In 1997, the Food and Drug Administration gave indication to the Thin-layer Rapid-Use Epicutaneous (T.R.U.E.) test for use as a valuable, first-line screening tool in the diagnosis of allergic contact dermatitis (ACD). Many dermatologists and allergists use this standard tool (see Table 1) in their practices and refer to contact dermatitis referral centers when the T.R.U.E test fails to identify a relevant allergen. Specifically, the T.R.U.E. test (panels 1.1 and 2.1) screens for 46 distinct allergens in addition to the Balsam of Peru mixture, and is thought to adequately identify an allergen in approximately 24.5% of patients.1
Recently, panel 3.1 has become available with five new allergens, including two new formaldehyde-releasing preservatives (diazolidinyl urea [Germall II] and imidazolidinyl urea [Germall]). This being said, many relevant allergens are not detected by use of this screening tool alone and, for this reason, “Allergen Focus” has been expanded to cover the notorious Allergens of the Year and other top relevant allergens identified by the North American Contact Dermatitis Group. This issue discusses dimethyloldihydroxyethylene urea (DMDHEU) and related cross-linking agents, additives that are used to make textiles wrinkle- and stain-resistant, among other things.
Contact DermatidesThe contact dermatides include allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), and contact urticaria (CU). Irritant contact dermatitis is the most common form, accounting 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 would be latex protein 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 resources.2,3
Allergic contact dermatitis is a T-cell-dependent delayed-type (Type IV) hypersensitivity reaction that has a high impact both in terms of patient morbidity and economics. This type of hypersensitivity reaction is primarily instigated by small lipophilic chemicals (haptens) with a molecular weight less than 500 Daltons. These chemical allergens trigger a complex immunologic cascade in the skin that leads to the clinical picture of ACD.
Case IllustrationA 51-year-old woman presented to the University Case Medical Center Contact Dermatitis Clinic with a
1-year history of pruritic vesicles on her volar fingertips and well demarcated erythematous pruritic scaly papules and plaques on her forearms. She worked as a dialysis technician, and her dermatitis almost completely cleared during a 2-week vacation. Use of gloves and a water-resistant laboratory coat improved her hand dermatitis, but the dermatitis on her forearms worsened. Of note, there was a sharp cut-off of the dermatitis at the edge of her T-shirt line.
Durable Press Resins in the Textile IndustryThe industrial revolution of the late 18th and early 19th centuries began the transformation of the textile industry from laborious hand spinning wool and cotton fabrics to mass production of cellulosic, synthetic and blended fabrics. As new methods for processing and providing unique appearances to fabrics became available, the desire for fashionable fabrics heightened. The first synthetic dye was created by William Henry Perkin in 1856 when he accidentally produced the first aniline purple (mauveine) while trying to make quinine.4 The ability to impart certain performance qualities to fabrics, i.e., better feel and durability, soon became essential as well.
More than 100 years ago (1906), X. Eschalier revitalized the cotton fabric industry when he first discovered that treatment of cellulosic fabrics with formaldehyde improved the strength of the fibers.5,6 The first stiffening agents used consisted of urea-formaldehyde resins later followed by melamine-formaldehyde. These synthetic resins reacted with formaldehyde and formed cross-links with adjacent cellulose fiber molecules. These inexpensive resins offered garments wrinkle resistance and shape retention (they held a crease) following wear and laundering.7 Garments with these qualities are referred to as “durable press” garments.
