Allergic contact dermatitis (ACD) affects more than 14.5 million Americans each year, notably defining itself as an important widespread disease.1 Due to overwhelming patient morbidity, loss of school and work time and significant expenditures for healthcare visits and medicaments, ACD presents with a high economic burden. Fortunately, through keen patient interviewing and patch testing, a culprit may be identified. Remission can occur with implementation of an allergen avoidance regimen.
Education becomes the critical bridging intervention to ensure treatment adherence and symptom resolution. Patients who are unable to comply with avoidance regimens are at risk for sustained, recurrent, progressive or even systemic dermatitis.2,3 To ensure patients have an appropriate understanding of all the potential outcomes and their central role in disease pathology and treatment, education of the patient may occur even before the diagnostic patch test is placed.
Important aspects of patient counseling include explaining the nature of their disease, for example, the delayed presentation of ACD [aka the importance of a delayed read at 96 hours]; the relationship with the immune system (sensitization to a chemical followed by elicitation of dermatitis with re-exposure) and the indifference to time (a substance the patient has been using regularly, briefly or intermittently can sensitize at any point). In certain cases, irritant contact dermatitis (ICD) and contact urticarial (CU) are also explained. Of note, unlike ACD, history rather than patch testing can often lead one to the correct diagnosis of ICD and CU.
ICD, the most prevalent form of contact dermatitis, can at times precede or be a concomitant diagnosis with ACD.4,5 Unlike ACD, ICD may occur on the first exposure to an irritating or abrasive substance. The innate immune system is activated and inflammation ensues. CU (wheal and flare reaction), on the other hand, represents one of the least prevalent forms of ACD. It is an immune-mediated phenomenon governed by a hallmark IgE and mast cell-mediated immediate-type hypersensitivity reaction. We acknowledge this form of hypersensitivity due to its potentially deadly anaphylactic reactions and direct the reader to key sources.6-8
Confirmatory diagnosis of ACD is through the use of the epicutaneous patch test procedure. Once a patient’s spectrum of allergy is defined, education regarding their specific set of chemicals and products to avoid is of the utmost importance. Although ACD is not “curable,” many individuals will achieve complete remission with assiduous avoidance. In this section focus, we highlight ACD and explore top relevant allergens, regional-based dermatitis presentations, topic-based dermatitis presentations and clinical tips and pearls for diagnosis and treatment. This article focuses on black rubber mix (BRM).
Rubber, The Early Years
The Aztec and Maya people realized the powers of the Hevea Braziliensis tree long before the industrialized world understood the power of rubber. Recent discoveries have shown that rubber extraction and processing dates back to more than 3,000 years ago within the cultures of Mesoamerica.9 Rubber was obtained in the form of latex from the aforementioned tree and was called “caoutchouc” in the Maya Indian language, meaning “weeping wood.”10 These ancient rubber makers not only harvested the white liquid from the naturally found Hevea trees, but also discovered the morning glory vines, when mixed with the latex, strengthened and solidified it. The morning glory vines, often found growing nearby the latex trees, are a natural source of sulfur — a substance much later discovered by Charles Goodyear to be a “vulcanizer” of rubber.10 Mayan artifacts at the Harvard University’s Peabody Museum include rubber figures, rubber handles and numerous rubber balls, as well as reports (but, unfortunately, no lasting examples) of rubber sandals.9
Natural rubber is a liquid hydrocarbon immersed in a sheath of proteins. Solid rubber may be obtained either by drying off the water, or by precipitation with acid.10 The word rubber, as we know it today, was coined by Joseph Priestley when he discovered that dried latex sap could be used to erase pencil marks — he called this pencil eraser a “rubber,” thus coining the word.11 The current use of the term rubber is applied to any material having similar mechanical properties to those of natural (or Hevea) rubber — this includes accelerated rubber products.
Interestingly, it was not until the 1880s that there was global demand for rubber wares.12 At the turn of the 20th century, rubber manufacturing involved mechanically stretching out (pulling), molding and cooling of the wares to achieve the desired structure. The word tire (from French la tire “to pull”) was originally used in reference to the production of toffee candy, which involves the same type of pulling and stretching.13 Like toffee, the original commercial rubber products remained sticky, gummy and non-durable with changing temperature/humidity conditions.
