Naphthenic acids, nickel salts

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for publication.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Allergic contact dermatitis in psoriasis patients: typical, delayed, and non-interacting.

Author:

Quaranta M, Eyerich S, Knapp B, Nasorri F, Scarponi C, Mattii M, Garzorz N, Harlfinger AT, Jaeger T, Grosber M, Pennino D, Mempel M, Schnopp C, Theis FJ, Albanesi C, Cavani A, Schmidt-Weber CB, Ring J, and Eyerich K.

Year:

2014

Bibliographic source:

PLoS One; 9(7): e101814 (11 pages).

Materials and methods

Type of study / information:

gene expression, immunohistochemistry, histology, and T cell secretion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Evaluation of gene expression, immunohistochemistry, histology, and T cell secretion in nickel patch tested patients with allergic contact dermatitis (ACD) or psoriasis

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Nickel sulphate

EC Number:

232-104-9

EC Name:

Nickel sulphate

Cas Number:

7786-81-4

Molecular formula:

NiSO4

IUPAC Name:

nickel(2+) sulfate

Details on test material:

- Name of test material (as cited in study report): Nickel, assumed to be nickel sulphate, as it is commonly used in patch testing.

Results and discussion

Any other information on results incl. tables

Whole genome expression analysis:

Mean expression of 531 genes (1293 probes) was significantly different in the psoriasis group. A GO term pathway analysis showed that numerous pathways related to metabolism of lipids, amino acids, saccharides, and hormones as well as proliferation and differentiation pathways such as telomere maintenance, stem cell proliferation, and regulation of cell proliferation, were altered in psoriasis patients even in clinically non-involved skin.

Immunohistochemistry:

In psoriasis plaques, non-significant trends of a higher infiltration of CD15+ neutrophil granulocytes (17.1 versus 8.9 positive cells per visual field, p =0.5), BDCA-2+ plasmacytoid dendritic cells (6.3 versus 4.5, p =0.3), and IL-17+ T cells (17.8 versus 10.0, p =0.3) as compared to ACD reactions was observed. Furthermore, the proliferation marker Ki67 was expressed higher in psoriasis plaques than in ACD lesions (108.6 versus 73.6, p = 0,3). Positivity for Ki67 was observed especially in basal layers of the epidermal compartment, but was also observed in higher epidermal layers in the case of psoriasis (Fig. 2). In contrast, a higher number of cytotoxic CD8+ T cells (29.2 versus 20.7, p= 0,46) and perforine positive cells (6.5 versus 4.6, p = 0,46) was observed in ACD reactions as compared to psoriasis plaques.

T cell secretion of cytokines, chemokines, and growth factors:

Higher secrtion in psoriasis for: IL-17, IL-6, and CXCL8

Higher secretion in ACD for: IL-4, IL-5, IL-9, IL-10, IL-13, IL-1 receptor alpha, TNF-alpha, CCL-5, PDGF-bb, G-CSF, GM-CSF, and VEGF

Histology of inflammatory reactions after challenging nickel-sensitized patients with nickel on top of pre-existing psorisasis plaques:

Histologic hallmarks of both diseases were observed, namely psoriasiform acanthosis with neutrophilic micro-abscesses and dilated capillaries in the papillary dermis for psoriasis and marked spongiosis, epidermotropism and keratinocyte apoptosis defining dermatitis.

Clinical course of psoriasis:

Clinically, epicutaneous application of nickel on psoriasis plaques induced a strong local inflammatory reaction already after 48 hours in sensitized individuals. This inflammatory reaction was more severe than the nickel patch test reaction on previously non-involved skin, but it cleared following the natural course of an ACD reaction within two weeks. After 3–4 weeks, ACD reactions had resolved completely, but the initial psoriasis plaque remained largely unaltered.

The subjective clinical investigation was confirmed by a laser blood flow analysis of the cutaneous reactions. This blood flow analysis confirmed that despite the strong temporary inflammation, the clinical course of psoriasis was not influenced by the local induction of an ACD reaction. This was confirmed by the degree of the local psoriasis area-and severity index (PASI), erythema, squamation and infiltration. All these parameter were similar, even if slightly reduced, in the psoriasis plaque after three weeks as compared to the plaque before nickel challenge (n =11).

Applicant's summary and conclusion

Executive summary:

Study was rated by an independent reviewer.