Diagnosis and Discussion - Case 1119

Final Diagnosis

Lead intoxication/ingestion (plumbism).

Discussion

Due to the patient’s history, symptoms, and domicile information, concern for lead intoxication was high. The results of the foreign body X-ray demonstrating intraluminal radiopacities were favored to represent lead-based paint ingestion. Venous heavy metal testing with ICP-MS demonstrated a significantly elevated blood lead level (BLL) of 67.0 µg/dL (RR: 0.0 – 3.4 µg/dL). Immediately following the results, the patient was admitted for lead chelation therapy with 2,3-dimercaptosuccinic acid, succimer (DMSA), and zinc protoporphyrin monitoring. The patient also received whole bowel irrigation with serial abdominal X-rays for radiopacity clearance. Reassuringly, the patient’s iron studies, renal function, liver transaminases, and CBC - without alterations in hemoglobin or mean corpuscular volume – were within normal limits suggesting a favorable outcome with treatment (Table 1).

Despite early reports addressing the deleterious effects of lead, widespread industrial lead use and environmental contamination were prevalent before the 1990s1,2. A recent report on exposure in the United States (US) estimated that over 170 million Americans alive today were exposed to elevated levels of lead in childhood, highlighting how pervasive lead intoxication can be 3. In pediatric patients, ingestion accounts for a majority of cases; whereas, in adults, industrial exposure is the most common means of intoxication4,5.

As lead accumulates in the body, toxicity affects nearly all organ systems. Due to its similarity to other minerals, such as calcium and zinc, it interferes with various cellular mechanisms as a multisystem intoxicant 6. The half-life of lead in adult patients is between 28 to 36 days 4,7. However, if lead reaches the brain, it is thought to remain there for 1 to 2 years resulting in neurologic impairment, irritability, fatigue, and other behavioral symptoms 6,8.  

Outside of venous heavy metal testing with ICP/MS, routine hematologic evaluation using zinc protoporphyrin levels is commonly used to monitor treatment response. Lead interferes with delta-aminolevulinic acid dehydratase and ferrochelatase, two essential enzymes in heme (porphyrin) synthesis 6,9. Inhibition of the aforementioned enzymes results in the blockade of iron insertion into protoporphyrins 6,9. This blockade leads to in increased free protoporphyrins and the incorporation of zinc, creating elevated levels of zinc protoporphyrin 6,9. Thus, as toxicity grows, so does the level of zinc protoporphyrins.

In 2021, the Centers for Disease Control and Prevention (CDC) updated the blood lead reference value (BLRV) from 5.0 µg/dL to 3.5 µg/dL10. To date, the BLRV has been set as the 97.5th percentile of blood lead distribution in children ages 1–5 years in the US based on the National Health and Nutrition Examination Survey (NHANES) data 10. The recent changes reflect the declining geometric mean in BLL in the US and growing efforts to combat structural inequities among at-risk patients10.

As previously mentioned, ICP-MS is routinely utilized for testing of BLL. Two different blood draw methods are available for BLL testing: capillary sampling (finger or heel stick) - as a screening method in pediatric patients - and venous sampling as a confirmatory test8. In adult patients, cases with a high clinical suspicion, or those with an elevated capillary BLL, direct venous sampling may be utilized as the initial or confirmatory test.  Regardless of order type, ICP-MS, a type of mass spectrometry that uses inductively coupled plasma to ionize the sample, followed by mass-to-charge (m/z) ratio separation, is used for all BLL testing11,12. The instrument first aerosolizes the sample, which is then ionized by an argon gas-based plasma at a temperature of nearly 10,000 kelvin 11. After ionization, a vacuum interface transfers the ionized sample to the mass spectrometer, where ion focusing/selection, mass filtration, and detection based on the m/z ratio occurs 11.  

Following admission, monitoring, and prolonged treatment with succimer therapy, the patient’s BLLs continued to tread downward from 67.0 to 6.7 µg/dl. The patient was discharged with a zinc protoporphyrin level of 92 µg/dL and continued oral succimer therapy. However, in cases concerning for ingestion, mitigation and removal of exposure are critical for prevention and meaningful long-term outcomes8. Unfortunately, in our case, re-exposure occurred and the patient was re-admitted for continued in-patient therapy.

In summary, this case presents several classic considerations and findings associated with lead intoxication. The risks and pathophysiology of lead exposure are well documented and highlighted in this case as well as recent changes in testing.  Fortunately, our patient did not demonstrate additional quintessential laboratory rearrangements such as anemia or renal dysfunction, suggesting a more favorable outcome but continued work is need to avoid re-intoxication.

References

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  2. Pirkle JL, Brody DJ, Gunter EW, et al. The decline in blood lead levels in the United States. The National Health and Nutrition Examination Surveys (NHANES). Jama 1994;272: 284-91.
  3. McFarland MJ, Hauer ME, Reuben A. Half of US population exposed to adverse lead levels in early childhood. Proc Natl Acad Sci U S A 2022;119: e2118631119.
  4. Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles Toxicological Profile for Lead. Atlanta (GA): Agency for Toxic Substances and Disease Registry (US), 2020.
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  10. Ruckart PZ, Jones RL, Courtney JG, et al. Update of the Blood Lead Reference Value - United States, 2021. MMWR Morb Mortal Wkly Rep 2021;70: 1509-12.
  11. Wilschefski SC, Baxter MR. Inductively Coupled Plasma Mass Spectrometry: Introduction to Analytical Aspects. Clin Biochem Rev 2019;40: 115-33.
  12. McShane WJ, Pappas RS, Wilson-McElprang V, et al. A rugged and transferable method for determining blood cadmium, mercury, and lead with inductively coupled plasma-mass spectrometry. Spectrochimica Acta Part B: Atomic Spectroscopy 2008;63: 638-44.