Mercury, hypersensitivity

Heavy metals, principally mercury and silver, are now rarely used as disinfectants. Mercury is an environmental hazard, and some pathogenic bacteria have developed plasmid-mediated resistance to mercurials. Hypersensitivity to thimerosal is common, possibly in as high as 40% of the population. These compounds are absorbed from solution by rubber and plastic closures. Nevertheless, thimerosal 0.001-0.004% is still used as a preservative of vaccines, antitoxins, and immune sera. 

The mercurial diuretics essentially contain in an organic molecule. They usually inhibit sodium reabsorption in the proximal tubuler and ascending loop of Henle. There may be slight effect in the distal tubule where inhibition of chloride reabsorption also occurs. The mercurials have been foimd to enhance excretion though potassium loss is less than that produced by many other diuretics. However, the overall action of mercurial diuretics is invariably increased by acidification of urine. The mercurial diuretics are not very much used in clinical practices due to their pronormced and marked side-effects viz., mercurialism, hypersensitivity and excessive diuresis which may lead to electrolyte depletion and vascular complications. Most of the mercurials are administered by intramuscular route and the availability of orally active diru etics has limited their use. 

Koch P, Bahmer FA (1995) Oral lichenoid lesions, mercury hypersensitivity and combined hypersensitivity to mercury and other metals histologically-proven reproduction of the reaction by patch testing with metal salts. Contact Dermatitis 33 323-328... 

Burrows, D. Hypersensitivity to Mercury, Nickel and Chromium in Relation to Dental Materials , International Dental Journal, 36, 30-34 (1986)... 

Contraindications Acute renal impairment, organic (short-chain alkyl) mercury poisoning, G6PD deficiency (unless a life-threatening situation exists), hepatic insufficiency (unless due to arsenic poisoning), use of iron, cadmium or selenium poisoning, hypersensitivity to dimercaprol or any component of the formulations... 

Mercury compounds are generally less toxic than mercury(II) compounds because of then-lower solubilities. Calomel, a preparation containing Hg2Cl2, was once widely used in medicine. Its use as a teething powder for children has been known to cause a hypersensitivity response in children called pink disease, manifested by a pink rash and swelling of the spleen and lymph nodes. 

In a UK study, single oral doses of dimercaptopropane sulfonic acid or succimer in different combinations with or without acetylcysteine and potassium citrate were given to 191 patients considered to have mercury toxicity from amalgam dental fillings (2). After a single dose, about 5% of patients complained of mild gastrointestinal discomfort, fatigue, mental fuzziness, headache, and diuresis. These usually cleared within 6 hours of the dose and were considered to be due to heavy metal mobilization. There were no cases of hypersensitivity. 

The aryl mercurials, such as thiomersal are particularly likely to elicit hypersensitivity reactions (10,28), including attacks of asthma in patients who have received hepatitis B vaccine (29). Ethyl mercury toxicity and sensitization from thiomersal-containing vaccines have been indecisively discussed (30,31). The toxicity of ethyl mercury has also been discussed (32). 

Thimerosal is widely used as an antimicrobial preservative in parenteral and topical pharmaceutical formulations. However, concern over the use of thimerosal in pharmaceuticals has increased as a result of a greater awareness of the toxicity of mercury and other associated mercury compounds. The increasing number of reports of adverse reactions, particularly hypersensitivity, to thimerosal and doubts as to its effectiveness as a preservative have led to suggestions that it should not be used as a preservative in eye drops or vaccines. In both Europe and the USA, regulatory bodies have recommended that thimerosal in vaccines be phased... 

The organomercurial derivatives thiomersal and phenylmercuric nitrate or acetate (PMN or PMA) (Fig. 17.6) are bacteriostatic and are primarily employed as preservatives. Use of both compounds has declined considerably due to concerns about mercury toxicity and risk of hypersensitivity or local irritation. They are absorbed from solution by rubber closures and plastic containers to a significant extent. 

Acrodynia is an idiosyncratic hypersensitivity response from exposure to mercury and is characterized by certain cardiovascular, dermal, and neurological effects, among others. In the section on health effects by route of exposure, the relevant symptoms are discussed under the appropriate headings without reference to the syndrome. This occurs, in part, because there is some overlap between symptoms characteristic of acrodynia and those seen in persons who are not hypersensitive and, in part, because not every report of a study in which the symptoms were observed states whether the authors considered the affected person to have suffered from acrodynia. 

