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Mercury intoxication: it still exists.

A3-year-old boy presented to the Hospital for Sick Children with systemic symptoms and oropharyngeal and peripheral extremity changes suggestive of Kawasaki disease. He was found to have severe hypertension. Investigation for a catecholamine-secreting tumor was negative. Toxins were considered when the patient's 20-month-old brother presented with similar symptoms, and the boys were subsequently diagnosed with elemental mercury poisoning. We review the literature on mercury intoxication and discuss the historical context, clinical syndrome (acrodynia), treatment, and radiologic findings of this unusual diagnosis.

Acrodynia↗

Mercury intoxication and arterial hypertension: report of two patients and review of the literature.

Two children in the same household with symptomatic arterial hypertension simulating pheochromocytoma were found to be intoxicated with elemental mercury. The first child was a 4-year-old boy who presented with new-onset seizures, rash, and painful extremities, who was found to have a blood pressure of 171/123 mm Hg. An extensive investigation ensued. Elevated catecholamines were demonstrated in plasma and urine; studies did not confirm pheochromocytoma. Mercury levels were elevated. These findings prompted an evaluation of the family. A foster sister had similar findings of rash and hypertension. Both had been exposed to elemental mercury in the home. The family was temporarily relocated and chelation therapy was started. A Medline search for mercury intoxication with hypertension found 6 reports of patients ranging from 11 months to 17 years old. All patients showed symptoms of acrodynia. Because of the clinical presentation and the finding of elevated catecholamines, most of the patients were first studied for possible pheochromocytoma. Subsequently, elevated levels of mercury were found. Three children had contact with elemental mercury from a broken thermometer, 2 had played with metallic mercury and 1 had poorly protected occupational exposure. All responded to chelation therapy. Severe systemic arterial hypertension in infants and children is usually secondary to an underlying disease process. The most frequent causes of hypertension in this group include renal parenchymal disease, obstructive uropathy, and chronic pyelonephritis associated with reflux and renal artery stenosis. Less frequent causes include adrenal tumors, pheochromocytomas, neurofibromas, and a number of familial forms of hypertension. Other causes include therapeutic and recreational drugs, notably sympathomimetics and cocaine, and rarely, heavy metals. In children with severe hypertension and elevated catecholamines, the physician should consider mercury intoxication as well as pheochromocytoma. The health hazards of heavy metals need to be reinforced to the medical profession and the general public.

Acrodynia↗

Mercury exposure and early effects: an overview.

OBJECTIVES: This paper was given as a keynote address at the conference on The Assessment of the Effects Due to Low Doses of Inorganic Mercury following Environmental and Occupational Exposures: Human and in vitro Studies on the Specific Mechanisms of Toxicity in Gargnano, Italy, in September 2001. METHODS: The most relevant literature over the past 40 years has been reviewed, and in particular, the proceedings of the World Health Organisation conferences on the health effects of inorganic and organic mercury exposure have been considered. RESULTS: In an uncontaminated environment the general population is exposed to mercury vapour from the atmosphere and from dental amalgam, while the diet, mainly from fish, is the principal source for methyl mercury absorption. Mercury vapour release from amalgam fillings increases with chewing, with absorption and uptake by the brain and kidneys. Infants exposed to phenyl mercury from treated diapers and young children ingesting mercurous chloride in teething powders have developed acrodynia (pink disease), and Kawasaki disease and the use of mercurial skin lightening creams has been followed by the development of the nephrotic syndrome. Both mercury compounds and mercury vapour have given rise to contact dermatitis in the general population. Epidemics of mercury poisoning have followed release of mercury into the environment from industrial activity, with uptake of methyl mercury from fish eating in Minamata Bay and uptake of both inorganic and methyl mercury following release of mercury vapour and deposition into waterways from gold recovery procedures in the Amazon basin. The ingestion of wheat and barley seed treated with an alkyl mercury fungicide for sowing, by a largely illiterate population in Iraq, led to a major outbreak of poisoning with a high fatality rate. Following exposure to mercury vapour, the earliest clinically observed adverse effects at urine mercury levels of the order of 30-100 mg/g creatinine, are objectively detectable tremor, psychological disorder and impaired nerve conduction velocity in sensitive subjects, with subjective symptoms of irritability, fatigue and anorexia. At these and at lower levels, proteinuria has also been observed. Both glomerular and tubular damage may occur at exposure levels lower than those giving rise to central nervous system effects. An immunological effect has also been observed in studies on clinically asymptomatic workers with low level exposure. CONCLUSIONS: As mercury can give rise to allergic and immunotoxic reactions which may be genetically regulated, in the absence of adequate dose-response studies for immunologically sensitive individuals, it has not been possible to set a level for mercury in blood or urine below which mercury related symptoms will not occur.

