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Expert Review of Clinical Immunology

Diagnostic Approach in Allergic and Irritant Contact Dermatitis

Iris S Ale; Howard A Maibach

Expert Rev Clin Immunol. 2010;6(2):291-310. 

In This Article

Patch Testing

Patch testing is currently used in clinical practice as the most important investigative and diagnostic method available for studying delayed contact hypersensitivity. It constitutes – together with a detailed clinical history and a complete physical examination – a fundamental step in the diagnostic work-up of ACD. By contrast, the diagnosis of ICD is made on clinical grounds alone, mostly by exclusion of ACD: a negative patch test result points towards irritation or endogenous disease. However, this is clearly insufficient for making a diagnosis of ICD. A negative patch test may represent not testing with the causal agent or, even when the causative allergen has been tested, the reaction may have been false negative. On the other hand, a true positive patch test result does not eliminate the possible coexistence of both diseases.

Indications for Patch Testing

Patch testing is indicated when an allergic component of the dermatitis is suspected. It has been shown to be significant both in confirming contact sensitivities suspected from the clinical history and in unveiling unsuspected sensitivities. Several studies have shown that history and physical examination alone are not adequate to consistently and fully evaluate a patient's contact allergens.[] Cronin studied 1000 patients by thorough clinical investigation and patch testing and demonstrated that the accuracy of the clinical prediction varied depending on the characteristics of the clinical dermatitis and the causative allergen.[] For Ni, the most frequent sensitizer in women, the allergy was anticipated in 64% of the subjects, whilst chromate, the most common sensitizer in men, was suspected only in 40% of cases. For other common allergens, such as lanolin and neomycin, sensitization was predicted in only 16 and 8% of the cases, respectively. Similarly, Fleming et al. demonstrated that clinical questions were accurate to predict the causative allergen in only 29–54% of ACD cases, depending on the allergen involved.[] Reliable identification of causative allergens by history alone represents an overwhelming task in which we are usually unsuccessful.

In addition to the investigation of probable ACD, patch testing should also be performed to uncover unsuspected ('occult') contact allergies in patients with chronic or nonresponsive eczematous dermatitis, especially those with hand or hand-and-foot dermatitis (dyshidrotic, hyperkeratotic and even pustulosispalmaris et plantaris), stasis dermatitis, atopic dermatitis, nummular eczema and unclassified eczema. Patch testing may also be considered in patients with eczematous psoriasis,[,] essential pruritus and suspected drug eruptions.[] When these patients are assessed clinically but without patch testing, they may not be suspected of having an allergic component. Moreover, in many cases, the offending agent is present in the topical products prescribed – or self-administered – for the treatment of the primary disease. Although patch testing is primarily conducted according to the clinical history and physical examination, the diagnostic process is bidirectional and test results will guide further questioning and investigation. Reconsidering the history in the light of the test results can lead to recognition of many concealed sources of causative exposure.[]

Patch Testing Materials & Procedure

Patch testing involves the application of specific allergens directly to the skin under controlled conditions, causing a local allergic reaction in a susceptible (sensitized) person. It employs the agent that causes the disease; it applies that agent to the target organ, and it reproduces locally the pathogenic and immunologic mechanisms and morphological changes of the disease itself, thus reproducing the dermatitis 'in miniature'. The allergens are usually incorporated in petrolatum, although for some allergens a different vehicle, such as water, acetone, ethanol 70%, or olive oil, must be used. Allergens are applied in hypoallergenic chambers, which are mounted on adhesive tape and attached to the upper back of the patients. There is also a ready-to-use test system (TRUE Test™ [Allerderm, AZ, USA]),[] in which the allergen is dissolved in an aqueous or ethanol solution and then incorporated in a dried-in-gel vehicle such as polyvidone or a cellulose derivative. A thin layer of this gel is then coated onto a polyester sheet and dried to form a patch. The sheet is cut into 9 × 9 mm2 patches and arranged in panels on strips of tape. The TRUE Test produces an exact dosage, even surface spread and high bioavailability for the allergens. This solves the problems of low bioavailability, uncertain dosage and uneven surface distribution, which are commonly seen when petrolatum is used as the vehicle.[]

