Fever R50.9

The first description of a febrile seizure goes back as far as Hippocrates: "Seizures occur in children when an acute fever sets in; these seizures occur mostly in children who are very young up to 7 years of age. Older children and adults are not equally affected by seizures and fever unless preceded by a bad event." (Kurlemann 2021).

The mean normal temperature of 37 degrees C was first established in the 19th century by Carl Wunderlich, a physician from Leipzig. He had the axillary temperature measured several times in 25,000 patients and illustrated this in a so-called "fever curve" (Torossian 2019).

A fever is an increase in body temperature that exceeds the normal level of diurnal variation and leads to an increase in the hypothetical set point (Kasper 2015). Fever is only a symptom of a disease and possibly influences the body's defense mechanisms favorably (Weihrauch 2022).

One speaks of subfebrile temperatures at < 38 degrees C auricular or rectal and febrile at > 38 degrees C auricular or rectal (Herold 2022). The orally measured temperature is usually about 0.5 degrees C lower (Schlosser 2022).

In people > 60 - 65 years, the normal body temperature is lowered overall. Here one speaks already of fever with

- oral temperature measured once of > 37.8 degrees C

- orally measured temperature of ≥ 37.2 degrees C measured several times

- rectally measured temperature of ≥ 37.5 degrees C

- An increase of 1.1 degrees C above the individual's baseline temperature (Runge 2018).

Fever can be acute, chronic, and recurrent (Runge 2018). A fever lasting more than 1 - 2 weeks always requires clarification (Battegay 2013).

One differentiates between different types of fever:

• Continua: In this case, there may be daily fluctuations of up to 1 degree C (Herold 2022). This is found preferably in bacterial infections such as typhoid abdominalis, pneumonia, erysipelas, etc. (Runge 2018).
• Remitting fever: The diurnal variation in this case is 1 - 2 degrees C (Herold 2022). However, the temperature does not return to the initial level. This form of fever is predominantly found in infections (Runge 2018).
• Intermittent fever: In this case, there are strong daily fluctuations of > 2 degrees C (Herold 2022). Intermittent fever is often found in e.g. neoplasms and sepsis (Runge 2018).
• Two-tailed: Two-tailed fever, also known as febris recurrens, is characterized by fever-free intervals of varying lengths (Runge 2018). It may result from complications of bacterial or viral infections (Herold 2022).
• Undulating: This refers to irregular phases of rising and falling temperatures interrupted by afebrile phases. Typically, this type of fever is found in brucellosis and Hodgkin's disease (Runge 2018).
• Ephemera: Also called one-day fever. It can occur, for example, after blood transfusions, i. v. administration of certain drugs, and in mild respiratory infections (Runge 2018).
• Fever in malaria disease: In this case, there are attack-like episodes of fever caused by the periodic release of the pathogens into the blood. Depending on the plasmodia species, different courses of fever occur (Runge 2018): malaria quartana 2 fever-free days, malaria tertiana 1 fever-free day, malaria tropica or irregular fever in mixed forms (Herold 2022).
• Septic fever: Septic fever is when there are high body temperatures with or without chills (Herold 2022).

Fever is one of the common symptoms during illness (Schlosser 2022).

Triggers of fever can be various diseases such as:

- Infections (> 50 %) such as infectious diseases, tuberculosis, bacterial endocarditis, pyelonephritis (Herold 2022)

- Autoimmune diseases (approx. 15 %) such as vasculitides and collagenoses (Herold 2022)

- Malignancies (approx. 7 %) such as renal cell carcinoma, Hodgkin's/ non- Hodgkin's lymphomas, tumors of the gastrointestinal tract (Herold 2022)

- Drug Reaction with Eosinophilia and Systemic Symptom(DRESS):

This is a fever triggered by drugs. Drug fever can be caused by allopurinol and antiepileptic drugs. In this case, the fever occurs about 3 - 4 weeks after the start of medication (Herold 2022).

DRESS can be triggered by carbamazepine and phenytoin in particular. After onset of DRESS, reactivation of viral infections may occur several weeks later (Herold 2022).

