The diagnosis of a contact allergy is made on the basis of a clinical
examination in which much attention is given to the nature and the location of
the lesions, the recording of a thorough anamnesis, the consideration of all
possible etiological factors, and the administration of patch tests, whereby
the determination of the relevance of the positive results obtained is
critical. The failure to recognize a
contact allergy can occur in any of the various stages of the allergological
investigation.
1. The clinical examination
The skin symptoms of a contact allergy manifest themselves classically
in the form of eczema that, of itself, can be very polymorphic and, depending
on the stage, is characterized by itching, erythematous-, squamous plaques,
papules, vesicles (occasionally with blister formation), skin thickening, and
fissures. However, a contact allergic
reaction can also produce non-eczematous lesions and thus follicular and dermal
lesions can determine the clinical picture to a greater or lesser degree. In addition, other forms of expression are
known, caused by both professional and non-professional allergens, such as:
erythema-, multiforme-like lesions or urticarial papular plaques; examples of such
allergens are tropical woods and many kinds of plants, local medication
- including steroidal - and non-steroidal anti-inflammatory drugs
(NSAIDs); lichen planus-like and lichenoid eruptions, the classic causes being
color developers (photography) and metals, the last also being responsible for
granulomatous and pustular reactions, although flavorings, synthetic resins,
textile allergens, and topical medications have occasionally been reported in
this regard. Lymphomatoid contact
dermatitis can also occur and has recently been reported to metals and textile
dyes; pigmentation disturbances, both hyper-pigmentation and hypo-pigmentation
(leukoderma) have been associated with several chemicals; even pemphigoid
lesions can express a contact allergy.
Finally, psoriasis, via the Köbner phenomenon, is also a possibility.
The location can be an important starting point in the identification of
the causal allergen since a contact eczema is generally restricted to the
contact site. The skin reactions,
however, can also occur on more sensitive sites such as the eyelids, where the
skin is thin and thus where substances can penetrate more easily. Sometimes, indeed, they are the only sites
when a facial cream or even a hair dye is the allergen source. So, too, the backs of the hands rather then
the palms are more affected by a contact allergy to gloves, while, in the case
of a textile dermatitis, often only friction and transpiration sites are
involved in the eczematous reaction.
Not only the intentional application to the skin but other exposure
possibilities occur: contact with allergenic or allergen-contaminated surfaces,
transfer of an allergen (for example, in nail polish) via the hands to the face
or other sites, which gives rise to an "ectopic" contact dermatitis,
a contact allergy caused by products that have come in contact with the partner
or other persons in the environment of the patient - what is called
"connubial" or "consort" dermatitis - and transfer through
the air of allergenic fumes, solutions, or powders, which gives rise to an
"airborne" dermatitis.
Id-like reactions, often in the form of small papules, may occur far
from the original contact site and may even be generalized. This can be explained by hematogenous
dissemination of the allergen.
After prior sensitization of the skin, allergic patients can also react
to oral or parenteral administration of the allergen or to a chemically related
substance that cross reacts. The
clinical picture can then be a flare up of the eczema at the previous contact
site or sites or have a diffuse, sometimes generalized eczematous aspect. Examples of this are certain antibiotics and
corticosteroids. In these cases, one
speaks of an endogenous or systemic contact dermatitis. Finally, there is photo-allergic contact
eczema, the consequence of exposure to a photo-contact allergen and sunlight.
2. The anamnesis
Essential is an extensive and standardized anamnesis that covers all
possible etiological factors like profession, leisure-time activities, use of
topical pharmaceutical products and cosmetics, and contact with plants. The patients can themselves provide many
indications but often need to be convinced that the allergenic product may not
have been introduced only recently into their environment. Indeed, it can take several days before the
clinical symptoms and signs appear after the contact. In addition, potential cross sensitizers the patient came in
contact with previously have to be considered and discussed.
3. Skin tests
The patch test remains at present the only reliable manner to identify a
contact allergy. It is a biological
test, so the results can be erroneously negative or positive. The causes of a false-negative reaction are
legion; the sensitization level of the patient may have been too low; the tests
may been administered in a refractory phase; the test concentration and/or the
amount of the substance may have been insufficient; the wrong test substance
may have been used; the vehicle may not have released a sufficient amount of
the allergen (the biological availability was too low); the occlusion might
have been insufficient; the test site might have been inappropriate; the
reading may have been made too soon; the reaction might have been suppressed
immunologically by exposure to sunlight, local application of corticosteroid,
or systemic administration of corticosteroids or other medications (e.g.
cyclosporine, pentoxifylline, or diltiazem, which can suppress the
immunological response. This list is
certainly not exhaustive. For the skin
tests, the possible risks of overlooking a contact allergy thus are centered on
the allergen itself, the test method, test concentration, and vehicle used, the
time of reading, and, finally, the relevance.
