CME Article Submitted: 18.3.2013 Accepted: 29.4.2013 Conflicts of interest None.

DOI: 10.1111/ddg.12143

Allergic contact dermatitis

Detlef Becker

Summary

Department of Dermatology, University Medicine Mainz, Germany

Allergic contact dermatitis is a frequent inflammatory skin disease. The suspected ­diagnosis is based on clinical symptoms, a plausible contact to allergens and a suitable history of dermatitis. Differential diagnoses should be considered only after careful exclusion of any causal contact sensitization. Hence, careful diagnosis by patch ­testing is of great importance. Modifications of the standardized test procedure are the strip patch test and the repeated open application test. The interpretation of the SLS ­(sodium lauryl sulfate) patch test as well as testing with the patients’ own products and working materials are potential sources of error. Accurate patch test reading is affected in particular by the experience and individual factors of the examiner. Therefore, a high degree of standardization and continuous quality control is necessary and may be supported by use of an online patch test reading course made available by the German Contact Dermatitis Research Group. A critical relevance assessment of allergic patch test reactions helps to avoid relapses and the consideration of ­differential diagnoses. Any allergic test reaction should be documented in an allergy ID card including the INCI name, if appropriate. The diagnostics of allergic contact dermatitis is endangered by a seriously reduced financing of patch testing by the German statutory health insurances. Restrictive regulations by the German Drug Law block the approval of new contact allergens for routine patch testing. Beside the consistent avoidance of allergen contact, temporary use of systemic and topical corticosteroids is the therapy of first choice.

Section Editor Prof. Dr. Jan C. Simon, Leipzig

Introduction The inflammatory reaction of the skin based on a contact sensitization is a typical cause of dermatitis in clinical dermatology. Due to the long tradition and deep embedding of this disease in our specialty, extensive basic knowledge exists that can be gained from textbooks [1, 2] as well as from guidelines on contact dermatitis [3], hand dermatitis [4] and patch testing [5]. Even though the fundamentals appear so clear, test substances for patch testing are easily available and the performance is technically uncomplicated, there are numerous sources of error in daily practice. In recent years interventions by lawmakers and shifts of emphasis in reimbursement have affected and even endangered the diagnostics of allergic contact dermatitis. This directly impacts current and future practical care of patients with contact allergies. This article cannot and does not intend to replace a textbook or guideline recommendations. Rather it is designed to help clinically active dermatologists to follow current developments in clinical aspects, diagnostics and therapy and to show ways to deepen this special knowledge. A further purpose of this article is to transmit experience on frequent interrelations and to illustrate typical shortcomings in quality in the daily practice that can only be eliminated by critically questioning of your own approach and routines.

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CME Article  Allergic contact dermatitis

Pathophysiology Allergic contact dermatitis belongs to the best-researched forms of allergy, as it is employed in many experimental systems as a model of a typical immune reaction of the delayed type. In recent times especially knowledge on the genetic fundamentals of the early processes in the sensitization phase, particularly the activation of the innate immune system, and the regulation of both sensitization as well as initiation have been gained. It has been reviewed in detail [6], but the extensive scientific background is not yet well-reflected in clinical practice.

Epidemiological and clinical significance Epidemiological studies currently provide no evidence for a significant change in prevalence and incidence of allergic contact dermatitis. Regressions in the diagnostic depth of contact allergy favor recurrences of the disease. Contact sensitizations towards not sufficiently avoidable occupational substances are next to variants of atopic dermatitis the most frequent causes of occupational disability.

Contact sensitizations represent a common, even if not the most frequent, cause of eczema in all age groups and social strata. Epidemiological studies currently provide no evidence for a significant change in prevalence and incidence of allergic contact dermatitis. Regulations of lawmakers and even more of the EU as well as trends in the use of certain substances actually do lead to shifts in the significance of individual allergens, but not to a perceptible in- or decrease of the disease itself. Other factors have a much greater effect on the frequency of the disease in daily practice. As will be shown later in detail, the basic conditions for diagnostics have in part worsened dramatically. As only identification of the causal allergen and its avoidance can prevent recurrences, it must be feared that the frequency in duration of eczema episodes will increase. Contact sensitizations towards not sufficiently avoidable occupational substances are next to variants of atopic dermatitis the most frequent causes of occupational disability with the corresponding personal consequences for those affected and high economic ­follow-up costs.

Clinical findings and differential diagnoses Irritant dermatitis and the various forms of atopic dermatitis are the most important differential diagnoses of allergic contact dermatitis.

The possible causes of allergic contact dermatitis are as diverse as the exposures, but can be usually be identified by utilizing the available test allergens selected on the basis of history.