Acrodynia↗

Antitumor activity of trans-bis(salicylaldoximato)copper(II): a novel antiproliferative metal complex.

trans-Bis(salicylaldoximato)copper(II) (CuSAO2), the parent compound of a new group of antiproliferative copper(II) complexes, was studied in vivo. It had marked antitumor activity against Ehrlich ascites carcinoma in NMRI mice. Survival was considerably increased, and, in some cases, total cures were encountered. No activity against leukemia L1210 was found in female DBA/2J mice, although CuSAO2 is equally effective against L1210 and Ehrlich carcinoma cells in vitro. The side effects of CuSAO2 included weight loss, weakness, acrodynia, and blindness; all of these side effects were transient.

Acrodynia↗

[False erythermalgia].

The differential diagnosis of erythermalgia is sometimes complicated by the absence of consensus on proposed diagnostic criteria. Unwarranted diagnosis can result from any clinical situation leading to burning sensations in the limbs. This can occurs in patients with peripheral neuropathies who often experience dysesthesia when going to bed when the legs are under the covers; in such cases, redness and local warmth are missing. Venous insufficiency can also produce sensations of warm feet, often at retiring, together with edema and an increase in local heat. Algodystrophy, during the inflammatory phase can also mimic erythermalgia with intense pain and local modifications. Nevertheless, the unilateral aspect and persistence of the symptoms together with the post-traumatic situation usually directs the diagnosis. Acrodynia is a rare disease caused by excessive mercury intake and should be discussed in children. Vasomotor impairment in the limbs is the main sign. The red color of the hands and feet is accompanied by intense paroxysmal burn-type pain. The diagnosis is confirmed by high mercury levels in urine. Fabry's disease is a hereditary sphingolipidosis transmitted on chromosome X and occurs predominantly in men, often starting early in childhood with burning sensation in the limbs. The diagnosis should be entertained in children with pseudo-erythermalgia and is confirmed by chromatographic search for abnormal sphingolipids in the urine.

Acrodynia↗

The dental amalgam issue. A review.

Using an interdisciplinary approach, the current position in the dental amalgam controversy and the potential impact of amalgam mercury on human health are reviewed. Aspects of materials science, corrosion, mercury exposure, toxicology, neurology and immunology are included. New data on mercury exposure from corroded amalgam fillings in vivo are presented. The exposure can reach levels considerably over known threshold limit values. Also, measurements of mercury absorption from intraoral air are presented. The vital importance of avoiding a galvanic amalgam-gold coupling is emphasized. The symptomatology of a disabled patient, who recovered after amalgam removal, has been included. It is concluded that discussion of the dental amalgam issue has suffered from the lack of an interdisciplinary approach. It would be wise to learn from the lesson of acrodynia, and consider amalgam mercury among other possible factors in neurological and immunological diseases of unclear etiology.

Dental Amalgam↗

A study of autoantibodies and circulating immune complexes in mercury-exposed chloralkali workers.

