The diagnosis of lead poisoning should be considered in any person potentially exposed to lead. Any detectable lead level is consistent with exposure to lead. A blood lead reference value of ≥0.17 micromoles/L (3.5 micrograms/dL) is used to identify children with the highest blood lead levels (within the top 2.5 % of US children aged 1-5 years from 2015-2016 and 2017-2018 National Health and Nutrition Examination Survey [NHANES] cycles).[47]Centers for Disease Control and Prevention. Blood lead reference value. October 2021 [internet publication].
https://www.cdc.gov/nceh/lead/data/blood-lead-reference-value.htm
A case definition for an elevated blood lead level in an adult (person ≥16 years of age) is ≥0.24 micromoles/L (5 micrograms/dL).[2]Centers for Disease Control and Prevention (CDC). Understanding blood lead levels. Adult Blood Lead Epidemiology and Surveillance (ABLES). National Institute for Occupational Safety and Health (NIOSH) workplace safety & health topics. Apr 2023 [internet publication].
https://www.cdc.gov/niosh/topics/lead/referencebloodlevelsforadults.html
[3]Centers for Disease Control and Prevention. Lead, elevated blood levels 2016 case definition. April 2021 [internet publication].
https://ndc.services.cdc.gov/case-definitions/lead-elevated-blood-levels-2016
In an adult, the US Occupational Safety and Health Administration considers a blood lead level of ≥1.2 micromoles/L (25 micrograms/dL) to be serious, requiring inspection.[2]Centers for Disease Control and Prevention (CDC). Understanding blood lead levels. Adult Blood Lead Epidemiology and Surveillance (ABLES). National Institute for Occupational Safety and Health (NIOSH) workplace safety & health topics. Apr 2023 [internet publication].
https://www.cdc.gov/niosh/topics/lead/referencebloodlevelsforadults.html
A history of exposure is the strongest suggestive feature, as symptoms are non-specific or may be absent. Lead toxicity may be identified during routine screening. Whole-blood lead measurement is the primary method of diagnosis, although interventions should begin at the first sign of increased exposure.
Although spot and 24-hour urine collections (often labelled heavy metal screens) are often requested by clinicians to diagnose lead toxicity, these tests do not add to diagnosis and are not recommended.
History
The main aim of the history is to thoroughly assess the risk of lead exposure. Key features include the following.
Age of patient: lead exposure peaks in children at age 18 to 24 months. All children in this age group should be considered for lead testing.[6]Harvey B, ed. Managing elevated blood lead levels among young children: recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Atlanta, GA: CDC; 2002.
http://www.cdc.gov/nceh/lead/casemanagement/managingEBLLs.pdf
Pica: a medical disorder in which children develop an appetite for non-nutritive substances. If the substances consumed contain lead, this may be a significant source of lead exposure.[39]Thihalolipavan S, Candalla BM, Ehrlich J. Examining pica in NYC pregnant women with elevated blood lead levels. Matern Child Health J. 2013 Jan;17(1):49-55.
https://www.doi.org/10.1007/s10995-012-0947-5
http://www.ncbi.nlm.nih.gov/pubmed/22302239?tool=bestpractice.com
[40]Martin G, Gupta V, Bhurawala H. A case of pica and elevated lead levels in a child. Aust J Gen Pract. 2021 Jan-Feb;50(1-2):60-61.
https://www.doi.org/10.31128/AJGP-04-20-5314
http://www.ncbi.nlm.nih.gov/pubmed/33543166?tool=bestpractice.com
Pica is strongly associated with iron deficiency, which is believed to drive the abnormal appetite.
Age and condition of housing: lead use in paints has been phased out in many countries, and most lead exposure occurs in housing built before 1950. Paint deterioration increases lead exposure. Screening of children (12 to 24 months of age) for elevated blood lead concentrations is recommended in communities or census block groups with ≥25% of housing built before 1960.[48]Council on Environmental Health. Prevention of childhood lead toxicity. Pediatrics. 2016 Jul;138(1):e20161493.
https://www.doi.org/10.1542/peds.2016-1493
http://www.ncbi.nlm.nih.gov/pubmed/27325637?tool=bestpractice.com
Socioeconomic status: patients with a low socioeconomic status are more likely to live in older and poorly maintained buildings, in which the risk of lead exposure is higher.
