Links To And Excerpts From Fever in Children: Pearls and Pitfalls

In this post I link to and excerpt from Fever in Children: Pearls and Pitfalls [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Children (Basel). 2017 Sep 1;4(9):81.

Here are excerpts:

1. Introduction

Fever, a physiologic response characterized by an elevation of body temperature above normal daily variation [1], is one of the most common causes for medical consultation in children, being
responsible for 15–25% of consultations in primary care and emergency departments [2–4]. Although fever can be concerning to parents and caregivers, the prevalence of serious infections in children is low, estimated at <1% in primary-care settings in industrialized countries [5]. However, this figure can increase up to 25% in emergency departments [6]. We performed a narrative review on the epidemiology, assessment, and management of fever in children, with the aim of providing
non-pediatric physicians with up-to-date information on the approach to febrile children.

2. Measurement of Fever in Children

[Normal temperature variation]  precludes the identification of a single universal upper limit of normal; therefore, fever can be generally defined as a thermoregulated elevation of body
temperature above normal daily variation [1]. However, for clinical and research purposes, fever is often defined as a core temperature of 38 ◦C or higher [11,12].

Body temperature can be measured in the axilla, rectum, mouth, skin, and ear. There are substantial differences among measurement sites [13]. Rectal temperature is considered to be the most accurate for estimating core body temperature [1,13], and is recommended by the American Academy of Pediatrics for children less than 4 years of age [14]. However, its use is discouraged by other clinical guidelines because of safety and practical issues, as well as for the physical and psychological discomfort it may cause [1,15]. Furthermore it is contraindicated in neutropenic or immunocompromised children [16]. Other measurement sites are less accurate than rectal temperature
but can be used in clinical practice.

Recommendations differ on the best site for temperature measurement in children. The National Institute for Health and Care Excellence (NICE) guidelines recommend measuring body temperature in the axilla, using an electronic thermometer for infants less than 4 weeks of age and chemical dot
or electronic thermometers in older children [1], while the American Academy of Pediatrics suggests rectal thermometry for children younger than 4 years of age and oral thermometry in older children [14].

Temporal artery thermometers and forehead non-contact infrared thermometers represent emerging techniques, but further studies are needed [26,27].*

* Please see The diagnostic accuracy of digital, infrared and mercury-in-glass thermometers in measuring body temperature: a systematic review and network meta-analysis [PubMed Abstract]  [Full Text HTML] [Full Text PDF]. Intern Emerg Med. 2020 Nov 25;1-13.

*Please see also Diagnostic test accuracy of new generation tympanic thermometry in children under different cutoffs: a systematic review and meta-analysis [PubMed Abstract] [Full Text HTML] [Download Full Text PDF]. BMC Pediatrics (2020) 20:210

Finally, even though it may be subject to interobserver differences, parental report of tactile fever should never be dismissed [1]. A prospective comparison of 322 febrile children found that mothers could accurately detect fever by tactile assessment (sensitivity 84%, specificity 76%) [28].

3. Increased Body Temperature as a Diagnostic Sign

Any abnormal elevation of body temperature in a child should be evaluated as a potential symptom of an underlying condition [12].

Fever is present when an increase in body temperature
occurs through a modification of the hypothalamic temperature set-point due to exposure to endogenous pyrogens [29]; in contrast, hyperthermia occurs when there is an increase in body
temperature because of a failure of thermoregulation, either because of increased heat absorption, heat production and/or reduced ability to dissipate it [30,31].

This difference implies that hyperthermia, in contrast to fever, may have potentially severe consequences on the body, since hyperthermia does not represent a controlled physiologic phenomenon.

Hyperthermia is less common in children, compared to fever. Most cases of hyperthermia are due to environmental hyperthermia, caused by massive heat exposure, which overcomes the body’s thermoregulation, such as in the case of “forgotten baby syndrome” involving children left in cars during hot season [32].

“Heat stroke” is defined as a core temperature ≥40 ◦C  [104 ◦F] accompanied by central nervous system dysfunction due to environmental heat exposure [30].

Young children have less efficient heat dissipation mechanisms, compared to older children and adults [31]. Other predisposing
factors include conditions characterized by excessive fluids loss or that adversely affect water-electrolyte balance (e.g., gastrointestinal illness, diabetes insipidus, diabetes mellitus, cystic fibrosis, diuretics, fever); conditions associated with suboptimal sweating (spina bifida, familial dysautonomia, hypo/anhidrotic ectodermal dysplasia, Crisponi syndrome, Fabry disease); diminished thirst/water intake (cognitive
impairment, young children); hypothalamic dysfunction; anorexia nervosa; and obesity [33].

Apart from environmental heat exposure, hyperthermia may be directly caused by conditions resulting in abnormal thermoregulation or increased heat production. Central nervous system conditions involving injury to the hypothalamus (either congenital or acquired) may lead to temperature dysregulation and hyperthermia (sometimes called “neurogenic” or “central fever”). Other causes include status epilepticus, thyrotoxicosis, and genetic syndromes associated with abnormal thermoregulation.

Intoxication from hyperthermia-inducing drugs may result in severe hyperthermia; involved drugs include stimulating/sympathomimetic drugs (cocaine, methamphetamine, MDMA), anticholinergic drugs (e.g., antihistamines, tricyclic antidepressants), serotoninergic drugs (serotonin syndrome), and salicylates.