- Postinfarction fever:

Before the time of coronary intervention, postinfarction fever occurred in 25-50% of patients. It remains unclear whether infarct size correlates with the level of body temperature. According to a 2007 study by Naito et al, a temperature elevation of ≥ 38 degrees C poses an increased risk of, for example, aneurysm formation, decreased left ventricular pump function, and re-hospitalization due to heart failure (Smid 2018).

- Postoperative fever:

Post-aggregation metabolism may cause an increase in temperature postoperatively. Normally, normalization occurs on day 2-3. If there are temperature increases over this period, especially if accompanied by leukocytosis, a workup should be performed immediately (Schumpelik 2010), as the fever may then be caused by wound infections, nosocomial pneumonias, urinary tract infections (through bladder catheters), deep vein thrombosis, or thromboembolism (Herold 2022).

- Other causes such as hyperthyroidism, etc.

- Fever of unclear et iology (Herold 2022):

Fever of unknown origin (FUO) is defined as multiple temperatures of ≥ 38.2 degrees C that persist for 2 to 3 weeks, the cause of which cannot be determined despite one week of intensive investigation according to Petersdorf and Beeson (1961). In the meantime, a revised version speaks of:

- Nosocomial FUO:

The causes of classic fever of unknown origin (FUO) are approximately:

- 25 % by infections

- 10 - 15 % by malignancies

- 40 % by autoimmunopathies, collagenoses or others

- 20 - 25 % ultimately remain unexplained (Weihrauch 2022)

In hospitalized patients, infected intravascular catheters, urinary tract infections, pneumonia, sinusitis, pulmonary embolism, deep vein thrombosis, or reactivation of a herpes simplex infection or cytomegalovirus infection can be particularly common (Herold 2022).

- FUO in neutropenic patients:

In this case, during or after cytostatic therapy, the number of neutrophil granulocytes is between 500 - 1,000 / µl. This is found in up to 75% of patients. In about 50 % the cause remains unclear. Even in these unexplained cases, one should suspect an infection. Most commonly, germs such as staphylococci, streptococci, gram-negative bacteria or fungi are the trigger (Herold 2022).

- FUO without neutropenia:

This is often found in abscesses, endocarditis , HIV- infection, opportunistic infections, and tuberculosis (Herold 2022).

- HIV-associated FUO:

Once CD4- lymphocytes are < 200 / µl, opportunistic infections may occur such as mycobacteria, P. jirovecii, etc (Herold 2022).

The hypothalamus controls body temperature. Neurons in the preoptic anterior and posterior hypothalamus receive signals for temperature control from:

- Peripheral nerves (these transmit information from the cold and heat receptors of the skin).

- Blood circulating around the region (Kasper 2015).

Exogenous pyrogens and pyrogenic cytokines can lead to a change in the set point (Smid 2018).

- Exogenous pyrogens:

These are derived from microbacterial toxins such as Gram-positive and Gram-negative bacteria as well as viruses, etc.

- Pyrogenic cytokines (obsolete term: endogenous pyrogens):

These are produced in the body during inflammatory processes (Smid 2018).

They include, for example, IL- 1, IL- 6, tumor necrosis factor (TNF), interferons (especially interferon alpha)

(Kasper 2015)

Cytokines lead to an elevation of the hypothetical set point in the hypothalamus. This activates neurons in the vasomotor center and leads to a reduction in heat loss through the skin via vasoconstriction in the extremities. Shivering may occur at this stage to thereby increase heat production by the muscles. The liver also contributes to heat production, as does putting on warmer clothing, hot water bottle, etc. when shivering. The processes of heat production and heat maintenance continue until the blood flowing through the neurons of the hypothalamus is at the temperature of the new thermostat setting. Once this temperature is reached, the hypothalamus maintains the designated temperature.

As soon as the hypothalamic set point is corrected downward again, e.g., by taking antipyretic drugs or by reducing the pyrogen concentration, vasodilatation and sweating occur in order to adjust the temperature to the new set point. (Kasper 2015).

Normal oral body temperature is established in early childhood. In old age, the ability to develop fever is (greatly) reduced, so that even in the case of severe infections, only low fever can occur (Kasper 2015),

Leading clinical symptoms when fever occurs may include:

- Respiratory symptoms such as cough, dyspnea, sputum, etc.

- Abdominal symptoms such as diarrhea, pain, etc.

- Genitourinary syndromes such as flank pain, pollakiuria, dysuria, etc.

