DESCRIPTION

Lead is a poisonous heavy metal.

FORMS AND USES

Sources of lead exposure:

• Paint. The most common source of lead exposure in children is dust and peeling paint from pre-World War II homes or homes painted before 1980.
• Parental occupation. A parent's clothing may be contaminated during smelting, battery manufacturing or recycling, painting, construction, mining, soldering, art work or restoration, welding, capacitor manufacturing, plumbing, radiator repair, metal refining, or bridge repair.
• Hobbies. Art, jewelry making, stained glass, painting, home renovation, target shooting, and ceramic work may all involve lead.
• Food. Lead can be found in ceramic dishes made outside the United States (especially from Mexico), lead crystal, water (lead pipes), wine, or canned foods sealed with lead solder.
• Folk remedies may contain lead.
  • Mexican. Azarcon, greta, abayalde, rueda, coral, alarcon, Maria Luisa.
  • Southeast Asian. Pay-loo-ah.
  • India. Maha yogran guggulu, ayurvedic herbal medications.
  • China. Hau ge fen.
  • Traditional remedies from Korea, Pakistan, and the Middle East have also been implicated.
• Foreign bodies. Bullets (ingested or retained near joints), curtain weights, fishing sinkers, and contaminated soil may all lead to lead poisoning.

TOXIC DOSE

Blood lead levels (BLL) are used instead of ingested amount.

• BLL greater than 10 µg/dl causes delayed cognitive development.
• BLL greater than 45 µg/dl may also cause gastrointestinal effects.
• BLL greater than 100 µg/dl may be life-threatening.

PATHOPHYSIOLOGY

• Lead combines with sulfhydryl groups (R-SH) and thereby inhibits the function of many enzymes.
• CNS development is altered by lead through undescribed mechanisms.
• Anemia is caused by interference with heme-biosynthesis.
• Iron deficiency increases the absorption of lead from the gastrointestinal tract.

EPIDEMIOLOGY

• Poisoning is common in poor children in cities with old deteriorated housing, but is generally uncommon in the western United States.
• Toxic effects following acute exposure are typically mild.
• Death occurs in young children with severe chronic exposure.

CAUSES

• Poisoning is usually caused by accidental chronic exposure.
• An unusual source of exposure (food, traditional remedy, water) should be considered, particularly if the patient is less than 1 year of age.

RISK FACTORS

• Children younger than 3 years of age are at greatest risk of lead poisoning because of hand-to-mouth behavior, increased bioavailability of lead, and an immature blood-brain barrier.
• Iron-deficient children are at risk because of increased pica behavior and increased gastrointestinal absorption of lead.

PREGNANCY AND LACTATION

An elevated cord blood lead level is associated with delayed neurologic development in the infant.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxic causes of encephalopathy appearing like lead encephalopathy include theophylline or salicylate toxicity.
• Nontoxic causes include encephalitis, meningitis, fulminant hepatic failure, or CNS mass or bleed.

SIGNS AND SYMPTOMS

• Patients are usually asymptomatic.
• Abdominal pain, headache, anemia, and fatigue may develop with a BLL of 45 to 60 µg/dl.
• CNS depression, seizures, and encephalopathy are rare and usually are associated with a BLL of more than 100 µg/dl.

HEENT

• Mild hearing loss may occur.
• Blue-black lines ("lead lines") may develop on the gums but are rare in children under 5 years of age.

Gastrointestinal

• Abdominal pain and constipation may develop with chronic intoxication.
• Nausea, vomiting, and diarrhea may develop with acute poisoning from lead salts.

Renal

Nephropathy, interstitial nephritis, decreased glomerular filtration rate, and proximal tubular dysfunction may develop with chronic poisoning.

Hematologic

• Anemia may develop from chronic exposure if the BLL is more than 40 µg/dl.
• Basophilic stippling may develop in patients with chronic exposure.

Musculoskeletal

• Muscle and joint pain may develop with chronic poisoning.
• Lead lines (radiodense areas in the metaphyses of growing bones) may develop with chronic lead poisoning.

