Mercury intoxication resembling pediatric rheumatic diseases: case series and literature review.

Mercury is the only metal that remains in liquid form at the room temperature. It is a very toxic metal and even short-term exposure can lead to poisoning. Mercury intoxication can affect many systems such as skin, cardiovascular, genitourinary, central and peripheral nervous, respiratory, and musculoskeletal system. Consequently, the diagnosis of mercury intoxication can be challenging due to its non-specific and multisystemic presentation. Herein, we report five pediatric cases with mercury intoxication from two families that were initially misdiagnosed as rheumatic disorders. We also performed a literature review about pediatric cases with mercury intoxication to investigate the clinical findings in children, the source of intoxication, and the current treatment preferences. As in our cases, reported patients were previously misdiagnosed as various infectious and/or rheumatic diseases before the diagnosis of mercury intoxication was established. A delay in diagnosis and treatment can cause serious morbidities and even mortality. We report this case series to emphasize the multisystemic presentation of mercury intoxication, and to remind and provide clues for physicians to recognize this rare toxicologic syndrome.

CYP3A Polymorphism and Chronic Mercury Intoxication.

We analyzed the relationship between polymorphic loci of CYP3A genes (CYP3A4 (rs2740574), CYP3A5 (rs776746) and CYP3A7 (rs2257401)) with the development of chronic mercury intoxication. Of 170 men examined, 120 were workers chronically exposed to mercury vapors and 50 were carriers of GG-HSPA1B (+1267A/G) genotype associated with chronic mercury intoxication. Urinary content of 4-hydroxyantipyrine (4-HAP) generated in the reaction predominantly catalyzed by CYP3A4/CYP3A5 was studied in workers without chronic mercury intoxication (group 1, N=46) and patients in the delayed period of chronic mercury intoxication (group 2, N=74) depending on the genotypes of CYP3A4 and CYP3A5. For polymorphic loci CYP3A5 and CYP3A7, a tendency to an increase in the frequency of genotypes with rare alleles was found (p=0.071 and p=0.078) in the combined group (group 2 together with GGHSPA1B genotype carriers) relative to group 1. The high level of linkage disequilibrium was noted, especially for the pair rs776746 and rs2257401 (LD (r)=0.89). In group 2, a trend to 4-HAP decrease compared to group 1 (p=0.056 and p=0.065) was revealed for carriers of AA-CYP3A4 and GG-CYP3A5 genotypes. The involvement of CYP3A in the development of mercury neurotoxic effect remains unclear.

The Association Between Mercury Exposure and Atopic Dermatitis in Early Childhood: A Mothers and Children's Environmental Health Study.

BACKGROUND: Atopic dermatitis is a chronic and relapsing inflammatory skin disease. Although mercury has been suggested as a risk factor, the underlying mechanism and the relationship between mercury and atopic dermatitis remains unclear. The objective of the present study was to investigate the relationship between mercury exposure and the presence of atopic dermatitis in early childhood. METHODS: This study is part of the prospective Mothers and Children's Environmental Health cohort study. A total of 1,751 pregnant women were enrolled in Mothers and Children's Environmental Health. After delivery, children were followed up. Blood samples were collected and mothers were asked about the presence of atopic dermatitis in their children via a questionnaire at 6, 12, 24, 36, and 60 months of age. RESULTS: After excluding participants who did not meet the inclusion criteria, a total of 1,061 mother-children pairs were included in the analysis. The geometric mean of mercury concentrations in cord blood was 5.1 µg/L. In adjusted models, cord blood mercury exposure (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 1.0, 1.2 at 12-24 months) and postnatal mercury exposure (OR = 1.2; 95% CI = 1.0, 1.5 at 24-36 months, OR = 1.4; 95% CI = 1.1, 1.8 at 48-60 months) were associated with the presence of atopic dermatitis in children. CONCLUSIONS: Postnatal mercury exposure at 24 months of age increases the risk of atopic dermatitis in children.

Effects of diphenyl diselenide diet on a model of mercury poisoning.

