Latex Free Claims: A White Paper on the Risks Associated with Latex Allergies and Latex in Healthcare Brought to you by: Allergy and Asthma Network: Sue Lockwood and Robert Hamilton, M.S., Ph.D. Avella Specialty Pharmacy: Eric Sredzinski, Pharm.D., AAHIVP and Jenna Vaughn, Pharm.D., PGY1
Executive Summary There is significant confusion as to the meaning of latex free in healthcare. The FDA has urged manufacturers to drop the term latex free or a does not contain latex claim from labels because of the challenge to ensure a product is completely devoid of natural rubber latex proteins which cause the allergic reactions. While there are no regulations requiring the labeling of a medical product to state natural rubber latex was not used as a material in the manufacturing process, the terms latex free or does not contain latex are used too broadly. According to the FDA, these labeling techniques are not sufficiently specific, not necessarily scientifically accurate, and may be misunderstood and applied too widely. On December 2, 2014, the FDA released the final latex guidance document [https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/ GuidanceDocuments/UCM342872.pdf] advising firms to use not made with natural rubber latex if no natural (Hevea brasiliensis) rubber latex was used in the manufacturing process. Not all types of latex are from natural rubber latex; for example, products that contain nitrile and polyvinyl chloride, will not cause a natural rubber latex allergy because these are synthetic formulations. In 2012, The Journal of Investigational Allergology and Clinical Immunology published a position paper on latex allergy that provides a comprehensive review on latex allergy and reviews processes to identify and manage patients with latex allergies. To best protect patients with a suspected but unverified latex allergy, a detailed patient history on past exposures and reactions must be obtained and documented. For patients with a known latex allergy, any products containing natural rubber latex must be avoided. However, it may be impossible to be 100% confident that a complete natural rubber latex environment can be achieved. Label confusion continues and understanding the labeling techniques as well as the FDA guidance document is key to be informed. If there is a question on the potential natural latex content of a product, the primary vendor or supplier should be contacted for additional information. On December 2, 2014, the FDA released the final latex guidance document advising firms to use "not made with natural rubber latex" if no natural (Hevea brasiliensis) rubber latex was used in the manufacturing process 2
Purpose The purpose of this white paper is to educate those involved in healthcare about important issues relating to the use of Hevea brasiliensis latex, latex allergies, and available alternatives. Introduction Latex as raw, natural rubber is harvested from the milky sap of the rubber tree, Hevea brasilienesis, which is principally grown throughout Indonesia, Thailand and Vietnam (2). Latex in its raw form contains 60 polypeptides proteins that have been identified as potentially allergenic, 15 of which are principal allergens (7, Table 1). Hevea latex has become prevalent in modern society because of its resistance to chemicals, elasticity, comfort, ease of manufacturing, and low cost. Due to these benefits, thousands of products contain natural rubber latex and most have the potential to trigger an allergic reaction (Table 2). Latex-caused allergic reactions, seen both in the general population and healthcare workers, are a serious medical concern. The risk of developing a latex allergy increases with repeat exposure and 8 12% of healthcare workers reportedly have developed a sensitivity to natural rubber latex compared to 1 6% of the general population (7). Steps must be taken to ensure that the risk of an allergic reaction is kept at a minimum, and the use of synthetic latex and other alternatives should be considered when feasible. Table 1 Latex Allergens Allergen Hev b 1 and 3 Properties Main allergen in spina bifida patients The risk of developing a latex allergy increases with repeat exposure and 8 12% of healthcare workers reportedly have developed a sensitivity to natural rubber latex compared to 1 6% of the general population Hev b 5 and 6 Hev b 2, 4, 7, and 13 Hev b 6.02 and 7 Hev b 8, 11, and 12 Main allergen in healthcare workers Secondary allergen in healthcare workers Seen in allergen cross-reactivity with fruits Panallergens with unknown cross-reactivity with fruits Table 2 Latex: Common and Medical Common Items Containing Hevea Latex Healthcare Items Containing Hevea Latex Balloons Catheters Compression Stockings Condoms Syringes Stethoscopes Toys Vial Stoppers Masks Erasers Bandages Tape Rubber Bands Gloves Adhesives Sports Balls (Tennis, Basketball) Blood Pressure Cuffs Injection Ports Therapy Bands Rubber Accelerators Electrode Pads Elastic 3