In 1839, Goodyear serendipitously pioneered vulcanization — the chemical acceleration of natural rubber from a liquid to a solid state, with an accidental sulfur spill on a hot stove.10 Although already used for thousands of years by the Mayans with the morning glory vine, the addition of the sulfur component to commercial rubber production “accelerated” the manufacturing process leading to the boom of the rubber accelerator industry (using thiurams, carbamates and mercaptobenzothiazole).14-16
With the ability to produce large-scale amounts of rubber came the challenge of protecting the rubber against the destructive forces of oxidation.
What Is Oxidation?
For thousands of years, scientists have been intrigued by the air around us. Was it an empty void without any weight or function, or did it possess unattainable powers not yet discovered? The first elemental theory focusing on air came from a French physician and chemist named Jean Rey. Upon observing rusted tin left out in the open air, he theorized that air became incorporated into the metal, accounting for the additional weight of the tin.17 Rey shocked the world with his groundbreaking theory because it meant that air must have a weight of its own. Despite mass skepticism, his theory on elements eventually gained widespread acceptance and, with time, led to several important inventions, most notably the thermometer and the barometer.18,19
The possibility of more than one “air” was entertained by Priestley, an English minister with a remarkable fascination for gases. While observing the fermenting process at the neighborhood brewery, he witnessed the presence of a gas (separate from the air above the grain) that seemed to “spill” down the sides of the barrel. This gas was later determined to be carbon dioxide.20 Priestley’s further experiments with carbon dioxide led to soda water, a discovery that earned him the Copley Medal from the Royal Society.11
In his later works, Priestley focused on the relationship of fire with gases. Using a vacuum chamber to collect the by-products of combustion, he noted that in the presence of mercuric oxide gas, the burning of a candle intensified, while all of the other gases he experimented with extinguished the flame. Priestley shared these observations with a friend, a French tax collector Antoine Lavoisier. Lavoisier, in turn, compulsively experimented with combustion gas chambers, weighing the substrates, reactants and products throughout the condensation reaction. He discovered that water was composed of 2 gases which, when combined and cooled, could reform into water. Furthermore, by observing that 1 of the gases was essential to maintain a flame, Lavoisier correctly deduced that it was necessary to initiate combustion. He also noted that this gas contributed to combustion products having an acidic taste. Lavoisier named this gas oxygene (from the Greek words oxys “sour” and genes “I produce”).21
From the discovery of oxygen, came the questions of its effect on the surrounding elements. Oxidation is by far the main cause of age-related deterioration in both organic (skin, internal organs) and inorganic (metals, rubber) systems. Technically, oxidation refers to the loss of at least 1 electron when 2 or more substances interact. At times, oxidation is the necessary step in a formation of a specific material — such as the formation of super-durable anodized aluminum. The production and harnessing of steam derived from the combustion (oxidation) of coal and wood set the stage for a multitude of technological advances, which would be the hallmark of the industrial revolution.
However, oxidation can often be destructive such as the rusting of metal and rotting of fruit. The Statue of Liberty, for example, gifted to the United States in 1886 by the French, befell to the powers of oxidation in its discolored green coat. When exposed to free air, the pure rubber molecule is susceptible to oxidation, which leads to a deterioration of its physical properties — aging.10 Unprotected rubber products, such as tires, would quickly demise to the elements around them and crumble under pressure. The Ford Motor Company struggled with this fact as its early models carried white rubber tires, which dried, cracked and quickly showed dirt and age.22
Article continues on page 2
Black Rubber Mix Emerges
Antidegradation agents such as antioxidants and antiozonants were developed to prevent rubber from drying by preventing oxidation or decreasing the effect of ozone.23 One of the first utilized antioxidants was hexamethylenetetramine (HMT), a formaldehyde-releasing antioxidant and vulcanizer. While it is still used today, the carcinogenic and allergenic potential of HMT led to its substitution with less toxic chemicals, such as the secondary amines of para-phenylenediamine (PPD). During the antioxidation process, the additives turn the rubber mixture black before damage to the rubber molecules can be done.24
PPD is an oxidative substance, which was formulated for hair dye use in 1907 by Eugene Schueller, a young French chemist and founder of L’Oreal. Schueller developed an entire industry based on the principle that, when oxidized, PPD turned hair black.25 The possibility of capitalizing upon the oxidation function of PPD led rubber scientists to experiment with PPD derivatives for use in the automotive tire industry. The secondary amine mixture of PPD derivatives were found to offer effective temperature stability, strength and flexibility, and resistance to oxidation over a wide range of physical conditions.16 By 1971, the tire industry had almost unanimously switched to the secondary amines of PPD, which became referred to as BRM. Table 1 summarizes the chemical components of BRM. Table 2 gives examples of chemicals that cross react (eg, hair dye-PPD) and co-react (eg, rubber accelerators).26
By 1918, half of all carriages on American roads were sporting a most notable innovation: weather-resilient black rubber tires which withstood the forces of oxidation.22 Currently, BRM can be found in various work and home environments including belts, masks, hoses, cables, aprons, flooring, racquet handles and medical and laboratory equipment (Tables 3 and 4).27
Allergies to Black Rubber Mix
ACD to the additives used in the rubber industry was noted as early as the 1943 by W. E. Obetz, who coined the dermatitis “rubber itch” or “rubber poisoning.”28 Prosser White, an occupational dermatologist of the time, named HMT as the most active culprit in the dermatitis. White noted that during the summer months, the slight increase in acidity of workers’ perspiration caused the HMT to release formaldehyde. The oxidation of the formaldehyde to formic acid was thought to be the actual perpetrator of the allergic reaction.28 Unfortunately, because the allergy affected only a small occupationally-based population, the dangers of these chemicals were not widely known by the general public.