The present standards for patch test methodology were established by the International Contact Dermatitis Research Group (ICDRG) in the 1960s and 1970s, but numerous variations have been introduced by the different groups. The test is generally kept in place for a period of 48 h, although in some centers it is applied for only 24 h. Furthermore, there are variations in reading times and even in the score grading of patch test reactions. Until a general agreement is reached, a complete description of the patch test methodology –including the source of allergens and the chambers used, the duration of patch test application, reading times and score grading of patch test reactions – should be included, allowing for inter-laboratory comparisons of test results.

Patch Test Standardization

During the last decades of the 20th Century, great effort was devoted to optimization and standardization of the patch testing materials and methodology.[] Significant research on chemical and toxicological aspects of test allergens, appropriate vehicles and skin penetration all contributed to the development of reliable and consistent patch test techniques. Yet, systematic studies for several important aspects are still lacking, and patch testing still confronts inherent methodological problems. Several factors may influence patch test reactions and many sources of unreliability still exist, including variations in patch test materials, technique and methodology, as well as inherent biological variability of patch test responses. Variations in the amount of material applied can lead to erroneous results. The ideal test situation is a test area completely covered with the test preparation without any spreading outside that area. Excessive amounts can provoke spillover and irritant reactions, while inadequate dosing may, conversely, result in false-negative and doubtful reactions. The amount of allergen applied with the Finn Chamber technique should approximate to 20 mg[] but, as a manually dispensed system, the amount of allergen applied is potentially variable depending on the technique.[,] This variation was reported to be higher when testing allergens in solution.[] Preprepared patch test systems, such as TRUE Test, prevent the inconsistencies in the concentration of the tested allergen, the amount of material applied and the possibility of error in the sequence of allergens. The use of an appropriate vehicle is crucial as it influences the bioavailability and subsequent percutaneous penetration of the allergen.[] Petrolatum remains the standard vehicle for most allergens, with the exception of the TRUE Test. Earlier studies demonstrated that patch test suspensions in petrolatum contained undispersed allergen particles, and both the particle size and number differed significantly between different test substances and different manufacturers.[] This was frequently seen with metal salts[] such as Ni sulphate.[] Other test substances, such as disperse dyes,[] also produced a number of problems. Ryberg et al. analyzed commercial patch test preparations of eight different disperse dyes from different suppliers and observed wide variations in concentration compared with the label, impurities and even the presence of a different dye allergen in the final preparation.[] Frick et al. performed chemical analyses of 14 commercial test preparations of diphenylmethane -4,4'-diisocyanate in petrolatum and observed a poor correlation between the stated and observed concentrations.[] Furthermore, many studies have found poor stability for some allergens.[] Allergenic degradation products can be formed during storage, mostly by oxidation, as in the case of terpenes, such as limonene and linalool.[] This may have several implications, including inappropriate diagnosis and incorrect counseling for the individual patient, as well as unfeasibility in the comparison of patch test results from different departments. Advances are being made in the optimization of patch test preparations and the dispersion of allergens, and the quality of these materials has significantly improved in the last 15 years,[] but not much significant research has been carried out on alternate vehicles in patch testing.[]

Patch Test Reading

The readings of the patch test results are performed 48 h after application, approximately 30 min after the removal of the patches and again after 72 h and/or preferably 96 h after application. Unfortunately, the timing of the reactions to different allergens does not necessarily follow the timing of the readings. Delayed readings, 1 week after application, are highly recommended, especially for some slow-reacting allergens, such as neomycin or corticosteroids, among others; even Ni may be a slow-reacting allergen.[]

