James S. Taylor MD1
1Head, Section of Industrial Dermatology, Department of Dermatology, Cleveland Clinic Foundation
The author receives grants for clinical research from Guidant Corp. and Mekos Laboratories AS and serves as a consultant for ConvaTec and Procter & Gamble.
Contact dermatitis is an acute or chronic skin inflammation resulting from interaction with a chemical, biologic, or physical agent.1 It is one of the most common conditions seen by physicians, accounting for more than 6.5 million physician visits a year and 95% of all reported occupational skin diseases.2 Substances that produce contact dermatitis after a single exposure or multiple exposures may be irritant or allergenic. Direct tissue damage results from contact with irritants. Tissue damage by allergic substances is mediated through immunologic mechanisms. Eczema or dermatitis is the most common clinical expression of this induced inflammation. Of the more than 85,000 chemicals in our environment, most can be irritants, depending on the circumstances of exposure.1 More than 3,700 substances have been identified as contact allergens.3 The potential for these substances to cause contact dermatitis varies greatly, and the severity of the dermatitis ranges from a mild, short-lived condition to a severe, persistent, job-threatening, and possibly life-threatening disease.
Major Types of Contact Dermatitis
IRRITANT CONTACT DERMATITIS
Irritants cause as much as 80% of cases of contact dermatitis, act by direct nonimmunologic chemical or physical action on the skin, and are divided into marginal and acute types. Marginal irritants are the most common. Repeated daily exposures to low-grade irritants such as soap, detergents, surfactants, organic solvents, and oils may not cause clinical changes for days or months. Dryness of the skin with a glazed, parched appearance are often the initial signs; erythema, hyperkeratosis, and fissuring may supervene.
In contrast, acute irritants cause a more immediate reaction. Some irritants, such as strong acids and alkalis, aromatic amines, phosphorus, and metallic salts, produce a marked observable effect within minutes.4,5 Others, such as hydrofluoric acid, ethylene oxide, podophyllin, and anthralin, produce a reaction within 8 to 24 hours after exposure.4 Acute irritant contact dermatitis (ICD) is usually easily diagnosed by the patient history and often results from occupational accidents. The clinical appearance varies depending on the irritant and ranges from burns and deep-red ulcerations with sharp circumspection of the dermatitis, sometimes with a gravitational, dripping effect, to a vesicular dermatitis that is indistinguishable from acute allergic contact dermatitis.
Almost any substance can be an irritant, depending on the conditions of exposure [see Figure 1]. The nature of the irritant (i.e., its pH, solubility, physical state, and concentration), the duration of contact, and the nature of the vehicle affect disease severity. Host factors that predispose to ICD include preexisting dermatitis, skin dryness, sweating, and decreased thickness or breaks in the stratum corneum; environmental factors include high temperature, low humidity, friction, and pressure.
Figure 1. Irritant Dermatitis in Infant
Wearing a plastic bib resulted in irritant dermatitis in an 18-month-old child.
ICD provoked by work materials is believed to be a frequent cause of occupational skin disease. In one large population-based study, the highest annual incidence rates of ICD were reported for hairdressers (46.9 per 10,000 workers per year), bakers (23.5 per 10,000 workers per year), and pastry cooks (16.9 per 10,000 workers per year).6 The causative factors of ICD are complex and usually involve exposure to a combination of irritants. The sentinel event for irritant hand eczema in hairdressers is dermatitis developing in moist areas that are difficult to rinse and dry, such as under rings and in the web spaces of the fingers.7 Dermatitis may spread to the dorsum of the hand, where the skin is thinner and less resistant than on the palms.
No universally accepted test exists for diagnosing ICD, which is often diagnosed by excluding allergic contact dermatitis (ACD). Because of the clinical similarities between allergic and irritant contact dermatitis, it is important that patients who are thought to have either disorder undergo patch testing, the results of which are positive with ACD and negative with ICD.
ICD may become chronic if it is not treated early [see Treatment of Irritant and Allergic Contact Dermatitis, below]. Even when the skin appears to be healed, its protective capacity remains impaired for weeks or months. Additionally, ICD impairs the barrier function of the skin, allowing penetration of potential contact allergens. Individuals who had childhood atopic eczema are more likely than others to develop ICD of the hands when their jobs involve wet work.
ALLERGIC CONTACT DERMATITIS
Allergic contact dermatitis is a type 4, T cell-mediated, delayed hypersensitivity reaction in the skin. The disorder affects only certain sensitized individuals, typically after two or more exposures, and accounts for about 20% of contact dermatitis cases.
