Allergic Contact Dermatitis of the Eyelid
Editor's Note: To see larger images of the tables in this article, please see the .PDF posted above.
Allergic Contact Dermatitis (ACD) is an important disease that notably affects 14.5 million Americans each year.1 The economic impact of this disease is high in terms of both patient morbidity and loss of income, school and work, not to mention significant expenditures for visits to health care providers and for medicaments.1 Once patch testing is performed and a culprit has been identified, education becomes the critical intervention to ensure adherence to an avoidance regimen. With allergen avoidance, remission of the dermatitis ensues. If the patient is unable to comply with the avoidance regimen, he or she becomes at risk for recurrent or sustained dermatitis or progression to a systematized presentation.2,3 In fact, education of the patient often begins before the diagnostic patch test is ever placed. This ensures that the patient has an appropriate understanding of potential outcomes and his or her central role in both disease and treatment.
During the initial consultation, patients are often taught about the pathophysiology of ACD: its delayed presentation, its relationship with the immune system (sensitization to a chemical and then elicitation of a dermatitis with re-exposure) and its occurrence at any point in time, even to something that the patient has been using regularly for a short period of time or intermittently for years. In certain cases, the other key players, such as irritant contact dermatitis (ICD) and contact urticaria, may be explained via patient history, rather than patch testing, as the correct diagnosis for the patient. It is important to note that ICD, the most prevalent form of contact dermatitis, can, at times, precede, or be a concomitant diagnosis with, ACD.4,5 Unlike ACD, ICD is not immune-mediated, but occurs secondary to contact with an irritating or abrasive substance. Contact urticaria (wheal and flare reaction), on the other hand, represents the least prevalent form of contact dermatitis. It is important to note that it is an immune-mediated phenomenon whose hallmark is an IgE and mast cell-mediated, immediate-type hypersensitivity reaction. We acknowledge this form of hypersensitivity due to the severity of the potential deleterious anaphylactic type reactions and direct the reader to key sources.6-8
In this section, we highlight ACD and explore top relevant allergens, regional-based dermatitis presentations, topic-based dermatitis presentations and clinical tips and pearls for diagnosis and treatment.
Allergic Contact Dermatitis of the Eyelid
The eyelid is one of the most sensitive areas of the body.9 The skin of the eyelid is extremely thin compared to facial skin, rendering it vulnerable to penetration by contact allergens. It is exposed to an extraordinary number of substances, in part due to the frequent rubbing of the eye area by our fingers and hands.9 In fact, ACD of the eyelids is more often an ectopic manifestation caused by cosmetics applied to the hair, face, scalp or fingernails than materials applied directly to the eyelid or periorbital area.9 The eyelid is also particularly susceptible to ACD from airborne substances.9
ACD is deemed one of the most common causes of eyelid dermatitis. In some published reports, ACD is estimated to be responsible for at least half of all cases.9-13 The manifestations of ACD of the eyelid depend on the chronicity of exposure.14 Acute ACD may present with intense pruritus and erythema with macules, papules or vesicles;11,14 whereas subacute and chronic forms of contact dermatitis are markedly less pruritic and characterized by dry, lichenified, scaly eyelids.14 The subjective symptoms and physical manifestations are usually limited to the area of the eyelid that came into direct contact with the allergen, and it is not uncommon for a primary site of substance application, remote from the eyelid area, to remain unaffected.9,14,15 Scratching or picking as a result of the dermatitis may have several adverse consequences, including an increased risk of infection, loss of eyelashes, disruption of tearing and visual obstruction secondary to eyelid and periorbital edema.13 Moreover, the eyes are often viewed as important cosmetic structures of the face; therefore, disfiguring visible changes to the aesthetic appearance of the eyes may have significant effects on the self-confidence and well-being of the individual.
