What could be the cause of recurrent episodes of paroxysmal (sudden, episodic) flushing of the whole body, slowed breathing, and hyperthermia (elevated body temperature) lasting less than 5 minutes in a 4-month-old full-term male infant, with no apparent provocation or post-episode changes?

Paroxysmal Flushing Episodes in a 4-Month-Old Infant

This presentation is most consistent with a Brief Resolved Unexplained Event (BRUE), which involves the autonomic nervous system and requires careful evaluation to exclude serious underlying conditions, though most cases are benign. 1

What This Could Be

The episodes you describe—paroxysmal whole-body redness (flushing), slowed breathing, and feeling hot, lasting less than 5 minutes with complete return to baseline—fit the clinical pattern of a BRUE, which is characterized by changes in breathing, skin color (including pallor or flushing), muscle tone, or altered responsiveness in infants under 1 year of age. 1, 2

Key distinguishing features of BRUE include:

• Duration typically less than 1 minute (usually 20-30 seconds), though your case describes episodes up to 5 minutes 1
• Complete resolution with return to normal activities 1
• No identifiable explanation after thorough evaluation 1, 2
• Infant appears well between episodes 1

However, facial flushing alone is common in healthy infants and is NOT consistent with BRUE 1. The combination of whole-body redness with slowed breathing and temperature changes raises concern for a more complex autonomic event.

System Involvement

This primarily involves the autonomic nervous system, which controls involuntary functions including:

• Skin blood flow and flushing (vasomotor control) 1
• Respiratory rate regulation 1
• Temperature regulation 1

The autonomic dysregulation could be benign or could signal an underlying neurologic, cardiac, metabolic, or infectious condition that requires exclusion. 1, 2

Concerning Features to Assess

Before diagnosing BRUE, you must exclude:

• Seizures or epilepsy: Look for eye deviation, rhythmic jerking, post-event drowsiness, or developmental concerns 1, 2, 3
• Cardiac arrhythmias: Family history of sudden death, syncope, or long QT syndrome 2
• Infections: Fever, nasal congestion, increased respiratory effort (these would exclude BRUE diagnosis) 1
• Metabolic disorders: Poor feeding, vomiting, lethargy, failure to thrive 1
• Child abuse: Unexplained bruising, inconsistent history, retinal hemorrhages 1
• Gastroesophageal reflux with aspiration: Vomiting followed by choking 1

Risk stratification is critical:

• Higher-risk features include: age <60 days, prematurity (<32 weeks corrected gestational age), event duration >1 minute, multiple events, or CPR required 2, 3
• Lower-risk BRUE (age >60 days, term infant, first event, <1 minute duration, no CPR) has <5% rate of serious diagnoses 2, 3

Which Specialty Should Investigate

Start with Pediatrics (general pediatrician or pediatric hospitalist) for initial evaluation, which should include: 1, 2

• Detailed witness account of the event (infant's state before, exact characteristics, intervention required) 1
• Assessment for fever, respiratory symptoms, feeding difficulties 1
• Complete physical examination including neurologic assessment 1
• Evaluation for signs of trauma or abuse 1

For a 4-month-old with these specific features, consider early involvement of:

1. Pediatric Neurology if there are: 2, 3

   • Concerns for seizures (most common serious diagnosis in BRUE, occurring in 4 patients out of 15 serious diagnoses in one study) 3
   • Abnormal neurologic examination 1
   • Developmental delays 1
   • Family history of epilepsy 4

2. Pediatric Cardiology if: 2

   • Family history of sudden cardiac death or arrhythmias
   • Abnormal cardiac examination
   • Event occurred during feeding or crying (can trigger arrhythmias)
   • Consider baseline ECG even in lower-risk BRUE 2

Differential Diagnoses to Consider

Benign paroxysmal conditions that can mimic concerning events:

• Benign Myoclonus of Early Infancy (BMEI): Presents at 4-7 months with brief myoclonic jerks, but consciousness is preserved and episodes occur during wakefulness 5
• Paroxysmal Tonic Upgaze: Sustained upward eye deviation without consciousness impairment, typically 5-18 months old 4
• Normal infant physiology: Periodic breathing, color changes with crying 1

Serious conditions that must be excluded:

• Seizures (most common serious diagnosis) 3
• Cardiac arrhythmias 2
• Airway abnormalities 2, 3
• Metabolic disorders 1
• Infection (though fever and respiratory symptoms would exclude BRUE) 1

Critical Pitfalls to Avoid

• Do not assume all episodes are benign without proper evaluation 1, 2
• Do not miss seizures: 4.6% of children initially diagnosed with epilepsy have a false-positive diagnosis, but 5.6% with unclear events have delayed epilepsy diagnosis 6
• Do not overlook child abuse: This is a critical differential that requires high suspicion 1
• Do not perform extensive testing in lower-risk BRUE: Guidelines advocate against routine admission, blood testing, and imaging for lower-risk events 2, 3
• Do not ignore recurrent events: Prior BRUE events are associated with serious diagnoses and episode recurrence 2

Recommended Initial Approach

For this 4-month-old with recurrent episodes:

• Obtain detailed event history from reliable witness 1
• Perform thorough physical and neurologic examination 1
• Assess risk stratification (higher vs. lower risk) 2
• Consider brief observation period (even for lower-risk) given recurrent nature 2
• Consider baseline ECG 2
• If higher-risk features present or recurrent events, hospitalization and subspecialty consultation (neurology and/or cardiology) are warranted 2, 3

Most infants with BRUE (82.1%) do not receive an explanatory diagnosis even after hospitalization, and the majority of identified diagnoses are benign or self-limited conditions 3. However, the 1.5% rate of serious diagnoses (primarily seizures) necessitates careful evaluation. 3