Predisposing factors to ACD include the patient's immunologic status, which in turn is influenced by genetics, age, gender, and the presence of systemic disease. Patients with AIDS, severe combined immunodeficiency, advanced lymphoma or other malignancy, sarcoidosis, lepromatous leprosy, cachexia, and atopic dermatitis may have impaired cell-mediated immunity or anergy.8 However, contact allergy should not be excluded in these individuals, especially those with atopic eczema. In experimental models, agents that affect the immune system, such as ultraviolet light (ultraviolet B or psoralen and ultraviolet A [PUVA]), glucocorticoids, cyclosporine, and various other drugs, may downregulate ACD.8 Administration of systemic corticosteroids below certain dosages (e.g., prednisone, 20 mg or less daily), however, does not inhibit strong patch-test reactions.9
In patients with occupational dermatitis, a form of natural hyporeactivity termed hardening may occur with diminished but continued exposure to chemical irritants. The process is inducible and is not localized.10 This acquired state of unresponsiveness, when describing adaptation to allergens, is called tolerance.8
The chemical environment in which we live defines opportunities for exposure to various allergens. A patient's age, gender, occupation, avocation, habits, and nationality are among the factors that determine the environment and thus the chemicals to which an individual is exposed. The most common source of contact allergy in the United States is Toxicodendron, a plant genus that includes poison ivy, poison oak, and poison sumac. In addition to Toxicodendron, 10 sources of contact allergens are commonly encountered in North America [seeTable 1],11 and numerous other allergens are known to cause contact reactions.3
Table 1 Body Sites Often Affected by 10 Common Contact Allergens
Other cutaneous disorders
Skin that is infected, inflamed, burned, or eczematous predisposes a patient to ACD. Patients with stasis, hand and foot eczema, or chronic actinic dermatitis are at high risk for ACD. ACD occasionally occurs with other skin disorders, including seborrheic dermatitis, psoriasis, prurigo nodularis, and benign familial pemphigus (Hailey-Hailey disease).12 Noneczematous contact reactions have also been reported: purpuric reactions caused by black rubber; lichen planus-like eruptions caused by color-film developers, gold, and other dental metals (oral mucosa); and granulomas caused by beryllium and zirconium.12
Some inflammatory immune reactions in ACD are the same as those in ICD—specifically, the two disorders have similar cytokine activity (tumor necrosis factor-α and interferon gamma) and accessory molecule activity (HLA-DR and intercellular adhesion molecule-1) producing the cascade of inflammation. However, there is no memory T cell function in ICD,13 and the extent of reaction is directly related to the amount of irritant and duration of exposure.14 In contrast, even small amounts of an allergen can trigger the T cell reaction in ACD. Minor variations in an allergen's physical and chemical properties may affect its ability to induce sensitization.8 Most environmental allergens are haptens-that is, they are small (< 500 daltons) molecules that penetrate the skin and undergo in vivo conjugation with tissue, or carrier, protein. Once the complex forms, the carrier protein is no longer recognized by the immune system as self. ACD represents a delayed-type hypersensitivity reaction to this complex.
During the sensitization phase, which usually takes a minimum of 5 to 21 days, an individual acquires a specific hypersensitivity to a particular contact allergen. Sensitization not only can evoke a type 4 delayed hypersensitivity response (mediated by lymphocytes) but also can produce a type 1 immediate hypersensitivity reaction (mediated by circulating antibodies).
On reexposure to an allergen, a hapten-carrier complex capable of eliciting a specific reaction re-forms. The reaction time—the time required for a previously sensitized individual to manifest a clinical dermatitis after reexposure to the antigen—is usually 12 to 48 hours but may range from 8 to 120 hours.
A spontaneous flare may occur within 10 to 21 days without reexposure, possibly because enough allergen remains at the site to cause a reaction once the sensitization phase has occurred.
Cross-sensitization occurs when a patient who is allergic to one chemical also reacts to structurally related chemicals. Examples includeToxicodendron antigens (poison ivy, oak and sumac Japanese lacquer, mango, and cashew nutshell oil), aromatic amines (p-phenylenediamine, procaine, benzocaine, and p-aminobenzoic acid), and perfumes or flavors (balsam of Peru, benzoin, cinnamates, and vanilla). This phenomenon may explain persistence or reactivation of dermatitis when such exposures are unknown.8,12,15
Diagnosis of ACD is based on the patient history; on the appearance, periodicity, and localization of the eruption; and on the clinical course. The history is especially important in cases of chronic dermatitis and putative occupational contact dermatitis. The history alone may be accurate only 50% of the time, on average, ranging from 80% accuracy for nickel to 50% accuracy for moderately common allergens to about 10% accuracy for less common allergens. Even with causes that are considered obvious, the specific allergen may not be known, and ACD that is caused by other chemicals may also be present. Skillful history taking is required to differentiate ACD from contact urticaria and ICD, with differentiation being especially difficult in chronic cases [see Table 2].16 Also important is detailed questioning of the patient about all topical medications (over-the-counter and prescription), systemic medication, cosmetics, other lotions and creams, occupation, hobbies, travel, and clothing. A history of hypersensitivity to one or more of the major contact allergens (e.g., nickel, rubber, topical medications, and cosmetics [fragrances, preservatives, and dyes]) or obvious occupational or avocational exposures to certain substances or chemicals (e.g., chrome, epoxy, acrylics, latex gloves, clothing, first-aid creams, preservatives, and plants) may point to the diagnosis of ACD in an otherwise unexplained eruption.16
Table 2 Common Misconceptions about ACD
In the acute stage, papules, oozing vesicles, and crusting lesions that are surrounded by inflammation predominate. These clinical features may occur anywhere, but they are best visualized on the palms, sides of the fingers, periungual areas, and soles of the feet. Frequently occurring or persistent episodes of ACD often become chronic; lesions associated with chronic ACD may appear thickened and exhibit lichenification, scaling, and fissuring [see Figures 2 and 3]. Post-inflammatory hyperpigmentation or hypopigmentation may occur. In the subacute stage of ACD, features characteristic of both acute and chronic ACD may be present. All forms of contact dermatitis frequently cause pruritus. The onset of ACD is often subtle. A low-grade, subacute to chronic eczema may appear as primarily a scaly or chapped eruption, especially on the face or on the dorsa of the hands.12,16
Figure 2. Poison Oak Dermatitis
Exposure to poison oak produced this acute Toxicodendron dermatitis with erythema, edema, and linear vesicles and bullae.