Although natural latex rarely causes delayed-type hypersensitivity reactions (Type IV), it has been linked to several life-threatening anaphylaxis reactions (Type I).29 Several papers have been published on latex allergy.30-33 Manufactured rubber, on the other hand, presents the opposite problem of causing a large number of Type IV reactions. Many of the additives including accelerators and activators (vulcanizers), anti-degradants, retardants, reinforcing agents, fillers and pigments have been named as sensitizers.29 It is important to note that these chemicals may become an occupational hazard, affecting both the skin and airway, especially if they are aerosolized during heating and pressurizing.
From1985 to 1990, the North American Contact Dermatitis Group determined the incidence of synthetic rubber allergy to be approximately 4%, with more than 55% of the exposures being from occupational sources (85% secondary to glove use).34 Among those who had a positive patch test to a rubber mix, thiuram mix (62%) and BRM (38%) were the most common culprits.35 The contact sensitization prevalence to BRM in the general population is estimated at 2.1% in men and 1.6% in women.26
In the 1990s, recycled tire shreddings were commonly used as fillers for playgrounds. Reports of shredding-associated carcinogens and increasing allergenic sensitization to BRM led to playgrounds being recovered with other substances.36
Another source of BRM exposure, albeit novel, is in the handrails on escalators. The BRM antioxidant materials in the handrails remain in their raw form and oftentimes not secondarily sealed before shoppers come into contact with them. Contact dermatitis to handrails has been causally linked to unilateral palmar dermatitis in at least 2 cases.37
Practicals of Patch Testing
Patch testing is often necessary to identify the relevant allergen(s) responsible for the patients’ ACD. Screening patch test trays are available to isolate the most common chemicals and offer the provider clues for potential sources. The American Contact Dermatitis Society (ACDS) Core Standard Series includes allergens from several different categories.38 Supplemental trays (such as hairdressing, dental materials, cosmetics and fragrance/flavors) are also available for purchase.26 Notably, the chance of demonstrating a relevant positive reaction is greater when cross-reactors are added to the test.39
Initially pioneered by Bonnevie in 1939, the use of patch test mixes compared to individual elements widened diagnostic abilities within the ACD field.40 Specifically, patch test screening for rubber allergy is recommended to be performed with “mixes” of rubber chemicals, in addition to selected single substances.26,41 In further refinement of rubber patch test mixtures, the individual component amounts were limited to less than 1% (except for carba mix) in order to reduce ICD cases.26
Pearls of Treatment: Every Dose Counts
A person may be exposed to and subsequently sensitized to a particular allergen for days to years before actually developing ACD. Exposures can be additive, eventually causing one’s immune system to become trained to identify a chemical, at which time a cutaneous response would be elicited upon exposure.4 The pathophysiologic trick behind ACD that can also be used as its cure is that just as repeated contact over time leads to an immune response, repeated avoidance over time will induce remission. Avoidance creativity, however, may be necessary by utilizing alternatives and being aware of indirect exposures. For example, patients allergic to BRM commonly have concomitant allergy to PPD.42 Both of these are derived from the same para-aminobenzoic acid (PABA) parent compound, and thus, may also cross-react with the other PABA derivatives such as PABA sunscreens, ester anesthetics, hydrochlorothiazide and sulfonamides.43
There are programs available to aid in the avoidance endeavor. The Contact Allergen Management Program, a service offered through ACDS, and the Contact Allergen Replacement Database, developed by the Mayo Clinic, can assist with identifying allergen-free products.44,45 Both programs allow the provider to personalize “shopping lists” of products void of specific dermatitis-inducing chemicals, as well as any cross-reactors.
