Evaluation of the relevance of day 7 readings in patch testing for diagnosing contact allergy

Proposal introduction:
Contact dermatitis is an inflammatory skin disease precipitated by direct contact with exogenous irritants and allergens {1}. It can be irritant or allergic. In allergic contact dermatitis, the
patho- mechanism involves an immunological hypersensitivity reaction, however, in irritant contact dermatitis, no immunological reaction is elicited {1,2}. It is a frequent problem with a
prevalence of 20% in the general population in Europe. It occurs twice as often in females as in males with sensitization occurring usually at a young age between 12–16 year olds {3,4}.
The typical morphology of allergic contact dermatitis is a sharply-demarcated, pruritic, eczematous eruption localized to the area of skin that has been directly exposed to a certain allergen. The
presentation may be acute, with vesiculation, erythema, oedema, or chronic with squamae and lichenification {5}.
Epicutaneous patch testing is the gold standard investigation to diagnose specific contact allergies, which may be the cause of allergic contact dermatitis, when there is relevant exposure {1,6,7}.
This test is based on the principle that in sensitized individuals, antigen-specific T lymphocytes circulate throughout the body and are able to elicit a delayed hypersensitivity reaction when
concentrations of the antigen are applied the skin {1,6}.
Several techniques might be used when applying patch tests such as the open test, semi-open test or closed patch testing. The latter is the most commonly applied technique, involving the
application of allergens under occlusion on the skin of the upper back of the test subject for 48 hours allowing for a sufficient occlusion time {1,6,8}. Allergens are applied in standardized
concentrations loaded in standard amounts of for example petrolatum or water in special chambers mounted on non-occlusive tape strips. According to the guidelines of the European Society of Contact
Dermatitis (ESCD), a minimum of two readings is mandatory. Ideally, three readings are performed at D2, D3 or D4, and D7 {1,6}.
Recent studies have demonstrated that an extra reading on day 7 yields less incidents of false negative results than day 2 or 3 readings alone {9,10,11}. This is particularly valid for reactions
involving allergens with a greater tendency to display a positive reaction after day 3, like corticosteroids, neomycin and nickel {9,10,16}. However, day 7 reading is not standard in all patch test
clinics. This may be attributed to many practical problems. One study has stated that adding a third visual reading will result in one of the readings being performed during the weekend,
furthermore, this will also raise issues with patients’ adherence due to multiple hospital visits {10,11}.
Although the patch test procedure is simple, reading and interpreting the test results are difficult and require experience. Results are measured by morphologic criteria recommended by the
International Contact Dermatitis Research Group (ICDRG) {12}. A positive patch test must be relevant to the dermatitis to be meaningful. Two types of relevance are considered; current and past
relevance. These two types correspond to current clinical symptoms or to past events, respectively {13}. Therefore, accurate history taking and information about past and current exposure to
allergens are essential {12,13}.
Yet, further studies with larger population are needed to investigate the relevance of readings at day 7. Moreover, accurate information about which allergens tend to manifest positive reactions
after day 3, and whether there are specific patients’ characteristics (e.g. atopic dermatitis) which might influence patch test results, are lacking.

Does a day 7 patch test reading have added value over only a day 3 reading in detecting contact allergy?
Secondary questions:
a- Are there specific allergens which, when patch tested, cause a significant number of positive reactions on day 7, but not on day 3?
b- How does the probability of developing a positive patch test reaction on day 7 change with patients’ characteristics?

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