Patch testing

INTRODUCTION — Patch testing is an essential investigation to identify specific allergens in allergic contact dermatitis (ACD) or, in some cases, to make the diagnosis of ACD. Patch testing is based upon the principle that in sensitized individuals, primed antigen-specific T lymphocytes of the Th1 phenotype circulate throughout the body and are able to recreate a delayed-type hypersensitivity reaction when nonirritating concentrations of the antigen are applied to normal skin.

This topic will discuss indications, techniques, and interpretation of patch testing. The basic mechanisms, clinical manifestations, diagnosis, and management of ACD are discussed separately. (See "Basic mechanisms and pathophysiology of allergic contact dermatitis" and "Clinical features and diagnosis of allergic contact dermatitis" and "Management of allergic contact dermatitis in adults".)

INDICATIONS FOR PATCH TESTING — Indications for patch testing may include:

●Persistent eczematous eruptions when contact allergy is suspected [1]

●Any chronic dermatitis, especially when involving the hands, feet, face, or eyelids

●Eczematous dermatitis in individuals involved in high-risk occupations for contact dermatitis (eg, health care workers, dental assistants, cosmetologists, machinists, or rubber and plastic workers)

●Dermatitis of unknown etiology

●Worsening of a previously stable dermatitis

Patch testing also may be indicated when allergic contact dermatitis (ACD) is suspected as a complication of:

●Atopic dermatitis

●Stasis dermatitis

●Seborrheic dermatitis

●Nummular eczema

●Asteatotic eczema

●Psoriasis

SELECTION OF ALLERGENS — Observational studies have identified more than 4350 chemicals as contact allergens with varying potential to cause allergic contact dermatitis (ACD) [2]. However, a high proportion of ACD are caused by a relatively small number of allergens commonly found in the environment.

Standard (baseline) series of allergens — Standard (baseline) or screening series of contact allergens, which are designed to include the most common sensitizers responsible for ACD in a given region, are recommended as the initial battery for patients undergoing patch testing. The standard series are revised on a regular basis, as new allergens are identified as a cause of ACD.

There are several baseline series throughout the world, including the North American Contact Dermatitis Group and the European standard series of approximately 35 allergens (determined by consensus of the European Society of Contact Dermatitis and the European Environmental and Contact Dermatitis Research Group). Details on the standard series most commonly used can be found at www.dermnetnz.org/topics/baseline-series-of-patch-test-allergens. The American Contact Dermatitis Society has developed a recommended core series of 90 allergens divided into nine panels [3].

The thin-layer rapid-use epicutaneous (TRUE) test, which includes 35 allergens and one control, is a commercially available ready-to-use test widely used in basic standard patch testing among dermatologists and allergists. Although it is easy to apply, it may have lower sensitivity than other standard series [4].

Additional series of patch testing — Supplemental series of patch tests suitable for specific exposures, including workplace exposures, are available to complement the standard series (eg, hairdressers, dental, shoe, lip and stomatitis, or cosmetic series). The patient's clinical presentation and history help to determine whether testing with supplemental series and/or products provided by the patient is necessary [5]. (See "Clinical features and diagnosis of allergic contact dermatitis", section on 'History'.)

Individualized patch testing — In the event that a standard series and supplemental series do not identify an offending antigen, patients may be patch tested with their own products. As a general rule, when patch testing patients with their own products, it is acceptable to use products that are left on the skin (eg, lotions, creams). However, products that typically are rinsed off the skin (eg, soap) should not be patch tested; when left on the skin these products may act as irritants. Rinse-off products may be tested with open testing. (See 'Open test' below.)

Specific allergens can also be customized [6].

PATCH TEST PROCEDURE

Preparing the patient — Patients need to be informed that patch testing is a time-consuming process that requires at least three visits during a specified week. Patients should avoid showering, exercising, and extremes of heat and humidity, and should be alerted that positive reactions can result in itching and discomfort.

Patch testing is usually performed on the back. If the back is excessively hairy it may be difficult to achieve adequate skin contact with the patches. To avoid irritation, it is advisable to clip the hair from the back one or two days before patch testing.

