Systemic Lead Toxicity

In this case, an anteroposterior radiograph of the knees bilaterally (Figure 1) showed abnormal sclerosis at the distal femoral and the proximal tibial and fibular metaphyses. The physes were well formed without fragmentation or deformation. There was no periosteal reaction. Imaging findings were characteristic of lead poisoning, which may account for the mental status of the child as well.

Figure 1: A 4-year-old girl with lead intoxication. Anteroposterior radiograph of the knees bilaterally. There is increased radiodensity at the distal femoral metaphyses and proximal tibial and fibular metaphyses. No fragmentation, physeal widening, or periosteal new bone can be seen.

Clinical Presentation

Although lead poisoning can affect both adults and children, the short- and long-term effects are greater in children because of their smaller size (and therefore lower lead dose to reach toxicity), and because of the impact on growth and development. Despite the widely recognized effects of lead toxicity and public programs promoting screening, there are at least 4 million households today that have living conditions resulting in children being exposed to high levels of lead.¹ There are approximately half a million children in the United States aged 1 to 5 years with blood lead levels above 5 µm/dL.¹ This is the reference level at which the Centers for Disease Control and Prevention recommends intervention for elimination of continued exposure, although medical management is not recommended until a level of 45 µm/dL is achieved. Ultimately, there is no definite safe blood lead level.¹

Lead is common in the environment, existing in dirt, dust, and toys.² All products with lead paint place children at risk. Although now banned in the United States, lead was previously a common additive to paint to enhance opacity and durability. Consequently, children living in turn-of-the-century homes are at risk for having high levels of lead. Children may ingest lead when mouthing objects painted with contaminated paint. Unfortunately, repeated exposure is encouraged by the sweet taste. Lead may also be ingested due to poor hygiene or sucking on fingers exposed to contaminated dust or paint chips. Further, lead may be inhaled in household dust. Ironically, exposure may be intensified when paint removal is attempted without appropriate precautions for containment.²

Of the many possible symptoms of lead poisoning, most are nonspecific, such as abdominal pain, behavioral changes, headaches, and irritability.³ Clinical signs of toxicity include intellectual decline, hearing decline, and renal in-sufficiency.³ More commonly, lead accumulation to toxic levels occurs slowly without symptoms. Therefore, screening programs are in place for at-risk populations. At the federal level, all children receiving Medicaid support are required to have serum blood levels tested at 12 and 24 months.¹ The American Academy of Family Practitioners and the American Academy of Pediatrics recommend this testing as part of well child checkups. The Centers for Disease Control and Prevention also recommends individual government mandates based on community risk factors, such as a dense population of older homes (≥27% pre-1950 era) or a large immigrant population.¹ Signs of lead poisoning can also be found on radiographs, making imaging a critical tool in identifying patients, especially when asymptomatic.

The focal arthropathic process described from retention of a lead-based foreign body is different from the sequelae of systemic intoxication. Proliferative synovitis and progressive erosive arthritis have been described in patients who have retained intra-articular lead bullet fragments. The severity of radiographic findings of the arthropathy is directly related to the amount of time the bullet has been in the joint, the degree of fragmentation of the original projectile, and the amount of lead surface exposed to the synovial fluid.⁴Systemic lead intoxication secondary to long-standing intra-articular lead bullets chronically bathed in synovial fluid is extremely uncommon. However, removal of lead bullets within a joint is recommended to avoid both of these complications.⁵

Imaging

Abdominal Radiographs

Anteroposterior radiographs of the abdomen are obtained if acute lead ingestion is suggested by clinical history. Pica, the ingestion of inedible material, and the eating of dirt may explain the ingestion. Multiple metallic particles in the stomach or colon would be radiographically apparent (Figure 2). Anteroposterior radiographs of the abdomen and the knees should be obtained for a child who presents with encephalopathy and demographic descriptors that suggest potential lead exposure.⁶ On occasion, the lead particles are identified on imaging of the abdomen obtained for unrelated reasons.

Figure 2: A 2-year-old girl with pica. Anteroposterior radiograph of the abdomen showing extensive scattered metallic particles (arrows) throughout the colon following particulate ingestion, likely lead paint chips.

Appendicular Radiographs

Radiographs are valuable during the first through sixth years of life, when bone growth is rapid; this also corresponds with the ages when the risk of lead ingestion is high. On imaging, identification of abnormally increased density of the metaphysis of the long bones (“lead lines”) warrants evaluation for systemic lead toxicity.

The pathophysiology of the radiographic lead line can be appreciated by understanding the pattern of growth of the long bones. The primary bone region accounting for long bone growth is the metaphysis, which has orderly enchondral bone development progressing from chondral scaffolding to mineralization. Bisgard and Bisgard⁷ showed migration of epiphyseal lines away from radiopaque markers placed in the diaphysis, proving that bone lengthening takes place only at the ends of the long bones.