Studies have consistently demonstrated a predominance of females (>80%) suffering from eyelid dermatitis,13,16-22 most likely due to the use of cosmetic substances.23 ACD affecting the eyelids has been previously reported secondary to allergens contained in makeups, eye shadows, lotions, fragrances, preservatives and applicators such as brushes.10 For example, shellac, a resin derived from the insect Coccus lacca that is present in popular brand mascaras, has been identified as a cause of ACD of the eyelid.24 Nail polishes containing the resins toluene-sulfonamide formaldehyde or tosylamide formaldehyde and nail acrylates containing benzophenone are well known sources of eyelid ACD due to frequent finger-to-eyelid contact.9 Hair products, such as shampoos, contain various fragrances, preservatives (formaldehyde releasers) and surfactants (cocamidopropyl betaine) that can induce eyelid ACD, sometimes even in the absence of concomitant scalp and facial dermatitis.9,25 The North American Contact Dermatitis Group (NACDG) recently identified the contact allergens most frequently causing eyelid dermatitis.25 Their results, collected between 2003 and 2004, demonstrated that, of 5,145 patch-tested patients, 268 patients (5.2%) had ACD dermatitis of the eyelids as the sole site of involvement. Moreover, 65% of these cases were the result of 1 of 26 clinically relevant contact allergens identified in the study, with fragrances and various ingredients in cosmetic and personal care products, including preservatives, comprising the majority of allergens. Of note, 33 cases yielded a positive patch test (PPT) to an allergen not included among 65 standard NACDG screening allergens and were primarily derived from personal care and beauty products. Likewise, Guin26 reported that 25% of 215 patients with eyelid dermatitis patch tested between 2001 and 2003 had a PPT to a cosmetic or personal care product, and 7% of those with ACD produced a reaction to cosmetic applicators. Similarly, Amin and Belsito18 determined that ACD was the cause of nearly 44% of 105 cases of eyelid dermatitis, of which 28.3% of patients had a relevant patch test reaction to fragrances and fragrance mix. Nethercott et al21 investigated 79 cases of eyelid dermatitis between 1980 and 1987, of which 46% of patients had ACD. Several relevant sources of reactions were identified, with fragrance ingredients and cosmetic preservatives occurring as contact allergens more frequently compared to patients without eyelid dermatitis.
Additional relevant sources of ACD affecting the eyelids include metals and rubber (jewelry, makeup tools), medicaments (topical corticosteroids, antibacterial and ophthalmic preparations), fingernail products, hair care product ingredients (surfactants, preservatives), cosmetics, plants (Rhus genus) and airborne allergens (volatile chemicals and sprays).9,10,13,17-21,23,26
Determination of the diagnosis and treatment plan for a patient presenting with eyelid dermatitis can be difficult. The differential diagnosis for eyelid dermatitis is broad and most commonly includes the conditions listed in Table 1. Notably, a single cause for eyelid dermatitis may be challenging to define and, in fact, may be the result of a multitude of factors. For example, ACD of the eyelid may be superimposed on or associated with another pre-existing condition such as atopic eczema10,21,26 or seborrheic dermatitis.18,26 In a large case series of 215 patients presenting for the first time with eyelid dermatitis, 89% of patients with atopic eczema of the eyelids had PPTs to contact allergens.26 Similarly, a retrospective analysis of 1,215 patients patch tested over a 10-year period demonstrated that several patients presenting with seborrheic dermatitis of the eyelids had an associated ACD.18 Given these findings, the authors suggested that patch testing is a valuable diagnostic modality for patients with recalcitrant seborrheic dermatitis.
