Symptomatic Lead Poisoning Research Articles

Pediatric Lead Chelation Managed During Critical Medication Shortages: Case Report and Literature Review.

Lead poisoning in children has the potential for devastating neurodevelopmental consequences. There is significant socioeconomic disparity in children with lead poisoning. Specific lead chelation regimens have been approved for children by the US Food and Drug Administration, however in the United States, there has been a recent national shortage of the primary therapy, edetate calcium disodium (CaNa2 EDTA). This case report presents a 23-month-old child with severe symptomatic lead poisoning during a national shortage of CaNa2 EDTA to highlight the need for advocacy regarding critical medication shortages, especially for antidote therapy. The infant's initial blood lead level was 364 mcg/dL and he received a continuous infusion of CaNa2 EDTA (1000 mg/m2/day), as well as dimercaprol (4 mg/kg intramuscularly every 4 hours). The supply of CaNa2 EDTA was exhausted on day 3 of therapy so he was transitioned to enteral succimer monotherapy. Initial parenteral therapy of 72 hours achieved a lead level of 72 mcg/dL; he then completed his enteral course of succimer along with environmental mitigation. However, elevated blood lead levels persisted and he subsequently required 3 more courses of enteral succimer, and he continues to have detectable blood lead levels 2 years after initial presentation. In the face of medication shortages including CaNa2 EDTA, and now also dimercaprol, clinicians must create and study alternative chelation therapy regimens for pediatric lead toxicity. Furthermore, public policy initiatives, including the development of a national supply stockpile of chelation agents, must be created in order to minimize supply chain disruption and ensure adequate and equitable antidote therapy for lead poisoning outbreaks.

The Weight of Lead: Effects Add Up In Adults

Lead toxicity is not a problem of the past, nor is it the exclusive domain of children. In fact, lead continues today to pose a serious threat to the health of many U.S. adults. It’s true that in the United States, environmental lead levels are much lower than before the toxic metal was removed from gasoline, food cans, and other products in the 1970s and early 1980s. The National Health and Nutrition Examination Surveys have shown that average adult blood lead levels have declined from about 15 μg/dL in the 1970s to today’s 1–2 μg/dL. But there are still pockets of high exposures, such as among workers in certain industries. Despite reductions in exposure following OSHA’s 1978 publication of lead standards for general industry, more than 80% of elevated lead levels in adults come from workplace exposures. Industries most affected include lead mining, refining, and smelting; construction work involving paint removal, demolition, and maintenance of outdoor metal structures such as bridges and water towers; auto repair; and battery manufacturing and recycling. When workplaces adhere to the OSHA standard, occupational exposures are usually reduced below levels that cause symptomatic lead poisoning. But as far back as 1990, studies have suggested that significant health effects happen at levels below those allowed by OSHA. “Historically people had huge lead exposures, so the OSHA standard, when it was originally established, was protective. But right now nobody thinks that that’s a protective standard,” says Rosemary Sokas, director of the Division of Environmental and Occupational Health Sciences at the University of Illinois at Chicago School of Public Health. Now scientists say the evidence is overwhelming that action needs to be taken to further reduce lead exposures in both the workplace and the general environment. “What’s driving concern over the need to reduce permissible levels of exposure in the workplace are . . . more subtle or chronic problems such as hypertension, and contributions to cognitive dysfunction,” says Michael Kosnett, an associate clinical professor of clinical pharmacology and toxicology at the University of Colorado Health Sciences Center. With the lower levels of lead found in the general population in the United States, much of the worry is about lead’s health effects over the long haul. The most recent evidence from epidemiological and toxicological studies suggests that low levels of exposure can, over time, damage the heart, kidneys, and brain. Some of these health effects, such as a 1-mm rise in blood pressure or a slight cognitive decline, seem small when expressed as the average impact to the entire population. In one individual, they may not even be noticed. But the overall impact on public health nevertheless worries scientists.

Prevention of Lead Toxicity in US Children

During the past 2 decades, the proportion of US children who have blood lead concentrations of 10 microg/dL or higher declined by over 80% after the elimination of leaded gasoline and lead solder from canned foods, and a ban on leaded paint used in housing and other consumer products. Fatalities and symptomatic lead poisoning are now rare. Residential lead hazards, which are exceedingly difficult to control, are currently the major source of lead intake for children. Undue lead exposure has retreated into 2 major risk groups; impoverished children who live in older, poorly maintained rental housing and more affluent children who live in older housing undergoing renovation. Despite the dramatic decline in children's blood lead levels, lead toxicity remains epidemic among impoverished children who live in older rental housing, especially those who live in the northeastern and midwestern regions of the United States. There are increasing data linking lead exposure with other systemic effects including delinquency, dental caries, and learning problems. Moreover, there is evidence indicating that there is no discernible threshold for lead-associated cognitive deficits. Thus, it is increasingly important to shift our efforts toward the primary prevention of childhood lead exposure from residential hazards. This article reviews the epidemiology and control of childhood lead exposure, focusing especially on steps necessary to shift toward primary prevention.

