1. 1
    Current Diagnosis
    • Fever is one of the most common clinical presentations encountered in primary care.
    • Numerous endogenous and exogenous factors play a role in determining body temperature. Current standards define fever as an oral temperature of ≥ 100.4 °F (≥ 38 °C).
    • Though temperature varies with measurement technique, in clinical practice, most recommendations refer to oral, rectal, and axillary temperature measurements, with rectal temperature being the standard of care in infants and young children.
    • With improvement in modern techniques, tympanic thermometers are commonly used due to parental convenience and ease of use along with improved accuracy. They should not be used in young children.
    • Fever is not an illness. It is the body’s physiologic response to a disease process and has beneficial effects in fighting infection.
    • All neonates with a fever should be admitted to the hospital for a full sepsis evaluation. For infants between 1 and 3 months of age, evidence-based guidelines, along with clinical evaluation, determine the diagnostic and therapeutic approach.
    • Fever of unknown origin (FUO) is defined as a temperature greater than 100.9 °F (38.3 °C) for longer than 3 weeks with no identified cause after 3 days of hospitalization or three outpatient visits.
    • FUO requires a systematic, thoughtful, and thorough evaluation based on the age of the patient and the existing clinical evidence, with repeated clinical assessments being essential.
    • Hyperthermia is an unregulated, significant elevation of core body temperature above the normal diurnal range due to failure of thermoregulation from a hypothalamic insult, not a pyogenic source, and is considered a medical emergency. It is not synonymous with fever and often requires immediate intervention to avoid deleterious central nervous system (CNS) effects.
  2. 2
    Current Therapy
    • Treating a fever significantly increases the patient’s level of comfort, activity, and oral feeding and fluid intake, in addition to decreasing the body temperature.
    • Multiple randomized, controlled trials reveal that treating fever does not shorten or prolong the overall duration of illness or reduce the occurrence of febrile seizures.
    • Many clinical recommendations state that a temperature less than 102.2 °F (39 °C) in healthy children does not require treatment. Antipyretics are known to provide comfort to children and their caregivers.
    • Antipyretic treatment for children includes acetaminophen (Tylenol) 10 to 15 mg/kg every 4 to 6 hours or ibuprofen (Advil, Motrin) 10 mg/kg every 6 hours.
    • Ibuprofen and acetaminophen have both been shown to reduce fever effectively and safely. Combination therapy has been shown in some studies to have an added benefit in both reduction of temperature and comfort without an increase in side effects, though caution should be taken to avoid dosing errors.
    • Antipyretic therapy for adults and adolescents includes acetaminophen 650 to 1000 mg orally (PO) every 6 hours to a maximum of 3 g per day, ibuprofen 200 to 400 mg PO every 6 hours, or aspirin (ASA) 325 to 650 mg every 6 hours as needed (PRN) for fever.
    • ASA should not be used in children due to the risk of Reye’s syndrome.
    • Sponge bathing should be done with tepid water and no alcohol. Recommendation: sponge bathing and other home remedies should not be used as sole treatment.

    Fever is one of the most common clinical presentations encountered by primary care physicians and the most common complaint of acute visits for children in the ambulatory or emergency department setting. Fever is a symptom and one of the most reliable signs of illness rather than a disease process itself. Most causes of fever are secondary to acute viral illnesses such as upper respiratory infections (URIs), which account for 50 million visits to primary care providers annually. Less commonly, bacterial infections may cause pharyngitis, otitis, sinusitis, pneumonia, and urinary tract infections (UTIs). A cost-effective, evidence-based approach using clinical protocols, guidelines, and consensus recommendations to the diagnosis and management of febrile illness, including the appropriate use of antibiotic therapy, is the cornerstone of quality medical care for this presentation. Fever produces significant anxiety for patients, parents, and health care providers, which can lead to overtreatment. Typically, fever is transient and only requires treatment to provide patient comfort.

  3. 3

    The definition of fever is dependent on numerous endogenous and exogenous factors that play a role in determining body temperature, including age, time of day, site, and measuring device, as well as operator variables. Fever is an elevation of body temperature due to the adjustment of the hypothalamic-pituitary set point. This usually occurs in response to a pathologic stimulus. Fever is a beneficial physiologic mechanism that helps to promote an augmented immunologic response.

