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Latex allergy: Epidemiology, clinical manifestations, and diagnosis

Latex allergy: Epidemiology, clinical manifestations, and diagnosis
Author:
Robert G Hamilton, PhD, DABMLI, FAAAAI
Section Editor:
Bruce S Bochner, MD
Deputy Editor:
Elizabeth TePas, MD, MS
Literature review current through: Sep 2022. | This topic last updated: Nov 22, 2021.

INTRODUCTION — Natural rubber latex (polyisoprene) is used in the manufacturing of a wide variety of commercial products ranging from airplane tires to protective medical gloves. Ninety-nine percent of natural rubber comes from one source: the sap-like fluid (latex) from the commercial rubber tree, Hevea brasiliensis (Hev b), grown in Africa and Southeast Asia (Thailand, Indochina, Malaysia, and India) [1].

A tube-like network of laticifer cells beneath the H. brasiliensis tree bark contains natural rubber (polymeric hydrocarbon 1,4 cis-polyisoprene), water, and cytoplasmic organelles. In addition, the cytoplasm contains a variety of enzymes and structural proteins that are involved in biosynthesis of polyisoprene, coagulation of latex, and plant defense against microbes. A number of these proteins are known to be potent allergens that elicit human immunoglobulin E (IgE) antibody, leading to sensitization in exposed individuals and a spectrum of allergic reactions upon subsequent exposure [2-4].

This topic gives an overview of latex processing and latex allergens and discusses the epidemiology, clinical manifestations, and diagnosis of latex allergy. The management of latex allergy is discussed separately. (See "Latex allergy: Management".)

TERMINOLOGY — The term "latex" has several meanings. In this topic, the term "latex" refers to natural polyisoprene, a milky, usually white, fluid that is produced by cells of various seed plants (eg, milkweed and poppy families) and is the source of natural rubber, gutta-percha, chicle, and gutta-balata used in medical and dental applications. The term "latex" is also used to describe a water emulsion of a synthetic polyisoprene, nitrile, neoprene, or plastic that is obtained by polymerization and used in coatings (eg. paint), adhesives, and the manufacture of medical gloves.

HEVEA LATEX ALLERGENS — Approximately 250 different natural rubber latex polypeptides have been identified, of which 60 are able to bind human IgE antibody. Only 15 of the principal allergens have been given official numbers (H. brasiliensis [Hev b] 1 through Hev b 15) by the International Nomenclature Committee of Allergens in the International Union of Immunological Societies (IUIS). These allergenic proteins are described in the table (table 1), including their molecular weight, plant family, and any known crossreactivity to structurally similar food, pollen, and mold allergens. The 15 allergenic Hevea proteins are involved in a broad range of activities in the rubber tree, including rubber biosynthesis, disease resistance, structure, and housekeeping. Nine additional Hevea proteins that can induce IgE antibody have been described (table 1).

Hev b 1, 2, 3, 4, 5, 6.02, 7.01, and 13 have been identified as the most highly sensitizing of the Hevea allergens [5-9]. There is disagreement as to the relative clinical importance of certain Hevea allergens, such as Hev b 2 and Hev b 13. However, this discussion is largely academic because management of a person with latex allergy involves avoidance of exposure to all Hev b allergens.

Hevea indicator allergens — Four Hevea proteins are particularly useful as "indicator" allergens for assessment of the allergen content of rubber products or as markers of the presence of latex in the environment (table 1) [10,11].

Hev b 1 (rubber elongation factor) and Hev b 3 (prenyltransferase) are associated with the surface of the polyisoprene rubber particle. These two allergens are more difficult to aerosolize, and, therefore, sensitization (IgE antibody production) to Hev b 1 and 3 requires direct mucosal exposure to Hevea rubber products that can occur during surgery.

Hev b 5 (acidic protein) and Hev b 6.01/6.02 (mature hevein) are soluble allergens that are present in the latex cytosol or C serum. Using recombinant latex allergens, Hev b 5 and 6.01/6.02 have been identified as major allergens involved in sensitizing health care workers. These proteins are released from dipped rubber products, mainly latex gloves, and transported via aerosolized powder used for glove donning or sloughed directly into the environment. Exposure to these allergens through direct contact or inhalation occurs most frequently in occupations in which protective rubber gloves are frequently worn.