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Irritant dermatitis and the various forms of atopic dermatitis are the most important differential diagnoses of allergic contact dermatitis. Even if contact dermatitis is frequently more inflammatory in comparison to the differential diagnoses ­(Figure 1), this in an insecure parameter. Only the total picture of clinical findings, comprehensible allergen exposure of the affected region and the clinical course in the history raise suspicion that can be confirmed or excluded by patch testing (Figure 2). Hardly any region is that frequently affected by dermatitis as the hands. The possible causes of allergic contact dermatitis are as diverse as the exposures, but can be usually be identified by utilizing the available test allergens selected on the basis of history. It is helpful to establish that in reality only the hands are affected. Thus, many substances can be excluded that contact the hands during personal hygiene (e.g. perfume, deodorant, shampoo, hair colors, decorative cosmetics, moist toilet paper, skin care creams, topical medications) but are also applied elsewhere. The clear dependence on occupational activities also provides important indications. Only by careful exclusion of possible sensitizations or lack of control of the dermatitis despite avoidance of possible allergens reactive in the patch test can the initial suspected diagnosis be excluded (Figure 2). Patients with chronic stasis dermatitis display an increased risk of sensitization to ointment bases and active ingredients repeatedly applied within the context

© The Author | Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1107

CME Article  Allergic contact dermatitis

Figure 1  Severe allergic contact dermatitis of the scalp following hair coloring with a customary hair dye due to contact hypersensitivity to p-phenylenediamine.

Figure 2  Flow chart for the diagnosis and therapy of allergic contact dermatitis. Several critical decisions have to be made and should lead to a successful and lasting cure of the disease or a differential diagnosis. The complete diagnostic procedure makes sense only if there is sufficient evidence for this suspected ­d iagnosis.

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CME Article  Allergic contact dermatitis

Due to the special environmental factors of stasis dermatitis, sensitizations can develop towards weak allergens that are otherwise only rarely observed.

True allergic reactions of the oral mucosa towards dental materials are very rare.

of therapy of the dermatitis and chronic ulcers. Due to the special environmental factors of stasis dermatitis, sensitizations can develop towards weak allergens that are otherwise only rarely observed. For rapid orientation, if an acute contact reaction is present, the employed therapeutic agents can be tested on the back under the conditions of the patch test as own substances. In the event of positive reactions, comprehensive diagnostics are needed to manage further therapy of the basic disease. Further typical locations are foot dermatitis, whose cause by leather allergens is more often suspected than is finally confirmed. Atopic dermatitis of the dorsa of the feet and vesicular plantar dermatitis are the most important differential diagnoses. Also in the face and particularly on the eyelids atopic dermatitis tops the charts. In dermatitis of the anogenital region environmental factors such as microbial colonization, irritant contacts to excrements and particularly occlusion and mechanical friction under tight clothing as well as maceration through sweating in the face of high temperatures must be considered. Similar conditions are found in the axillary vaults and body folds in morbid obesity. In contrast, the numbers of potential contact allergens in these special locations are limited and easily diagnosed. Besides clinically manifest or a history of eczema reactions, many patients in the office situation complain of in part diffuse symptoms in the mouth that they attribute to suspected allergy towards dentures or other dental materials. Only a very small share actually do have allergic contact stomatitis, due to incompletely hardened dentures in sensitizations towards methacrylate or chronic lichenoid ­reactions at the sites of contact to dental metals.

Patch testing Performance

The sensitivity and specificity of the patch test are in part critically impacted by comorbidities and medications, the skin status in the test area and deviations from the defined test conditions.

As the gold standard the patch test has a prominent place in the clinical management of allergic contact dermatitis. In contrast to in vitro diagnostics of immediate-type sensitizations, where only the existence of specific IgE independent of the functional status of the immune system is detected, the patch test is an in vivo test. Its sensitivity and specificity are in part critically impacted by comorbidities and medications, the skin status in the test area and deviations from the defined test conditions. Recommendations of the medical societies on details of performance exist [5], that are currently being expanded to an S3-guideline.

Important contact allergens The allergens of the standard series are of particular importance and are ­supplemented by special test series on the basis of history.

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Due to the frequency of reactions in the patch test, the allergens of the standard series (Table 1) are of particular importance. In addition, there are special test series, whose selection is oriented to a certain, usually occupational exposure (hairdressing, construction industry, dental technicians, etc.) or an exposure to certain products (rubber, fragrances, topical medications, etc.). Due to the high number of available allergens and their possible combinations in different situations, even an overview on this subject will remain incomplete within the context of this article. Various sources of information give advice on setting up a diagnostic spectrum sensibly. The test allergens in their entirety and their arrangement in series are found at the manufacturers of the substances (www.hautstadt.de) (www.hal-allergie.de). The respective recommendations of the German Contact

© The Author | Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1107

CME Article  Allergic contact dermatitis

Table 1  Standard patch test series recommended by the German Contact ­Dermatitis Research Group (DKG). Name of substance

Vehicle

Concentration

Potassium dichromate

PET

0.5 %

Thiuram mix

PET

1%

Cobalt (II) chloride, 6*H2O

PET

1%

Balsam of Peru

PET

25 %

Colophony

PET

20 %

N-isopropyl-N’-phenyl paraphenylenediamine

PET

0.1 %

Wool alcohols

PET

30 %

Mercapto mix without MBT (only CBS, MBTS, MOR)

PET

1%

Epoxy resin

PET

1%

Nickel (II) sulfate, 6*H2O

PET

5%

Paratertiarybutyl phenol formaldehyde resin

PET

1%

Formaldehyde

AQU

1%

Fragrance mix

PET

8%

Turpentine

PET

10 %

(Chloro)-methylisothiazolinone (MCI/MI)