UNLABELLED: Inorganic mercury may cause immunologically mediated disease: e.g., glomerulonephritis, acrodynia, and contact allergy. Animal models have demonstrated the importance of genetic factors in determining susceptibility and resistance to autoimmunity, as well as the specific manifestation of the autoimmune response. Findings in groups of workers with occupational exposure to inorganic mercury have been inconsistent. OBJECTIVE: To investigate whether an immune response, caused by exposure to inorganic mercury (Hg), could be shown in occupationally exposed workers. METHODS: Immunoglobulin G (IgG), antinuclear autoantibodies, antibodies against thyroid, stomach or kidney antigens using indirect immunofluorescence, antibodies against glomerular basement membrane using ELISA, and circulating immune complexes in serum, and albumin in urine, were examined in Hg-exposed workers and controls. The two groups, 41 male chloralkali workers exposed to Hg vapour (mean exposure time 9 years) and 41 unexposed controls were age-matched and recruited from the same company. Hg concentrations in whole blood (B-Hg), plasma (P-Hg), and urine (U-Hg) were determined using cold vapor atomic spectrometry. DESIGN: Cross-sectional study. RESULTS: The mean B-Hg, P-Hg and U-Hg levels were 46 nmol/l, 37 nmol/l, and 27 micrograms/g creatinine in the exposed group, and 17 nmol/l, 6.9 nmol/l, and 3.4 micrograms/g creatinine in the referents. No statistically significant differences were found regarding IgG levels, urinary albumin excretion, prevalence of abnormal titers of autoantibodies or circulating immune complexes. There were no statistically significant associations between autoantibodies or immune complexes on the one hand and mercury exposure indices on the other. CONCLUSION: The results indicate that, if and when lasting autoimmune response occurs at the mercury exposure levels of the present study, it is uncommon. A small fraction of humans may, however, be susceptible to the development of autoimmunity, and there is also a possible "healthy worker" selection. Thus cross-sectional studies of moderate numbers of active workers will have low power to demonstrate autoimmune effects.

Adolescent↗

Dose-response study of thimerosal-induced murine systemic autoimmunity.

The organic compound ethylmercurithiosalicylate (thimerosal), which is primarily present in the tissues as ethylmercury, has caused illness and several deaths due to erroneous handling when used as a disinfectant or as a preservative in medical preparations. Lately, possible health effects of thimerosal in childhood vaccines have been much discussed. Thimerosal is a well-known sensitizing agent, although usually of no clinical relevance. In rare cases, thimerosal has caused systemic immune reactions including acrodynia. We have studied if thimerosal might induce the systemic autoimmune condition observed in genetically susceptible mice after exposure to inorganic mercury. A.SW mice were exposed to 1.25-40 mg thimerosal/l drinking water for 70 days. Antinucleolar antibodies, targeting the 34-kDa protein fibrillarin, developed in a dose-related pattern and first appeared after 10 days in the two highest dose groups. The lowest observed adverse effect level (LOAEL) for antifibrillarin antibodies was 2.5 mg thimerosal/l, corresponding to an absorbed dose of 147 microg Hg/kg bw and a concentration of 21 and 1.9 microg Hg/g in the kidney and lymph nodes, respectively. The same LOAEL was found for tissue immune-complex deposits. The total serum concentration of IgE, IgG1, and IgG2a showed a significant dose-related increase in thimerosal-treated mice, with a LOAEL of 5 mg thimerosal/l for IgG1 and IgE, and 20 mg thimerosal/l for IgG2a. The polyclonal B-cell activation showed a significant dose-response relationship with a LOAEL of 10 mg thimerosal/l. Therefore, thimerosal induces in genetically susceptible mice a systemic autoimmune syndrome very similar to that seen after treatment with inorganic mercury, although a higher absorbed dose of Hg is needed using thimerosal. The autoimmune syndrome induced by thimerosal is different from the weaker and more restricted autoimmune reaction observed after treatment with an equipotent dose of methylmercury.

Animals↗

Mercury exposure from interior latex paint.

BACKGROUND: Many paint companies have used phenylmercuric acetate as a preservative to prolong the shelf life of interior latex paint. In August 1989, acrodynia, a form of mercury poisoning, occurred in a child exposed to paint fumes in a home recently painted with a brand containing 4.7 mmol of mercury per liter (at that time the Environmental Protection Agency's recommended limit was 1.5 mmol or less per liter). METHODS: To determine whether the recent use of that brand of paint containing phenylmercuric acetate was associated with elevated indoor-air and urinary mercury concentrations, we studied 74 "exposed" persons living in 19 homes recently painted with the brand and 28 "unexposed" persons living in 10 homes not recently painted with paint containing mercury. RESULTS: The paint samples from the homes of exposed persons contained a median of 3.8 mmol of mercury per liter, and air samples from the homes had a median mercury content of 10.0 nmol per cubic meter (range, less than 0.5 to 49.9). No mercury was detected in paint or air samples from the homes of unexposed persons. The median urinary mercury concentration was higher in the exposed persons (4.7 nmol of mercury per millimole of creatinine; range, 1.4 to 66.5) than in the unexposed persons (1.1 nmol per millimole; range, 0.02 to 3.9; P less than 0.001). Urinary mercury concentrations within the range that we found in exposed persons have been associated with symptomatic mercury poisoning. CONCLUSIONS: We found that potentially hazardous exposure to mercury had occurred among persons whose homes were painted with a brand of paint containing mercury at concentrations approximately 2 1/2 times the Environmental Protection Agency's recommended limit.

