Fever in Infants and Children

Most acute fevers in infants and young children are caused by infection. The most common are

• Viral respiratory or gastrointestinal infections (most common causes overall)

• Certain bacterial infections (otitis media, pneumonia, urinary tract infections)

However, potential infectious causes of acute fever vary with the child’s age. Neonates (infants < 28 days) are considered functionally immunocompromised because they often fail to contain infection locally and, as a result, are at higher risk of serious invasive bacterial infections most commonly caused by organisms acquired during the perinatal period. The most common perinatal pathogens in neonates are group B streptococci, Escherichia coli (and other gram-negative enteric organisms), Listeria monocytogenes, and herpes simplex virus. These organisms can cause bacteremia (viremia with herpes simplex), pneumonia, pyelonephritis, meningitis, and/or sepsis.

Most febrile children 1 month to 2 years of age without an obvious focus of infection on examination (fever without source [FWS]) have self-limited viral disease. However, a small number (perhaps < 1% in the postconjugate vaccine era) of such patients are early in the course of a serious infection (eg, bacterial meningitis). Thus, the main concern in a patient with FWS is whether occult bacteremia (pathogenic bacteria in the bloodstream without focal symptoms or signs on examination) is present. The most common causative organisms of occult bacteremia are Streptococcus pneumoniae and Haemophilus influenzae type b. The widespread use of vaccinations against both of these organisms has made occult bacteremia much less common.

Noninfectious causes of acute fevers include Kawasaki disease, heatstroke, and toxic ingestions (eg, of drugs with anticholinergic effects). Some vaccinations can cause fever either in the first 24 to 48 hours after the vaccine is given (eg, with pertussis vaccination) or 1 to 2 weeks after the vaccine is given (eg, with measles vaccination). These fevers typically last from a few hours to a day. If the child is otherwise well, no evaluation is necessary. Teething does not cause significant or prolonged fevers.

Acute recurrent or periodic fever is episodes of fever alternating with periods of normal temperature ( see Table: Some Common Causes of Fever in Children).

Fever that occurs daily for ≥ 2 weeks and for which initial cultures and other investigations fail to yield a diagnosis is considered fever of unknown origin (FUO).

Potential categories of causes ( see Table: Some Common Causes of Fever in Children) include localized or generalized infection, connective tissue disease, and cancer. Miscellaneous specific causes include inflammatory bowel disease, diabetes insipidus with dehydration, and disordered thermoregulation. Pseudo FUO is likely much more common than true FUO because frequent, minor viral illness may be overinterpreted. In children, despite the numerous possible causes, true FUO is more likely to be an uncommon manifestation of a common disease rather than an uncommon disease; respiratory infections account for almost one half of cases of infection-associated FUO.

History of present illness should note degree and duration of fever, method of measurement, and the dose and frequency of antipyretics (if any). Important associated symptoms that suggest serious illness include poor appetite, irritability, lethargy, and change in crying (eg, duration, character). Associated symptoms that may suggest the cause include vomiting, diarrhea (including presence of blood or mucus), cough, difficulty breathing, favoring of an extremity or joint, and strong or foul-smelling urine. Drug history should be reviewed for indications of drug-induced fever.

Factors that predispose to infection are identified. In neonates, these factors include prematurity, prolonged rupture of membranes, maternal fever, and positive prenatal tests (usually for group B streptococcal infections, cytomegalovirus infections, or sexually transmitted diseases). For all children, predisposing factors include recent exposures to infection (including family, caregiver, and school or daycare infection), indwelling medical devices (eg, catheters, ventriculoperitoneal shunts), recent surgery, travel and environmental exposures (eg, to endemic areas, to ticks, mosquitoes, cats, farm animals, or reptiles), and known or suspected immune deficiencies.

Review of systems should note symptoms suggesting possible causes, including runny nose and congestion (viral upper respiratory infection), headache (sinusitis, Lyme disease, meningitis), ear pain or waking in the night with signs of discomfort (otitis media), cough or wheezing (pneumonia, bronchiolitis), abdominal pain (pneumonia, strep pharyngitis, gastroenteritis, urinary tract infection, abdominal abscess), back pain (pyelonephritis), and any history of joint swelling or redness (Lyme disease, osteomyelitis). A history of repeated infections (immunodeficiency) or symptoms that suggest a chronic illness, such as poor weight gain or weight loss (tuberculosis, cancer), is identified. Certain symptoms can help direct the evaluation toward noninfectious causes; they include heart palpitations, sweating, and heat intolerance (hyperthyroidism) and recurrent or cyclic symptoms (a rheumatoid, inflammatory, or hereditary disorder).

