The New View on Latex Allergies

When latex allergies first became prevalent in the early 1990s, there were many misconceptions about what actually defined an allergy. Many healthcare workers (HCWs) who assumed they were allergic to latex actually had developed irritant contact dermatitis, not a true allergy.

“The emergence of latex protein allergy in the late 1980s and early 1990s — reported to have affected 3 percent to 16 percent of HCWs and about 1 percent of the general population¹ — has indeed caused much concern,” says Esah Yip, PhD, director of the Malaysian Rubber Export Promotion Council based in Washington, D.C.

“Because latex protein allergy is brought about by the presence of excessive residual soluble proteins found in some latex gloves, a number of non-latex or synthetic alternatives have since become available in the marketplace,” Yip says. “These include those made of vinyl (PVC), nitrile, polychloroprene, and other materials. While these synthetic gloves may not contain any plant proteins such as those found in natural rubber latex gloves, it is important for users to exercise caution when selecting gloves. They should be made aware of the following information:

Barrier protection against viral/bacterial transmission and other harmful infectious materials is the key reason for wearing gloves.

Comfort, fit and tactile sensitivity are important characteristics of glove use in healthcare settings. Failure of a glove to provide these could lead to early fatigue during use, hampering how medical procedures are carried out, and compromising barrier protection.

Cost — Synthetic gloves, which are derived from petrol chemicals, are generally more costly than latex gloves, with the exception of vinyl.

Environmental impact — Synthetic gloves are generally not biodegradable. Their disposal by burning often releases harmful substances. Latex gloves are derived from natural rubber latex, a plant material, and are biodegradable.”

New technologies are now being used with natural rubber latex to reduce the possibility of the development of allergic reactions to the latex. “Manufacturers, using improved technologies, now can produce latex gloves with significantly reduced amounts of residual soluble proteins. Today’s latex gloves can have protein content as low as 50 micrograms/ square decimeter and below, compared to levels that were sometimes more than 1,000 micrograms in the earlier generation of gloves. Clinical studies have indicated that gloves with such low protein levels have also low allergen content — markedly reduced allergenicity,” Yip explains.²

Research has shown that these “upgrades” can dramatically reduce the number of allergic or sensitivity reactions. “A number of independent hospital studies recently in the United States, Canada, Germany,⁴ and Finland demonstrate that wearing low-protein, low- or non-powdered latex gloves greatly diminishes the risk of allergic reactions and the likelihood of healthcare workers developing latex sensitivity,” she adds. “More importantly, the studies also show that latexallergic individuals wearing synthetic gloves can work alongside their co-workers using low-protein latex gloves and suffer no ill effects.”^3-11

Low-protein latex gloves “are clearly an appropriate choice for the non-allergic majority. However, there is currently no glove regulatory requirement for protein and powder, making it difficult for healthcare workers and clinicians to be certain that the gloves they buy are indeed low-protein,” Yip points out.

Malaysia, the major glove supplier to the United States, has recently developed the Standard Malaysian Glove (SMG) Program, which ensures the manufacture of quality low-protein gloves that are not only high in barrier protection, but also low in allergy risk. “The program was formulated in consultation with a number of relevant authorities such the Food and Drug Administration. SMG-certified gloves have to meet very stringent technical requirements, including strictly controlled low limits for residual extractable proteins and powder,” she adds.

Diane Sosovec, RN, MS, CNAA, manager of clinical resources for Cardinal Health, was first hired to educate Cardinal’s customers about latex sensitivities and allergies. “My focus was trying to help our customers understand what latex allergies and sensitivities were, vs. what they weren’t,” she says.

“Back then was when universal precautions and the Occupational Safety and Health Administration (OSHA)’s bloodborne pathogens standard hit the scene, and we had all these HCWs who previously had not worn gloves, who were now expected to wear gloves to comply with standards. All of a sudden we started to have HCWs reporting issues with their hands.

