TY - JOUR
T1 - Patch test–relevant concentrations of metal salts cause localized cytotoxicity, including apoptosis, in skin ex vivo
AU - Zhang, Yan
AU - de Graaf, Niels P.J.
AU - Veldhuizen, Rosalien
AU - Roffel, Sanne
AU - Spiekstra, Sander W.
AU - Rustemeyer, Thomas
AU - Kleverlaan, Cees J.
AU - Feilzer, Albert J.
AU - Bontkes, Hetty
AU - Deng, Dongmei
AU - Gibbs, Susan
N1 - Funding Information: Chinese Scholarship Council; Stichting voor de Technische Wetenschappen, Grant/Award Number: 13382 Funding information Funding Information: This work has been financed in part by Stichting voor de Technische Wetenschappen (Grant/Award Number 13382) and in part by Chinese Scholarship Council. We acknowledge Rosalien Veldhuizen for technical assistance in exposing skin to metal salts. Publisher Copyright: © 2021 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.
PY - 2021/11
Y1 - 2021/11
N2 - Background: Metal alloys containing contact sensitizers (nickel, palladium, titanium) are extensively used in medical devices, in particular dentistry and orthopaedic surgery. The skin patch test is used to test for metal allergy. Objective: To determine whether metal salts, when applied to freshly excised skin at patch test–relevant concentrations and using a method which mimics skin patch testing, cause in changes in the epidermis and dermis. Methods: Tissue histology, apoptosis, metabolic activity, and inflammatory cytokine release were determined for two nickel salts, two palladium salts, and four titanium salts. Results: Patch test–relevant concentrations of all metal salts caused localized cytotoxicity. This was observed as epidermis separation at the basement membrane zone, formation of vacuoles, apoptotic nuclei, decreased metabolic activity, and (pro)inflammatory cytokine release. Nickel(II) sulfate hexahydrate, nickel(II) chloride hexahydrate, titanium(IV) bis(ammonium lactato)dihydroxide, and calcium titanate were highly cytotoxic. Palladium(II) chloride, sodium tetrachloropalladate(II), titanium(IV) isopropoxide, and titanium(IV) dioxide showed mild cytotoxicity. Conclusion: The patch test in itself may be damaging to the skin of the patient being tested. These results need further verification with biopsies obtained during clinical patch testing. The future challenge is to remain above the elicitation threshold at noncytotoxic metal concentrations.
AB - Background: Metal alloys containing contact sensitizers (nickel, palladium, titanium) are extensively used in medical devices, in particular dentistry and orthopaedic surgery. The skin patch test is used to test for metal allergy. Objective: To determine whether metal salts, when applied to freshly excised skin at patch test–relevant concentrations and using a method which mimics skin patch testing, cause in changes in the epidermis and dermis. Methods: Tissue histology, apoptosis, metabolic activity, and inflammatory cytokine release were determined for two nickel salts, two palladium salts, and four titanium salts. Results: Patch test–relevant concentrations of all metal salts caused localized cytotoxicity. This was observed as epidermis separation at the basement membrane zone, formation of vacuoles, apoptotic nuclei, decreased metabolic activity, and (pro)inflammatory cytokine release. Nickel(II) sulfate hexahydrate, nickel(II) chloride hexahydrate, titanium(IV) bis(ammonium lactato)dihydroxide, and calcium titanate were highly cytotoxic. Palladium(II) chloride, sodium tetrachloropalladate(II), titanium(IV) isopropoxide, and titanium(IV) dioxide showed mild cytotoxicity. Conclusion: The patch test in itself may be damaging to the skin of the patient being tested. These results need further verification with biopsies obtained during clinical patch testing. The future challenge is to remain above the elicitation threshold at noncytotoxic metal concentrations.
KW - allergy
KW - apoptosis
KW - cytotoxicity
KW - excised skin
KW - nickel
KW - palladium
KW - patch test
KW - titanium
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U2 - https://doi.org/10.1111/cod.13940
DO - https://doi.org/10.1111/cod.13940
M3 - Article
C2 - 34268774
SN - 0105-1873
VL - 85
SP - 531
EP - 542
JO - Contact dermatitis
JF - Contact dermatitis
IS - 5
ER -