Past medical history should note previous fevers or infections and known conditions predisposing to infection (eg, congenital heart disease, sickle cell anemia, cancer, immunodeficiency). A family history of an autoimmune disorder or other hereditary conditions (eg, familial dysautonomia, familial Mediterranean fever) is sought. Vaccination history is reviewed to identify patients at risk of infections that can be prevented by a vaccine.

Vital signs are reviewed, noting abnormalities in temperature and respiratory rate. In ill-appearing children, blood pressure should also be measured. Temperature should be measured rectally in infants for accuracy. Any child with cough, tachypnea, or labored breathing requires pulse oximetry.

The child’s overall appearance and response to the examination are important. A febrile child who is overly compliant or listless is of more concern than one who is uncooperative. However, an irritable infant or child who is inconsolable is also of concern. The febrile child who looks quite ill, especially when the temperature has come down, is of great concern and requires in-depth evaluation and continued observation. However, children who appear more comfortable after antipyretic therapy do not always have a benign disorder.

The remainder of the physical examination seeks signs of causative disorders ( see Table: Examination of the Febrile Child).

The following findings are of particular concern:

• Age < 1 month

• Lethargy, listlessness, or toxic appearance

• Respiratory distress

• Petechiae or purpura

• Inconsolability

Although serious illness does not always cause high fever and many high fevers result from self-limited viral infections, a temperature of ≥ 39° C in children < 36 months indicates higher risk of serious bacterial infection.

Other vital signs also are significant. Hypotension should raise concern about hypovolemia, sepsis, or myocardial dysfunction. Tachycardia in the absence of hypotension may be caused by fever (10 to 20 beats/minute increase for each degree above normal) or hypovolemia. An increased respiratory rate may be a response to fever, indicate a pulmonary source of the illness, or be respiratory compensation for metabolic acidosis.

Acute fever is infectious in most cases, and, of these, most are viral. History and examination are adequate to make a diagnosis in children > 36 months who are otherwise well and not toxic-appearing. Typically, they have a viral respiratory illness (recent ill contact, runny nose, wheeze, or cough) or gastrointestinal illness (ill contact, diarrhea, and vomiting). Other findings also suggest specific causes ( see Table: Examination of the Febrile Child).

In infants and children < 36 months, the possibility of occult bacteremia, plus the frequent absence of focal findings in neonates and young infants with serious bacterial infection, necessitates a different approach. Evaluation varies by age group. Accepted categories are neonates (≤ 28 days), young infants (1 to 3 months), and older infants and children (3 to 36 months). Regardless of clinical findings, a neonate with fever requires immediate hospitalization and testing to rule out a dangerous infection. Young infants may require hospitalization depending on screening laboratory results and the likelihood that they will be brought in for follow-up.

Acute recurrent or periodic fever and chronic fever (FUO) require a high index of suspicion for the many potential causes. However, certain findings can suggest the disorder: aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome); intermittent headaches with runny nose or congestion (sinusitis); weight loss, high-risk exposure, and night sweats (tuberculosis); weight loss or difficulty gaining weight, heart palpitations, and sweating (hyperthyroidism); and weight loss, anorexia, and night sweats (cancer).

Testing depends on age, appearance of the child, and whether the fever is acute or chronic.

All febrile children < 1 month of age require a white blood cell (WBC) count with a manual differential, blood cultures, urinalysis and urine culture (obtained by catheterization, not an external bag), and cerebrospinal fluid (CSF) evaluation with culture and appropriate polymerase chain reaction (PCR) testing (eg, for herpes simplex, enterovirus) as indicated by historical risk factors. Inflammatory marker levels (C-reactive protein, procalcitonin, or both) may be measured to assist with risk assessment. Chest x-ray is done in neonates with respiratory manifestations. Stool is sent for culture or enteric PCR stool test in neonates with diarrhea.

acyclovir is stopped if CSF HSV PCR testing and mucocutaneous vesicle HSV culture (if done) results are negative.

