MM  | year = 2005 | title = Medical-Surgical Nursing: Assessment and Management of Clinical Problems | edition = 6th | location = Amsterdam, NL | publisher = Elsevier-Health Sciences | isbn = 9780323031059 | url = https://books.google.com/books?id=3TerPAAACAAJ |  access-date = 2 April 2020 }}</ref>{{rp|212}}

=== Advantages and disadvantages ===
A fever response to an infectious disease is generally regarded as protective, whereas fever in non-infections may be maladaptive.<ref name="kiek">{{cite journal |vauthors=Kiekkas P, Aretha D, Bakalis N, Karpouhtsi I, Marneras C, Baltopoulos GI |title=Fever effects and treatment in critical care: literature review |journal=Australian Critical Care |volume=26 |issue=3 |pages=130–135 |date=August 2013 |pmid=23199670 |doi=10.1016/j.aucc.2012.10.004 |url=}}</ref><ref name="pmid9917881">{{cite journal |vauthors=Kluger MJ, Kozak W, Conn CA, Leon LR, Soszynski D |date=September 1998 |title=Role of fever in disease |journal=Annals of the New York Academy of Sciences |volume=856 |issue=1 |pages=224–233 |bibcode=1998NYASA.856..224K |doi=10.1111/j.1749-6632.1998.tb08329.x |pmid=9917881 |s2cid=12408561|doi-access=free }}</ref> Studies have not been consistent on whether treating fever generally worsens or improves mortality risk.<ref name="SepticReview2017">{{Cite journal |last1=Drewry |first1=Anne M. |last2=Ablordeppey |first2=Enyo A. |last3=Murray |first3=Ellen T. |last4=Stoll |first4=Carolyn R. T. |last5=Izadi |first5=Sonya R. |last6=Dalton |first6=Catherine M. |last7=Hardi |first7=Angela C. |last8=Fowler |first8=Susan A. |last9=Fuller |first9=Brian M. |last10=Colditz |first10=Graham A. |year=2017 |title=Antipyretic Therapy in Critically Ill Septic Patients |journal=Critical Care Medicine |volume=45 |issue=5 |pages=806–813 |doi=10.1097/CCM.0000000000002285 |pmc=5389594 |pmid=28221185}}</ref> Benefits or harms may depend on the type of infection, health status of the patient and other factors.<ref name=kiek/>  Studies using [[warm-blooded]] [[vertebrates]] suggest that they recover more rapidly from infections or critical illness due to fever.<ref name="VUB">{{cite journal |vauthors=Su F, Nguyen ND, Wang Z, Cai Y, Rogiers P, Vincent JL |date=June 2005 |title=Fever control in septic shock: beneficial or harmful? |journal=Shock |volume=23 |issue=6 |pages=516–520 |pmid=15897803}}</ref> In [[sepsis]], fever is associated with reduced mortality.<ref>{{cite journal|display-authors=3 |last1=Rumbus |first1=Z |last2=Matics |first2=R |last3=Hegyi |first3=P |last4=Zsiboras |first4=C |last5=Szabo |first5=I |last6=Illes |first6=A |last7=Petervari |first7=E |last8=Balasko |first8=M |last9=Marta |first9=K |last10=Miko |first10=A |last11=Parniczky |first11=A |last12=Tenk |first12=J |last13=Rostas |first13=I |last14=Solymar |first14=M |last15=Garami |first15=A |title=Fever Is Associated with Reduced, Hypothermia with Increased Mortality in Septic Patients: A Meta-Analysis of Clinical Trials. |journal=PLOS ONE |date=2017 |volume=12 |issue=1 |pages=e0170152 |doi=10.1371/journal.pone.0170152 |pmid=28081244|pmc=5230786 |bibcode=2017PLoSO..1270152R |doi-access=free }}</ref>{{citation needed|date=December 2020}}