3.1. The allergen
First of all, only an allergen that is tested can be detected! In order to form an idea of the yield of
tests with the European standard series in contact-allergy examinations, the
patch-test results of 4 European centers were compared. It turned out that the proportion of contact-allergic
reactions diagnosed with the European standard series "only" varied
between 37 % and 73 % and for other allergens "only"
between 5 % and 23 %. This
indicates that a standard series must certainly be augmented by tests with
additional series and ingredients of products supplied by the patient. It happens that the cited allergen is not
itself the cause of the allergic reaction but an impurity in it. This is the case, for example, for cetyl
alcohol (pharmaceutical quality), which contains an unidentified impurity, so
patch tests with analytical quality cetyl alcohol thus give a "false"
negative reaction.
Of course, allergenic impurities occur much more in industrial products,
for example, allylglycidylether, a reactive epoxy thinner, was found as a
contaminant in a fixation additive in silicon and polyurethane resins. Allergenic degradation products can also be
formed during storage and then primarily by oxidation, as is the case of
limonene. Of course, this has immediate
implications for the patch-test material, thus the utility of stability checks.
Patch
tests are conducted with commercialized allergens and with substances that are
diluted in the recommended concentrations and vehicles. The products used, insofar as they are
having no irritant properties, are tested as such. However, when the concentration of an allergen is too low in the
final, solid product, as can be the case, for example, with rubber, shoes,
textiles, paper, and plants, or when insufficient amounts are released in
tests, extracts may have to be prepared.
When dermatitis occurs after repeated use or after the use of cosmetic
products on the more sensitive skin of the face and there is a negative test
result, use tests and/or "Repeated Open Application Tests" (ROATs)
are recommended. The intention is to
approximate as nearly as possible the use situation. Open or semi-open tests are indicated if the product would cause
irritation under occlusion. Highly
acidic or alkaline products are not tested unless they are buffered. In the case of a protein contact dermatitis,
only prick or scratch tests can reveal the allergen. In the case of a photo-allergic contact eczema, photo-patch tests
are, of course, administered.
3.3. Test concentration
Because the sensitivity threshold of each patient is not the same, there
is no optimal test concentration. For
most allergens, higher concentrations will elicit an allergic reaction more
frequently than lower concentrations and also more easily cause irritant
reactions. For corticosteroids,
however, because of their intrinsic anti-inflammatory properties, lower
concentrations seem to be required.
3.4. Test vehicles
The choice of the vehicle has an enormous influence on the biological
availability of an allergen. Petrolatum
is used most often for practical reasons.
When a contact allergy is assumed and the tests are negative, however,
another vehicle must be considered.
This has become clear primarily for corticosteroids.
3.5. Time of reading
Patch tests are read routinely after 2 and sometimes after 3 or 4
days. However, several articles have
recently been published demonstrating the importance of later readings, not
only for neomycin but also for allergens such as colophony, formaldehyde, and
certainly for corticosteroids.
3.6. Relevance
The allergy examination has reached a crucial phase when a positive
reaction has been found, for then the relevance of that reaction must be
determined. Bruze rightly points out
that one may not conclude too quickly that a test reaction is not relevant, for
such a determination depends primarily on the expertise of the investigator and
the possibility of detecting the allergen in the environment of the patient
(chemical analysis of the contacted products may be necessary). Finally, there is the possibility that the
patient could have been sensitized by a cross-reacting substance and that the
present test reveals only this allergy.
This is the case, for example, for tixocortol pivalate, which is a good
marker for corticosteroids of the hydrocortisone type, and for budesonide,
which is a marker for corticosteroids of the acetonide type and/or the labile
esters. If the results of the patch
tests are negative for a patient for whom a diagnosis of allergic contact
eczema has been proposed, one has to go back to the beginning, that is, with a
thoroughgoing anamnesis (perhaps with a visit to his or her environment). The assumed allergens must be re-tested
(perhaps in another concentration, with another vehicle, or with another
testing method), and additional allergens tested. The patient can also be asked to keep a journal in the hope that
a correlation can be discerned between exposure to a substance and the
occurrence of the skin problems.
The diagnosis of a contact allergy can be missed in the various stages
of the contact allergy investigation: the clinical examination of the patient,
the anamnesis, the skin testing (particularly as regards for the tested
allergen, the test concentration and vehicle, and the time of the reading) as
well as the determination of the relevance of a positive test.
Key words: clinical
symptoms - cross-reactions - diagnosis - false-negative tests - patch testing -
relevancy - test technique.