The gold standard for diagnostics of contact sensitisation is patch testing. The proce-dure is as follows. A standardised allergen preparation, usually in petrolatum or water, is filled into a small chamber which is mounted on adhesive plaster. The plaster is attached for 48 (or in some cases 24) hours to the patient’s upper back, so that the allergen preparation has occlusive skin contact. After this time (day 2, in case of 48 hours patch test exposure time), the test chambers are removed, and their position is marked on the skin. A first reading of the test is done 20-30 min after removal. A second reading on day 3 or day 4 is obligatory. Additional later readings may be performed and usually improve the validity of the patch test [Johansen et al. 2015, Lindberg and Matura 2011].
A positive patch test, indicating contact sensitisation to the respective allergen, is char-acterized by erythema, infiltration and possibly vesicles in the test area (i.e., an allergic contact dermatitis). Reactions with erythema only, but without any infiltration or vesi-cles, may indicate weak (low grade) sensitisation or unspecific irritation by the test.
Therefore, these reactions are called “doubtful” and are coded with a question mark.
Clear-cut irritant reactions also may occur. Table 1.2.1 gives an overview of patch test reactions, their morphology, coding and interpretation. Allergic reactions usually in-crease in intensity from day 2 to day 3 (or 4), or keep their reaction strength. This course is described as “crescendo reaction” or “plateau reaction”. In contrast, irritant reactions usually tend to fade or vanish from day 2 to day 3 (or 4), thus showing a
“decrescendo pattern”. Time course of a patch test reaction may help interpreting a reaction as irritant or (truly) allergic. Like in every biological test, false positive as well as false negative reactions may occur [Johansen et al. 2015, Lindberg and Matura 2011]. Depending on the substance, vehicle, and test concentration this may happen more or less frequently. Some patch test preparations are more prone to elicit doubtful, irritant, or weak (and putative false positive) reactions. These are commonly called
“problematic allergens” (table 1.2.2.) [Geier et al. 2003a, 2010].
Tab. 1.2.1 Patch test reactions [Schnuch et al. 2008]
Symbol
(Coding) Morphology Interpretation
- no reaction (normal skin) negative
? erythema only, no infiltration allergic, irritant or unclear f few follicular papules allergic, irritant or unclear + erythema, infiltration, papules weak allergic reaction ++ erythema, infiltration, papules, vesicles strong allergic reaction +++ erythema, infiltration, coalescing
vesi-cles very strong allergic reaction
ir soap effect, ring effect, blister, necrosis irritant reaction
Tab. 1.2.2So-called problematic allergens – patch test preparations which frequently elicit doubtful, irritant or even false-positive patch test reactions [Geier et al. 2003a, 2010].
Substance Concentration Vehicle
Preservatives and surface disinfectants
Benzalkonium chloride 0.1 % petrolatum
Benzyl hemiformal 1 % petrolatum
4-(2-Nitrobutyl)-morpholine /
4,4’-(2-Ethyl-2-nitrotri-methylene)-dimorpholine (Bioban P1487®) 1 % petrolatum
Methylen-bis(methyloxazolidine) 1 % petrolatum
4,4-Dimethyl-1,3-oxazolidine /
3,4,4-Trimethyl-1,3-ox-azolidine (Bioban CS 1135®) 1 % petrolatum
7-Ethylbicyclooxazolidine (Bioban CS 1246®) 1 % petrolatum
Glutardialdehyde 0.3 % petrolatum
Iodopropynyl butylcarbamate 0.2 % petrolatum
Methyldibromo Glutaronitril 0.3% petrolatum
Ointment bases and emuslsifiers
Amerchol L-101 50 % petrolatum
Cocamidopropyl betaine 1 % aqua
Octyl gallate 0.3 % petrolatum
Propylene glycol 20 % aqua
Sorbitan sesquioleate 20 % petrolatum
Triethanolamine (TEA) 2.5 % petrolatum
Drug components and skin disinfectants
Benzoyl peroxide 1 % petrolatum
Chlorhexidine digluconate 0.5 % aqua
Phenyl mercuric acetate 0.05 % petrolatum
Povidone iodine 10 % aqua
To date, about 4,500 substances (compounds) have been described to have caused allergic contact dermatitis [de Groot 2008]. About 250 allergen preparations are com-mercially available for patch testing. It is self-evident that not every substance can (and must) be patch tested in every patient. Selection of substances to be patch tested in every individual case mainly depends on the patient’s history and the availability of corresponding patch test preparations.
In clinical routine, contact sensitisation is diagnosed according to the following pattern.
A patient with suspected contact sensitisation seeks medical help. The consulted der-matologist performs a patch test. Normally, a baseline series including about 25-30 of the most frequent contact sensitisers is tested in every patient. Additional patch test series are applied according to the patient’s history [Johansen et al. 2015, Lindberg and Matura 2011]. This means that the selection of allergens beyond the baseline se-ries depends on factors which are hard to appraise, namely the patient’s ability to de-scribe her or his exposure or suspected allergen sources, the physician’s knowledge of potential allergen sources and exposures and her or his ability to take a correspond-ing anamnesis adequately (that is, to ask the right questions). In cases of suspected occupational contact allergy, the situation may sometimes be more complicated than in non-occupational cases, because assessing potential allergen exposures requires special knowledge on both sides the patient and the physician.
Allergen preparations for patch testing are medicinal products (drugs), according to German legislation [Arzneimittelgesetz 2017]. Every patch test preparation has to be approved by the responsible authority, which is the Paul-Ehrlich-Institute (PEI), in Ger-many. Following the 14th amendment of the German Pharmaceutical Act in 2005, new patch test substances have to undergo a complex and costly approval procedure. This brought development of new patch preparations to a complete standstill [Mahler et al.
2016]. Therefore, one must be aware that the currently available and diagnostically used spectrum of contact allergens for patch testing does not necessarily reflect cur-rent allergen exposure in daily life or in the working environment. In this concern, we are now 12 years behind.
Currently, there is only one company offering PEI-approved patch test preparations in Germany, namely SmartPractice. Their portfolio covers the biggest part (about 90%) of patch test allergens which are recommended for patch testing in the patch test series of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe;
DKG). However, especially in the occupational field, relevant diagnostic gaps remain.
There is a second company offering patch test preparations, Chemotechnique, in Swe-den, which also delivers allergen preparations to Germany (at least those which are not available as PEI-approved test substances elsewhere). Although the DKG recom-mends patch testing with these preparations in the individual case if medically indi-cated, they are by far not used as commonly as the PEI-approved patch test prepara-tions.
Summarized, it can be stated that
− patch testing is the gold standard for diagnostics of contact sensitisation,
− nevertheless, false negative as well as false positive reactions may occur,
− by far not every (current) contact allergen is available as standardised patch test preparation,
− the testing physician’s allergological expertise and the patient’s ability to recall the circumstances having caused his or her dermatitis substantially affect diag-nostic success, particularly in the occupational context.