Latex allergy: Management

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 NRL gloves or other dipped latex products (eg, dental dams, condoms, and balloons) in a medical or occupational setting.

Since its first identification as a concern in the 1980s, the mainstay of management of latex allergy has been avoidance of latex products. Several other therapeutic approaches have been under investigation, including symptomatic pharmacotherapy, immunotherapy (IT), and anti-immunoglobulin E (IgE) therapy, but they have not shown promise.

The management of latex allergy, including avoidance measures and experimental therapies that have been attempted, are reviewed here. Due to increase demand for locally produced personal protective equipment (including disposable gloves) as a result of the worldwide coronavirus disease 2019 (COVID-19) pandemic and other factors related to disposal issues, biodegradable properties, and climate change discussed in this review, it may be time to reconsider the use of a new generation of low-protein NRL medical gloves that meet rigorous performance and safety standards. 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

Types of allergic reactions — Latex allergy can involve delayed (type IV) or immediate type I reactions. Persons with delayed hypersensitivity that is manifested as a contact dermatitis associated with accelerator chemical sensitization are at increased risk for developing IgE-mediated (type I) systemic reactions. Thus, all persons with latex sensitivity, as documented by a positive Hevea latex-specific IgE antibody response, should be managed similarly.

Strategies for preventing or managing latex allergy — There are four possible strategies for preventing or managing allergic symptoms once a person is diagnosed with latex allergy:

●Avoidance – The most effective and least expensive method is avoidance of natural rubber latex (NRL) allergen exposure [1-4]. The prevalence of latex allergy among health care workers and the general public has dropped dramatically and, in some locations, to undetectable levels due to widespread avoidance measures involving a practical "latex-safe" (not "latex-free") environment strategy that has been adopted by most medical, dental, and nursing home facilities. (See 'Institutional avoidance' below and "Latex allergy: Epidemiology, clinical manifestations, and diagnosis", section on 'Epidemiology'.)

●Pharmacotherapy – The treatment of acute and chronic allergic symptoms with pharmacotherapy is possible. However, prevention of reactions and the possibility of increased sensitization are preferred. Unfortunately, preventive pharmacotherapy is rarely effective.

●Immunotherapy (IT) – The use of IT is limited due to the unavailability of approved therapeutic NRL extracts and a high frequency of adverse reactions when experimental extracts were used [2,5,6]. (See 'Immunotherapy' below.)

●Anti-IgE therapy – 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.

INSTITUTIONAL AVOIDANCE

Latex free versus latex safe — There is a general misconception that a "latex-free" environment means one totally devoid of natural rubber latex (NRL) products. It conceptually remains a requirement to establish a safe environment for patients and employees who are sensitized (IgE antibody positive) to NRL allergens. A completely NRL-free environment is not practically achievable. In contrast, effective institutional avoidance of latex allergen has been accomplished by establishing a latex-safe environment that involves recognizing the importance of controlling latex allergen exposure for health care workers, the general public, and, more specifically, persons with NRL allergy.

Latex advisory committees — Most medical institutions established a latex committee and an institutional program to eliminate NRL allergen exposure [3,9-11]. A multidisciplinary latex advisory committee typically has been 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]. While institutional latex advisory committees still exist on paper, most have not met in years because of the decline of latex allergy prevalence. Latex allergy has essentially disappeared from the general conscience of the medical and dental communities.

Latex-safe environmental policies — Establishment of latex-safe environmental policies involves replacing Hevea latex-containing products with non-Hevea-based synthetic products, if possible, or, at a minimum, identifying NRL products that do not release large quantities of latex allergen, such as powder-free latex gloves. Powder-free NRL products generally undergo extensive additional washes and a final chlorination step that removes Hevea-allergenic protein. (See 'NRL product and environmental monitoring' below.)

Medical/surgical gloves — The primary source of Hevea latex exposure in medical institutions in the 1980 to 2010 period was the powdered medical examination/surgical glove (both nonsterile and sterile gloves) [3,14,15]. The level of allergenic protein released from latex gloves can be determined [16-18]. Some institutions have globally converted only their examination gloves to synthetic alternatives because examination gloves have higher NRL content than surgical gloves, while others have transitioned completely to non-Hevea gloves [4,9,11,13,19]. A small number of institutions have created a latex-"safer" environment by replacing all powdered latex gloves with low-allergen-containing, powder-free latex gloves that are less allergenic [20].