The Downside of These ResinsFormaldehyde-based resins became widely used as a means to attain low-cost wrinkle resistance. There was a detriment though: Because of the instability of formaldehyde resins, not only was the fabric weakened but it attained a yellow hue when exposed to chlorines. In addition, formaldehyde fumes — up to 12,000 ppm — were released from the garments.5 This formaldehyde release was the cause of significant contact hypersensitivity.8,9
The introduction of synthetic fibers began in 1930 when Wallace Carothers discovered an extraordinarily soft but strong fiber: nylon.10 This new discovery spurred haste in the textile industry to create a finish that imparted strength and durable press to cellulosic fibers. In the 1950s, strong blended man-made fibers were developed that cross-linked cotton and cellulosic polymers (rayon) using cyclic ethylene and propylene urea resins. These resins had a distinct advantage over urea- and melamine-formaldehyde resins in that they were more stable, releasing less formaldehyde and chlorine/wash fast.5 The development of the cyclic urea derivative resin 1,3-bishydroxymethyl-4,5-dihydroxy-2-imidazolidinone in 1961 — better known as dimethyloldihydroxyethylene urea (DMDHEU, Fixapret CPN) — further decreased formaldehyde release to approximately 200 to 300ppm.11,12 However, despite their significantly decreased formaldehyde release, these resins continued to produce contact hypersensitivity.13
Developing Standards for Formaldehyde Release Within the past decade, Asian and European countries have developed strict standards for formaldehyde release from textile finishes. Once the most widely used durable-press resin, DMDHEU’s use is declining in favor of lower formaldehyde-releasing resins. The law for the Control of Household Products Containing Harmful Substances was enacted in Japan in 1973. This law restricted the amount of formaldehyde allowed in textile articles.
Since the late 1980s, several other countries have also instituted limits on formaldehyde in textiles. In Japan, the current standard level of formaldehyde allowed in products used by children must not exceed 20 ppm. The amount of formaldehyde in textile products for adults must not exceed 75 ppm.14 Oeko-Tex, a European organization that “fosters skin-friendly clothing” and has set limits on certain chemicals that can be found in clothing and other textiles, has adopted the 75 ppm limit. Their tag is a stamp of approval that informs the consumer that the textile does not contain dangerous levels of harmful substances.15
Currently DMDHEU is sparsely used in European countries because of its high free formaldehyde release, as opposed to modified dimethyloldihydroxyethylene urea (DMDHEU, methanol, and diethylene glycol; Fixapret ECO), which is gaining favor.16 Fixapret ECO maintains the same high quality and physical performance while releasing approximately 75 ppm free formaldehyde, which meets Japanese and Oeko-Tex standards. There are some resins that release zero free formaldehyde, including 1,3-dimethyl-4,5-dihydroxyimidazolidione-2 (DMeDHEU, Fixapret NF). But at this time, other than for use in infant fabrics, these resins are not as widely accepted. Their lower level of acceptance stems from the high complexity of production, high cost, and less reactivity (i.e., need to apply more to the fibers). Newly available fiber advancements that impart high strength and performance without chemical additives, such as nano-fibril technology, are increasingly popular overseas.17
When to Suspect Textile AllergyAccurately determining the percentage of true textile resin allergy is difficult because there have not been studies that measure the rate of textile resin allergy in the general population. Consider ACD in an individual who has longstanding recalcitrant or recurrent dermatitis. The patient’s history as well as area(s) of distribution are essential to determining a contact allergen as the cause of the patient’s dermatitis. With regard to allergic contact dermatitis from clothing resins (and dyes, for that matter), the body regions most commonly involved are areas that come into close direct contact with the skin. These include flexor surfaces (especially the popliteal and antecubital regions), posterior neck, anterior and medial thighs, and waistline. The anterior and posterior axillary folds are also commonly affected with sparing of the axillary vault. (See Figure 1.)18,19
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Environmental factors in these areas also play a role in allergic contact dermatitis and include heat, perspiration, pressure, and friction. These factors contribute to formaldehyde release from fabrics and enhance the allergic response.20 Unusual clinical presentations may occur in patients who are allergic to formaldehyde textile resins (FTR) on furniture or bedding, as well as individuals who use products made with formaldehyde-releasing preservatives. The most common formaldehyde releasing preservative that causes ACD is quaternium-15.21
