22_363_390* 05.11.2005 10:35 Uhr Seite 365 Chapter 22 Patch Testing 22 Jan E. Wahlberg, Magnus Lindberg Contents 22.1 Introduction . 366 22.5.5.3 The Patch (Item 11) . 380 22.1.1 The Purpose of Patch Testing . 366 22.5.5.4 Artifacts (Item 12) . 380 22.1.2 Standardization . 366 22.5.6 False-Negative Test Reactions . 380 22.1.3 Bioavailability . 366 22.5.6.1 Common Causes . 380 22.5.6.2 Compound Allergy (Item 6) . 381 22.2 Test Systems . 367 22.2.1 Original System (Allergen–Patch–Tape) . 367 22.6 Ethnic and Climatic Considerations . 381 22.2.1.1 Patches . 367 22.7 Effect of Medicaments and Irradiation 22.2.1.2 Allergens . 367 on Patch Tests . 381 22.2.1.3 Vehicles . 367 22.7.1 Corticosteroids . 381 22.2.1.4 Concentrations . 368 22.7.2 Antihistamines . 381 22.2.1.5 Tapes . 368 22.7.3 Immunomodulators . 382 22.2.1.6 Application of Test Preparations 22.7.4 Irradiation . 382 to the Patches . 368 22.7.5 Seasonal Variations . 382 22.2.1.7 Some Practical Suggestions . 368 22.2.2 Ready-to-use Systems . 370 22.8 Complications . 382 22.8.1 Patch Test Sensitization (Item 1) . 382 22.3 Allergens . 371 22.8.2 Subjective Complaints (Item 4) . 382 22.3.1 Numbers . 371 22.8.3 Penicillin (Item 9) . 382 22.3.2 Suppliers . 371 22.3.3 Screening Series . 371 22.9 Open Tests . 383 22.3.4 Variations Concerning Concentration 22.9.1 Open Test . 383 and Vehicle . 371 22.9.2 Semi-open Test . 383 22.4 Standard Series . 372 22.10 Use Tests . 383 22.4.1 Deciding What to Include 22.10.1 Purpose . 383 in the Standard Series . 372 22.10.2 Repeated Open Application Test . 383 22.5 Reading and Evaluation of Patch Tests . 373 22.11 Noninvasive Techniques . 384 22.5.1 Reading – When and How . 374 22.12 Quality Control of Test Materials . 384 22.5.1.1 Exposure Time . 374 22.12.1 Identification and Purity . 384 22.5.1.2 Reading When? . 374 22.12.2 Test Preparations Under the Microscope . 384 22.5.1.3 Compromise . 374 22.12.3 Fresh Samples . 384 22.5.2 Recording of Test Reactions . 375 22.12.4 Adhesive Tapes . 385 22.5.3 Interpretation of Reactions at Test Sites . 375 22.5.3.1 Discrimination Between Allergic 22.13 Tests with Unknown Substances . 385 and Irritant Reactions . 376 22.13.1 Warning! . 385 22.5.3.2 Ring-Shaped Test Reactions . 378 22.13.2 Strategy . 385 22.5.3.3 Ultrastructure . 378 22.13.3 Test or Not? . 385 22.5.3.4 Doubtful and One Plus Reactions . 378 22.13.4 Solid Products and Extracts . 385 22.5.3.5 Cross-Sensitivity . 378 22.13.5 Cosmetics and Similar Products . 386 22.5.4 Relevance . 378 22.14 The Future . 386 22.5.5 False-Positive Test Reactions . 379 22.5.5.1 The Compromise (Item 1) . 379 References . 386 22.5.5.2 Excited-Skin Syndrome – “Angry Back” (Items 7 and 8) . 379 22_363_390* 05.11.2005 10:35 Uhr Seite 366 366 Jan E.Wahlberg, Magnus Lindberg 22.1 Introduction – Suspected contact allergy to topical medicaments and their vehicles 22.1.1 The Purpose of Patch Testing – “Predictive testing” of alternative products such as gloves, skin care Patch testing is a well-established method of diag- products, medicaments nosing contact allergy– a delayed type of hypersensi- tivity (type IV reaction). Patients with a history and clinical picture of contact dermatitis are re-exposed to the suspected allergens under controlled condi- 22.1.2 Standardization tions to verify the diagnosis. Also testing patients with hand (dyshidrotic, hyperkeratotic), arm, face or leg eczema (stasis dermatitis), testing of other types The first patch tests according to present principles of eczema (atopic, seborrheic dermatitis, nummular were carried out in 1895 [8], but were preceded by eczema), including patients with chronic psoriasis, some preliminary experiments [9] (see Chap.1).Dur- vulval disorders or drug reactions (Chap. 24), is ing the last few decades much effort has been put into sometimes indicated, especially when they are recal- standardization of allergens, vehicles, concentra- citrant to prescribed treatment and the dermatolo- tions, patch test materials, tapes, and the scoring of gist suspects contact allergy to prescribed topical test reactions, and the method today is considered medicaments and their vehicles. accurate and reliable. A series of papers has demon- Apart from its use to confirm a suspected allergic strated good reproducibility of patch test results contact dermatitis, the patch test procedure can also [10–18]. Standardization has facilitated comparisons be used before recommending alternative medica- of contact allergy frequency in and between clinics, ments, skin care products, cosmetics, gloves, etc. in a geographical areas, and areas with various degrees of particular patient. If the patient does not react to the industrialization but some questions still remain, es- alternatives tested, it is unlikely that he or she will pecially concerning the reading and scoring of test react to the products in ordinary use. reactions. This will be discussed in detail below. Early classic publications on patch testing are re- viewed in Chap. 1. More recent, often quoted, guide- 22.1.3 Bioavailability lines are presented by Malten et al.