Distinguishing the etiology of a contact dermatitis as either allergic- or irritant-induced may prove especially challenging. In general, the inflammation associated with ICD tends to manifest earlier and more diffusely than ACD and is dependent on the dose of the agent, its duration of contact with the skin and the condition of the skin’s surface.9,14 Additionally, a vesicular eruption is rare in ICD compared to ACD.9 However, although ICD has consistently been shown to be less prevalent, ranging from less than 1% to 21% of all cases of eyelid dermatitis,10,12,17,18,21 the defining features of both are not always readily discernable. Both may present with equivalent degrees of inflammation and similar time intervals between exposure and the onset of symptoms.9
Therefore, when the cause of contact dermatitis involving the eyelid is elusive, a detailed exposure history is paramount, including inquiries about the time between substance exposure and development of symptoms; cosmetics and other agents applied to the eyelids in addition to the face, hair, scalp, hands and fingers; introduction of new products and the renewal of previously applied ones; cleansers and methods used for cosmetic removal; make up application techniques (eg, use of nickel- or rubber-containing eyelash curlers and foam rubber make up applicators); and occupational and hobby histories.9,11,15 Moreover, a thorough examination of the eyelids, face and hands is warranted, as previous studies have shown that the likelihood of ACD as the primary diagnosis for eyelid dermatitis may increase with all quadrants of the eyelid involved12 or concurrent dermatitis involving the face or other body areas.16,18
Results from patch testing patients with eyelid dermatitis have been extensively published, listing several allergens as common causes of ACD of the eyelid (see Table 2). As previously mentioned, chemicals contained in cosmetic and personal care products are the most frequently encountered agents responsible for eyelid ACD. For example, Herro et al22 cited formaldehyde, a preservative in various cosmetic and topical products, as the most common allergen inducing eyelid ACD. Likewise, the NACDG25 reported that fragrance mix 1, Myroxylon pereirae (balsam of Peru), methyldibromo glutaronitrile (preservative), quaternium-15 (formaldehyde releasing preservative) and methylchloroisothiazolinone/methylisothiazolinone (preservative), were among the main cosmetic allergens. Fragrance mix 1 was also listed as one of the most common relevant allergens in studies from the United States,13,18 United Kingdom19 and Italy.17
Additionally, in the NACDG analysis, gold was determined to be the most common contact allergen inducing eyelid-only ACD (8.2% of patients).25 It has been proposed that various cosmetic powders that contain abrasive agents such as titanium dioxide may chafe gold-containing jewelry, resulting in liberation of fine gold particulate that may subsequently travel and come in direct contact with the hands, face and eyelids, resulting in sensitization of the patient.33 Nickel was the fourth most common allergen in the NACDG study to induce ACD affecting only the eyelid;25 the prevalence of this allergy has been corroborated by several other studies.10,12,13,16-17,19-20,22,26 Likely sources of nickel include eyelash curlers and tweezers, which are commonly plated with nickel,23 mascara tubes,17 glasses,20 jewelry and other accessories,14 and handling of objects such as coins and keys.20
Pharmaceutical products are a frequent cause of ACD of the eyelids. The NACDG listed the antibiotic neomycin, an active principle ingredient in many topical ophthalmic preparations, as the fifth most common allergen.25 The finding of neomycin as a frequent contact allergen involved in eyelid ACD is similarly reported elsewhere.17,20,21 Moreover, tixocortol pivalate, a corticosteroid used as a marker for sensitivity to corticosteroids such as hydrocortisone, methylprednisolone and prednisolone,34 and budesonide, a marker for sensitivity to corticosteroids such as triamcinolone acetonide and amcinonide,34 were both included among the top 26 relevant allergens for eyelid ACD, according to the NACDG.25
As mentioned above, in addition to a thorough history and physical examination, patch testing is often necessary to distinguish ACD from other causes of eyelid dermatitis, and to identify the relevant allergen(s) responsible. The Thin-Layer Rapid Use Epicutaneous (TRUE) patch test is an FDA-approved, commercially available patch test panel that is widely used. The TRUE Test can help identify some of the common causes of eyelid ACD, such as nickel, thimerosal, cobalt, fragrance mix and balsam of Peru.35 However, several possible contactants inducing ACD of the eyelid are not represented on the TRUE Test, and, in comparison with the NACDG data, clinically relevant allergens may be overlooked.25,35 Since determination of the etiology of eyelid dermatitis may be challenging with routine patch testing, the top 38 most commonly relevant allergens based on recent publications that would constitute a reasonable initial screening series for the evaluation of patients with dermatitis exclusively involving the eyelids is defined in Table 3, above.
Patients may be tested with their own products alongside the standard trays to increase the yield of finding the culprit. It is important to note that many products containing putative allergens may require preparation prior to testing. For example, it is imperative that mascaras and liquid eyeliners be allowed to dry before occlusion.36 If topical medicaments, cosmetics or other personal care products are suspected to be the culprit, one may consider using a “repeat open application test” (ROAT) or “use test.” This is occasionally employed before formal closed patch testing when an allergen in a cosmetic or personal care product is unknown or if there is no known safe and standard concentration of that allergen chemical for formal patch testing.9 More commonly, the open use test is an additional measure to confirm that an allergen present in its typical-use concentration in a product is indeed capable of triggering ACD.9 In the open use test, the implicated cosmetic or personal care product is applied to intact skin of the antecubital fossa over a 3-cm diameter area twice daily for one week and the skin is subsequently assessed for evidence of dermatitis in the area.