    Despite individual variability, core body temperature is maintained at about 98.6 °F (37 °C). Diurnal variation results in lower body temperatures in the early morning and a temperature higher in the late afternoon or early evening, which is consistent with what is encountered in clinical practice.

    In adults, a morning oral temperature of 98.9 °F (37.2 °C) or higher, or an evening temperature of 99.9 °F (37.7 °C) or higher defines a fever. Rectal temperatures are generally considered to be 0.7 °F (0.4 °C) higher than oral readings.

    In infants and young children, rectal temperatures are still considered the standard of care and a rectal temperature greater than 100.4 °F (38 °C) is considered a fever.

    Axillary temperatures of greater than 98.6 °F (37 °C) are regarded as a fever, though this measurement site is generally considered less accurate. An accurate measurement of body temperature is dependent on site, measuring device, and the clinical skills of the operator. Site selection should be determined by the age of the patient.

    Young infants and older adults often have a diminished febrile response due to physiologic factors, thereby warranting the use of other clinical factors to guide diagnosis.

    Recent technologic advances, including electronic devices, tympanic membrane scanning, and temporal artery scanning, have replaced the older mercury-in-glass thermometers. These devices offer faster results and minimal inconvenience to the patient and are becoming increasingly reliable. Chemical content or liquid crystal thermometers applied to the skin are neither accurate nor cost-effective.

    Hyperthermia is an uncontrolled elevation of core body temperature that exceeds the body’s ability to lose heat. In hyperthermia, the setting of the hypothalamic thermoregulatory center is unchanged, in contrast to fever. Hyperthermia requires urgent medical intervention because it could be rapidly fatal and does not respond to antipyretics. Common etiologies include heat stroke, neuromalignant syndrome, serotonin syndrome, malignant hyperthermia, endocrinopathy, and CNS damage.

    Classic fever of unknown origin (FUO) is defined as a disorder with temperatures ≥ 100.9 °F (38.3 °C) that have persisted for at least 3 weeks, with no definitive cause elucidated after initial comprehensive inpatient or outpatient workup. The etiologies of FUO generally fall into four diagnostic categories: infectious, autoimmune or inflammatory, neoplastic, and miscellaneous.

  4. 4

    Fever occurs as part of an inflammatory response to an inciting stimulus. The response includes the production of various cytokines that ultimately increase the production of prostaglandin E2 (PGE2), which resets the hypothalamic thermoregulatory set point at a higher level. Important pyogenic cytokines include interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interferon-β (IFN-β), and interferon-γ (IFN-γ).


  5. 5
    Risks and Benefits of Fever

    Fever is known to enhance the immunologic response while suppressing the growth and replication of bacterial and viral infections. Though often uncomfortable for patients, caregivers, and health care providers, evidence supports the notion that fever is beneficial and ultimately protects against the development of asthma and other allergic disorders. In most instances, fever is not harmful. It does increase cardiac demand and metabolic needs, resulting in the common associated signs and symptoms of tachycardia, tachypnea, shivering, malaise, and diaphoresis.

    The use of antipyretic agents has not been shown to either prolong or shorten the duration of illness. Febrile seizures cause significant anxiety for parents. They occur most commonly in children between the ages of 6 months and 6 years. Most febrile seizures are uncomplicated and have not been shown to be associated with significant bacteremia or to lead to the development of seizure disorder in older children. Antipyretic agents have not been shown to decrease the incidence of febrile seizures.

  6. 6
    Diagnostic Evaluation of Fever

    In most cases, the etiology of a febrile illness is a self-limiting viral infection. From 5% to 10% of fevers may be associated with a more serious bacterial infection such as pneumonia, UTI, bacteremia, meningitis, or bone and joint infections. At times, these conditions may be challenging to distinguish, and a thoughtful, systematic, evidence-based approach to the diagnostic evaluation will be most cost-effective while avoiding the inappropriate use of antibiotics.

    All infants less than 28 days old with a fever should be admitted to the hospital for a full sepsis workup and empiric intravenous antibiotic therapy.

    Young infants, 1 to 3 months of age, with a febrile illness can be especially challenging. Numerous studies addressing this challenging population have led to the development of multiple guidelines and clinical protocols that utilize risk stratification criteria. The use of these age-specific stratification criteria, along with clinical treatment guidelines, helps guide the clinician in the evaluation of febrile illness. Clinical judgment remains the cornerstone of good clinical care.