“Unfortunately, most of the folks out there equated the reactions on their hands to latex sensitivities and allergies, when in fact the overwhelming reactions weren’t latex allergies,” she explains. “It was irritant contact dermatitis due to wearing gloves, washing their hands, not taking care of their hands appropriately, not using moisturizers and lotions, etc. At that time, many research articles being published were talking about sensitization rates of HCWs, just throwing these numbers out there based on very limited studies. Also at that time, the healthcare community was looking at these numbers, not understanding that latex sensitization didn’t necessarily mean you had a latex allergy. The actual numbers of sensitized individuals who had a true clinical allergic reaction to a natural rubber product was significantly smaller. I’m not trying to minimize this, because true latex allergy reactions can be very serious, even life-threatening, but it’s not any more or less serious than any other type of protein allergic reaction. I was focusing attention on what the real issues were of HCWs: dry skin, irritant contact dermatitis, and non-latex alternatives for people who have issues with latex gloves.”

For examination gloves, the alternatives are vinyl and nitrile. However, concern for the cost of synthetics may lead purchasers to choose a product that is not always appropriate. “In some healthcare facilities that have decided to go synthetic with their exam gloves, because of the cost of the two products, they’re trying to get clinicians to use vinyl for the most part, when in fact, it’s not an appropriate barrier. You can’t necessarily substitute vinyl for nitrile rubber, because it doesn’t have the same barrier properties. Vinyl synthetic exam gloves are made of plasticizers, plastisols, which means they may fracture or tear more easily; they are not manufactured to the same standard because it’s not the same material. Nitrile is the preferred synthetic option in exam gloves because the material it is made out of is more durable, it has more strength, and it is more resistant to chemicals,” Sosovec points out.

Is it possible to use any low-protein rubber latex gloves for latex-allergic individuals? “If you have a true allergic reaction to natural rubber, no matter what the natural rubber product is, even the lowest protein allergen product is still not safe for you,” Sosovec says. “Everyone has differences in their sensitization rate, their allergic reaction rate, so what may be safe for me if I have a mild sensitivity may not necessarily be a safe option for someone with a severe allergic reaction. There’s only one safe option for a natural rubber latex allergic person, and that is no natural rubber.”

She adds that when these issues surfaced more than a decade ago, many tried to make it a “glove issue” rather than remembering that latex appears in many more products. “There are 40,000 natural rubber latex products out there,” she points out. “Let’s not forget condoms and diaphragms, which have been used for decades by millions of people, and if all of a sudden there were these issues with natural rubber latex allergies, I think we would have seen it before the glove issue.

“With the influx of gloves, clinicians weren’t aware of the fact that it made a difference how you wore the gloves, how long you wore them, and if you were washing your hands before and after, if you were using lotions and moisturizers. You had this group of HCWs who previously weren’t wearing gloves, who were now wearing 10, 20, 30, 40 pairs of gloves a day, on top of washing their hands before and after glove removal.

Quite frankly, who wouldn’t have an irritation or a contact dermatitis with their hands? But back then, it wasn’t understood as it is today. Also, back then, the examination gloves for the most part were powdered gloves, and the powder could be a source of irritation.”

As for surgical gloves, the preferred material is still natural rubber latex, due to its tactile sensitivity and manual dexterity. “In the past, there was this belief that the more exposure there is, the higher the probability that you’ll develop a sensitization or allergy,” Sosovec adds. “When I lecture — I may have an audience of 100 to 150 people — I ask them, ‘How many of you eat fruits and vegetables?’ Everybody raises their hand. I ask all who raised their hands, ‘How many of you have been eating them all your life?’ Everybody raises their hand. I ask, ‘How many of you have an allergy to a fruit or vegetable?” Usually, in an audience of 100 people, I might have one or two raise their hand.

“The protein allergens in fruits and vegetables aren’t any different from the protein allergens in natural rubber. If you’re genetically predisposed, if you have a history of other allergies, if you are a clinically reactive person, that’s what is going to put you at risk. It’s not a cumulative effect. If it were true, what about all of these millions of condoms and diaphragms that are being used? Some of these beliefs out there have really not been accurate. They’ve been perceptions, not realities.”

One of the other misconceptions is that HCWs — because they had worn latex gloves for all these years — were at higher risk for latex sensitization. “That’s been disproved as well,” she says. “The reports in early research were not necessarily reporting results based on skin prick tests and serum tests. They had been done based on simple surveys, reports, individual assessments not necessarily made by an allergist. They were done based on seeing someone’s hands, or anecdotal information. I’ve never seen a study that actually quantifies true latex allergies. Sensitization rates, yes, but not true allergic reactions and allergies.”