Occupational history: there are multiple lead-hazardous occupations. In larger companies (e.g., battery production or construction), workers should be monitored for lead exposure. Small-business workers, such as painting contractors and plumbers are also at risk, but are not usually tested by their employers.[9]Centers for Disease Control and Prevention (CDC). Adult blood lead epidemiology and surveillance - United States, 2008-2009. MMWR Morb Mortal Wkly Rep. 2011 Jul 1;60(25):841-5.
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6025a2.htm
http://www.ncbi.nlm.nih.gov/pubmed/21716198?tool=bestpractice.com
[13]Association of Occupational and Environmental Clinics. Medical management guidelines for lead-exposed adults. Oct 2013 [internet publication].
http://www.aoec.org/documents/positions/mmg_revision_with_cste_2013.pdf
[49]Centers for Disease Control and Prevention (CDC). Adult Blood Lead Epidemiology and Surveillance (ABLES). National Institute for Occupational Safety and Health (NIOSH) workplace safety & health topics. February 2021 [Internet publication].
https://www.cdc.gov/niosh/topics/ables/default.html
Hobbies: certain hobbies such as constructing stained glass items that are soldered with lead materials, and making bullets and fishing sinkers in the home, often expose the hobbyist to high levels of airborne lead.[6]Harvey B, ed. Managing elevated blood lead levels among young children: recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Atlanta, GA: CDC; 2002.
http://www.cdc.gov/nceh/lead/casemanagement/managingEBLLs.pdf
[13]Association of Occupational and Environmental Clinics. Medical management guidelines for lead-exposed adults. Oct 2013 [internet publication].
http://www.aoec.org/documents/positions/mmg_revision_with_cste_2013.pdf
Self-renovation of an older property may also result in exposure to airborne lead.
Dietary history: diets low in minerals, especially calcium and iron, or high in fat, likely increase absorption of lead.[6]Harvey B, ed. Managing elevated blood lead levels among young children: recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Atlanta, GA: CDC; 2002.
http://www.cdc.gov/nceh/lead/casemanagement/managingEBLLs.pdf
[23]Mahaffey KR. Nutrition and lead: strategies for public health. Environ Health Perspect. 1995;103(suppl 6):191S-196S.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1518938&blobtype=pdf
http://www.ncbi.nlm.nih.gov/pubmed/8549473?tool=bestpractice.com
[33]Goyer RA. Nutrition and metal toxicity. Am J Clin Nutr. 1995;61(3 suppl):646S-650S.
http://www.ncbi.nlm.nih.gov/pubmed/7879732?tool=bestpractice.com
Pre-existing iron deficiency and other mineral deficiencies also increase the absorption of lead from the gastrointestinal tract.[23]Mahaffey KR. Nutrition and lead: strategies for public health. Environ Health Perspect. 1995;103(suppl 6):191S-196S.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1518938&blobtype=pdf
http://www.ncbi.nlm.nih.gov/pubmed/8549473?tool=bestpractice.com
The quality of the diet should be determined with particular attention to the mineral and fat content.
