Fever

Fever, also known as pyrexia and febrile response, is defined as having a above the  due to an increase in the body's temperature. There is not a single agreed-upon upper limit for normal temperature with sources using values between 37.5 and 38.3 C. The increase in set point triggers increased s and causes a feeling of. This results in greater heat production and efforts to conserve heat. When the set point temperature returns to normal, a person feels hot, becomes, and may begin to. Rarely a fever may trigger a. This is more common in young children. Fevers do not typically go higher than 41 to 42 C.

A fever can be caused by many ranging from non serious to life-threatening. This includes, and  such as the , , ,  and  among others. Non-infectious causes include, , side effects of medication, and among others. It differs from, in that hyperthermia is an increase in body temperature over the temperature set point, due to either too much heat production or not enough.

Treatment to reduce fever is generally not required. Treatment of associated pain and inflammation, however, may be useful and help a person rest. Medications such as or  (acetaminophen) may help with this as well as lower temperature. Measures such as putting a cool damp cloth on the forehead and having a slightly warm bath are not useful and may simply make a person more uncomfortable. Children younger than three months require medical attention, as might people with serious medical problems such as a or people with other symptoms. does require treatment.

Fever is one of the most common. It is part of about 30% of healthcare visits by children and occurs in up to 75% of adults who are seriously sick. While fever is a useful defense mechanism, treating fever does not appear to worsen outcomes. Fever is viewed with greater concern by parents and healthcare professionals than it usually deserves, a phenomenon known as.

Signs and symptoms
A fever is usually accompanied by, which consists of , , , , , and the inability to concentrate.

Diagnosis
A wide range for has been found. Central temperatures, such as rectal temperatures, are more accurate than peripheral temperatures. Fever is generally agreed to be present if the elevated temperature is caused by a raised set point and:
 * Temperature in the (rectum/rectal) is at or over 37.5 –
 * Temperature in the mouth (oral) is at or over 37.7 C
 * Temperature under the arm (axillary) or in the (tympanic) is at or over 37.2 C

In healthy adults, the for oral temperature is 33.2 –, for rectal it is 34.4 –, for  (the ear drum) it is 35.4 –, and for axillary (the armpit) it is 35.5 –. defines a fever as a morning oral temperature of >37.2 °C (>98.9 °F) or an afternoon oral temperature of >37.7 °C (>99.9 °F) while the normal daily temperature variation is typically 0.5 °C (0.9 °F).

Normal body temperatures vary depending on many factors, including age, sex, time of day, ambient temperature, activity level, and more. A raised temperature is not always a fever. For example, the temperature of a healthy person rises when he or she exercises, but this is not considered a fever, as the set point is normal. On the other hand, a "normal" temperature may be a fever, if it is unusually high for that person. For example, elderly people have a decreased ability to generate body heat, so a "normal" temperature of 37.3 C may represent a clinically significant fever.

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


 * Temperature remains above normal throughout the day and does not fluctuate more than $1 °C$ in 24 hours, e.g., , , , or . may show a specific fever pattern (Wunderlich curve of typhoid fever), with a slow stepwise increase and a high plateau.  (Drops due to fever-reducing drugs are excluded.)
 * The temperature elevation is present only for a certain period, later cycling back to normal, e.g., , , or . Following are its types:
 * Quotidian fever, with a periodicity of 24 hours, typical of 
 * Tertian fever (48-hour periodicity), typical of later in the course of ', ', or  malaria
 * Quartan fever (72-hour periodicity), typical of later in the course of  malaria.
 * Temperature remains above normal throughout the day and fluctuates more than $1 °C$ in 24 hours, e.g.,,.
 * A specific kind of fever associated with, 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.

A, also called , is a fever in the absence of normal immune system function. Because of the lack of infection-fighting s, a bacterial infection can spread rapidly; this fever is, therefore, usually considered to require urgent medical attention. This kind of fever is more commonly seen in people receiving immune-suppressing than in apparently healthy people.

Febricula is an old term for a low-grade fever, especially if the cause is unknown, no other symptoms are present, and the patient recovers fully in less than a week.

Hyperpyrexia
Hyperpyrexia is an extreme elevation of which, depending upon the source, is classified as a  greater than or equal to 40.0 or. Such a high temperature is considered a, as it may indicate a serious underlying condition or lead to problems including permanent , or death. The most common cause of hyperpyrexia is an. Other possible causes include, , , , , and.

Infections are the most common cause of fevers, but as the temperature rises other causes become more common. Infections commonly associated with hyperpyrexia include, and  infections. Immediate aggressive cooling to less than 38.9 C has been found to improve survival. Hyperpyrexia differs from 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  due to an outside source.

Hyperthermia
is an example of a high temperature that is not a fever. It occurs from a number of causes including, , , stimulants such as s and , s, and.

Differential diagnosis
Fever is a common of many medical conditions:
 * , e.g.,, primary infection, , , , , ,
 * Various skin s, e.g., ,
 * diseases, e.g.,, , s, , , , , ,
 * Tissue destruction, which can occur in, , , , , , etc.
 * Reaction to incompatible blood products
 * s, most commonly and  and s
 * s: ,
 * Inherited metabolic disorder:

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

is not a cause.

Pathophysiology
Temperature is ultimately regulated in the. A trigger of the fever, called a pyrogen, causes release of (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.