Cross-sensitization among latex, fruit, and pollen — Approximately 30 to 50 percent of individuals who are allergic to latex show an associated hypersensitivity to certain plant-derived foods, especially fresh fruits [12,13]. This is called latex-fruit or latex-food syndrome. Most patients with latex-food syndrome react to only a small number of foods. However, the reactions can be serious. In one case series, up to 50 percent of the reported food reactions were anaphylactic [14]. (See "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)" and "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)".)

Foods that contain cross-reactive allergens include banana, kiwi, avocado, chestnut, papaya, white potato, and tomato (figure 1) [14-20]. The Hev b allergens that have structural homology with selected proteins in these plant foods are listed in the table (table 1). The major panallergen responsible for much of the fruit-latex crossreactivity is a defense-related protein (class 1 chitinase) that displays structural homology to Hev b 6.01 [21-23]. Hev b 5 possesses homology with an acidic protein in kiwi fruit, peach, and apricot [24,25]. Hev b 6.02 (mature hevein) shares structural homology with wheat germ agglutinin and endochitinases in avocado and banana [21,26,27]. The Hev b 7 homologs (Hev b 7.01 and Hev b 7.02) are esterases that share structural homology with patatin (Sol t 1), the major storage protein in potato tubers [28]. Hev b 8 is a profilin (actin-binding protein) that contributes to clinically important crossreactivity with other highly sensitizing profilins from tree, grass, and weed pollens and foods (eg, the birch allergen, Bet v 2 and the Timothy grass allergen, Phl p 12) [29,30].

HEVEA LATEX PROCESSING — Hevea latex can be separated by centrifugation into three discrete layers [1,31,32]. The top layer contains particles of natural rubber (approximately 27 percent), which are water insoluble and rich in Hev b 1 and 3. The middle fraction or C serum (latex cytosol; approximately 48 percent) contains soluble proteins, including plant enzymes. This fraction contains Hev b 5, 7, 8, and 9. The lower layer contains the lutoid pellet (B-serum; approximately 30 percent), which is composed of luciferous organelles that contain hevamines with chitinase and lysozyme activity and hevein, a fungitoxic protein. It is rich in Hev b 2, 4, 6.01/6.02, 7, 10, 11, and 13. Both the B and C serum proteins are water soluble. A mixture of B and C serum proteins have been used to prepare diagnostic skin test extracts.

The milky fluid or latex from the rubber tree is processed by one of two pathways [33,34]:

Approximately 90 percent of Hevea latex is acid coagulated into dry sheets or crumbled particles and used to manufacture molded rubber products (eg, pneumatic tires for vehicles and airplanes, syringe plungers, vial stoppers, and shoe soles). This processing involves prolonged treatment at high temperatures, which decreases allergenicity. Solid rubber products contain low levels of latex allergens, mainly Hev b 1 and Hev b 3.

The remaining 10 percent of Hevea latex is ammoniated to prevent bacterial growth. A variety of low-molecular-weight chemical additives (eg, antioxidants, accelerators, preservatives) are often used in the process. Ammoniated latex is used to manufacture dipped rubber products on porcelain molds (eg, medical gloves, condoms, catheters, and toy balloons). Dipped rubber products contain higher levels of latex allergens, including Hev b 5, Hev b 6, and Hev b 13, and the majority of allergic reactions to Hevea latex proteins result from exposure to dipped rubber products. Total extractable latex protein is significantly reduced in commercially produced latex gloves by treatment with natural proteases (papain, bromelain) following dipping [35]. Even with these procedures that minimize protein content, results of a 2016 study confirm that concerning levels of allergenic latex protein from 215 to 1308 mcg/g remain in 50 percent of commercial latex gloves tested [36].

