Approach Considerations
The criterion standard is a whole blood lead level (BLL). Any BLL greater than 5 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.
Laboratory Studies
Blood lead level
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. Confirmation of BLL needs a venous blood sample. 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.
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:
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Eligible for or receiving Medicaid, or WIC benefits
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Living in a ZIP determined to be high-risk on the basis of age of housing and other factors
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Living in or regularly visiting a house or daycare center built before 1950
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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
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Living with or regularly visiting a sibling, housemate, or playmate with lead poisoning
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Living with an adult whose job or hobby involves exposure to lead
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Living near an active lead smelter, battery recycling plant, or other industry likely to release lead
Free erythrocyte protoporphyrin (FEP) level or zinc protoporphyrin (ZPP)
Lead inhibits enzymes involved in hemoglobin synthesis and causes elevated FEP and ZPP levels. A FEP or ZPP level may be useful in demonstrating the degree of biologic abnormalities that exist.
FEP and ZPP levels 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 and ZPP 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).
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.
Plain Radiography
Abdomen
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.
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.
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.
CT and MRI
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. [29] These lesions disappeared after chelation therapy with clinical laboratory improvement.
Other Studies
Electroencephalography
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.
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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.
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Growth arrest lines, also known as lead lines, in bones of child who recovered from lead poisoning.
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Lead line on gingival border of adult with lead poisoning.
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Wrist drop in adult with lead poisoning and renal failure.
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Abdominal flat plate showing multiple radiopaque foreign bodies, including paint chips and earring.
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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.
