The Allergy Alert Test, a proof of concept study

p-Phenylenediamine (PPD) is an important primary intermediate with a long
history of extensive use in oxidative hair colourants. PPD is a well-known
allergen and occlusive patch testing to PPD in the standard series have been
used for many years in dermatological practice to establish diagnosis of
contact allergy. Between 4 and 7% of the patch tested population is sensitized
to PPD. PTD is another component in oxidative hair colourants, which might
cause contact allergies.
In order to avoid the manifestation of contact dermatitis elicited by the
hair-dyeing procedure, hair dye manufacturers recommend an "allergy alert test"
or "skin self test" (skin sensitivity test, consumer open test) with the hair
colourant formulation, before hair colouring. This open test consists in the
application of the hair colourant to the skin for a defined period of time
followed by a reading 48 hours later. It should alert the hair colourant user
not to apply the product when experiencing any sensory or physically noticeable
deviation from normal conditions and to seek medical advice.

The effectiveness of 3 different alert test protocols was evaluated in
preceding studies carried out under dermatological control both with PPD
containing (1-3) and PTD-containing products (4).
During an EU workshop in April 2011, various aspects of the skin self test
protocol were discussed. It was recommended to harmonize the test protocol
across companies and that exposure time and test preparation used (colorant
formula mixed with developer) should reflect the actual use conditions.
Furthermore it should be ensured that the consumer can perform and understand
the potential alert signs of the test. More recently a population study
reported an adequate validity of self-testing for nickel allergy showing that
in most cases consumers are able to understand and correctly interpret alert
signs from self tests (5).
This study is a first step in the validity of skin self test for hairdyes,
therefore this proof of concept study will be carried out.

The study will be designed as a multicenter study to evaluate the impact of
several parameters influencing the sensitivity and specificity of skin self
tests.
The parameters are:
- Product applied: hair colouring formula mixed with developer (in use ratio)
- Reading time:
a) dermatological evaluation at 15 - 20 minutes after test removal, Day 2, Day
4 and later if considered necessary
b) independent daily self-evaluation by subjects: 15 - 20 minutes after test
removal, D1, D2, D3 D4 and later if necessary.
- Site: retro-auricular region versus volar aspect of forearms

Patients with a history of allergic reactions to hair dyes and a proven allergy
to PPD will carry out the skin self test with hair dyes containing different
concentrations of PPD corresponding to light, medium and dark shades of hair
colourants.
Positive results to the skin self test by dermatological evaluation or
self-evaluation will be validated against a defined *gold standard* for hair
dye allergy: the elicitation of clinical manifestations of allergic contact
dermatitis by the application of a particular hair dye product in real life
conditions. Sensitivity and specificity of the alert test will be evaluated
using this gold standard.

In addition, test site evaluations by dermatologists and by study subjects,
carried out independently, will be compared.

Observational study with the use of epicutaneous Skin Self Test and without the
use of a medicinal product.

No serious adverse events are expected during and after patch-testing. This
thought is supported by senior-researcher M. Krasteva MD PhD (see K6 safety and
risk assessment)
On the day of the patch-test application the time burden will be 90 minutes at
the most, in addition to travel time to the clinic. The actual application of
the patch will cause no harm or discomfort. The time burden for reading the
patch test reaction will be less than 15 minutes.
The total time burden on subjects depends on the reactions to each individual
test cycle. If a subjects reacts to a low dose PPD, the time burden is only one
cycles. Is someone does only reacts to a high dose of PPD, all the four cycles
will be completed.

It is anticipated that the majority of the PPD-sensitive subjects will develop
redness, possibly with some itching, at the site of the patch-test with the PPD
containing solution. This redness is transient, and will disappear within a few
days without leaving scars. Participants have the option to receive a one-time
application of a corticosteroid-containing cream to enhance the remission of
the reaction. Systemic effects from resorption of PPD are irrelevant at such a
short exposure time and small application area.

Subjects do not directly benefit from partcipation in this study.