Lead Poisoning: Why Won't This Problem Go Away?

Lead is omnipresent and continues to cause serious health problems.

Lead—non-biodegradable, soft, malleable, and heat and corrosion resistant—is environmentally omnipresent. Its known properties made it an ideal metal for the automobile, paint, smelting, ceramics, plastics, and toy industries at one time^.1,2 Unfortunately, lead is toxic to humans. Humans neither need lead nor derive benefits from it. Although lead toxicity has been a global concern since the industrial revolution in the late 1800s, civilization has been unable to prevent or control it satisfactorily. Overall incidence of lead poisoning among American children has fallen from 4.4% in the early 1990s to 1.4% in 2004.3 In 2002, around 10 of every 100,000 of adults had lead toxicity.^4,5

Venous blood lead levels (BLLs) of 10 mcg/dL and 25 mcg/dL have been considered toxic in children and adults respectively.^4-7 Since any level of lead can cause toxicity, the CDC announced a new, lower reference value for children in June 2012: 5 mcg/dL. Infants and children absorb a higher fraction of lead than adults do when exposed, increasing their vulnerability.⁸ Approximately 450,000 American children have BLLs >5 mcg/dL.⁹ It is still a problem.

Diagnosis and Clinical Presentation

Lead exposure can start with prenatal maternal-fetal transmission.¹⁰ Outside the womb, children may inhale (or eat) lead dust, often present in street debris, soil, and most frequently, aged house paint.^11-14 Lead-based paint was phased out in the 1970s, lowering but not eliminating risk of exposure by this means.¹⁴ Old pipes sometimes leach lead into drinking water.^12,13 Lead hazards are disproportionately found in low-income housing.¹⁵ Adults rarely develop lead poisoning, but risk is increased in workers in industries that use or manufacture lead-based products.^16,17

Health care providers use many tests to identify lead poisoning. In addition to the BLL, a blood smear may show basophilic stippling ribosomal clusters.^18,19 Increased urinary aminolevulinic acid concentrations are also reliable indicators.²⁰ Plain film radiographs can reveal visible lead lines in patients’ long bones.^{10,12,17,19,21} Astute clinicians sometimes diagnose lead poisoning after seeing a blue line along patients’ gums (Burton’s line) that forms when lead reacts with sulfur ions released by oral bacteria.²²

Lead affects every organ system, causing an unpredictable variety of symptoms.^18,21-23 The nervous system is most sensitive (centrally in children, peripherally in adults),^24-26 but lead affects hematopoietic, hepatic, and renal systems, producing serious disorders. Acute lead poisoning’s classic symptoms include colic, encephalopathy, anemia, neuropathy, and Fanconi syndrome (abnormal glucose, phosphates, and amino acid excretion).^8,27 Sometimes, classic signs and symptoms are absent, confusing the clinical picture.

Chronic lead exposure is slowly progressive, creating cognitive and neurobehavioral abnormalities that irreversibly reduce IQ even if BLLs are well below the old CDC standard.¹⁵ Rising BLLs correlate with diminished achievement on intelligence tests.^6,28 Lower BLLs (from 3 mcg/dL to 8 mcg/dL) can cause mild IQ decreases or attention-deficit hyperactivity disorder. Higher levels (over 40 mcg/dL) may completely stop neurobehavioral development and cause toxic encephalopathy.^6,18,28 Adults can also develop cognitive and neurobehavioral consequences after an acute exposure or low-level, exposure for months to years.^29,30 Table 1 describes other neurologic symptoms.

In other systems, lead wreaks havoc. Anemia is a common problem—lead inhibits hemoglobin synthesis pathways and shortens erythrocyte life-span, which manifests as fatigue.^18,19 Hypertension may occur after acute or chronic exposure; ischemic coronary heart disease, cerebrovascular accidents, and peripheral vascular disease also can occur.^31-33 Acute nephropathy with hypertension, gout, and proximal tubule dysfunction are also common.¹⁸ If it becomes chronic, end-stage renal disease are possible.^18,20,34

Gastrointestinal symptoms (discomfort, constipation, or vomiting) may be vague and nonspecific at low exposures. Higher BLLs cause recurrent, severe abdominal pain called lead colic.^19,20

Lead poisoning manifests in the ocular system as cataracts.³⁵ Decreased libido, infertility, abnormal spermatogenesis or impotence,^17,18 and musculoskeletal and endocrine complaints are possible.^12,16

Strategy

Since many lead toxicities are irreversible, the best strategy is prevention, individual intervention, and public health coordination.^36-38 The main preventive measure is screening children at high risk. When prevention fails, clinicians use BLL to manage lead toxicity in children (Table 2).

Chelators increase urinary lead excretion and extract lead from blood and tissue, including the brain.

