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This expert provides an enlightening, practical look at common allergens so that you can better educate your patients about the basis for their allergy and what products they need to avoid.
he thin-layer rapid use epicutaneous (T.R.U.E) Test of 23 common allergens 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.
A rich, interesting history accompanies each of the 23 allergens, and understanding these historic perspectives can help to better educate patients. Each column will also highlight appropriate products that patients should avoid when they are allergic to a specific allergen.
Contact Dermatides
Allergic contact dermatitis is an important disease with high impact on patient morbidity and economics.
ACD represents a T-helper cell Type 1 (Th1) dependent delayed-type (Type IV) hypersensitivity reaction. The instigating exogenous antigens are primarily small lipophilic chemicals (haptens) with a molecular weight less than 500 Da.1
On direct antigen exposure to the skin or mucosa, an immunologic cascade is initiated that includes cytokines, i.e., interleukin 2 (IL-2) and interferon gamma (IFN-gamma), T cells and Langerhan cells. This complex interaction leads to the clinical picture of ACD.
The contact dermatides include allergic contact dermatitis, irritant contact dermatitis and contact urticaria.
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 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 sources.1,2
The primary focus of this section is to highlight the educational component of allergic contact dermatitis.
|  | | This patient is suffering from a contact dermatitis to carbamates.
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Clinical Illustration
We report a case of a professional painter with an avid outdoor basketball hobby. He presented to the Contact Dermatitis Clinic at the University of Miami with severe hand dermatitis, which he attributed to his latex paint products. He related that despite wearing protective rubber gloves, his hand dermatitis had continued to worsen. Allergen-specific IgE antibody test (RAST) for latex demonstrated a normal IgE level.
The History of Rubber and Carbamates
On Columbus’s second voyage to Haiti in 1493, he observed natives playing with high bouncing balls, a noteworthy discovery that improved the enjoyment of ball games. He learned that the natives made these balls from procured tree sap which was then cured over the smoke of palm nuts.3 Rubber trees, especially Hevea brasiliensis, produce a milky fluid from the lactiferous cells: the latex. The natural rubber latex (NRL) has a high composition of poly-cis-isoprene, an organic polymer that confers strength and elasticity.4 It also contains a variety of proteins, such as hevamine, hevein and rubber elongation factor among the more than 10 Hevea brasiliensis allergens known to initiate type I (IgE-mediated) wheal and flare (hives) and anaphylactic reactions.5
Early Mesoamerican cultures (Mayans) found that rubber sap mixed with morning glory vine juice would become more durable with increased elasticity.6 The natives of the Amazon valley made shoes of this gum called “caoutchouc,” and Spanish soldiers had spread their cloaks with it to waterproof them.
Caoutchouc was derived from the Indian word “cahuchu” meaning “weeping wood”. It is the root of the commonly used Spanish word for rubber, “Caucho”.3
The modern world is highly dependent on rubber and rubberized products. Indonesia, Malaysia, Thailand and South America are the current-day main suppliers of freshly harvested latex.
To enable mass transport to worldwide factories, the harvested latex is treated with ammonia preservatives to prevent autocoagulation and bacterial contamination.4,6
At the factories, the long polymer chains are broken by mastication (applying mechanical forces to the rubber with rollers or rotating blades) to allow for further organic chemical compounding with antioxidants, accelerators and vulcanizing additives.7
The accelerators, such as carba chemicals (zinc-dithiocarbamates and diphenylguanidine) are added to speed the cross-linking of the natural rubber latex particles for proper alignment in producing a heat-stable, elastic, strong, and durable product, also known as vulcanization.
The compounded rubber is then sheeted, extruded into the desired shapes and molded.7 Finally, once the vulcanized rubber is dried and rinsed, it is dry-lubricated with cornstarch or talc powders to bind residual latex proteins.4,8
Charles Goodyear first made the observation that rubber mixed with sulphur produced an elastic and weatherproof compound, when these ingredients were accidentally dropped onto a hot stove. Ultimately, he patented the process for vulcanized rubber in 1844.3,7 The process was subsequently refined, and by the 1920s the role of accelerators was defined. The sulphur atoms, within the dithiocarbamates, were determined to participate in the cross-linking of the natural rubber latex molecules in the vulcanized endproduct with definitive improvement of the final physical properties of the rubber.