Medical Hevea latex gloves can be categorized by their application and degree of sterilization (nonsterile examination gloves and sterile procedure and surgeon gloves) and by the presence or absence of donning powder (powdered versus powder free). Allergenic protein that adheres to cornstarch donning powder readily distributes into the environment following powdered glove use. Allergic airway symptoms can result from the aerosolized latex allergen but rarely from the cornstarch powder itself. Powder-free latex gloves generally contain the lowest levels of allergens as a result of a final chlorination wash process. Avoidance of Hevea latex products in general and, specifically, powdered latex products is the most efficient means of reducing Hevea latex allergen exposure.

EPIDEMIOLOGY — The prevalence of latex sensitization/allergy skyrocketed in the mid- to late-1990s due to a significant increase in the use of natural rubber latex gloves by clinicians and other health care employees (nurses, dentists, laboratory workers, housekeepers, emergency medical technicians, patient transporters) [34].

Subsequent widespread avoidance of powdered latex gloves in many hospitals has resulted in a marked decrease in the number of new cases of latex allergy among health care workers and patients receiving multiple surgeries [37]. However, latex allergy continues to be a serious issue in countries where powdered latex gloves and other dipped natural rubber latex products such as urinary catheters are still widely used by medical personnel, patient groups (eg dialysis patients), and in select occupations (eg, florists, food handlers) [38-45]. (See 'Risk factors' below.)

Latex allergy epidemic — A number of factors contributed to the epidemic of latex allergy in North America and Europe. In 1992, the United States Occupational Safety and Health Administration (OSHA) issued the Bloodborne Pathogens Standard that required protective glove use. The introduction of "universal precautions" increased the use of medical gloves. This increased demand for natural rubber latex came at a time when the supply of latex was limited. Thus, latex was collected from increasingly younger trees that had been treated with stimulants to produce higher levels of latex per tree.

Both tapping of younger trees and the use of stimulant chemicals increased the level of allergenic proteins in the collected latex. The latex was processed without the customary delay when it arrived at the manufacturing facility, rather than being stored for extended periods. This rapid turnover of latex minimized the extent of protein denaturation that naturally occurs during storage at high pH caused by the presence of ammonia. Together, these factors increased the amount of allergenic protein in the raw material and ultimately in the finished latex medical gloves. Higher levels of protein exacerbated the problem of latex allergy among the medical and dental communities by increasing H. brasiliensis allergen exposure [46,47].

Prevalence in the general population — Prevalence estimates of sensitization to latex allergens are highly dependent upon the population studied and the techniques and reagents used to identify cases (questionnaire, IgE antibody skin testing/serology evaluation) [48]. As an example, diagnostic procedures using skin test or serology reagents will be biased toward detecting individuals sensitized to Hev b 6.02 because this protein is the most abundant allergen in latex extracts.

Hevea latex sensitization (IgE antibody positivity) among the general population was estimated at 3 to 9.5 percent in the mid-1990s [49-51]. The prevalence of latex sensitization in the general population fell to <1 percent by 2006 in countries where Hevea latex avoidance was promoted [48]. Rates of clinical IgE-mediated allergy are even lower. However, these numbers do not include persons with allergic contact dermatitis to latex, a reaction that is T cell rather than IgE antibody mediated. (See 'Clinical manifestations' below.)

Prevalence in the health care community — Significant numbers of cases of Hevea latex allergy were identified in the late 1980s [52]. By 1991, latex allergy was such a serious health issue that the US Food and Drug Administration (FDA) convened an international symposium on latex allergy. Increased occupational exposure to Hevea allergens occurred principally among the medical and dental communities. Use of powdered latex gloves resulted in both direct cutaneous contact with Hevea allergens and inhalation of aerosolized Hevea allergens [53,54].

Latex allergy achieved epidemic proportions in the medical community by the mid-1990s. An estimated prevalence of sensitization among the general health care worker population in one study was 12.1 percent [55]. A similar prevalence of sensitization to Hevea allergens of 10.7 percent was reported for routinely exposed operating room nurses [56]. Rates fell to approximately 4 to 7 percent with the introduction of powder-free gloves [43,57,58]. It can be assumed that rates have decreased even further with the increased use of nonlatex nitrile gloves. However, new cases of latex allergy still occur as a result of inadvertent repetitive exposures from high levels of Hevea allergen in less obvious sources, such as toy balloons and dental dams [59].

