Reliability of Expired Allergens in Patch Testing: A Comparative Study With Non-Expired Series

In brief, review of the medical literature showed two comparable studies out of India and Spain suggesting that expired allergen series may be used beyond their labeled expiry dates, with some variability noted amongst duration of expiry, that the investigators will also aim to analyze.

Regarding allergen stability, there were also several studies focused on this domain. The European Society of Contact Dermatitis (ESCD) released guidelines in 2015, outlining optimal methods for allergen storage such as storage at 4 degrees celsius and strict protection from ultraviolet light exposure. While most allergens are dispersed in petrolatum (white soft paraffin), some substances are better tested in solutions such as water (aqueous) or ethanol. Several allergens with high vapour pressure require more frequent renewal and strict storage conditions such as fragrance chemicals, acrylates and isocyanates. Other substances such as glutaraldehyde in petrolatum (pet.) and formaldehyde in aqueous solution (aq.) are susceptible to instability and deterioration. An additional study assessed volatility over time of several select compounds and described high volatility in acrylates, glutaraldehyde, and fragrances, while describing partial volatility of formaldehyde and low volatility of nickel sulfate.

Study participants will include all eligible adults seen in patch testing clinic who maintain an indication for patch testing and consent to participation. The study will be utilizing 10 allergens from the North American Contact Dermatitis Group (NACDG) 80 Series for inclusion in the study.

The allergen selections are primarily based on compounds with a higher likelihood for volatility, in addition to inclusion of two comparator compounds with lower volatility. Expiration intervals include 1 year, 2 years, 3 years, and 4 years. The compounds selected are as follows, including their dispersion compound: nickel sulfate hexahydrate (5% pet.), cobalt (II) chloride hexahydrate (2.5% pet.), hydroperoxides of linalool (1% pet.), hydroperoxides of limonene (0.3% pet.), fragrance mix 1 (8.0% pet.), myroxylon pereirae resin (balsam of Peru) (25.0% pet.), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) (0.02% aq.), formaldehyde (2.0% aq.), tixocortol-21-pivalate (1.0% pet.), and budesonide (0.1% pet.).

The patch testing results will be compared to corresponding non-expired allergens from the same manufacturer with the same preparation tested simultaneously. Both series will be placed simultaneously in differing locations on the participant's back, ensuring both are placed in sun protected areas with no underlying dermatitis.

Once in clinic, standard patch test series are applied on patch testing day, with the participant instructed not to shower or scratch the area throughout testing. At 48h, the patches are removed and photos are taken of the participant's back which are sent to the Dermatologist for virtual reading. At either 96h or 120h, the participant returns to the clinic for final reading. Both morphology and intensity of positives are graded on a standard patch test scale (irritant reaction), +/- for doubtful, + for erythema and infiltration, ++ for edematous or vesicular and +++ for spreading, bullous or ulcerative. Positive allergens scored + or greater are considered a true allergic contact allergen and assessed for relevance based on clinical context. The Dermatologist provides information sheets on all positive allergens, counsels on the relevance to their clinical history and allergen avoidance going forward, as well as providing the participant with a safe product list via the ACDS Contact Allergen Management Program (CAMP) database.

The investigators are aiming for enrolment of 100 participants which should theoretically provide the study with at least 5-10 participants testing positive to each of the four listed allergens with higher volatility and 20+ participants testing positive to the allergens with lower volatility. The investigators are aiming to assess concordance between expired and non-expired allergen reactions (positive vs negative), in addition to agreement in reaction intensity, differences in morphology, rates of false positives/negatives compared to control and concordance of irritant reaction between interventions.

The study will serve to lend valuable evidence as to whether expired allergens maintain clinical utility and could serve to reduce product waste, lower the economic burden and further improve accessibility of patch testing for use in resource limited settings.