The carbamate acceleration chemicals are present in almost every rubber product, in addition to medicinal and agricultural uses. (See Table 1.)4,8 Ironically, this highly used chemical was once a royalty restricted product. Carbamates were originally extracted from the Guinean Gulf calabar bean (Physostigma venenosum) grown near the mouth of the Old Calabar River.
This exotic West African plant, called Doomsday Plant by the natives, was originally an “ordeal poison”. People suspected of committing a crime were obligated to swallow an infusion of the seeds.
According to the native ordeal test, depending on the cholinomimetic effect produced on the accused, a verdict was given. A guilty verdict was placed if the imbiber passed away, designating them to a life of servitude. The accused were found innocent and liberated, if the seed was vomited.9 To consecrate this royal crime judgment, the native king ordered massive destruction of community crops of the ordeal seed.
This monopolization of the calabar bean plant barred early attempts at botanical classification.9 The classification of the calabar seed, however, finally became possible when a British missioner in Africa sent dark brown kidney-shaped seeds back to Edinburgh, for identification. Of medical historical note, these (Physostigma venenosum) seeds also became the source of a valuable alkaloid, Physostigmine (aka eserine). In 1863, Dr. Argyll Robertson first described the ophthalmologic miotic effect of this alkaloid, which is still is use today for treating glaucoma.9
On another note, carbamates are important agricultural fungicides and are an occupational hazard for pesticide handlers, field workers and gardeners.10
Carbamates, as reversible inhibitors of acetylcholinesterases, are among the most popular pesticides for home use, both indoors and for lawns and gardens.
Carbaryl is the best-known and most applied carbamate pesticide. Commer-cially, the fungicide Maneb (a dithiocarbamate) is used in the Midwest to prevent ginseng weed from producing potato blight11 and related compounds such as Oxamyl, among others, are used by tobacco growers in North Carolina. Contact dermatitis to carbamate fungicides is well known.4,8,10-12
An important note regarding the allergenicity of carbamate compounds was the discovery that these compounds can become greater antigens when exposed to common household bleach.
In 1975, Jordan and Bourlas12 reported the bleached rubber syndrome by which exposure of underwear elastic to hypochlorite (bleach) caused new chemical byproducts. For example, the rubber accelerator zinc dibenzyldithiocarbamate (ZDC) became N,N-dibenzylcarbamyl chloride when exposed to hypochlorite. This change in configuration proved to make a potent allergen that undoubtedly caused allergic dermatitis in the exposed subjects.
Testing for Carbamate Sensitivity
Patch testing for Carbamate allergy can be accomplished with the T.R.U.E. test [site # 15]. The T.R.U.E test recognizes only 23 of the more than 3,700 possible allergens that can cause allergic contact dermatitis. Therefore, it needs to be known that this test is a mere screening tool that could be used by general dermatologists everywhere.
Unfortunately, we are faced with important workforce economics. There are roughly 14,500 U.S. members of the American Academy of Dermatol-ogy and many of these dermatologists serve remote locations. In contrast, the Allergic Contact Dermatitis Society (www.contactderm.org) has about 450 members. This ratio translates to one comprehensive patch tester to every 33 dermatologists, if the distribution was evenly cast, which it isn’t.
Thus, in geographic areas with limited access, the T.R.U.E. test should be recognized and utilized as a basic and necessary screening tool and its limitations understood as such.
The American Contact Dermatitis Society (ACDS) recognizes the need for comprehensive patch testing and patch test support for general dermatologists and patients suffering from allergic contact dermatitis.
The ACDS is actively engaged in maintaining access to this important testing modality by training new providers (ACDS-Fujisawa mentorship program) and providing patient education materials through the Contact Allergen Replace-ment Database (CARD).
The Value of this Patient Case
Our patient with allergy to carbamates underscores the importance of appropriate patch testing and subsequent patient education. The presence of carbamates/rubber in such a wide variety of products makes it an especially common, difficult to avoid, contactant in daily activities. Rubber products can be tested for carbamate content by extraction with a methylisobutylketone and cuprous acetate solution (a positive reaction turns olive green).
To the greatest extent possible, we advised the patient to remove rubber products from his daily routine, including protective rubber gloves, rubberized toothbrush, paint roller gripper and the basketball. With these changes, the patient dramatically improved, consistent with the fact that the mainstay of treatment for allergic contact dermatitis is avoidance.
Disclosure:The authors have no conflict of interest with any subject matter discussed in this month’s column. |
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“MAUI DERM” CONFERENCE
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2007 Winter Dermatology Conference Hawaii®
2006 4th Annual Fall Conference Supplemental Proceedings