Figure 3. Chronic Eczematous Dermatitis
Chronic eczematous dermatitis, with scaling, lichenification, and hyperpigmentation, was caused by an allergy to leather components in a hatband.
The distribution of dermatitis is often the single most important clue to the diagnosis of ACD. The area of most intense dermatitis usually corresponds to the site of most intense contact with the allergen. Exceptions occur, such as nail-polish allergy, which typically appears on ectopic sites, especially the eyelids, face, and neck. In addition to the transfer of allergens to distant sites, volatile airborne chemicals may cause dermatitis on exposed body areas. Regional differences in susceptibility to contact allergens exist. Thinner eyelid and genital skin is more susceptible to both allergic and irritant contact dermatitis. Because head hair is often protective of the scalp, allergic reactions to hair cosmetics frequently involve the upper face, eyelids, postauricular area, and neck. Other areas of the body have higher or lower exposures to various allergens; these exposures are not always clear and are reflected in unusual distributions of dermatitis. Allergens in lotions and creams applied all over the body sometimes produce reactions in skin folds and intertriginous areas, where the chemicals tend to concentrate. Recognition of ACD on the basis of the physical examination alone may be only partially accurate. Linear vesicular streaks are commonly seen in poison ivy, poison oak, and poison sumac dermatitis, but contact with other plants can give a similar picture. Contact with liquids may also produce linear vesicles. Failure to examine the entire skin surface may result in misdiagnosis. Eczema on the trunk and arms may in fact represent autoeczematization from contact or stasis dermatitis of the legs. Significant regional variations are associated with contact dermatitis, and knowledge of substances that cause dermatitis of specific body sites facilitates the diagnosis. Three such areas are the hands, face and neck, and feet [see Figures 4, 5, 6, 7a, 7b, and 7c].
Figure 4. Contact Dermatitis from Sandals
Acute contact dermatitis caused by wearing sandals typically involves the dorsal surface of the feet.
Figure 5. Acute Allergic Dermatitis of Hands
Hairdresser with acute allergic contact dermatitis of the hands, caused by glyceryl thioglycolate.
Figure 6. Ectopic Dermatitis of Eyelids
Ectopic allergic contact dermatitis of the eyelids from tosyla mide formaldehyde resin in nail polish.
Figure 7a. Allergic Contact Dermatitis of the Hands in Violinist
Allergic contact dermatitis of the hands (shown here) and neck (see Figure 7b), with a positive patch test to rosin (colophony) (seeFigure 7c), which is used by violinists on their bows (see Figure 7d).
Figure 7b. Allergic Contact Dermatitis of the Neck in Violinist
Allergic contact dermatitis of the hands (see Figure 7a) and neck (shown here), with a positive patch test to rosin (colophony) (seeFigure 7c), which is used by violinists on their bows (see Figure 7d).
Figure 7c. Positive Patch Test to Rosin
Allergic contact dermatitis of the hands (see Figure 7a) and neck (see Figure 7b), with a positive patch test to rosin (colophony) (shown here).
If the history and clinical presentation reveal one or more risk factors for ACD, a patch test is indicated [see Table 3 and Patch Test, below]. The differential diagnosis of ACD is extensive, and a list of key points can be useful in establishing an accurate diagnosis [see Table 4].
