Epidemiology, clinical presentation, treatment, and follow-up of chronic mercury poisoning in China: a retrospective analysis.

BACKGROUND: There are no reports on the incidence of chronic mercury poisoning in a large population in China. This study investigated the epidemiology, clinical manifestations, treatment, and follow-up of Chinese patients with chronic mercury poisoning. METHODS: Data for 288 mercury poisoning patients were collected at our hospital from July 2014 to September 2019, including sex, age, admission time, blood mercury content, urine mercury content, creatinine, urinary mercury/creatinine ratio, 24-h urinary protein levels, electromyography (EMG) findings, renal biopsy, and follow-up. Patient characteristics were evaluated by statistical and correlation analyses. RESULTS: First, mercury poisoning in China mainly occurred through occupational exposure and the inappropriate use of mercury-containing cosmetics and Chinese folk remedies (CFRs). Second, the most common symptoms were nervous system (50.3 %), kidney (16.4 %) and breathing (8.0 %). Mercury poisoning-induced Nephrotic syndrome (NS) and peripheral neuropathy are common long-term complications. The complications of occupational and cosmetics-induced mercury poisoning are consistent with international belief. However, the NS caused by CFRs is mainly membranous nephropathy and the probability of peripheral neuropathy caused by CFRs is higher than other pathogens. Third, follow-up data shows that 13 patients with EMG-confirmed neurological injury, 10 showed full recovery after 38.50 ± 8.03 months. Furthermore, among 18 patients with NS, 15 had normal urine protein and serum albumin levels after 22.67 ± 10.26 months. CONCLUSIONS: Regulation of skin-lightening cosmetic products, safety surveillance of CFRs, and prevention and control of occupational exposure must be improved to decrease the incidence of mercury poisoning in China.

Treatment of lead and arsenic poisoning in anuric patients - a case report and narrative review of the literature.

BACKGROUND: Heavy metal poisoning can cause debilitating illness if left untreated, and its management in anuric patients poses challenges. Literature with which to guide clinical practice in this area is rather scattered. CASE PRESENTATION: We present a case of symptomatic lead and arsenic poisoning from use of Ayurvedic medicine in a 28-year-old man with end-stage kidney disease on chronic hemodialysis. We describe his treatment course with chelating agents and extracorporeal blood purification, and review the relevant literature to provide general guidance. CONCLUSION: Cumulative clinical experience assists in identifying preferred chelators and modalities of extracorporeal blood purification when managing such patients. However, a larger body of real-world or clinical trial evidence is necessary to inform evidence-based guidelines for the management of heavy metal poisoning in anuric patients.

Fixed drug eruption due To 2,3-dimercapto-1-propanesulfonic acid (DMPS) treatment for mercury poisoning: a rare adverse effect.

BACKGROUND: Fixed drug eruptions (FDE) are characterized by recurrent, usually solitary erythematous or dark red macular, plaque or bullous lesions, all at the same site. Among the first choices for antidotal treatment in mercury exposure, 2,3-dimercapto-1-propanesulfonic acid (DMPS) is generally a drug with a low incidence of side effects. FDE due to DMPS was not detected in our literature research and so we aimed to present this rare case. CASE REPORT: Forty-eight-year-old male patient, gunpowder and explosives factory worker, was admitted to our hospital because of mercury exposure and we started DMPS treatment. On the second day of chelation treatment, swelling and felting on lips and complaints of wound formation in genital areas started. Annular, purple color plaque on penis with no angioedema was observed. Case was regarded as FDE. Systemic and topical steroid therapy was started after termination of chelation therapy and lesions regressed with steroids. DISCUSSION: Drug eruptions are substantially common dermatological problems and can be seen in about 2.2% of inpatients. The most common unexpected effects of DMPS are allergic skin reactions. The clinical state regress rapidly after the cessation of chelation therapy.

Metal chelators and neurotoxicity: lead, mercury, and arsenic.

This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest that BAL in such cases acted as a shuttling Pb transporter from the intra- to the extracellular space. The present paper discusses if a combination of the extracellularly distributed DMSA with the ionophore, Monensin may provide a less toxic combination for Pb mobilization by increasing both the efflux of intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy with DMSA should be continued with several intermittent courses. DMPS and DMSA are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more efficient agent against As poisoning. However, new insight indicates that a combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to obtain mobilization of the intracerebral deposits into the circulation for subsequent rapid urinary excretion.