AQU

100 ppm

Paraben mix

PET

16 %

Cetyl stearyl alcohol

PET

20 %

Zinc bis(diethyldithiocarbamate)

PET

1%

Dibromodicyanobutane (methyldibromo glutaronitrile)

PET

0.2 %

Propolis

PET

10 %

Bufexamac

PET

5%

Compositae mix II

PET

5%

Mercaptobenzothiazole

PET

2%

Hydroxymethylpentylcyclohexenecarboxaldehyde (Lyral)

PET

5%

Bronopol (2-bromo-2-nitropropane-1,3-diol)

PET

0.5 %

Fragrance mix II

14 %

Sodium lauryl sulfate

AQU

0.25 %

Ylang-ylang (I + II) oil

PET

10 %

Sandlewood oil

PET

10 %

Jasmine absolute

PET

5%

Dermatitis Research Group (DKG) can be found on the website (http://dkg.ivdk. org/). Monographs have been developed with test recommendations and further­ valuable information on allergen occurrence for various occupational fields. These are available for the test practice in summarized form free of charge in the internet

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CME Article  Allergic contact dermatitis

Table 2  Reading criteria for patch test reactions used by the DKG. Symbol

Morphology

Evaluation

–

No reaction

Negative

?

Only erythema, no infiltrate

Questionable

f

Few follicular papules

Questionable

+

Erythema, infiltrate, discrete papules

Single positive reaction

++

Erythema, infiltrate, papules, vesicles

Double positive reaction

+++

Erythema, infiltrate, confluent vesicles

Triple positive reaction

Ir

Soap effect, blister, necrosis

Irritant

(www.hautstadt.de/hs/pages/intern/infozentrum/berufstestreihen/berufstestreihen. php). A recommendation of the DKG has been published on the special aspects of testing children from the age of 6 years [7].

Reading the test The reading of a reaction ideally is done only according to morphological criteria and at first disregards the question of the clinical relevance. Unfortunately, when at least a “+”-reaction is ­observed, it is often automatically assumed that a contact sensitization exists and sometimes it is concluded without further critical evaluation that this is also relevant for the disease process.

From large data bases by means of calculations problem allergens can be identified, whose relevance must be evaluated particularly critically.

612

Reading criteria for patch test reactions have been defined (Table 2) and are valid unchanged. The reading of a reaction ideally is done only according to morphological criteria and at first disregards the question of the clinical relevance. Unfortunately, when at least a “+”-reaction is observed, it is often automatically assumed that a contact sensitization exists and sometimes it is concluded without further critical evaluation that this is also relevant for the disease process. It should, however, not be forgotten that an extensive, more or less infiltrated erythema (Figure 3a) can actually correspond to a weak allergic reaction, that can just as well represent a dermatitis triggered by irritation. The decrescendo course postulated for irritant reactions is in fact a frequent occurrence, by which many irritant ­reactions at the first reading fade again until the reading at 72 hours. If the reaction remains unchanged, however, this is still no proof of a contact allergic reaction, but is still compatible with a false-positive, irritant reaction. Here the limits of a method based on purely morphologic criteria are reached. With increasing ­reaction intensity (Figure 3b) the probability of a plausible allergic genesis of the reaction rises exponentially. When a large number of test data are registered in data banks and analyzed, as is done in the Information Network of Departments of Dermatology (IVDK), evaluation parameters from the relationship between irritant, doubtful and weak test reactions as well as probable allergic reactions, such as the reaction index and the positivity ratio can be calculated [8], that express in which frequency the test substance elicits irritant or doubtful reactions. It is thus possible to describe problem allergens [8] that are characterized in the clinical routine by unclear, u ­ sually only doubtful or “+”-reactions. Frequent problem allergens are listed in Table 3; they demand particular care in the evaluation of the relevance. Reading of a patch test is learned under supervision during allergologic t raining. After this, however, the possibilities to compare one’s own reading ­ practice with a standard are lacking. Besides the classical reaction patterns of ­allergic or irritant reactions we must always again and again categorize and evaluate morphological peculiarities (Figure 3c, d). To promote continuing education and quality assurance in the reading of the patch test, the German Contact ­Dermatitis Research Group (DKG) offers on its website (http://dkg.ivdk.org/)

© The Author | Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1107

CME Article  Allergic contact dermatitis

Figure 3:  Examples of irritant, doubtful and positive patch test reactions. Weak positive reaction with erythema and palpable infiltrate to fragrance mix (a). Strong positive reaction to colophony (b). Follicular and hemorrhagic erythema without palpable infiltrate rated as irritant to cobalt chloride (c). Doubtful reaction with follicular papules to MCI/MI (d). Table 3  “Problem allergens” frequently eliciting doubtful, weak and false positive test reactions [8]. Substance

