Skin Reactions to Xenobiotics Ola Bergendorff

Transcription

1 Skin Reactions to Xenobiotics Ola Bergendorff Department of Occupational Dermatology University Hospital Malmö

2 This lecture has been prepared with help from Associate Professors Malin Engfeldt and Cecilia Svedman Department of Occupational Dermatology, University Hospital, Malmö

3 Overview 1. Skin barrier 2. Chemical burn 3. Phototoxic reactions 4. Urticaria 5. Contact allergy

4 The skin barrier

5

6 The skin Epidermis 0.1 mm

7 Skin blister

8 Epidermis Blister Dermis Scarring permanent tattoo

9 Stratum corneum

10 Tape strip

11 Psoriasis 4 days L M Milstone. Epidermal desquamation. Journal of Dermatological Science (2004) 36,

12 Skin barrier 0.1 mm E p i d e r m i s Stratum corneum Keratinocyte Melanocyte Langerhans cell

13 500 µm 20 µm Moghimi HR; Williams AC; Barry BW. A lamellar matrix model for stratum corneum intercellular lipids. 2. INTERNATIONAL JOURNAL OF PHARMACEUTICS. 131 (2) Hadgraft J. Skin deep. Eur J Pharm Biopharm 2004: 58:

14 Lars Norlen, Karolinska Institute

15 Lars Norlen, Karolinska Institute

16 How large particles will penetrate skin?

17 Nanoparticles < 0,1 µm Rolland A, Wagner N, Chatelus A, Shroot B, Schaefer H. SITE-SPECIFIC DRUG-DELIVERY TO PILOSEBACEOUS STRUCTURES USING POLYMERIC MICROSPHERES. Pharm Res 1993: 10:

18 Chemical burns

19 Chemical burns due to Kathon CG - an allergenic preservative in paint

20 Chemical burn Chemical Acids, bases Hydrogen fluoride Phenols Bromine, Iodine Treatment Water Calcium salt Alcohol, PEG Thiosulfate

21 Protect your skin! Wash your hands thoroughly after contamination Use moisturiser Use gloves but choose the right material Exchange gloves often TOO MUCH WATER CONTACT WILL DAMAGE YOUR SKIN BARRIER

22 Toxic (non-allergic) photo reactions

23 Fytophotodermatitis

24 Photochemical DNA addition

25 Crosslinks in DNA Psoralen

26 Fytophototoxic plants Dictamnus albus Burning bush / Mose brinnande buske Ruta graveolens Rue / Vinruta Citrus peel

27 Urticaria

28 Stinging nettle (Urtica dioica) Urticaria Histamine

29 Allergy towards rodents

30 Urticaria

31 Immunologic urticaria Allergy type 1 A fast antibody-mediated reaction to large molecules. Proteins from animal saliva, urine, dandruff. Pollen. House dust mites. Natural rubber latex Occupational allergic asthma from small molecules that form adducts with proteines in airway mucosa. Isocyanates in paints and polyurethane. Acid-anhydrides in polymer production. Acrylates in polymers. Dental technicians.

32 Skin prick test Blood tests are also available for most of the allergens.

33 Contact allergy

34 Allergic contact dermatitis Nickel Rubber additives

35 Contact allergens Metal salts: nickel, chromium, cobalt Electrophilic organic compounds, MW < known allergens Preservatives, fragrances, hair/textile-dyes, rubber vulcanisers, plastic monomers, natural products, pharmaceuticals

36 Contact allergens

37 Epicutaneous testings Patch test After a few days Reading at day 3 and 7

38

39

40 Stefan R Ahlfors, Thesis 2008, dept of Dermatology Lund

41 Metals metal ions Nickel: 15-20% sensitive to Ni(II) Jewellery is the main exposure Coins, keys Chromium: 4% sensitive to Chromium (VI) Leather and cement main exposure

42 Cr Chromium Legislation Ni Nickel Directive 2003/53/EG reduction of Cr (VI) to insoluble Cr (III) by addition of reducing agent. No more than 2 ppm Cr(IV) allowed. OCCUPATIONAL Regulation (EU) 301/2014 content of Cr(IV) in leather must not exceed 3 ppm. CONSUMER/OCCUPATIONAL Annex XVII in 1907/2006 (REACH) In products intended to come into direct and prolonged contact with the skin the Ni release must not exceed 0.5 µg/cm 2 per week after 2 yrs of normal use. Adopted in 1994, in force CONSUMER

