eMedicine Specialties > Radiology > Pediatrics

Lead Poisoning

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, Consultant Radiologist, North Manchester General Hospital, The Pennine Acute NHS Trust, Manchester UK
Coauthor(s): Usama Munir, MBBS, FRCS, Orthopedic Surgeon, Department of Surgery, Whiston Hospital, UK; Ian Turnbull, MB, ChB, MD, DMRD, FRCR, Lecturer, Department of Radiology, University of Manchester; Consulting Neuroradiologist, Hope Hospital, Salford, Manchester and North Manchester General Hospital, UK; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute
Contributor Information and Disclosures

Updated: Feb 3, 2009

Introduction

Background

Lead (Latin plumbum) is an element that has long been known, having been mentioned in the Book of Exodus. Alchemists believed that lead was the oldest metal, and they associated it with the planet Saturn.

Native lead occurs in nature, but it is rare. Lead is a bluish-white metal of bright luster. It is soft, highly malleable, and ductile; it is a poor conductor of electricity. Lead resists corrosion; in fact, lead pipes bearing the insignia of Roman emperors that were used as drains from the baths are still in service. In addition, lead is used in containers for corrosive liquids (such as sulfuric acid); it may be toughened by the addition of a small percentage of antimony or other metals.

Lead environmental pollution is a major health hazard throughout the world. Several mechanisms of lead poisoning have been identified. The most common are pica, industrial exposure, drinking moonshine liquor, inhalation, gunshot wounds, retained lead pellets or particles, and a variety of folk remedies and cosmetics.^1,2,3

The site and mode of action of lead had remained unsettled for over 2 centuries. With the advent of electrophysiology, it has become obvious that spinal cord involvement is the cause of lead neuropathy. The hypothesis of axonal degeneration in the dying-back variant, starting in the biochemical lesion of perikarya of the anterior horn cells in the spinal cord, is in full agreement with both the electromyographic signs of denervation and the electroneurographic normal range of conduction velocity. This presumptive conclusion confirming the spinal origin of human lead neuropathy is in line with the concepts of Tanquerel des Planches.^4,5

For excellent patient education resources, visit eMedicine's Poisoning Center. Also, see eMedicine's patient education article Poisoning.

Pathophysiology

Chemical characteristics of lead

In most of its chemical forms, lead may be toxic at the levels to which human beings are exposed in the workplace and in the general environment, whether exposure is by inhalation or ingestion in water or food.⁶

Lead and calcium are used interchangeably by bone. Lead has an affinity for bone and acts by replacing calcium. High concentrations of lead are deposited in growing bone; the greatest concentration of lead occurs in the metaphysis. In children, this deposition affects the distal femur, both ends of the tibia, and distal radii, because these are the most rapidly growing bones. Lead poisoning results in increased lead deposition in the trabeculae of the metaphysis; such deposition appears as opaque lead lines on radiographs. The human skeleton can store a reasonable quantity of lead in a relatively inert form. The absorption of lead from the gastrointestinal tract and the degree of lead retention vary widely, depending on the chemical environment of the gastrointestinal lumen, the age of the person, and the person's iron stores (nutritional status of the person).

Animal studies have shown that certain substances bind lead and increase its solubility, thereby enhancing its absorption. Sodium citrate, ascorbate, amino acids, vitamin D, protein and fat, and lactose increase lead solubility and hence its absorption. The human body has a 3-compartmental pool for lead metabolism: (1) blood; (2) skeleton; and (3) soft tissues, which include hair, nails, sweat, salivary, gastric and pancreatic juices, and bile. Bile is an important route of excretion in the gut. The primary site of lead absorption is the duodenum, where lead enters the epithelial mucosal cells. The total bodily amount of lead does not affect lead absorption, and lead does not have a feedback mechanism that limits absorption.

Effects of lead on the human body

Lead affects every system of the body. Acute exposure to high levels of lead may result in death or significant damage to the brain or other organs. Lead may affect children at lower levels than is necessary to affect adults. In children, the effects on the brain are worse than in adults, especially at higher levels (causing lead encephalopathy). In adults, the peripheral nervous system is commonly affected (peripheral motor neuropathy). This may lead to irritability, behavioral disorders, low intelligence quotient (IQ), ataxia convulsions, and coma in children and to wrist drop, foot drop, or lead colic in adults.

Studies confirm that exposure to lead causes renal damage, encephalopathy, and impaired cognitive function in children and in adults. Evidence indicates that children with levels less than 10 mcg/dL may have compromised development and intellectual performance later in life.

Nervous system

Lead disrupts the normal physiologic processes in the CNS, owing to the similarity of ionized lead to calcium; both are divalent cations. However, lead may disrupt the physiologic effects of calcium at concentrations lower than those of calcium. Lead intoxication affects the developing brain more severely. Lead causes an inappropriate release of neurotransmitter at rest and competes with calcium to interfere with evoked neurotransmitter release. This increase in basal release and the decrease in evoked release may interfere with selective pruning of synaptic connections in the brain during the first few years of brain development and may disrupt brain plasticity.

Glutamate is the most common neurotransmitter in the brain. It is always excitatory, usually through the presence of simple receptors that increase the flow of positive ions by opening ion channels. Glutamate stimulation is terminated by a chloride-independent membrane transport system that is used only for reabsorbing glutamate and aspartate across the presynaptic membrane. Glutamine is critical for learning in the developing brain. Lead interferes with glutamate, which is thought to be associated with neuronal development.

The receptor N -methyl-D-aspartate is responsible for the development of brain plasticity; it is blocked selectively by lead. This disrupts long-term potentiation, which compromises the permanent retention of newly learned information. Calcium is a physiologic activator of protein kinase C (PKC). Lead binds to PKC more avidly than calcium, causing further problems with neurotransmitter release. Impaired PKC function may also compromise the second-messenger systems within the cell, leading to changes in gene expression and protein synthesis. High blood lead levels (BLLs) impair endothelial cell function in the blood-brain barrier; this leads to hemorrhagic encephalopathy, characterized by seizures and coma.

