Nickel-epidermal interactions: Diffusion and binding

Diagnostic Testing for Nickel Allergic Hypersensitivity: Patch Testing versus Lymphocyte Transformation Test

“…False-negative results may occur due to actual allergen concentrations which fall short of label concentration [25] or the extremely long induction or lag times, demonstrated in skin penetration experiments with nickel salts [6][7][8]. In practice, also 2.5% nickel sulfate is used in the USA, Sweden and Japan instead of 5% [26], but, as Cronin [43] pointed out, up to 20% of true nickel sensitivities can thereby be missed [44].…”

“…In practice, also 2.5% nickel sulfate is used in the USA, Sweden and Japan instead of 5% [26], but, as Cronin [43] pointed out, up to 20% of true nickel sensitivities can thereby be missed [44]. Cases with a clinical history of nickel sensitivity have occasionally shown negative test results also when patch-tested with the standard 5% (0.19 M) nickel sulfate in petrolatum, possibly due to the considerable lag time involved in the salt's penetration through the SC and the likelihood of depot formation there [2,8,[45][46][47][48][49]. Upon pretreatment of nickel test areas with SDS, however, such an asymptomatic sensitivity will nevertheless become manifest, the inflammatory reaction elicited by the pretreatment facilitating the penetration of the immunogen [50].…”

“…For that reason, the role of the counterion on the irritation potential of nickel salts under simulated patch test conditions has been investigated in human skin in vivo, whereby the irritation potential was considered the expression of skin permeability [7][8][9]. The irritation potential of the salts was determined by application under occlusion to healthy volunteers and evaluation of irritancy by objective measurement with the laser Doppler technique.…”

“…The most common cause for a false-positive diagnosis is the irritant effect of the patch test concentration used, as testing is performed at levels close to the irritating dose; also uneven distribution of the salt (usually nickel sulfate crystals) in the vehicle (usually petrolatum) may cause foci of high concentration under the patch [6][7][8]. Intradermal testing has been proposed as an alternative, bypassing the SC barrier [36,37].…”

Oxidative Properties of Skin Exudates – A Determinant for Nickel Diffusion: A Review

“…Overall, depending on the polarity of the ion pair formed, three routes of entry appear available for skin penetration: (1) shunts (hair follicles, sweat glands and sebaceous glands) may serve for rapid passage of hydrophilic salts as an early-stage event, as they bypass the corneocytes and intercellular lamellae [7][8][9][10]; (2) this can be followed by slower but continuous, potentially more important intercellular diffusion; it appears reasonable to postulate that nickel ion pairs formed with fatty acids on the skin surface will preferably partition into the lipophilic environment [6]; the intercellular lipid domains in the SC may present a ready pathway for diffusion of lipophilic compounds, since transcellular penetration through keratin-packed corneocytes does not explain such phenomena as provocation of allergic reactions due to simple handling of metallic nickel; (3) the route of transcellular diffusion would appear to be of marginal immunological importance; it would be limited to adsorption in the outermost layers of the SC and possibly the epithelium of appendages; such adsorption may well be delayed, resulting from binding to the epidermis of such electrophilic, protein-reactive transition elements as nickel [11,12], or become terminal, by formation of depots through coordination bonding and formation of chelates with proteins [6,[13][14][15].…”