In Western countries, which have established general natural rubber latex glove avoidance polices, the emergence of the worldwide coronavirus disease 2019 (COVID-19) infection has changed medical glove-ordering practices. Increased virtual work practices among institutional purchasing departments have led to reduced central ordering and increased individual user ordering of medical gloves. This has reduced institutional control over the type (natural rubber latex or nitrile) of protective gloves ordered. Thus, institutions that have continued to maintain general latex glove avoidance policies are seeing increased purchasing of nonpowdered, lower-allergen, natural rubber latex nonsterile examination and sterile procedure/surgeon gloves. Despite this trend, the prevalence of new cases of latex allergy among health care workers appears to remain low, even though the precise prevalence has been difficult to determine. However, latex allergy remains problem for health care workers in regions such as Asia that have not effectively instituted general natural rubber latex avoidance practices [45,60].

Prevalence in patients receiving multiple surgeries — A second high-risk group involved individuals who were frequently exposed to latex as a result of multiple surgeries, especially abdominal or genitourinary surgery. The most high-profile group was children with spina bifida who were sensitized through direct mucosal exposure to Hevea rubber products as a result of multiple surgeries early in life and frequent bladder catheterization and manual rectal disimpaction [61-63]. It has been estimated that between one-third and two-thirds of children who underwent their surgeries in the 1990s became sensitized to Hevea allergens (developed IgE antibodies to latex allergens). A significant proportion manifested latex-induced allergic reactions upon subsequent exposure to latex gloves or urinary catheters. The rate of latex sensitization and allergy has decreased significantly in children with spina bifida since the implementation of latex avoidance compared with historical controls (55 versus 5 percent for sensitization and 37 versus 0.8 percent for allergy, respectively) [64]. In some parts of the world, the prevalence of latex allergy in patients with myelomeningocele remains high at 19.5 percent, and more than five surgeries is the single most important risk factor for this condition [65].

Risk factors — The main risk factors for latex allergy are occupational exposure and an atopic tendency. Rates of latex allergy are higher in patients sensitized to other allergens and those with eczema or fruit and vegetable allergy.

Occupations in which latex gloves are commonly used include:

Health care workers (medical and dental) [66]

Food handlers/restaurant workers

Domestic workers

Hairdressers

Security personnel

Construction workers

Greenhouse workers/gardeners

Painters

Funeral home workers

First responders, such as police officers, firefighters, and ambulance attendants

Atopic health care workers with latex allergy are more likely to have interleukin (IL) 13 and IL-18 promoter polymorphisms than nonatopic controls [67]. However, these polymorphisms do not occur with increased frequency in patients with spina bifida or bladder exstrophy and concomitant latex allergy [68]. Risk factors in these patients include the number of prior operations and history of atopic disease.

CLINICAL MANIFESTATIONS — Symptoms manifested during a latex-induced reaction depend upon the route of exposure, the amount of allergen in the natural rubber product, and the underlying mechanism of the reaction (irritant, non-IgE mediated, or IgE mediated) [69].

The most common complaint of individuals who wear Hevea latex medical gloves is of dry, crusted, and irritated skin [70]. Erythema and vesicle formation are common. This rash is similar in appearance to allergic contact dermatitis, but delayed-type hypersensitivity cannot be demonstrated to traces of additive chemicals in the gloves (see 'Allergic contact dermatitis' below). Rather, this rash is an irritant contact dermatitis. It is induced by a combination of factors: sweating associated with occlusion by the glove, prolonged contact with an alkaline pH due to cornstarch used in many powdered gloves, frequent hand washing, and the use of caustic hand sanitizers and detergents.

Individuals with latex allergy may also react to foods that contain cross-reactive proteins. (See 'Cross-sensitization among latex, fruit, and pollen' above.)

Allergic contact dermatitis — Allergic contact dermatitis presents as skin rash and itching one to four days after direct skin contact with a rubber latex product. The initial appearance of the rash is frequently an acute eczematous dermatitis, often with vesicles [71]. The rash takes on a more dry, crusted, lichenified appearance with continued exposure (picture 1).