For surgical gloves, the most popular alternatives to latex are neoprene and synthetic polyisoprene. “From an end-user perspective, I would have to say the preferred is the synthetic polyisoprene, because it has all of the attributes and physical characteristics and performance standards that natural rubber has, so it’s natural rubber without the protein allergens.”

Little new research has been done recently into latex allergies, because many of the earlier misconceptions have been cleared up. “There isn’t that much talk about it anymore; it has waned in its popularity because people have gotten their arms around it and they are dealing with it just like with any other allergy,” Sosovec says.

Non-Synthetic Alternatives

Of new interest to HCWs is guayule (pronounced “why-YOU-lee”), a desert plant that produces a different type of rubber, one that does not contain the tropical proteins found in rubber from Hevea brasiliensis, known as the “rubber tree.”

“Those proteins that are problematic in regular rubber latex are not there in the first place (in guayule),” says Katrina Cornish, PhD, senior vice president of research and development for Yulex Corporation. Cornish, a former USDA research scientist, developed the guayule processing technology now being commercialized by Yulex.

“Quite a large number of species make natural rubber, but apart from H. Brasiliensis, guayule is the only other one in commercial production. The proteins in Hevea latex are all different from the proteins in guayule latex,” she explains. “The plants are very distantly related; each of them is in a different superorder of the Dicotyledonous class. Those are broad-leaf flowering plants. They’re about as distantly related as they can be and still be a flowering plant. Guayule is actually in the sunflower family.”

Guayule is different from most rubber-producing species in that it produces rubber in particles, which are tiny balls of rubber in the cytoplasm of cells in the bark. Other rubberproducing species produce it in latex vessels, pipelike tubes that run inside the bark of plants. “You can cut into those plants and the rubber would bleed out like a milky liquid. With guayule, they’re in individual cells, so if you cut into a guayule plant, nothing happens. You don’t see anything bleed out. However, you can grind up the plant and release all those rubber particles into the liquid and then purify them, and then you get, in effect, an artificially produced natural rubber latex emulsion that you can then use in the same manufacturing processes you would use as any other latex for,” she adds.

“You get this very low-protein material, and none of those proteins cross-react with type 1 latex allergy. The low protein nature of the material means it’s unlikely to cause an allergy in its turn, because it’s lower than the amount that well-leached Hevea products had for many decades when they weren’t causing a problem, and the fact that it doesn’t cross-react means it can safely be used by somebody who’s got the allergy, much the same way that the synthetics can be.”

Unlike the synthetics, however, guayule actually has higher performance properties, because it does have the performance properties of natural rubber materials, Cornish explains.

Yulex worked in concert with several hospitals, including Johns Hopkins, to study the effect of guayule in latex-allergic individuals. “We’ve done studies with hundreds of type 1 latex allergic people, including testing their sera, but also some skin prick tests, and with adult HCWs, spine bifida children, and other people with latex allergies. We’ve not had any cases of cross-reaction with guayule latex materials.”

The results of another clinical laboratory study — using serum pools from individuals suffering from life-threatening type I tropical latex allergy — indicate no detectable allergic reaction to commercial grade natural rubber latex derived from guayule.

Immunologist Robert G. Hamilton, PhD, professor of medicine and pathology at Johns Hopkins University School of Medicine in Baltimore, presented the results during the 2005 annual meeting of the American Academy of Allergy, Asthma and Immunology in San Antonio, Texas.

These results indicate that proteins present in production lots of guayule latex are not cross-reactive with Hevea brasiliensis latex allergens. This suggests that devices manufactured with guayule latex as an alternative rubber source should be safe for use by H. brasiliensis latex-allergic individuals, reported Hamilton at the conference.

The study determined the level of allergenic protein with the CAP inhibition assay. Researchers used serum containing IgE antibodies from two groups of individuals allergic to products made of tropical latex from the tropical rubber tree, H. brasiliensis. The guayule materials showed the same negative results as the neoprene synthetic latex material control group. However, the Hevea-based gloves showed significant levels of allergenic protein.

