Considering the extensive use of fragrances, the frequency of contact allergy to them is relatively small. In absolute numbers, however, fragrance allergy is common. In a group of 90 student nurses, 12 (13%) were shown to be fragrance allergic . In a group of 1609 adult subjects, 196 (12%) reported cosmetic reactions in the preceding 5 years. Sixty-nine of these (35% of the reactors and 4.3% of the total population) attributed their reactions to products primarily used for their smell (deodorants, aftershaves, perfumes) . In 567 unselected individuals aged 15 to 69 years, 6 (1.1%) were shown to be allergic to fragrances as evidenced by a positive patch test reaction to the fragrance mix (vide infra) .
In dermatitis patients seen by dermatologists, the prevalence of contact allergy to fragrances is between 6 and 14%; only nickel allergy occurs more frequently. When tested with 10 popular perfumes, 6.9% of female eczema patients proved to be allergic to them  and 3.2 to 4.2% were allergic to fragrances from perfumes present in various cosmetic products . In cosmetics causing contact allergic reactions, perfumes account for up to 18% and deodorants/antiperspirants for up to 17% of all cases. When patients with
suspected allergic cosmetic dermatitis are investigated, fragrances are identified as the most frequent allergens, not only in perfumes, aftershaves, and deodorants, but also in other cosmetic products not primarily used for their smell [12-15].
Patients allergic to fragrances are usually adult individuals of either sex. They mainly become allergic by the use of cosmetics and personal-care products; occupational contact with fragrances is seldom important, not even in workers in the cosmetics industry .
Contact allergy to fragrances usually causes dermatitis of the hands, face, and/or armpits [16-18], the latter site being explained by contact allergy to deodorants and fragranced antiperspirants. In the face, the skin behind the ears and neck is exposed to high concentrations of fragrances in perfumes and aftershaves. Microtraumata from shaving facilitates (photo)contact allergy to aftershave fragrances. The sensitive skin of the eyelids is particularly susceptible to developing allergic contact dermatitis to fragrances in skincare products, decorative cosmetics, and cleansing preparations, as well as from fragrances spread through the air (airborne contact dermatitis) . Most reactions are mild and are characterized by erythema (redness) only with some swelling of the eyelids. More acute lesions with papules, vesicles, and oozing may sometimes be observed. Dermatitis attributable to perfumes or toilet water tends to be ''streaky.'' In some cases, the eruption resembles other skin diseases such as nummular eczema, seborrhoeic dermatitis, sycosis barbae, or lupus erythematosus . Lesions in the skin folds may be mistaken for atopic dermatitis. Psoriasis of the face may be induced or worsened by allergic contact dermatitis from fragrances. Hand eczema is also common in fragrance-sensitive patients [17,18]. However, fragrances are rarely the sole cause of hand eczema. Usually, patients first have irritant dermatitis or atopic dermatitis, which is later complicated by contact allergy to products used for treatment (fragranced topical drugs) or prevention (hand creams and lotions) of hand dermatitis, or to other perfumed products in the household, recreation, or work environment.
Patients appear to become sensitized to fragrances especially by the use of deodorant sprays and/or perfumes, and to a lesser degree by cleansing agents, deodorant sticks, or hand lotions . Thereafter, new rashes may appear or are worsened by contact with other fragranced products: cosmetics, toiletries, oral hygiene products, household products, industrial contacts (e.g., cutting fluids, electroplating fluids, paints, rubber, plastics, additives in air-conditioning water), paper and paper products, laundered fabrics and clothes, topical drugs, and fragrances used as spices in foods and drinks . By their §
ubiquitous use, virtually everyone is in daily contact with fragrance materials, which are s
very hard to completely avoid . The Fragrance Allergens
Over 100 fragrances have been identified as allergens . Most reactions are caused by g the eight fragrances in the perfume mix (vide infra), and of these oak moss, isoeugenol, and cinnamic aldehyde (cinnamal) are the main sensitizers. Other fragrances (and essential
Table 1 Fragrances and Essential Oils That May Cause Contact Allergy in > 1% of Patch-Tested Dermatitis Patients a-amylcinnamic aldehyde benzyl salicylate cananga oil cinnamic alcohol cinnamic aldehyde citral coumarin dehydro-isoeugenol
(in ylang-ylang oil) dihydrocoumarin eugenol geraniol geranium oil hydroabietyl alcohol hydroxycitronellal isobornyl cyclohexanol
(synthetic sandalwood) isoeugenol
jasmine absolute jasmine synthetic lilial majantol methoxycitronellal methyl heptine carbonate methyl salicylate musk ambrette narcissus oil oak moss absolute oil of bergamot patchouli oil rose oil sandalwood oil sandela santalol ylang-ylang oil oils used as fragrances) that cause contact allergy more than occasionally (> 1% positive patch-test reactions in dermatitis patients routinely tested) are listed in Table 1.
