INTRODUCTION — Natural rubber latex (NRL) allergy is caused by sensitization to proteins in the sap-like fluid (latex) from the commercial rubber tree, Hevea brasiliensis (Hev b). Most patients are sensitized through exposure to latex gloves or other latex products (eg, dental dams, condoms, and balloons) in a medical or occupational setting.
The mainstay of management of latex allergy is avoidance of latex products. Several other therapeutic approaches have been under investigation, including immunotherapy (IT) and anti-immunoglobulin E (IgE) therapy, but these have not shown promise.
The management of latex allergy, including avoidance measures and experimental therapies that have been attempted, will be reviewed here. An overview of latex processing and latex allergens and review of the epidemiology, clinical manifestations, and diagnosis of latex allergy are discussed separately. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis".)
OVERVIEW — Latex allergy can involve delayed or immediate-type reactions. Individuals with delayed hypersensitivity, manifested as a contact dermatitis, are at increased risk for developing IgE-mediated reactions. Thus, all individuals with latex sensitivity, as documented by a positive Hevea latex-specific IgE antibody response, should be managed similarly.
There are four possible strategies for preventing or managing allergic symptoms once an individual is diagnosed with latex allergy:
●Avoidance
●Pharmacotherapy
●Immunotherapy (IT)
●Anti-IgE therapy
Of these, the most effective and least expensive method is avoidance [1-4]. (See 'Institutional' below and 'Individual' below.)
The treatment of acute and chronic allergic symptoms with pharmacotherapy is possible. However, prevention of reactions is preferred. Unfortunately, preventive pharmacotherapy is rarely effective.
The use of IT is limited due to the high frequency of adverse reactions [2,5,6]. (See 'Immunotherapy' below.)
Anti-IgE therapy is under investigation for use in patients with IgE-mediated latex allergy as an off-label indication [7,8]. Anti-IgE is sometimes used together with an IT regimen. It is costly, and patients must have the appropriate body weight and total serum IgE level between 30 and 700 kU/L to be a candidate for omalizumab treatment.
AVOIDANCE — The primary method of management of latex allergy is avoidance.
Institutional — There is a general misconception that a "latex-free" environment, which is totally devoid of natural rubber latex (NRL) products, is both achievable and required to establish a safe environment for patients and employees with latex allergy. A completely latex-free environment is not readily achievable. In contrast, effective institutional avoidance of latex allergen can be accomplished by establishing a latex-"safe" environment. Creation of a latex-safe environment involves recognizing the importance of controlling latex exposure for allergic patients and employees, convening a latex committee, and establishing an institutional program to eliminate latex allergen exposures [3,9-11]. A multidisciplinary latex advisory committee should be composed of local experts with knowledge in legal matters, purchasing, occupational safety, allergy, and glove use, including surgery, medicine, and anesthesiology [1,9,12,13].
Establishment of latex-safe environmental policies involves replacing Hevea latex-containing products with non-Hevea-based synthetic products, if possible, or, at a minimum, powder-free latex products (see 'Hevea latex alternatives' below). Powder-free NRL products undergo a final chlorination step that removes a large percentage of Hevea-allergenic protein.
The primary source of Hevea latex exposure in medical institutions is the medical examination/surgical glove (both nonsterile and sterile gloves) [3,14,15]. Some institutions have globally converted only their examination gloves to synthetic alternatives, while others have transitioned all gloves to non-Hevea alternatives [4,9,11,13,16]. Other institutions have created a latex-"safer" environment by replacing all powdered latex gloves with low allergen-containing powder-free latex gloves [17].
Establishing a latex-safe environment in an institution leads to a decrease in latex-induced symptoms and reported employee and patient sensitivity. However, latex-specific IgE antibody can remain detectable in the skin and blood of individuals who avoid latex exposure for at least five years [3,4,11,18-21]. Thus, continued avoidance is recommended.
Reevaluation for continued sensitization is performed principally for information since a previously sensitized person is at risk for resensitization. Thus, latex avoidance precautions should still be followed even if subsequent testing is negative. However, a negative repeat analysis can be comforting as it suggests that the potential for an allergic response resulting from an inadvertent latex allergen exposure is minimal.
Repeat evaluations are typically performed just prior to a required medical or dental procedure to assess risk or during a yearly health checkup. IgE anti-latex serology is recommended for this reevaluation test due to the well-documented interassay consistency and semiquantitative (kUa/L) result of the serological assay methods available. In vivo skin test methods are less consistent since they are more highly dependent upon technique of the medical professional performing and evaluating the test. Moreover, federally cleared skin testing reagents are not available for use in certain countries (eg, US).
Environmental monitoring — Measuring the level of Hevea allergens in various products and occupational settings can document the risk for Hevea allergen exposure. This determination can be used to assess the necessity for an institutional transition to non-Hevea latex-containing products.