It may be time to more broadly reconsider the use of particular NRL gloves that are documented to release low or no latex-allergenic protein based upon analytical documentation along with synthetic medical gloves, a particularly relevant consideration with increased glove demands during the coronavirus disease 2019 (COVID-19) pandemic. However, there is no universally accepted criterion, such as the use of <0.15 mcg/g of glove of summed Hev b 1, 3, 5, and 6.02 allergens [21], that has been adopted by manufacturers or regulators for defining a glove as having a low allergenic potential, although it is under consideration. In addition, the question remains whether a "lot" or "batch" of NRL gloves manufactured on a production line can be shown to have <0.15 mcg/g of glove of summed Hev b allergen at the beginning, middle, and end of a run of thousands of gloves. (See 'NRL product and environmental monitoring' below.)

Hevea rubber stoppers (closures) have been the subject of intense debate. We and others have shown that puncturing a 100 percent NRL pharmaceutical vial closure can release low amounts of Hevea proteins into the pharmaceutical vial contents [22]. The levels of allergen are low, can be detected by skin testing, and increase with each puncture. Due to this observation, pharmaceutical companies have mostly eliminated the concern by switching to the use of synthetic butyl rubber stoppers that contain no Hevea proteins. If there is a question by a pharmacist whether a particular vial contains a Hevea protein-containing latex stopper, they are encouraged to use the "one stick rule" that we have demonstrated provides the safest protocol for the administration of a pharmaceutical after puncturing through a Hevea latex stopper [23]. For highly latex-allergic persons, injection of a drug containing Hevea proteins can evoke an allergic response, especially if administered intravenously. Thus, careful avoidance throughout their life is encouraged since chronic reexposure will lead to resensitization. The low levels of Hevea latex released by puncturing a 100 percent NLR are, however, not considered a concern for eliciting de novo sensitization in an otherwise non-latex-allergic person.

High-risk health care workers and sensitized patients — For high-risk health care workers and sensitized patients, latex avoidance is critically important to reduce symptoms and further sensitization. Institutions that have an employee with latex allergy must adhere to strict policies. At a minimum, such policies should permit only the use of low-protein, powder-free latex products for all employees and latex-free products for sensitized persons. 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 Hevea allergen-rich gloves. Use of low-protein, powder-free latex gloves by coworkers decreases, but does not eliminate, symptoms in health care workers with latex allergy [24].

NRL product and environmental monitoring — Measuring the release of Hevea allergens from various products (table 1), particularly medical gloves, and airborne levels of these allergens in occupational settings, is critical to documenting the suitability of newer-generation low-protein natural rubber latex (NRL) medical gloves in a latex-safe work environments. This determination can be used to document that an institution has transitioned to latex-safe status.

ASTM International (formerly the American Society for Testing Materials) has qualified three standardized assays for evaluating the relative safety of Hevea latex-containing products and aeroallergen environmental monitoring where Hevea latex products are used. Of these three assays, the immunoenzymetric assay (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 [25], remain research tools in selected laboratories due to their requirement for large amounts of human IgE anti-latex-containing serum [26].

●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 these indicator allergens in product extracts and environmental samples [26,30]. The sum of the Hev b 1, 3, 5, and 6.02 content in physiologic extracts reflects the allergenic potential of a Hevea latex-containing product or environment [21]. Quantification of Hev b 1 and Hevamine alone is insufficient to effectively assess rubber product allergen potency [31]. Summed concentrations of Hev b 1, 3, 5, and 6.02 totaling <0.15 mcg/g of glove were shown to have low allergenic potential as assessed independently by an IgE enzyme-linked immunosorbent assay (ELISA) inhibition assay [21].

An earlier study using an IgE antibody-based inhibition assay has suggested that a latex aeroallergen threshold of 0.5 nanograms/cubic meter of air indicates a safer work environment [32]. However, threshold environmental determinations have not been qualified using the ASTM D7427-08 IEMAs for allergen content.

●Hevea antigens – Hevea proteins that elicit an antibody response can be detected with the ASTM D6499 antigen ELISA [33,34]. The utility of this measurement depends on the ability of all Hevea allergenic proteins to elicit an antibody response that is detectable by the assay. Its major limitation is that it 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. Like the total protein assay, the Hevea antigen assay is not suitable for definitively identifying "latex-safe" products and environments that require the assessment of accurate allergen content.

●Total protein – The modified Lowry test (ASTM D5712) was the first assay developed to monitor total Hevea protein in product extracts or environmental specimens [33,35]. This assay, while the least expensive of the three tests, is the least useful for defining levels of Hevea allergenic protein as it has limited analytic sensitivity and is only able to quantify high levels of total extractable protein and does not discriminate between allergenic and nonallergenic Hevea proteins.

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 [36]. 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.

●Historically, a non-Hevea source of natural rubber is the Guayule plant (Parthenium argentatum) [37,38]. 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 cross-reactivity with Hevea latex allergens. Thus, Yulex-based rubber products should pose no risk to persons who are allergic to Hevea latex. In the United States, some Yulex-based products were cleared by the US Food and Drug Administration (FDA). As of 2021, the company making Guayale products converted from using Parthenium to low-protein Hevea latex from Central American sources to manufacture consumer products (eg, wet suits) and, in the future, medical gloves.

