Iron Toxicity

A 3 year old boy is brought to the emergency department with abdominal pain, nausea, vomiting and diarrhea. 10 minutes before arrival his father found the boy alone in the kitchen with an opened bottle of his wife’s prenatal vitamins. The father is unsure how many pills the boy ingested.

Epidemiology

The case above is a typical case of iron poisoning. Over 15,000 cases of iron exposure are reported to poison control centers annually. About 20% of these ingestions result in injury.

Most ingestion occurs unintentionally when children under the age of six ingest adult prenatal vitamins or ferrous sulfate pills. Such tablets especially appeal to children when they are sugar-coated or colored (see below). Children gain access to these pills when they or another child open child-resistant bottles or when parents leave the bottles open.

Iron supplement from the late 19th and early 20th century https://en.wikipedia.org/wiki/Iron_supplement

While toxicity related to adult pills can lead to fatality, excess intake of children’s chewable vitamins is very unlikely cause death.

Although most cases of iron exposure occur unintentionally in children younger than six, intentional ingestion also occurs. Additionally, iron exposure may be a form of child abuse and poisoning.

Iron Containing Pills and Toxicity

Pills containing significant amounts of iron are frequently accessible to children because many parents take these medications. The most common iron preparations are iron salts including ferrous gluconate, ferrous sulfate, and ferrous fumarate, which contain 12, 20, and 33% elemental iron, respectively.

Prenatal vitamins generally have 65 mg of elemental iron, while other multivitamins have 15 mg. The non-hormonal “placebo” pills in OCPs including Loestrin Fe and Estrostep Fe have 25 mg of elemental iron.  

While definitive toxicity levels have not been well established, ingestion of less than 20 mg/kg of elemental iron is typically clinically insignificant, while ingestion of greater than 60 mg/kg is often associated with serious symptoms. Levels between 20-60 may or may not lead to toxicity. Death has occurred with ingestions between 60-300 mg/kg.

Excess iron causes local damage in the GI tract and systemic damage throughout the body.  Iron is ingested in the ferrous form and absorbed in the mucosal cells of the duodenum and jejunum where it is oxidized to the ferric form. In toxic overdose, the proteins that usually transport and store iron in the body are overwhelmed, and the excess iron induces free radical production and lipids oxidation, damaging tissues throughout the body. The body’s mechanism of iron excretion is through sloughing of intestinal mucosal cells and menstruation in women.

Presentation

The clinical manifestations of iron poisoning are divided into four phases as outlined below. 

• Phase I:
  • Patients typically present during phase I with a chief complaint of vomiting and bloody diarrhea as well as fever and lethargy.  These symptoms can present 30 mins to 12 hours after ingestion.
  • Affected patients will have abdominal pain, diarrhea, nausea and vomiting. They may also have hematemesis and melena. 
                          
• Phase II:
                 
  • A latent period occurs between 8-36 hours from ingestion. During this largely asymptomatic time period it is important to distinguish between patients who have had mild GI toxicity that has now resolved and patients who have had severe toxicity and are now in the latent phase. Therefore, patient should continue to be monitored beyond 36 hours. Patients with severe toxicity may not experience a latent phase.
                 
• Phase III:
               
  • Systemic toxicity presents between 12-48 hours after ingestion. It is characterized by liver injury or failure. Hypoglycemia, metabolic acidosis, cardiovascular collapse, shock, bleeding, coma, and seizure can also occur.
                           
• Phase IV:
                     
  • Late complications are seen 4-8 weeks after ingestion and include intestinal, pyloric, and antral stenosis leading to bowel obstruction or CNS effects.

Differential

Because patients with iron overdose are generally under 6 years old and present with GI complaints, gastroenteritis, appendicitis, and intussusception should all be considered in the differential. Regarding other possible ingestions, aspirin, NSAIDs, colchicine, theophylline, arsenic, isopropanolol, and arsenic can all present with vomiting.

Workup

A thorough history should be taken to determine the amount of elemental iron ingested and the timing of ingestion. Patient’s who remain asymptomatic 6 hours after ingestion are unlikely to present clinically unless the source of iron was enteric-coated.  Patients who ingested more than 40 mg/kg or for whom the amount of iron ingested cannot be determined should undergo laboratory evaluation.

Patients with suspected iron toxicity should have an iron level drawn within 4-6 hours of ingestion as well as TIBC, CBC, BMP. An abdominal X-ray will show radio-opaque tablets in the stomach.

Test results will be significant for hyperglycemia, leukocytosis, metabolic acidosis, and increased serum iron. After six hours, iron levels will no longer be elevated. Iron levels are used only to determine if iron overdose has occurred, not to assess severity.

Patients with more severe intoxication may also require LFTs, ABG, and coagulation studies.

In cases where non-accidental ingestion is suspected, concurrent evaluation for ingestion of other drugs or medications (i.e., acetaminophen, salicylic acid) should be explored. 

Treatment

When toxic ingestion has occurred, parents or healthcare workers should call the Poison Control Center at 800-222-1222.  CLICK BELOW for more information on the services Poison Control offers.

Patients who have ingested less than 20 mg/kg require no treatment, whereas patients who have consumed more than 40 mg/kg should be taken to the emergency room for evaluation and management.

For serious overdose IV deferoxamine can be given at 15 mg/kg/hour to chelate iron. The patient’s urine will turn pink, “vin rose”, which signals that iron is being removed. Side effects of deferoxamine include erythema, hypotension, diarrhea, and tachycardia among others.

Activated charcoal does not effectively remove iron. Whole bowel irrigation is likely to benefit the patient without causing significant side effects. Surgical gastrostomy may be required when there are too many pills present to be removed by alternative means.

References

1. Fine, JS. Iron poisoning. Current Problems in Pediatrics 2000; 30:71.
2. Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2010 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 28th Annual Report. Clin Toxicol (Phila) 2011; 49:910.
3. Black J, Zenel JA. Child abuse by intentional iron poisoning presenting as shock and persistent acidosis. Pediatrics 2003; 111:197.
4. Juurlink DN, Tenenbein M, Koren G, Redelmeier DA. Iron poisoning in young children: association with the birth of a sibling. CMAJ 2003; 168:1539
5. Manoguerra AS, Erdman AR, Booze LL, et al. Iron ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2005; 43:553.