Neuroleptic malignant syndrome is a severe idiosyncratic reaction to antipsychotic agents, but also antiemetic agents such as metoclopramide [34], characterized by altered mental status, muscular rigidity, movement disorders, hyperthermia and autonomic dysfunction [35].

Malignant hyperthermia is a rare genetic disorder (1 in 14,000 pediatric general anesthesia) associated with several forms of
congenital myopathy and triggered by succinylcholine or inhalational anesthetics agents; clinical features include rapid onset of extremely high temperature (38.5–46 ◦C), usually heralded by masseters spasm*, muscle rigidity, metabolic acidosis, and hemodynamic collapse. Specific treatment, with
discontinuation of involved anesthetics, muscular relaxation with sodium dantrolene, and correction of metabolic acidosis, has dramatically reduced the mortality, once as high as 70%, to less than 5% [36,37].

*See Masseter Muscle Rigidity: Definition, Relationship to Malignant Hyperthermia, and Management from The Malignant Hyperthermia Association of The United States, accessed 12-16-2020.

Fever is the most common reason for increased body temperature in pediatric clinical practice. The most common causes of fever in children are infections; non-infectious causes include immune-mediated, inflammatory, and neoplastic conditions. When a cause for fever cannot be identified
by history and physical examination it is called “fever without source” (FWS) [38]. In industrialized countries, a minority of children with FWS will have a serious bacterial infection (SBI) (mainly urinary tract infection (UTI), less commonly pneumonia, sepsis, or meningitis), while the majority will have mild, self-resolving viral illnesses [39].

In a prospective series of 103 children with a temperature >41 ◦C, almost 50% had an SBI [42]. Temperatures above 41 ◦C have also been associated with a higher risk of meningitis [43]. Notably, however, children with SBI may also have a normal temperature or be hypothermic.

4. The Value of Associated Clinical Findings

Gathering as much information as possible in the first, hands-off, phase of the visit is pivotal. Physical signs such as pallor, mottled appearance, ashen or blue skin color, reduced activity (poor feeding, no smile, decreased response to stimuli, lethargy, weak high-pitched cry), tachypnea and tachycardia, capillary refill time >3 s, and a reduced urine output are all concerning for SBI (“red flags”) [1,38], and should prompt a through evaluation. The meaning of some of them, however, may be put in context.

Bulging fontanelle: while a bulging fontanelle can be a sign of bacterial meningitis, it may also be due to more benign causes (e.g., sixth disease). In a series of 153 febrile infants between 3 and 11 months of age with fever and a bulging fontanelle, only 1 (0.6%) had bacterial meningitis [48]. Of note, this patient also had other alarm features and leukopenia. These findings suggest that, in febrile infants with a bulging fontanelle who are otherwise well-appearing and have no laboratory evidence of bacterial infection, close observation without lumbar puncture is a reasonable option.

Non-blanching rash: although a non-blanching rash should always raise concern, well-appearing children with fever and petechiae (small, non-blanching, macular hemorrhagic skin spots <2 mm in diameter) are still at low risk of SBI [49]. In a series of 411 patients between 3 and 36 months of age,
none of the 357 well-appearing children had SBI, while 6 out of 53 ill-appearing children had SBI. In another series of 55 children (mean age 2.5 years) only 9% eventually had bacterial sepsis, and they also had other concerning clinical features or abnormal laboratory tests [50]. These studies suggest that well-appearing children with fever and petechiae, without frank purpura, and with normal blood tests, can be observed for 4–6 h, reassessed, and eventually discharged.

Rigors: The presence of rigors may be associated with a higher probability of SBI (15% vs. 6% in children without rigors) [51]. Furthermore, they are also common in serious non-bacterial illness such as malaria, dengue, and chikungunya. Leg pain has also been reported as a possible early sign of bacterial sepsis and meningococcal disease [52].

Night sweats are a relatively nonspecific symptom [53];
however, their presence in the context of prolonged and unexplained febrile illness should raise concern for occult infectious (tuberculosis, endocarditis, liver and lung abscess, brucellosis) and non-infectious diseases.

Finally, clinician’s intuition that “something is wrong” (i.e., “gut feeling”) has been also demonstrated to be of diagnostic value [5,54]. Gut feeling is definitely something “impalpable”; however, it likely reflects a gestalt evaluation of several clinical aspects that can be appreciated in the first, no touch approach to the ill child.

These aspects [above] have been further characterized and systematizedin the “Pediatric Assessment Triangle” (PAT) developed by the American Academy of Pediatrics for Pediatric Advanced Life Support programs, which includes three main aspects (work of breathing, general appearance, and circulation to the skin). The PAT allows the clinician to establish the severity of the child’s condition and helps articulating the general impression of the child [55,56].

A useful classification of alarming signs/symptoms for first approach to a febrile child can be found in the NICE traffic light system* [1], since it values some signs/symptoms more than others and sets a distinction between “red” and “orange” alarm features (see also the following sections).

*NICE Traffic Light System For Identifying Risk Of Serious Pediatric Illness
Posted on May 6, 2017 by Tom Wade MD

5. Evaluation of Infants and Young Children with a Fever

Start here.

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