Latex Allergies In the late 1980s, universal precautions in healthcare were introduced to prevent the spread of HIV. The use of latex gloves and other protective devices also increased, leading to an explosion of allergies of epidemic proportions. Healthcare workers are naturally at a greater risk for developing latex allergies due to repeat exposure to latex-containing gloves and medical equipment. However, after peaking in the mid-1990s, latex allergies have been on the decline with the increased use of synthetic substitutes and increased awareness of the risks associated with latex. The allergenic proteins found within the latex of natural rubber and the chemicals added in the manufacturing process can lead to three types of adverse effects: irritant contact dermatitis, allergic contact dermatitis, and immediate-type allergic reactions (4, Table 3). Irritant contact dermatitis is a non-allergic, localized inflammation of the skin caused by chemical irritation and not by latex allergens. Allergic contact dermatitis, known as type IV hypersensitivity, is limited to the skin and is a T-cell mediated reaction to chemicals added during production. Irritant contact dermatitis and type IV reactions are both marked by redness, lesions, or itching, which weakens the skin barrier and allows allergens easy access into the body. Immediate-type allergic reactions, known as type I hypersensitivities, are mediated by the Hevea latex-specific IgE antibodies in response to exposure to latex proteins. These can be deadly, with a 1% lethality rate. Type I reactions are caused by the release of histamine and leukotrienes from mast cells. Symptoms include: itching, papules, angioedema, asthma, and anaphylaxis (5). Table 3 Reactions to Latex Reaction Type Symptoms Cause Time of Onset Immediate hypersensitivity (Type I) Urticaria (hives), nausea, vomiting, rhinitis, conjunctivitis, bronchospasms, and anaphylactic shock Latex allergens -15 known types Immediate and within minutes Allergic contact dermatitis (Type IV) Rash, itching, vesicles, redness, and blisters Chemicals/rubber accelerators in latex Delayed, takes up to 48 hours after contact Irritant contact dermatitis Dry, cracked, red, and irritated skin Chemicals/rubber accelerators in latex Gradual and over several days Routine testing of all patients and healthcare workers who are at risk or suspected of having a latex allergy is essential to preventing a reaction. Latex allergy testing includes the patch test, skin prick, intradermal test, IgE antibody immunoassays, and a use (glove application challenge) test (1). The patch test is used to detect irritant contact dermatitis in patients and involves placing a patch with latex chemicals on a patient s skin for 2-3 days. The puncture/prick skin test looks for type I reactions; to perform it, a drop of latex extract is scratched into a patient s skin. An intradermal test is similar to a prick test as a latex solution is inserted into the skin and the patient is observed for a type I reaction. Intradermal tests must be performed cautiously as they generate higher levels of allergic reactions and have the potential to trigger anaphylaxis. Importantly, neither a puncture nor 4
intradermal skin test can be performed in the United States due to an absence of an FDA-cleared Hevea latex skin testing reagent. Thus, IgE immunoassays that are used to detect the presence of Hevea latex specific-ige antibodies in a patient s serum are the only confirmatory test available at present in the USA. However, latex skin test reagents are available elsewhere in the world. If a serological assay for IgE antibody is negative but the patient has reported symptoms of a latex allergy, then a simple use test may be cautiously performed. With a use test, the fingertip of a latex glove is dampened and then placed upon a patient s hand for 15 minutes. If the patient does not react to the fingertip, then the entire dampened latex glove is placed on the patient for another 15 minutes and they are observed for a reaction. The efficacy of this use test is highly dependent on the Hevea latex content in the glove used for the evaluation. Latex skin prick testing through a glove is NOT recommended in the United States, due to many reported adverse reactions. So, physicians must rely on clinical judgement and by obtaining an individual s history, including association between latex exposure and the development of symptoms. If a patient begins to show signs or symptoms of a natural rubber latex allergy, then