Symptomatic lead poisoning in infancy: A prospective case analysis

This report of a case of symptomatic lead poisoning in infancy reinforces the need for continued vigilance in screening and the application of effective therapies to prevent serious physiologic, neurocognitive, and behavioral sequelae. Furthermore, this case illustrates the efficacy of repeated courses of outpatient succimer therapy in limiting a rebound in blood lead concentrations. (J Pediatr 2000;137:568-71)

Childhood Lead Poisoning in 1994

To the Editor. —As described in the July 27, 1994, issue of JAMA , 1,2 the marked decrease in blood lead levels of the US population between 1976 and 1991, documented by NHANES III, is a tribute to effective preventive health measures, mainly the removal of lead from gasoline, cans, and paint. From 1976 to 1991, the mean blood lead level in the United States decreased more than fourfold, with a 10-fold decrease in prevalence of blood lead levels ≥0.48 μmol/L (≥10 μg/dL) among children aged 1 to 5 years, those most at risk. These results confirm clinical observations during the past 20 years—that symptomatic lead poisoning is disappearing among US children. This good news has been counterbalanced by claims that blood lead levels previously considered safe (

SIMULTANEOUS EXPOSURE TO LEAD, ARSENIC AND MERCURY FROM INDIAN ETHNIC REMEDIES

SUMMARY We report the case of an Asian woman who was exposed to toxic levels of lead, arsenic and mercury through the use of Indian ethnic remedies, and who suffered symptomatic lead poisoning. We know of no other case of exposure to such a combination of heavy metals from this source. We believe that control of the dispensing of these compounds is essential.

Exposición al plomo y sus efectos en la salud infantil

Childhood lead poisoning is a man-made disease whose magnitude has not yet been measured in Chile. In the U.S.A. it has been estimated that 4 percent of children have elevated blood lead levels and that among poor black children, this rate is as high as 18 percent. The main sources of symptomatic lead poisoning are lead-based paint used in interior and exterior house surfaces, airborne lead from leaded gasoline and industrial emissions. Lead can be transferred from any source to soil and dust. Other sources of lead are contaminated food and water, occupational sources, and lead glazed pottery. Neurological symptoms (hyperactivity, distractibility, lower intellectual development), psychological difficulties (behavioral deficits), hematologic abnormalities (reduction in the biosynthesis of heme, anemia), and metabolic changes (reduction in concentration of 1-25 dihydroxy vitamin D and in the metabolism of erythrocyte pyrimidine) have been shown to occur in lead poisoning. Recent data suggests that prenatal exposure to lead my be related to minor congenital abnormalities, tumors of the kidney, and growth abnormalities.

Lead Poisoning by Contaminated Flour

Between October 1982 and June 1983, 43 patients were identified with symptomatic lead poisoning in three Arab villages of the Nablus district. Because of the clustering of clinical poisoning by household units, investigation was focussed on potential sources common to all members of the households. After excluding water, olive oil and a variety of foodstuff, lead in high concentrations was discovered in locally ground flour in all affected households. The source of poisoning was lead poured into the fissures between the metal housing and the driveshaft of the millstone. Significant lead contamination of freshly ground flour was demonstrated in 23% of the 146 community flour mills operating in West Bank villages. Since the completion of these studies, similar outbreaks of lead poisoning caused by contaminated flourmills have been identified in the Upper Galilee and in Spain. As the methods of milling in the Mediterranean area are similar, a coordinated international effort is needed in order to eliminate this health hazard from countries where similar community stone mills are still in use.

Delta-Aminolaevulinic acid dehydratase as an index of the presence and severity of lead poisoning in acute and chronic lead exposure.

The activity of delta-aminolaevulinic acid dehydratase (ALA-D; porphobilinogen synthase) was measured in whole blood from a group of workers with acute exposure to lead and with low blood lead levels, a group of workers with chronic lead exposure and high blood lead levels, and a group of people without undue environmental lead exposure. The activity of ALA-D was reduced significantly at low blood lead levels only if undue exposure to lead had occurred, and was thus a reflection of low level lead poisoning. In chronic lead exposure the enzyme was not invariably reactivated fully with dithiothreitol, indicating more severe enzyme poisoning. The one lead worker with symptomatic lead poisoning had the most marked enzyme suppression. Measurement of both ALA-D activity and blood lead levels was more useful than the measurement of blood lead levels alone in the diagnosis and assessment of the severity of lead poisoning.