Once an institution elects to establish a latex-safe environment, members of the latex committee (typically purchasing, nursing, and surgical representatives) organize an in-house glove evaluation program in which (at a minimum) powder-free and (ideally) nonlatex (examination, procedure, and surgical) gloves are empirically tested by the institution's staff [16]. Gloves are selected for this in-house evaluation based upon available manufacturer-offered trial samples, the lowest level of latex allergen in available gloves as measured by the manufacturer using American Society for Testing Materials (ASTM)-qualified assays, the recommendations of other latex-safe institutions with alternative nonlatex gloves (and other products), the relative cost, and the empirically determined personal preference of the institution's staff. Alternatives to other latex-containing products listed in the table (table 1) are often evaluated at the same time as the gloves [9,12,13,16,18,22].
Since it is not known what the safe threshold limits are for latex aeroallergen exposure, candidate nonlatex gloves with the lowest airborne and contact latex allergen levels are selected to minimize potential exposure to patients and hospital staff. One earlier study using older assay methods suggested a latex aeroallergen threshold of 0.5 nanograms/cubic meter of air [23]. Similar threshold determinations have not been performed using the newer immunoenzymetric assays (IEMAs).
The ASTM provides an overview of the three standardized assays for Hevea product and environmental monitoring:
●Total protein – The modified Lowry test (ASTM D5712) was the first assay developed to monitor total Hevea protein in product extracts or environmental specimens [24,25]. This assay has limited analytic sensitivity. Thus, it is only able to quantify high levels of total extractable protein from Hevea rubber products. Moreover, it does not discriminate between allergenic and nonallergenic Hevea proteins.
●Hevea antigens – Hevea proteins that elicit an antibody response can be detected with the ASTM D6499 antigen enzyme-linked immunosorbent assay (ELISA) [24,26]. This assay does not distinguish between latex allergens (IgE inducing) and nonallergenic antigens (non-IgE inducing), and, therefore, it only provides an indirect measure of the allergenic potential of a product or environment.
●Hevea allergens – Of the 15 known Hevea allergens [27], H. brasiliensis (Hev b) 1, 3, 5, and 6.02 have been identified as the principal "indicator" allergens for monitoring products and environments (table 2) [28,29] (see "Latex allergy: Epidemiology, clinical manifestations, and diagnosis", section on 'Hevea indicator allergens'). Two-site monoclonal antibody-based IEMAs (ASTM D7427-08) are established as standard methods that provide quantitative estimates of the indicator allergens in product extracts and environmental samples [30,31]. The sum of the Hev b 1, 3, 5, and 6.02 content in physiologic extracts reflects the allergenic potential [32]. Quantification of Hev b 1 and Hevamine alone is insufficient to effectively assess rubber product allergen potency [22].
Of these three assays, the IEMA (ASTM D7427-08) is preferred because its results are most predictive of a product's latex "allergen" content. Other assays for Hevea allergens, such as the human IgE anti-latex-based competitive inhibition assay [20], remain research tools in selected laboratories due to their requirement for large amounts of human IgE anti-latex-containing serum [30].
Hevea latex alternatives — Synthetic elastomers and a non-Hevea rubber (Yulex) have been developed for use as alternatives in the manufacturing of commercial "rubber-like" products:
●The most common synthetic elastomers include butyl rubber, a completely petroleum-based product with no allergenic protein, polymers of 2-chlorobutadiene (neoprene), and copolymers of butadiene and acrylonitrile [33]. The predominant nonsterile, nonlatex examination gloves used in medical institutions today are made of nitrile, neoprene, vinyl, or synthetic polyisoprene rubber that is extracted from oil. Their color (white, blue, purple, or green) is arbitrary and does not reflect the type of material in the glove. Different glove materials vary in terms of their ability to be sterilized and still maintain their barrier properties.
●A non-Hevea source of natural rubber is the Guayule plant (Yulex) [34,35]. The raw material extracted from the shrub has an ultra-low protein content. The proteins that are present display no apparent in vitro or in vivo crossreactivity with Hevea latex allergens. Thus, Yulex-based rubber products should pose no risk to individuals who are allergic to Hevea latex. In the United States, Yulex-based products are cleared by the US Food and Drug Administration (FDA), and some products are commercially available.
Individual — All individuals with latex allergy, whether or not they come in contact with potentially contaminated body fluids, should use only non-Hevea medical gloves. In addition to gloves, there are as many as 40,000 consumer products in home and medical/dental environments that may contain latex [36,37]. Examples are listed in the table (table 1). Latex-containing forms of these products should be avoided as well. In the United States, Hevea latex-containing medical devices must be labeled "containing natural rubber latex" with a medical alert boxed warning. Unfortunately, there is no requirement for companies to label rubber products with their latex protein content. Consumer products do not have the same stringent labeling requirement; however, many are labeled as containing latex.