swift action is important to preventing further injury (1). For an irritant or allergic contact dermatitis reaction, washing the area with soap and water will quickly remove the allergen. If the rash is significant, the next step is to apply topical corticosteroids or hydrating creams to ease pain, inflammation, and itching. Dangerous type I reactions require immediate attention by removing the individual from the offending substance, washing the area of contact, monitoring vital signs, and administering emergency treatment if needed. Medications that may be used during an allergic reaction are antihistamines for mild to moderate symptoms, oral or topical steroids, and epinephrine for reversing the severe symptoms of anaphylaxis. Multiple routes of latex exposure can trigger a reaction, such as contact with the body s mucous membrane, skin, open wounds, surgical or IV exposure, and inhalation of latex proteins. Cornstarch, a common ingredient in powdered latex gloves, binds latex proteins and allows the resulting powder to become aerosolized in a room, triggering inhalation-related allergic responses (5). The accelerator chemicals used in latex production, frequent handwashing, soaps, and detergents can further irritate the hands of healthcare workers and increases the risk of an allergic reaction. Certain high-risk populations require extra precautions in healthcare settings to prevent latex exposure (7, Table 4). Spina bifida patients are at a particularly high risk, as they require multiple surgeries throughout their life. Historically 12-73% developed latex allergies, especially during the peak epidemic of latex allergen exposure In the 1990s (1). Patients who have food allergies to bananas, avocados or kiwi fruit are at risk as well due to cross-reactivity between IgE antibodies. Healthcare workers who have constant exposure to latex gloves and other forms of equipment are at risk, although this has decreased in recent years with the rise of synthetic latex products. Importantly, neither a puncture nor intradermal skin test can be performed in the United States due to an absence of an FDA-cleared Hevea latex skin testing reagent 5
Table 4 Latex Allergies Among High Risk Populations with High Latex Exposure Latex Allergy Population Patients Country Year Reported 11.4% Elderly Patients 88 Italy 2014 46% Spina Bifida Patients 35 Singapore 2013 20% Myelomeningocele Patients 55 Brazil 2013 4% Healthcare Students 619 Italy 2015 13.3% Healthcare Workers 4529 Thailand 2014 18% Nurses 899 Thailand 2013 5% Healthcare Workers 804 USA 2012 Latex and Synthetic Use in a Healthcare Setting The only way to decrease the risk of developing an allergic reaction is to prevent exposure, as there is no cure for latex sensitivity. When working with patients who have latex allergies, healthcare personnel must make efforts to ensure a latex-safe environment prior to visits. Scheduling the patient to have the first appointment of the day reduces the risk of latex exposure, as does removing latex-containing supplies from the room (4). Unfortunately, due to the nature of latex, it is often difficult to eliminate all traces from a product or location. On December 2, 2014, the FDA issued a document to guide healthcare facilities in labeling their items with regards to latex use (6). This document applies to all FDA regulated medical products where natural rubber latex or synthetic derivatives of natural rubber latex were not used as materials in their manufacture; or any container and/or packaging that was not made with natural rubber latex or synthetic derivatives of natural rubber latex. The FDA issued this guidance document in part because healthcare facilities were labeling their products with statements such as latex free, does not contain natural rubber latex, or does not contain latex. These statements are false and misleading, as there are no analytical methods to identify all the proteins and chemicals in latex that may trigger an allergic reaction. Instead, the FDA recommends that healthcare facilities use terminology such as not made with natural rubber latex. In certain situations, only part of the product may not have been made with Hevea rubber latex and should include more specific labels such as the <vial stopper> is not made with natural rubber latex. There are no analytical methods to identify all the proteins and chemicals in latex that may trigger an allergic reaction To create a latex-safe environment, healthcare facilities should use synthetic latex alternatives to prevent contamination of equipment, rooms and clothing. Sometimes contact with latex is unavoidable, as is often seen with medical necessities, such as vials containing natural rubber latex 6