Effect of systemic immunosuppression — The effect of topical or systemic immunosuppression on the accuracy of patch testing has not been well established. Potent topical corticosteroids applied to the test site or oral corticosteroids ideally should be discontinued at least two weeks before patch testing [7,8]. Topical treatment with potent corticosteroids or systemic treatment with corticosteroids or other immunosuppressant drugs may cause weak or negative reactions [1,7]. Studies on poison ivy, which usually induces strong positive reactions, have indicated that it may be acceptable to perform patch testing with doses of prednisone up to 20 mg per day [9]. However, this practice may be suboptimal for allergens that are weaker than poison ivy, and generally should be discouraged [10,11].

In two small studies, positive patch test reactions were seen in patients taking prednisone, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, infliximab, adalimumab, and etanercept [12,13]. An additional study found no difference in the prevalence or intensity of positive patch test reactions in psoriasis patients on etanercept, infliximab, adalimumab, and ustekinumab [14]. Based on a review of observational studies, recommendations have been published for patch testing in patients treated with systemic immunosuppressants [15]. For example, since inhibition from mycophenolate mofetil, cyclosporine, and azathioprine are dose dependent, patch testing may be performed in patients taking low doses of these medications; in contrast, it is suggested to hold the weekly dose of methotrexate [15].

A small case series and a few case reports suggest a variable and potentially allergen-specific effect of dupilumab on patch testing results [16-18]. In a cohort of 48 patients on dupilumab with persistent dermatitis, 10 percent of previously positive patch test reactions were lost [19]. No specific allergen was associated with a negative result, but most of the lost reactions were mild or equivocal originally. This study suggests that although it may be preferable to patch test patients prior to the initiation of dupilumab, patch testing can be performed during treatment with dupilumab, especially in patients with persistent dermatitis, to exclude concurrent allergic contact dermatitis (ACD).

Effect of oral antihistamines — Oral antihistamines may be continued during patch testing, as they have minimal if any effect on the mechanisms of delayed hypersensitivity. Since a positive patch test reaction is not a histamine mediated process, there is no pathophysiologic rationale to discontinue antihistamines prior to patch testing.

Effect of ultraviolet radiation — Patients should avoid irradiation from both artificial and natural (sunlight) sources of ultraviolet radiation before patch testing. Irradiation with ultraviolet B (UVB) can reduce the number of antigen-presenting cells in the skin and the intensity of patch test reactions. Patch testing should be deferred in heavily tanned patients, and a minimum of two weeks after significant sun exposure should be allowed before patch testing.

Patch test site — The optimal site for patch testing is the upper back. The outer aspects of the upper arms or thighs are alternatives. Placing patches on other skin areas may result in a higher degree of false-negative results. If the skin is oily, gentle degreasing can be performed with ethanol or another mild solvent. The sites of patch application are then marked with a suitable marker to identify the test sites.

Patch testing should be performed on intact skin without dermatitis to minimize the risk of nonspecific inflammatory responses with numerous false-positive tests ("angry back" syndrome). (See 'The "angry back"' below.)

Types of tests

Closed test — The most commonly accepted technique for patch testing involves the application of test allergens under occlusion onto the skin of the upper back for two days. Allergens are applied in standard amounts to aluminum or synthetic material chambers mounted on non-occlusive tape strips. Commercially available patch test units are described in the table (table 1).

Open test — Open test may be used to test products with a potential to create irritation on the skin, which include paints, soluble oils, soaps, glues, and other cleansing agents. Unlike traditional patch testing, the area is kept open. After 30 minutes, the materials are gently removed, and readings are performed in a delayed fashion similar to closed patch testing. If the reaction is negative but contact allergy is still suspected, closed patch testing with single ingredients in appropriate concentration and vehicle should be performed.

