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d-Limonene, obtained as a by-product from the citrus juice industry, was introduced on the market as a more environmentally friendly defatting and cleaning agent than the traditionally used organic solvents. Autoxidation of d-limonene readily occurs to give a variety of oxygenated monocyclic terpenes that are strong contact allergens. The aim of the present study was to investigate the prevalence of contact allergy to air exposed d-limonene among dermatitis patients. A fraction consisting of d-limonene hydroperoxides was also tested. Screening with oxidized d-limonene will detect cases of allergic contact dermatitis. Additional cases were detected when testing with the fraction of limonene hydroperoxides. The proportion of positive patch test reactions to oxidized d-limonene was comparable to that seen for several of the allergens within the standard series. An increased use of d-limonene containing allergenic oxidation products in industry where high concentrations are used, as well as in domestic exposure, might result in contact sensitization and dermatitis. Patients reacting to d-limonene often reacted to fragrance mix, balsam of Peru and colophony in the standard series.

Contact allergy to corticosteroids is not infrequent. The diagnosis is not easy because of the atypical clinical picture and difficulties encountered in testing these anti-inflammatory drugs. As in all cases of contact dermatitis, the therapy of choice is avoidance, but here also one has to keep in mind the frequent crossreactions between several corticosteroids. Groups of corticosteroids that behave in similar ways regarding contact allergy have been identified, but this does not relieve us from the need for testing all the other corticosteroid molecules.

S oaps and synthetic detergents (syndets) are used worldwide in many products-bar and liquid soaps, washing powders and liquids, facial scrubs, shaving soaps (creams and foams), cleansing lotions, shampoos (hair, body), and bath additives (foam, pearls, gels, tablets); however, there have been few reports of their sensitizing effects on the skin. In general, adverse reactions to soaps and syndets are more apt to be irritant effects of the surface-active agents present, which may facilitate sensitization to other substances in the formula, such as preservatives, perfumes, and, more exceptionally, coloring agents, lipids, and metal salts. This effect is used, among other things, to detect contact allergy to substances with low allergenic potential in what is called the “Kligman maximization test,” in which the skin is treated with sodium lauryl sulfate before the allergen is applied for an occlusive patch test.’ With regard to clinical situations, Allenby and Basketter concluded that skin damage by submersion of the arm in a sodium lauryl sulfate solution increased reactivity to nickel.* In this chapter, we shall review the literature and present our own experience with contact and photosensitivity for each of the surface-active agents and other allergens in cleansing products. (Their presence and sensitizing potential in other sources will not be discussed.) The figures from the Contact Allergy Unit of the Leuven University Hospital have been compiled from the patient population from 1978 to the present (10,340 patients tested up to November 1994). We can give percentages, however, only for balsam of Peru, wool alcohols, colophony, and formaldehyde, because the other substances have not been routinely tested since 1978, when we began to computerize our recordkeeping.

The present article reviews the literature (up to 1994) on contact sensitivity to imidazoles and presents the results obtained from 15 patients observed at the Contact Allergy Unit in Leuven. The frequency as well as the cross-reaction patterns described are analyzed. Although allergic contact reactions may have been missed in the past (mainly because of problems with the correct choice of vehicle for patch testing), they seem to be relatively infrequent in view of their widespread use. The imidazole derivatives most frequently reported to be allergens are miconazole, econazole, tioconazole, and isoconazole. As far as cross-reactivity is concerned, statistically significant associations were found in the patient data between miconazole, econazole, and isoconazole; between sulconazole, miconazole, and econazole; and also between isoconazole and tioconazole. Patients sensitive to phenylethyl imidazoles (except ketoconazole) needing antimycotic therapy should be advised to use ketoconazole, clotrimazole, bifonazole, or, perhaps, the new flutrimazole. Clearly, non-imidazole antifungals can also be used.

This review concentrates on some specific aspects of the chemistry of allergic contact dermatitis. The way low molecular weight chemicals react with skin proteins to form complete antigens will be discussed and the development of molecular modelling techniques to analyse molecular recognition presented. Subsequently, how knowledge of the chemical structure can be used to estimate the allergenic activity of a molecule will be considered. This aspect includes work with qualitative and quantitative structure-activity relationships (SAR) in the field of contact allergy.

Background: α-Amylase, an enzyme commonly used in flour additives, has been reported to be an important cause of rhinitis and asthma in bakers. Objective: Our purpose was to determine whether this enzyme could also cause dermatitis. We tested it routinely in bakers with hand eczema. Methods: Patch tests were administered with the International Contact Dermatitis Research Group standard series and a bakery series and scratch-chamber or prick tests were performed with the bakers' own material and with α-amylase powder. Results: Of 32 bakers tested, seven had an immediate wheal-and-flare reaction and two also had a delayed eczematous reaction. High dilutions of the α-amylase powder still gave strong reactions. Conclusion: α-Amylase is an important cause of skin reactions in bakers and should be tested routinely if a contact allergy is suspected.

