Lead Toxicity Workup
- Author: Pranay Kathuria, MD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS more...
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.[22, 23, 24, 25, 26]
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.
Blood lead level
Although not an accurate measure of the whole-body burden of lead, the BLL is a reasonable approximation of lead exposure, 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.
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.
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.
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.[24, 25] 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).
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.
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.
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. 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.
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.
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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