Table 3 Criteria* for Determinig Which ACD Patients Should Be Given a Patch Test
Table 4 Key Points in the Diagnosis of ACD
Biopsies are of limited help in diagnosing contact dermatitis. Microscopic findings vary according to the stage of the process: acute, subacute, or chronic. The hallmark of eczema is spongiosis, or intercellular edema, associated with spongiotic vesicles. Intracellular edema may cause reticular degeneration of the epidermis with multilocular bullae formation. Most types of eczema show similar pathologic changes and cannot be distinguished with certainty.17
The patch test is the only useful and reliable method—the gold standard—for the diagnosis of ACD. The proper performance and interpretation of this bioassay require considerable experience. Because the procedure is subject to patient variability and observer error, the technique has been standardized by the North American Contact Dermatitis Group. First, the allergen is diluted in petrolatum or water to a concentration that does not produce active sensitization or irritation. A widely used patch-test system consists of strips of paper tape, onto which are fixed aluminum disks 8 mm in diameter (Finn Chambers on Scanpor tape). A small amount of allergen is placed within these disks, covering slightly more than one half of its diameter [see Figures 8a and 8b]. Currently, the only commercially available patch-test system in the United States is the thin-layer rapid-use epicutaneous (T.R.U.E.) test. The T.R.U.E. test contains 23 preloaded allergens that are crystallized, micronized, or emulsified into gels that are affixed to paper tape.
Figure 8a. Finn Chambers for Patch-test Allergens
Patch-test allergens to be tested, usually in petrolatum and occasionally aqueous, are placed on Finn Chambers on Scanpor tape for application to the patient's back (see Figure 8b) for 48 hours. See patch testing in text and Figure 7c for a positive patch test.
Figure 8b. Scanpor Tape Application
Patch-test allergens to be tested, usually in petrolatum and occasionally aqueous, are placed on Finn Chambers on Scanpor tape for application to the patient's back for 48 hours. See patch testing in text and Figure 7c for a positive patch test.
With both systems, the tests are applied to the upper back or midback, which must be free of dermatitis. The patches are left in place and kept dry. When removed at 48 hours, the first reading is performed after 20 to 30 minutes, which allows time for pressure erythema to resolve. It is important to perform a second reading between 4 and 7 days after the patches are initially applied; otherwise, almost 20% of positive reactions will be missed. Neomycin, formaldehyde and formaldehyde-releasing preservatives, and tixocortol pivolate are often late reactors. Results at both readings are graded according to intensity of the reaction covering at least 50% of the patch-test site on a scale of 0 to 3+, as follows:
Both false positive and false negative reactions can result. Thus, patch testing is best done by physicians who are familiar with the intricacies of the procedure and who have been trained to advise patients about allergen substitution, relevance of the test, and prognosis. Reading test results and interpreting relevance are as important as performing the test. Any reaction must be evaluated with regard to the individual patient. Thus, when an allergen is found to be positive, it cannot always be assumed to be the cause of ACD.8,12,15 The relevance of positive reactions to present or past episodes of ACD ranges from a low of 7.2% for thimerosal to 93.4% for dimethylol-dimethylhydantoin (DMDM hydantoin) and diazolidinyl urea [see Table 5]. Thus, relevance is determined by correlating the patch-test results with chemicals, products, and processes encountered in the environment. Occasionally, when patients are allergic to chemicals in products they use, the allergen may be present in only minimal amounts and may not be responsible for the dermatitis.8 In these cases, repeat open application testing (ROAT), in which the patient applies the commercial product to normal skin twice daily for several days, can be helpful. ROAT is typically used with products that are left on rather than washed off after application.
Table 5 Patch-Test Results in North America from 2001 through 200211
In the United States, patch testing for ACD is often initially performed using the T.R.U.E. test; however, because there are over 3,700 environmental contact allergens and this test screens for only 23 allergens, testing with additional chemicals is imperative for a thorough evaluation. In one study, the T.R.U.E. test series of 23 allergens would have completely identified all allergens in only 25.5% of patients and clinically relevant allergens in 28% of patients.18 Additional substances can be obtained from chemical suppliers and prepared by a compounding pharmacist in appropriate concentrations, as detailed in a standard text, for testing with the Finn Chamber system. As an alternative, many centers in the United States use individual patch-test chemicals or series (e.g., corticosteroid, plastics and glues, acrylic, dental, machinist, hairdresser) that are available in Europe but have not been approved in the United States.11,19
Reproducibility and validity of patch testing
In a study in which 383 patients received simultaneous duplicate patch tests on opposite sides of the upper back, 8% of patients had completely discordant results: positive on one side of the back and negative on the other.20 The intensity of the reactions was not disclosed, and clinical relevance of this problem was considered small. The most reproducible positive patch tests were for fragrance mix, nickel, and balsam of Peru. Formaldehyde and lanolin were the least reproducible positive reactors, both of which may be weak irritants.20 The sensitivity, specificity, and validity of a standard screening series has been estimated at about 70%,21 indicating that about 30% of these patch-test results were not valid. The patients whose screening results were negative later had positive results to other allergens. It was assumed that the earlier screening results had been false negative. A study of 500 consecutive patients who received identical patch testing reported discordant results in 5% of patients; the investigators concluded that patch testing is a reasonably reproducible procedure as long as methodological error is minimized.22
The positive predictive value of a diagnosis of ACD is a function of the prevalence of ACD in the population and a function of the sensitivity and specificity of the patch test.23 A large dose-response study that tested the impact of seasonal variation on the irritant susceptibility of skin identified a stronger reaction to irritants in winter.24
TREATMENT OF IRRITANT AND ALLERGIC CONTACT DERMATITIS
Most cases of contact dermatitis can be effectively treated and controlled once the offending irritant or allergen is identified and eliminated. Identifying hidden sources of allergens is important, and patients who have positive patch-test results are given exposure lists identifying various names of allergens, cross-reacting substances, lists of potential products and processes containing the allergen, and nonsensitizing substitutes. Standard texts should be consulted for detailed information12,17; the Internet is also a source of information on treatment of contact dermatitis [see Sidebar Internet Resources on Contact Dermatitis]. Examples of allergen alternatives include topical erythromycin or mupirocin ointments as substitutes for neomycin.25 Neomycin may cross-react with gentamicin and tobramycin. Bacitracin should generally be avoided for neomycin-sensitive patients because of coreactivity.