To obtain data on the frequency of sensitization among European hairdressers, the patch test results from 9 centres were evaluated. 8 allergens recommended by the ICDRG and EECDRG in the hairdressing series and PPD from the standard series were used to patch test 809 hairdressers and 104 clients suspected of contact sensitization. Among hairdressers, the mean frequencies of sensitization ranked as follows: GMT 19%, PPD 15%, APS 8%, PTD 8%, ONPPD 4%, and PADH 4%. In contrast to GMT in acid permanent waves, the frequency of sensitization to AMT in alkaline permanent waves was only 4%. Frequencies of sensitization to pyrogallol and resorcinol were 0.8% and 0.6%, respectively. The frequencies of sensitization showed marked regional variations, particularly that to GMT, which was highest in Germany (51%), followed by Spain (22%) and London (19%). Clients of hairdressers showed a similar rank order of sensitization frequency, with the exception of APS, which was completely negative in this (small) series.

We cannot as yet fully answer the question of the safety of the new corticosteroids. Budesonide is frequently found to be an allergen now that it is being marketed, and it can certainly serve as a primary sensitizer. For the other new corticosteroids, too, we already had numerous positive tests even before they were marketed. This must be considered cross-sensitivity. We will have to wait to see whether or not they are primary sensitizers. For the pharmaceutical industry, there is one more challenge in the development of new corticosteroids: In addition to finding more effective corticosteroids with the fewest "classic" side effects, the industry will also have to identify the least sensitizing molecules.

The aim of this study was to elucidate the role of the C11-OH substituent of the corticosteroid molecule in relation to contact allergy to corticosteroids. This group, which is essential for glucocorticoid activity, is not present in other steroid molecules, such as deoxycortisol, progestagens, testosterone, and estrogen. Skin tests with these substances in hydrocortisone-allergic patients revealed a division between patients for whom the C11-OH group was essential to induce the allergic reaction and patients for whom this group did not seem to be essential. Some of the patients of the latter group also reacted to 17-alpha-OH-progesterone. This may indicate cross-sensitivity between hydrocortisone and 17-alpha-OH-progesterone, which might play an etiological role in autoimmune progesterone dermatitis.

SUMMARY From animal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune unresponsiveness. Such ‘oral tolerance’ is persistent, dose-dependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could be an effective way to prevent undesired T cell-mediated immune functions, such as playing a role in allograft reaction, autoimmune and allergic diseases. In the present study allergic contact hypersensitivity (ACH) to nickel, currently presenting the most frequent contact allergy in man, was chosen to establish the feasibility of oral prevention of undesired T cell-mediated immunity in man. Potentially tolerizing (oral nickel contacts via orthodontic braces) as well as sensitizing (ear piercing) events were studied retrospectively in 2176 patients attending nine European patch test clinics. Patients were interviewed by means of a confidential questionnaire. The results show that ear piercing strongly favoured development of nickel ACH. More importantly, patients having had oral contacts with nickel-releasing appliances (dental braces) at an early age, but only if prior to ear piercing, showed a reduced frequency of nickel hypersensitivity. Frequencies of other hypersensitivities, in particular to fragrance, were not affected. These results support our view that induction of specific systemic immunologic tolerance by timely oral administration of antigens is feasible in man.

The frequency of positive reactions to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (MCI/MI) were studied at 22 European contact dermatitis clinics over a period of 1 year. A total of 4713 patients participated. All the patients were patch tested with nickel sulphate, formaldehyde, paraben-mix, and MCI/MI. 19.4% of the patients had positive patch tests to nickel, making this the most common allergen. 3% of the patients reacted to 100 ppm MCI/MI, while 2.6% reacted to formaldehyde and 1.1% to parabens. There was great variation in the frequency of MCI/MI sensitivity among the 22 centres. MCI/MI contact allergy was most common among women and in patients with facial dermatitis, while it was rarely seen in patients with dermatitis on the lower legs. There were no fluctuations in the number of positive patch tests to MCI/MI on a monthly basis when the results from all centres were combined. 117 of the 141 MCI/MI sensitized patients included in the study were retested. 88% had positive patch tests when retested. 101 of the MCI/MI-sensitive patients participated in a double-blind, placebo-controlled product use test. This test showed that 31% of the MCI/MI-sensitive patients had a positive reaction to a MCI/MI-preserved product. Only a few patients reacted to a control product. It is concluded that the preservative MCI/MI is an important new contact allergen.

Contact and systemic contact-type dermatitis reactions to spices such as nutmeg, mace, cardamom, curry, cinnamon, and laurel may be rare but may well be overlooked. In our experience, patch testing with these spices "as is" is very useful; if there is a positive reaction, testing with dilutions is helpful. Scratch-chamber testing often leads to false-positive irritant reactions. As Hjorth and Niinimaki have pointed out, a positive test to balsam of Peru may indicate a spice allergy, but the absence of such a reaction does not rule it out. In all the cases in our experience, the careful drafting of the anamnesis or case history was critical in the diagnosis.

Because contact allergy to topically applied corticosteroids is being reported at an increasing rate, the literature was surveyed to evaluate the contact allergenic potential of inhalation corticosteroids, which are widely used to treat bronchial spasms and rhinitis. Such allergic reactions do not seem to be common, but there is a risk that patients previously sensitized by application to the skin will have an allergic reaction on the very first administrations of an inhalation corticosteroid.