2/22/2017. Contact Allergens of the Year Emerging Allergens Contact Allergen of the Year. Occupational Exposures. Consumer Exposure Shoe insoles

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Contact Allergens of the Year Emerging Allergens DISCLOSURE OF RELATIONSHIPS WITH INDUSTRY Michael P.

Michael P. Sheehan, MD, FAAD Dermatology Physicians Inc.

an organic compound structurally similar to urea.

Thiourea is a reagent used in organic synthesis.

1 Contact Allergens of the Year Emerging Allergens DISCLOSURE OF RELATIONSHIPS WITH INDUSTRY Michael P. Sheehan, MD F039- Contact Allergens of the Year Emerging Allergens DISCLOSURES Celgene speaker bureau. Michael P. Sheehan, MD, FAAD Dermatology Physicians Inc. Columbus, IN 2009 Contact Allergen of the Year Mixed Dialkyl Thioureas Mixed Dialkyl Thioureas Thiourea is an organic compound structurally similar to urea. Thioureas refers to a class of compounds with this basic structure. Thiourea is a reagent used in organic synthesis. 4 Rubber synthesis and antioxidant (Warshaw et all, 2008) Occupational Exposures Consumer Exposure Shoe insoles Orthopedic braces / prosthetics Healthcare workers Neoprene manufacturing Jewelers & Silversmiths Architects & builders CPAP straps Keyboard wrist supports Slimming suits Wet suits & diving equipment 1

Neoprene Widely used synthetic rubber. Soft, flexible, cushioning, and fire/oil/ozone resistant. Thiourea Clinical Pearls Most common source of exposure = neoprene products.

Propensity to develop papular and vesicular dermatitis at sites distant from direct skin contact with the offending article.

Included on NACDG Standard Series as mixed dialkyl thioureas 1% in petrolatum (diethylthiourea 0.5% and dibutylthiourea 0.5%). Relatively low rate of positive reactions 0.8%-1.3%.

2 Neoprene Widely used synthetic rubber. Soft, flexible, cushioning, and fire/oil/ozone resistant. Thiourea Clinical Pearls Most common source of exposure = neoprene products. Most common occupational exposure = gloves. Chloroprene or Polychloroprene is the common name. Neoprene is the trade name. Most common consumer exposure = footwear. Propensity to develop papular and vesicular dermatitis at sites distant from direct skin contact with the offending article. Allergic patients are twice as likely to react to other rubber accelerators (thiurams, carbamates, and MBTZ). Included on NACDG Standard Series as mixed dialkyl thioureas 1% in petrolatum (diethylthiourea 0.5% and dibutylthiourea 0.5%). Relatively low rate of positive reactions 0.8%-1.3% Contact Allergen of the Year Dimethyl Fumarate High rate of relevance with positive reactions. (Gimenez Arnau et al, 2009) Dimethyl Fumarate Dietary Exposures fumarate Citric Acid Cycle Methyl ester of fumaric acid (FA) Salts & esters of FA are known as fumarates Intermediate in the Citric Acid Cycle and byproduct of the Urea Cycle FA is used as a food additive in sweets and cakes. FA is poorly absorbed and passes through the gut without absorption. Human skin naturally produces FA when exposed to sunlight. Foodchem international corporation FA also found in some vitamins and supplements. 2

Clinical Use Esterification of FA leads to absorption. FA Esters have been used to treat psoriasis for over 30 years.

Clinical Use DMF approved by FDA in 2013 to treat adults with relapsing multiple sclerosis.

Other listed possible side effects include severe allergic reaction, PML, and low white blood cell count.

Leather products such as furniture, shoes, wallets Robust reactions Not part of the North American Standard Series.

3 Clinical Use Esterification of FA leads to absorption. FA Esters have been used to treat psoriasis for over 30 years. No currently available FDA approved agent. DMF appears to be the most clinically relevant ester. Hypothesized to shift from TH1 to TH2. Clinical Use DMF approved by FDA in 2013 to treat adults with relapsing multiple sclerosis. Flushing and GI side effects most common adverse events. Other listed possible side effects include severe allergic reaction, PML, and low white blood cell count. Consumer Exposure Dimethyl Fumarate Clinical Pearls Desiccant and anti-mold sachets Prevent mold growth Shoe dermatitis Furniture dermatitis Leather products such as furniture, shoes, wallets Robust reactions Not part of the North American Standard Series. Recommended patch test concentration is 0.1% DMF in petrolatum. Potential for evaporation from syringes may be decreased if frozen. Concurrent patch test reactions to other fumarates and low molecular weight acrylates are common. Positive patch test to methyl acrylate or ethyl acrylate may indicate DMF sensitivity. Cross Reactivity (Bruze et al, 2011) 3

2012 Contact Allergen of the Year are plastic materials derived from polymerization of monomers such as acrylic acid or methacrylic acid. Think strong glues and plastics.