    With the widespread use of Haemophilus influenzae type B (Hib) and pneumococcal vaccinations, the incidence of bacteremic illness has decreased significantly. Clinical judgment and a comprehensive assessment are required to guide appropriate diagnostic and therapeutic interventions. The increased use of rapid viral testing in the office and emergency department settings may alleviate the need for more invasive testing and antibiotic use because the risk of concurrent bacterial infection has been reported to be negligible.

    In this age group, an initial workup that reveals a white blood cell (WBC) count of less than 5000 or greater than 15,000 indicates an increased likelihood of a significant bacterial illness (SBI). Blood cultures, urinalysis, urine culture, and cerebrospinal fluid (CSF) evaluation should then be obtained and accompanied by intravenous antibiotic therapy. Elevated C-reactive protein (CRP) or procalcitonin levels have also been associated with SBI in children with a febrile illness and have shown increased specificity and sensitivity when compared to the WBC count. Using a combination of these tests has not been proven to be beneficial.

    Children age 3 to 36 months, who appear well and do not have any underlying medical history, require only a comprehensive clinical evaluation and do not warrant antibiotic therapy or diagnostic testing in most instances. Septic or ill-appearing children need a more aggressive evaluation, including complete blood count (CBC), inflammatory markers, urinalysis, urine culture, blood cultures, and a chest x-ray. High-risk children in this age group require empiric antibiotic therapy, and clinical judgment should guide the decision to hospitalize.

    Classic FUO is defined as a disorder with temperatures greater than

    100.9 °F (38.3 °C) that has persisted for at least 3 weeks with no clear etiology determined after 3 days of hospital evaluation or three outpatient visits. Common etiologic categories include infectious, neoplastic, inflammatory, and miscellaneous causes, of which drug fever has been shown to be the most prevalent.

    The initial approach includes a thorough history, physical examination, and appropriate laboratory testing. The initial choice of imaging should be guided by clinical findings and most commonly includes a chest x-ray and a CAT scan of the abdomen and pelvis. If the etiology remains elusive, positron emission tomography (PET) scanning or invasive diagnostic testing should then be considered.

  7. 7
    Differential Diagnosis

    Hyperthermia is an unregulated, significant elevation of core body temperature above the normal diurnal range due to failure of thermoregulation from a hypothalamic insult, not a pyogenic source, and is considered a medical emergency. It is not synonymous with fever and often requires immediate intervention to avoid deleterious CNS effects. Since the hypothalamic set point remains unchanged, antipyretics are ineffective in hyperthermia. The most common etiology is the inability to regulate or dissipate excess body heat.

    Hyperthermia is a medical emergency that requires immediate treatment to prevent excessive morbidity and mortality.


  8. 8

    Though controversy exists regarding the necessity of lowering fever, antipyretics have been shown to effectively and safely reduce temperature and improve symptoms with minimal side effects.

    Acetaminophen (Tylenol) is available in many formulations. Dosing should be based on body weight and not age of the patient. The dose is 10 to 15 mg/kg every 4 to 6 hours, not to exceed 3 g daily or 2 g in patients with renal or hepatic impairment. Ibuprofen (Advil, Motrin) is a nonsteroidal antiinflammatory drug (NSAID) that has both antiinflammatory and antipyretic effects. Dosing is 10 mg/kg every 6 to 8 hours in children and 200 to 400 mg every 6 hours in adolescents and adults. Ibuprofen is also available in multiple formulations, including a newer intravenous preparation (ibuprofen [Caldolor]) that may be beneficial in oral-intolerant hospitalized patients. Some studies suggest that ibuprofen may be a more effective antipyretic agent than acetaminophen.

    In adults, aspirin (ASA) remains a therapeutic alternative for lowering fever at a dose of 325 to 650 mg every 4 to 6 hours. It should not be used in children with a febrile illness due to the risk of Reye’s syndrome.

    A combination of acetaminophen and ibuprofen in alternating doses has been shown in some studies to have an added benefit in both reduction of temperature and comfort without an increase in side effects, though caution should be taken to avoid dosing errors.

    Nonpharmacologic therapies such as sponge bathing with tepid water and other environmental measures to control temperature, including adjusting room temperatures and sipping cool fluids to avoid dehydration, are used commonly and do provide symptom relief and comfort. These measures should never be used as the sole therapy for fever reduction.

  9. 9

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