title: High frequencies of positive nickel/cobalt patch tests and high sweat nickel concentration in patients with intrinsic atopic dermatitis.
abstract: BACKGROUND
  Atopic dermatitis (AD) is classified into extrinsic AD with high serum IgE levels and impaired barrier, and intrinsic AD with low serum IgE levels and unimpaired barrier. Intrinsic AD has a lower frequency of FLG mutations and a higher frequency of circulating Th1 cells, implying that non-protein antigens, represented by metals, may be an exacerbation factor in intrinsic AD.
  
  
  OBJECTIVE
  To investigate metal allergy in intrinsic AD.
  
  
  METHODS
  Enrolled in this study were 86 Japanese AD patients seen in three university hospitals, consisting of 55 extrinsic and 31 intrinsic AD patients. Patch testing was performed, focusing on nickel, cobalt, and chrome, in parallel with other 14 metals. FLG mutations were analyzed in 49 patients (extrinsic, 29; intrinsic, 20). In 17 patients (extrinsic, 12; intrinsic, 5), sweat was collected from the forearms by exercise, and the concentration of nickel was fluorometrically measured.
  
  
  RESULTS
  Nickel, cobalt, and chrome were the major positive metals. Intrinsic AD showed significantly higher percentages of positive reactions than extrinsic AD to nickel (intrinsic 41.9% vs extrinsic 16.4%, P=0.019) and cobalt (38.7% vs 10.9%, P=0.005). There was no significant difference between FLG mutation-bearing and non-bearing patients. The concentration of nickel was higher in the sweat of intrinsic AD than extrinsic AD patients (333.8 vs 89.4ng/g, P=0.0005) and inversely correlated with serum IgE levels.
  
  
  CONCLUSIONS
  Nickel and cobalt allergy may be involved in intrinsic AD. Given that the metals are excreted through sweat, intrinsic AD might be exaggerated by highly metal-containing sweat.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Rieko
authors.initials: R
authors.lastname: Kabashima-Kubo
authors.forename: Toshinori
authors.initials: T
authors.lastname: Bito
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sakabe
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Shimauchi
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirakawa
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.forename: Koetsu
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002857:Chromium / Q000276:immunology; D003035:Cobalt / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000209:etiology*; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009532:Nickel / Q000032:analysis / Q000276:immunology*; D010328:Patch Tests; D013542:Sweat / Q000737:chemistry; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D002857:Chromium; D003035:Cobalt; D009532:Nickel
keywords: Barrier impairment; Extrinsic; Filaggrin (FLG); Metal patch test; Piercing; Toll-like receptor (TLR)