A Mercury Toxicity Case Complicated by Hyponatremia and Abnormal Endocrinological Test Results.

Mercury (Hg) poisoning is considered a rare disease by the National Institutes of Health and the diagnosis can present great challenges to clinicians. Children who are exposed to Hg can present with a wide variety of symptoms, including acrodynia, tremor, excessive salivation, and psychiatric symptoms, including insomnia. However, endocrinologic manifestations from Hg exposure are less well known. This is a case report of a 12-year-old boy who presented with body rash, irritability, insomnia, and profuse sweating after returning from a summer camp. The child was initially managed in the outpatient setting, and the investigation was mainly targeted toward infectious etiology, including Rocky Mountain spotted fever and Lyme disease. He was eventually admitted to the hospital with altered mental status and was noted to have hyponatremia with serum sodium of 121 mEq/L. Thyroid studies also revealed elevated free thyroxine levels in the presence of normal triiodothyronine and thyrotropin. The patient developed hypertension and tachycardia, and was found to have elevated 24-hour vanillylmandelic acid and metanephrines. Finally, heavy metal measurements revealed a blood Hg level that was greater than the reference values of 0 to 9 ng/mL. Chelation treatment with 2,3-dimercaptopropane-1-sulfonate was subsequently initiated and over a period of 8 months his symptoms resolved and his thyroid function test returned to normal. This case highlights some of the challenges commonly encountered in identifying Hg exposure. More importantly, it illustrates that exposure to Hg should be considered in children who present with the symptoms and abnormal endocrinologic test results described in this report.

Survival without peripheral neuropathy after massive acute arsenic poisoning: Treated by 2,3-dimercaptopropane-1-sulphonate.

WHAT IS KNOWN AND OBJECTIVE: Massive acute arsenic poisoning is rare yet potentially life-threatening. 2,3-dimercaptopropane-1-sulphonate (DMPS) appears to have the appropriate chelating property. However, clinical experience on the use of DMPS in massive arsenic poisoning is limited. CASE DESCRIPTION: A 37-year-old woman attempted suicide by ingesting 37.5 g of arsenic trioxide. DMPS was promptly initiated based on history and clinical symptoms. The patient recovered completely, with no complications or side effects of the therapy. WHAT IS NEW AND CONCLUSION: TDMPS is useful for the treatment of massive acute arsenic poisoning.

Clinicopathological features, diagnosis, and treatment of IgA nephropathy with minimal change disease related to exposure to mercury-containing cosmetics: a case report
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AIM: Membranous nephropathy and minimal change disease (MCD) have been involved in mercury-induced nephrotic syndrome. IgA nephropathy is not known to be a common pathological type. In the present article, we report a case of IgA nephropathy with MCD following exposure to mercury-containing skin lightening cream. MATERIAL AND METHODS: The patient was a 39-year-old woman who presented with nephrotic syndrome. She had a 6-month history of using as many as 8 kinds of skin-lightening creams, and urinary mercury excretion was high. Renal biopsy revealed IgA nephropathy with MCD. The use of cosmetics was stopped and chelation therapy was given. After 4 courses (1 month) of chelation therapy, there was a complete remission of proteinuria and hematuria, and urine tests remained normal during the 5-year follow-up period. RESULTS AND CONCLUSIONS: The unique clinical and pathological features of IgA nephropathy with MCD had raised the controversial question of whether MCD and IgA deposition are separate entities or a common pathophysiology. Repeated renal biopsy and similar cases were helpful and should be carried out as far as possible.
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Is Chelation Therapy Efficient for the Treatment of Intravenous Metallic Mercury Intoxication?

The efficacy of treatment for intravenous elemental mercury intoxication has not been fully studied with regard to clinical outcome, and treatment recommendations vary. We treated a 41-year-old man with a history of drug abuse and depression who attempted suicide using 1 mL (13.53 g) metallic Hg i.v. He was admitted to the hospital 2 months later for dyspnoea and thoracic pain and was diagnosed with pneumonia. Hg deposits were seen in the lungs and extra-pulmonary organs. His blood level (372 µg/L) exceeded the population level of 5 µg/L by more than 70 times. Dimercaptopropane sulphonate sodium (DMPS; 600 mg/day orally) was administered for 14 days. One year later, the patient presented with dyspnoea on exertion, fatigue, depression and impaired sleep. His chest X-ray showed multiple opacities (size up to 2.8 cm), and psychological testing revealed a selective cognitive deficit in the area of visual attentiveness, flexibility, source memory and impairment of the motor speed of the dominant upper extremity. Mercury blood level was 158 µg/L and mercury urine output was 1380 µg/24 hr. DMPS (800 mg/day orally) was administered for 40 days; the patient eliminated up to 18 mg Hg/day. His Hg blood level and Hg urine output belong to the highest among reported cases. In spite of the therapy, the patient's blood Hg, complaints and psychological tests showed no improvement. This case report confirms that DMPS does not effectively remove intravenous deposits of metallic Hg.