Lead affects heme synthesis, causing microcytic anemia with a compensatory increase in the number of RBCs at low BLLs. Lead irreversibly bonds with the sulfhydryl group of proteins, causing impaired function without any discernible threshold. Delta-aminolevulinic acid dehydratase, which is a catalyst for the formation of the porphobilinogen ring, and ferrochelatase, which is responsible for the insertion of iron into the protoporphyrin ring, are both impaired by lead.

Low-level lead exposure has been linked to age-related kidney decline in renal function. Strong circumstantial evidence suggests a link between renal disease, hypertension, and gout with lead poisoning. Studies have shown that exposure to even low levels of lead may have hazardous effects on the kidneys and on the speed of progression of kidney failure.

Chronic lead nephropathy or chronic tubulointerstitial nephritis (as seen on biopsy) occurs in the setting of long-term lead exposure and is often associated with hypertension and gout. There are 3 forms of lead nephropathy:

• First is acute lead poisoning resulting from an acute, massive exposure to lead. This causes the classic symptoms of colic, encephalopathy, anemia, neuropathy, and Fanconi-type syndrome. Blood and urinary laboratory abnormalities are often diagnostic and are associated with acute intoxication.
• Second is chronic lead nephropathy, a slowly progressive interstitial nephritis caused by excessive cumulative exposure to lead. This is often associated with hypertension and gout; it is more difficult to diagnose because the laboratory changes of acute lead intoxication are not present. The typical clinical picture and the exclusion of other causes of renal disease aid in diagnosis.
• The third form is lead hypertension.

Any part of the CNS or peripheral nervous systems may be affected by lead intoxication, depending on the level and duration of exposure. The occurrence of motor neuron disease, peripheral neuropathy, and encephalopathy are not mutually exclusive disorders for patients suffering from the toxic effects of lead. Clinical and electrical evidence of subclinical involvement of peripheral nerves appears to be common in adults and children who are exposed to lead, as shown by measurements of motor nerve conduction velocity.

The toxic effects of heavy metals on the CNS are well known. Several metals have toxic effects on the neurons and on neurobehavior. Toxicity may manifest itself in developmental effects, or it may increase the risk of neurodegenerative diseases in old age. The major metals causing neurobehavioral effects after developmental exposure are lead and methyl mercury.

Lead exposure in young children results in a permanent loss of IQ of approximately 5-7 IQ points. It also results in a shortened attention span and in expression of antisocial behaviors. There is a critical period (age <2 y) for the development of these effects. After this, the effects do not appear to be reversible, even if BLLs are lowered with chelation.

Lead, mercury, manganese, and copper have also been implicated in amyotrophic lateral sclerosis and in Parkinson disease.⁷ A number of hypotheses have been put forward to explain the mechanism of lead toxicity on the CNS. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interfering with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and the binding of calcium ions.⁸

Winder et al reviewed the pathologic changes in the CNS of lead-exposed humans and laboratory animals.⁹ In humans, changes are related to relatively high exposure levels. In children, lead encephalopathy occurs with BLLs in the range of 100-800 mcg of lead per milliliter of blood. Edema, vacuolation, hemorrhage, and reactive glial changes appear to be secondary to microvascular lesions. No primary neuronal lesions have yet been clearly identified.

Neurologic signs and a pathologic picture closely resembling that seen in human lead encephalopathy are also noted in young lead-exposed rats with BLLs above 500 mcg/100 mL. Edema and hemorrhage, cyst formation, reactive glial changes, and nerve cell alterations are observed subsequent to changes in capillary endothelial cells and basement membranes. High-level lead exposure in rats produces disturbances in myelinated axons and may affect neural network formation in the CNS.

With intermediate lead levels (200-500 mcg/100 mL), vascular changes and their sequelae are not seen, but nutritional effects occur; these may produce neuropathologic changes. Data from studies on developing rats with low BLLs (up to 100 mcg/100 mL) appear to show effects of lead on maturing and differentiated nerve cell populations. The relevance of these changes to human subclinical lead intoxication remains unclear.

Otto and Fox studied the effects of lead exposure on sensory function; in particular, they studied subtle impairments of visual processes, auditory processes, or both that may have profound effects on learning.¹⁰ Evidence from both human and animal studies reveals that lead poisoning impairs auditory function. The cochlear nerve and more central structures are particularly sensitive to the toxic affects of lead in both developing and mature humans and in animals.

Elevations in hearing thresholds and increased latencies of brainstem auditory evoked potential have been reported at low to moderate levels of lead exposure. Higher doses of lead cause an increase in the threshold of the auditory nerve action potential, resulting in segmental demyelination and axonal degeneration of the cochlear nerve; they appear to have no effect on cochlear microphonics or structure.

Lead exposure affects both the retina and visual cortex of the developing and mature visual system. Low to moderate levels of lead exposure during development produce selective rod deficits that may be detected with electrophysiologic and behavioral techniques. At slightly higher levels of lead exposure, the visual cortex is affected. So far, rod-mediated visual functions have not been examined in children exposed to lead. Otto and Fox state that undetected sensory deficits of these kinds may have profound impact on the motor and mental development of children and also on the quality of life of affected adults.¹⁰

Cardiovascular system

Kopp et al described the overt clinical symptoms of cardiac and vascular damage, emphasizing the potentially lethal consequences of acute and chronic lead poisoning.¹¹ Previous studies showed cardiac morphologic, biochemical, and functional derangements in patients after exposure to excessive lead levels. Alterations in cardiac electrical and mechanical activity have been supported by autopsy evidence of myocardial morphologic and biochemical derangements after excessive exposure to lead in humans. Similar cardiovascular complications have been detected after excessive lead exposure in animals.

Reported cardiovascular disturbances linked to lead poisoning include the following: myocarditis; ECG disturbances; heightened catecholamine sensitivity; altered myocardial contractile responsiveness to inotropic stimulation; degenerative structural and biochemical changes affecting the musculature of the heart and vasculature; hypertension; hypercholesterolemia; atherosclerosis; and increased vascular reactivity to alpha-adrenergic agonists. Exposure to lead may increase the risk of hypertension.

