OFFICIAL ABP TOPIC: 

Understand the differential diagnosis, evaluation, and management of fever without a source in children 3 to 36 months of age

BACKGROUND

Fever without a source is a fever lasting up to 7 days with no clear cause identified after a careful history and physical exam. While most fevers in young children are caused by common, self-limited viral illnesses, fever can occasionally indicate a serious bacterial infection requiring prompt diagnosis and treatment.

DIFFERENTIAL DIAGNOSIS OF FEVER WITHOUT A SOURCE

“Fever without a source” should be differentiated from “fever of unknown origin” (prolonged daily fever beyond one week). While fever without a source may eventually progress to fever of unknown origin and a broader differential diagnosis, a self-limited viral illness is the most common cause of fever without a source in a well-appearing child. However, an occult bacterial infection should be identified promptly, and less common causes of fever without a source are included in the differential below:

Undervaccinated children, especially those lacking Hib or PCV13, are more vulnerable to invasive bacterial infections.

EVALUATION OF FEVER WITHOUT A SOURCE IN CHILDREN 3-36 MONTHS OLD

In a child 3-36 months of age with no infectious source identified, a rectal temperature of ≥39°C (102.2°F) is recommended as the threshold for considering evaluation for an occult bacterial infection.

HISTORY

• Fever: Onset, duration, maximum temperature, response to antipyretics
• Immunization history
• Associated symptoms: Fussiness, eating/drinking changes, vomiting, diarrhea, cough, rhinorrhea, ear tugging, rash, joint swelling, dysuria
• Exposures: Ill contacts, travel, daycare attendance
• Past medical history: Prior hospitalizations, NICU stays, chronic illnesses that increase infection risk (e.g. sickle cell, immunodeficiency)

PHYSICAL EXAMINATION

• Vital signs including temperature
• General appearance/toxicity
• HEENT: Assess tympanic membranes for otitis media
• Neck: Check for stiffness, adenopathy
• Pulmonary: Evaluate for tachypnea or crackles (occult pneumonia)
• Skin: Look for petechiae (bacteremia), erythema (cellulitis), or rashes
• Neurologic: Assess for irritability or lethargy (meningitis)

DIAGNOSTIC TESTING

Well-appearing with fever <5 days:

• If completely immunized (completed primary series of PCV and Hib): Obtain U/A for children at increased risk for UTI (girl <24 months, uncircumcised boy <12 months, or history of UTI). No other studies needed if well-appearing.
• If underimmunized: Obtain CBC with diff and procalcitonin, as well as U/A for children at increased risk for UTI (history of UTI, girl <24 months, uncircumcised boy <12 months, fever >48 hours)
• Urine culture: Send if urine dipstick or U/A show signs of UTI
• Blood culture: Consider if undervaccinated, WBC >15,000, ANC >10,000, or procalcitonin >0.5 ng/mL

Well-appearing with fever ≥5 days:

• Consider Kawasaki disease (at least 4 of the following: bilateral conjunctivitis, oral mucous membrane changes, peripheral extremity changes, polymorphous rash, cervical lymphadenopathy). If only 2 or 3 clinical criteria are met, obtain ESR and CRP to assess for incomplete Kawasaki disease.
• Consider broader workup, especially for infants <6 months or fever ≥7 days: CBC with diff, inflammatory markers, BMP, LFTs, U/A, blood culture, urine culture

Additional testing:

• Chest x-ray: Obtain if clinical signs of lower respiratory infection (cough, tachypnea, crackles) or WBC >20,000
• CSF studies: Strongly consider if ill-appearing, altered mental status, inconsolable crying, nuchal rigidity, or other signs concerning for meningitis. Lumbar puncture is essential for definitive diagnosis.

Red flags:

• Toxic appearance: Emergent evaluation for possible sepsis (CBC, CRP/procalcitonin, blood culture, urinalysis/urine culture, CSF studies, CXR)
•  Petechiae/purpura: Urgent evaluation for bacteremia or meningitis.
• Poor perfusion: Assess for sepsis. Monitor closely for signs of shock.

MANAGEMENT

Most cases of fever without a source are caused by self-limited viral illnesses that only require supportive care. Other conditions should be treated appropriately according to the specific cause.

Ill or toxic-appearing children

• Emergent evaluation and stabilization
• Empiric IV antibiotics after obtaining cultures (e.g., ceftriaxone or cefotaxime +/- vancomycin)

Antibiotics for bacterial infection

• UTI: Oral antibiotics for mild disease. First-generation cephalosporin is usually first-line treatment for children 3-36 months old; tailor according to urine culture results. Consider IV if vomiting, not tolerating PO, or ill-appearing.
• Pneumonia: High-dose amoxicillin for well-appearing children 3-36 months old with community-acquired pneumonia
• Bacteremia: Admit and administer IV ceftriaxone. Tailor regimen based on culture results.
• Meningitis: Emergent lumbar puncture. Start IV ceftriaxone +/- vancomycin and admit.

Kawasaki disease:

• Treat with IVIG and aspirin
• Add glucocorticoids if at high risk for poor outcome (<6 months old, coronary artery dilation on initial echo)

REFERENCES

https://www.uptodate.com/contents/fever-without-a-source-in-children-3-to-36-months-of-age-evaluation-and-management 

https://www.uptodate.com/contents/fever-of-unknown-origin-in-children-etiology 

https://publications.aap.org/pediatricsinreview/article/36/9/380/34928/Pediatric-Fever-of-Unknown-Origin 

https://www.uptodate.com/contents/kawasaki-disease-initial-treatment-and-prognosis