Acute mercury vapor poisoning in a 3-month-old infant: A case report.

BACKGROUND: We investigated the clinical characteristics of a 3-month-old infant with acute mercury vapor poisoning. Clinical symptoms of acute mercury poisoning in infants include acute onset, rapid progression, severe illness with respiratory symptoms that may result in pneumothoraces and aspiration pneumonias. CASE PRESENTATION: A 3-month-old girl presented with pneumothoraces and respiratory failure to the hospital. Two days before hospitalization, the girl had stayed in a room containing mercury vapor for several hours. She was hospitalized for acute mercury poisoning. We used sodium dimercaptosulphonate (DMPS) for treatment. CONCLUSION: Pulmonary disease was mainly induced by the inhalation of mercury vapor. The disease was characterized by acute respiratory distress, pneumothorax and acute chemical pneumonitis. It responded to chelation therapy with the agent DMPS.

Chelation in metal intoxication--Principles and paradigms.

The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review.

Chelation therapy in intoxications with mercury, lead and copper.

In the present review we provide an update of the appropriate use of chelating agents in the treatment of intoxications with compounds of mercury, lead and copper. The relatively new chelators meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-propanesulphonate (DMPS) can effectively mobilize deposits of mercury as well as of lead into the urine. These drugs can be administered orally and have relatively low toxicity compared to the classical antidote dimercaptopropanol (BAL). d-Penicillamine has been widely used in copper overload, although 2,3-dimercaptosuccinic acid or tetrathiomolybdate may be more suitable alternatives today. In copper-toxicity, a free radical scavenger might be recommended as adjuvant to the chelator therapy.

Clinical manifestation and management of intravenous mercury injection: a case report.

Intentional self-injection of metallic mercury case report is presented. A 22 year old man with a past medical history of ethylene glycol suicidal poisoning was admitted to a Acad. N. Kipshidze Central University Clinic in Tbilisi, four months after deliberate intravenous injection of an unknown quantity of metallic mercury from several thermometers into his antecubital vein. After 2 months of asymptomatic period, the patient began to complain of pain and tremor in limbs, fatigue and skin rash. CT scan of the thorax and the abdomen confirmed multiple small opacities of metallic density in both lungs, liver and right kidney. After the procedure the patient was transferred to the toxicology center in Baku, Azerbaijan for chelation therapy. On arrival no biochemical abnormalities in hepatic or renal function or clinical pulmonary malfunction were detected, despite presence of slight symptoms of erethism, tremor mercuralis, knee joints arthralgia and lower extremities weakness. Chelation therapy with intramuscular injection of Unithiol (DMPS) was started in dose of 20mg/kg/day. After one month of chelation therapy, mercury blood concentration slowly decreased from initially 134 microgram/L to 105 microgram/L. This case report demonstrates mild acute toxicity following intravenous administration of unknown amounts of elemental mercury. Because of chelation therapy can remove approximately 1 mg of mercury per day the patient was recommended further long-term DMPS treatments under the control blood mercury levels. It is concluded that clinical manifestations of intravenous elemental mercury intoxication may be delayed despite significant increase in blood mercury level.

The role of chelation in the treatment of arsenic and mercury poisoning.

Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication.

Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease.

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.

Mercury toxicity and treatment: a review of the literature.

Mercury is a toxic heavy metal which is widely dispersed in nature. Most human exposure results from fish consumption or dental amalgam. Mercury occurs in several chemical forms, with complex pharmacokinetics. Mercury is capable of inducing a wide range of clinical presentations. Diagnosis of mercury toxicity can be challenging but can be obtained with reasonable reliability. Effective therapies for clinical toxicity have been described.

Inorganic mercury poisoning associated with skin-lightening cosmetic products.