Use of folk medications: Mexican folk remedies (e.g., azarcon and greta), pay-loo-ah (a Hmong folk remedy), and Ayurvedic medicines have resulted in lead toxicity.[10]Breeher L, Mikulski MA, Czeczok T, et al. A cluster of lead poisoning among consumers of Ayurvedic medicine. Int J Occup Environ Health. 2015;21(4):303-7.
http://www.ncbi.nlm.nih.gov/pubmed/25843124?tool=bestpractice.com
[11]Breyre A, Green-McKenzie J. Case of acute lead toxicity associated with Ayurvedic supplements. BMJ Case Rep. 2016 Jun 30;2016:bcr2016215041.
http://www.ncbi.nlm.nih.gov/pubmed/27364782?tool=bestpractice.com
[15]Centers for Disease Control and Prevention (CDC). Lead poisoning associated with use of traditional ethnic remedies - California, 1991-1992. MMWR Morb Mortal Wkly Rep. 1993 Jul 16;42(27):521-4.
http://www.ncbi.nlm.nih.gov/pubmed/8321177?tool=bestpractice.com
[16]Leads from the MMWR. Folk remedy-associated lead poisoning in Hmong children. JAMA. 1983 Dec 16;250(23):3149-50.
http://www.ncbi.nlm.nih.gov/pubmed/6644996?tool=bestpractice.com
Some ethnic groups are reluctant to reveal such use to conventional physicians.[6]Harvey B, ed. Managing elevated blood lead levels among young children: recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Atlanta, GA: CDC; 2002.
http://www.cdc.gov/nceh/lead/casemanagement/managingEBLLs.pdf
Family history of lead poisoning: several children in a family often have common exposures. Housing is the most common source, but lead workers can also bring lead home on clothing.[50]Dolcourt JL, Hamrick HJ, O'Tuama LA, et al. Increased lead burden in children of battery workers: asymptomatic exposure resulting from contaminated work clothing. Pediatrics. 1978;62:563-566.
http://www.ncbi.nlm.nih.gov/pubmed/714588?tool=bestpractice.com
Physical examination
Most patients are asymptomatic and are identified as part of a screening programme or because a high-risk history of lead exposure is identified. Clinical examination is usually unremarkable.
The key symptoms of lead toxicity are neurological and can affect either the central or peripheral nervous system. Although lead toxicity can cause a microcytic anaemia, this is uncommon in the absence of other risk factors such as iron deficiency anaemia, and its absence does not rule out lead toxicity.
Extremely severe lead poisoning has been associated with renal Fanconi's syndrome, particularly in children. It produces a range of cardiovascular toxicities in adult patients. The key toxicity is hypertension, but coronary artery disease, increased stroke mortality, and peripheral artery disease are also seen. Lead toxicity should be suspected in hypertensive patients with a history of possible lead exposure.
Agency for Toxic Substances and Disease Registry: case studies in environmental medicine: lead toxicity
Opens in new window
Adults commonly present with colicky abdominal pain, and lead toxicity should be considered in any patient in whom this symptom is persistent and unexplained. Peripheral neuropathies can also occur in adults.
Neurological symptoms
Nervous system examination may reveal peripheral neuropathy or cerebellar signs such as intention tremor, past-pointing, or dysdiadochokinesia.
In children, headaches, loss of appetite, constipation, agitation, somnolence, or clumsiness are signs of central nervous system (CNS) toxicity that require urgent treatment, as they may progress to encephalopathy. Lead encephalopathy is a medical emergency that presents with altered mental state ranging from subtle alterations in level of arousal and behavioural abnormalities to coma. Patients with lead encephalopathy may develop seizures.
Lead-induced CNS damage in children causes cognitive impairment, which can lead to learning difficulties and delay in reaching developmental milestones. Previously achieved milestones may also regress. Hyperactive and inattentive behaviour can also occur, although this is less commonly caused by lead exposure.
Childhood lead exposure has been associated with long-term consequences in adult life, including lower cognitive function, decline in IQ, psychopathology, and low socioeconomic status.[51]Reuben A, Schaefer JD, Moffitt TE, et al. Association of childhood lead exposure with adult personality traits and lifelong mental health. JAMA Psychiatry. 2019 Apr 1;76(4):418-25.
https://www.doi.org/10.1001/jamapsychiatry.2018.4192
http://www.ncbi.nlm.nih.gov/pubmed/30673063?tool=bestpractice.com
[52]Reuben A, Caspi A, Belsky DW, et al. Association of childhood blood lead levels with cognitive function and socioeconomic status at age 38 years and with IQ change and socioeconomic mobility between childhood and adulthood. JAMA. 2017 Mar 28;317(12):1244-51.