Contact allergy to a particular product or chemical is established by means of patch testing. A perfume may contain as many as 200 or more individual ingredients. This makes the diagnosis of perfume allergy by patch-test procedures complicated. The fragrance mix, or perfume mix, was introduced as a screening tool for fragrance sensitivity in the late 1970s. It contains eight commonly used fragrances: a-amylcinnamic aldehyde, cinnamic alcohol, cinnamic aldehyde (cinnamal), eugenol, geraniol, hydroxycitronellal, isoeugenol, and oak moss absolute. It is estimated that this mix detects 70 to 80% of all cases of fragrance sensitivity ; this may be an overestimation because it was positive in only 57% of patients who were allergic to popular commercial fragrances . The response rate to the fragrance mix in dermatological patients nowadays ranges worldwide from 6 to 14% [3,24]; only nickel sulphate yields more positive reactions.
In the United States, cinnamic aldehyde is routinely tested and scores 2.4% positive reactions . In cases of suspected allergic cosmetic dermatitis, patients' personal products are always tested and may give positive patch-test reactions, proving that the patient is allergic to that product . In addition, many investigators test (a series of) additional fragrances.
The fragrance mix is an extremely useful tool for the detection of cases of contact allergy to fragrances, but unfortunately is far from ideal: it misses 20 to 30% of relevant reactions or more, and may cause both false positive (i.e., a ''positive'' patch test reaction in a non-fragrance-allergic individual) and false negative (i.e., no patch test reaction in
an individual who is actually allergic to one or more of the ingredients of the mix) reactions .
Another useful test in cases of doubt (e.g., with weakly positive patch-test reactions that are difficult to interpret) is the repeated open application test (ROAT). The suspected allergen, which may be both an individual fragrance or scented product, is applied to the elbow flexure twice daily for a maximum of 14 days. A positive reaction confirms the existence of contact allergy and makes relevance of the reaction (vide infra) more likely.
The Relevance of Positive Patch Test Reactions to the Fragrance Mix
The finding of a positive reaction to the fragrance mix should be followed by a search for its relevance, i.e., if fragrance allergy is the cause of the patient's current or previous complaints or if it at least contributes to it. Often, however, correlation with the clinical picture is lacking and many patients can tolerate perfumes and fragranced products without problem . This sometimes may be explained by irritant (false positive) patch-test reactions to the mix. Alternative explanations include the absence of relevant allergens in those products or a concentration too low to elicit clinically visible allergic contact reactions.
It is assumed that between 50 and 65% of all positive patch-test reactions to the mix are relevant, although this is sometimes hard to prove [24,26]. Nevertheless, there is a highly significant association between the occurrence of self-reported visible skin symptoms to scented products earlier in life and a positive patch test to the fragrance mix, and most fragrance-sensitive patients are aware that the use of scented products may cause skin problems .
In perfume-mix-allergic patients with concomitant positive reactions to perfumes or scented products used by them, interpretation of the reaction as relevant is highly likely. In such patients the incriminated cosmetics very often contain fragrances present in the mix, and thus the fragrance mix appears to be a good reflection of actual exposure . Indeed, one or more of the ingredients of the mix are present in nearly all deodorants , popular prestige perfumes , perfumes used in the formulation of other cosmetic products , and natural-ingredient-based cosmetics , often in levels high enough to cause allergic reactions [30,31]. Thus, fragrance allergens are ubiquitous and virtually impossible to avoid if perfumed cosmetics are used.
Contact allergy to fragrance materials is common in both eczema patients and in the general population. Allergic contact dermatitis caused by perfumes and scented cosmetics is usually located in the face (including the eyelids), on the hands, and in the axillae. Patients appear to become sensitized to fragrances especially by the use of deodorant sprays and/ or perfumes, and to a lesser degree by cleansing agents, deodorant sticks, or hand lotions. Thereafter, new rashes may appear or be worsened by contact with other fragranced products: cosmetics, toiletries, oral-hygiene products, household products, industrial contacts, paper and paper products, laundered fabrics and clothes, topical drugs, and fragrances used as flavors in foods and drinks.
Over 100 fragrances have been identified as allergens. The diagnosis of fragrance allergy is established by positive patch-test reactions to the fragrance mix (a mixture of eight commonly used fragrances) and/or to the patients' personal perfumes or scented products. Most reactions to the mix are relevant, i.e., fragrance allergy is the cause of the
patient's current or previous complaints, and most fragrance-sensitive patients are aware that the use of scented products may cause skin problems. One or more of the ingredients of the mix are present in nearly all deodorants, perfumes, and scented cosmetics, often in levels high enough to cause allergic reactions. Industry is advised to pay special attention to the safety evaluation of fragrance materials, notably those used in perfumes and deodorants.
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