The classification and score grading of patch test reactions depends on descriptive morphology. Typical morphological features of an allergic test response are erythema, edema, papules and vesicles (or bullae). At least an erythematous infiltration and/or papules should be present for a reaction to be considered allergic, while reactions that show only erythema without infiltration – called doubtful reactions – are frequently nonspecific or correspond to irritancy. Allergic patch test reactions are traditionally scored in terms of intensity, and a grading scale from 1+ to 3+ is currently accepted for ranking these allergic reactions ().[] However, there is still controversy concerning patch test readings and the grading scale. For instance, there are discrepancies in the reading of the 1+ reaction between the different CD groups. Some groups define the 1+ reaction as homogeneous redness in the whole test area with scattered papules, while others only require redness and homogeneous infiltration in the whole test area. No real consensus has been reached in this matter so far. Menné and White have proposed introducing an extra grade of patch test reaction in the scoring:[] (+) homogeneous redness in the test area with scattered papules; (++) homogeneous redness and homogeneous infiltration in the test area; (+++) homogeneous redness and infiltration with vesicles; and (++++) homogeneous redness and infiltration with coalescing vesicles. However, it is debatable whether this distinction has any practical benefit. By contrast, other authors have suggested that a simplified score may reduce the inter-individual variations in patch test readings.[]

The substantial challenge in diagnostic patch testing is that reading is subjective, based on inspection and palpation of the test responses; therefore, there exists considerable inter-individual variation in how patch tests are both read and then interpreted by clinicians. The reader's background knowledge and experience can greatly affect the results.[]

Validity of Patch Testing Results

The validity of any test system is its intrinsic ability to detect which individuals have the target disease and which do not, relying on the test capability to detect both true positive and true negative reactions, while minimizing the number of false-positive and false-negative reactions.

False-positive & False-negative Patch Test Reactions A false-negative reaction can occur for a number of reasons. One easily correctable mistake is the failure to perform a delayed test reading after allergen removal and evaluation at 48 h. This is especially important for allergens known to elicit delayed reactions and in elderly patients, who may present a protracted immunologic response. Furthermore, false-negative reactions may be present when the allergen concentration is too low to elicit a response; the vehicle may not have released a sufficient amount of the allergen; the test site might have been inappropriate, or the patient's skin is unresponsive by prior sun exposure, concurrent immunosuppressive therapies or other causes; or because of methodological flaws, such as insufficient occlusion or inadequate replication of the clinical dermatitis conditions by the test. When patch testing with a particular substance is negative in a patient who has an evident dermatitis from contact with that substance, the putative allergen should be retested (perhaps in a different concentration, with a different vehicle or with a different testing method, such as open or semi-open tests, provocative use tests (PUT) and/or the repeated open application test (ROAT). Likewise, the investigator must be aware of the pitfalls of false-positive reactions. A false-positive reaction may be due to several causes, such as testing with allergens that are marginally irritant, such as metals, formaldehyde or epoxi resin; testing with allergens at concentrations that exceed their irritancy thresholds; spill-over reaction from a nearby true-positive reaction; multiple simultaneous positive reactions; or testing patients with active dermatitis or otherwise sensitive or irritable skin. It is difficult sometimes to discriminate between false-positive reactions and true allergic reactions; in such cases, the true nature of false-positive reactions can sometimes be unveiled by repeat patch testing of the individual allergen with lower concentrations or serial dilutions, repeated patch testing with 24 h occlusion, or by performing additional tests such as the ROAT.[,] Irritation reactions in ROAT are very limited compared with patch tests but, for some patients, open tests are less sensitive than classical patch tests. False-negative reactions are more difficult to detect and require high levels of suspicion to unveil. Even if the allergic nature of a positive reaction as read by international guidelines cannot be taken for granted, for most common allergens a positive patch test reaction is predictive for contact sensitization.[,] The validity of patch testing may, therefore, be considered as good for many allergens, if tested under controlled conditions and at the proper concentration, and if performed and evaluated according to the international guidelines.[,]

Sensitivity, Specificity & Predictive Value The significance of a patch test result is determined not only by the sensitivity and the specificity of the test itself, but also by the prevalence of the condition in the studied population. If the rate of contact allergy in the population tested is low, then the negative predictive value increases and the positive predictive value decreases. Conversely, when the rate of allergic persons tested increases, then the positive predictive value will increase at the same test sensitivity, while the negative predictive value will decrease.[,,,] This substantiates the importance of achieving a high prevalence rate of truly sensitized patients. We should critically consider all the information about clinical history and physical examination and generate precise pretest probabilities of meeting the case definition for ACD before patch testing.[,,,] In other words, the technique of patch testing is most effectively utilized as a confirmatory tool in those patients in which a diagnosis of ACD was made based on strict clinical criteria. Performing patch test as a 'last recourse' for managing refractory patients who otherwise do not meet the clinical criteria for ACD would not be expected to yield the best results.