Febrile children between 1 month and 3 months of age require a different approach, which has evolved over the last few decades because the number of children in this age group who turn out to have a potentially serious bacterial infection has been markedly reduced by routine immunization against H. influenzae type b and S. pneumoniae. Clinicians must nonetheless maintain vigilance because, although serious bacterial infections have been reduced, they have not been eliminated. Therefore, clinicians who choose to observe without treatment or send home under parental observation need to have a greater certainty regarding that child's low-risk status than that of a child who is tested, admitted, and treated.

Infants in this 1- to 3-month age group are differentiated based on

• Temperature

• Clinical appearance (ill- or well-appearing, as below)

• Laboratory results

Febrile children between 3 months and 36 months of age who have an apparent source of fever on examination and who do not appear ill or toxic can be managed based on the clinical diagnosis. Children in this age group who are ill-appearing should be fully evaluated for serious bacterial infection with WBC count and cultures of blood, urine, and, when meningitis is suspected, CSF. Those with tachypnea or a WBC count > 20,000/mcL (> 20 × 10⁹S. pneumoniae, Staphylococcus aureus, Neisseria meningitidis, H. influenzae type b) and be admitted to the hospital pending culture results.

Well-appearing children in this age group who have a temperature > 39° C and no identifiable source on examination (fever without source) and who are not fully immunized have a risk of occult bacteremia as high as 5% (equal to the risk before the pneumococcal and H. influenzae conjugate vaccines came into use). These children should have a complete blood count with differential, blood culture, and urinalysis and urine culture. A chest x-ray should be done if the WBC count is ≥ 20,000/mcL (≥ 20 × 10⁹/L) . Children who have a WBC count ≥ 15,000/mcL (≥ 15 × 10⁹≥ 38° C) after 48 hours or earlier if they become sicker or if new symptoms or signs develop.

Well-appearing children in this age group who have a temperature > 39° C and fever without identifiable source and who are completely immunized have a risk of bacteremia < 0.5%. At this low-risk level, most laboratory testing and empiric antibiotic therapy are neither indicated nor cost-effective. However, because urinary tract infection (UTI) can be an occult source of infection in fully immunized children in this age group, girls < 24 months, circumcised boys < 6 months, and uncircumcised boys < 12 months should have a urinalysis and urine culture (obtained by catheterization, not an external bag) and be appropriately treated if UTI is detected. For other completely immunized children, urine testing is done only when they have symptoms or signs of UTI, they have a prior history of UTI or urogenital anomalies, or fever has lasted > 48 hours.

For all children, caregivers are instructed to return immediately if fever becomes higher, the child looks sicker, or new symptoms or signs develop.

For febrile children > 36 months of age, testing is directed by history and examination. In this age group, a child's response to serious illnesses is sufficiently developed to be recognized clinically (eg, nuchal rigidity is a reliable finding of meningeal irritation), so empiric testing (eg, screening WBC counts, urine and blood cultures) is not indicated.

For acute recurrent or periodic fever, laboratory tests and imaging should be directed toward likely causes based on findings from the history and physical examination. PFAPA syndrome should be considered in young children who have periodic high fever at intervals of about 3 to 5 weeks with aphthous ulcers, pharyngitis, and/or adenitis. Between episodes and even during the episodes, the children appear healthy. Diagnosis requires 6 months of stereotypic episodes, negative throat cultures during episodes, and exclusion of other causes (eg, specific viral infections). In patients with attacks of fever, arthralgia, skin lesions, mouth ulcers, and diarrhea, IgD levels should be measured to look for hyperimmunoglobulinemia D syndrome (HIDS). Laboratory features of HIDS include elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and markedly elevated IgD (and often IgA).

Genetic testing is available for familial Mediterranean fever (FMF), TNF receptor–associated periodic syndrome (TRAPS), and HIDS.

1. 1. Pantell RH, Roberts KB, Adams WG, et al: Evaluation and management of well-appearing febrile infants 8 to 60 days old. Pediatrics 148(2):e2021052228, 2021. doi: 10.1542/peds.2021-052228

Wiping the body down with isopropyl alcohol should be strongly discouraged because alcohol can be absorbed through the skin and cause toxicity. Numerous folk remedies exist, ranging from the harmless (eg, putting onions or potatoes in socks) to the uncomfortable (eg, coining, cupping).

1. 1. Sheehan WJ, Mauger DT, Paul IM, et alN Engl J Med 375(7):619–630, 2016. doi: 10.1056/NEJMoa1515990