==Management==
Fever does not necessarily need to be treated,<ref>{{cite journal |vauthors=Ludwig J, McWhinnie H |date=May 2019 |title=Antipyretic drugs in patients with fever and infection: literature review |journal=Br J Nurs |volume=28 |issue=10 |pages=610–618 |doi=10.12968/bjon.2019.28.10.610 |pmid=31116598 |s2cid=162182092}}</ref> and most people with a fever recover without specific medical attention.<ref name=CDC_symptoms>{{cite web |url=https://www.cdc.gov/h1n1flu/sick.htm |publisher=[[Centers for Disease Control and Prevention]] |title=What To Do If You Get Sick: 2009 H1N1 and Seasonal Flu |date=2009-05-07 |access-date=2009-11-01 |url-status=live |archive-url=https://web.archive.org/web/20091103195142/http://www.cdc.gov/h1n1flu/sick.htm |archive-date=3 November 2009  }}</ref> Although it is unpleasant, fever rarely rises to a dangerous level even if untreated.<ref>{{Cite journal |last1=Klein |first1=Natalie C. |last2=Cunha |first2=Burke A. |title=Treatment of Fever |date=1996-03-01 |journal=Infectious Disease Clinics of North America |volume=10 |issue=1 |pages=211–216 |doi=10.1016/S0891-5520(05)70295-6 |pmid=8698992 |issn=0891-5520|doi-access=free }}</ref> Damage to the brain generally does not occur until temperatures reach {{convert|40.0|C}}, and it is rare for an untreated fever to exceed {{convert|40.6|C}}.<ref name=revben>{{cite journal |author=Edward James Walter |author2=Mike Carraretto| title=The neurological and cognitive consequences of hyperthermia  |date=2016 |journal=Critical Care | volume=20 | issue=1 | page=199 | doi=10.1186/s13054-016-1376-4 |pmid=27411704| pmc=4944502 |doi-access=free }}</ref> Treating fever in people with [[sepsis]] does not affect outcomes.<ref>{{cite journal | vauthors = Drewry AM, Ablordeppey EA, Murray ET, Stoll CR, Izadi SR, Dalton CM, Hardi AC, Fowler SA, Fuller BM, Colditz GA | title = Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis | journal = Critical Care Medicine | volume = 45 | issue = 5 | pages = 806–813 | date = May 2017 | pmid = 28221185 | pmc = 5389594 | doi = 10.1097/CCM.0000000000002285 }}</ref> Small trials have shown no benefit of treating fevers of {{Convert|38.5|C}} or higher of critically ill patients in ICUs, and one trial was terminated early because patients receiving aggressive fever treatment were dying more often.<ref name=":0" />

According to the NIH, the two assumptions which are generally used to argue in favor of treating fevers have not been experimentally validated. These are that (1) a fever is noxious, and (2) suppression of a fever will reduce its noxious effect. Most of the other studies supporting the association of fever with poorer outcomes have been observational in nature. In theory, these critically ill patients and those faced with additional physiologic stress may benefit from fever reduction, but the evidence on both sides of the argument appears to be mostly equivocal.<ref name=":0" />

===Conservative measures===
Limited evidence supports sponging or bathing feverish children with tepid water.<ref>{{cite journal | vauthors = Meremikwu M, Oyo-Ita A | title = Physical methods for treating fever in children | journal = The Cochrane Database of Systematic Reviews | issue = 2 | page = CD004264 | year = 2003 | volume = 2003 | pmid = 12804512 | doi = 10.1002/14651858.CD004264 | editor1-last = Meremikwu | editor1-first = Martin M | pmc = 6532675 }}</ref> The use of a [[mechanical fan|fan]] or air conditioning may somewhat reduce the temperature and increase comfort. If the temperature reaches the extremely high level of [[hyperpyrexia]], aggressive cooling is required (generally produced mechanically via [[conduction (heat)|conduction]] by applying numerous ice packs across most of the body or direct submersion in [[Ice bath|ice water]]).<ref name=EM01/> In general, people are advised to keep adequately hydrated.<ref>{{cite web|title=Fever|url=https://www.nlm.nih.gov/medlineplus/fever.html|work=National Institute of Health|url-status=live|archive-url=https://web.archive.org/web/20160430014050/https://www.nlm.nih.gov/medlineplus/fever.html|archive-date=30 April 2016}}</ref> Whether increased fluid intake improves symptoms or shortens respiratory illnesses such as the [[common cold]] is not known.<ref name="pmid21328268">{{cite journal | vauthors = Guppy MP, Mickan SM, Del Mar CB, Thorning S, Rack A | title = Advising patients to increase fluid intake for treating acute respiratory infections | journal = The Cochrane Database of Systematic Reviews | issue = 2 | page = CD004419 | date = February 2011 | volume = 2011 | pmid = 21328268 | doi = 10.1002/14651858.CD004419.pub3 | pmc = 7197045 }}</ref>