INDIVIDUAL AVOIDANCE

General approach — All persons 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 natural rubber latex (NRL) [39,40]. 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, which refers to NRL.

Duration of avoidance and reevaluation in persons with latex allergy — It is well established that employing 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 for at least five years in the skin and blood of persons with latex allergy who avoid latex exposure [3,4,11,25,41-43]. Thus, continued avoidance of allergen exposure is recommended. (See 'Strategies for preventing or managing latex allergy' above.)

Reevaluation, principally by IgE anti-NRL serology assays, to assess continued sensitization is performed primarily for information since a previously sensitized person is at risk for resensitization. Thus, latex allergen avoidance precautions should still be followed even if subsequent serologic testing is negative. However, a negative repeat IgE anti-NRL serology analysis is 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 the only available evaluation test available in the US due to its well-documented inter-assay latex allergosorbent consistency and its ability to generate a semiquantitative (kUa/L) result. In vivo skin test methods are not available in the US, due to an absence of approved NRL skin test extracts. European medical institutions, in contrast, can perform both serology and puncture skin testing because of the availability of at least one well-characterized approved NRL extract.

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 [1,12,19]. In the US, this is an IgE antibody analysis by one of several US Food and Drug Administration (FDA) cleared immunoassay auto-analyzers. In Europe, it can also involve the use of an NRL extract-based puncture skin test. Confirmation of latex sensitization can justify efforts put forth for cessation of further NRL exposure in the patient's workplace. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis", section on 'Objective tests to demonstrate latex allergy'.)

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 [44]. 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 contact [Hev b 1/3]).

One must 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 their 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 NRL allergy in a student in a school program begins with development of an individualized health care plan and a schoolwide avoidance plan. Education of the student on self-management skills is vital if the child has a risk of anaphylaxis [45].

Individuals — Several measures for the person with latex allergy are recommended to prevent and manage allergic reactions [39,46]:

●A medical alert bracelet indicating latex allergy should be worn.

●Self-injectable epinephrine should be prescribed for all persons with a clinical history of systemic reactions to latex. (See "Prescribing epinephrine for anaphylaxis self-treatment" and "Anaphylaxis: Emergency treatment", section on 'Epinephrine'.)

●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 [47]. (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 absence of regulator-approved extracts and the frequency and severity of reactions to IT [5].

Several small, randomized trials were performed with conventional subcutaneous immunotherapy (SCIT) using crude latex extracts [48-50]. Efficacy was variable. One trial demonstrated decreased symptoms of urticaria and rhinoconjunctivitis but not asthma [48], whereas another did show reduced airway hyperreactivity to latex [49]. A third trial failed to demonstrate any difference in medication use or symptom scores [50]. 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 [48].

Some studies suggest that the frequency and severity of adverse events are lower with sublingual immunotherapy (SLIT) compared with SCIT [51-55]. However, results vary, and anaphylaxis has been reported with SLIT [56-59].

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 [39,60]. 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 AND RECOMMENDATIONS

●Avoidance – 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 strategies – Institutional policy changes in the use of Hevea products can reduce occupational and patient exposures. One approach is to use the "one stick rule" for a patient who is highly allergic to latex when administering a pharmaceutical after puncturing through a Hevea latex stopper or when the stopper material is not known. Another is a universal criterion for insuring low allergenic potential of low-protein powder-free natural rubber latex (NRL) medical gloves. Once this is adopted by glove manufacturers and accepted by governmental regulators (eg, <0.15 mcg per gram of glove of summed Hev b 1, 3, 5, and 6.02 allergens), it may be time to reconsider the reinstitution of these low-allergen NRL gloves back into institutions that have historically had a NRL-free policy. (See 'Institutional avoidance' above.)

●Individual strategies – Nonlatex-containing gloves should be used by persons 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 person with latex allergy in most cases. The policy of using of nonlatex gloves by all is poised to change once qualified low-allergen, low-protein, powder-free NRL gloves become available. Other latex-containing products should also be avoided. (See 'Individual avoidance' above.)

●Assessment of NRL allergens in products and the environment – Standardized assay methods for the quantification of allergenic Hevea proteins facilitate differentiating between highly allergenic Hevea-containing products and occupational environments and those with low allergenic potential. (See 'NRL product and environmental monitoring' above.)

●Hevea latex alternatives – Synthetics are alternative products are considered safe for use in Hevea-sensitized individuals. (See 'Hevea latex alternatives' above.)

●Additional management measures – Additional measures advised 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. Although allergy to latex has decreased in prevalence, clinicians should not discount the risk of anaphylaxis in a patient with a "latex allergy" label that is reported in their medical record. (See 'Individuals' above.)