This work investigated the preventive effect of diphenyl diselenide [(PhSe)2] against the toxic effects of mercury in silver catfish (Rhamdia quelen). The animals were treated during 30 consecutive days with a (PhSe)2 supplemented feed (3.0 mg kg-1) or commercial feed. During the last 5 days the animals received a daily intraperitoneal dose of HgCl2 (1.7 mg kg-1) or Saline (0.9%). Twenty-four hours after the last HgCl2 injection, the animals were euthanized by spinal cord section to biological material obtainment. Hepatic (AST and ALT) and renal (ammonia and creatinine) toxicity biomarkers, δ-ALA-D activity, TBARS, total and non-protein thiols levels and hepatic, renal and blood mercury (Hg) and zinc (Zn) content were evaluated. Considering renal parameters, HgCl2 exposition increased serum creatinine levels and decreased δ-ALA-D activity, total and non-protein thiols and TBARS levels. HgCl2 exposure also decreased blood δ-ALA-D activity. With exception of blood δ-ALA-D activity and total thiols levels, (PhSe)2 supplementation partially prevented mercury induced alterations. Animals exposed to HgCl2 presented an increase in liver and kidney Hg content and a decrease in liver and blood Zn content. The alteration in blood Zn content was partially prevented with (PhSe)2 supplementation. With the exception of mercury and zinc content, no effects of HgCl2 exposure on hepatic tissue were observed. These results show that (PhSe)2 supplementation can represent a promising alternative to prevent the toxic effects presented by Hg exposure.

Low doses of mercuric chloride cause the main features of anti-nucleolar autoimmunity in female outbred CFW mice.

The growth of the influence of anthropogenic factors aimed on the improvement of human life has its side effect, for example, living organisms receive increasing exposure to toxic mercuric compounds. Experimental data show that mercury (Hg) salts are able to induce systemic autoimmunity in rodents. This Hg-induced autoimmune process (HgIA) is characterized by T cell-dependent polyclonal activation of B lymphocytes, increased level of serum immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), production of antinucleolar autoantibodies (ANoA), and immune complex deposition in multiple organs. HgIA in mice is used as a model of human systemic autoimmune disorders. However, the dose of mercuric chloride (HgCl2) usually used in laboratory mice to induce HgIA is above the allowable limit for everyday levels of Hg exposure in humans. So, we decided to determine the lowest dose of HgCl2 that is able to trigger autoimmunity in outbred Carworth Farms Swiss Webster (CFW) mice not genetically prone to HgIA development. The lowest dose (50 µg/kg body weight (b.w.)/week) was chosen to match the World Health Organization provisional weekly tolerable intake of total Hg for humans. We also tested HgCl2 at 500 and 1500 µg/kg b.w./week (6.5- and 2-fold less than usually used for induction of HgIA in mice). We found that even the lowest dose of Hg resulted in a statistically significant increase in serum level of IgG1 after 8 weeks of treatment. HgCl2 in doses 500 and 1500 µg/kg b.w./week resulted in a significant increase in serum level of IgG1 after 4 weeks of treatment, followed by ANoA production. Sera of HgCl2-treated mice stained the regions in which the major autoantigen in HgIA, fibrillarin, was revealed. These results suggest that low doses of Hg are able to induce the main features of HgIA in genetically heterozygous mice, and that humans chronically exposed to low doses of Hg may be at risk of autoimmunity induction regardless of their genetic background.

Prenatal Maternal Occupational Exposure and Postnatal Child Exposure to Elemental Mercury.

OBJECTIVES: Young children are highly vulnerable to elemental mercury toxicity, and elementary mercury exposure in young children in China unfortunately occurs regularly because of the wide use of fluorescent lamps, glass thermometers, and other mercury-contained items. This study aimed to summarize such recent cases in a referral clinic and to make recommendations for postexposure treatment and prevention of future exposure. METHODS: Patients were evaluated between January 2007 and December 2009 in environmental health facilities throughout China and were referred to our clinic. A total of 6 children younger than 4 years with significant elemental mercury exposure were included in this case series analysis. The total mercury content in blood and hair (fetal hair if necessary) and average 24-hour urine mercury concentrations were analyzed. Meso-2,3-dimercaptosuccinic acid or surgery was prescribed for the patient if necessary. RESULTS: Young children were found to be exposed in 3 ways as follows: prenatal exposure through maternal occupational contact in compact fluorescent-lamp factories (2 cases), broken thermometers (3 cases), and other causes of accidental inhalation of mercury vapor during the embryonic and lactation periods (1 case). For 3 cases caused by broken thermometers, x-ray images helped to identify the position of mercury residues. Local excision was used to remove mercury from the floor of the mouth in 1 case. One child was prescribed oral meso-2,3-dimercaptosuccinic acid, and a good response was received. CONCLUSIONS: Substitution of mercury-in-glass thermometers and vigilance to prevent women of childbearing age from occupational mercury exposure were suggested. Treatment selection should vary according to patient situations.