Typical use

Benzalkonium chloride

Disinfectant and preservative

Benzylhemiformal

Technical preservative

Methylene-bis(methyloxazolidine) Technical preservative Glutardialdehyde

Surface and device disinfectant

Iodopropynyl butylcarbamate

Preservative

Amerchol L-101

Emulsifier in topical products

Cocamidopropyl betaine

Detergent

Octyl gallate

Antioxidant

Sorbitan sesquioleate

Emulsifier in topical products and fragrance mix

Triethanolamine (TEA)

Emulsifier and technical use

Benzoyl peroxide

Acne medication, polymerization of synthetics

Chlorhexidine digluconate

Skin disinfectant, preservative

Phenylmercuric acetate

Preservative in topical ophthalmological ­products (only isolated)

Povidone iodine

Skin disinfectant

1,3-diphenylguanidine

Rubber chemical

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CME Article  Allergic contact dermatitis

An online reading training of the German Contact Dermatitis Research Group (DKG) is available for quality ­assurance and further education.

r­ eading training with which any physician working in the field of allergology can test her/his own reading habits online for correspondence to and deviations from the standard. This reading tool is also suitable for didactic purposes within the context of training.

Irritant control

An abnormal irritant control ­ nderscores the need for careful u ­interpretation of other weak positive erythema reactions, that can hide ­false-positive reactions. Contact sensitizations towards ­sodium lauryl sulfate do not occur; the ­substance is a pure irritant.

Since inclusion of an irritant control with 0.25 % sodium lauryl sulfate in the standard series, such reactions are also interpreted as an indicator for increased skin sensitivity in general. This statement, however, is not supported by the underlying study data [9] that in the event of a reaction to this concentration of sodium lauryl sulfate only prove an increased irritability at the time point of the test. This fact underscores the need for careful interpretation of other weak erythema reactions that can hide false-positive reactions. Totally wrong is the conclusion that a contact sensitization towards sodium lauryl sulfate is present. The attempt of avoidance presents great problems due to the wide distribution in detergents of all kinds and is not sensible, as the substance is a pure irritant and contact sensitizations do not occur. Documentation of the reaction in an allergy ID card must be avoided, as this can be misunderstood by patients and be misinterpreted as a recommendation to avoid the substance.

Modifications of the patch test and further diagnostics In the strip patch test a disturbance of the barrier function is simulated in order to test allergens with poor ­penetration capabilities.

A ROAT can be very helpful to evaluate mixtures, such as cosmetics and ­contact substances at the workplace, for ­e xisting sensitizations towards one of the ingredients. In vitro diagnostics with the lymphocyte transformation test (LTT) hardly has a place in the clinical management.

Histologically, the various causes of an eczema cannot be differentiated ­sufficiently.

For the differentiation from a fungal ­infection and an atopic dermatitis appropriate diagnostics may be necessary.

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The intact stratum corneum represents a distinct barrier for some contact ­allergens, so that the elicitation of a positive test reaction is made more difficult ­despite an existing sensitization. On previously damaged skin, in contrast, allergen ­contact leads to a reaction. This problem is addressed by the strip patch test that has ­recently been standardized and evaluated [10] and is of value in targeted use. When the relevance of a test reaction for the use of an end-product is unclear, a repeated open application test (ROAT) can be performed [11]. For this purpose there is controlled twice daily open use on a defined area of the forearm for up to two weeks. A ROAT can also be very helpful to evaluate mixtures such as cosmetics and contact substances at the workplace, for existing sensitization towards one of the ingredients, when this question cannot be clarified due to lack of suitable test allergens or information. This method demands skin tolerability of the product and can only be justified when concentration and application time in the ROAT correspond to the real exposure to the diseased skin. In vitro diagnostics with the lymphocyte transformation test (LTT) hardly has a place in the clinical management. Performance is costly and time-consuming and usually can be offered only by the larger allergological centers. Finally, the LTT can only confirm the result of the patch test and in only very special cases, such as the contraindication for patch testing or as a building block in the diagnostics of endoprosthesis intolerance, independently deliver additional information. This method often located on the border to complementary medicine is not validated for the study of sensitizations in denture problems and is disapproved by evidence-based medicine in this context. When doubts about the diagnosis of eczema exist, a biopsy may be requested. This makes no sense for the differentiation between the various causes of eczema, as still even with the most modern molecular methods, no secure differentiation can be made between an allergic and non-allergic reaction. To exclude a fungal infection as a differential diagnosis or secondary problem, the appropriate diagnostics may be needed. Due to the increasing significance of atopy as a cause or at least partial cause of dermatitis, basic diagnostics to uncover an atopic diathesis is recommended. Even in face of obvious elicitation of the

© The Author | Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1107

CME Article  Allergic contact dermatitis

dermatitis by a contact allergen, an atopic skin diathesis can exist in combination. This can lead to unjustified doubts on the cause of the contact allergic disease share or allergen avoidance, respectively, when an in parallel provoked atopic ­dermatitis process is superimposed on the course of healing.

Sensible extent of patch testing The exclusive testing of the standard ­series is not sufficient in many cases.

Occupationally-related diagnostics, when an occupational contact dermatitis is suspected, as well as the testing of occupational contact substances is reimbursed much more favorably within the context of the medical fee schedule of the statutory occupational accident insurance (UV-GOÄ) since 2010.