Semi-open test — The semi-open or semi-occlusive test is used for products with a slight irritant potential, including [20,21]:

●Pharmaceutical products – Products containing antiseptic agents such as mercurial compounds (eg, phenylmercuriborate), quaternary ammonium salts such as benzalkonium chloride and iodine; antiseptics containing emulsifiers such as lauraminoxyde and nonoxynol; products containing solvents such as propylene glycol in high concentrations; creams based on the emulsifier sodium laurylsulfate.

●Cosmetic products – Products containing emulsifiers, solvents, or other potentially irritant substances such as mascara, nail lacquers, hair dyes, shampoos, permanent-wave solutions, liquid soaps, and peels.

●Household and industrial products – Paints, resins, varnish, glue, ink, wax, and soluble oils (after having verified that the pH is >3 and <11 or that a corrosive material is not involved).

For a semi-open test, minute amounts of allergens (1 to 2 microL) are applied to the skin and allowed to dry (water-soluble products can be tested as 1% or 2% solution). After complete drying, the test site is covered with a non-occlusive tape for two days and read at two and four days in a fashion similar to closed patch testing.

Repeated open application test — The repeated open application test (ROAT) may be useful to evaluate the clinical relevance of doubtful positive patch test reaction to preparations in which the putative allergen is present in a low concentration [22,23].

The ROAT is performed by applying 0.1 mL of the test substance to a specified area twice daily for up to 28 days or until an eczematous reaction develops. The antecubital fossa and the outer aspect of the upper arm are the most suitable areas for ROAT, as patients can easily perform the test and observe any reactions. A positive reaction may establish the clinical relevance of the product for the patient and confirm the source of the allergy.

Usage test — If a closed patch test or open test is negative despite a history suggestive of ACD, the patient is asked to use the product under real world conditions. This method reproduces all the factors associated with the original dermatitis, for example sweating, friction, or application of allergen on damaged or presensitized skin and is especially helpful in suspected clothing and cosmetic dermatitis. However, usage tests may fail to differentiate irritative from allergic dermatitis.

Patch test reading

Initial reading — The patches typically are left in place for a period of two days (48 hours), which allows adequate penetration of the allergen into the skin. To reduce the number of false-positive readings, the initial evaluation is generally performed between 15 and 60 minutes after the patches are removed, when the transient erythema has resolved. Patients should avoid removing the skin marks before the second reading is performed.

Second reading — A second reading is critically important to distinguish irritant reactions (which fade) from true allergic reactions (which persist) and to identify allergic reactions that do not appear at the time of patch removal [24]. The time of the second reading varies among different patch testing centers, but generally is on day four or five. Day four readings appear to be associated with a low number of false-negative reactions [25]. Performing the second reading too soon may miss some delayed reactions, whereas performing the second reading too late may result in missing some positive reactions that fade rapidly, such as those due to fragrances. An additional reading at day six or seven may be useful to identify a small number of late, positive reactions, in particular to nickel, neomycin, and corticosteroids [26].

PATCH TEST INTERPRETATION — Correct reading and interpretation of patch test reactions require the skills of a trained clinician. The International Contact Dermatitis Research Group has developed a scoring system for evaluating patch test reactions that has been accepted by the North American Contact Dermatitis Group (table 2) [27].

Strong positive allergic reactions are erythematous and infiltrated, often with minute papules or vesicles that may coalesce into bullae (picture 1A-B). The reaction may extend beyond the margins of the patch and is usually associated with pruritus. In all cases, positive reactions should be evaluated within the clinical context to establish their relevance. (See 'Determining the clinical relevance' below.)

It may be difficult to distinguish true-positive weak reactions from irritant (false-positive) reactions. In addition, a variety of morphologic patterns can be seen in irritant patch test reactions, depending upon the nature and/or concentration of irritants (table 3) [28].

DETERMINING THE CLINICAL RELEVANCE — The relevance of a positive reaction in the diagnosis of allergic contact dermatitis (ACD) is established by examining the patient's clinical manifestations and history. (See "Clinical features and diagnosis of allergic contact dermatitis", section on 'Diagnosis'.)

In many cases, relevance to the current problem can be clearly established and avoidance advice given. In some cases the relevance is found to a past episode or may be uncertain. Some individuals may have a positive patch test reaction but still tolerate the contact with the allergen.