stoppers (3). In 1997, latex stoppers were deemed by the FDA to pose no significant risk for individuals with latex sensitivity based on testing using the Lowry assay. However, it has been subsequently determined that the Lowry assay is not sensitive enough to detect low levels of latex allergens within vial stoppers. Due to this, many hospitals began to pop the top of vial stoppers prior to use to avoid latex contamination. The problem with this method is that it is possible that latex leaches from vial stoppers into the medication and the open top exposes the contents to microbial contamination. In an attempt to limit latex exposure, some hospitals initiated a single stick rule, with a single stick allowed per stopper to maintain a closed system environment for the medication and theoretically limit latex leaching. To date, there are few studies available to determine whether latex allergen risk is significantly lowered by either the pop the top technique or the, single stick rule with latex-topped vials. It is up to the individual organization to determine which method they would prefer, noting that the American Association of Nurse Anesthetists employs the pop the top method for at-risk patients and the American Academy of Allergy Asthma and Immunology suggests the single stick rule. Synthetic polymers such as neoprene, polyisoprene, butadiene, and elastiprene gloves are all recommended for surgical procedures, but are expensive A 2005 masked prospective clinical study by Hamilton et al. explores the use of the single stick rule. This study used 5 different types of vial stoppers, ranging from synthetic to full latex, punctured 1-40 times (3). The study involved 23 patients, 12 of whom had confirmed latex allergies, and all had received puncture and intradermal skin tests with solutions from Hevea latex-stoppered vials. Of the 12 latex-sensitive patients, two had reactions to the one puncture stoppers, and five reacted to the 40 puncture stoppers. Based on these results, Hamilton recommends that healthcare facilities employ the single stick rule when dealing with latex-containing stoppers and to take special precautions in high risk individuals. Latex gloves are another source of allergens and are amongst the most common triggers for allergic reactions in both patient and healthcare worker alike. Since the 1990s, several synthetic alternatives to latex gloves have been created, such as neoprene, polyvinyl chloride, silicone, and polyurethane (2). However, not all gloves used in healthcare are made equally with regards to cost, comfort, use, or protection. Vinyl gloves have not been found to have the same barrier quality as latex and may have a decreased protection against infective agents. Nitrile gloves offer similar levels of protection and infection resistance when compared to latex. Synthetic polymers such as neoprene, polyisoprene, butadiene, and elastiprene gloves are all recommended for surgical procedures, but are expensive. While each type of synthetic glove differs with regard to both strengths and weaknesses, all have the benefit of not containing latex. Other types of gloves contain low levels of latex allergens, have a reduced risk for triggering a reaction, and are powder free to prevent inhalation. Allergies among healthcare workers have been decreasing around the world since their peak in the 1990s thanks to the availability of latex alternatives. Multiple studies have also shown a reduction in latex sensitivity with the reduced use of latex (5). A 2002 study from the Mayo Clinic shows a significant A 2002 study from the Mayo Clinic shows a significant decrease in latex allergies from 150 cases per 100,000 healthcare workers to a mere 27 cases since 1993 7
decrease in latex allergies from 150 cases per 100,000 healthcare workers to a mere 27 cases since 1993. A study of seven German hospitals noted a similar outcome, with a decrease of 68 cases of latex allergies per 100,000 healthcare workers to 21 cases since 1998. With the rise of latex alternative products, healthcare facilities are now more capable than ever to develop the latex safe protocol necessary to protect both employees and patients. Table 5 includes a list of websites that offer the first steps towards reducing the risk of latex allergies with topics including current clinical management, educational resources, and available alternative products (1, Table 5). Table 5 Latex Alternative Resources and Information Organization Information Website Allergy & Asthma Network (AAN) American Academy of Allergy Asthma & Immunology Latex allergy educational resources Latex alternatives for both consumers and healthcare facilities Allergy information and protocol http://www.allergyasthmanetwork.org http://www.aaaai.org/ American