For high-risk health care workers and sensitized patients, latex avoidance is critically important to reduce current symptoms and further sensitization. Institutions that have an employee with latex allergy must adhere to strict policies. At a minimum, such policies permit only the use of powder-free latex products for all employees and latex-free products for the sensitized individual. It is not acceptable to give special latex-free gloves only to the worker with latex allergy, since their environment can endanger them if a coworker inadvertently uses a Hevea allergen-rich glove. Use of powder-free latex gloves by coworkers decreases, but does not eliminate, symptoms in health care workers with latex allergy [38].
ADDITIONAL MANAGEMENT ISSUES
Workplace — A systematic approach for managing a worker with suspected natural rubber latex (NRL) allergy begins with confirmation of the diagnosis of latex allergy using validated diagnostic methods [1,12,16]. Confirmation of latex sensitization can justify efforts put forth for cessation of further NRL exposure in the patient's workplace.
Despite the extensive research on the diagnostic potential of the 15 well-characterized Hevea latex allergenic components, IgE antibody measurements specific for these individual latex allergen components do not increase diagnostic sensitivity for latex-driven occupational asthma compared with just detecting IgE antibody to the natural extract [39]. IgE anti-latex component measurements do, however, aid in discriminating between different routes of latex allergen exposure (eg, inhalation [Hev b 5/6.02] versus mucosal [Hev b 1/3]).
One must then document that impairment and disability results from latex exposure in the workplace. The employer then needs to be educated about the patient's diagnosis and his/her responsibility to provide effective interventions to create a latex-safe environment. If the patient cannot be effectively accommodated, workers' compensation benefits and rehabilitation may be appropriate.
Schools — A systematic approach for managing a confirmed natural rubber latex (NRL) allergy in a student in a school program begins with development of an individualized health care plan and a school-wide avoidance plan. Education of the student on self-management skills is vital if the child has a risk of anaphylaxis [40].
Individuals — Several measures for the latex-allergic individual are recommended to prevent and manage allergic reactions [36,41]:
●A medical alert bracelet indicating latex allergy should be worn.
●Self-injectable epinephrine should be prescribed for all individuals with a clinical history of systemic reactions to latex. (See "Prescribing epinephrine for anaphylaxis self-treatment".)
●Nonlatex gloves should be carried.
●Patients should report their allergy prior to any medical, dental, gynecologic, or surgical procedure and request a latex-safe environment [42]. (See "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions", section on 'Latex'.)
Immunotherapy — The use of immunotherapy (IT) for the treatment of IgE-mediated latex allergy is limited by the frequency and severity of reactions to IT [5].
Several small, randomized trials were performed with conventional subcutaneous immunotherapy (SCIT) using crude latex extracts [43-45]. Efficacy was variable. One trial demonstrated decreased symptoms of urticaria and rhinoconjunctivitis but not asthma [43], whereas another did show reduced airway hyperreactivity to latex [44]. A third trial failed to demonstrate any difference in medication use or symptom scores [45]. A high frequency of adverse events, including systemic reactions, was reported in all studies. In one trial, adverse events occurred with similar frequency in both the induction and maintenance phases of the regimen [43].
Some studies suggest that the frequency and severity of adverse events are lower with sublingual immunotherapy (SLIT) compared with SCIT [46-50]. However, results vary, and anaphylaxis has been reported with SLIT [51-54].
Novel IT approaches are under investigation to decrease the risk of severe adverse reactions (allergenicity) and yet maintain or improve efficacy (immunogenicity). These approaches include recombinant allergens, T cell epitope-based peptides, and adjuvants that are conjugated to or coadministered with the allergen [36,55]. These therapies are still in the experimental stages.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Latex allergy".)
SUMMARY
●Once latex allergy is diagnosed, avoidance should be instituted as the primary method of management. Pharmacotherapy, immunotherapy (IT), and anti-immunoglobulin E (IgE) therapy are not substitutes for effective avoidance. (See 'Overview' above and 'Immunotherapy' above.)
●Institutional policy changes in the use of Hevea products are needed to reduce occupational and patient exposures. (See 'Institutional' above.)
●Use of nonlatex-containing gloves is recommended for individuals with latex allergy who use protective gloves. In addition, use of low-powder latex gloves by coworkers decreases exposure and sufficiently decreases symptoms in the latex-allergic individual in most cases. However, use of nonlatex gloves by all is preferred. Other latex-containing products should also be avoided. (See 'Individual' above.)
●Standardized assay methods for the quantification of antigenic and allergenic Hevea proteins facilitate the identification of highly allergenic Hevea-containing products and occupational environments. (See 'Environmental monitoring' above.)
●Synthetics and Yulex, a non-Hevea rubber, are alternative products that are considered safe for use in Hevea-sensitized individuals. (See 'Hevea latex alternatives' above.)
●Additional measures recommended for patients with latex allergy include having autoinjectable epinephrine available, carrying nonlatex gloves, wearing a medical alert bracelet, and requesting a latex-safe environment for procedures or employment. (See 'Individuals' above.)