Occupational lead exposure: Studies in two brothers showing differential susceptibility to lead

Unexpected differences in clinical and biochemical findings in two brothers occupationally exposed to the same source of lead for dissimilar lengths of time are presented. Only the brother with the shorter period of lead exposure was anemic and afflicted by nausea, vomiting, abdominal colic and arthralgia. His urinary PBG output yielded the high orders of magnitude found in acute intermittent porphyria in relapse. Prior to administration of a single dose of EDTA (1 g of the calcium disodium salt given intravenously in 325 mL 0.15 mol/L NaCl), his blood lead levels averaged 3.6 mumol/L. The amount of chelatable lead retrieved from his urine, 31 mumol/day, was more than twice that found in his asymptomatic counterpart who was exposed to lead for 13 months and whose pre-EDTA blood lead levels averaged 4.0 mumol/L. Not only the activity of delta-aminolaevulinic acid dehydratase, but also that of uroporphyrinogen I synthetase, was markedly inhibited by lead in red cells of both brothers. These activities were restored to normal levels in vitro by addition to the assay system of zinc and dithiothreitol. This ruled out a coexisting genetic deficiency of either enzyme. The anemia of the symptomatic brother with the shorter period of lead exposure was alleviated by folic acid, 15 mg/day. The differences in findings between the two brothers point to differential susceptibility to lead and illustrate the extent to which symptomatic lead poisoning may mimic biochemical and clinical features of the acute porphyrias.

660 MILD LEAD POISONING IS STRONGLY ASSOCIATED WITH IRON DEFICIENCY

Anemia is often found in children with severe or symptomatic lead poisoning and is attributed to the inhibition of heme synthesis by lead. During a one year period of using Erythrocyte Protoporphyrin (EP) as a screening test in an urban pediatric clinic, 191 children had elevated EP (≥ 35 μg/dl whole blood) and had further evaluation of lead and iron status. 43 children had a confirmed elevation of blood lead (Pb ≥ 30 μg/dl),33 (77%) with EP ≥ 50 fulfilling the diagnosis of undue lead absorption, a relative mild form of lead poisoning. Of the 43 children with evidence of mild lead poisoning, 38 (86%) also had evidence of iron deficiency based on ferritin ≤ 15 ng/ml and/or transferrin saturation < 16%; 13 (30%) were anemic. This is significantly higher than the rate of iron deficiency of 9% and rate of anemia of 4% in the same general population. This strong association of mild lead poisoning with iron deficiency is in accord with the observation of increased lead absorption in iron deficiency. It is likely that iron deficiency strongly predisposes to lead poisoning and explains, at least in part, the high prevalence of anemia associated with lead poisoning.

Age and sensitivity to lead toxicity: a review.

During the past 20 years considerable attention has been focused on the epidemiologic features of childhood lead poisoning in the United States. Large numbers of children with symptomatic intoxication, as well as those with incipient symptoms, were commonplace a decade ago for physicians working in inner-city hospitals. With the recent availability of improved screening techniques, as well as a variety of environmental control measures, the incidence of symptomatic lead poisoning in children has diminished significantly in recent years. With the focus shifting from children with dangerously elevated body lead burdens to those with less significant exposures, increased attention has been directed to the various inherent metabolic and physical characteristics of the young that may influence the toxic effects of lead exposure. A number of differences with respect to lead exposure, absorption and retention, and varying nutritional conditions between children and older individuals are discussed. Experimental studies dealing with age differences of lead-treated animals are examined, and relevant human studies are reviewed.

Age and Sensitivity to Lead Toxicity: A Review

During the past 20 years considerable attention has been focused on the epidemiologic features of childhood lead poisoning in the United States. Large numbers of children with symptomatic intoxication, as well as those with incipient symptoms, were commonplace a decade ago for physicians working in inner-city hospitals. With the recent availability of improved screening techniques, as well as a variety of environmental control measures, the incidence of symptomatic lead poisoning in children has diminished significantly in recent years. With the focus shifting from children with dangerously elevated body lead burdens to those with less significant exposures, increased attention has been directed to the various inherent metabolic and physical characteristics of the young that may influence the toxic effects of lead exposure. A number of differences with respect to lead exposure, absorption and retention, and varying nutritional conditions between children and older individuals are discussed. Experimental studies dealing with age differences of lead-treated animals are examined, and relevant human studies are reviewed.

Prophylactic chelation therapy in occupational lead poisoning: a review

Chelating agents are useful in the therapy of acute overexposure to lead. However, prophylactic use of chelating agents, particularly under conditions of continued exposure to lead can be harmful to health. Potential adverse effects include kidney damage, symptomatic lead poisoning, increased absorption of lead from the gastrointestinal tract and disruption in the metabolism of trace metals other than lead. Prophylactic chelation is an unacceptable medical practice which cannot be condoned.