Testing with the Standard Allergen Series With the premise of increasing the sensitivity of the patch test procedure and detecting as many clinically relevant allergic subjects as possible, we commonly employ arrays of many test substances grouped as tests series in the routine evaluation of patients with suspected ACD. Habitually, the patch test evaluation starts with one of the standard screening series of allergens, such as that proposed by the ICDRG,[] the European and Environmental Contact Dermatitis Research Group (EECDRG) and the North American Contact Dermatitis Group (NACDG),[] which comprise a variety of chemically defined compounds and mixes of allergens, both natural and synthetic, found in industrial and domestic settings. Their constitution is based on the statistics of allergens and they are periodically revised to adapt to changes in exposure, introduction of new environmental allergens onto the market, and information regarding irritation, active sensitization and so on. Requirements to include a chemical in a standard series have been formulated by Bruze et al.[] Demands on a sensitizer in the standard series are: being a common sensitizer and being common in the environment; having a high prevalence of contact allergy with a rate exceeding 0.5–1% of true allergic reactions in routinely tested patients with suspected contact dermatitis; and giving reliable patch test results with a high degree of clinical relevance and minimal adverse effects, particularly patch test sensitization. Minor variations are due to differences in cultural customs and practices, industrialization and use in different countries. It was believed that testing with the standard series detected up to 80% of all contact allergies.[] However, this percentage is currently deemed too high.[] In a multicenter study including 4824 consecutive patients from five European CD departments, the sensitivities detected by the standard series alone ranged from 37 to 73%, depending on the testing institution.[] Sherertz and Swartz found that 36% of positive reactions occurred to allergens in the standard series exclusively and, overall, 76% reacted to one standard allergen.[] Most patients should be tested to a standard series, and also to additional series or individual allergens that are believed to be associated with the clinical situation and will be selected depending on the clinical history and the distribution of the dermatitis, the patient's occupation or the geographic area where the patient resides.

In series, chemicals are tested in well-defined concentrations in order to reduce the chance of false-positive and false-negative reactions. It should be taken into consideration, however, that many substances are tested simultaneously, which may, because of multiple testing, give rise either to false-positive reactions or to reactions not relevant to the specific situation. On the other hand, if only a small panel of chemicals selected on the basis of history of exposure is tested, relevant allergies may be missed.

Testing with Additional Allergens Testing with additional allergens depending on the exposure gives a substantial number of additional positive reactions.[,] Furthermore, testing with the products used by the patient in the workplace or at home, as well as the ingredients and/or product extracts, is often required. However, testing with nonstandard allergens, other than those of the recommended series, should be undertaken with caution. These may be chemically pure substances, but they are often compound products and may contain unknown components. Even some components can be irritants, such is the case for many industrial products, and special prudence should be exerted when testing with them. Besides producing false-positive irritant reactions, the injudicious use of undiluted industrial substances in patch testing increases the risk of active sensitization. Therefore, it is better not to use these materials in patch testing unless there is a definite clinical suggestion of their role in the causation of the dermatitis. Specialized textbooks regarding test concentrations and vehicles for many nonstandardized materials are currently available and may constitute a starting point when testing with these substances.[] Should any substance be considered potentially irritant, an open use test may be envisaged. It should be performed with diluted substances, whose concentration can be progressively increased as far as no response, either allergic or irritant, appears. In addition, before any human test is performed, complete toxicological information of the material must be procured.