Avoidance of specific allergens, especially in cosmetic and personal care products, is the foremost way to treat ACD of the eyelids. Although this can prove to be a tedious task, especially for women, there are programs available to aid in this endeavor. Both the Contact Allergen Management Program (CAMP), a service offered through the American Contact Dermatitis Society (ACDS),37 and the Contact Allergen Replacement Database (CARD), developed by Mayo Clinic,38 enable a provider to enter a patient’s known contact allergens and produce a “shopping list” of products void of those particular chemicals. The programs also have the ability to exclude cross-reactors.
Detailed education about allergen avoidance is also crucial. For example, patients must understand the difference between “unscented” and “fragrance-free” products in order to ensure avoidance of a sensitizing contactant. “Unscented” products are devoid of odor but not necessarily fragrance, as many “unscented” products contain masking fragrances designed to disguise underlying scents that may be present in the product.39 Conversely, “fragrance-free” products generally do not contain fragrance chemicals, including odor-masking agents,39 and thus may be more appropriate for individuals with known fragrance allergies. Individuals with a gold allergy may be counseled to wear gold jewelry for short periods of time on special occasions only,9 and individuals allergic to nickel may look for tweezers and eyelash curlers plated with stainless steel.23 Patients with an allergy to cocamidopropyl betaine, a surfactant contained in many makeup removers and also listed among the top 26 relevant eyelid allergens by the NACDG,25 should avoid wearing waterproof makeups that necessitate use of special makeup removal products.36 Instead, sensitive individuals should opt for wearing exclusively water-soluble eye makeups requiring only a gentle cleanser for removal. In general, patients should be encouraged by their healthcare providers to carefully read the labels of their personal care and cosmetic products and inspect the packaging or the insert for the ingredient list. The first item listed is present in the greatest concentration and subsequent items are listed in the order of decreasing concentrations present in the product.9 By developing the habit of reading product labels, patients will be more successful at avoiding the allergens to which they are most sensitive.
If relief from symptoms is not achieved following avoidance of the putative allergen, the application of low potency topical corticosteroids, preferably with a vinyl glove to ensure isolation of the eyelids from contactants present on the hands, may be necessary for resolution of acute flares.10,15,26,34 However, an extended duration of topical corticosteroids use in the periorbital region is not without potential side effects and has been associated with the development of cataracts, elevated intraocular pressure, increased risk of ocular infections, poor wound healing and eyelid skin pigmentation changes, atrophy and telangiectasias.40 Topical immune modulators such as calcineurin inhibitors (eg, tacrolimus) are steroid-sparing agents that may serve as viable alternatives to topical steroids. These agents have been shown to reduce erythema, edema and lichenification associated with eyelid ACD.41 Common side effects include burning and itching41 and, currently in the United States, these agents carry a controversial black box warning due to concerns for promoting malignancy and lack of long term safety data.41,42 For severe flares of eyelid ACD, systemic steroids may be used to decrease inflammation; however, due to significant side effects, they should not be used as a long-term treatment strategy.
In conclusion, the delicate eyelid skin is particularly susceptible to dermatitis, and ACD is considered among the most common causes. Although the etiologies of eyelid ACD are vast and often elusive, chemicals contained in fragrances, cosmetics and personal care products are some of the most implicated agents in eyelid ACD. Moreover, patients suffering from eyelid dermatitis are mostly women, given the frequency of cosmetic and fragrance use. It is important to have a high suspicion for ACD in patients presenting with recalcitrant dermatitis involving the eyelids, especially when the manifestation is bilateral or involves additional, including non-facial, areas of the body. Moreover, the practitioner must keep in mind that eyelid ACD is most often caused by materials applied to the hair, face, scalp or fingernails. Therefore, a comprehensive exposure history is essential for an accurate diagnosis and to inform management, which always begins with strict avoidance of the offending allergen.
Dr. Maier is an Assistant Professor in the University of Michigan Department of Dermatology.
Ms. Russo is a fourth-year medical student at Michigan State University and will begin her dermatology residency at the University of Cincinnati in 2013.
Dr. Jacob, the Section Editor of Allergen Focus, is Associate Clinical Professor of Medicine and Pediatrics WOS (Dermatology) at the University of California, San Diego.
Disclosure: Dr. Jacob is the principal investigator for Smartchoice USA PREA-2 trial.
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