- Encephalitic or meningitic symptoms such as meningismus, headache, etc. (Herold 2022).

The symptom fever may present with additional symptoms that may provide diagnostic clues such as with:

- Skin symptoms

- lymphadenopathy

- joint pain

- neurological symptoms

- hepatomegaly

- splenomegaly (Runge 2018)

The chronology of events preceding the fever is important from an anamnestic point of view, as is contact with possibly infected persons (Kasper 2015), travel abroad, contact with animals, ingestion of medication, etc. (Herold 2022).

Monitoring of body temperature should always be done in the same place e.g. always in the mouth, eardrum, rectum (Kasper 2015).

It should be noted that only an attenuated febrile response is possible in the following patients:

- neonates

- Elderly people (in 20-30%, even in severe infections, fever reactions are only diminished or not detectable at all [Battegay 2013]).

- patients with chronic liver or kidney failure

- after taking

- glucocorticoids

- Anticytokines [Kasper 2015].

In addition, leading symptoms should be inquired about such as cough, dyspnea, sputum, dysuria, pollakiuria, pain, nausea, diarrhea, pain in bones or joints, headache, etc. (Herold 2022).

Since the Duke criteria (see d.) have a high specificity for endocarditis, they should also be applied (Mourad 2003).

X-ray thorax

This may reveal evidence of:

- infiltrates

- effusion

- space occupation

- enlarged lymph nodes (Runge 2018)

Abdominal sonography

Indications of:

- liver abscess

- cholecystitis

- pancreatitis

- space-occupying lesion

- urinary retention

- Determination of spleen size (Runge 2018)

ECG

To detect cardiac abnormalities (Runge 2018).

If there is evidence of involvement of other organ systems, investigations in this regard should be performed (Runge 2018)

- Differential blood count

Leukocytosis is typical for bacterial infections, leukopenia for viral infections, brucellosis, typhoid fever, after cytostatic or immunosuppressive therapy and after increased peripheral consumption of granulocytes (Herold 2022).

- C- reactive protein

- Erythrocyte sedimentation rate (Kasper 2015).

- Transaminases

If transaminases are elevated, hepatitis serology should be considered (Runge 2018).

- Bilirubin

- Creatinine

- Urea

- Electrolytes

- Lactate dehydrogenase (LDH)

- ESR

- Urinalysis

- Blood cultures

- Lumbar puncture for evidence of inflammatory changes in the CNS (Runge 2018).

- Rheumatism serology

- TSH basal (Herold 2022)

• Norm variants of the body temperature:

This is a physiological increase in temperature. It generally reaches maximum values up to 37.9 degrees C (Battegay 2013).

Norm variants can occur in e.g.:

- Women in the 2nd half of the cycle

- after an opulent meal

- after physical exertion (Battegay 2013).

• Hyperthermia:

In hyperthermia, an increase in body temperature is found, but there is no increase in the set point (Smid 2018). This is an uncontrolled increase in body temperature where the body's ability to release heat has been exceeded (Runge 2018).

Hyperthermia can be exogenously caused by e.g. sunbathing (Kasper 2015), heating pad, sauna, hot tub bath or endogenously caused by e.g. strong muscle work. At the same time, body heat dissipation is disturbed by e.g. high air temperatures with high humidity, inappropriate clothing, etc. (Battegay 2013).

The core body temperature can reach values > 40 degrees C, in addition, neurological symptoms usually occur (Smid 2018). The skin is typically hot but dry over the entire body. Hyperthermia does not respond to antipyretic drugs and can rapidly lead to death (Kasper 2015).

• Malignant hyperthermia:

This is a rare hereditary disorder with autosomal dominant inheritance. It leads to hyperthermia during anesthesia, especially when halothane and succinylcholine are administered (Battegay 2013).

• Hyperpyrexia:

Hyperpyrexia refers to temperatures of > 41.5 degrees C. It may be caused, for example, by severe infections. However, it most commonly occurs in the setting of CNS hemorrhage (Kasper 2015).

• Hypothalamic fever:

This term is used to describe the rise in body temperature due to hypothalamic dysfunction caused by, for example, tumor, hemorrhage, local trauma, or intrinsic dysfunction (Kasper 2015).