===Medications===
Medications that lower fevers are called ''[[antipyretic]]s''.<ref>{{Cite journal |last=El-Radhi |first=A. S. |date=2000-10-01 |title=Physical treatment of fever |url=https://adc.bmj.com/content/83/4/369.4 |journal=Archives of Disease in Childhood |volume=83 |issue=4 |pages=369c–369 |doi=10.1136/adc.83.4.369c |pmid=11032580 |pmc=1718494 |issn=0003-9888}}</ref> The antipyretic [[ibuprofen]] is effective in reducing fevers in children.<ref name=Per2004>{{cite journal | vauthors = Perrott DA, Piira T, Goodenough B, Champion GD | title = Efficacy and safety of acetaminophen vs ibuprofen for treating children's pain or fever: a meta-analysis | journal = Archives of Pediatrics & Adolescent Medicine | volume = 158 | issue = 6 | pages = 521–526 | date = June 2004 | pmid = 15184213 | doi = 10.1001/archpedi.158.6.521 | doi-access = free }}</ref> It is more effective than [[acetaminophen]] (paracetamol) in children.<ref name=Per2004/> Ibuprofen and acetaminophen may safely be used together in children with fevers.<ref name="pmid19454182">{{cite journal | vauthors = Hay AD, Redmond NM, Costelloe C, Montgomery AA, Fletcher M, Hollinghurst S, Peters TJ | title = Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial | journal = Health Technology Assessment | volume = 13 | issue = 27 | pages = iii–iv, ix–x, 1–163 | date = May 2009 | pmid = 19454182 | doi = 10.3310/hta13270 | doi-access = free | hdl = 10044/1/57595 | hdl-access = free }}</ref><ref name="pmid19606950">{{cite journal | vauthors = Southey ER, Soares-Weiser K, Kleijnen J | s2cid = 31653539 | title = Systematic review and meta-analysis of the clinical safety and tolerability of ibuprofen compared with paracetamol in paediatric pain and fever | journal = Current Medical Research and Opinion | volume = 25 | issue = 9 | pages = 2207–2222 | date = September 2009 | pmid = 19606950 | doi = 10.1185/03007990903116255 | url = https://figshare.com/articles/journal_contribution/11815293 }}</ref> The efficacy of acetaminophen by itself in children with fevers has been questioned.<ref name="pmid12076499">{{cite journal | vauthors = Meremikwu M, Oyo-Ita A | title = Paracetamol for treating fever in children | journal = The Cochrane Database of Systematic Reviews | issue = 2 | page = CD003676 | date = 2002 | volume = 2002 | pmid = 12076499 | doi = 10.1002/14651858.CD003676 | pmc = 6532671 }}</ref> Ibuprofen is also superior to [[aspirin]] in children with fevers.<ref name="pmid9049576">{{cite journal | vauthors = Autret E, Reboul-Marty J, Henry-Launois B, Laborde C, Courcier S, Goehrs JM, Languillat G, Launois R | s2cid = 27519225 | title = Evaluation of ibuprofen versus aspirin and paracetamol on efficacy and comfort in children with fever | journal = European Journal of Clinical Pharmacology | volume = 51 | issue = 5 | pages = 367–371 | date = 1997 | pmid = 9049576 | doi = 10.1007/s002280050215 }}</ref> Additionally, [[aspirin]] is not recommended in children and young adults (those under the age of 16 or 19 depending on the country) due to the risk of [[Reye's syndrome]].<ref>{{cite book |title=British National Formulary for Children |chapter=2.9 Antiplatelet drugs |year=2007 |page=151 |publisher=British Medical Association and Royal Pharmaceutical Society of Great Britain|title-link=British National Formulary for Children }}</ref>