Dr. Jacob, the Section Editor of Allergen Focus, is an associate professor, dermatology, director of the Contact Dermatitis Clinic at Loma Linda University in Loma Linda, CA.
Ms. Goldenberg is a medical student at the University of California San Diego in La Jolla, CA.
Disclosure: Dr. Jacob has served as an independent investigator on the safety and efficacy of T.R.U.E. Test™ (Smart Practice; Phoenix, AZ) panels 1.1, 2.1 and 3.1 in children and adolescents, Pediatric Research Equity Act (PREA-1) trial and now serves as an investigator on PREA-2. She has served as a consultant for Johnson & Johnson.
Ms. Goldenberg reports no relevant financial relationships.
1. Bickers DR, Lim HW, Margolis D, et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55(3):490-500.
2. Hsu JW, Matiz C, Jacob SE. Nickel allergy: localized, id, and systemic manifestations in children. Pediatr Dermatol. 2011;28(3):276-280.
3. Salam TN, Fowler JF, Jr. Balsam-related systemic contact dermatitis. J Am Acad Dermatol. 2001;45(3):377-381.
4. Nijhawan RI, Matiz C, Jacob SE. Contact dermatitis: from basics to allergodromes. Pediatr Ann. 2009;38(2):99-108.
5. Militello G, Jacob SE, Crawford GH. Allergic contact dermatitis in children. Curr Opin Pediatr. 2006;18(4):385-390.
6. Valks R, Conde-Salazar L, Cuevas M. Allergic contact urticaria from natural rubber latex in healthcare and non-healthcare workers. Contact Dermatitis. 2004;50(4):222-224.
7. Walsh ML, Smith VH, King CM. Type 1 and type IV hypersensitivity to nickel. Australas J Dermatol. 2010;51(4):285-286.
8. Gimenez-Arnau A, Maurer M, De La Cuadra J, Maibach H. Immediate contact skin reactions, an update of contact urticaria, contact urticaria syndrome and protein contact dermatitis -- “A Never Ending Story.” Eur J Dermatol. 2010;20(5):552-662.
9. Halber D. Rubber processed in ancient Mesoamerica, MIT researchers find. MIT Tech Talk. July 14, 1999. http://web.mit.edu/newsoffice/1999/rubber-0714.html. Accessed December 15, 2014.
10. Treloar LRG. The Physics of Rubber Elasticity. New York, NY: Oxford University Press Inc.; 1975.
11. Crosland M. Priestley Memorial Lecture: A practical perspective on Joseph Priestley as a pneumatic chemist. Br J Hist Sci. 1983;16:223-238.
12. Congo free state, 1885-1908. Yale University Genocide Studies Program website. http://www.yale.edu/gsp/colonial/belgian_congo/. Accessed December 15, 2014.
13. Hendrickson R. Encyclopedia of Word and Phrase Origins. 2nd ed. New York, NY: The Facts On File, Inc.; 1997.
14. Jacob SE, Dimson O. Focus on T.R.U.E. test allergen #24: thiuram. The Dermatologist. 2006;14(2).
15. Jacob SE, Villafradez-Diaz LM. Focus on T.R.U.E. test allergen #15: carbamates. The Dermatologist. 2005;13(10).
16. Jacob SE. Focus on T.R.U.E. test allergen #19 mercaptobenzothiazole & #22 mercapto mix. The Dermatologist. 2006;14(9).
17. Rey J. Essays of Jean Rey, Doctor of Medicine, On an Enquiry into the Cause Wherefore Tin and Lead Increase in Weight on Calcination, 1630 (1895). Whitefish, MT: Kessinger Publishing; 2010.
18. Shampo MA, Kyle RA. Italian physicist-mathematician invents the barometer. Mayo Clin Proc. 1986;61(3):204.
19. McGee, TD. Principles and Methods of Temperature Measurement. Hoboken, NJ: John Wiley & Sons, Inc.; 1988.
20. American Chemical Society International Historic Chemical Landmarks. Discovery of Oxygen by Joseph Priestley. http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/josephpriestleyoxygen.html. Accessed December 15, 2014.