[1],Fregert [2] and Bandmann and Wohn [3]. Several studies (e.g. [4–6]) have shown that de- To obtain optimal bioavailability of a hapten one can tailed patch testing is beneficial for patients and im- influence the following five variables: prove their quality of life (QoL). However, it has also been claimed that random patch testing with a stan- í Intrinsic penetration capacity dard series should be discouraged due to low pretest í Concentration, dose probability [7]. í Vehicle When performing patch testing it has to be re- í Occlusivity of patch test system and tape membered that the patch test is a biological provoca- í Exposure time tion test and as such the outcome is dependent on multiple factors including the test system and test material, the biological/functional status of the test- Since it is desirable to remove all test strips at the ed person, and the responsible dermatologist. Most same time – usually at day 2 (48 h) – four factors re- of theses aspects will be discussed in this chapter. main and can be varied and optimized by the manu- facturers of patch test materials and allergen prepar- ations and by the dermatologist responsible for the Core Message testing. The penetration capacity can depend upon the salts used; for example, there is a big difference í Indications for patch testing: between the penetration of nickel achieved by nickel – Cases of contact dermatitis sulfate and nickel chloride [19]. The higher penetra- – Other types of eczema and dermatoses, tion of nickel from the chloride is probably explained where a superimposed contact allergy by the partition skin/vehicle of the salts, when ap- is suspected, particularly if recurrent plied in the same vehicle in equimolar concentration 22 and nonresponsive to treatment and under occlusion. 22_363_390* 05.11.2005 10:35 Uhr Seite 367 Patch Testing Chapter 22 367 22.2 Test Systems patch testing is recommended repeatedly to request the manufacturers to provide results of chemical analyses. One can distinguish two test systems: the original The test preparations are presented in plastic sy- one, where the allergens, patches, and tapes are sup- ringes or bottles of inert material to prevent degrada- plied separately, and the modern ready-to-use sys- tion or other chemical changes due to air, humidity, tem, where only a covering material has to be re- and light. The suppliers’ recommendations on stor- moved before the test is applied. age must be followed in order to minimize these risks. It is suspected that several of the contact aller- gies reported earlier were due to impurities or degra- 22.2.1 Original System dation products [24]. It has not been possible to con- (Allergen–Patch–Tape) firm the allergenic potential of some claimed “aller- gens.” 22.2.1.1 Patches Some of the patch test units available are depicted in 22.2.1.3 Vehicles Fig. 1. In Finn chamber (Epitest, Finland) the test ar- ea is circular and in van der Bend (van der Bend, Each allergen almost certainly has its own optimal Netherlands) and IQ chambers (Chemotechnique vehicle; it is improbable that just one vehicle (e.g., Diagnostic, Sweden) they are square. The latter is petrolatum) could be optimal for all allergens. White claimed to facilitate distinguishing allergic from irri- petrolatum is the most widely used vehicle, but its tant reactions, since an irritant reaction tends to look general reliability can be questioned. It gives good square, while an allergic reaction tends to look round occlusion, keeps the allergens stable and is inexpen- [1]. Based on a comparative study with ordinary sive. On the other hand, it can retain the allergen (see (8 mm) and large (12 mm) Finn chambers, it was Sect. 22.5.6.1, Common Causes), irritate the skin, and found that the larger chambers may be useful for de- even give rise to allergic skin reactions [25]. Liquid tection of weak sensitization to some contact aller- vehicles such as water and solvents (acetone, ethanol, gens [20–22]. However, the larger chambers are usu- methyl ethyl ketone) are recommended since they fa- ally recommended for experimental studies when cilitate penetration of the skin, but they also have testing for irritancy. some drawbacks.Solvents may evaporate,which does not favor exact dosing, and most test solutions must be freshly prepared.