Fever in children

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Zaida Obeidat, M.D.

Synonyms and keywords: Fever in kids

Historical Perspective

• [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

Classification

• Fever may be classified based on duration into:
  • Acute fever: (<7 days duration), if untreated it can become persistent or chronic, attributes to infectious disease such as upper respiratory tract infection (URTI) and malaria.
  • Sub-acute fever:(<2 weeks), seen in typhoid fever and intra-abdominal abscess.
  • Chronic fever: (>2 weeks), typical of chronic bacterial infections (tuberculosis TB), viral infections (HIV), cancers and connective tissue diseases.

• Fever also can be classified based on height of body temperature into:
  • Low grade fever
  • Moderate grade fever
  • High grade fever (attributes to Serious bacterial infections in infants)
  • Hyperpyrexia

• The height of fever may correlate with severity of illness, such as in dengue fever, shigellosis, and acute falciparum malaria.
• There are three major fever type: Sustained/continuous fever, intermittent fever and remittent fever.
  • Continuous or sustained fever does not fluctuate more than about 1°C (1.5°F) during 24hours, but never touches normal, characteristics of lobar and gram negative pneumonia, typhoid, acute bacterial meningitis, and urinary tract infection.
  • Fever with bradycardia (Faget’s sign or sphygmothermic dissociation)is characteristic of untreated typhoid, leishmaniasis, brucellosis, Legionnaire’s disease and psittacosis, and Yellow Fever.
  • Intermittent fever is defined as fever present only for several hours during the day. It can be seen in malaria, pyogenic infections, tuberculosis (TB), schistosomiasis, lymphomas, leptospira, borrelia, kala-azar, or septicemia.
  • Sources of continuous, intermittent or transient bacteraemia may lead to continuous, intermittent or transient fevers respectively. Inmalaria, depending on the specie of parasite, fever can occur with a periodicity of 24h (quotidian-due to plasmodium falciparum), 48h (tertian plasmodium ovale and vivax), or 72h (quartan Plasmodium malaria). The Pel-Epstein’s feveris an intermittent low grade fever characterised by3—10 days of fever with subsequent a febrile peri-ods of 3—10 days[31,40]. It is thought to be a typical but rare manifestation of Hodgkin’s lymphoma.
  • Remittent fever is defined as fever with daily fluctuations exceeding 2◦C but at no time touches normal. Remittent fevers are often associated with infectious diseases such as infective endocarditis, rickettsiae infections, and brucellosis. Relapsing fevers refer to those that are recurring and separated by periods with low-grade fever or no fever. Periodic orrelapsing fevers are seen in malaria, lymphoma,borrelia, cyclic neutropenia, and rat-bite fever. Fever associated with night sweats has been described in infectious diseases such as TB, Nocardia, brucellosis, liver or lung abscess and sub-acute infective endocarditis, as well as in non-infectious diseases such as polyarteritis nodosa and cancers such as lymphomas.

Body temperature	°C	°F
Normal	37-38°C	98.6-100.4°F
Mild/low grade fever	38.1-39°C	100.5-102.2°F
Moderate grade fever	39.1-40°C	102.2-104.0°F
High grade fever	40.1-41.1°C	104.1-106°F
Hyperpyrexia	>41.1°C	>106.0°F

Pathophysiology

The pathophysiological mechanisms for the injurious effects of a fever, classified as follows:

• Direct cellular damage:
  • Membrane, mitochondrial and DNA damage
  • Stimulation of excitotoxic mechanisms
  • Protein denaturation
  • Cell death
• Local effects:
  • Cytokine stimulation
  • Inflammatory response
  • Vascular stasis
  • Extravasation
  • Oedema
• Systemic effects:
  • Endotoxaemia
  • Gut bacterial translocation

Causes

Common conditions that can cause fevers include:

• Upper respiratory tract infections (URTI)
• Flu
• Ear infections
• Roseola
• Tonsillitis
• Urinary tract infections (UTI)
• Chickenpox and Pertussis (Whooping cough)

Fever in children can sometimes associated with more serious signs and symptoms, such as:

• Dyspnea
• Vomiting
• Rash
• Seizures

Serious bacterial infections include:

• Meningitis
• Septicaemia
• Pneumonia

Causes of undiagnosed fever in children include:

• Infection
  • Viruses
  • Pyogenic Inection
  • Salmonella Infection
  • Brucellosis
  • Tuberculosis
• Collagen Vascular Diseases
• Neoplasm

Differentiating [disease name] from other Diseases

For further information about the differential diagnosis, click here.

Epidemiology and Demographics

• Following the widespread use of immunizations against Streptococcus pneumoniae and Haemophilus influenzae b, incidence of fever caused by infection due to these organisms has been decreased.
• Since 1990, rates of invasive Hib infection (including meningitis) in children 5 years and younger have declined by more than 99%.
• In 2005, the incidence of fever caused by invasive pneumococcal infection in children declined by 77% from 1998.

Age

• Fever caused by urinary tract infections (UTIs) are the most common source of serious bacterial infection in children younger than 3 months, commonly from E.coli or Klebsiella species.
• According to a case series, fever caused by pneumonia is the most common serious bacterial infection in children 3 to 36 months of age, followed by UTI.

Gender

• [Disease name] affects men and women equally.

• [Gender 1] are more commonly affected with [disease name] than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

• There is no racial predilection for [disease name].

• [Disease name] usually affects individuals of the [race 1] race.
• [Race 2] individuals are less likely to develop [disease name].

Risk Factors

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• [Disease name] is usually asymptomatic.
• Symptoms of [disease name] may include the following:

• [symptom 1]
• [symptom 2]
• [symptom 3]
• [symptom 4]
• [symptom 5]
• [symptom 6]

Physical Examination

• Initial history and physical examination in infants and young children with fever is aim to identify serious illness. Immunocompromised patients (cancer, asplenia, or HIV infection) need more evaluation and treatment.
• Benign causes of fever such as vaccination in the past 24 hours are reassuring. Teething is rarely associated with a fever of more than 100.4°F
• A meta-analysis of febrile children older than one month has identified red flags associated with a high likelihood of serious infection.

• Clinical Red Flags for Serious Infection in Children Older than One Month
• Global assessments
  • Parental concerns
  • Physician instinct
• Child behavior
  • Changes in crying pattern
  • Drowsiness
  • Inconsolability
  • Moaning
• Circulatory/respiratory
  • Crackles
  • Cyanosis
  • Decreased breath sounds
  • Poor peripheral circulation
  • Rapid breathing
  • Shortness of breath
• Other factors
  • Decreased skin elasticity
  • Hypotension
  • Meningeal irritation
  • Petechial rash
  • Seizures
  • Unconsciousness

Laboratory Findings

• There are no specific laboratory findings associated with [disease name].

• A [positive/negative] [test name] is diagnostic of [disease name].
• An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
• Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Electrocardiogram

There are no ECG findings associated with [disease name].

OR

An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

X-ray

There are no x-ray findings associated with [disease name].

OR

An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with [disease name].

OR

Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

CT scan

There are no CT scan findings associated with [disease name].

OR

[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

MRI

There are no MRI findings associated with [disease name].

OR

[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Other Imaging Findings

There are no other imaging findings associated with [disease name].

OR

[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

• [Disease name] may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

• Fever plays a physiologic role in response to infection, inhibiting bacterial growth and viral replication, and enhancing the immune response.
• There is no evidence that use of antipyretics prolongs illness in children
• Antipyretic treatment should be reserved for distressed children, aiming at improving the child’s wellbeing rather than achieving normothermia.
• Antipyretic treatment has not been shown to prevent recurrence of febrile seizures.
• Response to antipyretics cannot predict the severity of the underlying illness, since children with bacterial and viral illnesses have a similar response to antipyretics [134]. However, evaluating if the child’s conditions markedly improve with antipyretic treatment may be useful to discern whether it was related to fever or to the severity of the underlying illness.
• In children with inherited metabolic and mitochondrial diseases, catabolic stressors should be avoided, and both fever and underlying infections should be treated
• Fever may increase metabolic and oxygen consumption; therefore, aggressive treatment may be more important in children with a limited cardiopulmonary or metabolic reserve, and it is recommended in patients recovering from cardiac arrest.
• Ibuprofen and acetaminophen are the only drugs approved for treatment of fever in children and they are generally considered to be equally safe and effective for reducing temperature and relieving discomfort.
• Combination therapy with acetaminophen plus ibuprofen seems to be slightly more effective in reducing body temperature compared with monotherapy alone