The present downward trend in the extent and availability of patch testing delays the diagnosis and prolongs the treatment-requiring duration of an ­allergic contact dermatitis.

In increasing degree in some dermatology offices only the standard series or even only a fragment of it is routinely tested. With the exception of some frequent ­sensitizations, such as towards nickel, fragrances and colophony, this is not sufficient for well-founded diagnostics. Particularly occupational contact sensitizations thus remain undetected or are referred to dermatologic centers. This often results in a distinct delay in the diagnosis and in rural regions long distances. The cause is the reform of the reimbursement of the patch test in the currently valid Uniform Value Scale (EBM). The patch test is no longer reimbursed according to its extent, but only represents a share of the standard service volume. The increased effort of diagnostics with special test series is no longer reflected leading a not inconsiderable number of offices to limit themselves to the standard series. Occupationally-related diagnostics, when an occupational contact dermatitis is suspected, as well as the testing of occupational contact substances is reimbursed much more favorably within the context of the medical fee schedule of the statutory occupational accident insurance (UV-GOÄ) since 2010. This was done with the intent to make the supply of occupational test series independent of the statutory health insurance care. The aim is preservation of the up to now natural extensive diagnostics within the context of the dermatologist’s procedure. All relevant ­innovations can be found in the brochure “Honorare in der Berufsdermatologie” (“Reimbursement in Occupational Dermatology”) as a download on the website of the German Social Accident Insurance Institution for the Health and Welfare Services (BGW) (www.bgw-online.de). The present downward trend in the extent and availability of patch testing delays the diagnosis and prolongs the treatment-requiring duration of an allergic contact dermatitis. In addition, the danger exists, that special allergens, that can be of great significance in the individual case, but are hardly tested on a large ­scale, will be removed from the market by the manufacturers of the test allergens on economic grounds. They will then also not be available in specialized centers with a direct impact on the quality of medical care.

Impediments to the further development of patch testing Allergologic test substances are drugs and therefore are regulated with respect to manufacturing and licensing by the German Drug Law (AMG).

Due to the stipulations of the AMG, since 2008 no new contact allergens have been licensed for testing.

Allergologic test substances are drugs and therefore are regulated with respect to manufacturing and licensing by the German Drug Law (AMG). This demands also for new contact allergens a costly and time-consuming licensing process with the corresponding studies. It is well-known that the associated costs are enormous and one of the grounds for the high prices of newly licensed medication. This type of financing is, however, not realistic for test substances, so that the manufacturers neither actively perform nor sufficiently promote such licensing studies [12]. Since the expiration of interim arrangements in the fall of 2008, it has therefore come to a complete stop in the licensing of new test allergens. As technological further developments also produce new contact allergens, the discrepancy between exposure and the available allergens for diagnostics is continually increasing. Therefore, particularly for occupationally induced diseases, the possibility must be considered, that the decisive cause for a contact dermatitis is not detected with the available

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CME Article  Allergic contact dermatitis

commercial test allergens. Therefore, testing with the patients’ own substances is of increasing significance.

Testing of patients’ own substances The testing of patients’ own substances will become more important in order to close gaps in the diagnostic spectrum.

Diagnostics with patients’ own ­substances requires consideration of additional quality criteria.

Since the 15th reform of the AMG t­ esting of patients’ own substances requires reporting to the responsible state authority.

Due to the blockade of the further development and actualization of commercially available test substances, situations are on the rise, where the suspicion for contact sensitization can only be clarified by the testing of patients’ own substances from the private and occupational surroundings. As far as it is possible to avoid false-positive reactions to the often complicated substance mixtures or at least to recognize them, the question then still remains, which individual allergen is responsible for the reaction, so that targeted avoidance is possible. Surely, the detection of an allergic reaction to a suspected agent is better than no diagnostics at all. The testing of patients’ own substances cannot, however, replace well-founded diagnostics with defined individual substances. Diagnostics with patients’ own substances requires consideration of additional quality criteria. Practical advice on the proper selection of suitable substance samples and their dilution including the selection of the dilution medium are found on the website of a large test allergen manufacturer (www.hautstadt.de) in the login area for physicians. The recommendations were drawn up with the cooperation of the experts of the DKG and IVDK. Textbooks provide detailed information on testing of special substances and substance mixtures [13]. The Working Group on Occupational and Environmental Dermatology (ABD) and the DKG have developed a checklist for the process of testing workplace substances (Table 4). Since the 15th reform of the AMG testing of patients’ own substances requires reporting to the responsible state authority, in which it must be stated that test preparations and thus drugs in the sense of the AMG for testing on individual patients are being manufactured. Further important details on reporting are available on the website of the DKG (http://dkg.ivdk.org/). Through a substantial increase in the fee for patch testing of workplace substances within the context of the UV-GOÄ since 2010 the increased efforts are reimbursed. Thus, quality loss due to stagnation of the further development of the test spectrum will be prevented at least in the occupational dermatology sector. Prerequisite for this is the responsible utilization of this option through serious diagnostics oriented on the literature and following a concrete suspicion.