^36-38

If effective, they alleviate acute encephalopathy, vomiting, abdominal pain, anemia, and renal insufficiency. They cannot reverse neurologic complications.

^39-41

• Dimercaprol cannot be used in patients with hepatic insufficiency or peanut allergies. Caution is needed in children with renal impairment, hypertension, or G6PD deficiency. Adverse effects (AEs) include nausea and vomiting (N/V), headache, tachycardia, and leukopenia. Concurrent iron therapy will increase N/V, and must be stopped.^37,38
• Calcium disodium versenate is considered second line because it may increase CNS lead concentration and subsequently elevate intracranial pressure, but can be given intravenously (IV) or intramuscularly (IM). IV administration creates constant chelation and is less painful than IM. AEs include local injection site reactions, fever, hypercalcemia, renal insufficiency, and excretion of other essential minerals.^36-38
• Succimer is an oral water-soluble dimercaprol analogue associated with fewer AEs than parenteral chelators. AEs include rash, neutropenia, elevated transaminases, and gastrointestinal upset. Patients may object to succimer’s sulfur odor, and opening the capsules and sprinkling the beads onto food or dissolving in juice can help.^36-38
• The oral copper chelator D-penicillamine also chelates lead in children with low-level toxicity; this is an off-label use. AEs include nausea and vomiting, transient neutropenia and thrombocytopenia, rash, abdominal pain, and abnormal liver function. If drug-induced rash develops, therapy may need to be stopped. ^36-38,42 Chelation’s efficacy in adults with lead toxicity is unclear.¹⁷ Treatment starts with identifying the exposure source, removing it, then using chelation in patients with a BLL greater than 80 mcg/dL; between 60 and 80 mcg/dL with symptoms; or between 40 and 60 mcg/dL if symptoms continue after the exposure source is removed.⁴³

Why Won’t It Go Away?

Lead poisoning is more likely in low income areas, and in children who suffer from poor nutrition.⁴⁴ Lead is everywhere, and almost impossible to remove entirely from the body once it enters. There is no safe blood level and fixing this problem is very costly. This is why public health strategy is essential: it targets areas where lead poisoning is likely, and encourages preventive strategies like sequestering industries dealing with lead apart from inhabited areas and banning the use of lead when appropriate replacements are available.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance clinical writer.

References:

• Shevell M, Ashwal S, Donley D, et al. Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2003;60:367-380.
• Flora G, Gupta D, Tiwari A. Toxicity of lead: a review with recent updates. Interdiscip Toxicol. 2012;5:47-58.
• Center for Disease Prevention and Control. CDC’s Third National Report on Human Exposure to Environmental Chemicals: Spotlight on Lead. NCEH Pub 05-0664. Published July 2005.
• Roscoe RJ, Ball W, Curran JJ, et al. Adult blood lead epidemiology and surveillance--United States, 1998-2001. MMWR Surveill Summ. 2002;51:1-10.
• Center for Disease Prevention and Control. Adult blood lead epidemiology and surveillance--United States 2002. MMWR. 2004;53:578.
• Bellinger D, Sloman J, Leviton A, et al. Low-level lead exposure and children's cognitive function in the preschool years. Pediatrics. 1991;87:219-227.
• Roberts JR, Allen CL, Ligon C, Reigart JR. Are children still at risk for lead poisoning [published online November 14, 2012]? Clin Pediatr (Phila).
• Flora SJS, Flora G, Saxena G. Environmental occurrence, health effects and management of lead poisoning. In: José SC, José S, eds. Lead. Amsterdam: Elsevier Science BV; 2006:158-228.
• Centers for Disease Control and Prevention. CDC response to Advisory Committee on Childhood Lead Poisoning Prevention recommendations in “Low Level Lead Exposure Harms Children: A Renewed Call of Primary Prevention.” MMWR. 2012;61:383.
• Gomaa A, Hu H, Bellinger D, et al. Maternal bone lead as an independent risk factor for fetal neurotoxicity: a prospective study. Pediatrics. 2002;110:110-118.
• Adgate JL, Weisel C, Wang Y, et al. Lead in house dust: relationships between exposure metrics. Environ Res. 1995;70:134-147.
• Lanphear BP, Burgoon DA, Rust SW, et al. Environmental exposures to lead and urban children’s blood lead levels. Environ Res. 1998;76:120-130.
• Hurwitz RL, Lee DA. Childhood lead poisoning: exposure and prevention, and childhood lead poisoning: clinical manifestations and exposure. In: Rose BD, ed. UpToDate. Waltham, MA; 2007.
• Silbergeld EK. Implications of new data on lead toxicity for managing and preventing exposure. Environ Health Perspect. 1990;89:49-54.
• US Environmental Protection Agency. Fast Facts on Children’s Environmental Health. Washington, DC: 2008. http://yosemite.epa.gov/ochp/ochpweb.nsf/content/fastfacts.htm. Accessed December 11, 2012.
• Shih RA, Hu H, Weisskopf MG, et al. Cumulative lead dose and cognitive function in adults: a review of studies that measured both blood lead and bone lead. Environ Health Perspect. 2007;115:483-492.
• Goldman RH, Hu H. Adult lead poisoning. In: UpToDate. Rose BD, ed. Waltham, MA: 2007.
• Hu H, Watanabe H, Payton M, et al. The relationship between bone lead and hemoglobin. JAMA. 1994;272:1512-1517.
• Shiri R, Ansari M, Ranta M, Falah-Hassani K. Lead poisoning and recurrent abdominal pain. Ind Health. 2007;45:494-496.
• Patrick L. Lead toxicity, a review of the literature: part I: exposure, evaluation, and treatment. Altern Med Rev. 2006;11:2-22.
• Kuruvilla A, Pillay VV, Adhikari P, et al. Clinical manifestations of lead workers in Mangalore, India. Toxicol Ind Health. 2006;22:405-413.
• Pearce JM. Burton’s line in lead poisoning. Eur Neurol. 2007;57:118-119.
• Rischitelli G, Nygren P, Bougatsos C, et al. Screening for elevated lead levels in children and pregnancy: an updated summary of evidence for the US Preventive Services Task Force. Pediatrics. 2006;118:e1867-e1895.
• Cory-Slechta DA. Legacy of lead exposure: consequences for the central nervous system. Otolaryngol Head Neck Surg. 1996;114:224-226.
• Brent J. Review of: “Medical Toxicology.” Clin Toxicol. 2006;44:355-365.
• Bellinger DC. Lead. Pediatrics. 2004;113:1016-1022.
• Rastogi SK. Renal effects of environmental and occupational lead exposure. Indian J Occup Environ Med. 2008;12:103-106.
• Lanphear BP, Dietrich K, Auinger P, Cox C. Cognitive deficits associated with blood lead concentrations <10 mcg/dL in US children and adolescents. Public Health Rep. 2000;115:521-529.
• Schwartz BS, Byung-Kook L, Bandeen-Roche K, et al. Occupational lead exposure and longitudinal decline in neurobehavioral test scores. Epidemiology. 2000;16:106-113.
• Shih RA, Glass TA, Bandeen-Roche K, et al. Environmental lead exposure and cognitive function in community-dwelling older adults. Neurology. 2006;67:1556-1562.
• Martin D, Glass TA, Bandeen-Roche K, et al. Association of blood lead and tibia lead with blood pressure and hypertension in a community sample of older adults. Am J Epidemiol. 2006;163:467-478.
• Cheng Y, Schwartz J, Sparrow D, et al. Bone lead and blood lead levels in relation to baseline blood pressure and prospective development of hypertension. Am J Epidemiol. 2001;153:164-171.
• Navas-Acien A, Guallar E, Silbergeld EK, Rothenberg SJ. Lead exposure and cardiovascular disease--a systematic review. Environ Health Perspect. 2007;115:472-482.
• Muntner P, Menke A, Batuman V, et al. Association of tibia lead and blood lead with end-stage renal disease: a pilot study of African-Americans. Environ Res. 2007;104:396-401.
• Schaumberg DA, Mendes F, Balaram M, et al. Accumulated lead exposure and risk of age-related cataract in men. JAMA. 2004;292:2750-2754.
• American Academy of Pediatrics Committee on Environmental Health. Lead exposure in children: prevention, detection, and management. Pediatrics. 2005;116:1036-1046.
• Garcia RC, Snodgrass WR. Lead toxicity and chelation therapy. Am J Health-Syst Pharm. 2007;64:45-52.
• Hurwitz RL, Lee DA. Childhood lead poisoning: treatment. In: Rose BD, ed. UpToDate. Waltham, MA: 2007.
• Dietrich KN, Ware JH, Salganik M, et al. Effect of chelation therapy on the neuropsychological and behavioral development of lead-exposed children after school entry. Pediatrics. 2004;114:19-26.
• Perlstein MA, Attala R. Neurologic sequelae of plumbism in children. Clin Pediatr. 1966;5:292.
• Rogan WJ, Dietrich KN, Ware JH, et al. The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead. N Engl J Med. 2001;344:1421-1426.
• Liebelt EL, Shannon MW. Oral chelators for childhood lead poisoning. Pediatr Ann. 1994;23:616-626.
• Kosnett MJ, Wedeen RP, Rothenberg SJ, et al. Recommendations for the medical management of adult lead exposure. Environ Health Perspect. 2007;115:463-471.
• Hsu PC, Guo YL. Antioxidant nutrients and lead toxicity. Toxicology. 2002;180:33-44.