Assessment of Clinical Relevance

Patch testing results require biological and clinical interpretation. The fact that contact allergy to certain allergen(s) has been reliably demonstrated by careful patch testing does not prove that such allergen(s) is responsible for the patient's ACD. A true positive patch test reaction only indicates that the patient has been previously exposed and sensitized to the substance. Patients may suffer major changes in their lifestyle on the basis of patch testing results, therefore it is crucial to establish that the positive reaction is actually linked to the clinical dermatitis, either as a primary cause or as an aggravating factor. Based on the presence of a putative allergen in materials that come into contact with the skin, either occupationally or during leisure activities, the pattern of distribution of the skin lesions, and the effect of elicitation by exposure and healing of the dermatitis by avoidance, positive patch test results are judged as possible, probable or certainly relevant. According to the ICDRG criteria,[,] we consider that a positive patch test reaction is 'relevant' if the allergen is traced. If the source of a positive patch test is not traced, we consider it as an 'unexplained positive'. We use 'current' or 'present' relevance if the positive patch test putatively explains the patient's present dermatitis. Likewise, when the positive patch test explains a past clinical disease not directly related to the current symptoms, we refer to this as 'past' relevance. From a practical perspective, establishing that a positive reaction has past relevance or possible relevance does not direct the clinician to intervene directly for the very problem for which past testing was performed. However, reporting not currently relevant data serves an important epidemiological role and may be useful in preventing further outbreaks of ACD in a patient. The determination of relevance primarily depends on the expertise of the investigator and the possibility of detecting the allergen in the environment of the patient. In many cases, a positive reaction is judged as nonrelevant owing to insufficient environmental information. If the results of the patch tests are negative for a patient in whom a diagnosis of ACD has been proposed, one has to go back to the beginning – that is, to a thorough anamnesis and physical examination. The assumed allergens should be retested (perhaps in another concentration, with another vehicle or with another testing method) and additional allergens should be tested.[,] Often, a visit to the patient's workplace proves rewarding. We must perform a rigorous environmental evaluation, investigating the existence of allergenic exposures, characteristics of this exposure and possible concurrent factors. Relevance scores and accuracy of the assessment are significantly improved by a comprehensive knowledge of the patient's chemical environment. In we propose practical guidelines and additional testing procedures for assessment of relevance.

Besides patch testing, other types of skin tests, such as open and semi-open tests, tests with product extracts, ROAT and PUT, may be required to establish a definite causative relationship between the positive patch test result and the clinical dermatitis.[] ROAT has significant potential in refinement of the evidence-based diagnosis of clinical relevance. This test is not standardized to the same extent and it is time-consuming, but mimics some real-life exposure situations. However, for general validation, a standardized measurement of the results of use testing, such as the ICDRG scoring system for patch testing, is required.[] Several studies have shown a significant relationship between the patch test threshold and the ROAT threshold,[] but the amount of allergen required to elicit a reaction for these two study methods is not the same. Fischer et al. demonstrated that the dose per application eliciting a reaction in the ROAT is substantially lower than the dose required to elicit a reaction in the patch test.[,] This could be explained by the accumulation of allergen in the skin from repeated exposure and/or the repeated stimulation of the immune system. The stronger response in the ROAT compared with the patch test threshold is relevant for risk evaluation of the elicitation potential of allergens in final products, since the same dose per unit area eliciting a negative patch test result might elicit a reaction when applied repeatedly in an open test.[]

Once the patch testing procedure is completed, the allergens have been identified and relevance has been established, the next step is education. Even when properly conducted and interpreted, patch testing loses its value if education is not systematic and comprehensive.[] It is imperative that the patient fully understands the test and complies with the procedure and resultant avoidance regimen. Providing the patient with written information on specific allergens, synonymous names and crossreactors, in addition to suggestions on how to avoid the allergens, is the final step of patch testing.

Next Section

Expert Rev Clin Immunol. 2010;6(2):291-310. © 2010  Expert Reviews Ltd.

Cite this: Diagnostic Approach in Allergic and Irritant Contact Dermatitis - Medscape - Mar 01, 2010.