Evaluation of relevance of positive test reactions As the test result presents the sum of all sensitizations acquired in the past, even strong reactions must always be critically analyzed for their actual relevance for the current disease.

Even reactions whose developments are puzzling should be brought to the attention of the patient. This succeeds by handing out an allergy ID card in which the listing of the allergens with the INCI terminology mandated for the declaration of ingredients is documented.

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As the test result presents the sum of all sensitizations acquired in the past, even strong reactions must always be critically analyzed for their actual relevance for the current disease. Premature conclusions delay the management of the disease, because when another allergen is the cause, targeted avoidance fails. Should no contact allergic disease be present, but a dermatitis provoked by irritation or constitutional factors, important steps in secondary prevention are not taken. Every reaction clearly identified as allergic is ideally discussed with the patient in order to determine past relevance and thus avoid future dermatitis. Even reactions whose developments are puzzling should be brought to the attention of the patient. This succeeds by handing out an allergy ID card in which the listing of the allergens with the INCI terminology mandated for the declaration of ingredients is documented. The common substance names sometimes deviate considerably from this terminology (Table 5) and thus do not allow for consistent allergen avoidance. Manufacturers of the test allergens provide information on the occurrence of each

© The Author | Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1107

CME Article  Allergic contact dermatitis

Table 4  Checklist for patch testing of workplace materials. √  W  hat does the occupational product consist of?

[Security data sheet does not content all information; inquiry to manufacturer]

√  C  an the occupational product be patch tested at all?

[Specialist literature]

√  Which test concentration is appropriate?

[Specialist literature]

√  Which test vehicle is appropriate?

[Specialist literature]

√  Was the pH value of the product controlled? √  W  hich individual components of the product come into question as allergens?

[Specialist literature]

√  H  ow do I obtain the individual components of the product?

[Inquiry to manufacturer]

√  Which test concentrations are appropriate?

[Specialist literature]

√  Which test vehicle is appropriate?

[Specialist literature]

√  D  ocumentation of test results (including ­vehicle, test concentration, etc.) and feedback of results to manufacturer

Table 5  Relevant differences in the designation of contact allergens from the ­standard series in German versus the mandatory declaration by INCI. German term

INCI name

Perubalsam

Myroxylon pereirae

Wollwachsalkohole

Lanolin alcohol

Terpentin

Turpentine

Cetylstearyalkohol

Cetearyl alcohol

Dibromodicyanobutan

Methyldibromo glutaronitrile

Lyral

Hydroxyisohexyl 3-cyclohexene carboxaldehyde

Bronopol

2-bromo-2-nitropropane-1.3-diol

Ylang-ylang (I + II) Öl

Cananga odorata

Sandelholzöl

Santalum album

allergen. These are available for patients via open internet websites. As this information also lists rare occurrences or are even outdated, at least an informative discussion of the realistic contact possibilities is highly recommendable. Anxious characters otherwise tend to a severe and only sometimes sensible avoidance behavior that can result in drastic effects on the quality of life. In sensitizations with occupational relevance, expanded knowledge on the occurrence and the legal evaluation is offered by monographs with open access in the internet (http://abd.dermis.net/content/e03abd/e1046/e1047/index_ger.html).

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CME Article  Allergic contact dermatitis

Therapy Topical corticosteroids are still the mainstay in the therapy of allergic ­contact dermatitis. An important prerequisite for therapy success is allergen avoidance.

Short-term pulse therapy with systemic corticosteroids helps to bring extensive contact dermatitis rapidly under control.

Alitretinoin cannot be recommended for the therapy of allergic contact ­dermatitis.

An effective protocol for hyposensitization of allergic contact dermatitis is still not available.

Topical corticosteroids are still the mainstay in the therapy of allergic contact ­dermatitis. A broad spectrum of active ingredients of varying potency in diverse galvanic bases allows in the end for an adaptation to the severity and the location of the dermatitis. An important prerequisite for therapy success is, however, allergen avoidance. This demands in the beginning often an unselective avoidance of potential causes and ideally after successful diagnostics the consistent elimination of the contact substance from the private or occupational surroundings or at least effective protection measures. If it is not possible to avoid the causative allergen, a satisfactory and particularly long-lasting treatment success will fail. For this reason the indispensable corticosteroid-free treatment paths for chronic eczema with topical immunomodulators (tacrolimus, pimecrolimus), UV therapies and tar preparations can hardly be employed sensibly. Either it succeeds to eliminate the causes and thus achieve rapid healing with corticosteroids or a chronic course develops that can hardly be managed with therapy methods that are weaker in comparison to corticosteroids. A systemic immunosuppressive therapy is surely rarely indicated. Nonetheless, there are situations conceivable in which allergen avoidance is impossible or would lead to a dramatic loss in quality of life. Therapeutic benefits and side effects must be balanced in such individual cases. Uncomplicated and commonly recommended is, in contrast, the short-term pulse therapy with systemic corticosteroids. It helps to bring extensive and especially spreading contact dermatitis under rapid control and in consistent allergen avoidance will be required for only a short period of time. Alitretinoin has opened new possibilities in the past years for the therapy of ­severe, chronic hand dermatitis. The active agent has, however, not been explicitly tested for contact allergic dermatitis. Comprehensible experience on efficacy is lacking, even the impact of alitretinoin on the course of patch testing is open. Alitretinoin can therefore not be recommended for the therapy of allergic contact dermatitis. Despite the long tradition of clinical and basic scientific research in the field of contact allergy, the desire for an effective protocol for hyposensitization, as is available for some immediate-type sensitizations, has remained unfulfilled. With the exception of individual experimental approaches to date no validated and ­clinically utilizable procedure has been established. References 1 2 3 4

