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lead poisoning (plumbism)

Etiology: 1) most cases of lead poisoning result from inhalation or ingestion a) paint (major source) b) drinking water c) contaminated soil d) airborne particles & dust e) ceramics & stained glass f) folk remedies g) cosmetics h) food i) retained bullets j) 'Moonshine' alcohol 2) children are at increased risk of lead poisoning a) repeated hand to mouth activity b) higher gastrointestinal absorption of lead than adults c) pica 3) cosmetic use in immigrant children - traditional Nigerian eye makeup 'tiro' [6] 4) occupational exposure of parent [9] - electronics recycling facility where cathode ray tubes are crushed (cathode ray tubes are made from leaded glass) Epidemiology: 1) CDC set safe limit for blood lead level as < 10 ug/dL 2) previously < 25 ug/dL was considered acceptable 3) nearly 3% of U.S. children age 1-5 years have elevated blood lead levels [7] 4) lead poisoning confirmed in children of Flint Michigan after their water source was switched from the Detroit Water Authority (DWA), sourced from Lake Huron, to the Flint Water System (FWS), sourced from the Flint River [10] - corrosion control was not used at the FWS water treatment plant, & the levels of lead in Flint tap water increased over time [10] 5) 400,000 deaths/year in U.S. related to lead exposure [12]* * higher baseline blood lead levels associated with higher risk of cardiovascular mortality (RR=1.29) & all-cause mortality (RR-1.18), 90th percentile (6.7 ug/dL) vs 10th percentile (1.0 ug/dL) [12] * RR=1.27 for mortality due to ischemic heart disease [12] Pathology: 1) lead inhibits heme synthesis by inhibiting delta-aminolevulinic acid dehydratase 2) nephrotoxicity a) lead inhibits uric acid secretion b) chronic renotubular interstitial nephritis c) Fanconi-like syndrome - glycosuria with normglycemia - hypophosphatemia - aminoaciduria 3) > 90% of total body lead with chronic lead exposure resides in bone Clinical manifestations: 1) most patients are asymptomatic 2) gastrointestinal a) abdominal pain c) nausea/vomiting d) constipation 3) myalgias 4) central nervous system a) lethargy b) cognitive deficits - with cumulative exposure [2] - cognitive damage with levels > 10 ug/dL [5] c) irritability d) seizures e) encephalopathy f) coma with levels > 100 ug/dL 5) developmental deficits in children a) change in behavior b) decreased intelligence c) reduced attention span d) poor school performance 6) hypertension & renal failure in adults 7) Burton's lines with chronic chewing of lead-contaminated opium [14] Laboratory: 1) complete blood count: microcytic anemia [18] - peripheral blood smear: basophilic stipling of erythrocytes (non-specific) [3] 2) blood lead level a) a federal advisory panel has recommended lowering the cutoff for lead poisoning in children from 10 to 5 ug/dL [5] b) blood lead levels may not be an adequate indicator of chronic lead exposure, especially if exposure was in the past [3] c) in the U.S. population baseline blood lead levels - 90th percentile 6.7 ug/dL - 10th percentile 1.0 ug/dL [12] 3) erythrocyte protoporphyrin was test of choice for lead screening in past, but insufficiently sensitive for blood lead levels < 10 ug/dL - levels do not reflect total body lead [3] 4) iron studies a) serum iron b) total iron-binding capacity (TIBC) c) serum ferritin 5) calcium EDTA provocative chelation test when lead poisoning suspected, but blood lead level within normal limits [3] 6) tibia lead level reflects long-term lead stores, but declines over time after exposure ends [2] 7) serum uric acid levels may be elevated [3] 8) urinalysis - low-grade proteinuria; rare WBC, RBC 9) urine glucose, serum glucose: glycosuria with normoglycemia 10) aminoaciduria [3] 11) serum phosphate: hypophosphatemia Radiology: 1) plain films of the abdomen may show ingested lead chips 2) "lead lines" may be seen on radiographs of long bones of growing children [3] 3) cumulative exposure associated with white matter lesions in brain MRI [2] Complications: - increased risk for gout - lead exposure in childhood is associated with slightly lower cognitive function & socioeconomic status in adulthood [11] Differential diagnosis: 1) other neurologic diseases 2) developmental delay 3) behavioral disturbance 4) anemia of other origin 5) gastrointestinal disorder 6) erythropoietic protoporphyria Management: 1) general - identify source of exposure - notify local health department 2) asymptomatic patients a) 10-19 ug/dL - recheck in 3-4 months - environmental investigation b) 20-44 ug/dL - complete medical & environmental evaluation - effectiveness of chelation therapy not established c) 45-69 ug/dL - chelation therapy - environmental evaluation d) >70 ug/dL: hospitalize for chelation therapy 3) chelation therapy for symptomatic patients a) calcium EDTA - 35-75 mg/kg/day IV in divided bid/tid for 3-5 days - monitor renal & hepatic function during therapy b) dimercaprol (BAL in oil) - 3-4 mg/kg IM q4h for 5-7 days - do not use in children allergic to peanuts or patients with G6PD deficiency c) D-penicillamine (Cuprimine) - 25-35 g/kg/day PO - do not use in patients allergic to penicillin - not FDA approved for plumbism d) succimer (DMSA) (Chemet) PO, for outpatient chelation - 3 weeks of therapy - 10 ug/kg PO q8h for 1st 5 days - 10 ug/kg PO q12 for next 14 days 4) patient education 1) educate parents about potential sources of lead poisoning 2) review with patients the symptoms of lead poisoning 3) screen household members 5) follow-up a) Source of lead exposure should be removed (abated) before patient is to return to environment b) blood lead level (BLL) should be checked 7-21 days after chelation therapy (rebound increases in BLL may occur) 6) insufficient evidence to recommend for or against screening of asymptomatic children or pregnant women [13]

