The thin-layer rapid-use epicutaneous (T.R.U.E.) test is a valuable, first-line screening tool used by many dermatologists. Although the test focuses on common allergens, frequent questions have arisen from colleagues and patients as to where a specific allergen is derived or what products patients should avoid. With this in mind, this column was developed to provide educational information about the T.R.U.E. test allergens. The Contact DermatitidesAllergic contact dermatitis is an important disease with high impact both in terms of patient morbidity and economics. The contact dermatitides include irritant contact dermatitis, contact urticaria and allergic contact dermatitis. Irritant contact dermatitis, the most common form, accounts for approximately 80% of environmental-occupational based dermatoses. Contact urticaria (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis, the foremost example of this being latex hypersensitivity. While this is beyond the scope of this section, we acknowledge this form of hypersensitivity due to the severity of the potential reactions and direct the reader to key sources.1,2 Allergic contact dermatitis affects more than 70 million Americans each year and has a high impact both in terms of patient morbidity and economics. The primary focus of this section is to highlight the educational component of this important inflammatory disorder.Case IllustrationA patient presented to the University of Miami Allergic Contact Dermatitis Clinic for evaluation of facial dermatitis. She noted no improvement despite multiple changes to the type of cleansing and moisturizing agents she had been using.On BathingThe act of bathing began as a religious or magical ritual with the purpose of removing the “stains” of life such as touching the dead, contact with childbirth, murder, disease, or contact with persons of inferior caste.3 In ancient Rome, daily bathing for physical cleanliness was introduced with the advent of public bath houses around 500 B.C. Roman citizens were encouraged to bathe daily in these facilities.4 These public baths were large, and can still be seen today in Bath, England, and in the ruins of Pompeii (circa 79 AD).Bathing became a wholly private affair rather than public event when people realized the medical benefits of bathing. By the second century AD, the famous Greek physician Galen recommended soap for both medicinal and cleansing purposes.5 In fact, during the Crimean War (1854-1857) when the British soldiers were dying of diseases rather than combat injuries, British nurse Florence Nightingale realized that hygienic reforms in field hospitals dramatically decreased the death rate.6 On the Art of BubblesIn more modern times, bathing is used not only to achieve physical cleanliness, but also as a means of relaxation and physical therapy, particularly through submerging in a bathtub or sauna, as opposed to a shower. The local drugstore is full of products from oils to soaps that are bath water adjuncts marketed for aromatherapy, stress-relief therapy, or simply skin softening. Bubble bath products corner a large portion of this market. They’re fun and appeal to a wide age range, from young children for bedtime bathing to adults for relaxation. As early as the seventeenth century, Flemish paintings depicted children blowing bubbles with clay pipes as playthings and objets d’amusee. Jean-Baptiste Siméon Chardin used his abstract compositional skill to paint still-lifes and domestic interiors. He later became a major figure in eighteenth century art; his “Blowing Bubbles” is showcased in the Metropolitan Museum in New York.In 1886, the Pears Soap Company in England used a painting by Sir John Everett Millais, originally titled “A Child’s World” (later renamed “Bubbles”), to market its first transparent soap. This original Pears’ soap formulation was developed and successfully marketed as a gentler and purer soap for the more sensitive “alabaster” complexion that typified the upper class.7 This nineteenth century “Bubbles” campaign promoted by the Pears Soap Company popularized both soap bubbles and bubble blowing. On BubblesBubbles are physical wonders. The role of soap is to stabilize, not strengthen, a bubble via the Marangoni Effect. “As the soap film stretches, the concentration of soap decreases, which causes the surface tension to increase. Thus, soap selectively strengthens the weakest parts of the bubble and tends to prevent them from stretching further.”8 The delightful attributes of bubbles engendered them well to mass marketing as a bathing component, wedding favor and childhood toy. In the 1940s the Chicago company Chemtoy began selling bubble solution.9 “By the time the 1960s rolled around, bubbles