Association of Nurse Anesthetists (AANA) American College of Allergy, Asthma & Immunology (ACAAI) Guidelines for latex allergy management Guidelines for the management of latex allergies and safe latex use in health care facilities (Sussman &, Gold) http://www.aana.com/resources2/ professionalpractice/pages/latex- Allergy-Protocol.aspx http://acaai.org/ Conclusions To best protect patients with an unknown natural latex allergy, a detailed patient history on past exposures and reactions must be obtained and documented. When working with patients who have latex allergies, healthcare personnel must make efforts to ensure a latex-safe environment prior to visits. Hospitals and pharmacy facilities should consider adopting the single stick rule with latex-stoppered vials to lower the risk of latex allergen exposure for employees and patients. Resources 1. Binkley, Helen M., Traci Schroyer, and Jennifer Catalfano. Latex Allergies: A Review of Recognition, Evaluation, Management, Prevention, Education, and Alternative Product Use. Journal of Athletic Training 38.2 (2003): 133-40. PubMed. Web. 24 Feb. 2017. 2. Cabanes, N., J. M. Igea, and B. Hoz. Latex Allergy: Position Paper. J Investig Allergol Clin Immunol 22.5 (2012): 313-30. Web. 21 Feb. 2017. 3. Hamilton, Robert G., et al,. Administering pharmaceuticals to altexallergic patients from vials containing natural rubber latex closures. Am J Health-Syst Pharm 62 (2005): 1822-1827. Web. 4. Pollart, Susan, Crista Warniment, and Takahiro Mori. Latex Allergy. American Family Physician 80.12 (2009): 1413-418. Web. 8
5. Ranta, Peter M., and Dennis R. Ownby. A Review of Natural-Rubber Latex Allergy in Health Care Workers. Clin Infect Dis 38.2 (2004): 252-56. Oxford Academic. Web. 24 Feb. 2017. 6. Recommendations for Labeling Medical Products to Inform Users That the Product or Product Container Is Not Made with Natural Rubber Latex: Guidance for Industry and Food and Drug Administration Staff. U.S. Department of Health and Human Services (December 2, 2014): 1-5. Food and Drug Administration. 28 Feb. 2017. 7. Centers for Disease Control and Prevention (CDC). Latex allergy. Retrieved from: https://www.cdc.gov/healthcommunication/ toolstemplates/entertainmented/tips/latexallergy.html 8. Food and Drug Administration. (December 2nd, 2014). Recommendations for Labeling Medical Products to Inform Users that the Product or Product Container is not Made with Natural Rubber Latex Guidance for Industry and Food and Drug Administration Staff. Retrieved from https://www.fda.gov/ downloads/medicaldevices/deviceregulationandguidance/ GuidanceDocuments/UCM342872.pdf 9. Food and Drug Administration. (March 30th, 2015). Don t be misled by latex Free claims. Retrieved from https://www.fda.gov/ ForConsumers/ConsumerUpdates/ucm342641.htm With the rise of latex alternative products, healthcare facilities are now more capable than ever to develop the latex safe protocol necessary to protect both employees and patients Glossary of Terms 1. Allergen: a substance, often a protein that induces an allergy. 2. Panallergan: families of related proteins, such as the HEV proteins in the rubber tree plant 3. IgE: Immunoglobulin E is a class of antibodies that mediate an allergic reaction 4. Antibodies: proteins produced in the blood in response to the presence of an antigen 5. Rhinitis: inflammation of the mucus lining of the nose 6. Conjunctivitis: inflammation of the transparent surface of the eye (conjunctiva) 7. Immunoassays: a laboratory technique to identify and quantify a protein 8. Corticosteroids: natural or synthetic hormones that assist in the homeostasis of the body 9. Anaphylaxis: a sudden, usually allergic reaction, induced by exposure to a secondary exposure to a foreign substance, such as an antigen 10. Lowry assay: a biochemical assay (test) for determining the total level of protein in a solution 11. Microbial: a microorganism 12. Nitrile: an organic compound 9
About the Authors Sue Lockwood Latex Allergy Expert & Co-Founder of the Former American Latex Allergy Association A leader in Latex Allergy & Co-Founder of the Former American Latex Allergy Association, Lockwood co-founded the American Latex Allergy Association, a nationwide latex allergy support organization that closed in 2016 after 23 years. She has now joined Allergy & Asthma Network expanding the Network s reach in Latex Allergy and Outreach Services. She has worked closely with allergy researchers and latex glove companies, and partnered with leading allergy organizations, including the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology, to provide evidence-based resources. Allergy & Asthma Network is the leading national nonprofit organization dedicated to ending needless death and suffering