(Sasseville, 2012) Methyl methacrylate Acrylic bone cement Acrylic inks Solvent based adhesives Medical spray adhesives Dental technology Ethyl acrylate Acrylic paints Industrial coatings Acrylic

2-Hydroxyethyl methacrylate (2-HEMA) 2-Hydroxypropyl acrylate (2-HPA) 2-Hydroxypropyl methacrylate (2-HPMA) Polyfunctional Prepolymer Epoxy acrylates Bisphenol A Glycidyl methacrylate (GMA)

materials Artificial nails Printing inks Engine coolants Dimethacrylates Ethyleneglycol dimethacrylate (EGDMA) Diethyleneglycol dimethacrylate (DEGDMA) Triethyleneglycol dimethacrylate (TREGDMA)

4 2012 Contact Allergen of the Year are plastic materials derived from polymerization of monomers such as acrylic acid or methacrylic acid. Think strong glues and plastics. Monomers act as sensitizers & allergens. (Sasseville, 2012) Methyl methacrylate Acrylic bone cement Acrylic inks Solvent based adhesives Medical spray adhesives Dental technology Ethyl acrylate Acrylic paints Industrial coatings Acrylic rubber & plastics Denture materials Floor polishes & sealants Monofunctional Ethyl acrylate (EA) Butyl acrylate (BA) Methyl methacrylate (MMA) Ethyl methacrylate (EMA) 2-Hydroxyethyl acrylate (2-HEA) 2-Hydroxyethyl methacrylate (2-HEMA) 2-Hydroxypropyl acrylate (2-HPA) 2-Hydroxypropyl methacrylate (2-HPMA) Polyfunctional Prepolymer Epoxy acrylates Bisphenol A Glycidyl methacrylate (GMA) Cyanoacrylates 2-Hydroxyethylmethacrylate (HEMA) Artificial nails UV Inks Adhesives Lacquers Dental material Paint resins Ethyleneglycol dimethylacrylate Plastic bottles for soft drinks Dental materials Artificial nails Printing inks Engine coolants Dimethacrylates Ethyleneglycol dimethacrylate (EGDMA) Diethyleneglycol dimethacrylate (DEGDMA) Triethyleneglycol dimethacrylate (TREGDMA) 1,4-Butanediol dimethacrylate ( BUDMA) Trimethylol propane trimethacrylate 1,6-hexanediol diacrylate (HDDA) Triethyleneglycol diacrylate (TREGDA) 1,6- Hexanediol diacrylate Pentaerythritol triacrylate (PETA) Trimethylpropane triacrylate (TMPTA) Methyl-2-cyanoacrylate Ethyl-2-cyanoacrylate n-butyl-cyanoacrylate 2-octyl-cyanoacrylate Occupational Exposures Nail Salon Acrylic Nails & Gel Nails Dentists & Health Care Providers Bone Cement Dentures Printing Industry Acrylic Ink Silk Screen Printing Painters Acrylic Paint Manufacturing & Construction Adhesives Caulk Plexiglas Machinists or Mechanics Loctite, Sta-Lok Consumer Exposure Acrylic or gel nails Diapers Sanitary pads Dentures Spectacle frames Hearing aids 4

Acrylate Clinical Pearls Hands & airborne pattern typical in occupational cases Robust dermatitis Potential for delayed and persistent patch test reactions Strong irritants.

5 Acrylate Clinical Pearls Hands & airborne pattern typical in occupational cases Robust dermatitis Potential for delayed and persistent patch test reactions Strong irritants. Potential for inducing sensitization with patch testing. Acrylate sensitive patients often show multiple concurrent positive patch test reactions which may represent cross-reactions or coreactors. Volatile and unstable chemicals. Rapidly evaporates if exposed to air over a few hours. Late Reactors North American Contact Dermatitis Group Standard Series Allergens Corticosteroids Metals Neomycin 2-Hydroxyethyl methacrylate (2-HEMA) 2% Petrolatum Bisphenol A epoxy resin 1% Petrolatum Ethyl acrylate 0.1% Petrolatum Methyl methacrylate 2% Petrolatum T.R.U.E. Test Allergens Epoxy Resin (Diglycidylether of bisphenol A) Protection Acrylate monomers penetrate most gloves within minutes (especially vinyl and latex). Laminated polyethylene/ethylene vinyl alcohol gloves provide the best protection but provide poor dexterity. Double gloving with nitrile gloves or polyethylene gloves under nitrile gloves has been suggested to be adequate for tasks under minutes. Citations Warshaw EM, Cook JW, Belsit DV et al. Positive patch-test reactions to mixed dialkyl thioureas: cross-sectional data from the North American Contact Dermatitis Group, 1994 to Dermatitis 2008:19; Kanerva L, Estlander T, Jolanki R. Occupational allergic contact dermatitis caused by thiourea compounds. Contact Dermatitis 1994:31(4); Dooms-Goossens A, Chrispeels MT, De Veylder H, Roelandts R, Willems L, Degreef H. Contact and photocontact sensitivity problems associated with thiourea and its derivatives: a review of the literature and case reports. Br J Dermatol 1987:116; Warsaw EM, Belsito DV, DeLeo VA et al. North American Contact Dermatitis Group patch-test results, study period. Dermatitis 2008:19; Mark JG, Belsito DV, DeLeo VA, et al. North American Contact Dermatitis Group patch-test results, Am J Contact Dermat 2003;14: Gimenez Arnau A, et al. Shoe contact dermatitis from dimethyl fumarate: clinical manifestations, patch test results, chemical analysis, and source of exposure. Contact Dermatitis 2009:61; Bruze M, Zimerson E. Dimethyl fumarate. Dermatitis 2011;22(1):3-7. Sasseville D. in contact dermatitis. Dermatitis 2012:23(1):6-16. Makela EA, Jolanki R, Chemical permeation through disposable gloves. In: Boman E, Estlander T, Wahlberg JE et al, eds. Protective Gloves for Occupational Use. 2 nd ed. Boca Raton, FL: CRC Press; 2005: North by Honeywell Silver Shield 2.7 mil Chemical Resistant Gloves. Image retrieved from 5

Dictionary of Contact Allergens: Chemical Structures, Sources and References

Dictionary of Contact Allergens: Chemical Structures, Sources and References 1.1 Introduction This chapter has been written in order to familiarize the reader with the chemical structure of chemicals implicated