INTRODUCTION: Mercury and mercury salts, including mercurous chloride and mercurous oxide, are prohibited for use in cosmetic products as skin-lightening agents because of their high toxicity. Yet, the public continue to have access to these products. METHODS: Reports of skin-lightening cosmetic products containing mercury and cases of mercury poisoning following the use of such products were identified using Medline (1950 - 28 March 2011) with mercury, mercury compounds, mercury poisoning, cosmetics and skin absorption as the subject headings. These searches identified 118 citations of which 31 were relevant. TOXICOKINETICS: The rate of dermal absorption increases with the concentration of mercury and prior hydration of the skin. The degree of dermal absorption varies with the skin integrity and lipid solubility of the vehicle in the cosmetic products. Ingestion may occur after topical application around the mouth and hand-to-mouth contact. After absorption, inorganic mercury is distributed widely and elimination occurs primarily through the urine and feces. With long-term exposure, urinary excretion is the major route of elimination. The half-life is approximately 1-2 months. FEATURES: The kidneys are the major site of inorganic mercury deposition; renal damage includes reversible proteinuria, acute tubular necrosis and nephrotic syndrome. Gastrointestinal symptoms include a metallic taste, gingivostomatitis, nausea and hypersalivation. Although penetration of the blood-brain barrier by inorganic mercury is poor, prolonged exposure can result in central nervous system (CNS) accumulation and neurotoxicity. Inorganic mercury poisoning following the use of skin-lightening creams has been reported from Africa, Europe, USA, Mexico, Australia and Hong Kong. Nephrotic syndrome (mainly due to minimal change or membranous nephropathy) and neurotoxicity were the most common presenting features. As mercury-containing cosmetic products can contaminate the home, some close household contacts were also reported to have elevated urine mercury concentrations. ASSESSMENT: Prevention from further exposure is the first step. Cream users and their close contacts should be evaluated for evidence of mercury exposure, the presence of target organ damage and the need for chelation treatment. Laboratory evaluation of affected subjects should include a complete blood count, serum electrolytes, liver and renal function tests, urinalysis, urine and blood mercury concentrations. Since blood mercury concentrations tend to return to normal within days of exposure, blood samples are useful primarily in short-term, higher-level exposures. Estimation of the urine mercury concentration is the best marker of exposure to inorganic mercury and indicator of body burden. A 24-hour urine for measurement of mercury excretion is preferred; a spot urine mercury concentration should be corrected for creatinine output. MANAGEMENT: Chelation therapy is indicated in patients with features of mercury poisoning and elevated blood and/or urine mercury concentrations. Unithiol (2,3-dimercapto-1-propanesulfonic acid, DMPS) is the preferred antidote though succimer (dimercaptosuccinic acid, DMSA) has also been employed. CONCLUSIONS: The use of mercury in cosmetic products should be strictly prohibited. The public should be warned not to use such products as their use can result in systemic absorption and accumulation of mercury causing renal, gastrointestinal and CNS toxicity.

Blood, urine, and hair kinetic analysis following an acute lead intoxication.

A case of lead exposure resulting from the accidental ingestion of a lead-containing solution is reported. Because of clinical management rapidly performed through chelation therapy by 2,3-dimercaptopropane sulfonate sodium and meso-2,3-dimercaptosuccinic acid, blood lead levels of this 51-year-old patient were moderate (412.9 µg/L) and no clinical symptoms were observed. Numerous blood and urine samples were collected for kinetic analysis of lead elimination. However, we report the first case in which hair samples were analyzed to determine the excretion level of lead after acute intoxication.

[Dithiols as chelators. A cause of bullous skin reactions]. / Chelatbildner mit Thiolaktivität. Auslöser bullöser Hautreaktionen.

Chelation therapy with (RS)-2,3-Bis(sulfonyl)propane-1-sulfonic acid (DMPS) after an occupational lead exposure led to the development of a severe bullous drug eruption. Skin tests and histology/immunohistology of the test reactions indicated a T-cell-mediated immune response against DMPS. Metal-binding thiol groups as in DMPS are chemically highly reactive and therefore effectively mediate the development of immunogenic hapten (DMPS)-protein complexes. Therefore, the pharmacological effects and sensitization potential of dithiols are tightly connected. Cross-reactivity of DMPS to other chelators like D-penicillamine is possible; the indications for chelation therapy should be weighed carefully.