Internet Resources on Contact Dermatitis
American Contact Dermatitis Society
American Academy of Dermatology
Occupational Contact Dermatitis
National Institute for Occupational Safety and Health
Canadian Centre for Occupational Health and Safety
Spina Bifida Association of America
Reasons for persistence of ACD include unidentified sources of allergens or irritants at home or at work, exposure to cross-reacting allergens, presence of underlying endogenous (e.g., atopic) eczema, and adverse reactions to therapy [see Topical-Medication Allergy,below].
Reduction of Trigger Factors
In the case of hand dermatitis, practical management must include protective measures, topical corticosteroids, and lubrication. The use of vinyl gloves with cotton liners to avoid the accumulation of moisture that often occurs during activities involving exposure to household or other irritants and foods (e.g., peeling or chopping fruits or vegetables) may be helpful. However, it is important to verify that gloves are safe to use in the workplace around machinery before recommending them. Protective devices themselves may introduce new allergic or irritant hazards in the form of rubber in gloves and solvents in waterless cleansers. Barrier creams are generally the last resort and are probably best for workers who do not have dermatitis.26 Hand alcohol may be a superior disinfectant to soap and water in occupations that require extensive wet-work exposure.27 A barrier agent containing quaternium-18 bentonite has been shown to be effective with exposure to a specific allergen, such as poison ivy.28 Principles of treatment of atopic dermatitis may also be applied to treatment of contact dermatitis [see 2:IV Eczematous Disorders, Atopic Dermatitis, and Ichthyoses].
Treatment of contact dermatitis depends on the severity of the dermatitis. When acute serous oozing is present, cool, wet compresses should be applied for 15 minutes two or three times a day. Isotonic saline or Domeboro powder dissolved in tap water to make a 1:40 dilution (aluminum acetate) may be used. A soft cloth, such as Kerlex gauze or a towel, is immersed in the solution. The cloth is wrung slightly and applied to the affected area of the skin. The solution should not be poured directly on the dressing. Lukewarm to cool water baths or sitz baths are antipruritic and anti-inflammatory; they also aid in cleansing and removing crusts and medications. Oatmeal in the form of Aveeno Oilated Bath Treatment (colloidal powdered oatmeal with oils) may be added to the bath for its antipruritic and drying effects.
In acute vesicular dermatitis such as that caused by poison ivy, treatment with compresses and baths should be followed by the application of a topical corticosteroid spray (either triamcinolone acetonide [Kenalog aerosol] or betamethasone dipropionate [Diprosone aerosol]). A spray of 2 or 3 seconds' duration on each affected area supplies sufficient coverage, providing the container is held 6 in. from the skin. In cases in which the dermatitis is extensive or less vesicular, one of the many topical corticosteroid creams may be used. Corticosteroid creams range in potency from extremely potent (e.g., clobetasol propionate [Temovate]), to potent (e.g., betamethasone dipropionate [Diprosone topical cream]), to midstrength formulations. In addition, a lotion of camphor, menthol, and hydrocortisone (Sarnol-HC) is soothing, drying, and antipruritic. Pramoxine, a topical anesthetic in a lotion base (Prax), may also relieve pruritus.