Correspondence to Priv.-Doz. Dr. Detlef Becker Department of Dermatology University Medicine Mainz Langenbeckstraße 1 55131 Mainz, Germany E-mail: detlef.becker@ unimedizin-mainz.de

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Johansen JD, Frosch PJ, Lepoittevin JP (eds). Contact Dermatitis, 5th edn., Berlin, Springer, 2011. Saloga J, Klimek L, Buhl R et al. (eds), Allergologie-Handbuch, 2nd edn., Schattauer, Stuttgart, 2011. Brasch J, Becker D, Aberer W et al. Kontaktekzem. Leitlinie der Deutschen ­Dermatologischen Gesellschaft. Allergo Journal 2007; 16: 176–85. Diepgen TL, Elsner P, Schliemann S et al. Guideline on the management of hand ­eczema ICD-10 Code: L20. L23. L24. L25. L30. J Dtsch Dermatol Ges 2009; 7(Suppl 3): S1–16. Schnuch A, Aberer W, Agathos M et al. Durchführung des Epikutantests mit ­Kontaktallergenen. J Dtsch Dermatol Ges 2008; 9: 770–5. Martin SF. Allergic contact dermatitis: xenoinflammation of the skin. Curr Opin ­Immunol 2012; 24: 1–10. Worm M, Aberer W, Agathos M et al. Patch testing in children – recommendations of the German Contact Dermatitis Research Group (DKG). J Dtsch Dermatol Ges 2007; 5: 107–9. Geier J, Weisshaar E, Lessmann H et al. Bewertung von Epikutantestreaktionen auf „Problemallergene“ mit vermehrt fraglichen oder schwach positiven Reaktionen. ­Dermatol Beruf Umwelt 2010; 58: 34–8.

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Löffler H, Becker D, Brasch J et al. Simultaneous sodium lauryl sulphate testing improves the diagnostic validity of allergic patch tests. Results from a prospective multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG). Br J Dermatol 2005; 152: 709–19. 10 Dickel H, Altmeyer P, Brasch J. „New“ techniques for more sensitive patch testing? J Dtsch Dermatol Ges 2011; 9: 889–96. 11 Hannuksela M, Salo H. The repeated open application test (ROAT). Contact Dermatitis 1986; 14: 221–7. 12 Becker D. Neue Kontaktallergene für die Epikutantestung: ein Auslaufmodell? ­Hautarzt 2009; 60: 22–5. 13 de Groot AC. Patch testing, acdegroot publishing, Wapserveen, 2008: 1–455.

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Fragen zur Zertifizierung durch die DDA Welche Aussage ist falsch? Kontaktallergien sind häufige ­Ursachen einer Berufsunfähigkeit. b) Die Inzidenz des allergischen ­Kontaktekzems ist relativ konstant. c) Eine unzureichende Diagnostik ­erschwert die Krankheitskontrolle. d) Das allergische Kontaktekzem ist die mit Abstand häufigste ­Ekzemerkrankung. e) Allergische Kontaktekzeme kommen in allen Altersgruppen vor. 1. a)

2. Welche Aussage ist falsch? a) Auf intertriginöse Bereiche wirkt eine große Zahl potenzieller ­Kontaktallergene ein. b) Allergische Kontaktekzeme sind oft stark entzündliche Hautreaktionen. c) Die Lokalisation gibt wichtige ­Hinweise auf die möglichen Ursachen. d) Kontaktsensibilisierungen sind ­häufige Komplikationen einer ­Stauungsdermatitis. e) Allergische Reaktionen der ­Mundschleimhaut gegen dentale Werkstoffe sind selten.

3. Welche Aussage ist richtig? a) Der Epikutantest ist ein überholtes Verfahren und wird zunehmend durch In-vitro-Methoden ersetzt. b) Die Testung weiterer Allergene ­ außerhalb der Standardreihe ist nur in begründeten Ausnahmefällen ­nötig. c) Testempfehlungen für spezielle ­Berufe sind wegen der Heterogenität der Arbeitsplätze nicht sinnvoll. d) Die Verwendung von Testblöcken ist zugunsten einer individuellen ­Zusammenstellung von ­Testallergenen abzulehnen. e) Für die Epikutantestung von Kindern gelten gesonderte Testempfehlungen.