https://www.doi.org/10.1001/jama.2017.1712
http://www.ncbi.nlm.nih.gov/pubmed/28350927?tool=bestpractice.com
[53]Schwaba T, Bleidorn W, Hopwood CJ, et al. The impact of childhood lead exposure on adult personality: Evidence from the United States, Europe, and a large-scale natural experiment. Proc Natl Acad Sci U S A. 2021 Jul 20;118(29):e2020104118.
https://www.doi.org/10.1073/pnas.2020104118
http://www.ncbi.nlm.nih.gov/pubmed/34253605?tool=bestpractice.com
Lifetime lead exposure can be expressed later in life, where it may accelerate the rate of decline in cognition.
Whole-blood lead measurement
The measurement of whole-blood lead is diagnostic. Any detectable lead level is consistent with exposure to lead.
A rise in whole-blood lead from 0.1 micromoles/L (2-3 micrograms/dL) to 0.5 micromoles/L (10 micrograms/dL) results in a significant loss of IQ in children; the loss is more pronounced at these concentrations than at levels above 0.5 micromoles/L (10 micrograms/dL).[27]Lanphear BP, Hornung R, Khoury J, et al. Low-level environmental lead exposure and children's intellectual function: an international pooled analysis. Environ Health Perspect. 2005;113:894-899.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1257652
http://www.ncbi.nlm.nih.gov/pubmed/16002379?tool=bestpractice.com
[28]Jusko TA, Henderson CR, Lanphear BP, et al. Blood lead concentrations < 10 microg/dL and child intelligence at 6 years of age. Environ Health Perspect. 2008;116:243-248.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18288325
http://www.ncbi.nlm.nih.gov/pubmed/18288325?tool=bestpractice.com
[30]Canfield RL, Henderson CR Jr, Cory-Slechta DA, et al. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med. 2003;348:1517-1526.
http://www.nejm.org/doi/full/10.1056/NEJMoa022848#t=article
http://www.ncbi.nlm.nih.gov/pubmed/12700371?tool=bestpractice.com
[54]Centers for Disease Control and Prevention (CDC) Advisory Committee on Childhood Lead Poisoning Prevention. Interpreting and managing blood lead levels < 10 microg/dL in children and reducing childhood exposures to lead. MMWR Recomm Rep. 2007;56:1-16.
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5608a1.htm
http://www.ncbi.nlm.nih.gov/pubmed/17975528?tool=bestpractice.com
However, most environmental interventions at these lower levels have not been demonstrated to decrease blood lead, so prevention is key to preventing this IQ loss.
Diagnostic and therapeutic interventions become more intense as the blood level rises above these thresholds. Plasma or serum lead determinations, although useful in determining the available unbound lead, are not used for diagnosis because they are technically difficult and not widely available.[6]Harvey B, ed. Managing elevated blood lead levels among young children: recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Atlanta, GA: CDC; 2002.
http://www.cdc.gov/nceh/lead/casemanagement/managingEBLLs.pdf
[13]Association of Occupational and Environmental Clinics. Medical management guidelines for lead-exposed adults. Oct 2013 [internet publication].
http://www.aoec.org/documents/positions/mmg_revision_with_cste_2013.pdf
The US Occupational Safety and Health Administration publishes blood lead level reference guides and regulatory recommendations related to adult lead exposure in the workplace.[2]Centers for Disease Control and Prevention (CDC). Understanding blood lead levels. Adult Blood Lead Epidemiology and Surveillance (ABLES). National Institute for Occupational Safety and Health (NIOSH) workplace safety & health topics. Apr 2023 [internet publication].