43 Chromate allergy Cement vs During construction of the bridges over Öresund and Stora Bält no one of the builders suffered from chromate induced dermatitis. In contrast, 17% of the concrete workers suffered from chromate dermatitis during construction of the tunnel between England and France. Irvine C et al. Cement dermatitis in underground workers during the construction of the Channel Tunnel, Occup Med 44:17-23

44 Fragrances naturally occuring substances More than 2500 synthetic fragrances

45 Limonene (citrus scent) Autoxidizes at 10 weeks: 40% limonene, 7% limonene OOH Allergenic oxidation products Hydroperoxides main allergens, also carvone, limonene oxide formed Concentration Karlberg et al. Contact Dermatitis 1997: 36: Oxidation time (weeks)

46 Limonene (citrus scent) Autoxidizes at 10 weeks: 40% limonene, 7% limonene OOH Allergenic oxidation products Hydroperoxides main allergens, also carvone, limonene oxide formed

47 Allergenicity from air oxidation 12M

48 Poison oak

49 Polymers Plastics : Epoxy, acrylates, phenolic etc monomers are allergens Rubber : Additives are allergens

50

51 ACRYLATES Exposure Dental fillings UV-curable paint Artificial nails Eye lash elongation

52 ACRYLATES UV-curing nail gel Oligomer Methacrylate monomer Photoinitiator Pigment

53 MSDS Oligomer Methacrylate monomer Photoinitiator Pigment

54 MSDS + Pigments

55

56

57

58

59 Rubber

60 Rubber polymer Polyisoprene. Isoprene monomers Hevea brasiliensis Palaquium gutta 100% cis-isomer i natural rubber % cis-isomer i synthetic polyisoprene Trans-isomer i gutta-percha. Dental material: fillning of root canal.

61 Natural rubber

62

63 VULCANIZATION

64 Rubber additives Allergenic accelerators and antioxidants

65 Accelerators Thiurams Name Abbrev. Structure Tetramethylthiuram monosulfide TMTM Tetramethylthiuram disulfide TMTD S N S S S N Tetraethylthiuram disulfide TETD Dipentamethylenthiuram disulfide DPTD S N S S S N

66 Acceleratorer Mercaptobenzothiazoles Name Abbrev. Structure 2-Mercaptobenzotiazole MBT 2,2 -Dibenzotiazyl disulfide MBTS N SH S N N S S S S 2-(4-Morfolinylmercapto) benzotiazole MOR N S S N O N-Cyclohexyl-2- benzotiazolsulfenamide CBS N S S H N

67

68

69 Soga F, Katoh N, Inoue T, Kishimoto S. Contact Dermatitis, 2008;58(2):

70 Preservatives In water based products Liquid soaps, shampoos, cosmetics, skin care products Paint, metal working fluids Isothiazolinones (MCI/MI) Formaldehyde (formaldehyde releasers)

71 Preservatives

72 Preservatives

73 Preservatives

74 Preservatives

75 Formaldehyde releasers Bronopol Diazolidinylurea Quaternium 15 Imidazolidinylurea DMDM hydantoin

76 Formaldehyde releasers 6 HCHO Bronopol Diazolidinylurea Quaternium 15 Imidazolidinylurea DMDM hydantoin

77 Summary Chemical burn Can result in an allergy Important to wash thoroughly ph-indicator Phenolics HF (hydrogen fluoride)

78 Summary Phototoxic reaction Furocoumarin (psoralen) + UV DNA-damage Wild plants Cultivated plants Citrus peel

79 Summary Urticaria Immunologic: type 1-allergy to macromolecules Antibody-mediated Skin Prick Test Immediate reaction Allergic asthma to small molecules in some cases

80 Summary Contact allergy Immunologic: type 4-allergy to small molecules Epicutaneous test (patch test) Delayed reaction T-cell-mediated Activation / air oxidation mechanisms Photoallergy to NSAID and Sunscreens

81 Black henna tattooing

82 p-phenylenediamine in henna tattooing Life-long allergy to: Hair dyes Textile dyes Black rubber

83 Black henna = Risk! Brown-orange henna = Minimal risk