The cardiovascular effects of subclinical lead poisoning are less certain. Chronic low-level lead exposure has been linked to hypertension and other cardiovascular disturbances in both clinical and experimental studies, although this relationship remains controversial. The mechanisms by which the cardiovascular system is affected by lead poisoning remains to be elucidated.

Zou et al have described impairment of systolic and diastolic cardiac function in individuals exposed to lead.¹²

Renal system

In the kidneys, exposure to lead may lead to Fanconi-like syndromes, chronic (lead) nephropathy, and gout associated with lead-induced hyperuricemia. Lead impairs heme synthesis and therefore may cause anemia.

Lin et al showed that low-level environmental lead exposure may accelerate progressive renal insufficiency in patients without diabetes who have chronic renal disease.¹³

Reproductive system

Lead not only reduces the sperm count in males but also increases abnormal sperm frequencies. At present, its role in male or female infertility is controversial. There is an association between high levels of lead exposure and adverse outcomes in pregnancy, but studies of women exposed to lower environmental levels of lead are needed.

Carcinogenesis

Lead has been classified as a group 2B carcinogen in animals. The National Toxicology Program classifies lead, along with its compounds, as beng reasonably anticipated to be a human carcinogen on the basis of limited studies in humans and more sufficient animal studies.¹⁴ The International Agency for Research on Cancer considers inorganic lead compounds as "probably carcinogenic to humans" on the basis of limited evidence in humans.¹⁵

Causes of lead poisoning

New information on the nature and extent of lead poisoning, as well as on sources of lead pollution, is relevant not only to the development of effective public health policy but also to clinical radiologists, who may be the first to raise the possibility of lead poisoning in a child.

Residential and environmental exposure

Deteriorated lead paint in older buildings remains one of the primary sources of lead in our environment. Lead was used in house paint until 1978 in the United States. The older the home, the more likely its paint has high levels of lead. Repairing a lead-painted home may release dangerous amounts of lead.

Although some sources of lead have been controlled, notably lead in gasoline, there are persistent lead sources associated with past uses of lead in paints, plumbing, and gasoline. In Baltimore, nearly 50% of children screened in 1993 had BLLs in excess of guidelines issued by the Centers for Disease Control and Prevention (CDC). Much of this exposure is associated with lead-based paint in housing.¹⁶

The use of lead in toys and paint for children's toys and furniture, nipple shields, foil and food wrappings and cans, cooking utensils, and gasoline has largely been eliminated. Lead-containing ointments, lotions, and dusting powder still remain possible sources of lead poisoning in infants.

Environmental exposure mainly occurs through the inhalation of lead dust; drinking water supplied through leaded pipes; and food that has been processed, preserved, or stored in containers made with lead. (See Lead in food and food containers, below.)

Occupational exposure

An estimated 90-95% of cases of elevated BLLs reported in the United States in the Adult Blood Lead Epidemiology and Surveillance program (ABLES) result from occupational exposures. The cars and homes of workers in the lead industry may become contaminated with lead dust, which may be carried on a worker's body, clothes, and shoes. Jobs that may expose a worker to lead include automobile radiator repair, construction, painting, and metal salvaging.

The major source of lead is occupational exposure from jobs dealing with lead and lead-based components; there is a high prevalence of lead toxicity in the population exposed to such activities. Occupational exposure of workers is seen in the manufacturing of lead batteries and cables, as well as rubber and plastic products. Soldering and foundry work, such as casting, forging, and grinding activities, are also associated with occupational exposures. Construction workers involved in painting or paint stripping, plumbing, welding, and cutting are also exposed to lead.

Gittleman et al showed that 12 (75%) of 16 children of lead-exposed workers in the battery reclamation industry had elevated BLLs.¹⁷  This study reported that the average BLL in these children was higher than that of neighborhood control subjects (22.4 vs 9.8 mcg/dL, P = 0.049). They reported that only a minority of workers showered or changed before going home.

Kaye et al conducted a study of the children of workers who manufactured ceramic-coated capacitors made with fritted glass that contained lead.¹⁸ The case-control study of 51 children younger than 6 years (20 exposed, 31 control subjects) showed higher average BLLs in the exposed children (13.4 vs 7.1 mcg/dL, P < 0.001).

A CDC report from California described workers involved in furniture refinishing and chemical stripping. The process was thought to be lead-free, but 6 workers and 3 of their children (aged 4-18 mo) had high levels of lead.¹⁹

Whelan et al conducted a case-control study of 50 children of construction workers (31 exposed, 19 control subjects); the children were younger than 6 years.²⁰ Approximately 25.8% of the workers' children had elevated BLLs, as compared with 5.3% of the children of control subjects (odds ratio = 6.1). The children's parents were inadvertently taking home lead dust on their skin and clothes.

Lussenhop et al and Nunez et al have shown that 18 children (<7 y) of parents who repaired radiators by soldering had a mean BLL of 10 mcg/dL.^21,22

Lead in food and food containers

Carney and Garbarino reported lead poisoning in a 7-year-old child after the consumption of cider.²³ The beverage was made in a maple-syrup evaporator that had lead solder joining the interior seams.

Eisenberg et al investigated symptomatic patients from the Middle East who had consumed lead-contaminated flour from lead fillings used in stone mills.²⁴ They examined 43 symptomatic patients 0-8 years of age, their families, and 563 children 10-18 years of age. The investigators found that 33 (23%) of 146 community stone mills had lead contamination and that 171 (30.4%) of 563 children had BLLs exceeding 30 mcg/dL.

The CDC (California) reported that 2 brothers 2 and 3 years of age, as well as their parents, had lead poisoning after consuming lozeena, which is an orange powder used to color rice and meat. This powder contains 7.8-8.9% lead. In addition, 9 of 18 extended family members had elevated BLLs.