Tables

Table 1.  Clinicopathological spectrum of skin irritancy. Type of irritation Onset and type of exposure Clinical characteristics
Acute ICD   Acute; often single exposure to strong irritant   Erythema, edema, weeping, vesicles, bullae, necrosis, burning, pain  
Acute-delayed ICD   Delayed onset of clinical lesions: 8–24 h or longer after exposure; induced by special irritants   Erythema, papules, vesicles, bullae  
Irritant reaction   Develops in weeks; often seen in individuals involved in wet work and appears after multiple exposures   Erythema, papules, dryness, scaling; it may resolve or, with continued exposure, may progress to a full-blown ICD  
Cumulative ICD   Develops in months to years; multiple exposures to different agents; often weak irritants, capable of inducing a reaction only after repetitive exposure   Erythema, papules, dryness, scaling, fissuring, lichenification. Burning, itching, soreness  
Traumiterative ICD   Develops in months to years; multiple exposure to a single agent   Erythema, papules, dryness, scaling, fissuring, lichenification  
Traumatic ICD   Develops in weeks to months after skin trauma   Erythema, papules, dryness, scaling, fissuring, lichenification, callus  
Friction ICD   Develops in weeks to months by repetitive microtrauma   Erythema, papules, dryness, scaling, lichenification  
Pustular and acneiform CD   Develops in weeks to months; exposure to special agents (comedogenic-pustulogens), frequently occurs with occlusion   Papules, pustules, comedones  
Exsiccation Eczematide   Develops in weeks; multiple exposure   Dryness, scaling, fissuring, itching, soreness  
Nonerythematous (sub-erythematous) irritation   Variable onset   Dryness, scaling, stinging or itch sensation  
Subjective (sensory) irritation   Variable onset (frequently acute onset); exposure to special agents   Nonvisible changes, stinging or itch sensation  

CD: Contact dermatitis; ICD: Irritant contact dermatitis.

Tables

Table 2.  Clinical differences between irritant contact dermatitis and allergic contact dermatitis. ICD ACD
Morphology
• Acute ICD includes erythema and edema and sometimes vesicles or bullae, oozing and pustules
• Necrosis and ulceration may also be seen with corrosive materials
• ICD is mostly characterized by dryness, roughness, glazed or scalded appearance of the skin
• Chronic ICD may have hyperkeratosis, desquamation, lichenification and fissuring
• Lesions are characteristically sharply circumscribed to the contact area
• Usually there is absence of distant lesions, but sometimes dermatitis may be generalized, depending on the nature of the exposure   • Pustules, necrosis or ulceration are rarely seen
• ACD is mostly characterized by edema, vesicles and oozing, however, these features are usually not present in subacute or chronic ACD
• Chronic ACD may display hyperkeratosis, desquamation, lichenification and fissuring
• Clinical lesions are more intense in the contact area, but they usually exceed this area and their limits are ill defined
• Dissemination of the dermatitis with distant lesions may occur  
Symptoms
• Symptoms of acute ICD are burning, stinging, prickling, pain and soreness of the skin (pruritus may be present)   • Pruritus is the main symptom of ACD  
Clinical course
• Acute ICD may appear after first exposure (at least with strong irritants)
• In acute ICD, lesions appear rapidly, usually within minutes to a few hours after exposure, but delayed reactions can be seen
• Irritant reactions are characterized by the 'decrescendo phenomenon'
• The reaction reaches its peak quickly, and then starts to heal   • Sensitizing exposure(s) is required
• Clinical lesions appear after subsequent challenges with re-presentation of the antigent to already primed (memory) T cells
• Lesions usually appear 24–72 h after the last exposure to the causative agent, but they may develop as early as 5 h or as late as 7 days after exposure
• Allergic reactions are characterized by the 'crescendo phenomenon' and the kinetics of resolution may be slower  

ACD: Allergic contact dermatitis; ICD: Irritant contact dermatitis.