[Differential diagnostic method of initial implications and degree I of the chronic mercury intoxication].

Currently available methods for diagnosis of chronic mercury intoxication (CMI) are applied at the any stage of the disease. Changes in these indices sometimes have no the specificity for any CMI stage, and a conclusion on them has the descriptive character. In addition, the above mentioned methods possess not sufficiently high accuracy in the diagnosis of intoxication at early stages of the development of the disease. The purpose of the research is the development of the method permitting to make the differential diagnosis between the initial symptoms of mercury poisoning and its first degree. 118 men who work/worked in the contact with mercury vapor were examined. There were evaluated electroencephalogram, long-latency auditory and cognitive evoked potentials, cerebral hemodynamics, noradrenaline (NA)content in the blood plasma. Statistical processing was performed with the use of «Statistica 6.0¼ software. The levels of NA in the development of CMI were shown to increase, by the time of the shaping of this disease the noted change was decompensated in the nature. The study of reactivity of cerebral vessels revealed the presence of abnormal responses during hypercapnic load in 14 - 24% of examined cases. In the analysis of auditory evoked potentials there was established the change in indices of latency and amplitude of the V- wave, which pronounced in the prolong response time, significant elongation in the P1 peak latency and the gain in the latency of N1 peak. There was established the presence of the wave-like change in the index of the latency of P300. In workers without an occupational disease, there was noted the marked elongation of the latent period of cognitive potential, while in patients with the newly made diagnosis the latency of P300 corresponded to standard values, and in the long term there was observed a sharp deterioration in this index. With the aid of the discriminant analysis with the calculation of canonical value there were revealed the most informative neurobiochemical indices, reoencephalogric ones and evoked potentials. The developed method of diagnosis allows to distinguish between the initial symptoms of mercury intoxication and the first stage of the disease.

Ophthalmic findings in acute mercury poisoning in adults: A case series study.

The aim of this study is to report ophthalmic findings of acute mercury poisoning in 48 adults referred to emergency department. Full ophthalmologic examination including the best corrected visual acuity, external eye examination, reaction to light, a slit-lamp examination, funduscopy, intraocular pressure measurements, and visual field (VF) and color vision (CV) tests were performed at the presentation and repeated after 6 months. The parametric values of VF test, the mean deviation (MD), and pattern standard deviation (PSD) were recorded in order to compare patients and the 30 healthy controls. The mean parameter of color confusion index in patients was found to be statistically different than controls (p < 0.01). The MD and PSD in patients were different from controls statistically significant (p < 0.01 and p < 0.01, respectively). There was no correlation between the ocular findings and the urine and blood mercury levels. Methyl mercury, held in the school laboratory for experimental purpose, may be a source of poisoning. In this case series, we showed that acute exposure to mercury had hazardous effect on the visual system, especially CV and VF. We propose that emphasizing the public education on the potential hazards of mercury is crucial for preventive community health.

Novel biomarkers of mercury-induced autoimmune dysfunction: a cross-sectional study in Amazonian Brazil.