https://www.cdc.gov/niosh/topics/lead/referencebloodlevelsforadults.html
Urinary lead measurement
Urinary lead is measured during chelation therapy to judge the efficiency of chelation by comparing lead-to-chelant ratios. Adequate chelation is defined as a ratio of more than 1 microgram lead to 1 milligram of chelant.[6]Harvey B, ed. Managing elevated blood lead levels among young children: recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Atlanta, GA: CDC; 2002.
http://www.cdc.gov/nceh/lead/casemanagement/managingEBLLs.pdf
[13]Association of Occupational and Environmental Clinics. Medical management guidelines for lead-exposed adults. Oct 2013 [internet publication].
http://www.aoec.org/documents/positions/mmg_revision_with_cste_2013.pdf
Other investigations
A full blood count and ferritin are used to exclude associated iron deficiency anaemia.
Plain radiographs of the abdomen are recommended if lead ingestion is suspected. Radio-opaque material is not usually observed in the abdomen of children on plain films, but when present it indicates the need to evacuate the gut of the material.[6]Harvey B, ed. Managing elevated blood lead levels among young children: recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Atlanta, GA: CDC; 2002.
http://www.cdc.gov/nceh/lead/casemanagement/managingEBLLs.pdf
Plain radiographs of long bones have previously been recommended in the diagnostic evaluation of paediatric patients, but their value is uncertain. 'Lead lines' in long bones represent growth arrest and are not specific for lead exposure.[55]Gandhi D, Shanbag P, Vaidya M. Lead lines. Lancet. 2003 Jul 19;362(9379):197.
https://www.doi.org/10.1016/S0140-6736(03)13946-3
http://www.ncbi.nlm.nih.gov/pubmed/12885480?tool=bestpractice.com
Furthermore, they are not always present even in heavily exposed children.
Electrophysiology studies are particularly useful in adults with peripheral neuropathies. Nerve conduction studies can document the defects and can be used to follow disease progression.
Emerging investigations
X-ray fluorescence of long bones can estimate long-term exposure to lead using a direct measurement of lead in bone. This has been an exceptionally useful research tool in defining adverse effects of long-term exposure, and this remains its principle use. The high cost and lack of interlaboratory standardisation of methods and results have limited its clinical application.[56]Hu H, Rabinowitz M, Smith D. Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms. Environ Health Perspect. 1998;106:1-8.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1532948&blobtype=pdf
http://www.ncbi.nlm.nih.gov/pubmed/9417769?tool=bestpractice.com
[57]Barry V, Todd AC, Steenland K. Bone lead associations with blood lead, kidney function and blood pressure among US, lead-exposed workers in a surveillance programme. Occup Environ Med. 2019 May;76(5):349-4.
http://www.ncbi.nlm.nih.gov/pubmed/30661026?tool=bestpractice.com
Lead exposure, including during childhood, has been associated with altered brain structure and function.[58]Schwartz BS, Caffo B, Stewart WF, et al. Evaluation of cumulative lead dose and longitudinal changes in structural magnetic resonance imaging in former organolead workers. J Occup Environ Med. 2010;52:407-414.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869464
http://www.ncbi.nlm.nih.gov/pubmed/20357679?tool=bestpractice.com
[59]Brubaker CJ, Dietrich KN, Lanphear BP, et al. The influence of age of lead exposure on adult gray matter volume. Neurotoxicology. 2010;31:259-266.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866835
http://www.ncbi.nlm.nih.gov/pubmed/20226811?tool=bestpractice.com
[60]Brubaker CJ, Schmithorst VJ, Haynes EN, et al. Altered myelination and axonal integrity in adults with childhood lead exposure: a diffusion tensor imaging study. Neurotoxicology. 2009;30:867-875.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789851
http://www.ncbi.nlm.nih.gov/pubmed/19619581?tool=bestpractice.com
MRI scanning can be considered; it may show decreased brain volume and alterations in myelination and axonal integrity.[61]Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med. 2008 May 27;5(5):e112.
https://www.doi.org/10.1371/journal.pmed.0050112
http://www.ncbi.nlm.nih.gov/pubmed/18507499?tool=bestpractice.com