In the subacute and chronic stages of contact dermatitis, an emollient lotion (Eucerin) or ointment (Aquaphor) may be applied to moist skin after bathing for lubrication. Oil-in-water emulsions that contain perfluoropolyethers have been shown to significantly inhibit ICD caused by a wide variety of hydrophilic and lipophilic irritants.29 A potent or midstrength topical glucocorticosteroid cream or ointment is often used in the treatment of subacute and chronic contact dermatitis. Hydrocortisone 1% is only occasionally effective. Fluorinated corticosteroids should be used with discretion; frequent and prolonged use of these agents in skin-fold areas may cause atrophy, telangiectasia, or striae, and their use on the face may cause steroid rosacea. For patients with chronic dermatitis, crude coal tar preparations may be used to control eczema. Topical PUVA treatment may be effective for contact dermatitis of the palms and soles.30
Intense itching may be relieved with sedating antihistamines such as diphenhydramine hydrochloride (Benadryl), hydroxyzine hydrochloride (Atarax), and doxepin hydrochloride (Sinequan), administered at night. Most cases of ICD and ACD are effectively managed without the use of systemic corticosteroids. However, short courses of systemic corticosteroids are indicated for patients with severe vesiculobullous eruptions of the hands and feet or the face [see Figure 9] or with severe disseminated ACD, such as poison ivy. Strategies to reduce the side effects of corticosteroid use are especially important in patients who have diabetes, hypertension, glaucoma, latent or active tuberculosis (as indicated by a positive skin-test reaction to purified protein derivative), and diseases that could be affected by steroid therapy. Attempts at desensitization have generally been unsuccessful.8 Secondary infection sometimes arises as a complication of ICD and ACD; in such cases, systemic antibiotics may be indicated.29
Figure 9. Facial Edema in Contact Dermatitis
For this patient with allergic contact dermatitis with marked facial edema, a short course of therapy with systemic corticosteroids is indicated.
Specific Etiologic Forms of Contact Dermatitis
Reactions to topically applied medications include allergic and irritant contact dermatitis, photosensitivity, airborne contact dermatitis, and contact urticaria and anaphylaxis. ACD is the most common skin reaction to topically applied drugs. The three most important contact allergens are topical antibiotics, anesthetics, and antihistamines. Neomycin and bacitracin are among the most frequently prescribed medications and are common causes of ACD.15 Mupirocin ointment infrequently causes ACD.25 Benzocaine, the most common topical anesthetic allergen, is still widely used in topical agents, and there have been a number of reports of contact allergy to topical doxepin.31,32
ACD from topical corticosteroids is most often caused by the steroid itself rather than the vehicle. Studies indicate that in patients screened for contact dermatitis, the prevalence of allergy to one or more corticosteroids ranges from 0.55% to 5.98%.33,34 Patch testing for allergy to the corticosteroid markers tixocortol pivolate and budesonide detects a great majority of cases of ACD caused by topical corticosteroids.34Further patch or ROAT testing using commercial preparations from the major cross-reacting classes may identify additional allergenic steroids or, alternatively, nonreacting steroids. Delayed readings are important at 5 to 7 days, because without a late reading, up to 30% of cases of contact allergy to corticosteroid markers can be missed.34 Allergy to inhaled corticosteroids may present as perinasal or perioral itching or dermatitis, mimicking impetigo and herpes simplex or worsening asthma or allergic rhinitis. In such cases, prior sensitization by the cutaneous route is the usual occurrence, although allergy occasionally develops in response to corticosteroid inhalation.35
Topical-drug allergy is particularly common in patients with other forms of dermatitis, especially stasis dermatitis [see Figure 10]. In patients with stasis dermatitis, allergy to topical drugs often presents as a nonhealing dermatitis, which can mask the underlying cause of the eruption. A detailed history is important and should include the patient's use of nonprescription preparations, topical agents meant for animal use, medicated bandages, borrowed medications, transdermal devices, and herbal medicines. Patch testing with the standard screening tray and the patient's topical medications is invaluable in diagnosing ACD caused by topical medications.
Figure 10. Stasis Dermatitis
Patients with stasis dermatitis are at high risk for allergic contact dermatitis, especially from topical medications. Bacitracin was the cause in this case.
SYSTEMIC CONTACT DERMATITIS
Systemic contact dermatitis occurs in individuals with contact allergy to a hapten when they are exposed systemically to the hapten via the oral, subcutaneous, transcutaneous, intravenous, inhalational, intra-articular, or intravesicular route. The disorder has been caused by a number of medications, metals, and other allergens, including food components, but occurs infrequently compared with allergic and irritant contact dermatitis. Systemic contact dermatitis presents with the following clinically characteristic features36,37:
Systemic contact dermatitis may start a few hours or 1 to 2 days after experimental provocation, suggesting that more than one type of immunologic reaction is involved. Documentation rests on patch testing and investigational oral-challenge studies. Well-controlled oral-challenge studies in sensitized individuals have been performed with medications but are more difficult to perform with ubiquitous contact allergens, such as metals and natural flavors. A relatively high dose of hapten is usually needed. Other variables include route of administration, bioavailability, individual sensitivity to the allergen, and interaction with amino acids and other allergens.36 These variables can have dramatic effects on test results. For example, when 12 leg-ulcer patients with neomycin allergy were challenged with an oral dose of the hapten, 10 reacted.37 However, of 29 patients with confirmed localized ACD caused by transdermal clonidine, only one had a skin reaction to oral clonidine.38
CLOTHING AND TEXTILE DERMATITIS
ACD from clothing is usually not caused by the fibers but rather by the dyes used to color the garments or by formalin finish resins added to make them wrinkle-resistant, shrink-proof, or wash-and-wear. Disperse blue dyes (especially blue 106 and blue 124) are highly valuable screening agents for diagnosing an important cause of textile dermatitis.39 In a study in which 4,913 patients were patch tested using 65 allergens, disperse blue dye resulted in positive reactions in 3% of the study population [see Table 5].11
The distribution of dermatitis corresponds to areas where garments fit snugly, such as the upper and inner anterior thighs, popliteal fossae, buttocks, and waistband areas. Other areas include, in men, the parts of the neck that come in contact with stiff collars and, in women, the anterior or posterior axillary folds, vulva, and suprapubic area. Diagnosis is confirmed by patch testing with disperse dyes (especially blue 106 and blue 124) and formaldehyde-releasing fabric-finish resins (e.g., dimethyloldihydroxyethyleneurea and ethyleneurea melamine formaldehyde). Patch testing with the clothing (particularly acetate and polyester liners) of patients with dye allergy may yield positive results.40
Textile-dye dermatitis can be managed in the following ways41:
Many of these principles also apply to managing fabric-finish allergy, especially avoiding wrinkle-resistant, shrinkproof, and wash-and-wear clothing.