Tables

Table 3.  Scoring of patch tests according to the International Contact Dermatitis Research Group. Score Reaction
− (0)   Negative reaction  
?+   Doubtful reaction; erythema only  
+ (1+)   Weak (nonvesicular) positive allergic reaction; erythema, infiltration and possibly papules  
++ (2+)   Strong (vesicular) positive allergic reaction; erythema, infiltration, papules and vesicles  
+++ (3+)   Extreme positive allergic reaction; bullous reaction  
IR   Irritant reaction  

Tables

Box 1.  Clinical history for the assessment of contact dermatitis. Clinical characteristics of the dermatitis

Characteristics of initial lesions and clinical evolution

Time of onset and possible relationship with exposure to allergens or irritants

Dermatitis area corresponding to exposure site

Dermatitis morphology suggesting specific contactants

 
History of occupational exposure

Job description; occupational gestures and characteristics of the working milieu

Potential allergens and irritants in the working environment

Characteristics of the exposure: dose, frequency and site

Concomitant exposure factors: temperature, humidity, occlusion, friction, and so on.

Time relationship to occupation; effect of holidays and time off work

Personal protective measures at work (gloves, masks and barrier creams)

Other workers similarly affected?

 
History of nonoccupational exposure

Domestic products: cleansers and detergents

Skin care products, fragrances, nail and hair products

Pharmaceutical products (under prescription and over the counter)

Personal protective measures at home (gloves)

Jewellery and clothing

Homework and hobbies

 
Variants on exposure

Direct contact with the agent

Contact through fomites or contaminated surfaces

Combination of contact with the causative agent and sun exposure, resulting in a photocontact or photoaggravated dermatitis

Contact with spouses, partners, relatives or friends who convey the agent, which results in connubial or consort dermatitis

Transfer from other body sites, generally by the hands, to more sensitive areas, such as eyelids or neck, resulting in an ectopic dermatitis

Exposure to gases, droplets or particles in the atmosphere, which results in airborne dermatitis

Systemic exposure in previously sensitized patients

 
History of previous dermatitis, atopy and other skin/general diseases

Past contact dermatitis (occupational or not)

Previous patch testing

Other exogenous or endogenous dermatitis: atopic dermatitis, stasis dermatitis, psoriasis and sensitive skin

Mucosal atopy (asthma and rhinoconjunctivitis)

Family history of atopy and other skin diseases

 

Tables

Box 2.  Assessment of relevance of patch test reactions. 1. Perform a complete and standardized history (including sex, age, occupation, occupational and domestic exposures, adverse reactions, time course, effect of elicitation of the dermatitis by exposure and healing by avoidance)

The patch test results will guide further interrogation

 
2. Carry out a detailed physical examination

Consider the primary site of dermatitis and the pattern of distribution of the skin lesions

Look for clinical clues of specific exposure and the possible correlation with products containing the allergen in question

 
3. Determine the existence of allergenic exposure

Qualitative exposure assessment (shows the presence or absence of the allergen in question – or a cross-reacting substance – in the patient's occupational or domestic environment)
– Product information (product labeling, material safety data sheets, information from manufacturers or suppliers, textbooks and product databases)
– Chemical analysis of suspected products

Quantitative exposure assessment
– Removal techniques, such as skin washing and wiping
– Surrogate skin techniques, where a chemical collection medium is placed on the skin
– Fluorescent tracer techniques
– Biological monitoring

 
4. Assess all exposure parameters

Consider all possible types of exposure: direct, indirect, sporadic and concealed

Consider the possible route of exposure

Evaluate the specific site(s) of contact and the presence of skin damage or previous dermatitis in the contact area(s)

Determine the concentration of the substance in the suspected product

Appraise the intensity of exposure (i.e., dose, duration, frequency and total surface area)

Determine the existence of simultaneous exposure factors: humidity, occlusion, temperature and mechanical trauma

 
5. Repeat the patch test and/or perform additional testing procedures

Test the suspected allergen(s) with a different concentration (including serial dilution), vehicle, occlusion time or other variables

Test with products brought by the patient presumably containing the suspected allergen and/or product extracts

Perform repeated open application test, provocative use test, open or semi-open tests