Neurologic

• Subclinical cognitive dysfunction, decreased IQ, and difficulties with attention are reported in children with chronic poisoning and BLL higher than 10 µg/dl; irritability, headache, and fatigue also may develop.
• Encephalopathy, coma, and seizures occur rarely and typically with a BLL above 100 µg/dl.
• Peripheral neuropathy is unusual in children.

Endocrine

Chronic poisoning is associated with decreased levels of growth hormone and 1,25 dihydroxy vitamin D in children.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Blood lead level
  • BLL of 10 to 14 µg/dl. The family should be educated to avoid future lead exposure, and the BLL reassessed after 3 months.
  • BLL of 15 to 19 µg/dl. The family should be educated to avoid future lead exposure, and the BLL reassessed after 2 months.
  • BLL of 20 to 44 µg/dl. A complete assessment of the child and the home environment should be performed. The family should be educated to avoid lead exposure, and the BLL reassessed within 1 month (if BLL is 20 to 29 µg/dl) or within 1 week (if BLL is 29 to 44 µg/dl).
  • BLL of 45 to 69 µg/dl. A complete assessment of the child should be performed and chelation treatment initiated. If the home is the likely source, the patient should be moved to other housing immediately.
  • BLL of more than 69 µg/dl. The patient should be hospitalized and chelation treatment started. Environmental assessment should be performed immediately and the source remediated before the child can return.
• Environmental assessment
  • Although the mechanism varies geographically, it is critical to perform assessment of the child's environmental source of lead.
  • The county or state health department should be contacted for further information.
• Complete blood count. Hypochromic microcytic anemia may indicate the need for iron supplementation.
• Serum iron, ferritin, and total iron-binding capacity are measured to determine iron deficiency (which will increase lead absorption).

Recommended Tests

• Abdominal or kidney-ureter-bladder (KUB) radiography should be performed to evaluate for radiopaque foreign bodies in any child who has a suspected recent ingestion, whose BLL has recently increased, in whom oral chelation is considered, or whose BLL is greater than 45 µg/dl.
• A radiograph of long bones (tibia or radius) may reveal lead lines: linear areas of increased density that develop at the metaphyses of growing bones in chronically lead-poisoned children.
  • Lead lines have no prognostic value.
  • Generally they are not present in children with BLLs of less than 30 to 40 µg/dl.
• X-ray fluorescence is a procedure being developed to measure lead in bone noninvasively; it is not widely available.

Not Recommended Tests

Free erythrocyte protoporphyrin and zinc protoporphyrin are not sensitive nor specific tools for screening.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • HEENT
  • Gastrointestinal
  • Renal
  • Hematologic
  • Musculoskeletal
  • Neurologic
  • Endocrine
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

• Treatment focuses on determining the source of exposure; eliminating lead exposure; initiating chelation in appropriate patients; and educating parents on sources of lead exposure, hygiene measures to limit exposures, and dietary measures to reduce lead exposure.
• In cases of lead encephalopathy, supportive care with appropriate airway management is vital.
• Temporary relocation of the patient is an important component of therapy when the home environment may be the source of exposure.

DIRECTING PATIENT COURSE

• Consultation with a physician experienced in the management of pediatric lead poisoning is strongly encouraged.

The health-care provider should call the poison control center when:

• Seizure, encephalopathy, or other severe effects are present.
• Toxic effects are not consistent with lead poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Environmental exposure to lead cannot be stopped.
• BLL is higher than 45 µg/dl.
• Seizure, encephalopathy, or other severe effects are present.
• Oral chelation is necessary, and the patient is not in a lead-free environment.

Admission Considerations

Inpatient management is warranted for:

• Patients who have seizure, encephalopathy, or other severe effects.
• Patients who require parenteral chelation.
• Patients who require oral chelation but are not in a lead-free environment.

DECONTAMINATION

• Whole-bowel irrigation is recommended before initiating chelation for patients who have evidence of radiopaque matter on KUB radiographs.
• A polyethylene glycol solution is administered orally at a rate of 10 to 20 ml/kg/h until the rectal effluent is clear and radiopacities have resolved.

