Etiology of Hand ACD
Allergic contact dermatitis is an immune-mediated type IV delayed hypersensitivity reaction. The North American Contact Dermatitis Group reported that the top 5 clinically relevant hand allergens were methylisothiazolinone (MI), nickel, formaldehyde, quaternium-15, and fragrance mix I.3 Similarly, the European Surveillance System on Contact Allergies demonstrated that the most common hand allergens were nickel, preservatives (quaternium-15 and formaldehyde), fragrances, and cobalt.18 In health care workers, rubber accelerators often are relevant in patients with hand ACD.5,19 Hand hygiene products are known to contain potential allergens; a recent study demonstrated that the top 5 allergens in common hand sanitizers were tocopherol, fragrance, propylene glycol, benzoates, and cetylstearyl alcohol,20 whereas the most common allergens in hand cleansers were fragrance, tocopherol, sodium benzoate, chloroxylenol, propylene glycol, and chlorhexidine gluconate.21
Preservatives
Preservatives can contribute to hand ACD. Methylisothiazolinone was the most commonly relevant allergen in a recent North American study of hand contact allergy,3 and a study of North American products confirmed its presence in dishwashing products (64%), shampoos (53%), household cleaners (47%), laundry softeners/additives (30%), soaps and cleansers (29%), and surface disinfectants (27%).22 In addition, in a study of 139 patients with refractory MI contact allergy, the hands were the most common site (69%) and had the highest rate of relapse.23 Because of the common presence of this preservative in liquid-based personal care products, patients with MI hand contact allergy need to be vigilant.
The same North American study highlighted formaldehyde and the formaldehyde releaser quaternium-15 as commonly relevant hand contact allergens.3 Formaldehyde is not commonly found in personal care products, but formaldehyde-releasing preservatives frequently are found in cosmetic products, topical medicaments, detergents, soaps, and metal working fluids. Another study noted that the most relevant contact allergen in health care workers was quaternium-15, possibly due to increased hand hygiene and exposure to medical products used for patient care.24,25
Metals
Nickel is used in metal objects and is found in many workplaces in the form of machines, office supplies, tools, electronics, uniforms, and jewelry. Occupationally related nickel ACD of the hands is most common in hairdressers/barbers/cosmetologists,26 which is not surprising, as hairdressing tools such as scissors and hair clips can release nickel.27,28
Although nickel contact allergy is more common than cobalt, these metals frequently co-react, with up to 25% of nickel-sensitive patients also having positive patch test reactions to cobalt.29 Because cobalt is contained in alloys, the occupations most at risk pertain to hard metal manufacturing. Furthermore, cobalt is used in dentistry for dental tools, fillings, crowns, bridges, and dentures.30 Cobalt also has been identified in leather, and leather gloves have been implicated in hand ACD.31
Fragrances
Fragrances can be added to products to infuse pleasing aromas or mask unpleasant chemical odors. In the North American study of hand ACD, fragrance mix I and balsam of Peru were the sixth and seventh most clinically relevant allergens, respectively.3 In another study, fragrances were found in 50% of waterless cleansers and 95% of rinse-off soaps and were the second most common allergens found in skin disinfectants.21 Fragrance is ubiquitous in personal care and cleansing products, which can make avoidance difficult.
Rubber Accelerators
Contact allergy to rubber additives in medical gloves is the most common cause of occupational hand ACD in health care workers.5,19 Importantly, it usually is rubber accelerators that act as allergens in hand ACD and not natural rubber latex. Rubber accelerators known to cause ACD include thiurams, carbamates, 1,3-diphenylguanidine (DPG), mixed dialkyl thioureas, and benzothiazoles.32 In the setting of hand ACD in North America, reactions to thiuram mix and carba mix were the most common.3 Notably, DPG is a component of carba mix and can be present in rubber gloves. It has been shown that 40.3% of DPG reactions are missed by testing with carba mix alone; therefore, DPG must be patch tested separately.33