 

References

Authors and Disclosures

Authors and Disclosures

Iris S Ale
Professor, Department of Dermatology, Republic University of Uruguay, Arazati 1194, PC 11300, Montevideo, Uruguay. Fax: +598 2481 1107, irisale@gmail.com

Howard A Maibach
Professor, Department of Dermatology, School of Medicine, Surge 110 PO Box 0989, University of California in San Francisco, San Francisco, CA 94143-0989, USA. Tel.: +1 415 666 2717, Fax: +1 415 753 5304, maibachh@derm.ucsf.edu

†Author for correspondence
Department of Dermatology, School of Medicine, Surge 110 PO Box 0989, University of California in San Francisco, San Francisco, CA 94143-0989, USA. Tel.: +1 415 666 2717, Fax: +1 415 753 5304, maibachh@derm.ucsf.edu

Sidebar

Sidebar Key Issues

Making a correct diagnosis of allergic contact dermatitis (ACD) or irritant contact dermatitis (ICD) and identifying the causative agent(s) is of the utmost importance for the institution of appropriate therapeutic and preventive measures. The identification and avoidance of triggers will help to avert the distress and suffering of chronic contact dermatitis.

ACD and ICD are similar in many aspects, such as clinical aspects and histopathology, and no pathognomonic clinical signs and symptoms can unambiguously discriminate between ACD and ICD.

The mechanisms at the origin of the clinical lesions are dissimilar in the two types of dermatitis, at least in which concerns the early stages of the inflammatory response. ICD follows the activation of innate immunity, while in ACD both the innate and acquired immunity are activated and, as a result, antigen-specific effector T cells will drive the inflammatory response. The later stages giving rise to an eczema lesion may, on the other hand, be very similar and involve cytokines, chemokines, phenomena of apoptosis and cellular necrosis, and the recruitment of a polymorphic inflammatory infiltrate. This explains why ACD and ICD lesions can be confused clinically and histologically.

Irritancy is believed to play a crucial role in the development of ACD. Skin cell damage and cytokine release induced by irritants may represent a 'danger signal' for the immune system, activating antigen-presenting dendritic cells (DCs) and recruiting DC precursors into the skin, thus predisposing to contact sensitization. Hence, early recognition and opportune treatment of ICD will contribute to prevent the development of ACD.

Patch testing is currently used in clinical practice as the most important investigative and diagnostic method available for studying delayed contact hypersensitivity. Together with a detailed clinical history and a complete physical examination, it constitutes a fundamental step in the diagnostic work-up of ACD.

Several studies have shown that clinical history and physical examination alone are not adequate to consistently and fully evaluate a patient's contact allergens; therefore, patch testing with the standard series of epicutaneous allergens, as well as additional allergens according to the clinical situation, must be performed. It has been shown to be significant both in confirming contact sensitivities suspected from the clinical history and in unveiling unsuspected sensitivities.

The validity of patch testing may be considered as good for many allergens – especially those from the standard series – when tested under controlled conditions and in the proper concentration, and when the test is performed and evaluated according to the international guidelines.

To further investigate the possibility of false-positive or false-negative patch test reactions, additional tests should be carried out, such as testing with a different concentration or performing serial dilutions with a different vehicle, with a different occlusion time or with a different testing method, such as provocative use tests or repeated open application tests. Using a range of concentrations rather than a single concentration would allow us to rule out false-positive irritant reactions more accurately as well as establishing the elicitation threshold in allergic reactions. Ascertaining the patient's degree of sensitization may have important practical implications vis à vis the implementation of rational avoidance measures.

Patch testing results require biological and clinical interpretation. A true positive patch test reaction only indicates that the patient has previously been exposed and sensitized to the substance. It is indispensable to determine the relevance of the patch test reactions to the clinical situation.

A significant problem with patch testing is the possibility of inducing adverse changes in the patients' immune status. Therefore, development of in vitroimmunological procedures for delayed contact sensitivity testing, leading to a less invasive diagnostic of contact dermatitis, may be valuable.