This reaction is a T cell-mediated delayed-type hypersensitivity (type IVc) to a number of the additive oxidant and accelerator chemicals (thiurams, carbamates, benzothiazoles, thiourea, amines) that are used in the latex manufacturing process [70,72]. It is not a reaction to Hev b allergens. However, breaches in the skin barrier secondary to contact dermatitis may increase the risk of IgE-mediated latex sensitization because of increased absorption of allergens [53].

Allergic contact urticaria — IgE-mediated immediate-type hypersensitivity (type 1) is manifested as contact urticaria [3,73]. Contact urticaria is the most common allergic reaction reported by health care workers who use latex medical gloves.

Redness, itching, and wheal and flare reactions occur at the site of rubber-skin contact within 10 to 15 minutes. The acute reaction can be followed by a delayed-type allergic contact dermatitis [53,74]. (See 'Allergic contact dermatitis' above and "New-onset urticaria".)

Rhinoconjunctivitis and asthma — Manipulation of powdered latex gloves produces an aerosol of Hevea allergens that can trigger rhinitis and asthma symptoms in latex-sensitive individuals [54,69,75,76]. Latex-induced sneezing, ocular tearing and itching, nasal congestion, and rhinorrhea are similar to symptoms of acute seasonal pollenosis. Therefore, recognizing the temporal relationship between symptoms and latex exposure is critical.

Preexisting asthma is not a prerequisite for the development of latex-related asthma. The upper- and lower-airway allergic symptoms can be so severe that some occupationally exposed workers must leave their place of employment unless the institution can eliminate or sufficiently decrease exposure [49,69]. (See "Occupational asthma: Definitions, epidemiology, causes, and risk factors" and "Occupational rhinitis".)

Anaphylaxis — Anaphylactic reactions have occurred after use of various latex-based products in both medical and nonmedical settings [71,77-81]. The most common products that have caused anaphylaxis include (see "Perioperative anaphylaxis: Clinical manifestations, etiology, and management" and "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions" and "Fatal anaphylaxis"):

Gloves

Balloon-tipped catheters (eg, used during barium enema examination, arterial catheterization)

Dental cofferdams

Condoms

Adhesives for hair extensions

Toy balloons

Pacifiers, teethers, bottle nipples

DIAGNOSIS — Establishing the presence of latex allergy can be challenging. The most reliable indicator of allergy is a strong clinical history, associating exposure and symptoms. Confirmatory tests (skin tests, serology, and provocation) are limited by reagent availability, varying reagent sensitivity/specificity and composition, and significant potential risks for triggering serious reactions. Thus, a negative test in the setting of high clinical suspicion does not necessarily rule out latex allergy. Empiric avoidance or referral to an allergy specialist for further evaluation is appropriate for these patients.

Clinical history — The diagnosis of latex allergy begins with a clinical history of allergic reactions that are temporally associated with exposure to Hevea latex-containing products (table 2) [62,82]. A careful evaluation of all possible allergens should be performed if a patient has an immediate-type hypersensitivity reaction to a consumer product within minutes of contact and natural rubber latex is suspected since another allergen may be the culprit. As an example, casein, a component of cow's milk that was incorporated into the spongy padding of boxing gloves, and not Hevea latex, was identified as the trigger of a life-threatening anaphylactic reaction that occurred in a woman with cow's milk allergy immediately after she donned a new pair of kickboxing gloves [83].

Risk factors associated with latex allergy include hand dermatitis, fruit/vegetable allergy, and atopy (see 'Risk factors' above). Once there is a high clinical suspicion of latex allergy, the next step is testing to try to confirm sensitization (IgE antibody positivity) to Hevea allergens by skin testing or detection of Hevea-specific IgE in serum [82,84,85]. Patch testing can be used to distinguish dermatitis caused by cell-mediated delayed-type hypersensitivity reactions to Hev b latex components [86] and chemicals added to rubber [87] from immediate-type hypersensitivity responses elicited by IgE antibody.

Objective tests to demonstrate latex allergy — The diagnostic tests recommended to demonstrate latex allergy vary in different countries.