Normal metaphyseal enchondral bone growth, in the zone of provisional calcification, requires the maintenance of a balance between osteoblastic bone deposition and osteoclastic bone remodeling, which is disrupted by lead deposition. Initially, lead ions deposit on the hydroxyapatite crystal preferentially in the zone of provisional calcification. Subsequent lead incorporation by phagocytic osteoclasts during the remodeling process results in osteoclastic failure and reduced bone resorption. Maintenance of this mineralized cartilage accounts for the relative radiodensity at the metaphyses. It is not the lead itself that explains the radiodensity.⁸ Ingalls⁹ confirmed that the zone of active enchondral bone formation at the metaphysis is the first osseous zone to show pathologic change, and disturbances in growth pattern due to ingestion of substances such as lead can be shown in this space after a few days. The width of the dense metaphysis correlates with the length of the period of toxic exposure. Although it was initially reported that the appearance of a lead line required a minimum blood lead concentration of 70 to 80 µm/dL,⁸ further research has shown that a lead line may appear at lower lead levels.¹⁰

The standard radiographic survey consists of a posteroanterior view of the wrists and an anteroposterior view of the knees (Figure 3).⁸ Lateral views are considered redundant and therefore not recommended. These anatomical sites reflect the most metabolically active regions in the body contributing to long bone growth. Therefore, disturbance of physeal growth will be easily detected in these regions. However, dense metaphyseal bands can be seen at other long bone physes (Figures 4–5).

Figure 3: A 6-year-old boy with lead intoxication. Posteroanterior radiograph of the left wrist showing broad radiodensity of the distal radial (arrow) greater than the ulnar metaphyses.

Figure 4: A 2-year-old girl with lead toxicity. Anteroposterior radiograph of the tibia and fibula showing increased density at the proximal and distal metaphyses (arrows), as well as the distal femoral metaphysis.

Figure 5: A 4-year-old girl with lead toxicity. Anteroposterior radiograph of the left knee showing dense metaphyseal bands or “lead lines.”

Differential Diagnosis for Dense Metaphyseal Bands

The radiographic finding of radiodense metaphyseal bands is not specific to lead intoxication. Broad transverse metaphyseal bands may also be found in healthy children with no lead exposure¹¹ (Figure 6). Differentiation between normal variant and lead lines is possible by assessing (1) the patient’s age (children with lead ingestion are usually younger than 4 years, whereas those with physiologic bands are older than 4 years); (2) migration of the dense band (persistence and migration of the bands in lead intoxication, but resolution in healthy children); and (3) blood lead levels (greater than 70–80 µm/dL in children with lead toxicity).⁸ In addition, in healthy patients, the metaphyseal zone of the tibia may appear dense but the proximal fibula does not. Conversely, in patients with lead poisoning, the dense line is present at both the proximal tibial and proximal fibular metaphyses.¹⁰

Figure 6: A 6-year-old boy with normal variant. Anteroposterior (A) and lateral (B) radiographs of the left knee showing increased density at the femoral and tibial metaphyses (white arrows), with sparing of the fibular metaphysis (red arrow).

Key differential pathologic diagnoses to consider include treated leukemia, healing rickets, vitamin D toxicity, congenital hypothyroidism, transplacental infections, or other heavy metal poisoning.^11,12 Although radiographically similar, medical history should clearly distinguish cases of post-leukemic sequelae and treated rickets (Figure 7). Similarly, accurate history taking should delineate the overzealous administration of vitamin D. Manifestations of congenital hypothyroidism are not confined to radiographic dense metaphyseal bands (including stippled or diminutive epiphyses, delayed physeal closure, and delayed bone age), with characteristic clinical signs of hypotonia, lethargy, failure to thrive, and poor weight gain.¹¹ Transplacental infections generally manifest in infancy with a variety of clinical signs and identifiable serum laboratory abnormalities.¹¹

Figure 7: A 2-year-old girl receiving treatment for rickets. Posteroanterior radiograph of the wrists showing increased metaphyseal density at the distal radius and ulna with slight cupping and minimal fraying (arrows) (A). Anteroposterior radiograph of the right ankle showing similar increased metaphyseal density at the tibial (arrow) and fibular metaphyses (B).

Treatment

Treatment for systemic lead intoxication requires 2 approaches. The most important step is identification of the source of ingestion and prevention of further exposure.¹ Accurate assessment of all environmental and occupational exposures is essential. The second prong of treatment is medical intervention. If metallic particles are identified within the gastrointestinal tract, stomach lavage or per-rectal enemas may reduce additional absorption. Chelation is the mainstay of treatment to actively reduce serum lead, with the route of administration (intravenous vs oral) and the agent dependent on the severity of symptoms and serum lead levels.^1,3

Radiographs can document the progress of therapy. During chelation treatment, the newly mineralized, healthy metaphysis appears relatively lucent adjacent to the lead line. The preexisting lead line seems to migrate toward the diaphysis as the healthy metaphysis grows in height. With subsequent remodeling and reorganization of the abnormal segment due to restored balance of bone deposition and resorption, the dense band gradually disappears, usually being undetectable within 4 years.⁸

Conclusion

Lead exposure remains a serious problem among children in the United States. Many children with abnormal serum lead levels are identified through government-mandated screening or through compliance with Centers for Disease Control and Prevention recommendations, most commonly performed at 12 and 24 months of age.

However, laboratory analyses of serum lead levels in children are not always performed or readily accessible. Radiographs can be used both in an emergent setting when acute ingestion is suspected and to identify sequelae of chronic heavy metal exposure. Although the differential diagnosis is broad, radiographs can be used to initiate the evaluation for toxic lead ingestion when discovered incidentally. Further, any child who presents with unexplained encephalopathy should undergo radiography of the knees, as the presence of metaphyseal dense bands will support the diagnosis of lead toxicity. Accurate interpretation of important radiographic findings allows initiation of appropriate management, with restoration of normal bone growth and stabilization or improvement of clinical signs.