AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

Background

Lead (Anglo-Saxon, lead; Latin plumbum) is long-known element, having been mentioned in Exodus. Alchemists believed that lead was the oldest metal and associated 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, ductile, and a poor conductor of electricity. Lead resists corrosion, and 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 sulphuric acid) and 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.

About 160 years ago, a young but distinguished French scientist L. Tanquerel des Planches published a comprehensive work dealing with almost every known clinical, epidemiological, and occupational aspect of lead poisoning. On the basis of his accumulation of human cases of lead palsy, he postulated that the neurotoxic action of lead on the spinal cord is of outstanding importance.

The site and mode of action of lead had remained unsettled 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.

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 can be toxic at the levels to which human beings are exposed in the workplace and in the general environment, whether by inhalation or ingestion in water or food (DeMichele, 1984).

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. Thus, in children, this deposition affects the distal femur, both ends of the tibia, and distal radii, as these are the most rapidly growing bones. Lead poisoning results in increased lead deposition in the trabeculae of the metaphysis, appearing 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 lead and the degree of lead retention varies widely depending on the chemical environment of the gastrointestinal lumen, the age of the person, and the iron stores (nutritional status of the subject).

Animal studies have shown that certain substances bind lead and increase its solubility, 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 can result in death or significant damage to the brain or other organs. Lead can affect children at lower levels than those in adults. In children, the effects on brain are worse, especially at higher levels (lead encephalopathy). In adults, the peripheral nervous system is commonly affected (peripheral motor neuropathy). This can 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 so far confirm that exposure to lead causes renal damage, encephalopathy, and impaired cognitive function in children and in adults. Recent evidence indicates 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 due to the similarity of ionized lead to calcium, as both are divalent cations. However, lead can 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 decrease in evoked release may interfere with selective pruning of synaptic connections in the brain during the first few years of brain development and disrupt brain plasticity.

Glutamate is the most common neurotransmitter in the brain. It is always excitatory, usually due to 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 the glutamate, which is thought to be associated with neuronal development.

The receptor N-methyl-D-aspartate is responsible for the development of brain plasticity and 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 can bind to PKC more avidly than calcium, which causes 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 leading to hemorrhagic encephalopathy, characterized by seizures and coma.

Lead can affect 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 the age-related kidney decline in renal function. Strong circumstantial evidence also suggests a link between renal disease, hypertension, and gout with lead poisoning. Recent studies show that exposure to even low levels of lead may have potentially 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. Lead nephropathy is recognized in 3 forms. First is acute lead poisoning due to 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 associated with acute intoxication. Second is chronic lead nephropathy, a slowly progressive interstitial nephritis due to an excessive cumulative exposure to lead. This is often associated with hypertension and gout and 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 can 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 affects of heavy metals on the CNS are well known. Several metals have toxic effects on the neurons and neurobehavior. Toxicity can be expressed either as developmental effects or as an increased 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 and also results in a shortened attention span and expression of antisocial behaviors. There is a critical time 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 Parkinson disease (Carpenter, 2001). 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 interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions (Clarkson, 1987).

Winder et al reviewed the pathologic changes in the CNS of lead-exposed humans and laboratory animals. Data in man 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 consequent to changes in capillary endothelial cells and basement membranes. High-level lead exposure in rats also 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 recent 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 subtle impairments of visual and/or auditory processes that can have profound effects on learning. 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 experimental animals.

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

Lead exposure also 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 can 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 lead-exposed children. 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.

Cardiovascular system

Kopp et al emphasized the overt clinical symptoms of cardiac and vascular damage with potentially lethal consequences of acute and chronic lead poisoning. Previous studies have shown cardiac morphological, biochemical, and functional derangements in patients after exposure to excessive lead levels. Cardiac electrical and mechanical activity alteration has 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 experimental 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 lead to an increased risk of hypertension.

The cardiovascular effects of subclinical lead poisoning are less certain. Chronic low-level lead exposure has also 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 shown impaired systolic and diastolic cardiac function in individuals exposed to lead.

Renal system

In the kidneys, lead can give rise to Fanconi-like syndromes, chronic (lead) nephropathy, and gout due to lead-induced hyperuricemia. Lead impairs heme synthesis and therefore can give rise to 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.

Reproductive system

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

Carcinogenesis

Lead has been classified as group 2B carcinogen in animals, but data to support its role in human carcinogenesis are insufficient.

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 allowed 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 can 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 City, 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 (Silbergeld, 1996).

The use of lead in toys and paint for children's toys and furniture, nipple shields, foil and food wrappings and cans, and 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 lead dust inhaling, drinking water supplied through leaded pipes and consuming food 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. Workers in lead industry can contaminate theirs car and home with lead dust carried on their 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, resulting in high prevalence of lead toxicity in the population exposed to such activities. Occupational exposure to workers is seen in industries such as lead battery, cable, rubber and plastic, soldering, and foundry work such as casting, forging, and grinding activities. 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 (battery reclamation) had elevated BLLs and a higher average BLL than that of neighborhood control subjects (22.4 vs 9.8 mcg/dL, P = .049). They reported that only a minority of workers showered or changed before going home.

Kaye et al conducted a study on the children of workers on ceramic-coated capacitors made with fritted glass containing lead. The case-control study of 51 children younger than 6 years (20 exposed, 31 control subjects) showed higher average BLLs in exposed children (13.4 vs 7.1 mcg/dL, P <.001).

In 1998, 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.

Whelan et al conducted a case-control study of 50 children younger than 6 years (31 exposed, 19 control subjects) of construction workers. Approximately 25.8% of the workers' children had elevated BLLs compared with 5.3% of the children of control subjects (odds ratio = 6.1). These 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 did soldering to repair radiators had a mean BLL of 10 mcg/dL.

Lead in food and food containers

Carney and Garbarino have reported lead poisoning in a 7-year-old child after the consumption of cider. 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. They examined 43 symptomatic patients aged 0-80 years, their families, and 563 children aged 10-18 years. 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) has reported that 2 brothers aged 2 and 3 and 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 an 13-month-old infant after the consumption of infant formula that was made with contaminated tap water from copper pipes with lead solder.

The CDC (California) has 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. During the manufacturing process, the candied jam was packaged in stoneware or terra cotta ceramic jars that can leach lead.

Some clay cookware and dishes may contain high levels of lead that are introduced during the glazing process or form decoration 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 can 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 (Browder, 1972). A lead test kit can be used to test ceramics for lead.

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

Dickinson et al has reported a family of 1 adult and several children aged 4, 5, and 14 years who had lead poisoning from lead leached from cocktail glasses.

A samovar (Iranian urn) is 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 with seizures and a 4-month-old child with lead poisoning who were given baby formula with water boiled in a samovar.

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 report on a 3-month-old infant and a 1-day-old baby who had lead poisoning from such a source.

Exposure to lead in home remedies

Traditional or folk remedies may contain lead and other heavy metal contaminants and may be ingested for a variety of ailments. Such remedies should be considered possible sources of lead poisoning in adult patients with 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, or 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 (Baer, 1989).

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

Bint Al Zahab is an Iranian folk remedy made by grounding 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 aged 2 days to 3 months with lead poisoning after the use of such a remedy.

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

Bokhoor is a traditional practice of burning wood (Kuwait) and lead sulphide to produce pleasant fumes to calm infants. Fernando et al reported on 4 children aged 16 days to 4.5 months with lead poisoning.

Ghasard is an Asian Indian folk remedy that is used as a tonic to aid digestion. It comes in a brown powder form. Death from lead poisoning has been reported in a 9-month-old child (CDC Report Florida, 1984).

Jin Bu Huan is a Chinese herbal medicine used to relieve pain. A report of 3 children aged 13 and 23 months and 2.5 years with lead poisoning have been recorded (CDC Colorado, 1993).

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 (CDC Minnesota, 1983; CDC California, 1993).

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

Santrinj is an amorphous red powder containing 98% lead oxide. This 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 teething. McNiel and Reinhard have reported lead poisoning in 10 children aged 7 days to 13 months, including 7 who took santrinj.

Surma is a black lead containing black powder 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 the children had increased BLLs (P <.001).

Herbal vitamin preparations are used in China, India and 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."

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

Use of Asian eye cosmetics

Kohl (Al Kohl) is a gray or black eye cosmetic that can 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 also believed to strengthen and protect the eyes against disease.

Al-Saleh et al conducted a study of 538 girls aged 6-12 years and found that the application of kohl was associated with increased BLLs (P = .0461).

Eye cosmetics used in India and Pakistan often contains high levels of lead, and these cosmetics are often applied to the eyes of children. Sprinkle retrospectively reviewed the charts of 175 children aged 8 months to 6 years and found an average BLL of 4.3 mcg/dL for Pakistani or Indian children not using eye cosmetics and 12.9 mcg/dL for those using eye cosmetics (P = .03).

Ali et al conducted a case-control study of 62 children using surma and found that they had increased BLLs (P <.001).

Accidental ingestion or inhalation of lead compounds

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

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

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

Fishing sinkers are often made of lead. Mowad et al report a case of an 8-year-old child with lead poisoning after the ingestion of a lead-containing fishing sinker.

Lead bullets and lead shots that are lodged in body tissues or accidentally ingested can cause lead intoxication (Dillman, 1979; Kikano, 1992; Roberts 1998; Gittleman, 1994).

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

Imported vinyl plastic 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 report on 92 children aged 6-72 months attributed 9% of the cases of lead poisoning cases to exposure to vinyl miniblinds.

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

Miller et al report on 2 children aged 28 and 27 months with elevated BLLs after exposure to lead contained in pool cue chalk.

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 due to 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 due to industrial pollution, environmental factors, and cultural factors such as the use of lead-containing folk remedies and cosmetics. (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 can complement other efforts to prevent lead exposure and reduce lead toxicity.

• An MMWR Morbidity and Mortality Weekly Report from 2001 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.

  However, the report concluded that risk for elevated BLLs among children remains high in some neighborhoods and populations, including 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. The cases were traced 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 effects of lead poisoning in childhood may persist throughout life and may be experienced differently by men and women.

• Kaufmann et al evaluated trends in lead poisoning–related deaths in the United States between 1979 and 1998. 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 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 1979-1998. Most were among males (74%), Blacks (67%), adults aged 45 years or older (76%), and Southerners (70%). The death rate was significantly lower in more recent years. An alcohol-related code was a contributing cause for 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 due to lead poisoning have dropped dramatically since earlier decades and were continuing to decline. However, 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 cases continue to occur and some, at least, 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 homes with decaying lead-based paint in low-income urban centers, are clearly at increased risk of lead poisoning.

• 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 can be a source of lead. Likewise, Kohl is a widely used traditional cosmetic. Individuals living in the Middle East, Asia, and Africa wear this, mainly around the eyes. Lead was a predominant constituent of kohl, with contents of 2.9-100%. The predominance of lead in the 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 from regions where its use prevails.

Sex

Men are generally thought to be affected more often than women because they are more involved in the professions prone to 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. Societies in which folk remedies are frequently used might unwittingly expose their children 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.)

• Other risk factors for children include age less than 6 years, low income, and urban dwelling. Maternal exposure to lead decades before pregnancy can 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 in milk at a higher concentration than the level found in maternal plasma at the same point. The lead in maternal blood readily crosses the placenta and enters the brain of the fetus.
• Recent findings have suggested that even low levels of exposure can harm not only the young and the occupationally exposed but also the older people. This is because they may have had more potential exposures to lead and, moreover, they may have been exposed while working in unregulated occupations or environments. Several large epidemiologic studies have found that older people have higher blood and bone lead levels than those of younger adults.
• Children living in older homes with 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, and daily intake should not exceed 500 mcg. Lead has a half-life of approximately 62 years.

Most human exposure to lead occurs 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 (with children generally absorbing a higher percentage than adults). The absorption of lead and its fate in the body mainly depends on physiologic characteristics of the exposed person, including nutritional status, health, and age. Adults can absorb 20% of the ingested lead while children and pregnant women can 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. Blood lead 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 the 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, which occurs 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, and 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.

Clinical Details

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, progressing 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, impaired 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 can occur regardless of socioeconomic group and indicate a loss of 3 IQ points 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 with suspected lead exposure. Lead poisoning should be considered whenever a child presents with peculiar symptoms that do not match any particular disease entity.

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 so 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:

• Irritable, temperamentally labile children



• Behavioral disorders



• Altered activity levels: hyperactive or excess lethargy



• Sleeplessness



• Delayed developmental milestones



• Language delay



• 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 and also in establishing 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, as 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 with decreased reflexes and weakness of extensor muscles. Sensory function is usually spared in lead poisoning.

Hwang et al studied the clinical, biochemical, hematologic, and erythrokinetic profile of 63 patients with chronic industrial exposure to lead. The most common findings were abdominal pain (62%), gingival lead lines (48%), headache and/or dizziness (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 more frequent in the subjects 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, more reduction in chromium Cr 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 subjects with urinary lead excretion of greater than 100 mcg/d in comparison with the remainder and healthy control subjects. Their findings suggest that minimal chronic exposure to lead causes an increased hemolysis with resultant increased production of erythrocytes.

Heavy metals, such as lead and mercury, cause damage to the nervous system, which manifests differently in children and adults. Other toxins, both endogenous and exogenous, usually affect the nervous system with no age dependence.

Wong and associates report on a 2-month-old girl with acute lead poisoning who demonstrated electrophysiologic evidence of neurotoxicity. 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 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 associated have reported a 36-year-old woman who had progressively marked and diffuse abdominal pain for 2 months. The pain was at times colicky, and she also had nausea, vomiting, and severe constipation. In addition, 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 due to 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.

In all of these patients, treatment was undertaken with sodium calcium edetate (20 mg/kg) in several 3-day cycles. This course resulted in a gradual decreased in serum lead concentration. When the level had fallen to below 4 μmol/L, the symptoms disappeared. 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 have described a case of lead poisoning in a 44-year-old man presenting with acute right upper quadrant pain Acute cholecystitis was initially diagnosed. However, after further questioning and detailed history taking, the diagnosis of lead poisoning was entertained and 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. Retained bullet fragments 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, symptoms, and laboratory data consistent with lead intoxication. The bullet and metallic fragments were removed surgically with a good clinical response. Two patients whose bullets were entirely within the femoral head and whose joints showed smaller degrees of lead fragmentation had no symptoms of lead intoxication. The degree of intra-articular fragmentation of the bullet and the surface area of lead exposed to synovial fluid are emphasized as decisive factors with respect to appropriate therapy.

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

The total body lead burden and efficacy of treatment given can be assessed by performing a provocative chelation test. The tests involve obtaining a timed urine collection after administering a dose of calcium disodium edetate (a chelating agent). However, recently, the potential dangers of such provocative chelation have decreased the frequency of its use.

Radiologic differential diagnoses

Albers and Bromberg describe a case of X-linked bulbospinomuscular atrophy, or Kennedy disease, masquerading as lead neuropathy. They describe a 43-year-old man referred by a veterinary surgeon who evaluated his dog for a seizure and who suspected a toxic lead exposure in both. 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 increased urine lead excretion without symptomatic improvement. His brother worked part-time with him and developed similar findings but also had difficulty chewing, dysphagia, perioral twitching, gynecomastia, and multifocal denervation of extremity and facial muscles. The brother's lead levels were not elevated, but 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). 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 in the presence of dense metaphyseal bands strongly supports the diagnosis of lead poisoning. Plain radiography of the knee is an inexpensive and widely available investigation that can 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 (due to pica) may highlight the diagnosis and prompt immediate intervention. Plain abdominal radiographs may also guide therapy, eg, 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 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 list of differential diagnosis of 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 with limited availability, particularly MRI. Young children undergoing CT or MRI may need heavy sedation or general anesthesia. Disrupted brain plasticity, as seen on MRIs, is not confined to lead intoxication. Other clinical disorders, such as metabolic and epileptic encephalopathies and psychosocial deprivation, may arise from disrupted brain plasticity. Several mental retardation syndromes and cognitive disorders have been recognized as being secondary to genetic disruption of intracellular signaling cascades.

DIFFERENTIALS

Section 3 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

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

RADIOGRAPH

Section 4 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

Findings

In patients with chronic lead poisoning, opaque transverse metaphyseal bands appear in growing tubular bones. These metaphyseal bands, or lead lines, usually do not occur until BLLs reach 70-80 mg/dL, and they are not an early manifestation of lead intoxication. These lines, which are actually growth arrest lines, are not pathognomonic for lead poisoning.

The lead lines may persist after the lead exposure ends. Normal bone is laid down on the epiphyseal side of the lead line, and with recovery, the lead line becomes broader and less dense and may eventually disappear. The band migrates into the substance of bone at a rate correlated with bone growth. If normal BLLs are maintained, the lead lines gradually decrease in density and disappear in about 4 years. If the lead exposure is prolonged, there may be lack of bone modeling. In children, the density and width of the lead bands are well correlated with the concentration of lead ingestion or inhalation as well as the duration of lead exposure.

As lead and calcium are used interchangeably by bone, lead deposition occurs in high concentrations in growing bones, with the greatest concentration in the metaphyses, particularly those in the distal femora, ends of the tibiae, and distal radii, as these are the parts of the skeleton that grow most rapidly. Thus, lead lines are most prominent at the knees, but can also be seen in the wrist, any other long bone metaphysis, in the axial skeleton, and in the margins of flat bones.

Single transverse lines predominate, but multiple bands may be seen with episodic lead poisoning. In infants with severe lead poisoning, the bands may be wide and prevent normal remodeling. In addition, the distal ends of the long bones may disappear and appear clubbed. A bone-within-a-bone appearance has also been described.

Woolf and associates examined 15 Omani infants (aged 2-4 mo), with acute lead encephalopathy. Plain skeletal radiography revealed opaque metaphyseal bands in all 15 infants; these were best seen around the knee joint. Six infants had evidence of multiple lead lines, which indicated previous episodes of exposure to lead. Four infants also had lead lines in the axial skeleton.

The authors concluded that any young infant presenting with unexplained encephalopathy should undergo radiography of the knee and that the presence of opaque metaphyseal bands strongly supports the diagnosis of lead poisoning. Plain radiography of the knee is inexpensive, widely available, and rapidly performed.

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

A k x-ray fluorescence instrument can be used to measure low levels of lead in vivo.

Hu et al measured bone led levels in 34 adults with no known history of excessive lead exposure. The investigators used a questionnaire to gathered information about the participants' occupational and environmental lead exposure. A 30-min measurement with an average estimated uncertainty of 6 mcg of lead per gram of bone mineral was obtained at the midtibial diaphysis. Eighteen subjects had bone lead levels below the measurement uncertainty. The remainder had BLLs up to 21 mcg/g. Bone lead levels were greater among older subjects.

Among young adults, bone lead levels greater than the measurement uncertainty were confined entirely to subjects who had grown up in housing that was estimated to have been built before 1955. Such a childhood environment fosters exposure to biologically absorbable lead through the ingestion of dust contaminated with lead paint and water contaminated from lead pipe. The authors concluded that the k x-ray fluorescence technique can help in distinguishing low levels of lead burden, as shown in epidemiologic studies.

Ahlgren et al used x-ray fluorescence analysis to determine the lead concentration in the male human skeleton in vivo. Five former workers from a metal industry were examined. The mean lead concentration in their skeletons was estimated to be 62 mcg/g with a standard error of ± 5 mcg/g. This level was about 3-9 times higher than those found in people from southern Sweden.

Degree of Confidence

Sachs has shown that the serial radiographs of lead-poisoned children show the separation of lead lines from the zone of provisional calcification at sites of rapid growth; these changes appear within 4 weeks. Lead lines do not appear until blood lead attains a concentration 70-80 mcg/dL. These findings are not affected by treatment, but they disappear spontaneously within 4 years. As long as these lines remain in the diaphysis, they provide a marker for the time of onset of lead toxicity and the subsequent rate of bone growth.

Blickman et al reviewed the lead bands that develop at the metaphyseal ends of growing bones after prolonged heavy metal exposure. The investigators assessed the role of the proximal fibula in distinguishing physiologic sclerosis from pathologic thickening of the zone of provisional calcification. In addition, they compared laboratory values with radiographic findings in a controlled fashion to establish the levels at which the lead bands appear.

Blickman et al found that lead levels were useful adjunct in the radiographic diagnosis of plumbism; their results also indicated that the minimum blood levels at which the lead bands appear are lower than previously thought.

False Positives/Negatives

A negative radiograph does not rule out lead poisoning in children. In healthy infants aged 3 years or younger, the finding of increased metaphyseal opacity is not unusual. This can sometimes be pronounced and can lead to a false-positive diagnosis of lead intoxication. This increased metaphyseal opacity is a normal variant and represents exuberant calcification of the zone of provisional calcification. It is often seen in healthy children, especially after sunlight exposure after winter. Opaque metaphyseal bands are also seen after poisoning with other heavy metals; with hypervitaminosis D; and with the healing stages of leukemia, rickets, and scurvy.

CT SCAN

Section 5 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

Findings

Reyes et al described the CT findings of cerebral and cerebellar calcification in 3 adults with known exposure to lead for 30 years or longer and increased serum lead levels at admission (54-72 mcg/dL; normal range, 0-30 mcg/dL). All 3 patients had nonspecific neurologic symptoms of dementia, loss of visual acuity, peripheral neuropathy, syncope, dizziness, nystagmus, easy fatigue, or back pain.

On images, the patterns of calcification varied and were punctiform, curvilinear, specklike, or diffuse. These patterns were found in the subcortical area, basal ganglia, vermis, and cerebellum. Two patients developed chronic renal disease and hypertension; in both, serum parathormone levels were elevated but serum calcium and phosphorus levels were normal in all 3. No other abnormality was depicted on CT.

Benson and Price evaluated elderly subjects who grew up in a high-lead environment in Queensland, Australia. Their childhood residence and occupational status provided circumstantial evidence of a relationship between excessive lead intake and cerebellar calcification, as seen on CT scans. The researchers found experimental and neuropathologic studies demonstrating an association between exposure to lead and perivascular cerebellar calcification.

Previous autopsy studies have shown that cerebellar calcification is more common in Queensland than elsewhere. Results of cranial CT, which is more sensitive than skull radiography, has confirmed that cerebellar and basal ganglia calcification occurs more commonly in patients examined in Queensland than patients in North America. Although no distinctive neurologic syndrome could be demonstrated, the affected patients had a high incidence of hypertension, hyperuricemia, and increased serum creatinine levels.

Evidence suggests that cerebellar calcification is a marker of previous lead intoxication. The common occurrence of renal impairment in these patients may be due to associated lead nephropathy. Subclinical lead exposure is associated with hyperuricemia.

Schrote and associates reported a case in a 59-year-old potter who presented with lead polyneuropathy after 37 years of occupational exposure. The patient had a 25-year history of normochromic normocytic anemia with moderate basophilic stippling, mild renal failure, hyperuricemia, and abnormal porphyrins. The patient also reported history of 3 short psychotic episodes.

Cranial CT showed extensive, bilateral, symmetrical calcification in the cerebellar hemispheres and minor calcification in the subcortical area of the cerebral hemispheres and basal ganglia. T2-weighted MRI showed high signal intensity in the periventricular white matter, basal ganglia, insula, posterior thalamus, and pons.

Degree of Confidence

CT 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.

False Positives/Negatives

Although the pathophysiologic mechanism of these findings remains poorly understood, it is suggested that chronic lead exposure should be included in the differential diagnosis of unexplained intracranial calcifications in adults.

MRI

Section 6 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

Findings

Lead encephalopathy cause symptoms mainly as a result of cerebral edema. Focal signs may predominate, mimicking a brain tumor in what is generally diffuse brain edema.

Perelman et al reported such a case in which MRI results excluded a focal mass. Early treatment for edema prevented neurosurgical exploration. Since Biemond and Van Creveld first described the condition in 1939, a total of 7 cases of lead encephalopathy with a clinical presentation of a cerebellar tumor have been reported.

The developing brain is subject to major changes during fetal life and for at least the first decade of childhood. Initially, the brain develops more neurons and synaptic connections than are needed for function in later life. These excess neurologic units are "sculpted" away during early brain development before the mature brain finally develops. This process is thought to be the basis for the plasticity of the developing brain or its capacity to adapt in behavior and circuitry to stimulation in response to the external environment.

Functional MRI now offers the means to noninvasively study this plastic reorganization of the brain in children and adults. MRI can demonstrate how the brain's functional maps undergo major reorganization in response to early environmental changes. The neurobiology of brain reorganization during development is also being studied with use of new insights into the molecular mechanisms for activity-dependent neuronal plasticity. Clinical disorders such as lead poisoning may arise from disrupted brain plasticity (Johnston, 2001).

Trope et al examined 2 male cousins who were living in the same household. One subject, a 10-year-old boy, had elevated BLLs. His cousin, a 9-year-old boy, was not exposed to lead. Both underwent a comprehensive neuropsychological evaluation. High-resolution MRI and magnetic resonance spectroscopy (MRS) were performed in both children by using a 3-in surface coil.

Neuropsychological evaluation demonstrated areas of impairment in the lead-exposed child; these included difficulties in the academic skills of reading, writing, and performing arithmetic, as well as deficient linguistic skills and attention mechanisms. His cousin, who was not exposed to lead, had normal neuropsychological function. Although both children had a normal brain MRIs, s the lead-exposed boy had significant alterations in brain metabolites, with reduced ratio of N-acetylaspartate to creatine ratio in both gray matter and white matter. This study demonstrates that MRS is a feasible noninvasive technique for in vivo examination of the brain of children exposed to lead.

In another study Trope et al concluded that lead has an effect on brain metabolites, as detected by MRS in vivo. More specifically, they found significantly reduced levels of brain metabolites in gray matter but not white matter in individuals exposed to lead. Their results imply that MRS can depict metabolic abnormalities in individuals with lead poisoning.

Degree of Confidence

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 (those these are better seen on CT scans).

False Positives/Negatives

Disrupted brain plasticity is not confined to lead intoxication and other clinical disorders such as metabolic and epileptic encephalopathies, and psychosocial deprivation may arise from disrupted brain plasticity.

Several mental retardation syndromes and cognitive disorders recently recognized as being secondary to genetic disruption of intracellular signaling cascades. Understanding how the brain's circuitry is sculpted during development provides an important perspective for thinking about neurodevelopmental disorders (Johnston, 2001).

ULTRASOUND

Section 7 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

Findings

Ultrasonography is not routinely used in the diagnosis of lead intoxication, though transcranial sonography can be used to investigate congenital lead poisoning and lead intoxication in infant patients presenting with lead encephalopathy.

Zou et al studied the effects on systolic and diastolic cardiac function in 54 individuals exposed to lead and in 24 workers not exposed. Doppler echocardiographic results suggested that cardiac systolic function increased in the exposed group as a compensatory response for the effect of lead on myocardium. Pulsed Doppler imaging showed that time-related parameters were comparable among all groups but that blood flow velocity through the mitral valve and Doppler area fractions changed significantly in lead-exposed groups. This change was evidenced by increased A values, and decreased E values and E/A ratios.

The decrease in diastolic cardiac function was more significant in the lead-intoxication group than in the nonexposed group. In addition, the serum activity of the MB isoenzymes of creatine phosphokinase (CPK-MB), one of the indices of myocardial damage, was significantly higher in exposed group than that in control subjects (P <.05), and a positive correlation was found between CPK-MB activity and Pb-B. These findings suggest that the increasing of lead burden leads to more release of CPK-MB from the myocardial cells and suggests the existence of slight myocardial damage, which might conceivably impair diastolic cardiac function.

Tutar and associates describe a case of a 12-year-old girl presenting with recurrent pericardial effusion due to firearm pellet injury to the left ventricle. The pellet was localized by means of 2-dimensional echocardiography of the left ventricular apical wall. Because the patient was asymptomatic, left ventriculotomy was avoided to extract the pellet, and only pericardial tube drainage was carried out. A slightly elevated BLL of the patient was alarming because of potential subsequent lead poisoning due to retained pellets.

ANGIOGRAPHY

Section 8 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

Findings

Hollerman et al describe the substantial contribution radiologists can make to the evaluation and treatment of the patient with a gunshot wound. Plain radiographs, CT, angiography, and sometimes MRI can all be used to localize the missile, to determine what path it followed in the body, to assess missile and bone fragmentation, and to identify missile emboli. Certain locations of missile fragments predispose the patient to lead poisoning or lead arthropathy.

Angiography is useful for both diagnosis and treatment. Both angiographic hemostasis and percutaneous foreign-body removal may be used.

INTERVENTION

Section 9 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to recognize lead poisoning might lead to irreversible neurologic deficit, as the symptoms and signs of lead toxicity are subtle and easily overlooked. The presenting clinical features are nonspecific. The radiologist may be the first to suggest the diagnosis when conventional radiographs are reviewed.
• In acute lead encephalopathy, brain edema occurs predominantly in the cerebellar vermis, which may act as a midline posterior fossa mass occluding the fourth ventricle. This presentation may mimic that of brain tumor, which, if considered, may have disastrous consequences. The resultant transient obstructive hydrocephalus may need emergency drainage of cerebrospinal fluid. The hydrocephalus is transient as vermis edema subsides with medical treatment.
• Pappas et al reviewed a case of lead poisoning in a 9-month-old child who clinically and radiographically presented with a posterior fossa mass effect and obstructive hydrocephalus. The predominance of edema of the cerebellum sufficient to achieve obstruction of the ventricular system represents a particularly unusual presentation of this disease process. They reviewed the literature for similar cases of lead encephalopathy.

Special Concerns

• The populations most vulnerable to lead exposure are pregnant women, infants, and young children.
• • Pregnant women can transfer their body burden of lead to the growing fetus, as there is no placental barrier to heavy metals. Because lead crosses the placenta throughout pregnancy, the fetus is at risk of lead poisoning. BLLs tend to remain constant throughout pregnancy in women who were previously exposed to lead, even if no additional exposure to lead is present. Further lead exposure may result in harm to the fetus.
  • Lead in bone has implications for toxicology during pregnancy and lactation. Mobilization of lead from bone is likely to occur during periods of altered mineral metabolism. Since calciotropic factors determine the uptake and storage of lead in this compartment, changes in calcium-related regulatory factors are likely to affect lead compartmentalization.
  • Calcium metabolism significantly changes during pregnancy and lactation. Although relatively little is known of lead kinetics during these critical periods, bone lead may be mobilized and transferred to the more bioavailable compartment of the maternal circulation, with potential toxic effects on the fetus and mother (Silbergeld, 1991).
  • After birth, the child may continue to be exposed through the mother's milk.
  • Children are especially exposed to lead by playing with painted toys, repeatedly ingesting non-food substances, and similar activities.

• The CDC has progressively lowered the BLLs of concern for lead exposure. Although the evidence is not definitive, several studies have demonstrated neurobehavioral impairment in lead-exposed children with BLLs as low as 10-14 mcg/dL, and there may not be a threshold. If 12% or more children in a given community have BLLs 10 mcg/dL or higher (or if 27% or more of the housing stock is built before 1950), CDC recommends universal screening, and community-wide interventions should be considered by the appropriate agencies.
• Lead poisoning is a preventable condition that can affect almost every system of the body. The toxic effects range from subtle common childhood symptoms, but lead poisoning can also cause severe illness leading to death. Lead poisoning can mimic common childhood illnesses.
• • Clinicians need to be aware of the many sources of lead intoxication, particularly the use folk remedies in ethnic minorities.

  • Symptoms from lead encephalopathy can involve focal signs mimicking those of a cerebral or cerebellar neoplasm. The importance of good history taking cannot be overemphasized.

  • Lead may have a deleterious affect on the CNS of a child, when the BLL is as low as 0.48 µmol/L (10 mcg/dL). Lead-induced encephalopathy is a serious, end-stage disorder of lead poisoning that happens when the BLL is around 3.86 µmol/L (80 mcg/dL).

  • In adults, lead poisoning predominantly affects the peripheral nervous system and usually manifests as peripheral neuropathy.

• Pearl and Boxt describe a full-term asymptomatic child born with congenital lead poisoning secondary to maternal pica. Radiographic findings of an opaque cranial vault, lead lines, and delayed skeletal and deciduous dental development were noted at birth. After chelation therapy when the patient was 7 months old, radiographs revealed normal skeletal maturation. Tooth eruption did not occur until age 15 months.

• Hu studied the long-term consequences of childhood plumbism among 35 survivors of lead poisoning in 1930-1944. The participants were interviewed, along with 22 control subjects matched for age, sex, and town of residence. The results suggest that women with a history of childhood lead poisoning may be at risk for spontaneous abortions or stillbirths and for having children with significant learning disabilities.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Angiography
• Intervention
• Multimedia
• References

Media file 1:  Lead poisoning. Pica. Plain abdominal radiograph in a 3-year-old patient shows multiple metallic particles due to ingested flakes of lead paint.
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Media type:  X-RAY

Media file 2:  Lead poisoning. Opaque metaphyseal bands in the lower femur, upper tibia, and the upper fibula secondary to lead poisoning in a child.
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Media type:  X-RAY

Media file 3:  Lead poisoning. Opaque metaphyseal bands in the upper and lower tibia and the upper fibula secondary to lead poisoning in a child.
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Media type:  X-RAY

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Differentials