Mercury is a ubiquitous environmental contaminant, causing both neurotoxicity and immunotoxicity. Given its ability to amalgamate gold, mercury is frequently used in small-scale artisanal gold mining. We have previously reported that elevated serum titers of antinuclear autoantibodies (ANA) are associated with mercury exposures of miners in gold mining. The goal of this project was to identify novel serum biomarkers of mercury-induced immunotoxicity and autoimmune dysregulation. We conducted an analysis of serum samples from a cross-sectional epidemiological study on miners working in Amazonian Brazil. In proteomic screening analyses, samples were stratified based on mercury concentrations and ANA titer and a subset of serum samples (N=12) were profiled using Immune Response Biomarker Profiling ProtoArray protein microarray for elevated autoantibodies. Of the up-regulated autoantibodies in the mercury-exposed cohort, potential target autoantibodies were selected based on relevance to pro-inflammatory and macrophage activation pathways. ELISAs were developed to test the entire sample cohort (N=371) for serum titers to the highest of these autoantibodies (anti-glutathione S-transferase alpha, GSTA1) identified in the high mercury/high ANA group. We found positive associations between elevated mercury exposure and up-regulated serum titers of 3760 autoantibodies as identified by ProtoArray. Autoantibodies identified as potential novel biomarkers of mercury-induced immunotoxicity include antibodies to the following proteins: GSTA1, tumor necrosis factor ligand superfamily member 13, linker for activation of T cells, signal peptide peptidase like 2B, stimulated by retinoic acid 13, and interferon induced transmembrane protein. ELISA analyses confirmed that mercury-exposed gold miners had significantly higher serum titers of anti-GSTA1 autoantibody [unadjusted odds ratio=89.6; 95% confidence interval: 27.2, 294.6] compared to emerald miners (referent population). Mercury exposure was associated with increased titers of several autoantibodies in serum including anti-GSTA1. These proteins play a wide variety of roles, including as antioxidants, in the regulation of pro- and anti-inflammatory cytokines, as well as danger and oxidative stress signaling. Dysregulation of these proteins and pathways is believed to play a role in autoimmune diseases such as rheumatoid arthritis, Sjögren׳s syndrome, and multiple sclerosis. Taken together, these results suggest that mercury exposure can induce complex autoimmune dysfunction and the immunotoxic effects of this dysfunction may be measured by serum titers to autoantibodies such as anti-GSTA1.

Subacute motor neuron hyperexcitability with mercury poisoning: a case series and literature review.

Motor neuron hyperexcitability (MNH) indicates a disorder characterized by an ectopic motor nerve discharge on electromyogram (EMG). Here, we present a series of three cases of subacute MNH with mercury poisoning. The first case showed hyperhidrosis, insomnia, generalied myokymia, cramps, tremor, weight loss, and myokymic and neuromyotonic discharges, followed by encephalopathy with confusion, hallucinations, and memory decrease. The second case was similar to the former but without encephalopathic features. The third case showed widespread fasciculation, fatigue, insomnia, weight loss, and autonomic dysfunction, including constipation, micturition difficulty, and impotence, with multiple fibrillation, unstable fasciculation, widened motor neuron potential, and an incremental response at high-rate stimulation in repetitive nerve stimulation. Based on the symptoms, the three cases were diagnosed as Morvan's syndrome, Isaacs' syndrome, and Lambert-Eaton myasthenic syndrome with ALS-like syndrome, respectively. Mercury poisoning in the three cases was confirmed by analysis of blood and urine samples. All cases recovered several months after chelation therapy and were in good condition at follow-up. Very few cases of MNH linked with mercury exposure have been reported in the literature. The mechanism of mercury-induced MNH may be associated with ion channel dysfunction.

[Genotype-phenotype characteristics of biochemical markers of endothelial dysfunction in patients with chronic mercury intoxication].

The paper presents data on the frequency of polymorphisms of candidate genes involved in the formation of endothelial dysfunction--endothelin-1 (EDN1 Lys198Asn) and endothelial nitric oxide synthase (NOS3 T786C) together with the concentrations of their active products (nitric oxide, endothelin-1) in individuals with chronic mercury intoxication. The concentration change of nitric oxide and endothelin-1 indicates the presence of endothelial dysfunction in the individuals examined. The studied polymorphisms appeared to play a minor role in the pathogenesis of endothelial dysfunction in patients with chronic mercury intoxication.

An analysis of mercury exposures among the adult population in New York State.