due to asthma, allergies, and related conditions. Allergy & Asthma Network specializes in sharing family-friendly, medically accurate information through its award-winning publication Allergy & Asthma Today magazine, E-newsletter, AllergyAsthmaNetwork.org, and numerous community outreach programs. Robert Hamilton, M.S., Ph.D. Director, Dermatology, Allergy & Clinical Immunology (DACI) Reference Laboratory Professor of Medicine Robert G. Hamilton, Ph.D., D(ABMLI) is currently Professor of Medicine and Pathology at The Johns Hopkins University School of Medicine in Baltimore, Maryland. He joined the Division of Allergy and Clinical Immunology of the Department of Medicine in 1981 and is the Director of the Dermatology-Allergy Clinical Immunology (DACI) Reference Laboratory. He is a fellow of the American Academy and College of Allergy, Asthma and Immunology. He has served as co-editor the past 2 editions of the Manual of Molecular and Clinical Laboratory Immunology. He has authored more than 300 peer-reviewed publications, reviews and book chapters. He lectures on a variety of topics, including laboratory diagnosis and management of human allergic disease and assessment of immunogenicity and allergenicity of new drugs. Eric Sredzinski, Pharm.D., AAHIVP Avella Specialty Pharmacy, EVP, Clinical Affairs & Quality Assurance Pharmacy Program Director, ADAP Dr. Eric Sredzinski is responsible for the clinical management, disease state management, training, and implementation of patient adherence and persistence programs for Avella Specialty Pharmacy. Working closely with the company s oncology, infectious disease, and transplant teams for presentations and business development, Dr. Sredzinski, a member of Avella Specialty Pharmacy s top management since joining the company in 2001, is also responsible for the management of manufacturer contracted data sets, including the participation in the development and testing of the data layout. Dr. Sredzinski is an active member of ASHP, The Arizona Pharmacists Association, HOPA, ASCO, and the AAHIVP. 10
Jenna Vaughn, Pharm.D. Pharmacy Resident Avella Specialty Pharmacy As a PGY1 resident for the Avella Specialty Pharmacy, Dr. Jenna Vaughn is involved in a variety of different rotations within the company involving areas such as: direct patient care, compounding, clinical education, limited distribution, business development, and pharmacy management. Dr. Vaughn spends her time working within different departments throughout several Avella locations and has gained valuable experience with HIV, fertility, pain, and oncology specialty medications. Dr. Vaughn is also responsible for co-teaching an Introduction to Specialty Pharmacy class at the Arizona Midwestern University with the residency program director and director of clinical services, Kelly Mathews. Dr. Vaughn recently graduated from the University of Colorado School of Pharmacy on May, 2016 with a Doctor of Pharmacy degree and entered into the Avella residency shortly after. Dr. Vaughn has spent this last year focusing on her residency and intends to continue working in specialty pharmacy once it has ended. Prior to graduation, Dr. Vaughn worked as an intern at a King Soopers with a strong HIV department and volunteered at the University of Colorado Hospital pharmacy in her free time. About Allergy & Asthma Network Allergy & Asthma Network is the leading national nonprofit organization dedicated to ending needless death and suffering due to asthma, allergies and related conditions. Allergy & Asthma Network specializes in sharing family-friendly, medically accurate information through its awardwinning publication Allergy & Asthma Today magazine, E-newsletter, AllergyAsthmaNetwork.org and numerous community outreach programs. Follow Allergy & Asthma Network on Facebook and Twitter @AllergyAsthmaHQ. Join the Network at AllergyAsthmaNetwork.org/join. About Avella Specialty Pharmacy Headquartered in Phoenix, Arizona, Avella Specialty Pharmacy is a National Accredited Specialty Pharmacy, providing individualized care and support to patients since 1996. Avella s clinical pharmacists and staff members are experts in managing complex disease states and providing compassionate care. The company offers a nationwide distribution service to complement its retail locations. In 2016, Avella was named Specialty Pharmacy of the Year by NASP, a nationally recognized pharmacy trade committee. Inc. Magazine s 2016 list of the 5,000 fastest-growing private companies in the country included Avella for the tenth consecutive year and also recognized Avella as the fastest-growing woman-led company in 2015. For more information, please visit www.avella.com. 11
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