Nickel contamination of gold salts: link with gold-induced skin rash

Abstract

Intramuscular chrysotherapy is a well-established treatment for rheumatoid arthritis. Its therapeutic use has been limited by the high incidence of dermatological side-effects. The pathogenic mechanisms of these are unknown, but could include allergic reactions to gold or to nickel contaminating the gold. In order to investigate these mechanisms further, 15 patients, who developed cutaneous eruptions after chrysotherapy, were assessed using skin biopsy and lymphocyte transformation stimulated by gold and nickel salts in vitro. Chrysotherapy induced two main cutaneous eruptions: lichenoid reactions and non-specific dermatitis. Peripheral blood mononuclear cells from patients with lichenoid reaction proliferated to gold salts in vitro, while those who developed non-specific dermatitis responded mainly to nickel. Nickel was a significant contaminant of the gold preparation (sodium aurothiomalate, Myocrisin, Rhone-Poulenc Ltd), amounting to a total of 650 ng after 6 months treatment. We suggest that a significant percentage of skin reactions during chrysotherapy are due to nickel contamination of the gold preparation.

Gold compounds as anticancer agents: chemistry, cellular pharmacology, and preclinical studies

“…one of the main intracellular storage sites for gold compounds, injected gold(I) drugs may be oxidized to gold(III) by hypochlorite (generated by myeloperoxidase). 25,26 This represents an effective and unexpected biochemical pathway whereby the usually unstable gold(III) species are formed in vivo.…”

Chrysotherapy: a synoptic review

“…52, 2003 Chrysotherapy 489 include a number of associations in reducing inflammation. These associations are arbitrarily grouped into three sometimes overlapping groups: (a), Au + and Au + metabolites, including Au(CN) 2 - [1,2,43,51,58,59], Au +3 [2,3,47,51,58,60], and Au o [60,61]; (b), immunomodulatory activity, including alterations of peptides, macrophage phagocytosis, histamine release, monocyte migration, T cells, B cells, and immunoglobulins [12, 14, 36, 38, 42, 44, 51, 53, 62-64, 74, 75]; and (c), others. This last category includes tumor necrosis factor [38, 65 -67]; bone resorption [68]; leukocyte infiltration [69], and leukocyte antigens [39,52]; lysosomal enzymes [1,49]; protein-gold complexes [1,2,70]; polymorphonuclear neutrophils [58,71]; sulfhydryl binding sites [1,72]; superoxide ion radical [4,73]; and thioredoxin reductase, a selenoenzyme [34].…”

“…Au + Injectable Au + complexes are oxidized by hypochlorite (generated by myeloperoxidase) to Au +3 species in the phagolysomes of activated macrophages and granulocytes [47,58]. Trivalent gold, but not Au + , can induce proliferation of lymphocytes in up to 73 % of patients with Au + -induced cutaneous eruptions.…”

“…Parenteral gold drugs modified the course of RA when given in sufficient dose over a protracted period [46]. Gold drugs, such as sodium gold thiomalate, have been used since 1929 in the treatment of patients with RA and are still considered as important disease modifying antirheumatic drugs [39,47,48]. Approximately 50 % of treated patients are usually markedly improved or cured, but toxic side effects were observed in about 40 % of the cases [1].…”

“…Adverse side effects included skin rashes; protein in the urine; inflammation of the mouth; reduction in the number of circulating leukocytes; decreased number of blood platelets; aplastic anemia due to organ damage; lung abnormalities; adverse immune reactions, such as stomatitis, eosinophilia, lymphadenopathy, hypergamma globulinemia; severe hypotension, angina, myocardial infarction, nephrotoxicity and nephrotic syndrome; hepatitis; colitis; and chrysiasis (pigmentation) of the cornea, lens, and skin [3,8,14,44,50,52,53,57]. The most common side effect of chrysotherapy was skin toxicity, accounting for up to 60 % of all adverse reactions, especially lichenoid eruptions and non-specific dermatitis [3,47,54,55]. When chrysotherapy was discontinued, it was usually due to adverse mucocutaneous side effects during the first 2 years, and inefficacy after 4 years [56].…”