The extent of methylmercury exposures among adults in New York State (NYS) has not been well characterized. Over the past few years, the NYS Heavy Metals Registry (HMR) has seen an increase in both blood mercury tests being reported, and nonoccupational exposures to mercury, which appear primarily due to fish consumption. This study will, (1) Characterize the adults who are tested for blood mercury in NYS; (2) Examine the circumstances for blood mercury testing; and (3) Characterize this population in terms of exposure history, specifically those individuals who are non-occupationally exposed through a diet of seafood consumption in reference to blood mercury levels. Data available from HMR laboratory results, including basic demographics and test results, were combined with data from telephone interviews. The interview contains information on the reasons for testing, possible sources of exposure, and the individual's work and home environment. Approximately 99 % of adults reported to the HMR, with identifiable exposures to mercury, had non-occupational exposures resulting from seafood consumption. Common types of fish consumed include salmon, tuna, and swordfish, with 90 % of adults eating seafood a few times or more per week. Information will be provided on the reasons for being tested and the range of blood mercury levels in relation to their seafood consumption. NYS residents who frequently eat fish should be aware of what types of fish contain mercury and avoid or reduce consumption of fish with high mercury levels.

Mercury toxicity in wildland firefighters.

OBJECTIVE: Recent studies have shown that significant levels of mercury are being released into the atmosphere by wildland fires throughout the United States. Eagle populations in the western United States are experiencing mercury toxicity in areas where many of these massive fires are occurring. We hypothesized that wildland firefighters exposed to smoke and other contaminates from these extensive fires would also reflect elevated blood levels of mercury. METHODS: Wildland firefighters in the western United States were studied during the summers of 2007, 2008, and 2009. Pre- and post-fire season blood samples were tested for mercury in a cohort of firefighters and control subjects. RESULTS: Over the course of 3 summers, 66 firefighters were studied (41 had pre- and postseason blood draws). In 2008 and 2009 a control group was added with a total of 39 subjects (24 had pre- and postseason blood draws). Detectable blood levels of mercury were found in 6 firefighters, and 1 elevated level was found over the course of the study period. Six control subjects had detectable mercury levels, and no elevated levels were found. CONCLUSIONS: This study did not show statistically significant elevated blood levels of mercury in our cohort of wildland firefighters. However, as forest fires continue to ignite, we recommend continued investigation to ensure the health and safety of firefighting crews.

Elemental mercury toxicity due to aspiration following intentional massive ingestion.

Deliberate poisoning with intentional ingestion of elemental mercury is reported not to result in systemic toxicity due to minimal absorption from the gastrointestinal tract. We report a case of a 43 year old male who intentionally ingested 200 ml elemental mercury which resulted in abdominal pain and vomiting. The patient subsequently aspirated globules of mercury which was confirmed on chest x-ray and his blood mercury levels were markedly raised. He was treated with chelating agents and managed in a negative pressure room to reduce the risk of staff being exposed to exhaled mercury vapour from the patient.

Mercury vapor inhalation and poisoning of a family.

Acute mercury vapor poisoning is a rare but fatal toxicological emergency. People are exposed to mercury in daily life by the way of foods, vaccines, antiseptics, ointments, amalgam or occupation. We present here, the clinical picture and management of four members of the same family who were exposed to elemental mercury. Three of the family members were seen in another hospital with malaise, fever, eritematous rash and pulmonary problems. Their questioning revealed the mercury exposure. Having a suspicion of heavy metal intoxication, blood and urine mercury levels were measured and mercury intoxication was diagnosed. On admission to our hospital, two patients already had chelation therapy. In three of them we found three distinct abnormalities: encephalopathy, nephrotic syndrome and polyneuropathy. The fourth family member had minor symptoms. This family is an example for the inhalation exposure resulting from inappropriate handling of liquid mercury. During the first days, flu like illness ensues. Then, severe pulmonary, neurological, renal, hepatic, hematological and dermatological dysfunctions develop. Blood and urine mercury levels should be tested on suspicion, but it must be kept in mind that blood level is unreliable in predicting the severity of mercury toxicity. The priority in the treatment should be removing the patient from the source of exposure. Then British anti-Lewisite, edetate calcium disodium, penicillamine, Sodium 2,3-dimercaptopropane-1-sulfhonate and 2,3-dimercaptosuccinic acid can be used for binding the mercury. We conclude that since mercury-containing devices are present in daily life, physicians must be able to recognize the clinical manifestations and treatment of mercury poisoning.

Use of toe clips as a nonlethal index of mercury accumulation and maternal transfer in amphibians.