Testing strategies and available reagents — In the United States, the available option for diagnostic testing involves the use of US Food and Drug Administration (FDA) cleared autoanalyzers to detect natural rubber latex-specific IgE antibody in serum. The ImmunoCAP and Immulite systems are used in clinical immunology laboratories. In other parts of the world, where a characterized skin test reagent is available, prick/puncture skin test can be performed first. This may be followed by a latex-specific IgE antibody serology with one of the autoanalyzer methods if the skin test data remain inconsistent with the history-driven diagnosis. Provocation testing with powdered natural rubber latex glove exposure is generally not recommended.

Skin testing — Skin testing with extracts prepared with Hevea latex B and C serum proteins is a safe and effective diagnostic procedure when extracts are standardized in terms of their allergen content and stability [9,84,88,89]. (See 'Hevea latex processing' above.)

Prick/puncture skin testing with extracts of Hevea latex is widely performed in Europe and Canada, where at least three commercial H. brasiliensis extracts are available in a glycerinated form [88]. Commercially available skin test extracts are prepared using sterile filtered C serum from either nonammoniated or ammoniated Hevea latex, which is then glycerinated to maintain stability and increase its shelf life. The C serum contains both soluble and lutoid allergens that are released from the rubber particles. The nonammoniated form of C serum used in the skin test reagents in Europe is remarkably comprehensive in its allergen composition.

The skin test procedure involves performing a puncture with one of several lancet devices through a drop of latex extract at sequential concentrations ranging from 0.001 to 1 mg/mL of protein. The results are read after 15 minutes and compared with the positive histamine and negative saline controls. Caution should be exercised when performing skin testing with a latex extract since there is a report of anaphylaxis triggered by a skin prick test using Hevea latex [63]. (See "Overview of skin testing for allergic disease", section on 'Prick/puncture method'.)

The sensitivity ranged from 65 to 96 percent and specificity from 88 to 94 percent for use of the available extract products in pediatric patients with a history of urticaria, rhinoconjunctivitis, and/or asthma suspected to be triggered by natural rubber latex allergy [90].

There is no commercial skin test reagent available in the United States [84]. This has forced allergists in the United States who want to attempt skin testing to create extracts prepared in the office from Hevea latex products that vary widely in their allergen content [91-93]. Extracts prepared from examination gloves are unstable, uncharacterized, and of highly variable potency. The inability to document the presence and content of Hevea allergens in office-prepared extracts has led to concerns about false-negative diagnostic skin test results. Another concern is the potential for systemic reactions occurring as a result of skin testing with nonstandardized Hevea extracts due to potentially high levels of Hevea allergens [62]. For these reasons, use of these preparations is discouraged.

Puncturing through a Hevea-containing product (powdered glove) as an alternative or secondary testing method is also not encouraged, since it is not possible to know how much allergen has been distributed into the skin. There is a risk of a systemic allergic reaction from high-dose exposure or inadvertent inhalation with this testing method [62,90].

Serology testing — A preferred alternative to a prick/puncture skin test for confirming sensitization when commercial skin test reagents are not available is the measurement of Hevea latex-specific IgE antibody in serum [62,82,85,90,94]. Two serologic methods are widely used throughout the world: the ImmunoCAP and the Immulite autoanalyzers [94,95]. One US FDA-cleared autoanalyzer also in use in Europe (Noveos) addresses concerns of IgE anti-carbohydrate and exogenous biotin interferences that can occur with the ImmunoCAP and Immulite, respectively. These assays involve incubation of test human serum with an immobilized Hevea latex allergen-containing reagent. Bound IgE antibody is detected with an enzyme-labeled anti-human IgE reagent. Results are interpolated from a total IgE calibration curve in kUa/L. The nominal reported lower limit of quantitation (analytic sensitivity) of these assays is 0.1 kUa/L (0.24 ng/mL). The ImmunoCAP and Immulite assays display a diagnostic sensitivity and specificity of approximately 70 percent and >95 percent, respectively, when compared with the puncture skin test (lower detectable limit of these serologic assays at the time of this study was 0.35 kUa/L) [96,97].