If the relevance of the positive patch test is not easily apparent, it is important to reexamine in greater detail the history of exposure to the allergen or cross-reacting substances, and evaluate the outcome after the patient avoids the allergen.

A detailed exposure history must include occupational exposure, hobbies, personal care products, topical medications, and protective measures (table 4). (See "Clinical features and diagnosis of allergic contact dermatitis", section on 'History'.)

In some cases of occupational ACD, history must be supplemented with a detailed environmental evaluation. This might include a workplace visit, assessment of materials contacted in the workplace, evaluation of the physicochemical properties of a substance, and evaluating the exposure parameters. The exposure parameters include the route and site of exposure, dose, duration, frequency, and surrounding environmental conditions.

Sometimes provocation with the allergen in the form of a usage test or repeated open application test (ROAT) may be required to determine the clinical relevance. (See 'Usage test' above and 'Repeated open application test' above.)

There is no consensus regarding the definition, scoring, and determination of clinical relevance [29,30]. One set of criteria for scoring clinical relevance is provided in the table (table 5) [31]. The most reliable "test" of relevance is the finding of clearance of the dermatitis with avoidance of identified allergens.

COMPLICATIONS OF PATCH TESTING — Although generally safe, patch testing may cause adverse reactions (table 6).

Active sensitization — Patch testing is associated with a small risk of sensitization. A late reaction appearing 10 to 20 days after the test may indicate active sensitization from the patch test, although some "normal" patch test reactions may be observed at this late time. However, the risk of active sensitization from patch testing appears to be very low [32-36].

The "angry back" — The "angry back" or "excited skin syndrome" occurs when a few strong positive reactions cause a chain of multiple reactions to other patch tests that would otherwise be negative [37]. In most cases, one or two strong reactions create an array of false-positive reactions. The cause of this phenomenon is not known. One hypothesis is that some individuals who have an active dermatitis at other body sites or exhibit a strong patch test reaction develop a nonspecific hyperreactivity of the skin [37]. Another hypothesis is that placing substances with a similar chemical affinity in the same area induces multiple positive reactions [38]. Patients with the "angry back" should be retested with the positive allergens separately and sequentially. Additional validation of positive reactions can be performed by using repeated open application tests. (See 'Repeated open application test' above.)

Other — Patients undergoing patch testing may develop a flare of dermatitis, which provides additional validation of a positive test result. Occasionally, a positive reaction may persist for several weeks. Other uncommon adverse reactions are summarized in the table (table 6).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Contact dermatitis".)

SUMMARY

●Indications for patch testing – Patch testing is an essential investigation to identify specific allergens in allergic contact dermatitis (ACD). Indications for patch testing include persistent eczematous dermatitis; chronic dermatitis, especially of the hands, feet, face, or eyelids; eczematous dermatitis in individuals in high-risk occupations; and suspicion of ACD as a complication of other forms of dermatitis. (See 'Indications for patch testing' above.)

●Standard and specific series of allergens – Standard series of contact allergens, which are designed to include the most common sensitizers responsible for ACD in a certain geographic region, are recommended as the initial battery for patients undergoing patch testing. Additional series may be used to complement the standard series (eg, hairdressers, dental, or cosmetic series). (See 'Selection of allergens' above.)

●Patch test techniques – The most common accepted technique for patch testing involves the application of test allergens to the skin of the upper back under occlusion for two days (closed test). Alternative methods, including open or usage tests, may be useful for irritant allergens, pharmaceutical products, or cosmetics. (See 'Types of tests' above.)

●Interpretation of positive reactions – Correct reading and interpretation of patch test reactions require the skills of a trained clinician (table 2). Strong positive reactions are erythematous and infiltrated, often with minute papules or vesicles (picture 1A-B). It may be difficult to distinguish true-positive weak reactions from irritant reactions (table 3). The clinical relevance of a positive patch test is established by reexamining the patient's clinical manifestations and history. (See 'Patch test interpretation' above.)