Adolescent↗

From Morvan's fibrillary chorea to the "mal des ardents".

The authors present a case of Morvan's fibrillary chorea. We compare this observation with cases in the past such as the "mal des ardents", the plague of Athens, acrodynia and the epidemic of Pont St Esprit which were all characterized clinically by pain, burning sensations, hallucinations and insomnia. Since aetiological aspects remain uncertain, the similarity in clinical observations establishes a close relationship between the "mal des ardents" and the clinical features of our patient.

Chorea↗

Effects of epsilon-pyridoxyllysine bound to dietary protein on the vitamin B-6 status of rats.

The nutritional properties of protein bound epsilon-pyridoxyllysine residues in a phosphopyridoxyl bovine serum albumin (PP-BSA) preparation were examined by rat bioassay employing various levels of PP-BSA and pyridoxine (PN) fortification in the diets. Previous studies have shown that vitamin B-6 aldehydes can reductively bind to food proteins as epsilon-pyridoxyllysine complexes during processing and storage. The bound pyridoxyllysine was found to possess 50% molar vitamin B-6 activity, as indicated by slope ratios for rat growth, feed efficiency and liver pyridoxal 5'-phosphate concentration. The response curves indicated that high dosages of epsilon-pyridoxyllysine would fully satisfy the vitamin B-6 requirement. Direct antivitamin B-6 activity of epsilon-pyridoxyllysine was observed in diets containing low levels of PP-BSA. Classical rat acrodynia symptoms, depression of erythrocyte aspartate aminotransferase (AspAT) activity and elevation of in vitro coenzyme stimulation of AspAT were observed to be inversely related to PP-BSA concentration in the diet. The antivitamin B-6 effects were readily prevented by the presence of added 0.5--1.0 micrograms pyridoxing/g diet. In contrast to the previous study, the presence of PP-BSA in the diet did not inhibit the utilization of added PN. This difference was postulated to be due to a difference in vitamin B-6 concentration of the basal diets. The results of this study indicate that protein bound epsilon-pyridoxyllysine is nutritionally significant, presumably by its participation in the normal metabolism of vitamin B-6. The metabolic implications are discussed.

Animals↗

Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored childhood signs of Fabry disease.

Generalized anhidrosis with heat collapse, painful fingers, and angiokeratomas were the presenting signs in a 23-year-old man who was shown by enzyme studies and electron microscopy to have Fabry disease. His 6-year-old brother had the early diagnostic findings of episodic painful fingers, heat intolerance, and retroauricular telangiectasia. Both had an absence of alpha-galactosidase. Over 6 years of observation, the older brother developed progressive renal failure and the younger one developed acrodynia and anhidrosis. Their mother had diminished alpha-galactosidase activity and several angiomatous papules on one breast. A review of Fabry disease emphasizes the need for skin inspection for angiomas and telangiectasia, and enzyme assay in patients with inexplicable complaints or findings. Carrier females are most easily recognized by the presence of unique corneal opacities.

Adult↗

Immune thrombocytopenia and elemental mercury poisoning.

Three cases of severe mercury toxicity occurring within a family are reported. Two cases of thrombocytopenia occurred in this family and represent the second such report in the literature of an association between elemental mercury toxicity and thrombocytopenia. Three of the children presented with a combination of dermatologic and neurologic manifestations reminiscent of acrodynia or pink disease. Each of the four children in this family were treated with dimercaptosuccinic acid. The hazard of vacuuming spilled mercury and appropriate clean-up procedures are described.

Adolescent↗

[Tholozan: military physician].