Related

erythropoietic protoporphyria (EPP) lead in blood lead [Pb]

General

heavy metal toxicity

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1167-68
  2. Stewart WF et al, Past adult lead exposure is linked to neurodegeneration measured by brain MRI. Neurology 2006, 66:1476 PMID: 16717205
  3. Medical Knowledge Self Assessment Program (MKSAP) 14, 16, 18. American College of Physicians, Philadelphia 2006, 2012, 2018.
  4. U.S. Preventive Services Task Force Screening for Lead Levels in Childhood and Pregnancy http://www.ahrq.gov/clinic/uspstf/uspslead.htm
  5. Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention Report of the Advisory Committee on Childhood Lead Poisoning Prevention of the Centers for Disease Control and Prevention http://www.cdc.gov/nceh/lead/ACCLPP/Final_Document_010412.pdf - Centers for Disease Control and Prevention Advisory Committee On Childhood Lead Poisoning Prevention (ACCLPP) http://www.cdc.gov/nceh/lead/ACCLPP/acclpp_main.htm
  6. Centers for Disease Control and Prevention Infant Lead Poisoning Associated with Use of Tiro, an Eye Cosmetic from Nigeria - Boston, Massachusetts, 2011 MMWR. August 3, 2012 / 61(30);574-576 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6130a3.htm
  7. Centers for Disease Control and Prevention Blood Lead Levels in Children Aged 1-5 Years - United States, 1999-2010 MMWR. April 5, 2013 / 62(13);245-248 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6213a3.htm
  8. Ekong EB, Jaar BG, Weaver VM. Lead-related nephrotoxicity: a review of the epidemiologic evidence. Kidney Int. 2006 Dec;70(12):2074-84 PMID: 17063179
  9. Newman N, Jones C, Page E et al Investigation of Childhood Lead Poisoning from Parental Take- Home Exposure from an Electronic Scrap Recycling Facility - Ohio, 2012. MMWR Weekly. July 17, 2015 / 64(27);743-745 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6427a3.htm
  10. Kennedy C, Yard E, Dignam T, et al. Blood Lead Levels Among Children Aged < 6 Years - Flint, Michigan, 2013-2016. MMWR Morb Mortal Wkly Rep. ePub: 24 June 2016 http://www.cdc.gov/mmwr/volumes/65/wr/mm6525e1.htm
  11. 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;317(12):1244-1251 PMID: 28350927 http://jamanetwork.com/journals/jama/article-abstract/2613157 - Bellinger DC Childhood Lead Exposure and Adult Outcomes. JAMA. 2017;317(12):1219-1220 PMID: 28350907 http://jamanetwork.com/journals/jama/article-abstract/2613136
  12. Lanphear BP, Rauch S, Auinger P, et al Low-level lead exposure and mortality in US adults: a population-based cohort study. Lancet Public Health. March 12, 2018 PMID: 29544878 Free full text http://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(18)30025-2/fulltext
  13. US Preventive Services Task Force Screening for Elevated Blood Lead Levels in Children and Pregnant Women. US Preventive Services Task Force Recommendation Statement. JAMA. 2019;321(15):1502-1509. PMID: 30990556 https://jamanetwork.com/journals/jama/fullarticle/2730621 - Cantor AG, Hendrickson R, Blazina I et al Screening for Elevated Blood Lead Levels in Childhood and Pregnancy. Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2019;321(15):1510-1526. PMID: 30990555 https://jamanetwork.com/journals/jama/fullarticle/2730620 - Spanier AJ, McLaine P, Gilden RC. Screening for Elevated Blood Lead Levels in Children and Pregnant Women. JAMA. 2019;321(15):1464-1465. PMID: 30990534 https://jamanetwork.com/journals/jama/fullarticle/2730594
  14. Helmich F, Lock G. Burton's Line from Chronic Lead Intoxication. N Engl J Med 2018; 379:e35. Nove 8, 2018 PMID: 30403939 https://www.nejm.org/doi/full/10.1056/NEJMicm1801693
  15. Zamani N, Hassanian-Moghaddam H Ingestion of Lead-Contaminated Packs of Opium. N Engl J Med 2018; 379:1861. Nov 8, 2018 PMID: 30403949 https://www.nejm.org/doi/full/10.1056/NEJMicm1807901
  16. Lin JL, Lin-Tan DT, Li YJ, Chen KH, Huang YL. Low-level environmental exposure to lead and progressive chronic kidney diseases. Am J Med. 2006 Aug;119(8):707.e1-9. PMID: 16887418
  17. ARUP Consult: Trace Elements - Deficiency and Toxicity The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/trace-minerals
  18. Rothaus C Lead Astray NEJM Resident 360. Aug 5, 2020 https://resident360.nejm.org/clinical-pearls/led-astray
  19. National Institute of Environmental Health Sciences Lead https://kids.niehs.nih.gov/topics/chemicals/lead/index.htm