Patch TestingPatch testing for FTR ACD can be challenging. The 1% aqueous formaldehyde used for patch testing established approximately 70% of those individuals with FTR allergy. In a recent study by Lazarov, patch testing with the formaldehyde releasing preservative quaternium-15 was reported to produce a positive reaction in 9% of patients with concomitant FTR.22 Since the rate of positive patch test results using aqueous formaldehyde is suboptimal in suspected FTR, it is necessary to conduct patch testing using specific FTRs. The six formaldehyde resins that are available for patch testing are listed in Table 2. Of these six formaldehyde resins, ACD is most often diagnosed using ethylene urea, melamineformaldehdye (Fixapret AC) and dimethylol dihyroxyethyleneurea (Fixapret CPN). There have also been positive patch test results to an FTR in the absence of a positive response to aqueous formaldehyde, reinforcing the necessity to patch test using specific FTRs if ACD to formaldehyde resins is suspected.13,23,24
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Formaldehyde Resins and ACDFTRs constitute approximately 1.2% to 6.2% of patch test diagnosed ACD.13,22,25 Free formaldehyde at levels of 500 ppm to 750 ppm is needed to cause an allergic sensitization, and many patients are sensitized at work. For example, it has been shown that FTR dermatitis is very common in machinists who are commonly sensitized to formaldehyde in biocides.13 In a sensitized patient, low levels produced today by textiles made in the United States containing 100 ppm to 200 ppm and even fabrics that meet the Oeko-Tex strict standards of 75 ppm, may elicit ACD.26,27,28
Due to processes involved in producing permanent press fabrics with formaldehyde resins, it may be impossible to completely eliminate free formaldehyde release. The chemical reaction involved in cross-linking cellulose and cellulosic fibers requires a cross-linking agent, a catalyst, and heat. Some of the catalyst used in this process may remain in the fabric, and heat produced by the body may cause release of free formaldehyde. It has also been suggested that some of the formaldehyde resin may not completely cross-link and may degrade when laundered in chemicals such as sodium hypochlorite (bleach).23,29,30
Avoidance and EducationFormaldehyde is encountered in the workplace in textile workers, machinists (biocides in coolants), and the medical field (dialysis machines, plaster dental molds and in clothing such as lab coats, scrubs and masks).24 Workers sensitized to formaldehyde, such as the dialysis technician in our clinical illustration, may then react to FTRs in clothing or personal protective equipment.
In order to avoid ACD to FTRs it is best to avoid permanent press/wrinkle-resistant, color-fast, stain-resistant, blended fabrics, and other clothing treated with formaldehyde-releasing preservatives. (See Table 3.) Clothing that is made with 100% silk, polyester, acrylic, or nylon is recommended.13 Patients should be reminded that increased temperature and sweating as well as tight-fitting clothing may increase release of allergens from clothing. Patients should be encouraged to discard any of the above clothing that may cause ACD, and when purchasing new clothing, to pay particular attention to the composition and how the fabrics are processed on the tag. Patients may be encouraged to buy clothing made in Japan, as well as clothing labeled with the Oeko-Tex tag or from companies that promote no-finish fabrics. The American Contact Dermatitis Society maintains a Web site for members that lists alternatives for allergic patients, including those allergic to FTRs. Patients who are not able to avoid fabrics treated with FTRs should wear undergarments made of the above appropriate fabric that could prevent contact with potential allergens, although this is often insufficient to prevent dermatitis.
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Significance of Case PresentationOur patient’s job as a dialysis technician involved cleaning the dialysis machine with a formaldehyde disinfectant. She also wore a stiff water-impermeable lab coat while at work. We suspected ACD to formaldehyde, and her patch tests were positive for formaldehyde, ethyleneurea formaldehyde resin, and quaternium-15. She was educated appropriately on avoidance of formaldehyde preservatives and FTRs, and she was advised to avoid wearing her lab coat. Our patient attained complete clearance of her dermatitis by complete avoidance of formaldehydecontaining preservatives and not wearing her lab coat.
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THE MANY FACES OF ROSACEA
CME Critical Reviews of Clinical Data:
Fall Clinical Dermatology 2007
Acne Case Reports
2007 ADVANCES IN COSMETIC &
MEDICAL DERMATOLOGY
“MAUI DERM” CONFERENCE
July 2007 CME Supplement
2007 Winter Dermatology Conference Hawaii®
2006 4th Annual Fall Conference Supplemental Proceedings