Stages of Iron Toxicity in Pediatric Patients
Iron toxicity in children under 6 years progresses through five distinct clinical stages, with the most critical being Stage II (latent phase) which can falsely reassure clinicians before life-threatening Stage III develops.
Stage I: Gastrointestinal Phase (0-6 hours post-ingestion)
- Direct corrosive injury to the GI mucosa causes vomiting, diarrhea, abdominal pain, and hematemesis 1, 2
- Symptoms occur within the first 6 hours and reflect local tissue damage from free iron 1
- Severe or persistent vomiting and bloody diarrhea indicate significant toxicity requiring immediate referral 2
- Hyperglycemia and leukocytosis may develop as early metabolic markers 1
Critical Pitfall: Mild vomiting and diarrhea are common and do not necessarily warrant hospital referral if the ingested dose is <40 mg/kg elemental iron 2. However, persistent or severe symptoms always require evaluation.
Stage II: Latent Phase (6-24 hours post-ingestion)
- This deceptively quiescent period represents the most dangerous phase because symptoms may temporarily resolve while cellular toxicity progresses 1
- Free iron continues to cause mitochondrial dysfunction and cellular damage despite apparent clinical improvement 1
- Asymptomatic patients beyond 6 hours post-ingestion are unlikely to develop subsequent toxicity and may not require prolonged observation 2
Critical Pitfall: Clinicians may discharge patients during this phase, missing the window for intervention before cardiovascular collapse occurs 1.
Stage III: Shock and Metabolic Acidosis (12-48 hours post-ingestion)
- Cardiovascular collapse with profound shock develops from mitochondrial poisoning and vasodilation 1, 3
- Severe anion gap metabolic acidosis results from lactic acid accumulation and iron-induced metabolic dysfunction 4, 1
- Altered mental status progressing to coma indicates severe toxicity 4, 1
- Coagulopathy develops as hepatic synthetic function fails 5
Management at this stage requires:
- Aggressive fluid resuscitation and vasopressor support 1, 3
- Immediate deferoxamine chelation therapy 4, 1
- Consideration of hemodialysis for massive overdoses with serum iron >2000 mcg/dL 4
Stage IV: Hepatotoxicity (2-5 days post-ingestion)
- Fulminant hepatic failure manifests with elevated transaminases, coagulopathy, and encephalopathy 5
- Hepatocellular necrosis results from direct iron toxicity to hepatocytes 1, 5
- Presence of coagulopathy and acute liver failure are associated with high mortality in pediatric patients 5
- Plasmapheresis may be considered for severe cases, though evidence is limited 5
Stage V: Gastric Outlet Obstruction (2-8 weeks post-ingestion)
- Late complication from scarring and stricture formation at sites of corrosive injury 1
- Presents with persistent vomiting and feeding intolerance weeks after apparent recovery 1
- Requires endoscopic evaluation and potential surgical intervention 1
Dose-Based Risk Stratification
The following thresholds guide initial management decisions:
- <40 mg/kg elemental iron: Home observation with follow-up if asymptomatic or mild symptoms only 2
- ≥40 mg/kg elemental iron: Immediate referral to healthcare facility regardless of symptoms 2
- >60 mg/kg elemental iron: Potentially serious toxicity requiring aggressive intervention 1
Special considerations for young infants:
- Premature infants and neonates face additional challenges from physiologic immaturity of developing organs 3
- Even standard therapeutic iron supplementation errors can cause severe toxicity in this age group 3
- Include toxic iron exposure in the differential diagnosis of unexplained neonatal shock 3
Key Clinical Indicators of Severe Toxicity
Immediate hospital referral is mandatory for:
- Persistent or severe vomiting and diarrhea 2
- Hematemesis or bloody diarrhea 2
- Altered level of consciousness 2
- Metabolic acidosis 4, 1
- Shock or cardiovascular instability 1, 3
- Coagulopathy 5
Radiographic findings: