For centuries, lead toxicity has been one of the most significant preventable causes of neurologic morbidity from an environmental toxin. A heavy metal, lead is ubiquitous in our environment but has no physiologic role in biological systems. Lead toxicity is a particularly insidious hazard with the potential of causing irreversible health effects. It interferes with a number of body functions primarily affecting the central nervous, hematopoietic, hepatic and renal system producing serious disorders. Acute toxicity is related to occupational exposure and is quite uncommon. Chronic toxicity on the other hand is much more common. Research on the effects of lead on adults has prompted the suggestion that acceptable levels of lead in adults be dropped almost to those of children.[1]
The ongoing emphasis on abatement of lead environments places added emphasis on occupational exposure to lead (eg, among workers at smelters or battery recycling plants).[2] Such exposure is a continuing problem. Whereas occupational exposure remains an occasional concern, the greatest public health issue related to lead at present is exposure of young children to decaying fragments of leaded paint.
Pediatric lead poisoning
Compared with adult lead poisoning, pediatric lead poisoning is a somewhat newer problem. First reported in the late 1800s in Australia, interest in childhood lead poisoning and its manifold clinical presentations has burgeoned. It should be noted that toxic metals, including lead, can be transmitted from a mother to her child via breast milk.[3]
Lead poisoning is probably the most important chronic environmental illness affecting modern children. Despite efforts to control it and despite apparent success in decreasing incidence, serious cases of lead poisoning still appear in hospital emergency departments (EDs), clinics, and private physicians’ offices.
In children, virtually no organ system is immune to the effects of lead poisoning. Perhaps the organ of most concern is the developing brain. Any disorganizing influence that affects an individual at a critical time in development is likely to have long-lasting effects. Such is the effect of lead on the developing brain. Effects on the brain appear to continue into the teenaged years and beyond. A high index of suspicion is necessary for physicians treating pediatric patients.
The literature suggests that significant insult to the brain of children occurs at very low levels and that medical intervention with chelation fails to reverse such effects.[4, 5, 6, 7, 8]
The major mechanism of lead toxicity is due to increased generation of reactive oxygen species (ROS) and interference with generation of antioxidants. Lead causes the generation of ROS like hydroperoxide, hydrogen peroxide, and singlet oxygen. ROS are stabilized by glutathione in the body. Ninety percent of glutathione in the cell exists in reduced form and 10% in oxidative form, and it typically acts as an antioxidant defense mechanism. Glutathione stabilizes ROS, and after being converted (oxidizing) to glutathione disulfide, it is reduced back to GSH by glutathione reductase. Lead inactivates glutathione by binding to GSH’s sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. Lead also interferes with the activity of other antioxidant enzymes including superoxide dismutase and catalase. The increase in oxidative stress leads to cell membrane damage due to lipid peroxidation. Lead blocks the activity of 5-aminolevulinic acid dehydratase and leads to hemoglobin oxidation, which along with the lipid peroxidation can result in red cell hemolysis.[9]
Lead entering the intravascular space binds quickly to red blood cells. Lead has a half-life of approximately 30 days in the blood, from where it diffuses into the soft tissues, including the kidneys, brain, liver, and bone marrow.
Lead then diffuses into bone and is stored there for a period that corresponds to a half-life of several decades. Increased bone turnover with pregnancy, menopause, lactation, or immobilization can increase blood lead levels. Estimations of blood lead levels are more useful for diagnosing acute lead poisoning, whereas the extent of past lead exposure can be estimated by determining the body burden of lead on the basis of results from the edetate (EDTA) calcium disodium (CaNa2 EDTA) lead mobilization test.
Lead is primarily excreted in urine and bile, but the elimination rate varies, depending on the tissue that absorbed the lead. The kidney excretes lead by means of glomerular filtration and tubular secretion. Lead has bidirectional transport across the tubular epithelium. The clearance of lead ranges from 1 to 3 mL/min and is relatively independent of kidney function.
The effects of lead poisoning on the brain are manifold and include delayed or reversed development, permanent learning disabilities, seizures, coma, and even death. 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.
The most significant lead exposure in adults usually occurs at the workplace, whereas for children, other forms of environmental exposure are more important. Although lead toxicity can occur after a single event, it is usually a result of chronic exposure.
Workplace exposure
Sites and occupations associated with lead exposure include pipe cutting, lead mining and ore crushing, lead and copper smelting, welding operations, construction, the rubber industry, the plastic industry, radiator repair, battery manufacturing, soldering of lead products, the printing industry, glass manufacture, organic lead production, solid waste combustion, frit manufacture, and paint and pigment manufacture. Persons employed in these occupations may also expose family members to lead by transporting lead dust from the workplace to their homes.
Other environmental exposure
Exposure from lead-based paint was significant among children in the past. Although lead was banned from use in residential paint, it continues to be used in nonresidential settings, and as a result of its past use, lead paint can still be found in many older homes.
Leaded gasoline contaminates the atmosphere. Although lead has been removed from gasoline in Western countries, leaded gasoline continues to be used in the developing world. Huffing of leaded gasoline (ie, deeply inhaling fumes to achieve a “high”) could also cause poisoning.
Food has been an important source of lead exposure. Surface contamination of homegrown vegetables, storage cans with lead solder seams (banned in 1991), and kitchenware are sources of lead contamination in food. Strong animal evidence suggests that malnutrition is highly significantly associated with increased levels of blood lead.[10]
Water remains an important source of lead poisoning because lead from the atmosphere contaminates bodies of water.[11] The nature of plumbing also may be important in this regard. Although use of lead pipes (largely replaced by copper or polyvinyl pipes) has declined considerably since the 1950s, old public water systems continue to have networks that include lead piping. Because the use of lead-based soldering of copper pipes was permitted until 1986, homes with copper plumbing may have substantial lead in the water. In May 2015, at least 28 children under the age of five have been killed by drinking stream water contaminated with lead in Nigeria's Niger state.[12]
Some hobbies are associated with exposures to lead. These hobbies may include making bullets, making fishing-weights, soldering, indoor firearm shooting, and remodeling older homes.
Soil contaminated with lead, such as may be found surrounding lead smelters and in homes from deterioration of exterior surfaces, can be an important source of lead exposure.
Moonshine ethanol (ie, illegally distilled corn whiskey) made in lead-containing vessels, such as discarded automobile radiators, has been associated with lead poisoning and even local epidemics.[13]
Topical agents that contain lead, such as kohl and surma, may be ingested accidentally.
Several reports exist of lead poisoning that develops as the result of absorption of lead from retained bullet or shrapnel fragments. Bullets located in areas bathed by fluids are more likely to dissolve, while those embedded in soft tissues are likely to be walled off by inflammation.
An incidental finding of bullet or shrapnel fragments on an x-ray should prompt consideration of possible elevated lead levels, though most of these cases occur only with intra-articular fragments. Of particular concern is a retained bullet in the spine, an area where removal is often considered too dangerous to attempt.[14]
Familial factors
Frequently, 1 or 2 children in a family develop more lead poisoning than other siblings. This observation may be related to age, activity, or genetics. Identical twins seem to have concordant lead levels and biologic evidence of lead’s effects, but this is less likely to be the case with fraternal twins.
For further information on etiology, see Pathophysiology and Etiology of Lead Toxicity.
Lead poisoning is said to be the most common environmental illness of children in the United States. The incidence varies with age, socioeconomic status, the population of a given community, race, and the age of the home.
Although no blood level of lead is considered safe, the Centers for Disease Control and Prevention (CDC) has established 10 µg/dL as the level of concern. Approximately 9% of children aged 1-5 years have blood levels higher than 10 µg/dL. Because low socioeconomic status is also a risk factor for lead exposure, children in inner cities are at highest risk. In some rural areas of the United States, 20% of children have been reported to have levels higher than 10 µg/dL.[15]
Lead poisoning occurs in every group, and only the frequency varies; it is not just a disease of black inner-city children. According to the 1997 National Health and Nutrition Examination Survey (NHANES), 16.4% of children living in cities with more than 1 million people and in homes built before 1946 have elevated lead levels.
Of interest is the remarkable decrease in the prevalence of elevated lead levels in children in the 1999-2004 time frame as compared with the 1988-1991 time frame. According to the NHANES data, the prevalence of children with lead levels over 10 µg/dL was 8.4% in 1988-1991 but only 1.4% in 1999-2004, representing an 84% decline.[16] levels continue to be highest among non-Hispanic black children, Mexican American, and non-Hispanic white children, with the greatest risk being in the non-Hispanic black population.
Generally, adults develop lead poisoning as the result of an occupational exposure or from exposure through a hobby. Several states cooperate in the SENSOR program, which monitors lead exposure in adults from occupational sources.
According to a report from the CDC’s Adult Blood Lead Epidemiology and Surveillance (ABLES) program, the incidence of BLLs of 25 µg/dL or higher in adults (persons aged 16 years or older) declined nationally from 14.0/100,000 in 1994 to 6.4/100,000 in 2011.[17] (Although BLLs lower than 40 µg/dL have been considered acceptable in adults, research data have raised concerns about the effects of low-level lead exposure.)
The highest numbers of workers exposed to lead with BLLs of 25 µg/dL or greater included employees in the storage battery manufacturing and lead and zinc ore mining industries, according to the ABLES report.[18]
International statistics
Lead poisoning has been reported in almost every country on earth. Blood lead levels are higher in developing countries because of continued use or later phaseout of leaded gasoline and paint. Occupational exposure in these countries is higher as well. In particular, the old “iron-curtain” countries had less strict guidelines for occupational and environmental exposures than other places in the world; thus, exposures there were common.
A Swedish study by Evans et al, which reported on 926 patients with incident severe CKD and 998 controls with a 7- to 9-year follow-up, suggested that low-level exposure to lead may not cause an increased risk of severe chronic kidney disease (CKD).[19] However, the authors cautioned that because only native Swedes were used in their study, the generalizability of the data may be limited; they also noted that whereas an expert rating method was used to assess lead exposure, BLLs were not measured to confirm the rating method’s validity.[19]
Age-related demographics
Young children who are independently mobile are at greatest neurologic risk from chronic exposure to low or moderate levels of lead. From the time children are able to crawl until they enter school, they are at risk of ingesting lead-containing dust. Although this sometimes is associated with pica and intentional ingestion of paint chips, lead poisoning often occurs without such behavior. Children may also be at risk for lead toxicity if folk remedies are used or if their parents, siblings, or caregivers are involved in lead-related occupations.
Children younger than 3 years are at the greatest risk for lead poisoning. This is because these children are most likely to put things containing lead into their mouths and because their brains are rapidly developing and are most vulnerable to any disorganizing influence. However, physicians and other health care professionals must be aware that lead poisoning can occur in children of any age.
Adults are now believed to be affected at a lower level of exposure than was once assumed. This has sparked renewed interest in occupational exposure to lead and its consequences. Careful attention must be paid to the occupations of adults who present with uncommon peculiar symptoms and signs.
Sex-related demographics
Because of occupational exposures, men have higher lead levels than women. No sex difference in incidence is reported in children.
Racial differences in incidence
Although no compelling evidence exists that any particular race is biologically predisposed to lead toxicity, covariant conditions such as poor nutrition and lower socioeconomic status clearly are associated with chronic lead poisoning.
Certain populations, such as African American children and new immigrants living in homes with decaying lead-based paint in low-income urban centers, are at increased risk of lead poisoning. The NHANES III data have shown higher lead levels among non-Hispanic blacks and Mexican Americans. Whether this translates into a higher incidence of lead nephropathy among these persons is not known.
Overall, black non-Hispanic children appear to have the greatest risk of developing lead poisoning. The NHANES figures for 1997 reveal a prevalence rate 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 subsequent to 1973.
This compares to a prevalence of 13%, 2.3%, and 1.6% among Mexican-American children and 5.6%, 1.4%, and 1.5% among white non-Hispanic children living in homes built before 1946, living in homes built in 1946-1973, and living in homes built subsequent to 1973, respectively.
An analysis of trends in blood lead levels over the past 20 years shows that, although the overall geometric mean blood lead level in children has dropped dramatically, disparities still exist, causing increased risk to certain populations. The factors of living in older housing, poverty, age, and being non-Hispanic black places a child at risk for elevated blood lead levels.[16]
Essentially, 2 syndromes of lead poisoning exist, depending on exposure: one syndrome is associated with acute or subacute high-level lead exposure, and the other is associated with chronic low-level lead exposure.
With exposure to high levels of lead, patients develop lethargy, progressing to coma and seizures. Death is uncommon with appropriate medical management. Long-term sequelae depend on the duration, as well as the amount, of exposure. Acute lead nephropathy is usually completely reversible with chelation therapy. Deaths may result from the elevated intracranial pressure (ICP) associated with lead encephalopathy.
With chronic exposure to low or moderate levels of lead, subacute symptoms develop. Patients with chronic lead nephropathy may have a progressive decline in kidney function and eventually require renal replacement therapy.
Mortality related to lead toxicity is rare today. However, morbidity remains common. Because lead is an enzymatic poison, it perturbs multiple essential bodily functions, producing a wide array of symptoms and signs.
Adults generally do not develop central effects but may develop distal motor neuropathies. Some reports document an increase in depressive disorders, aggressive behavior, and other maladaptive affective disorders in adult patients with lead poisoning. Men with lead poisoning tend to have lower sperm counts and may experience frank impotence; women have an increase in miscarriages and smaller babies.
In the pediatric population, fatalities associated with lead encephalopathy were reported in the 1960s. Today, with aggressive management of ICP, these deaths are preventable. Occasional cases of acute lead encephalopathy still occur, and these often result in severe neurologic damage. Mounting evidence suggests that lead poisoning in childhood produces a long-term problem with learning, intelligence, and earning power. Asymptomatic lead poisoning has a far better prognosis.
In cooperation with local health departments, the physician should educate families about the following:
Causes and effects of lead poisoning
Relationship between blood lead level and anticipated medical or neuropsychological problems
Importance of follow-up or serial blood lead level determinations to monitor effects of treatment and environmental lead abatement
Identifying and eliminating possible sources of lead exposure
Increased lead absorption in patients with iron-deficiency anemia
Local resources about lead exposure and treatment
All patients must be educated in lead avoidance. The termination of exposure to lead is imperative. In particular, workers should be educated regarding the health risks of lead and sources that may cause poisoning.
A good, substantial diet is important; lead absorption is increased when a diet rich in fats is consumed. Also, diets low in iron, calcium, and vitamin C increase the likelihood of lead absorption and resultant lead poisoning. Dietary fiber helps promote good peristalsis and decreases the opportunity for lead absorption; thus, at least 15 g of dietary fiber is suggested for children each day.
The clinical presentation varies widely, depending upon the age at exposure, the amount of exposure, and the duration of exposure. Organic lead, because of its higher lipid solubility, causes greater toxicity and affects the neurological system predominantly. Younger patients tend to be affected more than older children and adults, because lead is absorbed from the gastrointestinal (GI) tract of children more effectively than from that of adults.
Neurological Toxicity
The neurological system is most vulnerable to lead toxicity. Children are more likely to develop central nervous system toxicity while the peripheral nervous system is more often affected in adults.
The manifestations in children include temperamental lability, irritability, behavioral changes, hyperactivity or decreased activity, loss of developmental milestones and language delay. Lower IQ and ADHD like symptoms may be present. Severe toxicity can cause delirium, convulsions and encephalopathy. Depression and anxiety are more common in patients. Lead causes demyelination of the peripheral nervous system and the abnormalities mostly affect the extensor motor nerves and may result in hand and foot drop.
Hematological Toxicity
Anemia may develop with lead poisoning due to impaired synthesis of heme, hemolysis of red cells and shortened red cell survival. Anemia is usually mild and is more commonly seen in adults.
Gastrointestinal Toxicity
Patients may develop lead colic, nausea, vomiting and anorexia. Occasionally, some patients with acute poisoning can develop severe diarrhea and dehydration.
Renal Toxicity
Acute nephropathy manifests with tubular defects, which may include phosphaturia, glucosuria and amino aciduria. This combination of tubular defects is referred to a Fanconi’s syndrome. Chronic lead nephropathy is characterized histologically by chronic interstitial nephritis and is frequently associated with hypertension and gout. Furthermore, lead exposure, at much lower levels than those causing lead nephropathy, acts as a cofactor with more established renal risk factors to increase the risk of chronic kidney disease and the rate of progression. Adverse renal effects have been reported at mean blood lead levels of less than 5 mcg/dL. Cumulative lead dose has also been associated with worse renal function.
Cardiovascular Toxicity
Lead exposure has been associated with the development of hypertension. The development of hypertension may be secondary to oxidative stress or an association with chronic nephropathy. Studies have also documented an association between lead toxicity and cardiovascular disease and stroke.
Reproductive Effects
In men, lead causes a reduction in libido, abnormal spermatogenesis, chromosomal damage and infertility. Women experience an increase in the incidence of stillbirth, miscarriage, pregnancy induced hypertension and prematurity.
Children
No pathognomonic symptoms exist. When symptoms do occur, they are typically nonspecific. Consider lead poisoning whenever a small child presents with peculiar symptoms that do not match any particular disease entity. Common nonspecific symptoms include the following:
More significant exposure to lead may cause symptoms in children that are more likely to lead to a medical evaluation. They are as follows:
Abdominal pain, loss of appetite, vomiting, constipation
Headache, ataxia, somnolence
Lethargy, seizures, stupor, coma
The presence of fever does not rule out the diagnosis, which still must be given full consideration.
Inquiries should be made regarding possible sources of lead exposure. For example, query families about the condition of the home, the presence of peeling or cracking paint and plaster, the occupations or hobbies of the family members, and the presence of industry in the immediate vicinity.
Determine the approximate age of the home. Homes built from 1920 to 1950 are more likely to contain lead pigment-based paint than newer homes. Houses built after 1978 are unlikely to contain lead-pigmented paints. Lead contamination still may be present in plumbing fixtures, but the lead dose in plumbing fixtures is an order of magnitude less than that of paint.
Determine whether the home contains any lead-based kitchen utensils, pottery, or imported toys. In addition, inquire about other homes where the child stays, and determine whether a parent is working as a painter or renovator or in a battery factory, shooting range, or other workplace where that lead is used.
Ask about exposure to foods and additives produced outside the United States. Some spices or food coloring may also contain lead pigments, and some candies have been reported to be contaminated with lead. Also ask about the use of herbal folk remedies. Hispanic and Asian families occasionally use herbal folk remedies that may contain lead.
Investigate the patient’s past medical history, including developmental milestones or delays, hygiene, pica, and previous exposure to lead. Evidence suggests that delayed weaning is associated with excessive pica and lead poisoning. It is commonly found that lead-poisoned children are bottle-fed for protracted periods. Inquire about the patient’s siblings (eg, ages, developmental history, school performance, and blood lead levels [BLLLs] if known).
Adults
In adults, similar symptoms may develop, although cognitive changes may be discerned more easily, especially since exposures are more typically acute. In addition, adults with chronic exposure may develop other symptoms, such as the following:
Weakness of extensor muscles (eg, foot drop, wrist drop)
Delirium, hallucinations
Adults with lead poisoning frequently have sleep disorders. They may be hypersomnolent or have difficulty falling asleep at the appropriate time.
A meticulous environmental history is necessary in patients with suspected lead exposure. Depending on whether it is tailored to children or adults, it should include the following information:
Inquire about present and recent residences, including the location, age, and condition of the building; any history of renovations, inspections, or deleading programs; and any analyses of indoor and outdoor surfaces, water, and soil (if available). Ask about practices concerning changing of clothes and the presence of any work areas in the home.
In adults, obtaining a careful occupational and hobby history is important. More than 900 occupations have been associated with cases of lead poisoning. Always ask patients not just the name of their job but also the duties the job entails. This may uncover an obvious cause of exposure.
A history of ingesting illicit liquor may be an important clue to the etiology of lead poisoning. According to a study from a large urban emergency department (ED) involving patients who reported ingesting “moonshine” sometime during the previous 5 years, 51% had elevated BLLs, and 31% had BLLS in the very elevated range (ie, ≥ 50 µg/dL).[20]
Additionally, numerous reports document lead poisoning resulting from retained bullet or shrapnel fragments; thus, a history of military or other penetrating trauma may be important.
Subtle changes in cognitive performance are not identified easily on physical examination. Careful mental status examination may detect changes in more severe cases, while formal neuropsychological testing may be needed to detect changes in other cases.
A child with lead toxicity is frequently iron deficient and pale because of anemia. The child may be either hyperactive or lethargic.
Impaired fine-motor coordination[21] or subtle visual-spatial impairment may be seen. In adults, chronic distal motor neuropathy (eg, foot drop or wrist drop) may be seen with decreased reflexes and weakness of extensor muscles; sensory function is relatively spared (see the image below). This is a classic, though not very common, presentation of occupational lead toxicity.
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Wrist drop in adult with lead poisoning and renal failure.
It is important to evaluate the patient for papilledema, cranial nerve abnormalities, and signs of increased intracranial pressure (ICP). Cranial nerve involvement, particularly involvement of the optic nerve, is not uncommon. Chronic lead exposure has been shown to cause optic neuritis and blindness.[22]
Lead lines appearing on gingival tissue (see the image below) are very unusual in children. The dentition of children does not promote poor enough hygiene to produce pyorrhea and the subsequent precipitation of lead sulfide. Adults with poor dental hygiene may demonstrate this characteristic finding in any heavy metal poisoning.
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Lead line on gingival border of adult with lead poisoning.
A report indicates that relative hypertension is related to elevated lead levels, but this finding has never been duplicated.
Lead exposure can precipitate a gout attack. The patient should be observed for joint changes suggestive of acute arthritis. In patients with history of penetrating or military trauma, gunshot wounds must be identified.
Lead poisoning, with or without encephalopathy, may result in neurologic, renal, hepatic, or cardiac damage. All organ systems may be potentially damaged by lead. A possibility that symptoms may progress with chelation exists, and the treating physician must be prepared to manage them. Such complications may consist of syndrome of inappropriate excretion of antidiuretic hormone (SIADH), increased ICP, renal impairment from the chelated lead complex, and hypertension.
Nervous system
Neuropsychiatric problems, impaired cognition, learning difficulties, and antisocial behavior are described in both children and adults.
Peripherally, lead selectively affects motor axons, causing segmental demyelination and axonal degeneration. The upper extremities are affected more often than the lower extremities, and extensors are affected more often than flexors. Hand drop and foot drop are common manifestations of axonopathy.
Kidneys
An increased prevalence of renal adenocarcinoma is reported among lead workers. Variability in individual susceptibility may be explained by differences in lead-binding proteins.
Anemia
Inhibition of enzymes in the heme synthetic pathway, including aminolevulinic acid synthase, delta-aminolevulinic acid dehydratase (ALAD), and ferrochelatase, causes anemia. With kidney disease, erythropoietin production is impaired and thus causes anemia.
Bones
Lead can interfere with bone development, leading to the formation of lead lines at bone metaphyses. These lines represent periods of growth arrest, not lead toxicity per se.
Lead interferes with the conversion of 25-hydroxy vitamin D to 1,25-dihydroxy vitamin D and causes rickets or osteomalacia. Patients with Fanconi syndrome may develop vitamin D–resistant rickets.
Reproductive system
Lead is a known reproductive toxin. In males, it causes reductions in sperm count and fertility. In females, it increases the risk of spontaneous abortions, stillbirths, and preterm births. Offspring may experience lead poisoning in utero and may have developmental delay. Research has demonstrated that these reproductive effects occur at relatively low levels of exposure, even those previously considered safe. Skeletal lead may be mobilized during pregnancy and lactation and can be transported to the fetus or the neonate.
The criterion standard is a whole blood lead level (BLL). Any BLL higher than 10 µg/dL is considered positive and consequential. Patients with BLLs between 10 and 20 µg/dL require removal from the exposure, repeated testing, and follow-up.
A free erythrocyte protoporphyrin (FEP) level may be useful in demonstrating the degree of biological abnormalities that exist. Significantly elevated BLLs are associated with a microcytic anemia. Iron deficiency, also associated with anemia, may produce an elevation of FEP, confounding the significance of FEP measurement.
Workup guidelines for the use of investigative studies in patients with different BLLs (see below) are based on the recommendations from the Centers for Disease Control and Prevention (CDC) Advisory Committee on Childhood Lead Poisoning Preventions, the National Center of Environmental Health/Agency for Toxic Substances and Disease Registry, and the American Academy of Pediatrics Committee on Environmental Health.[23, 24, 25, 26, 27]
Imaging studies are ordered as appropriate.
Lead may produce subtle nephrogenic effects, which, if unappreciated, may lead to treatment failures or complications. For example, a child may appear to have a mild degree of dehydration based on decreased urine output, increased urine specific gravity, and poor appetite while actually suffering from the syndrome of inappropriate excretion of antidiuretic hormone (SIADH). Such patients have hypo-osmolar hyponatremia and, in fact, are often treated with fluid restriction.
Although not an accurate measure of the whole-body burden of lead, the BLL is a reasonable approximation of lead exposure,[28] in that levels decline in a predictable manner after removal from the source of lead.
Capillary (ie, fingerstick) blood levels do provide a reliable measurement if performed correctly, though samples improperly collected may be contaminated by lead dust on the skin or from the collecting equipment. The blood must be drawn in an anticoagulated tube and one certified to be lead-free. Trace metal tubes and anticoagulated tubes are available, but aside from certified tubes, they all tend to give high-biased levels. Because of laboratory limitations, the result may not be immediately available at all institutions.
Classification
The CDC has established 5 classes of lead toxicity, based on BLLs. Recommendations for further evaluation and treatment are different for each class.
BLLs higher than 70 µg/dL (ie, class V) are considered medical emergencies, regardless of whether neurologic symptoms are present. The risk of encephalopathy is high and treatment is required. However, lead levels should be reviewed in the context of the clinical examination and history.
For example, a child may swallow a lead foreign body, show a documented BLL higher than 70 µg/dL within 2 days, and still have a low total-body burden (the lead would be predominantly within the blood compartment in this scenario). Encephalopathy would not be expected in this scenario. However, a child who chronically ingests lead paint dust may have a lower BLL but a much higher total-body burden and may subsequently exhibit neurologic findings (in this scenario, the lead has had time to redistribute amongst all the compartments).
BLLs ranging from 45 to 69 µg/dL (ie, class IV) warrant chelation therapy, according to CDC criteria, and a medical evaluation that includes further blood testing and possibly an abdominal radiograph to look for lead paint chips. Removal from the source of lead exposure is paramount.
BLLs ranging from 20 to 44 µg/dL (ie, class III) require medical evaluation, including further laboratory testing and possible abdominal radiographs. Removal of the source of lead and an environmental evaluation are also required. There is no good evidence that treatment with chelation agents for BLLs lower than 45 µg/dL is beneficial; in fact, the evidence tends to suggest that chelating at lower levels is potential harmful.[29]
BLLs ranging from 15 to 19 µg/dL (ie, class II) require repeat blood lead level screening and lead prevention education. If elevated levels persists in this range or rise over a 3-month period, the patient should be treated as would be appropriate for BLLs of 20-44 µg/dL).
BLLs ranging from 10 to 14 µg/dL (ie, class I) require no further treatment other than lead prevention education, but periodic screening in young children should continue.
Testing criteria
Most children with elevated blood lead levels demonstrate few, if any, symptoms that immediately suggest lead poisoning. For this reason, the CDC advocates obtaining blood lead levels in children at ages 1 and 2 if they meet any of the criteria noted below. In addition, children aged 3-5 years who have not previously been tested and meet any of the criteria below should be tested.[25, 26] The criteria are as follows:
Eligible for or receiving Medicaid, or WIC benefits
Living in a ZIP determined to be high-risk on the basis of age of housing and other factors
Living in or regularly visiting a house or daycare center built before 1950
Living in or regularly visiting a house that was built before 1978 with peeling or chipping paint or that has recent (within the last 6 months), ongoing, or planned renovation
Living with or regularly visiting a sibling, housemate, or playmate with lead poisoning
Living with an adult whose job or hobby involves exposure to lead
Living near an active lead smelter, battery recycling plant, or other industry likely to release lead
Free erythrocyte protoporphyrin level
Lead interferes with the enzyme ferrochelatase, blocking the incorporation of iron into the protoporphyrin molecule; thus, an FEP level may be useful in demonstrating the degree of biologic abnormalities that exist.
FEP can also be used to help distinguish recent acute lead exposure from chronic exposure. If FEP in normal in the context of high blood lead levels, the exposure is more likely acute; if both are elevated, the exposure is more likely chronic. FEP elevation lags behind the blood lead elevation that causes it.
Other blood studies
Lead toxicity causes a hypochromic microcytic anemia and basophilic stippling of red blood cells. Hypochromia and microcytosis are typically seen in iron-deficiency anemia, which often coexists with lead toxicity. Assessing iron storage status (ferritin) in all cases of lead poisoning is important. In pregnant women, some evidence suggests that lead also causes a decrease in erythropoietin production and a depression in red blood cell (RBC) production. Lead is a surface-acting poison and may produce increased RBC fragility and acute hemolytic anemia (see the image below).
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Peripheral smear taken from 8-year-old Pakistani girl who presented with acute hemolytic anemia and lead level of 125 µg/dL.
A chemistry profile including renal studies, liver studies, and a uric acid is advisable. Children often have low uric acid levels and leak uric acid into their urine. Adults, because of the disturbance of enzymatic aminohydrolases, manifest elevated uric acid levels and, possibly, clinical gout.
Obtain a radiograph of the abdomen in children with suspected elevated lead levels. In selected cases, abdominal radiographs may demonstrate lead-containing paint chips or other lead-containing objects (see the image below). Retained lead objects within the gastrointestinal (GI) tract are an acute emergency and should prompt referral for potential removal. A radiograph also helps guide therapy aimed at preventing further absorption through GI decontamination.
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Abdominal flat plate showing multiple radiopaque foreign bodies, including paint chips and earring.
Long bones
Radiographs of the long bones in growing children may reveal the characteristic lead lines. These lines, actually growth arrest lines, are not pathognomonic but are associated with BLLs higher than 40 µg/dL over a protracted period (see the image below). A radiodensity in the distal metaphyseal plate is a frequent occurrence in children with chronic lead poisoning of a moderate degree. These findings are unlikely to be observed in adults.
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Growth arrest lines, also known as lead lines, in bones of child who recovered from lead poisoning.
The classic findings of lead lines on radiographs of long bones are rarely seen, because most cases of lead poisoning in children are due to exposures to low or moderate amounts of lead. Obtaining radiographs in search of lead lines is not recommended by the CDC.
In general, neuroimaging (eg, with magnetic resonance imaging [MRI] or computed tomography [CT]) does not play an important role in the diagnosis of lead poisoning. However, cerebral edema and microhemorrhages may be seen in patients presenting with acute encephalopathy on both CT and MRI. With chronic exposure to lead, patchy calcifications may be seen. Atrophy and white matter changes may be present with chronic exposures.
Atre et al reported a case of lead encephalopathy with MRI findings of symmetric occipital lobe lesions that were bright on T2-weighted and fluid-attenuated inversion recovery images and hypointense on T1-weighted images.[30] These lesions disappeared after chelation therapy with clinical laboratory improvement.
Findings from electroencephalography (EEG) may be normal or may show nonspecific findings; they generally are not helpful in the diagnosis.
Lumbar puncture
A lumbar puncture (spinal tap) may be needed for evaluation of patients with altered mental status. However, it is contraindicated in patients with lead encephalopathy, because of the possible risk of herniation resulting from elevated intracranial pressure (ICP).
Provocative chelation test
A provocative chelation test may provide additional information (eg, total-body burden). It should not be done in acute lead poisoning because of the potential of precipitating or worsening encephalopathy. Urine is collected after administering a dose of a chelation agent. Edetate (EDTA) calcium disodium (CaNa2 EDTA) is the most commonly used chelator for this test.
Neuropsychological testing
Formal neuropsychological testing provides the best measure of a patient’s cognitive impairment. This is effective in tracking improvement in attention, visual-spatial abnormalities, and memory as a result of treatment and in establishing the extent and nature of long-term impairment.
The most important step in treatment is to prevent further exposure to lead. Accurate assessment of environmental and occupational exposure is essential. Modifying children’s behavior to decrease hand-to-mouth activity is beneficial.
The US Occupational Safety and Health Administration (OSHA) has recommendations for occupational lead exposure. Under these guidelines, the permissible exposure limit is 50 µg/m3 for an 8-hour, time-weighted average. Workers with blood lead levels (BLLs) of 60 µg/dL or higher must be removed from the workplace. Additionally, employees should be removed from the workplace if the average of their last 3 BLLs is 50 µg/dL or higher. Individuals with BLLs of 40 µg/dL or higher must undergo medical evaluation.
Community-wide preventive actions are recommended when children are found to have BLLs of 10 µg/dL or higher. With BLLs of 15-19 µg/dL, nutritional and educational interventions are recommended. With BLLs of 20 µg/dL or higher, medical evaluations and environmental interventions are recommended.
Medical treatment (ie, chelation therapy) is but one element of a comprehensive treatment plan for exposure to lead; removal of the source of lead exposure is more important. The interventions described below relate to chelation therapy for the most severe cases of lead poisoning. Chelation is of only transient benefit in the patient whose source of lead exposure has not been identified and removed.
Chelation therapy, especially in the setting of encephalopathy, can be complicated. If appropriate facilities for treatment are not available, consider transfer to an institution that is capable of managing an encephalopathic patient and also has a provider experienced in lead poisoning and chelation therapy. Ideally, children should be treated in specialized pediatric intensive care units.
Chelation agents
Succimer is a water-soluble, oral chelating agent that is appropriate for use with BLLs higher than 45 µg/dL.[22, 31] In a retrospective study from Nigeria, chelation therapy using dimercaptosuccinic acid (DMSA) lowered blood lead levels in children with severe lead poisoning.[32]
D-penicillamine is a second-line oral chelating agent, although it is not approved by the US Food and Drug Administration (FDA) for use in lead poisoning.
Edetate (EDTA) calcium disodium (CaNa2 EDTA) is a parenteral chelating agent. It should never be used as the sole agent in patients manifesting with lead encephalopathy, because it does not cross the blood-brain barrier and can potentially lead to exacerbation of lead encephalopathy; dimercaprol, which does cross the blood-brain barrier, should be administered first. Life-threatening hypocalcemia has been reported when disodium EDTA was inadvertently substituted for CaNa2 EDTA.
Dimercaprol (also referred to as British antilewisite [BAL]) is another parenteral chelating agent recommended as an agent of first choice for patients with lead encephalopathy. With high BLLs (ie, > 100 µg/dL), it is used in conjunction with CaNa2 EDTA.
Acute lead poisoning and nephropathy
In the acute setting, if suggestive radiopacities are observed on a plain radiograph of the abdomen, gastric lavage, cathartics, or whole bowel irrigation may be used to limit lead absorption.
With acute lead poisoning, the indications for chelation therapy are well defined. Institute chelation therapy in children with BLLs of 45 µg/dL or higher. Treat children whose BLLs are 70 µg/dL or higher as medical emergencies.
Succimer and penicillamine may be given orally. Penicillamine may be used when blood lead levels are 25-40 µg/dL, especially with a negative CaNa2 EDTA mobilization test result. Succimer may be an alternative; its main indication is in persons whose BLLs are 45 µg/dL or higher.
Intravenous (IV) therapy is preferable for persons with BLLs of 70 µg/dL or higher. Use the combination of dimercaprol and CaNa2 EDTA with BLLs of 70 µg/dL or higher and in the presence of lead encephalopathy.
In adults, consider chelation therapy for patients with blood lead levels BLLs of 70 µg/dL or higher. Also consider chelation therapy in symptomatic adults with BLLs exceeding 50 µg/dL. Available chelation agents for adults are dimercaprol and CaNa2 EDTA; penicillamine and succimer do not have US Food and Drug Administration (FDA) approval for this application, although they are effective treatments.
Chelation therapy reverses Fanconi syndrome, transient hypertension, and tubular structural changes observed on histopathology findings.
Chronic lead nephropathy
Patients with chronic lead nephropathy, in the absence of marked interstitial fibrosis and with only minimal impairment in kidney function, may respond to chelation therapy.
Extremely limited data are available regarding the benefits of chelation therapy with documented lead nephropathy. In 1979, Wedeen et al treated patients with occupational lead nephropathy and found a 20% improvement in the GFR in 4 of 8 patients given EDTA 3 times a week for 6-50 months.[33] The reported improvements in kidney function could be from reversal of acute-on-chronic lead nephropathy.
Lin and coworkers from Taiwan performed 3 well-designed studies addressing populations of patients with high-normal BLLs and chronic kidney disease.[34, 35, 36]
The first of these studies included 32 subjects with chronic kidney disease (serum creatinine level [SCr] of 1.5-4 mg/dL) and mildly elevated body lead burden (lead excretion value of 150-600 µg with the 3-D CaNa2 EDTA lead mobilization test). Subjects were randomly assigned to receive EDTA chelation therapy or placebo weekly for 2 months and were followed for an additional 12 months. The reciprocal of serum creatinine (1/SCr) versus time data suggested that using chelation may slow the progression of renal disease.
The second study described the results of chelation therapy in 36 subjects (24 study group subjects and 12 controls) with serum creatinine values of 1.5-4 mg/dL and high-normal bone lead burden. This time, chelation therapy with CaNa2 EDTA was administered weekly for 3 months. In the treated group, creatinine clearance improved by as much as 10.2% at 1 year, whereas in the control group, kidney function declined by as much as 11%.
The third study included 202 subjects who were followed for 2 years. In this study, 64 patients with a high-normal body lead burden (urinary lead excretion > 80 µg and < 600 µg after 1 g of CaNa2 EDTA infusion) and SCr lower than 4.2 mg/dL were randomized to chelation or placebo.
In the initial 3 months, the chelation group received 1 g of CaNa2 EDTA every week, and the controls received placebo. In the ensuing 24 months, repeated chelation therapy was administered weekly to patients with a high-normal lead burden unless, on repeated testing, the body lead burden fell below 60 µg.
The glomerular filtration ate (GFR) increased by 11.9% (+3.4 mL/min) in the chelation group at the end of the initial 3 months, whereas it fell by 3.6% (-1 mL/min) in the control group. Thereafter, no further improvement in the GFR was observed in these patients. At the end of 27 months, the mean change in GFR was +2.1 mL/min in the chelation group and -6 mL/min in the control group over the 27-month study.
These studies suggest that in patients with an increased lead burden, chelation with small doses of CaNa2 EDTA at longer intervals might be safe for treating chronic kidney disease. However, repeated and chronic exposure to CaNa2 EDTA may create its own nephrotoxicity; therefore, use caution when deciding to institute chelation therapy. Exclude other causes of kidney disease, and define an endpoint of therapy, such as normalization of the CaNa2 EDTA test results or improvement in kidney function.
Supplementary measures
Closely monitor cardiovascular and mental status in patients with lead poisoning. Maintain an adequate urine output. Assess renal and hepatic functions.
Diphenhydramine may help alleviate the adverse effects of dimercaprol. Iron supplementation should be avoided in patients receiving dimercaprol chelation therapy because dimercaprol forms a complex with iron, leading to toxicity.
The diet should be adequate in energy (caloric) intake and replete in calcium, zinc, and iron. Data from the Normative Aging Study suggest that low dietary intake of vitamin D may increase accumulation of lead in bones, whereas low dietary intake of vitamin C and iron may increase lead levels in blood in subjects who range in age from middle-aged to elderly.
Similar data associate calcium and iron deficiency with lead absorption in children. Although no studies have specifically addressed treatment of lead exposure with calcium and iron supplementation, it is a logical therapy to help limit the absorption of lead.
The 2010 Healthy People objective to eliminate childhood lead poisoning can be achieved through primary prevention. Pediatricians and family practitioners provide a fundamental role with anticipatory guidance about potential sources of lead exposure and its hazards for the development of children.
A successful primary prevention should focus on the 2 main exposure sources for children in the United States: lead in housing and nonessential uses of lead in certain products, such as imported and domestically manufactured toys, eating and drinking utensils, cosmetics, and traditional medicines.
Environmental measures for prevention of lead toxicity include abatement of lead paint usage, removal of lead from gasoline, and removal of lead solder from cans. Lead abatement in dwellings must be performed by skilled and experienced workers.
For adults, occupational measures focus on engineering controls, such as isolation by containment and local exhaust systems, personal protective equipment (eg, respirators), and good work practices. Workers should be educated regarding the health risks of lead and sources that may cause poisoning.
OSHA standards should be followed in the workplace. These standards for permissible exposure limit lead in the workplace to a maximum of 50 µg/m3 of air averaged over an 8-hour period. Medical surveillance is indicated when workers are exposed to lead levels exceeding 30 µg/m3 for more than 30 days a year (regardless of respiratory protection).
Secondary
Efforts to prevent lead poisoning have focused primarily on secondary prevention because the cost of primary prevention in the form of environmental inspection and abatement of all homes and other sources of lead is prohibitive. This focus does not reflect the true importance of primary prevention.
Secondary prevention focuses on the early detection of lead poisoning. The CDC has devised screening criteria to determine which children are at high risk for lead poisoning; screening of BLLs should be carried out according to these criteria (see Workup). Medical evaluation, treatment, and environmental and public health follow-up are essential in individuals with elevated BLLs.
Consultation with a toxicologist and a nephrologist is appropriate. Medical toxicology services can typically be located by contacting a local poison center.
All occupational exposures must be reported to OSHA. The local or county health departments responsible for monitoring children with lead toxicity, should be informed about patients with elevated lead levels or those undergoing medical treatment, so that they may initiate appropriate environmental evaluation and lead abatement.
Many local health departments have programs for appropriate lead screening of children, in cooperation with local pediatricians. Stressing the need for screening in any patient at risk (because of housing, industrial, ethnic, recreational concerns) is important. Repairs of older homes must be done carefully to avoid lead exposure. Proper lead abatement in older homes prevents future exposure to lead and, thus, prevents further lead poisoning.
All patients treated for lead poisoning require extensive outpatient follow-up. The intent of such follow-up is to avoid further exposure to lead and to maintain lead levels in the acceptable range.
After chelation, the blood lead level should be rechecked in 7-21 days to determine whether repeat chelation therapy is required. Chelation therapy, either oral or intravenous, may be continued in an outpatient setting if indicated. Carefully monitor kidney and liver function during therapy.
Assess the source of lead. Involvement of the local health department can assist in this regard. Do not discharge patients from the hospital until they can go to a lead-free environment. Children in particular should not be allowed to return to a lead-contaminated environment; if they are exposed to more lead, their lead levels will rapidly rise again.
There is a general belief, probably incorrect, that once chelation is terminated, BLLs will rebound rapidly. Numerous publications have discussed the effect of lead stored in bone.[37, 38, 39, 40, 41, 18] In the light of the known kinetics of lead in the body and the reports of expected decreases in lead level over time, this would not appear to be expected, because the half-life of lead in bone is measured in years. Thus, significant elevations in BLL after termination of chelation should be considered probable reexposure.
The mainstay of treatment is chelation therapy. Chelation agents contain sulfhydryl groups that bind or chelate lead, and the resulting complex is excreted either renally or hepatically. The chelation agents succimer and penicillamine are given orally, whereas dimercaprol and edetate (EDTA) calcium disodium (CaNa2 EDTA) are administered parenterally.
These agents reduce body stores of lead. Reducing blood lead levels also may mobilize skeletal stores of lead. Therefore, caution must be exercised in using chelation agents, both because of their adverse effects and because of their ability to mobilize lead.
Dimercaptopropanesulfonic acid (DPMS) has received much attention worldwide, but it is not yet available in the United States, except under special FDA Investigational New Drug (IND) permits. In Europe and Asia, DPMS has become the drug of choice for most heavy metal intoxications. It is available both in an oral form and in a water-based parenteral form.
Clinical Context:
Succimer, or meso 2,3-dimercaptosuccinic acid (DMSA), is an analogue of dimercaprol used in lead poisoning. It has high sensitivity for lead, but its ability to chelate essential trace metals is low. It is available as capsules of 100 mg. Succimer is generally well tolerated after oral (PO) administration and produces a linear dose-dependent reduction in serum lead concentration. It forms a water-soluble chelate with heavy metals and is excreted in urine. It produces plumburesis approaching that achieved with the combination of CaNa2EDTA and dimercaprol.
In January 1991, succimer became the only drug approved by the US Food and Drug Administration (FDA) specifically for lead chelation in children and the only drug approved to treat a specific laboratory test—namely, a blood lead level (BLL) higher than 45 µg/dL (2.17 mmol/L). It has been shown to be an effective oral chelator.
Although never a substitute for careful environmental controls, succimer produces a rapid decline in lead level and reverses many of the biochemical indicators of toxicity. It is not currently licensed for use in adults. Although experience suggests that this agent is safe and effective, its use must be considered carefully. Adults exposed from an occupational source must be carefully excluded from further exposure.
Patients with extremely high lead levels may experience abnormalities in gastrointestinal (GI) motility; thus, the absorption of succimer may be unpredictable or erratic. Use of this agent in patients with lead levels higher than 60 µg/dL has not been carefully studied. Therefore, consideration should be given to the use of parenteral therapy until lead levels drop below this value.
Clinical Context:
CaNa2EDTA is nearly the perfect chelator. It is water-soluble, can be administered either intravenously (IV) or intramuscularly (IM), allows lead to be renally eliminated, is not metabolized, and has few toxic effects. Its main limitation is that it removes lead from extracellular spaces only.
CaNa2EDTA should generally be given IV, diluted to a concentration of less than 0.5% in 5% dextrose in water (D5W) or isotonic saline. In patient with acute lead encephalopathy and increased intracranial pressure, dilution to concentration of less than 3.0% may be necessary, or the IM route may be preferred to limit fluids. Ideally, the first dose of dimercaprol should be given at least 4 hours before CaNa2EDTA. Note that CaNa2EDTA initially may aggravate symptoms of lead toxicity because of its mobilization of stored lead.
CaNa2EDTA may induce central nervous system (CNS) toxicity if BAL therapy is not initiated first when blood lead levels are higher than 70 µg/dL in children or 100 µg/dL in adults and in encephalopathy. To prevent hypocalcemia, only CaNa2EDTA should be used for chelation in heavy metal toxicity.
When CaNa2EDTA is given IM, the same daily dose is used, divided into 2-6 doses. IM preparations of CaNa2EDTA are extremely irritating to muscle and intensely painful. Lidocaine or procaine with the IM preparation lessens the pain.
Clinical Context:
Dimercaprol (British antilewisite [BAL], or 2,3-dimercapto-1-propanol) was the first chelator used in encephalopathic individuals and is the drug of choice for treatment of lead toxicity. It is a chelating agent for intracellular and extracellular lead that and diffuses into red blood cells (RBCs) and rapidly crosses the blood-brain barrier. Sulfhydryl groups combine with ions of heavy metals to form soluble, nontoxic complexes that are excreted renally. Dimercaprol is excreted primarily in bile, making it an agent that can be used in patients with renal failure.
Combination therapy with dimercaprol and CaNa2EDTA is recommended in all cases of severe, acute intoxication (eg, BLL > 100 µg/dL), particularly when encephalopathy is present. Dimercaprol is administered IM every 4 hours, mixed in a peanut oil base; therefore, it should not be used in patients allergic to peanuts. In very severely poisoned patients, the dose is increased to 7 mg/kg, with great caution.
Adverse effects are fever, pain at the injection site, nausea, vomiting, headache, and sterile abscess formation.
Clinical Context:
D-penicillamine (3-mercapto-D-valine), a second-line oral chelating agent, is a hydrolysis product of penicillin that is FDA-approved for the treatment of Wilson disease and cystinosis. It has been used as an oral chelator of lead for 30 years but has never been licensed for this indication by the FDA.
Penicillamine is effective orally and has few adverse effects. It can be administered over an extended period (weeks to months) for children with lead levels below 45 µg/dL. Penicillamine is available as capsules of 125 mg and 250 mg. Pyridoxine supplementation is required. Adjust the dose for patients with compromised renal function.
Antidotes are used to prevent intoxication resulting from lead poisoning. These agents bind lead in the vascular compartment and prevent it from reaching the end organs of toxicity. Chelators promote the excretion of lead.
Pranay Kathuria, MD, FACP, FASN, FNKF, Professor of Medicine, Director, Division of Nephrology and Hypertension, Program Director of Nephrology Fellowship, University of Oklahoma School of Community Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Adam K Rowden, DO, Assistant Professor of Emergency Medicine, Jefferson Medical College of Thomas Jefferson University; Director, Division of Toxicology, Department of Emergency Medicine, Albert Einstein Medical Center; Consulting Toxicologist, Children's Hospital of Philadelphia
Disclosure: Nothing to disclose.
Rika Nagakuni O'Malley, MD, Instructor, Department of Emergency Medicine, Thomas Jefferson University Hospital
Disclosure: Nothing to disclose.
Specialty Editors
Nicholas Lorenzo, MD, MHA, CPE, Co-Founder and Former Chief Publishing Officer, eMedicine and eMedicine Health, Founding Editor-in-Chief, eMedicine Neurology; Founder and Former Chairman and CEO, Pearlsreview; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc; Chief Strategy Officer, Discourse LLC
Disclosure: Nothing to disclose.
Chief Editor
Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS, Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital
Disclosure: Nothing to disclose.
Acknowledgements
David A Griesemer, MD, Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina
David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Epilepsy Society, Child Neurology Society, and Society for Neuroscience
Disclosure: Nothing to disclose.
Christopher P Holstege, MD Associate Professor of Emergency Medicine and Pediatrics, University of Virginia School of Medicine; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Center; Associate Medical Toxicology Fellowship Director, Veterans Affairs Department of Health
Christopher P Holstege, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, European Association of Poisons Centres and Clinical Toxicologists, Medical Society of Virginia, Society for Academic Emergency Medicine, Society of Toxicology, and Wilderness Medical Society
Disclosure: Nothing to disclose.
J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Jonathan S Rutchik, MD, MPH Assistant Professor, Department of Occupational and Environmental Medicine, University of California at San Francisco
Jonathan S Rutchik, MD, MPH is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Occupational and Environmental Medicine, and Society of Toxicology
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Herman SS, Geraldine M, Venkatesh T. Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure. J of Hazardous Materials. In press.
Elevated Lead in D.C. Drinking Water - A Study of Potential Causative Events, Final Summary Report. EPA; August 2007:
Onuah, F and Abrak, I. At Least 28 Children Killed by Lead Poisoning in Nigeria. Medscape Medical News. Available at http://www.medscape.com/viewarticle/844746. May 18, 2015; Accessed: September 22, 2015.
CDC. US Department of Health and Human Services, National Institute for Occupational Safety and Health; 2013. Adult Blood Lead Epidemiology and Surveillance (ABLES).
American Academy of Pediatrics Committee on Environmental Health. Lead. In:. Handbook of Pediatric Environmental Health. American Academy of Pediatrics. Elk Grove, IL: AAP; 1999:131-43.:
CDC. Preventing Lead Poisoning in Young Children. DC, United States Department of Health and Human Services:1991:
CDC. Screening Young Children for Lead Poisoning. Guidance for State and Local Public Health Officials. . Atlanta, GA: United States Department of Health and Human Services; 1997:
Wrist drop in adult with lead poisoning and renal failure.
Lead line on gingival border of adult with lead poisoning.
Peripheral smear taken from 8-year-old Pakistani girl who presented with acute hemolytic anemia and lead level of 125 µg/dL.
Abdominal flat plate showing multiple radiopaque foreign bodies, including paint chips and earring.
Growth arrest lines, also known as lead lines, in bones of child who recovered from lead poisoning.
Peripheral smear taken from 8-year-old Pakistani girl who presented with acute hemolytic anemia and lead level of 125 µg/dL.
Growth arrest lines, also known as lead lines, in bones of child who recovered from lead poisoning.
Lead line on gingival border of adult with lead poisoning.
Wrist drop in adult with lead poisoning and renal failure.
Abdominal flat plate showing multiple radiopaque foreign bodies, including paint chips and earring.
Kidney biopsy results from patient with chronic lead nephropathy show nonspecific tubular atrophy and interstitial fibrosis. Note absence of interstitial infiltrate. Single glomerulus included in section is normal. Image courtesy of Vecihi Batuman, MD, FACP.
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