In many respects, the hypothalamus works like a. When the set point is raised, the body increases its temperature through both active generation of heat and retention of heat. Peripheral both reduces heat loss through the skin and causes the person to feel cold. increases in, and muscle contraction through shivering raises the. If these measures are insufficient to make the blood temperature in the brain match the new set point in the hypothalamus, then begins in order to use muscle movements to produce more heat. When the hypothalamic set point moves back to baseline either spontaneously or with medication, 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, 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 or an adverse reaction to drugs. Fever can be differentiated from hyperthermia by the circumstances surrounding it and its response to medications.

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

Endogenous
In essence, all endogenous pyrogens are, molecules that are a part of the. They are produced by activated and cause the increase in the thermoregulatory set point in the hypothalamus. Major endogenous pyrogens are (α and β) and  (IL-6). Minor endogenous pyrogens include, , -α and macrophage inflammatory protein-β as well as , , and. also acts as a pyrogen. It is mediated by (IL-1) release.

These cytokine factors are released into general circulation, where they migrate to the s of the due to easier absorption caused by the 's reduced filtration action there. The cytokine factors then bind with s on vessel walls, or interact with local s. When these cytokine factors bind, the is then activated.

Exogenous
One model for the mechanism of fever caused by exogenous pyrogens includes, which is a cell wall component of. An immunological protein called (LBP) binds to LPS. The LBP–LPS complex then binds to the receptor of a nearby. This binding results in the synthesis and release of various endogenous 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. The highly toxic -boosting supplement induces  via the inhibition of  production by, resulting in impairment of. Instead of producing ATP, the energy of the is lost as heat.

PGE2 release
PGE2 release comes from the pathway. This pathway (as it relates to fever), is mediated by the s (PLA2),  (COX-2), and. 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 (POA) through the  (EP3). EP3-expressing neurons in the POA innervate the (DMH), the rostral  pallidus nucleus in the  (rRPa), and the  (PVN) of the. Fever signals sent to the DMH and rRPa lead to stimulation of the 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 and various.

Hypothalamus
The brain ultimately orchestrates heat effector mechanisms via the or primary motor center for shivering. These may be: In infants, the autonomic nervous system may also activate to produce heat (non-exercise-associated, also known as non-shivering thermogenesis). Increased heart rate and vasoconstriction contribute to increased in fever.
 * Increased heat production by increased, and hormones like  (adrenaline)
 * Prevention of heat loss, such as.

Usefulness
There are arguments for and against the usefulness of fever, and the issue is controversial. There are studies using  with some suggesting that they recover more rapidly from infections or critical illness due to fever. Studies suggest reduced mortality in bacterial infections when fever was present.

In theory, fever can aid in host defense. There are certainly some important immunological reactions that are sped up by temperature, and some s with strict temperature preferences could be hindered.

Research has demonstrated that fever assists the healing process in several important ways:
 * Increased mobility of
 * Enhanced leukocyte
 * effects decreased
 * Increased of

Management
Fever should not necessarily be treated. Most people recover without specific medical attention. Although it is unpleasant, fever rarely rises to a dangerous level even if untreated. Damage to the brain generally does not occur until temperatures reach 42 °C (107.6 °F), and it is rare for an untreated fever to exceed 40.6 °C (105 °F). Treating fever in people with does not affect outcomes.

Conservative measures
Some limited evidence supports sponging or bathing feverish children with tepid water. The use of a or air conditioning may somewhat reduce the temperature and increase comfort. If the temperature reaches the extremely high level of, aggressive cooling is required (generally produced mechanically via by applying numerous ice packs across most of the body or direct submersion in ice water). In general, people are advised to keep adequately hydrated. Whether increased fluid intake improves symptoms or shortens respiratory illnesses such as the is not known.

Medications
Medications that lower fevers are called s. The antipyretic is effective in reducing fevers in children. It is more effective than (paracetamol) in children. Ibuprofen and acetaminophen may be safely used together in children with fevers. The efficacy of acetaminophen by itself in children with fevers has been questioned. Ibuprofen is also superior to in children with fevers. Additionally, 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.

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. It is not clear if it increases child comfort. Response or nonresponse to medications does not predict whether or not a child has a serious illness.

Epidemiology
About 5% of people who go to an emergency room have a fever.

History
A number of types of fever were known as early as 460 BC to 370 BC when was practicing medicine including that due to  (tertian or every 2 days and quartan or every 3 days). It also became clear around this time that fever was a symptom of disease rather than a disease in and of itself.

Etymology
Pyrexia is from the Greek pyr meaning fire. Febrile is from the word , meaning fever, and archaically known as ague.

Fever phobia
Fever phobia is the name given by medical experts to parents' misconceptions about fever in their children. Among them, many parents incorrectly believe that fever is a rather than a, 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. They are also afraid of harmless side effects like s and dramatically overestimate the likelihood of permanent damage from typical fevers. The underlying problem, according to professor of pediatrics Barton D. Schmitt, is "as parents we tend to suspect that our children’s brains may melt."

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.

Other animals
Fever is an important feature for the of. The body temperature of animals, which is taken rectally, is different from one species to another. For example, a is said to have a fever above $101 °F$ ($38.3 °C$). In species that allow the body to have a wide range of "normal" temperatures, such as s, it is sometimes difficult to determine a febrile stage.

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 °C higher than normal in order to inhibit the growth of fungal pathogens such as ' and '. Honeybee colonies are also able to induce a fever in response to a fungal parasite Ascosphaera apis.