became a symbol of peace and harmony to hippies and flower children, and further popularized the sport of bubble blowing.”10 According to one industry estimate, approximately 200 million bottles of bubble solution are sold annually.9 Bubble business is big industry, and the more recent technological advance of adding dyes to soaps has led to the first colored bubbles — Zubbles — which are expected to be available in 2006.Preservatives in the BubbleAnother unique property of bubbles is their compatibility with both non-polar and polar moieties, allowing for the structural addition-combination with other chemicals (such as fragrances and preservatives) to the base mixture, while still retaining emulsification.11 Chemically, the preservatives methylchloroisothiazolinone (MCI, 5-chloro-2-methyl-4-isothiazolin-3-one) and methylisothiazolinone (MI, 2-methyl-4-isothiazolin-3-one) are highly compatible with surfactants and emulsifiers, irrespective of the ionic nature. Furthermore, their ability to maintain biocidal activity over a wide pH range (normally encountered in cosmetics) makes them a popular choice for surfactant preservation.12 MCI and MI were first registered in the United States in 1977 as Kathon CG and Euxyl K100.13 Since the 1980s, these preservatives have been extensively added to bubble bath, bubble solutions, soaps and cosmetic formulations.14,15  The Biocidal Effect of MCI/MIIsothiazolinones exert their biocidal effect on microorganisms by interacting and oxidizing accessible cellular thiols.16 As the oxidation of cellular thiols has been shown to be neurotoxic (with other biocidal agents), the potential neurologic/neurotoxicity of MI/MCI is under investigation. In vitro studies have determined that brief exposure to MI is highly toxic to cultured neurons, but not to glia.17 As of yet, no in vivo neurotoxic effects have been reported, despite common use of the chemical.Allergic Contact Dermatitis to MCI/MIIn a study of 15 different European countries and the United States in the late 1980s, MCI was implicated as a contact allergen in 2.9% of cases in Finland, 3.6% in the United States, 5.7% in Germany, and up to 8.4% in Italy. Importantly, shampoos and rinse-off products were less common culprits at causing dermatitis in these groups, when compared to leave-on cosmetics, such as moisturizers in which the concentrations of MI/MCI exceeded 15ppm.18 Furthermore, in a German cohort of 54,000 patch tested patients, positive reactions to MCI were observed more frequently among patients with anogenital complaints.19 At lower levels (usually <10 ppm) and as a rinse-off product, the prevalence of hypersensitivity is acceptably low and those who are allergic still may tolerate products preserved with it.20 A recent case report describing a patient with known MCI/MI allergy who developed an allergic contact dermatitis to topical metronidazole gel after less than 1 day of use, has led researchers to question the possibility of cross-reactivity between these agents.21 Lastly, airborne contact dermatitis also has been attributed to isothiazolinones used as preservatives in a number of paint formulations.22 In certain instances, it has been necessary for the painted walls to be treated with inorganic sulfur salt to inactivate the allergenic component of MCI/MI.Testing for MCI/MI SensitivityPatch testing for MCI/MI (aka Kathon CG/Euxyl K100) allergy can be accomplished with the T.R.U.E. test (site #17). The component consists of an isothiazolinone mix in a polyvidone vehicle at a concentration of 0.004 mg/cm2. The Value of This Patient CaseOur patient changed her personal hygiene products regularly to try to resolve her facial dermatitis, while unknowingly continually selecting products containing the same ingredient, MCI/MI. With appropriate patch testing and subsequent patient education our patient was able to select safe alternatives free of her allergen and to resolve her dermatitis. (See Table 1.)This case highlights the need to provide alternative product substitutions to patients to ease avoidance. The Contact Allergen Replacement Database (C.A.R.D.) was designed by Yanianis and is available to all members of the American Contact Dermatitis Society at www.contactderm.org. This database allows for rapid entry and cross-referencing of the patients allergens, followed by an efficiently generated list of products that do not contain these allergens. In a recent study from the Mayo clinic it was shown that patients who were provided with the CARD and expert advice had better clinical outcomes than patients who only received the expert advice.23Disclosure: The authors have no conflict of interest with any subject matter discussed in this month’s column.