OCCUPATIONAL CONTACT DERMATITIS
Contact dermatitis, particularly of the hands, is one of the most common types of occupational skin disorders. Special issues associated with these disorders include the following:
Prevention and treatment of occupational contact dermatitis is the same as for ACD.16
Subtypes of Contact Dermatitis
Photosensitivity refers to a condition in which ultraviolet light in combination with endogenous or exogenous substances, usually drugs or chemicals, evokes an eruption on sun-exposed skin. Most cases are evoked by ultraviolet A, but on occasion, eruptions are caused by ultraviolet B (sunburn irradiation) or by visible light. The most common causes are systemic exposure to photosensitizing drugs [see Table 6] or cutaneous exposure, usually accidental, to psoralen in plants.
Table 6 Topical and Systemic Photosensitizers
Photosensitivity reactions are of two types: phototoxicity and photoallergy. Many substances that are photoallergic at low concentrations may be phototoxic at high concentrations.43
Phototoxicity is analogous to irritation and occurs in any individual after one exposure to sufficient amounts of chemical and light. Phototoxicity has been likened to an exaggerated sunburn response, consisting of delayed erythema and edema followed by pigmentation and desquamation. Asphalt workers and roofers working with pitch develop the so-called smarts when exposed to sufficient sunlight. Phytophotodermatitis, or meadow dermatitis, is a particularly striking phototoxicity characterized by streaky bullae after contact, sometimes while sunbathing, with psoralen containing umbelliferones. Berloque dermatitis is a phototoxic dermatitis characterized by the appearance of hyperpigmented, droplike patches on the neck, face, and breast. This reaction is caused by exposure to 5-methoxypsoralen present in perfumes or colognes containing oil of bergamot, and the hyperpigmentation may persist for many months. Photo-onycholysis has been reported with tetracyclines, psoralen, and other phototoxic drugs. Not all cases exhibit obvious skin phototoxicity.43 Most cases of phototoxicity are caused by administration of phototoxic systemic drugs [see Table 6].
Photoallergy is analogous to ACD and is an immunologic reaction in which exposure of the photosensitizing compound to UV light plays a role in formation of a complete antigen. A delayed eruption, usually eczematous, appears in sun-exposed body areas, usually the face and dorsal hands, typically sparing the submental and retroauricular areas [see Figure 11]; shaded areas and covered areas remain relatively clear but occasionally are involved. Most cases are caused by topical photoallergens [see Table 6], and the most common photocontact allergens are sunscreen chemicals, which act by absorbing ultraviolet light. Oxybenzone is a common allergen; however, other sunscreen chemicals, such as padimate O and the dibenzoylmethanes, have also been reported to cause photoallergic contact dermatitis.43
Figure 11. Photocontact Dermatitis
Photocontact dermatitis characteristically involves areas exposed to the sun.
Photoallergic contact dermatitis is reproduced and diagnosed by photopatch testing, a procedure in which ultraviolet light (usually ultraviolet A) is combined with patch testing. This form of testing is particularly helpful in differentiating eruptions caused by polymorphous light from photoallergic contact dermatitis. Photopatch testing is not indicated in phototoxic drug eruptions. In some persons, photoallergic reactions can persist as chronic actinic dermatitis (CAD), which can be difficult to treat (see below). Patients with photoallergic contact dermatitis often have contact allergy and should also be patch tested.
Treatment of Phototoxicity and Photoallergy
Elimination of exposure to the photoallergen or phototoxic agent is effective for most patients, except for a few with CAD. Broad-spectrum sunscreens or sunblocks, especially those containing micronized titanium, along with sun-protective clothing, may be helpful. Topical corticosteroids are helpful for mildly affected patients, but severely affected patients with CAD may require azathioprine, with or without systemic corticosteroids; psoralen ultraviolet A therapy and cyclosporine have also been used in some severe cases.17
Latex allergy is an IgE-mediated hypersensitivity to one or more of a number of proteins present in raw or uncured natural rubber latex (NRL). The paradigm for immunologic contact urticaria is latex allergy, which, over the past decade, has become a significant medical and occupational health problem.