The organic alkylmercury compound thimerosal (sodium ethyl-mercury thiosalicylate) is another modem facet of mercury. Rare cases of systemic hypersensitivity with skin (Zenarola et al., 1995) and respiratory (Maibach, 1975) manifestations as well as acrodynia (Matheson et al., 1980) have been reported. Thimerosal in vaccines is discussed more in chapter 9. 

Mercurous (Hg ) salts of mercury are less corrosive and toxic, possibly because they are also less soluble. Calomel (HgCl) has been used in medicine for many years and more recently (in the 1940s and 1950s) as a "teething powder". It is known to be responsible for acrodynia or "pink disease". This was probably a hypersensitivity response to mercury salts on the skin. Affected children developed a pink rash and fever, with swelling of fingers, soles, spleen and lymph nodes and thickened skin. Irritability and insomnia were also, not surprisingly, a feature of the disease. 

Exposure to elemental mercury vapour may cause effects on the central nervous system, with a change of personality and tremor (cf. Skerfving and Vostal, 1972). Also, mercury may affect the kidney this may occur as a tubular (BarregSrd et al.. 1987) and/or glomerular (cf. Berlin, 1986 WHO, 1991) malfunction. Further, mercury may provoke hypersensitivity with skin manifestations. 

D. Heavy Metals Mercury and silver precipitate proteins and inactivate sulfhydryl groups of enzymes but are used rarely because of toxicity. Organic mercurials such as nitromersol and thimerosal frequently cause hypersensitivity reactions but continue to be used as preservatives for vaccines, antitoxins, and immune sera. Merbromin is a weak antiseptic and stains tissues a bright red color. In the past silver nitrate was commonly used for prevention of neonatal gonococcal ophthalmia, but it has been largely replaced by topical antibiotics. Silver sulfadiazine (a sulfonamide) is used to decrease bacterial colonization in bums. 

A number of metal salts have been found to induce delayed hypersensitivity, mainly of the contact type, in humans or in laboratory animals. Sensitivity to ions of chromium, mercury, platinum, nickel, beryllium, and others seem well established and Table 2 shows some recent findings. The best studied metal sensitizers are the chromium salts, since chromium eczema due to cement is the most important occupational dermatosis (Polak et al. 1973). Hexavalent chromium, in the form of potassium dichromate, is a better sensitizer than trivalent chromium. This seems related to the much better skin penetrating capacity of the dichromate, since numerous studies have shown that trivalent chromium compounds as opposed to hexavalent salt are the actual sensitizers (Polak et al. 1973). The same authors conclude that chromium is probably a component of the determinants formed with autologous carriers and does not produce autoantigens without further participation of the metal ion. In particular, oxidation reactions as generators of determinants seem inoperative in chromium hypersensitivity, since other strong oxidizers like... 

Penicillamine is a chelating agent which binds copper, mercury, zinc, and lead. It has been used to treat poisoning from these chemicals and also for disorders of copper metabolism such as Wilson s disease and primary biliary cirrhosis. Penicillamine has been tried in scleroderma and arthritis. Hypersensitivity reactions are common. About 20%-30% of the patients show hypersensitivity reactions suchs as morbilliform exanthema, urticaria, purpura, anorexia, lymphadenopathy, leukopenia, and thrombocytopenia (Meyboom 1975 Balme and Huskisson 1977). More severe skin symptoms associated with penicillamine therapy are Stevens-Johnson syndrome, pemphigus, myasthenia gravis, cholestatic jaundice (Barzilai et al. 1978), nephropathy (Lange 1978) and lupus-like syndrome (Harpey et al. 1972). 

Indeed, in 1896, J. Jadassohn, after applying a mercurial plaster to the arm of a patient, observed for the first time a local reaction. He thus produced experimentally a bullous lesion and he was able to affirm that the eczematous lesions presented by this patient were caused by a hypersensitivity to mercury. This first experiment permitted the separation of contact eczema from the large group of eczemas of indeterminate origin. 

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