ANTIDOTES

Succimer (Chemet)

• Indications
  • Succimer is the preferred treatment in children with BLLs higher than 45 µg/dl and less than 100 µg/dl without evidence of encephalopathy.
  • It is also used for treatment of children with BLLs of 25 to 45 µg/dl in many centers, but the precise application for this use varies.
  • In severe poisoning, succimer is used orally after initial stabilization with a parenteral chelator.
• Contraindications. Documented allergy to succimer precludes use.
• Method of administration
  • The clinician should ensure that lead exposure has ended and that there are no radiopacities on KUB radiographs prior to initiation.
  • The dose is 10 mg/kg (or 350 mg/m²) administered orally three times a day for 5 days followed by 10 mg/kg twice a day for 14 days. (The capsules contain microspheres that may be mixed into food or drink for consumption by small children.)
  • BLL is reassessed several days after completion of therapy and every 2 to 4 weeks thereafter until level stabilizes.
    • If BLL rebounds to 45 µg/dl or higher, the clinician should investigate whether repeat exposure has occurred.
    • If repeat exposure may have occurred, the patient is moved to lead-free housing and the course of chelation is repeated.
    • If repeat exposure has not occurred, the course of chelation is repeated.
    • If BLL rebounds to 20 to 45 µg/dl, treatment recommendations are uncertain; many centers would perform at least one more course of chelation.
• Adverse effects: Nausea, vomiting, sulfur odor to body fluids, mild transient elevation of transaminase levels, and rash.

EDTA (Calcium Disodium EDTA)

• Indications
  • Lead toxicity without CNS toxicity
  • Treatment of patients whose BLL is less than 100 µg/dl and who cannot tolerate oral medication
  • Severe lead toxicity or lead encephalopathy
    • EDTA should be used in conjunction with BAL (see SECTION III, British Anti-Lewisite chapter).
    • Severe lead poisoning is defined as (1) lead level higher than 100 "amp;#181;g/dl in a child, (2) evidence of CNS toxicity (seizure, altered mental status, encephalopathy), or (3) severe gastrointestinal effects precluding oral administration (severe abdominal pain and dehydration from recurrent vomiting).
• Contraindications. Documented allergy or renal failure.
• Method of administration
  • Lead poisoning without CNS toxicity
    • A continuous infusion of 1,000 mg/m²/day is administered over 24 hours or divided every 8 to 12 hours.
    • Dosage should not exceed 50 mg/kg/day.
    • EDTA is continued for 5 days, then is interrupted for 2 days to reassess the need for further chelation.
    • BLL is reassessed several days after completion of therapy and every 2 to 4 weeks thereafter until level stabilizes.
    • If BLL increases substantially, the clinician should investigate whether repeat exposure could have occurred in the interim.
    • If repeat exposure has not occurred, the course of chelation is repeated; however, succimer is the preferred drug if the patient can take medication orally.
    • If repeat exposure has occurred, the patient should be moved to lead-free housing and chelation repeated.
  • With CNS effects
    • First, BAL therapy is initiated (see SECTION III, British Anti-Lewisite chapter).
    • A continuous infusion of EDTA, 1,500 mg/m²/day, is administered over 24 hours.
    • A total dose of 75 mg/kg/day should not be exceeded.
• Adverse effects
  • Redistribution of lead to the brain. BAL is administered prior to EDTA, and EDTA is administered by continuous infusion if BLL is higher than 100 µg/dl or if there is evidence of encephalopathy.
  • Dose-related acute tubular necrosis. The recommended dose should not be exceeded.

British Anti-Lewisite (BAL, Dimercaprol)

• Indications. Parenteral treatment of severe poisoning with BLL higher than 100 µg/dl or evidence of encephalopathy.
• Contraindications
  • Allergy to BAL or peanuts or hepatic dysfunction precludes use.
  • BAL may cause hemolysis in glucose-6-phosphate dehydrogenase-deficient patients.
• Method of administration
  • A dose of 2.5 to 5 mg/kg is administered intramuscularly every 4 to 6 hours or 75 mg/m² intramuscularly every 4 hours.
  • The dose is tapered over 1 to 2 days to intervals of every 6 to 12 hours until an oral antidote can be tolerated.
  • It is discontinued after 5 days; sooner if severe adverse effects develop.
• Adverse effects. Headache, hypertension, tachycardia, fever, nausea, vomiting, pain at injection site.