4. Welche Aussage ist falsch a) Die Ablesung der Epikutantest-­ Reaktionen erfolgt nach rein ­morphologischen Kriterien.

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b) Eine wenigstens einfach positive Reaktion gilt als Beweis für eine ­Kontaktsensibilisierung. c) Ein konstanter Reaktionsverlauf ist mit einer irritativen, falsch positiven Testreaktion vereinbar. d) Aus den Verhältnisse zwischen irritativen, schwach positiven und fraglichen Testreaktionen lassen sich Bewertungsgrößen für die ­diagnostische Zuverlässigkeit eines Allergens berechnen. e) Ein fortlaufendes Training in der Bewertung von Epikutantestreaktionen verbessert die Qualität der Diagnostik.

5. Was verstehen Sie unter einem „Problemallergen“? a) eine Substanz, die nach dem Arzneimittelgesetz nicht routinemäßig getestet werden darf b) eine toxikologisch bedenkliche ­Testsubstanz c) eine Testsubstanz, die viele ­z weifelhafte, kritisch zu bewertende Reaktionen auslöst d) ein Kontaktallergen, das sehr s­ chwere und lang anhaltende ­Ekzeme auslöst e) eine Testsubstanz, die trotz b ­ ekannter Sensibilisierung häufig falsch negativ reagiert

6. Welche Aussage ist richtig? a) Natriumlaurylsulfat ist ein seltenes Kontaktallergen. b) Bei einer Reaktion gegen 0,25 % ­Natriumlaurylsulfat im Epikutantest profitieren Patienten von der ­Meidung des Stoffs im Alltag. c) Der Abrisstest simuliert das Einwirken von Testsubstanzen auf eine Haut mit gestörter Barrierefunktion. d) Beim repetitiven offenen Anwendungstest wird eine Testsubstanz offen auf das vorerkrankte Hautareal aufgetragen. e) Der repetitive offene Anwendungstest ist nur für definierte Einzelallergene geeignet.

© The Author | Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1107

7. Welche Aussage ist falsch? a) Eine mykologische Untersuchung kann zur Differenzierung der ­Ursachen sinnvoll sein. b) Der Lymphozyten-TransformationsTest ist für die klinische Routinediagnostik nicht geeignet. c) Bei Kontraindikationen für den Epikutantest kann der LymphozytenTransformations-Test eingesetzt werden. d) Mischbilder aus einem atopischen Ekzem und einem allergischen ­Kontaktekzem kommen vor. e) In diagnostisch schwierigen Fällen kann histologisch zwischen einer kontaktallergischen und nicht-­ allergischen Ursache des Ekzem ­differenziert werden.

8. Welche Aussage ist richtig? a) Die Testung berufsbezogener ­Kontaktallergene im Hautarztverfahren wird seit 2010 besser vergütet. b) Der Umfang der Epikutantestung hat in der kassenärztlichen Versorgung in den letzten Jahren erheblich zugenommen. c) Kontaktallergene stehen als ­Testsubstanzen außerhalb des ­Arzneimittelgesetzes. d) Studien zur Zulassung ­neuer ­Kontaktallergene für die ­Routinediagnostik werden von Bundesbehörden mit Fördermitteln unterstützt. e) Die Testung komplexer Eigensubstanzen kann die Austestung ­definierter Einzelsubstanzen ­regelhaft ersetzen.

9. Welche Antwort ist falsch? a) Die Testung von Eigensubstanzen und Arbeitsstoffen erfordert ­besondere Sorgfalt und die Beachtung von Empfehlungen zum Vorgehen. b) Die grundsätzliche Durchführung von Testungen mit Eigensubstanzen

CME Article  Allergic contact dermatitis

muss der zuständigen Landesbehörde angezeigt werden. c) Die Auslösung einer allergischen Testreaktion durch ein Testallergen beweist nicht dessen Relevanz für das aktuelle Krankheitsgeschehen. d) Nur Reaktionen gegen aktuell ­relevante Allergene sollten mit den Patienten erörtert werden, um Missverständnisse zu vermeiden. e) Für die im Allergiepass dokumentierten Allergene sollten immer auch die Bezeichnungen nach INCI angegeben werden.

10. Welche Antwort ist falsch? a) Topische und systemische Kortikoide sind die Therapie der ersten Wahl beim allergischen Kontaktekzem. b) Alitretinoin hat sich als eine ­wirksame Behandlungsalternative für therapieresistente allergische ­Kontaktekzeme erwiesen. c) Die Meidung ursächlicher Allergenkontakte ist ein unverzichtbarer Teil der Therapie. d) Eine systemische immunsuppressive Therapie kann in Ausnahmefällen nötig sein. e) Ein wirksames Protokoll zur Hyposensibilisierung einer Kontaktallergie steht bisher nicht zur Verfügung.

© The Author | Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2013/1107

Liebe Leserinnen und Leser, der Einsendeschluss an die DDA für ­diese Ausgabe ist der 16. August 2013. Die richtige Lösung zum Thema „Nagelpsoriasis – eine therapeutische Herausforderung in Klinik und Praxis“ in Heft 3 (März 2013) ist: 1c, 2b, 3a, 4c, 5d, 6b, 7d, 8d, 9e, 10d. Bitte verwenden Sie für Ihre Einsendung das aktuelle Formblatt auf der folgenden Seite oder aber geben Sie Ihre Lösung online unter http://jddg.akademie-dda. de ein.

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