Using both paracetamol and ibuprofen at the same time or alternating between the two is more effective at decreasing fever than using only paracetamol or ibuprofen.<ref name=Wong2013/> It is not clear if it increases child comfort.<ref name=Wong2013>{{cite journal | vauthors = Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, Johnson DW | title = Combined and alternating paracetamol and ibuprofen therapy for febrile children | journal = The Cochrane Database of Systematic Reviews | issue = 10 | page = CD009572 | date = October 2013 | volume = 2013 | pmid = 24174375 | doi = 10.1002/14651858.CD009572.pub2 | pmc = 6532735 }}</ref> Response or nonresponse to medications does not predict whether or not a child has a serious illness.<ref name="pmid23846358">{{cite journal | vauthors = King D | s2cid = 32438262 | title = Question 2: does a failure to respond to antipyretics predict serious illness in children with a fever? | journal = Archives of Disease in Childhood | volume = 98 | issue = 8 | pages = 644–646 | date = August 2013 | pmid = 23846358 | doi = 10.1136/archdischild-2013-304497 }}</ref>

With respect to the effect of antipyretics on the risk of death in those with infection, studies have found mixed results, as of 2019.<ref>{{cite journal | vauthors = Ludwig J, McWhinnie H | title = Antipyretic drugs in patients with fever and infection: literature review | journal = British Journal of Nursing | volume = 28 | issue = 10 | pages = 610–618 | date = May 2019 | pmid = 31116598 | doi = 10.12968/bjon.2019.28.10.610 | s2cid = 162182092 }}</ref>

==Epidemiology==
Fever is one of the most common [[medical signs]].<ref name=Peds2011/> It is part of about 30% of healthcare visits by children,<ref name=Peds2011/> and occurs in up to 75% of adults who are seriously sick.<ref name=Ki2013/> About 5% of people who go to an emergency room have a fever.<ref name=EMP2012>{{cite journal | vauthors = Nassisi D, Oishi ML | title = Evidence-based guidelines for evaluation and antimicrobial therapy for common emergency department infections | journal = Emergency Medicine Practice | volume = 14 | issue = 1 | pages = 1–28; quiz 28–29 | date = January 2012 | pmid = 22292348 }}</ref>

==History==
A number of types of fever were known as early as 460 BC to 370 BC when [[Hippocrates]] was practicing medicine including that due to [[malaria]] (tertian or every 2 days and quartan or every 3 days).<ref name=Sajadi2012>{{cite journal | vauthors = Sajadi MM, Bonabi R, Sajadi MR, Mackowiak PA | title = Akhawayni and the first fever curve | journal = Clinical Infectious Diseases | volume = 55 | issue = 7 | pages = 976–980 | date = October 2012 | pmid = 22820543 | doi = 10.1093/cid/cis596 | doi-access = free }}</ref> It also became clear around this time that fever was a symptom of disease rather than a disease in and of itself.<ref name=Sajadi2012/>

Infections presenting with fever were a major source of mortality in humans for about 200,000 years. Until the late nineteenth century, approximately half of all humans died from infections before the age of fifteen.<ref>{{cite journal|doi=10.1146/annurev-pathol-031920-101429|title=Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories|year=2021|last1=Casanova|first1=Jean-Laurent|last2=Abel|first2=Laurent|journal=Annual Review of Pathology: Mechanisms of Disease|volume=16|pages=23–50|pmid=32289233|pmc=7923385|doi-access=free}}</ref>

