What is the differential diagnosis for an infant presenting with hematochezia (blood in stool)?

Differential Diagnosis for Blood in Stool in Infants

Most Common Causes by Age and Presentation

The differential diagnosis for hematochezia in infants is age-dependent, with anal fissures, food protein-induced enterocolitis syndrome (FPIES), and infectious colitis being the most common benign causes, while necrotizing enterocolitis and volvulus with intussusception represent life-threatening emergencies requiring immediate recognition. 1, 2

Benign and Self-Limiting Conditions

Anal fissures are the most common cause of rectal bleeding in infants, presenting as streaks of bright red blood on the stool surface or toilet paper, typically associated with constipation and painful defecation. 2, 3

Food Protein-Induced Enterocolitis Syndrome (FPIES):

• Non-IgE-mediated food allergy causing colonic inflammation with rectal bleeding, most commonly triggered by cow's milk or soy 1
• Acute FPIES presents with vomiting 1-4 hours after ingestion, lethargy, pallor, and may progress to hypotension and metabolic acidosis 4
• Chronic FPIES presents in infants <6 months with intermittent vomiting, chronic diarrhea with occult or frank blood, failure to thrive, and hypoalbuminemia 4
• Stool examination reveals occult blood, neutrophils, eosinophils, Charcot-Leyden crystals, and/or reducing substances 4
• Colonoscopy shows red, fragile, hemorrhagic mucosa with severe inflammation and increased eosinophils on biopsy 1
• Diagnosis requires resolution of symptoms within days after elimination of the offending food and recurrence with reintroduction 4

Infectious Colitis:

• Bacterial infections (Salmonella, Shigella, Campylobacter, E. coli O157:H7) and parasitic infestations are responsible for most cases of bloody diarrhea in children 3
• Presents with frequent scant stools with blood and mucus (dysentery), fever, and abdominal pain 5
• Stool examination for pathogens is essential 3

Swallowed Maternal Blood (Melena Neonatorum):

• Occurs in newborns within the first days of life from ingestion of maternal blood during delivery or from cracked nipples during breastfeeding 6
• Alkali denaturation test (Apt test) confirms maternal origin of blood 6
• Infant remains clinically stable without systemic symptoms 6

Life-Threatening Emergencies

Necrotizing Enterocolitis (NEC):

• Primarily affects premature infants but can occur in term infants 7
• Presents with bloody stools, abdominal distension, feeding intolerance, and systemic instability 7
• Abdominal radiograph may show pneumatosis intestinalis, portal venous gas, or pneumoperitoneum 4, 7
• Critical pitfall: Intramural gas in FPIES can be misdiagnosed as NEC 4

Intussusception:

• Most common in infants 4-12 months, but can occur earlier 8
• Classic triad: severe colicky abdominal pain, vomiting, and "currant jelly" stools (blood mixed with mucus) 8
• Early stage presents with diarrhea and mucus before progression to bloody stools as bowel ischemia develops 8
• Requires urgent ultrasound and possible air or contrast enema reduction 8

Midgut Volvulus:

• Presents in first weeks to months of life with bilious vomiting, abdominal distension, and bloody stools indicating bowel ischemia 2
• Requires emergent upper GI series and surgical intervention 2

Less Common but Important Causes

Vitamin K Deficiency Bleeding:

• Occurs in newborns who did not receive prophylactic vitamin K at birth 7
• Presents with prolonged INR, PT, and PTT with bloody stools and other bleeding manifestations 7
• Requires immediate vitamin K administration 7

Inflammatory Bowel Disease (Very Early Onset):

• Rare in infancy but can present with chronic bloody diarrhea, failure to thrive, and perianal disease 5, 2
• Fecal calprotectin and lactoferrin are highly sensitive for detecting intestinal inflammation 5
• Requires colonoscopy with biopsy for diagnosis 5

Vascular Malformations:

• Rare cause of rectal bleeding in infancy 2
• May present with painless, intermittent bleeding 2

Critical Diagnostic Approach

Immediate Assessment for Shock:

• Approximately 15% of acute presentations of bright red rectal bleeding in children involve hypovolemic shock requiring aggressive fluid resuscitation 1
• Assess vital signs, capillary refill, mental status, and hemodynamic stability first 1

Exclude Upper GI Source:

• 10-15% of patients with severe hematochezia have an upper GI bleeding source 1
• Consider nasogastric lavage if massive bleeding or hemodynamic instability present 1

Key Historical Features:

• Age of onset: <2 months suggests chronic FPIES with blood in stool and failure to thrive; 4-12 months suggests solid food FPIES or intussusception 4, 8
• Timing relative to food introduction: FPIES occurs once cow's milk, soy-based formulas, or solid foods are introduced 4
• Associated symptoms: vomiting (FPIES, intussusception), fever (infection), abdominal pain severity (intussusception vs. gastroenteritis), failure to thrive (chronic FPIES, IBD) 4, 8, 1
• Stool characteristics: streaks of blood (fissure), blood mixed with mucus (intussusception, colitis), blood mixed throughout stool (upper GI or proximal colonic source) 4, 8

Physical Examination:

• Digital rectal examination to assess for fissures, masses, or stool consistency 1
• Abdominal examination for distension, tenderness, masses 1
• Assess for signs of systemic illness: lethargy, pallor, dehydration 4, 1

Laboratory Evaluation:

• Complete blood count to assess for anemia, thrombocytosis (seen in 65% of acute FPIES), leukocytosis with left shift 4, 1
• Basic metabolic panel if dehydration or significant bleeding present to assess for metabolic acidosis (seen in FPIES) 4, 1
• Coagulation studies (PT, PTT, INR) if bleeding disorder suspected or vitamin K deficiency possible 7
• Stool examination for blood (guaiac), leukocytes, eosinophils, pathogens, and reducing substances 4, 3
• Fecal calprotectin if chronic symptoms or IBD suspected 5

Imaging:

• Abdominal radiograph if obstruction, perforation, or NEC suspected 7
• Ultrasound for suspected intussusception 8
• Do not obtain routine radiographic testing for suspected FPIES 4

Common Pitfalls to Avoid

• Never assume hemorrhoids without proper evaluation, as symptoms attributed to hemorrhoids frequently represent other pathology; hemorrhoids are extremely rare in infants 4, 1
• Do not rely on stool tests alone to diagnose FPIES, though they may show eosinophilic debris; diagnosis is clinical with food elimination and rechallenge 1
• Always consider a broad differential, as many infantile gastrointestinal disorders cause overlapping symptoms with chronic FPIES, including infectious colitis, IBD, and anatomic abnormalities 4, 1
• Do not miss intussusception: the presence of mucus in stool represents an early stage before progression to bloody stools, and severe pain distinguishes it from viral gastroenteritis 8
• Intramural gas can lead to misdiagnosis of NEC when the actual diagnosis is FPIES 4
• Child abuse should always be considered when bleeding presents with other concerning features 1