Born in 1820 Joseph-Desire Tholozan joined in 1841 as "chirurgien sous-aide auxiliaire" the French military Health Service, being still a medical student in Marseille where the School of Medicine was directed by his uncle F. Cauviere. He was later appointed at the hospital of Bastia, obtained his M.D. (Paris 1843), went back to Marseille and later to Metz (1845) and Paris, at the Val-de-Grace (1846-47). He returned there as assistant physician (1851) and later as professor "agrege" of Medicine (1852), his agregation thesis devoted to hematology being presided by Andral. Tholozan later participated to the Crimean war (1854-55) during which he performed important observations on infectious diseases (cholera, dysentery, typhus, typhoid fever) or deficiency ones (scurvy, acrodynia). An unpublished report given here deals with a probable epidemic of murine typhus occurring in soldiers returning from Crimea on an American ship which had been used to transport horses. Promoted first class major physician (1857) Tholozan was chosen in 1858 by the French ministry of Foreign Affairs to become the physician of the Shah of Persia, Nasreddin Shah. In this country where he remained until his death (1897) he will have a threefold activity as organizer of the medical teaching, epidemiologist (of plague and cholera) and as a surgeon. Principal first class physician (the equivalent of Physician-Colonel) in 1868, he was definitely dismissed from the Army in 1880.

France↗

[Acquired ulcero-mutilating acropathies in adults. Critical study of 150 personal cases].

The authors review critically a series of cases, followed up by the authors, of acrodynia and trophic ulcers occurring either in alcoholics (119 cases) or in diabetics (28 cases), who were also often alcoholic as well. The symptoms were similar in both groups. However, the poor nutrition was generally more market in the alcoholics. The trophic disorders were very similar, together with the sensory disorders. However, the deep sensitivity was less rarely involved in diabetics. Above all, the study of the rate of conduction of the motor nerve fibers showed axonal involvement in alcoholics and segmental demyelinisation in diabetics. The treatment was mainly dietary, together with proper hygiene and immobilisation of the foot.

Adult↗

[Erythromelalgia, arterial hypertension and increased excretion of urinary catecholamines].

A 7 year-old girl was hospitalized with acute, severe and drug resistant erythromelalgia. During her stay in the hospital, she presented with an epileptic seizure associated with hypertension (220-120 mmHg). Catecholamine urinary excretion was markedly increased. Diagnoses of pheochromocytoma and acrodynia were excluded. Erythromelalgia and hypertension both disappeared in a few days without any relapse after a 2 year-follow-up. Catecholamine urinary excretion returned to normal levels in a few weeks. A skin biopsy which was performed in an affected site, showed a slight and questionable reduction of the density of autonomic adrenergic nerve terminals in the periarterial and glandular plexuses. The relevance of transitory excess catecholamine excretion and its link with erythromelalgia and hypertension are discussed. The hypothesis that the disorder could be explained by an abnormality of distal autonomic axons is likely.

Catecholamines↗

[Treatment of 700 cases of bilharziasis with the new drugs oxamniquine, oltipraz, praziquantel].

The authors study the results of a treatment of 700 cases of bilharziasis seen in Paris and in two foci in Togo, by oxamniquine, oltipraz or praziquantel. The three drugs are well tolerated; only a few mild side-effects were reported such as discomfort, nausea, headaches (two cases of acrodynia with oltipraz ). The three drugs are very efficacious in the case of schistosomiasis mansoni (85,5% success rate with oxamniquine, 92,9% with praziquantel, from 76,5 to 92% with oltipraz depending on the different strains) at day 180. As far as schistosomiasis haematobium is concerned, oltipraz and praziquantel have a 87,5% success rate with oltipraz and 80% with praziquantel; however, in the case of oltipraz , it is necessary to increase the dose. The action of praziquantel seems to be slower on Schistosoma haematobium than on S. mansoni. By the study of the evolution of antibodies, the fast action of praziquantel was noticed, explaining the peak of serological titers and of eosinophilia as early as day 10 after treatment; in the case of oltipraz , the apparition of this peak is only recorded at the 30th day. The slower effect of oltipraz on worms implicates not to judge its efficacy by too early controls.

Adolescent↗

Urine mercury levels in Kawasaki disease.

Six patients with diagnostic criteria for Kawasaki disease had abnormally high urinary excretions of mercury. They were compared by age, sex, and geographic location with matched controls. Improvement of one patient was temporally related to chelation of mercury with penicillamine. There are numerous clinical similarities between acrodynia and Kawasaki disease and the appearance of the mucocutaneous lymph node syndrome (Kawasaki disease) has been related temporally and geographically to environmental pollution with mercury. The mucocutaneous lymph node syndrome (Kawasaki disease) may represent a disease caused by environmental pollution with mercury, or clinical symptoms compatible with Kawasaki disease may indicate environmental exposure to mercury.

Adolescent↗