An older term, [[:wikt:febricula|febricula]] (a [[diminutive]] form of the [[Latin language|Latin]] word for fever), was once used to refer to a low-grade fever lasting only a few days. This term fell out of use in the early 20th century, and the symptoms it referred to are now thought to have been caused mainly by various minor [[Virus|viral]] [[respiratory infection]]s.<ref>{{cite journal |journal=[[Bulletin of the New York Academy of Medicine]] |volume=46 |issue=9 |date=September 1970 |orig-date=first presented at a conference on 27 May 1970 |first=Bernard |last=Straus |title=Defunct and Dying Diseases |pages=686–706 |pmid=4916301 |pmc=1749762 }}</ref>

==Society and culture==
===Mythology===
[[File:Virgil Solis Febris.jpg|thumb|Febris]] 
*[[Febris]] (''fever'' in [[Latin]]) is the goddess of fever  in [[Roman mythology]]. People with fevers would visit her temples. 
*Tertiana and Quartana are the goddesses of tertian and quartan fevers of malaria in Roman mythology.<ref>{{Citation |last=Scheid |first=John |title=Febris |date=2015-12-22 |url=https://oxfordre.com/classics/view/10.1093/acrefore/9780199381135.001.0001/acrefore-9780199381135-e-2651 |encyclopedia=Oxford Research Encyclopedia of Classics |publisher=Oxford University Press |doi=10.1093/acrefore/9780199381135.013.2651 |isbn=978-0-19-938113-5 |access-date=2023-01-23|url-access=subscription }}</ref>
*[[Jvarasura]] (''fever-demon'' in [[Hindi]]) is the personification of fever and disease in [[Hindu mythology|Hindu]] and [[Buddhist mythology]].

===Pediatrics===
Fever is often viewed with greater concern by parents and healthcare professionals than might be deserved, a phenomenon known as fever phobia,<ref name=Peds2011/><ref name = Crocetti2001>{{cite journal | vauthors = Crocetti M, Moghbeli N, Serwint J | title = Fever Phobia Revisited: Have Parental Misconceptions About Fever Changed in 20 Years? | journal = Pediatrics | volume = 107 | issue = 6 | pages = 1241–1246 | date = June 2001 | pmid = 11389237 | doi = 10.1542/peds.107.6.1241 | url = https://pediatrics.aappublications.org/content/107/6/1241 | access-date = 31 March 2020 | url-access = subscription }}</ref> which is based in both caregiver's and parents' misconceptions about fever in children. Among them, many parents incorrectly believe that fever is a [[disease]] rather than a [[medical sign]], that even low fevers are harmful, and that any temperature even briefly or slightly above the oversimplified "normal" number marked on a thermometer is a clinically significant fever.<ref name = Crocetti2001/> They are also afraid of harmless side effects like [[febrile seizure]]s and dramatically overestimate the likelihood of permanent damage from typical fevers.<ref name = Crocetti2001/> The underlying problem, according to professor of pediatrics Barton D. Schmitt, is that "as parents we tend to suspect that our children's brains may melt."<ref>{{cite news |title=Lifting a Veil of Fear to See a Few Benefits of Fever |author=Klass, Perri |newspaper=The New York Times |date=10 January 2011 |url=https://www.nytimes.com/2011/01/11/health/11klass.html |url-status=live |archive-url=https://web.archive.org/web/20150929041558/http://www.nytimes.com/2011/01/11/health/11klass.html |archive-date=29 September 2015  }}</ref> As a result of these misconceptions parents are anxious, give the child fever-reducing medicine when the temperature is technically normal or only slightly elevated, and interfere with the child's sleep to give the child more medicine.<ref name = Crocetti2001/>