New Alternatives to Old Standards

Ansell Healthcare Products has a continually expanding collection of both latex and latexfree examination gloves. The Micro-Touch® Nitrile E.P.® is a textured, all nitrile, powder-free examination glove. The glove is FDA-approved for handling chemotherapy drugs and provides excellent chemical and puncture resistance, and offers an extended cuff for extra protection over the wrist and arm.

Ansell also offers the Affinity®, a textured, latex-free (polychloroprene), powder-free examination glove that is designed to provide the fit and feel of latex. There is the Elite®, a soft-stretch, latex-free (polyvinyl chloride), powder-free examination glove for low-risk applications. There is the ErgoGrip™, a handspecific latex, powder-free examination glove with polymer coating for ease of donning. The NextStep® is a textured latex, powderfree examination glove with glycerol that is designed to provide superior tactile sensitivity, fit, and comfort. And the Micro-Touch® Plus is another textured, latex, powder-free examination glove with polymer coating for ease of donning.

Regent Medical offers a deproteinised natural rubber latex surgical glove. The latex, powder-free Biogel Eclipse™ is made from highly-refined deproteinised natural rubber latex. Deproteinised natural rubber latex is the finished product of a patented process that reduces extractable latex proteins in the raw material by 90 percent.12 According to the Leap Testing Service at the Guthrie Foundation for Education and Research, the levels of extractable latex protein are below detection levels in the finished gloves.¹³ The new glove category also represents a costeffective safety option for facilities wanting to reduce exposure of healthcare workers and patients to antigenic proteins found in standard latex surgical gloves without having to incur the higher cost of non-latex gloves for those not sensitized to latex proteins.

The Science Behind Improvements

In 2004, a review of natural rubber latex allergy in healthcare workers was done by Peter M. Ranta, MD, and Dennis R. Ownby, MD of the departments of pediatrics and internal medicine in the section of allergyimmunology at the Medical College of Georgia in Augusta.¹⁴

The use of latex, they point out, has been documented back to 1600 B.C. However, it was not until 1979 that the first clear description of immediate-type hypersensitivity — a type 1 allergy — was published. A “plague” of latex allergies increased and then peaked in the mid-1990s, but their incidence has decreased ever since. The authors attribute this decrease to adoption of low-allergen, powder-free latex gloves.

“Latex gloves are associated with three types of adverse reactions: irritant contact dermatitis, immediate-type (type 1) allergic reactions, and allergic contact dermatitis (type IV or delayed-type hypersensitivity reactions),” the authors write. Type 1 reactions are the only responses that can be general rather than local responses.

Reported occurrence of type 1 sensitivity has ranged from 2.9 percent to 12.1 percent, the authors add. However, they note, “latexallergic healthcare workers who carefully avoid latex exposure have been observed to gradually lose their sensitivity.” But there is still a risk of re-sensitization if they are re-exposed to latex.

Once a healthcare worker develops an allergy to latex, the costs attributed to the disability can be enormous. The authors reference another study that attests to these increased expenses, saying, “Tyler reports that the average cost of lost work time due to disability from latex allergy was $38,077 per case in 1996 in a Michigan healthcare organization; during the same year, the average cost of non-lost time associated with latex allergy was $219 per case.” They define “non-lost work time” as medical expenses paid.

They then question the cost efficacy of switching to latex-free gloves. “Phillips et al did a cost analysis in Georgia in 1999 of three types of medical care settings: a tertiary care hospital, a community hospital, and a large internal medicine clinic. According to their estimates, the annual cost of switching to latex-free gloves was $515,789, $117,468, and $48 per facility, respectively … if greater than 1 percent of workers become fully disabled, or if greater than 2 percent become partially disabled, these authors conclude that it would be cost-effective for a tertiary-care facility to switch to latex-free gloves.”

However, a complete switch to latex-free is not always necessary; “The Mayo Clinic reported a cost saving of $200,000 per year with a switch to low-allergen, powder-free latex gloves; similarly, a Canadian teaching hospital in Ontario reported no increase in cost with this approach as a result of consolidated glove purchases,” they add.