Shannon and Graef reported lead intoxication in a 13-month-old infant after the child consumed infant formula that was made with contaminated tap water from copper pipes with lead solder.²⁵

The CDC (California) reported that 2 children younger than 6 years, 6 older children, and an adult had lead poisoning after eating Mexican candied jam made with tamarind.²⁶ During the manufacturing process, the candied jam was packaged in stoneware or terra cotta ceramic jars, which may leach lead.

Some clay cookware and dishes contain high levels of lead; the lead may be introduced during the glazing process or in decorations made with lead-containing pigments. In particular, some terra cotta pots and dishes from Mexico have a large lead content and should not be used as food containers. Glazed ceramic containers may be a source of lead poisoning when lead leaches into stored beverages, especially with acidic fruit juices. The risk is highest for improperly fired containers.²⁷ A lead test kit may be used to test ceramics for lead.

Bulk water-storage tanks may be a source of lead contamination if lead leaches from their soldered seams and brass fittings. A CDC report (Arizona and California) describes children 6, 12, and 14 months of age who experienced lead poisoning from such a source.²⁸

Dickinson et al described a family of 1 adult and 3 children 4, 5, and 14 years of age who had lead poisoning from lead leached from cocktail glasses.²⁹

Samovars (Iranian urns) are used extensively in central Asia for boiling water and making tea. Lead spot solder from the original manufacturing process may leach into water. Shannon has reported on a 10-week-old infant who experienced seizures and a 4-month-old child with lead poisoning who were given baby formula with water boiled in a samovar.³⁰

Lead-soldered kettles are a rare source of lead poisoning when water is boiled in such kettles used to make infant formula. Ng and Martin described a 3-month-old infant and a 1-day-old baby who had lead poisoning from such a source.³¹

Exposure to lead in home remedies

Traditional or folk remedies may contain lead and other heavy metal contaminants. Such remedies may be ingested for a variety of ailments; they should be considered possible sources of lead poisoning in adult patients who have no history of an occupational exposure to lead. Lead adulteration may occur in a variety of Asian remedies. Folk remedies and cosmetics from Bangladesh, India, Pakistan, Tibet, China, and Latin America may contain variable amounts of lead; examples include Alarcon, alkohl, azarcon, Bali goli, coral, gliasard, Greta, kohl, liga, pay-loo-ah, rueda, Koo Sar pills, and surma. Other sources of lead ingestion include contaminated ground paprika, ayurvedic metal-mineral tonics, Deshi Dewa (a fertility drug), hai gen fen (clamshell powder) added to tea, and pigment used in plastic wire insulation.

Azarcon is a bright orange powder that is 95% lead. Azarcon is also known as Alarcon, coral, luiga, Maria Luisa, and rueda. It is a Mexican folk remedy used to treat empacho, an illness believed to be caused by blockage of the gastrointestinal tract resulting in diarrhea and vomiting. Various fatalities have been reported from lead poisoning with its use.³²

Cheng et al examined 319 children 1-7 years of age who had consumed Ba-Baw-San, a Chinese herbal medicine used to treat colic pain and to pacify young children.³³ The researchers found increased BLLs (P = .038).

Bint Al Zahab is an Iranian folk remedy made by grinding rock into a powder and mixing it with honey and butter. This remedy is given to newborn babies for colic and for the early passage of meconium after birth. Rahman et al reported on 6 children 2 days to 3 months of age who had lead poisoning after the use of such a remedy.³⁴

Bint Dahab (Arabic for "daughter of gold") is yellow lead oxide used by jewelers and as a home remedy. McNiel and Reinhard reported on 10 children 7 days to 13 months of age who had lead poisoning associated with its use.³⁵

In Kuwait, bokhoor is a traditional practice of burning wood and lead sulfide to produce pleasant fumes to calm infants. Fernando et al reported on 4 children 16 days to 4.5 months of age who experienced lead poisoning through this practice.³⁶

Ghasard is an Asian Indian folk remedy that is used as a tonic to aid digestion. It is a brown powder. Death from lead poisoning has been reported in a 9-month-old child (CDC Report).³⁷

Jin Bu Huan is a Chinese herbal medicine used to relieve pain. It was reported to have caused lead poisoning in 3 children 13 months, 23 months, and 2.5 years of age.³⁸

Pay-loo-ah is a Vietnamese folk remedy that comes as a red powder. It may contain lead and is given to children to cure fever or rash. A report of a 6-month-old child with lead poisoning after its use appears in the literature.^39,40

Po Ying Tan is a Chinese herbal medicine used to treat minor ailments in children. Chan et al reported on a 4-month-old child who experienced lead poisoning after its use.⁴¹

Santrinj is an amorphous red powder containing 98% lead oxide. It is used principally as a primer for paint for metallic surfaces. In Saudi Arabia, santrinj is also applied as a home remedy for gum boils and for teething. McNiel and Reinhard reported the occurrence of lead poisoning in 10 children 7 days to 13 months of age; of these children, 7 took santrinj.⁴²

Surma is a black powder containing lead; it is used as an eye cosmetic and a teething powder on the Indian subcontinent. Ali et al conducted a case-control study of 62 children who had used surma and found that BLLs were increased in the children (P < 0.001).⁴³

Herbal vitamin preparations are used in China, India, Tibet, and other South Asian countries. Moore and Adler reported lead poisoning in 5-year old child after the ingestion of Tibetan herbal vitamin used to "strengthen the brain."⁴⁴

Abu Melha et al reported on 3 Saudi Arabian children 11, 22, and 44 months of age. The patients had lead intoxication after using an orange powder prescribed by traditional medicine practitioners for teething; this powder also has an antidiarrheal effect.⁴⁵

Use of Asian eye cosmetics

Kohl (Al Kohl) is a gray or black eye cosmetic that may contain up to 83% lead. It is applied to the conjunctival margins of the eyes in the Middle East, India, Pakistan, and parts of Africa. Besides the cosmetic affect, kohl is believed to strengthen and protect the eyes against disease.

Al-Saleh et al conducted a study of 538 girls 6-12 years of age and found that the application of kohl was associated with increased BLLs (P = 0.0461).⁴⁶

Eye cosmetics used in India and Pakistan often contain high levels of lead. These cosmetics are often applied to the eyes of children. Sprinkle retrospectively reviewed the medical records of 175 children 8 months to 6 years of age; he found the average BLL to be 4.3 mcg/dL for Pakistani or Indian children who did not use eye cosmetics; for those using eye cosmetics, the average BLL was 12.9 mcg/dL (P = 0.03).⁴⁷

Ali et al conducted a case-control study of 62 children who used surma and found that the children had increased BLLs (P < 0.001).⁴³

Accidental ingestion or inhalation of lead compounds

Biehusen and Pulaski reported lead poisoning in a 23-month-old child after the ingestion of a key chain containing lead.³⁵

Esernio-Jenssen et al reported severe lead poisoning in a 3-year-old child after the ingestion of a play watch made of lead.⁴⁸ The child required endoscopy.

Blank and Howieson reported the deaths of a 23-month-old child and a 2-year-old child after the ingestion of lead-containing curtain weights.⁴⁹

Fishing sinkers are often made of lead. Mowad et al reported a case of an 8-year-old child who experienced lead poisoning after ingesting a lead-containing fishing sinker.⁵⁰

Lead bullets and lead shots that are lodged in body tissues or that are accidentally ingested may cause lead intoxication.^17,51,52,53

Eastwell reported high BLLs in 6 of 7 siblings 10-17 years of age who sniffed gasoline.⁵⁴

Imported vinyl miniblinds manufactured before 1996 were made with lead. The lead becomes a hazardous dust on the surface of the blinds. Children would touch the blinds with their hands, which they then put in their mouths. Washing the blinds does not make them safe. Norman et al reported on 92 children 6-72 months of age; he attributed 9% of the cases of lead poisoning to exposure to vinyl miniblinds.⁵⁵

Perkins and Oski reported elevated BLLs in 6-month-old breast-fed infants.⁵⁶ The infants inhaled lead released from a burning log made of newsprint.

Miller et al reported on 2 children 27 and 28 months of age who experienced elevations in elevated BLLs after exposure to lead contained in pool cue chalk.⁵⁷

Atypical Sources

A variety of atypical sources of lead poisoning in children in the United States was reviewed with an objective of increasing awareness of poisoning from these sources. The authors formulated a questionnaire that may assist in the identification of atypical lead sources in the home. The sources include fashion accessories, folk remedies, imported condiments and candies, pellets and bullets, and recreational and domestic items.⁵⁸

Frequency

United States

The exact incidence of lead poisoning is not known, but the incidence in children in the United States has declined sharply over the past 3 decades as a result of public education and sustained effort from governmental agencies to publicize the dangers of lead.

International

Lead is the number 1 environmental pollutant worldwide, causing health hazards. The exact incidence is not known. Regional variations are related to industrial pollution, environmental factors, and cultural factors such as the use of lead-containing folk remedies and cosmetics.^59,60,61 (See also Mortality/Morbidity, below.)

Mortality/Morbidity

Mortality from lead toxicity is rare in developed countries, especially the United States. However, because of its widespread effects in the body and because of inadequate measures to control its use in developing countries, the morbidity rate associated with it is still high.

A relatively inexpensive and effective way to reduce the substantial morbidity that results from widespread lead exposure is the fortification of a variety of foods with low levels of calcium. This approach may complement other efforts to prevent lead exposure and reduce lead toxicity.

• An MMWR Morbidity and Mortality Weekly Report from New Hampshire concluded that fatal pediatric lead poisoning was rare in the United States because of multiple public health measures that have reduced BLLs in the population.⁶² However, the report concluded that the risk of elevated BLLs among children remains high in some neighborhoods and populations; among those at risk are children living in older housing with deteriorated lead paint. The report described the investigation of the first reported death of a child from lead poisoning since 1990. The investigation implicated lead paint and dust in a home environment as the most likely source of the poisoning.
• McDonald and Potter examined the case records of 454 pediatric hospital patients with lead poisoning between 1923 and 1966.⁶³ The cases were followed to 1991 to examine possible mortality effects. Numbers of observed deaths were compared with those expected based on the rates of the US population. A total of 86 deaths were observed (observed-to-expected [O/E] ratio = 1.7, 95% confidence interval [CI] = 1.4-2.2). Among these, 17 were attributed to lead poisoning. The mortality rate from all cardiovascular diseases was elevated (O/E = 2.1, 95% CI = 1.3-3.2), and cerebrovascular deaths were particularly common among women (O/E = 5.5, 95% CI = 1.1-15.9). Among men, 2 deaths resulted from pancreatic cancer (O/E = 10.2, 95% CI = 1.1-36.2), and 2 deaths resulted from non-Hodgkin lymphoma (O/E = 13, 95% CI = 1.5-46.9). Chronic nephritis was not a significant cause of death.Despite limitations in the data, the pattern of mortality suggests that the effects of lead poisoning in childhood may persist throughout life and that the effects in men and women may be different.
• Kaufmann et al evaluated trends in lead poisoning–related deaths in the United States between 1979 and 1998.⁶⁴ The predictive value of relevant codes from the International Classification of Diseases, Ninth Edition (ICD-9) was also evaluated. Multiple cause-of-death files were sought from records containing relevant ICD-9 codes, and underlying causes and demographic characteristics were assessed. For the period 1979-1988, death certificates were reviewed; lead source information was abstracted, and accuracy of coding was determined. An estimated 200 lead poisoning-related deaths occurred in the period 1979-1998. Most were among males (74%), blacks (67%), adults 45 years of age or older (76%), and Southerners (70%). The death rate was significantly lower in more recent years. An alcohol-related code was a contributing cause in 28% of adults. Only 3 of 9 ICD-9 codes for lead poisoning were highly predictive of lead poisoning – related deaths. The authors concluded that death rates for persons with lead poisoning have dropped dramatically since previous decades and are continuing to decline. The findings imply that moonshine ingestion remains a source of high-dose lead exposure in adults.
• Elliott et al examined the occurrence of clinical lead poisoning in England based on routine sources of data. They assessed 3 routine data sources over different periods according to the availability of data: (1) mortality for England in 1981-1996; (2) hospital episode statistics data for England for the 3 years (April 1, 1992, to March 31, 1995); and (c) statutory returns to the Health and Safety Executive under the reporting of injuries, diseases, and dangerous occurrences regulations (RIDDOR) (April 1, 1992, to March 31, 1995). Analyses of BLLs from 1991-1997 were also examined. The analyses were performed for both industrial screening purposes and in cases of suspected lead poisoning. The authors concluded that both mortality and hospital admissions ascribed to lead poisoning in England were rare but that cases continue to occur and some seem to be associated with considerable morbidity. Lead poisoning was confirmed as a probable cause of clinical signs and symptoms in only a small proportion of those in whom a BLL test was requested.

Race

No statistics support the fact that one race is more biologically predisposed to lead toxicity than another. However, socioeconomic conditions such as poor diet and poverty are clearly associated with chronic lead poisoning. Therefore, certain groups, such as African-American children living in low-income urban centers in homes with decaying lead-based paint, are clearly at increased risk of lead poisoning.⁶⁵

• Black non-Hispanic children have a greater risk of developing lead poisoning than others. The Health and Nutrition Examination Surveys from 1997 reports a prevalence of 21.9% among black non-Hispanic children living in homes built before 1946, a rate of 13.7% in those living in homes built in 1946-1973, and a rate of 3.4% in those living in homes built after 1973.
• The comparative prevalence among Mexican-American children is 13%, 2.3%, and 1.6% for those living in homes built before 1946, those living in homes built 1946-1973, and those living in homes built subsequent to 1973, respectively. For white non-Hispanic children, the respective rates are 5.6%, 1.4%, and 1.5%.
• Surma is a lead-based cosmetic used in India and Pakistan and may be a source of lead. Kohl is a widely used traditional cosmetic in the Middle East, Asia, and Africa, used mainly around the eyes. Lead was a predominant constituent of kohl, with lead content levels of 2.9-100%. The predominance of lead in kohl preparations is of major concern because of the documented adverse effects in humans and the increased susceptibility of children to lead intoxication. Exposure to lead-containing kohl should be considered in patients with symptoms of lead intoxication who come from regions where its use is prevalent.

Sex

Men are generally thought to be affected more often than women because they are more involved in professions associated with lead exposure. Data suggesting any difference in the sex distribution in children are limited.

Age

Lead poisoning is primarily considered a pediatric problem related to the habit of chewing on cribs, toys, furniture, and fallen paint flakes containing lead. In societies in which folk remedies are frequently used, children may be unwittingly exposed to lead. Parents, siblings, and caregivers who work in lead-related occupations may also expose children to toxic levels of lead. (See also Special Concerns, below.)

• Other risk factors for children include age younger than 6 years, low income, and urban dwelling. Maternal exposure to lead decades before pregnancy may subsequently result in exposure of the developing fetus to elevated levels of lead. Moreover, the lead concentration in maternal blood has been shown to increase during pregnancy and lactation because of the mobilization of stored lead from bone; typically, lead is found at higher concentrations in milk than in maternal plasma. The lead in maternal blood readily crosses the placenta and enters the brain of the fetus.
• Some studies have suggested that even low levels of exposure may harm not only the young and the occupationally exposed but also older people. This is because older people may have had more exposures to lead; moreover, they may have been exposed while working in unregulated occupations or environments. Several large epidemiologic studies have found that the level of lead in blood and bone is higher in older people than in those of younger adults.
• Children living in older homes where there is lead-based paint are particularly at risk for lead toxicity. Young children who are independently mobile are at greatest neurologic risk from chronic exposure to low or moderate levels of lead. Children younger than 3 years are at particular risk because they are more likely to put lead-containing items in their mouths and to swallow paint chips (pica). The long-term effect of lead exposure is maximal during the first 2 or 3 years of life, when the developing brain is in a critical formative stage.

Anatomy

The human body contains approximately 120 mg of lead; daily intake should not exceed 500 mcg. Lead has a half-life of approximately 62 years.

Most human exposures to lead occur via ingestion, but in some cases, inhalation is the mode of entry into the body. Almost all inhaled lead is absorbed, whereas from 20-70% of ingested lead is absorbed (in children, the percentage of lead that is absorbed is generally higher than in adults). The absorption of lead and its effects in the body mainly depend on physiologic characteristics of the exposed person, including nutritional status, health, and age. Adults may absorb 20% of the ingested lead, whereas children and pregnant women may absorb as much as 70%.

Once in the body, the kidneys and liver rapidly excrete lead. Absorbed lead that is not excreted gets distributed into blood, soft tissues, and bones. Approximately 99% of the lead in blood is associated with RBCs (erythrocytes); the remaining 1% resides in blood plasma. The level of lead in the blood is also important because the BLL is the most widely used measure of lead exposure. From the blood, lead accumulates in soft tissues and bones. The liver, kidney, lungs, and brain bear most of the burden.

Most of the retained lead in the human body is ultimately deposited in bones. The bones and teeth of adults contain about 94% of their total lead body burden; in children, the percentage is approximately 73%.

In bones, lead is mainly distributed to those areas that are rapidly undergoing growth and calcification; growth and calcification occur predominantly in trabecular bone in childhood in the metaphyseal portion of the bone. During metaphyseal bone formation in children, lead and calcium are deposited to produce the increased bone densities (lead lines), seen radiographically at the metaphysic, thereby providing evidence of increased body stores of lead in children.

The growth plate may be one of the key target tissues, accounting for the adverse effects of chronic lead exposure on skeletal development; studies have shown that lead inhibits growth-plate development. Bones, teeth, hair, and nails represent a tightly bound pool of lead that is not generally regarded as harmful. By contrast, the amount of lead in the brain, liver, kidneys, and bone marrow is directly related to its toxic effects.

Presentation

After exposure to lead, the clinical presentation may take an acute or chronic form, depending on the degree, rapidity, and mode of exposure. After an acute exposure to high levels of lead, patients may present with lethargy; their condition may progress to coma and seizures, leading to death.

With appropriate medical management, death is now uncommon; however, long-term sequelae may ensue. Long-term sequelae in children include lower IQ scores, learning difficulties, impairment of attention, impairment of fine motor coordination, and impairment of both receptive and expressive language. Abnormalities in verbal comprehension and auditory processing have also been reported in affected children.

Prospective cohort studies have demonstrated effects with BLLs as low as 10 mcg/dL. These effects may occur regardless of socioeconomic group; a loss of 3 IQ points may be experienced for every 10 mcg/dL BLL above 10 mcg/dL.

Clinical findings

Lead intoxication has no pathognomonic symptoms. A meticulous environmental history is necessary in patients suspected of being exposed to lead. Lead poisoning should be considered whenever a child presents with peculiar symptoms that do not match any particular disease.

The clinical presentation is variable in terms of symptoms and depends on the child's age, degree of exposure, and duration of exposure. Younger patients tend to be affected more than older children and adults because lead is absorbed more effectively from the gastrointestinal tract of children than from the gastrointestinal tract of adults. Despite elevated BLLs, most children have no symptoms. In general, children with this finding are periodically screened.

Signs and symptoms include the following:

• Irritability and temperamental lability in children
• Behavioral disorders
• Altered activity levels: hyperactive or excessive lethargy
• Sleeplessness
• Delayed developmental milestones
• Delay in the development of language skills
• Poor appetite
• Headaches
• Vomiting
• Constipation
• Abdominal pain
• Ataxia
• Somnolence, seizures, stupor, and coma

In adults, cognitive dysfunction is more prominent, particularly with acute exposure, although symptoms similar to those in children may occur. Motor neuropathy (eg, foot and wrist drop), delirium, and hallucinations are more common in adults.

Results of physical examination and other tests

Neuropsychological testing provides the best measure of a patient's cognitive impairment. This is an effective way to track improvement in attention, visual-spatial abnormalities, and memory as a result of therapy, as well as to establish the extent and nature of long-term impairment.

No physical stigmata of lead poisoning may be present, but children with lead toxicity are frequently iron deficient and may be pale because of anemia. Children may be hyperactive or lethargic. Subtle changes in cognitive performance are not easily identified on physical examination.

Lead lines at the gingival margins are more common in adults and unusual in children, because the dentition of children does not promote hygiene poor enough to produce pyorrhea and the subsequent precipitation of lead sulfide. Adults with poor dental hygiene may have this finding, which is characteristic of heavy metal poisoning. Impaired fine-motor coordination or subtle visual-spatial impairment may be seen. In adults, chronic distal motor neuropathy may occur, characterized by decreased reflexes and weakness of extensor muscles. Sensory function is usually spared in patients with lead poisoning.

Hwang et al studied the clinical, biochemical, hematologic, and erythrokinetic profile of 63 patients with chronic industrial exposure to lead.⁶⁶ The most common findings were abdominal pain (62%); gingival lead lines (48%); headache, dizziness, or both (33%); muscle cramps (32%); anemia (19%); and fatigue (18%). Colicky abdominal pain (27%) and gingival lead lines were correlated with urinary lead excretion. Anemia was mild and was more frequent in the patients with the greatest urinary lead excretion.

Other associated findings were the following: increased reticulocyte counts and basophilic stippling of the RBCs; more sideroblasts and greater erythroid hyperplasia of the bone marrow; a reduction in chromium-51–tagged RBC survival time; smaller RBC mass; a more rapid plasma iron clearance; a greater plasma iron turnover; and greater utilization of iron-59 in patients with urinary lead excretion of greater than 100 mcg/d, in comparison with the remainder of patients and with healthy control subjects. Their findings suggest that minimal chronic exposure to lead causes an increase in hemolysis, with a resultant increase in the production of erythrocytes.

Heavy metals, such as lead and mercury, cause damage to the nervous system; such damage manifests differently in children and adults. Other toxins, both endogenous and exogenous, usually have the same effect upon the nervous system in persons of all ages.

Wong and associates reported on a 2-month-old girl with acute lead poisoning who demonstrated electrophysiologic evidence of neurotoxicity.⁶⁷ Motor nerve conduction studies of the median, ulnar, peroneal, and posterior tibial nerves revealed both axonal and demyelinating neuropathy. Somatosensory evoked potential studies of the median and posterior tibial nerves demonstrated evidence of cortical involvement. Brainstem auditory evoked potentials suggested the possibility of acoustic nerve involvement, but there was no evidence of a brainstem lesion. Postmortem examination revealed cerebral edema and focal segmental demyelination of the median nerve.

Importance of the differential diagnosis

Horing and associates reported on a 36-year-old woman who had progressively marked and diffuse abdominal pain of 2 months' duration. The pain was at times colicky. The patient also had nausea, vomiting, and severe constipation. Paresthesias and motor weakness developed in the thighs; this was accompanied by a normochromic, normocytic anemia, with a hemoglobin concentration of 9.6 g/L.

A short time after presentation, the patient's mother and daughter also fell ill with similar symptoms. After symptomatic treatment failed, secondary coproporphyria caused by lead poisoning was found. The poisoning had resulted from criminal contamination of food, especially cocoa powder, with lead acetate. Increased serum lead concentrations were found in 2 other family members.

All of these patients underwent treatment with sodium calcium edetate (20 mg/kg) in several 3-day cycles. This course resulted in a gradual decrease in serum lead concentration. When the level had fallen to below 4 μmol/L, the symptoms disappeared. At levels below 3 μmol/L, porphyria was no longer demonstrable, and the anemia regressed. The authors pointed out that lead poisoning should be considered in the differential diagnosis of acute abdominal colic of unclear cause, especially because it can be fatal.

Dequanter and associates described a case of lead poisoning in a 44-year-old man who presented with acute right upper quadrant pain.⁶⁸ The initial diagnosis was acute cholecystitis. However, after further questioning and after taking a detailed history, the diagnosis of lead poisoning was entertained; this diagnosis was confirmed by means of biochemical examination. This case emphasizes the need to include lead poisoning in the differential diagnosis of abdominal pain.

Lead arthropathy may be a cause of delayed-onset lead poisoning. Bullet fragments that are retained within the body usually have no clinical sequelae.

Peh and Reinus described 3 patients with bullets retained in their hip joints. One patient, who had extensive, ground, intra-articular bullet fragments and secondary osteoarthritis of the hip, presented with signs and symptoms consistent with lead intoxication; laboratory data were also consistent with that diagnosis The bullet and metallic fragments were removed surgically, and the patient experienced a good clinical response. Two patients whose bullets were entirely within the femoral head and whose joints showed lesser degrees of lead fragmentation had no symptoms of lead intoxication. The degree of intra-articular fragmentation of the bullet and the increase in the surface area by which the lead was exposed to synovial fluid were emphasized as decisive factors with respect to appropriate therapy.

Sensirivatana and associates described a case of an unusual manifestation of lead encephalopathy in a 2-month-old child.⁶⁹ The child presented with metallic, brownish discoloration of the nails and a subdural effusion.

The total-body lead burden and the efficacy of treatment may be assessed by performing a provocative chelation test. The test involves obtaining a timed urine collection after administering a dose of calcium disodium edetate (a chelating agent). However, the potential dangers of such provocative chelation have led to a decrease in its use.

Radiologic differential diagnoses

Albers and Bromberg reported a case of X-linked bulbospinomuscular atrophy, or Kennedy disease, masquerading as lead neuropathy.⁷⁰ They described a 43-year-old man who was referred by a veterinary surgeon who evaluated the man's dog for a seizure; the veterinarian suspected a toxic lead exposure in both the dog and its owner. The patient had worked on refurbished houses, removing old paint, and complained of decreased cognition, fatigue, and muscle cramps. He had a depressed affect, postural tremor, right-arm weakness with partial denervation on electromyelography, and borderline-low sensory nerve action potential amplitudes. A mild anemia and elevated serum and urine lead levels supported a diagnosis of lead neuropathy.

Chelation therapy led to an increase in urine lead excretion without symptomatic improvement. The patient's brother worked part-time with him and developed similar findings; in addition, the brother had difficulty chewing and experienced dysphagia, perioral twitching, gynecomastia, and multifocal denervation of extremity and facial muscles. The brother's lead levels were not elevated; an androgen receptor mutation identified on the X chromosome in both brothers confirmed the diagnosis of X-linked bulbospinomuscular atrophy.

Osteosclerotic metaphyseal dysplasia

Mennel and John reported a case of a 23-month-old boy with osteosclerotic metaphyseal dysplasia (OMD).⁷¹ The patient presented with hypotonia, developmental delay, and complex seizures. Radiographs revealed profound sclerosis of the metaphyses and epiphyses of the long and short bones in the extremities, with a unique pattern of distribution. Sclerosis involved the anterior ribs, iliac crests, talus, and calcaneus. The skull and vertebral bodies appeared unaffected.

The overall appearances were suggestive of lead poisoning. BLLs were normal. OMD is a rare sclerosing bone disorder inherited in an autosomal recessive manner. The syndrome is clinically characterized by developmental delay of a progressive nature, hypotonia, elevated alkaline phosphatase levels, and late-onset spastic paraplegia. Analysis of the metaphyseal bone changes should help distinguish OMD from lead poisoning and other causes of metaphyseal sclerosis.

Preferred Examination

Plain skeletal radiographs have been used extensively in the diagnosis of lead poisoning in children. These images have been found to be reliable in young infants presenting with an unexplained encephalopathy. A radiograph of the knee showing dense metaphyseal bands strongly supports the diagnosis of lead poisoning. Plain radiography of the knee is an inexpensive and widely available investigation that may be rapidly performed.

In select cases, abdominal radiographs may demonstrate paint chips or other objects. The presence of lead foreign bodies in the gastrointestinal tract (caused by pica) may highlight the diagnosis and prompt immediate intervention. Plain abdominal radiographs may also guide therapy (eg, by allowing the prevention of further absorption through gastrointestinal decontamination).

Neuroimaging, as with CT and MRI, plays a minor role in the diagnosis of lead poisoning. However, cerebral edema and microhemorrhages may be seen in patients presenting with encephalopathy. With chronic exposure to lead, patchy calcifications may be seen on CT scans in adults. Anecdotal reports of angiography and ultrasonography have appeared in the literature; these modalities have been used in the diagnosis of lead poisoning.

Limitations of Techniques

A normal skeletal radiograph does not rule out lead poisoning in children. The differential diagnosis for cases involving opaque metaphyseal lines is wide and includes poisoning with other heavy metals; hypervitaminosis D; and the healing stages of leukemia, rickets, and scurvy.

Neuroimaging, as with CT and MRI, is expensive and the availability is limited, particularly with regard to MRI. Young children undergoing CT or MRI may need heavy sedation or general anesthesia. A finding of disruption of brain plasticity, as seen on MRIs, is not a finding unique to lead intoxication. Other clinical disorders, such as metabolic and epileptic encephalopathies and psychosocial deprivation, may be associated with disrupted brain plasticity. Several mental retardation syndromes and cognitive disorders have been recognized as being secondary to genetic disruption of intracellular signaling cascades.

Differential Diagnoses

Other Problems to Be Considered

Clinical differential diagnoses

Acute confusional states
Acute memory loss disorders
Epilepsy
Encephalopathies
Frontal lobe syndromes
Depression
Attention deficit hyperactivity disorder
Learning disorder
Developmental delay
Language disorder
Autism or pervasive developmental disorder
Organic solvent poisoning
Other heavy-metal poisoning
Radial mononeuropathy and other peripheral neuropathies
Diabetic neuropathy
Anemias, acute and chronic
Constipation
Guillain-Barré syndrome

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