== Other animals ==
{{main|Thermoregulation}}
Fever is an important metric for the [[medical diagnosis|diagnosis]] of [[livestock disease|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 {{val|101|u=°F}} ({{val|38.3|u=°C}}).<ref>{{cite web|url=http://www.equusite.com/articles/health/healthVitalSigns.shtml|title=Equusite Vital Signs|publisher=equusite.com|access-date=2010-03-22|url-status=dead|archive-url=https://web.archive.org/web/20100326053227/http://www.equusite.com/articles/health/healthVitalSigns.shtml|archive-date=26 March 2010}}</ref> In species that allow the body to have a wide range of "normal" temperatures, such as [[camel]]s,<ref>{{cite journal | vauthors = Schmidt-Nielsen K, Schmidt-Nielsen B, Jarnum SA, Houpt TR | title = Body temperature of the camel and its relation to water economy | journal = The American Journal of Physiology | volume = 188 | issue = 1 | pages = 103–112 | date = January 1957 | pmid = 13402948 | doi = 10.1152/ajplegacy.1956.188.1.103 | df = dmy-all }}</ref> whose body temperature varies as the environmental temperature varies,<ref>{{cite journal |last1=Leese |first1=A.S. |title='Tips' on camels, for veterinary surgeons on active service |journal=The British Veterinary Journal |date=March 1917 |volume=73 |page=81 |url=https://books.google.com/books?id=XcYfAQAAIAAJ&pg=PA81 |via=[[Google Books]] |name-list-style=vanc}}</ref> the body temperature which constitutes a febrile state differs depending on the environmental temperature.<ref>{{cite journal |last1=Tefera |first1=M. |title=Observations on the clinical examination of the camel (Camelus dromedarius) in the field |journal=Tropical Animal Health and Production |date=July 2004 |volume=36 |issue=5 |pages=435–449 |doi=10.1023/b:trop.0000035006.37928.cf |pmid=15449833 |s2cid=26358556 |name-list-style=vanc}}</ref> Fever can also be behaviorally induced by invertebrates that do not have immune-system based fever. For instance, some species of grasshopper will thermoregulate to achieve body temperatures that are 2–5&nbsp;°C higher than normal in order to inhibit the growth of fungal pathogens such as ''[[Beauveria bassiana]]'' and ''[[Metarhizium acridum]]''.<ref name="Thomas2003">{{cite journal|vauthors = Thomas MB, Blanford S|title=Thermal biology in insect-parasite interactions|journal=Trends in Ecology & Evolution|date=July 2003|volume=18|issue=7|pages=344–350|doi=10.1016/S0169-5347(03)00069-7}}</ref> Honeybee colonies are also able to induce a fever in response to a fungal parasite ''Ascosphaera apis''.<ref name="Thomas2003" />

== References ==
{{Reflist}}

== Further reading ==
* {{cite book |vauthors=Rhoades R, Pflanzer RG | year = 1996 | title = Human Physiology | edition = 3rd | chapter = Chapter 27: Regulation of Body Temperature (Clinical Focus: Pathogenesis of Fever) | pages = <!--820--> | isbn = 9780030051593 | location = Philadelphia | publisher = Saunders College | url = https://archive.org/details/humanphysiology00rhoa | url-access = registration | access-date = 2 April 2020 }}

== External links ==
{{Medical resources
| ICD10          = {{ICD10|R|50||r|50}}
| ICD9           = {{ICD9|780.6}}
| ICDO           =
| OMIM           =
| MedlinePlus    = 003090
| eMedicineSubj  = med
| eMedicineTopic = 785
| DiseasesDB     = 18924
| MeshID         = D005334
}}
{{Commons category}}
* [http://kidshealth.org/parent/general/body/fever.html Fever and Taking Your Child's Temperature]
* [https://www.nlm.nih.gov/medlineplus/ency/article/003090.htm US National Institute of Health factsheet]
* [http://www.drugcite.com/indi/?i=PYREXIA Drugs most commonly associated with the adverse event Pyrexia (Fever) as reported the FDA] {{Webarchive|url=https://web.archive.org/web/20120309114919/http://www.drugcite.com/indi/?i=PYREXIA |date=9 March 2012 }}
* [https://medlineplus.gov/fever.html Fever] at MedlinePlus
* [https://www.nytimes.com/2021/01/11/well/live/fever-benefits.html Why are We So Afraid of Fevers?] at ''The New York Times''

{{General symptoms and signs}}
{{Authority control}}

[[Category:Fever| ]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia emergency medicine articles ready to translate]]
[[Category:Symptoms and signs]]
[[Category:Thermoregulation]]