21. Jackson J. A World on Fire: A Heretic, An Aristocrat and the Race to Discover Oxygen. New York, NY: Viking; 2005.
22. The Life of Henry Ford. Henry Ford Museum website. http://www.hfmgv.org/exhibits/hf/. Accessed
December 10, 2014.
23. Nicholas PP, Luxeder AM, Brooks LA, Hammes PA. Antioxidants and antiozonants. In: Kirk-Othmer Encyclopedia of Chemical Technology. Vol. 3, 3rd ed. New York, NY: Wiley-Interscience; 1978.
24. Menné T, White IR, Bruynzeel DP, Dooms-Goossens A. Patch test reactivity to the PPD-black-rubber-mix (industrial rubber chemicals) and individual ingredients. Contact Dermatitis. 1992;26(5):354.
25. Nagan V. Allergy to paraphenylenediamine. DermNet NZ website. www.dermnetnz.org/dermatitis/paraphenylenediamine-allergy.html. Accessed December 15, 2014.
26. Rietschel RL, Fowler JF Jr, eds. Fisher’s Contact Dermatitis. 6th ed. Hamilton, ON: BC Decker Inc; 2008.
27. T.R.U.E. test: black rubber mix. http://www.truetest.com/PatientPDF/Black-Rubber-Mix-Patient-Info.pdf. Accessed December 15, 2014.
28. Schwartz TL, Birmingham DJ. Dermatoses in the manufacture of rubber. In: Occupational Diseases of the Skin. Philadelphia, PA: Lea & Febiger; 1957.
29. Horn HM, Aldridge RD. Contact urticaria due to nitrile gloves. Contact Dermatitis. 2003;49(3):163-164.
30. Cohen DE, Scheman A, Stewart L, et al. American Academy of Dermatology’s position paper on latex allergy. J Am Acad Dermatol. 1998;39(1):98-106.
31. FDA. Allergic reactions to latex-containing medical devices. FDA Med Bull. 1991.
32. Forstrom L. Contact urticaria from latex surgical gloves. Contact Dermatitis. 1980;6(1):33-34.
33. Warshaw EM. Latex allergy. Skinmed. 2003;2(6):359-366.
34. Conde-Salazar L, del-Rio E, Guimaraens D, González Domingo A. Type IV allergy to rubber additives: a 10-year study of 686 cases. J Am Acad Dermatol. 1993;29 (2 Pt 1):176-180.
35. von Hintzenstern J, Heese A, Koch HU, Peters KP, Hornstein OP. Frequency, spectrum and occupational relevance of type IV allergies to rubber chemicals. Contact Dermatitis. 1991;24(4):244-252.
36. Anderson ME, Kirkland KH, Guidotti TL, Rose C. A case study of tire crumb use on playgrounds: risk analysis and communication when major clinical knowledge gaps exist. Environ Health Perspect. 2006;114(1):1-3.
37. Weinberger LN, Seraly MP, Zirwas MJ. Palmar dermatitis due to a rubber escalator railing. Contact Dermatitis. 2006;54(1):59-60.
38. allergEAZE Allergens. allergEAZE website. http://www.allergeaze.com/allergens.aspx?ID=Series. Accessed December 10, 2014.
39. Nijhawan RI, Jacob SE. Patch testing: the whole in addition to the sum of its parts is greatest. Dermatitis. 2009;20(1):58-59.
40. Bonnevie P. Aetiologie and Pathogenese der Ekzemkrankheiten. Leipzig, Barth. 1981.
41. Marks JG, Jr, Belsito DV, DeLeo VA, et al. North American Contact Dermatitis Group patch-test results, 1998 to 2000. Am J Contact Dermat. 2003;14(2):59-62.
42. Feinman SE. Sensitivity to rubber chemicals. J Toxicol Cutan Ocul Toxicol. 1987;6(2):117-153.
43. Jacob SE, Steele T. How to increase your patch testing efficacy. The Dermatologist. 2006;14(5):34-44.
44. ACDS CAMP. American Contact Dermatitis Society website. http://www.contactderm.org/i4a/pages/index.cfm?pageID=3489. Accessed December 15, 2014.
45. CARD: Contact Allergen Replacement Database. https://card.preventice.com/. Accessed December 15, 2014.