D-Penicillamine

• Indications
  • It is a less effective, more toxic, and less expensive alternative to succimer.
  • It is used in some areas for treatment of children with BLL less than 100 µg/dl and without evidence of encephalopathy.
  • It is used after initial stabilization with parenteral chelator in patients with severe poisoning in some centers.
• Contraindications. Allergy, encephalopathy, or BLL higher than 100 µg/dl precludes use.
• Method of administration. A dose of 20 to 30 mg/kg/day is administered orally, divided four times a day up to 250 to 500 mg/dose.
• Adverse effects. Rash, fever, leukopenia, thrombocytopenia, eosinophilia, or hemolytic anemia may occur.

ADJUNCTIVE TREATMENT

• Encephalopathy is treated, as in other causes, with osmotic diuretics, corticosteroids, and control of fluid balance.
• Seizures are treated in the standard manner, beginning with benzodiazepine administration (see SECTION II, Seizure chapter).

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
• ANTIDOTES
  • Succimer (Chemet)
  • EDTA (Calcium Disodium EDTA)
  • British Anti-Lewisite (BAL, Dimercaprol)
  • D-Penicillamine
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

• BLL is repeated several days to 2 weeks after chelation and periodically thereafter to detect rebound or reexposure.
• Follow serial BLL in children with BLL higher than 10 µg/dl as indicated in Essential Tests section.

EXPECTED COURSE AND PROGNOSIS

• Children with mild to moderate poisoning (levels less than 60 or 70 µg/dl) have nonspecific symptoms but may sustain permanent, subtle intellectual impairment.
• Children with severe poisoning (BLL higher than 70 µg/dl, seizures, encephalopathy) are often left with neurologic impairment.
• Without aggressive chelation, children with encephalopathy may die.
• Developmental delay, hyperactivity, and learning disabilities are possible complications.

DISCHARGE CRITERIA AND INSTRUCTIONS

Patients may be discharged from the hospital to continue oral chelation when BLL is lower than 50 µg/dl, evidence of encephalopathy has resolved or stabilized, and a lead-free environment has been arranged.

PATIENT EDUCATION

• Homes with chipping, peeling leaded paint require remediation.
• Caregivers who work in the lead industry or who have hobbies that involve lead should shower and change clothes before returning home.
• Caregivers should avoid vacuuming hard floors and surfaces (because it stirs up lead dust) and to wash hard surfaces with phosphate-based detergents.
• Caregivers need to control pica behavior and make sure the children wash hands frequently especially before eating and avoid taking toys or other equipment outdoors.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA AND INSTRUCTIONS
• PATIENT EDUCATION

DIAGNOSIS

• A low threshold for evaluation of potential lead poisoning is important because children with BLL less than 60 µg/dl may suffer CNS injury but typically have few symptoms.
• Blood obtained by capillary stick may be contaminated with lead on skin; venipuncture is preferred.
• Screening children at risk is the most effective way to detect lead poisoning.

TREATMENT

BLL usually rebounds even after chelation; repeat courses are often needed.

FOLLOW-UP

• Ensuring a lead-free environment is often difficult and must be pursued vigorously.
• Levels may rebound even after repeated courses of chelation over months because most of the body burden of lead is stored in bone.

Section Outline:

• DIAGNOSIS
• TREATMENT
• FOLLOW-UP

Toxic effect of lead and its compounds.

See Also: SECTION II, Seizure chapter. SECTION III, British Anti-Lewisite, EDTA, d-penicillamine, Succimer, and Whole-Bowel Irrigation chapters.

RECOMMENDED READING

Bellinger DC, Leviton A, Waternaux C, et al. Longitudinal analysis of prenatal and postnatal lead exposure and early cognitive development. N Engl J Med 1987;316:1037-1043.

Bellinger DC, Stiles KM, Needleman HL. Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. Pediatr 1992;90:855-861.

Centers for Disease Control. Screening young children for lead poisoning: guidance for state and local public health officials. Atlanta, GA: Centers for Disease Control, February 1997.

Author: Katherine M. Hurlbut

Reviewer: Richard C. Dart