A chip-based microarray containing eight recombinant Hev b allergens was shown to more clearly define the specificity of IgE anti-latex with no loss in diagnostic sensitivity compared with the singleplex ImmunoCAP [98]. A commercial version of this chip microarray (ImmunoCAP-ISAC) that contains recombinant Hev b 1, 3, 5, 6, and 8 has essentially remained a research tool as it is more expensive, less analytically sensitive, and more interfered with by immunoglobulin G (IgG) anti-latex than the singleplex latex allergen extract-based IgE assays. Results from one study suggest that this technique can distinguish between patients with latex allergy and sensitization [98,99]. Evaluation of skin test-positive patients with latex allergy revealed that the diagnostic sensitivity of the ImmunoCAP-ISAC is low (55 percent) for detecting IgE antibody to at least one Hev b allergen [97]. One strength of the ImmunoCAP-ISAC is in identifying sensitized, but asymptomatic individuals, with IgE positivity caused by cross-reactive latex profilin (Hev b 8) [100].

Provocation testing — Concerns about the safety, reproducibility, and interpretation of provocation methods have kept the methods in this category as last resort tests when all other tests are negative but the patient's history strongly suggests latex sensitization. A variety of glove use, nasal provocation, and inhalation challenge procedures have been reported. Latex-induced skin reactions or upper and lower airway allergic symptoms are used as the provocation tests' endpoint [5,54,101-105]. Most of these methods have remained research procedures that are not suitable for routine clinical use.

Testing for allergy to latex-related foods — If a patient with latex allergy has reacted to a latex-related food in the past, then that specific food should be avoided, and further testing to this food is not required. Patients who are uncertain as to whether they tolerate latex-related foods that they may encounter are not routinely evaluated for sensitization to these foods. Rather, skin prick testing with extracts or fresh food or serum food-specific IgE testing and possibly oral challenge are reserved for patients with latex allergy who specifically request evaluation for possible cross-sensitization. The primary reason for limiting testing is that performing skin or serology testing in the absence of a positive history of a reaction to a cross-reactive food can lead to "positive" IgE antibody results of unknown clinical significance and inappropriate avoidance practices.

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

There are 15 International Union of Immunological Societies (IUIS) documented Hevea latex allergens: Hevea brasiliensis Hev b 1 through Hev b 15. Four Hevea proteins are particularly useful as "indicator" allergens for assessment of the allergen content of rubber products or as markers of the presence of latex in the environment: Hev b 1, 3, 5, and 6.02. (See 'Hevea latex allergens' above.)

Clinical associations exist between latex allergy and allergic responses to a number of fruits and vegetables, including banana, kiwi, avocado, chestnut, papaya, potato, and tomato, because of crossreactivity among various proteins. (See 'Cross-sensitization among latex, fruit, and pollen' above.)

The prevalence of latex allergy peaked in the 1990s in many countries due to the introduction of "universal precautions." Rates in the general population and high-risk populations have decreased to low levels since then with extensive latex-safe hospital programs that employ powder-free, low-protein latex gloves and nonlatex (nitrile, neoprene) alternatives. However, rates of latex glove use and associated latex allergy remain high in some countries and in certain occupations. (See 'Epidemiology' above.)

The most common complaint of persons who wear Hevea latex medical gloves is of dry, crusted, and irritated skin. This does not represent an allergic reaction but rather is an irritant contact dermatitis. Clinical manifestations of latex allergy include non-immunoglobulin E (IgE) mediated allergic contact dermatitis and IgE-mediated urticaria, rhinoconjunctivitis, asthma, and anaphylaxis. (See 'Clinical manifestations' above.)

Establishing the presence of latex allergy can be challenging. The most reliable indicator of allergy is a strong clinical history that associates exposure with symptoms. Confirmatory tests (skin tests, serology, and provocation) are limited by reagent availability, varying reagent sensitivity/specificity and composition, and significant risks for triggering serious reactions. In the United States, serology is the principal test of choice. In other parts of the world where a characterized skin test reagent is available, prick/puncture skin test can be performed first. Provocation testing is generally not recommended. (See 'Diagnosis' above.)

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Topic 5543 Version 16.0

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