“Reduction of exposure to latex is a safe and more economical alternative to complete removal from the place of employment,” they conclude.

Travis W. Honeycutt, the founder and chairman of Vystar Corporation, presented a paper at the Latex 2006 conference in Frankfurt, Germany, describing the technological and physical properties of a new, low-antigenic protein natural rubber latex.15

The paper describes a unique method of lessening the impact of normal levels of antigenic proteins, while not negatively impacting the necessary chemical and physical properties of the latex.

“Vystar Corporation has developed a novel, patented method for the deactivation of the antigenic protein (AP) in liquid natural rubber latex (NRL) that involves the denaturing of these proteins. This new, patented method for fixing the protein problem results in equal or slightly improved chemical and physician properties in NRL, thus allowing a seamless transition for manufacturers using the current commercially available product. Of particular interest is that the low-antigenic NRL appears to have a slightly reduced initial modulus when compared to untreated NRL. A reduced initial modulus translates into greatly reduced fatigue for items such as surgeon’s gloves or examination gloves that are worn for a considerable period of time,” the authors write.

The method involves treating the NRL in the liquid phase with selected inorganic chemicals, which include AI(OH)3 and SiO2 as alkali solutions, before vulcanization. The resultant product has been trademarked as Vytex™ by Vystar.

Glove leakage tests performed on Vytex revealed that gloves made with anti-protein additives had better liquid barrier protection as compared to untreated latex gloves. Of note, a “defined concentration” of anti-protein additives is necessary to maintain the desirable physical properties of products made from natural rubber latex. “Some parameters, such as tensile strength, ultimate elongation, and resistance against aging are increased when the amount of anti-protein additives in NRL was increased within a certain range,” the authors write. “Exceeding the desired concentration amount will result in a deterioration of the mechanical properties of latex products.”

The addition of alkali solution of aluminum hydroxide or silicon oxide to liquid latex “allows the production of high-quality products from new low-protein latex without changing existing technology,” the authors conclude. “Antiprotein additives increase the elasticity and strength of the latex films if concentrations of these additives are not exceeded. Removal of the antigenic protein occurs at sub-critical concentrations of anti-protein additives. Simultaneously, the barrier properties and resistance against aging of latex products with these additives are not only maintained, but also essentially improved.”

By Kathy Dix

References
1. Based on ASTM D6499-03 Inhibition ELISA Assay. Testing conducted at Guthrie Foundation for Education and Research, LEAP Testing Service, February 2005. Detection limit 0.2Êg/g.

2. Ibid.

3. Liss GM, Sussman GL. Latex Sensitization: Occupational versus general population prevalence rates. Am. J. Ind. Med 1999; 35: 196-200.

4. Yip E, Cacioli P. The manufacture of gloves from natural rubber latex. J Allergy Clin Immunol. 2002; 110: S3-14.

5. Tarlo SM et. al. University of Toronto, J Allergy Clin Immunol. 2001; 108: 628.633;

6. Rueff F. et. al. Dermatologie & Allergologie, University of Ludwig- Maximillians, Munich, Germany, AAAAI meeting, 2000;

7. Hunt, LW. et. al. Mayo Clinic, J Allergy Clin Immunol. 2002; 110: S94-106;

8. Allmers H. et. al. Germany, J Allergy Clin Immunol. 2002; 110(2):318-323;

9. Turjanmaa C. et. al. Finland, J Allergy Clin Immunol. 2002; 110:S70-74.

10. Allmers H. et. al. Germany. J Allergy Clin Immunol. 1998; 102:841-846;

11. Kelly KJ, et. al. Wisconsin, U.S.A. J Allergy Clin Immunol. 2003; 3(2), #2, #426.

12. Allmers H. et. al. AAAAI meeting 2004, Abstract # 138;

13. Renuala T. et. al. AAAAI meeting 2004, Abstract # 140.

14. Ranta PM and Ownby DR. A Review of Natural-Rubber Latex Allergy in Health Care Workers. Clin Infect Diseases 2004;38:252-6.

15. Honeycutt T, et al. Technological and Physical Properties of a New, Low Antigenic Protein Natural Rubber Latex. Latex 2006; January 24-25, 2006. Frankfurt, Germany.

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