• Dehydration:

Fluid requirements increase by 0.5 - 1.0 l / 24 h for every 1 degree C (Herold 2022).

• Increased oxygen demand:

Oxygen demand also increases with the onset of fever; a 1 degree C increase in temperature increases oxygen demand by 12 - 13% (Schumpelik 2010).

• Febrile seizure

Febrile convulsion (FC) is an age-dependent response of the immature CNS to an increase in body temperature. Genetic reasons also play a role. Febrile convulsions occur in 2 - 5% of children between 6 months and 6 years of age (with a peak around 2 years of age). They are among the most common provoked epileptic seizures. It is important to differentiate benign FC from an epilepsy syndrome (Kurlemann 2021).

There are no adequately supported studies that the prophylactic use of antipyretics can prevent a febrile seizure (Marek 2021).

Causal therapy depends primarily on the cause of the fever (Runge 2018).

Routine lowering is not indicated, especially in cases of unclear fever. However, there are situations in which lowering body temperature may be of vital importance, such as:

- malignant hyperthermia

- heat stroke

- grand mal epilepsy

- other diseases of the CNS

- elderly patients

- patients with pre-existing:

- heart failure

- coronary heart disease

- pregnancy

In this group of patients, fever reduction has not been shown to have a detrimental effect on infection resistance (Frankincense 2022).

• Symptomatic Therapy:

In all patients with fever, symptomatic measures should be taken in the form of:

- adequate fluid substitution (Runge 2018). Fluid requirements increase by 0.5 - 1.0 l / 24 h for every 1 degree C (Herold 2022).

- Removal of warming blankets and excessive clothing (Weihrauch 2022).

- Antipyretics if necessary

Inhibitors of cyclooxygenase such as paracetamol, ibuprofen or acetylsalicylic acid are particularly suitable in this case

- Non-essential drugs should be discontinued immediately because of the possibility of drug fever (Herold 2022).

- Calf Wrap:

These are always indicated if there is a contraindication to antipyretics. In all other patients with elevation of the temperature set point, it has been shown that calf wraps - as long as the temperature set point is still elevated - are not very effective, actually increase peripheral vasoconstriction and shivering, and are usually subjectively perceived as unpleasant. In studies, the combination of calf wraps and antipyretics was not shown to be superior to antipyretic administration alone (Weihrauch 2022).

Only in cases of hyperthermia without an increase in the temperature set point are calf wraps still indicated (Weihrauch 2022).

• Fever in viral diseases:

The majority of febrile illnesses occur in the context of self-limited infections (especially viral infections). The use of antipyretic drugs in this case is neither harmful nor does it delay healing (Kasper 2015).

• Fever in bacterial diseases:

Withholding antipyretic medications in bacterial diseases can be helpful in evaluating antibiotic efficacy, especially in the absence of positive cultures (Kasper 2015).

• Fever in autoimmune or autoinflammatory diseases:

In this case, fever can be reduced by anticytokines, although fever in autoinflammatory diseases is triggered by interleukin- 1beta (Kasper 2015).

• Postinfarction fever:

According to Herlitz (2008), early administration of a beta-blocker can prevent a rise in fever. The need for symptomatic therapy using antipyretics has not been systematically investigated in studies to date (Smid 2018).

• Febrile seizure:

Rectal diazepam is available for therapy (Kurlemann 2021).

• Fever of unknown origin (FUO):
  • FUO in neutropenic patients: Treatment with a broad-spectrum antibiotic i. v. should be started as soon as possible, as the chances of success are higher the earlier therapy is started (Herold 2022).
  • FUO without neutropenia: Unless patients show threatening symptoms, they should initially be observed for 2 - 3 days. During this period, fever can be objectified. If fever persists after this time, a detailed diagnosis should be initiated (Herold 2022).

The prognosis depends on the cause of the fever.

In fever of unclear et iology, several studies indicate a good course with spontaneous recovery between 51 - 100 % (Mourad 2003).

Measurements with an ear thermometer are meaningful, but they can be more variable than oral or rectal measurements (Kasper 2015).

If serological testing for antibodies is negative at the onset of the disease, under immunosuppression, or immunodeficiency, this does not exclude the respective disease (Herold 2022).

There are no sufficiently proven studies that the prophylactic use of antipyretics can prevent a febrile convulsion (Marek 2021).

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