Populations at Risk
Individuals at highest risk are patients with spina bifida (30% to 65% prevalence), health care workers, and other workers with significant NRL exposure.44 Most reported series of occupational cases of latex allergy involve health care workers; 5% to 11% of those studied are affected.45 Studies of populations of non-health care workers are infrequent; however, evidence indicates that sensitization to NRL is more common in food handlers, construction workers, painters, hairdressers, cleaners, and miscellaneous other occupations in which NRL is utilized.46 Children with chronic renal failure appear to be at increased risk for latex sensitization.47
Risk Factors and Etiology
Predisposing risk factors are hand eczema, allergic rhinitis, allergic conjunctivitis, or asthma in individuals who frequently wear NRL gloves; mucosal exposure to NRL; and multiple surgical procedures.44,45 The majority of cases of latex allergy involve reactions from wearing NRL gloves or being examined by individuals wearing NRL gloves. Reactions from other medical and nonmedical NRL devices have occurred; these include balloons, rubber bands, condoms, vibrators, dental dams, anesthesia equipment, and toys for animals or children.
The route of exposure to NRL proteins includes direct contact with intact or inflamed skin and mucosal exposure, such as inhalation of powder from NRL gloves, especially in medical facilities and in operating rooms.47 Most immediate-type NRL reactions result from exposure to dipped NRL products (e.g., gloves, condoms, balloons, and tourniquets). Dry-molded rubber products (e.g., syringes, plungers, vial stoppers, and baby-bottle nipples) contain lower residual protein levels or have less easily extracted proteins than do dipped NRL products.
NRL allergy is sometimes associated with allergic reactions to fruit (especially bananas, kiwi, and avocados) and to chestnuts. This allergic reaction results from cross-reactivity between proteins in NRL and those found in some fruits and nuts. Symptoms range from oral itching and angioedema to asthma, gastrointestinal upset, and anaphylaxis. Cross-reactivity to NRL may be a factor in other skin eruptions. One report suggests that the use of commercially available black henna tattoos may cause hypersensitivity to NRL.48
Clinical signs of NRL allergy include contact urticaria [see Figure 12], generalized urticaria, allergic rhinitis, allergic conjunctivitis, angioedema, asthma, and anaphylaxis.45 More than 600 serious reactions to NRL, including 16 fatal anaphylactic reactions, were reported to the Food and Drug Administration by the early 1990s.
Figure 12. Urticaria in Latex Allergy
Contact urticaria of the hands in a nurse allergic to her powdered natural rubber latex gloves (latex allergy). She also experienced allergic rhinitis and asthma while at work. Urticaria is often short-lived after gloves are used and may be absent at the time of examination.
Diagnosis of NRL allergy is strongly suggested by a history of angioedema of the lips when inflating balloons and by a history of itching, burning, urticaria, or anaphylaxis when donning gloves; when undergoing surgical, medical, and dental procedures; or after exposure to condoms or other NRL devices. Diagnosis is confirmed by a positive wear or use test with NRL gloves, a valid positive intracutaneous prick test with NRL, or a positive serum radioallergosorbent test with NRL.44 Severe allergic reactions have occurred from prick and wear tests; epinephrine latex-safe resuscitation equipment free of NRL should be available during these procedures.45
Treatment and Risk Reduction
Hyposensitization to NRL is not yet feasible, and NRL avoidance and substitution are imperative. Because many patients with NRL allergy have hand eczema, have immediate allergic symptoms, or both, the most important issues for physicians are accurate diagnosis, appropriate treatment, and counseling.
Preventive measures have significantly reduced the prevalence of reported reactions to NRL.45 Risk reduction and control of NRL allergy include latex avoidance in health care settings for affected workers and patients. Synthetic non-NRL gloves should be available to replace latex gloves. Also, in many cases, low-allergen NRL gloves should be worn by coworkers so as to minimize symptoms and decrease induction of NRL allergy in those allergic to NRL. Allergen content of gloves should be requested from manufacturers and suppliers; lists of glove allergen levels have also been published. Patients with NRL allergy should wear Medic-Alert bracelets identifying them as NRL sensitive, and they should inform health care providers of their sensitivity. These patients should be given lists of substitute gloves, other non-NRL devices, potentially allergenic fruits, latex-safe anesthesia protocols, occult sources of NRL exposure such as toys (for animals and children), and dental prophylaxis cups. Some of this information is available in published sources, government agencies, and latex-allergy support groups that publish newsletters and other relevant information. Some sources have Web sites [see Sidebar Internet Resources on Contact Dermatitis].
Figure 7 Courtesy of James R. Nethercott, M.D. (deceased), Department of Dermatology, University of Maryland, Baltimore.
Figure 11 Courtesy of Kristina Turjanmaa, M.D., and Arto Lahti, M.D., Tampere and Oulu, Finland.
Editors: Dale, David C.; Federman, Daniel D.