Nonlethal indices of contaminant exposure can facilitate research on the accumulation and effects of contaminants in wildlife. Here, we tested the efficacy of using amputated toes ("toe clips"), a common byproduct when marking amphibians in population and genetic studies, to determine mercury (Hg) concentrations in amphibians. We examined total mercury (THg) concentrations in American toads (Bufo americanus) collected along a contamination gradient at a Hg-contaminated field site. We found significant positive correlations between toe THg and blood THg concentrations in adult males and females collected in two different years. We also found that blood and toe clips could be used to predict maternal transfer of Hg, an important mechanism of reproductive toxicity in wildlife. Maternal toe THg concentrations were more highly correlated with egg THg concentrations than were maternal blood THg concentrations. Our results indicate that amputated toes are effective for identifying Hg concentrations in amphibians.

Serum hormone and biochemical activity as biomarkers of mercury toxicity in the yellowfin seabream Acanthopagrus latus.

This study was undertaken in two separate environmental and experimental conditions. The environmental test was carried out at creeks in the Persian Gulf and the experimental test was undertaken in seawater re-circulatory tanks. Mercury concentrations were determined using a standard cold vapour atomic absorption method. Serum enzymes were determined with Diagnostics Infinity reagent kit. Serum glucose and total protein were measured photometrically. Serum hormones were assayed using diagnostic ELISA kits. Results of the present investigation indicated that the sub-acute and chronic mercury concentrations tested may cause several changes in the biochemical and hormone parameters of the studied fish and we can use these changes as biomarkers for mercury detection. The range of mercury concentrations found in the creek water and specially sediments along the Mahshahr coast was higher than the other marine environment. It was declared that between enzymatic indices serum acid phosphatase (ACP) amount and ACP activity, between hormonal indices testosterone, T3 and T3/T4 and between metabolite index total protein can be considered as suitable and effective biomarkers of mercury pollution in yellowfin seabream.

Dependence of blood levels of HSP70 and HSP90 on genotypes of HSP70, GSTT1, and GSTM1 gene polymorphism in individuals chronically exposed to mercury.

The relationship between blood levels of HSP72, HSP72+HSP73, and HSP90 and genotypes of three polymorphisms of the HSP70 family, HSPA1L (2437T/C) and HSPA1B (2074G/C and 1267A/G) as well as GSTT1 and GSTM1 polymorphisms was studied in 82 men chronically exposed to mercury. Of these, 40 men were exposed to mercury for more than 10 years (group 1) and 42 developed chronic mercuric intoxication (group 2). The groups differed significantly by TT (p=0.004) and TC (p=0.007) genotypes of HSPA1L gene locus 2437T/C. Differences in the heat shock protein content associated with HSP70 gene polymorphism were detected only for HSPA1B gene locus 2074G/C and consisted in reduction of HSP90 (p=0.020) and HSP72 (p=0.056) for GG genotype in group 2 in comparison with group 1. Combination of GSTT1(+)/GSTM1(0/0) genotypes was associated with reduction of the protein levels, while variants including GSTT1(0/0) were associated with a significant elevation thereof.

[Metallic mercury poisoning caused by intravenous injection in vague circumstances--a case report]. / Zatrucie rtecia metaliczna podana dozylnie w niejasnych okolicznosciach--opis przypadku.

UNLABELLED: Mercury is a heavy metal found in nature in three forms: metallic mercury, organic and inorganic compounds. It is a general protoplasmatic toxin. The pathophysiology of mercury toxicity is related to its binding to sulfhydryl groups of different receptor proteins and cellular enzymes, interrupting cellular metabolism and in this way causing cell death. In the paper we present a case of 57-year-old woman, who was admitted due to suspicion of metallic mercury parenteral poisoning. The computed tomography (CT) scan of abdomen accidentally revealed multiple disseminated tiny metallic densities. The blood mercury level was high (41.9 microg/l), as well as mercury urine level (85.7 microg/g creatinine which was 42.8 microg/l). Neurologic examination revealed unobtrusive symptoms of cerebellum affection. Psychological examination revealed disturbances of cognitive abilities reliant on the efficiency of vision organ. The results of A. Benton's organic test were abnormal. Psychiatric examination revealed no abnormalities. Results of pulmonary function tests were within normal limits. CONCLUSIONS: The intravenous injection of metallic mercury did not cause serious clinical effects. Followup examination in order to reveal chronic toxic effects is necessary. Diagnostics and treatment of metallic mercury intoxications by parenteral injection should be carried out in the clinical toxicology departments.