Share this article on:

Latex Allergy: An Update

Hepner, David L. MD*,; Castells, Mariana C. MD, PhD†

doi: 10.1213/01.ANE.0000050768.04953.16
REGIONAL ANESTHESIA: Review Article

Departments of *Anesthesiology, Perioperative, and Pain Medicine and

†Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

November 21, 2002.

Address correspondence and reprint requests to David L. Hepner, MD, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115. Address e-mail to dhepner@partners.org.

The rate of latex sensitization has been increasing since its first recognition in 1979, and anesthesiologists encounter patients with a diagnosis of latex allergy more and more often (1). Latex is a ubiquitous material that is found in balloons, condoms, and many surgical and nonsurgical products. Anesthesiologists, like many other types of physicians who often wear latex gloves, may also become sensitized to latex (2,3), and there are cases of disability of health care professionals because of latex allergy (4,5). Latex anaphylaxis may lead to significant morbidity, and deaths have been reported (4,5). It is essential to recognize which patients and colleagues are sensitized to latex to provide appropriate treatment and to establish adequate prevention.

The purpose of this article is to review recent findings and developments on latex allergy. This article reviews the general concepts of latex allergy in the perioperative setting and specifically addresses natural rubber latex (NRL) proteins, reactions associated with NRL, and high-risk groups for developing latex allergy. In addition, we discuss the diagnosis, management, and prevention of latex allergy and conclude with a discussion of future therapies.

The literature was searched using Medline from 1966 until July 2002. A literature search with the key words anesthesia, anesthesiology, operating room (OR) or surgery, and latex, latex allergy, or latex hypersensitivity produced 80 articles. The references of these manuscripts were reviewed to identify other relevant articles. Finally, additional references were identified from reviews and abstracts on latex allergy from the allergy and clinical immunology literature from the last 5 yr.

Back to Top | Article Outline

NRL: Description, Proteins, and Biochemistry

NRL (cis-1,4-polyisoprene) is a milky fluid obtained primarily from the Hevea brasiliensis tree (6). Latex and natural rubber by-products are substances found in many products present in hospital and home environments. Since the 1980s, the increase in the incidence of latex anaphylaxis has been associated with the increased use of latex gloves because of Universal Precautions. The use of Universal Precautions promoted by the Centers for Disease Control and Prevention to decrease the spread of the human immunodeficiency virus and hepatitis B and C viruses has lead to a 25-fold increase in the use of latex-containing surgical gloves (7). Over the last two decades, latex has emerged as the second most common cause of anaphylaxis in surgical suites (16.6% of cases) (8). However, a recent French report (9) found that the incidence of cases of latex anaphylaxis is decreasing as a result of the identification of at-risk patients, improved testing, and preventive measures. In addition, many manufacturers are decreasing latex in a variety of products (10). There is currently no cure for latex allergy, and avoidance of latex-containing products is mandatory for affected individuals.

Latex gloves are the major source of latex proteins and are implicated in most cases of latex-mediated reactions (11,12). Latex gloves contain proteins that are subject to hydrolysis and denaturation during processing. Latex particles are generally insoluble in water but are made more soluble in the presence of ammonia, which is used to stabilize and preserve commercial latex. Ammonia has been implicated in the rupturing of organelles (i.e., lutoids) present in the latex with the release of soluble material (B-serum). B-serum fragments of latex protein result in low molecular weight polypeptides (13). Hevea brasiliensis latex contains several well-characterized proteins (14–18). The rubber elongation factor of rubber trees (Hevea brasiliensis or Hev b) is the major allergen in latex (18) and there are 11 Hev b proteins (Hev b 1 to Hev b 11) of which latex profilin (Hev b 5, 18–20 kd) and hevein (Hev b 6.02, 4.7 kd) are common examples (14,18). In addition, others have reported a 14-kd component as being an important allergen in latex (15–17). Hev b 5 sensitization is common among health care workers.

The increased demand for gloves also led to a decrease in processing time, and this in turn has led to an increase in latex proteins. Different manufacturers of gloves use different methods, standards, and processing times. There is a 3000-fold difference in latex contents in 10 different brands of gloves (11). There are no government regulations that require glove companies to label the protein content. Cornstarch, used as a donning agent for gloves, acts as a carrier for latex allergens by binding to latex proteins. The cornstarch-latex particles are released into the air and inhaled and may lead to respiratory symptoms (3).

Frequently used products that contain latex include urinary catheters, tourniquets, rubber plunger of syringes, IV tubing, tape, and electrocardiogram pads (Table 1). It is very difficult to predict which device and brand may contain latex without appropriate labeling. Starting on September 30, 1998, the Food and Drug Administration (FDA) mandated that the products that contain latex be labeled as such, including packaging devices containing NRL that require labels such as “Caution: The Packaging of this Product Contains Natural Rubber Latex Which May Cause Allergic Reactions”(19). Labeling statements relating to hypoallergenicity are prohibited because the FDA has received several reports of allergic reactions to medical gloves labeled as hypoallergenic.

Natural rubber includes all materials made from or containing natural latex. The production of latex involves the use of natural latex in a concentrated colloidal suspension. In contrast, dry natural rubber production involves the use of coagulated natural latex dried or milled sheets. Dry natural rubber is less allergenic than latex and carries a softer warning by the FDA as follows: “This Product Contains Dry Natural Rubber”(19). However, dry natural rubber can cause allergic reactions and should not be used in a latex-allergic patient (20–23). It is of note that the FDA does not require manufacturers to recall nonlabeled devices already in interstate commerce before September 30, 1998.

Back to Top | Article Outline

Reactions Associated with Latex

Latex sensitization is defined as the presence of immunoglobulin (Ig)E antibodies to latex but without clinical manifestations. Latex sensitization does not always lead to latex allergy, even if there is further contact with latex products. Latex allergy refers to any immune-mediated reaction to latex associated with clinical symptoms, which include Type I mediated hypersensitivity reactions to the latex protein itself and Type IV mediated hypersensitivity (24). Another reaction associated with latex, but not caused by latex itself, is irritant contact dermatitis.

Back to Top | Article Outline

Irritant Contact Dermatitis.

The most common reaction associated with latex is an irritant contact dermatitis that may develop minutes to hours after exposure to latex-powdered gloves or chemicals. It may occur on the first exposure, is usually benign, and not life threatening. It looks similar to a localized powder abrasion with a loss of the epidermoid skin layer, eventually leading to soreness, pruritus, and redness. The extent of the reaction depends on physical factors such as the duration of exposure and skin temperature. The alkaline pH of most powdered gloves is the most likely cause of this reaction (25).

Back to Top | Article Outline

Allergic Contact Dermatitis or Type IV Cell-Mediated Hypersensitivity Reaction.

This is a delayed onset immunologic reaction and results from T-cell-mediated sensitization to the additives of latex. It is not life threatening, and it is far more common than a Type I reaction. This is usually secondary to a reaction to antioxidants and rubber accelerators such as thiurams, carbamates, and mercapto compounds. On a repeated exposure, a reaction begins within 48–72 h of exposure, often leading to erythema with vesicles and scales. One can diagnose this type of reaction with a patch test to one of these antioxidants or accelerators (26).

Back to Top | Article Outline

Type I IgE-Mediated Hypersensitivity Reaction.

This is the most severe reaction and may lead to significant morbidity and mortality. It requires sensitization and the production of IgE antibodies. On first exposure, patients are sensitized and produce IgE specific for Hev b. Hev b proteins act as antigens, activate CD4+ T-helper cells Type II (Th2 cells), and induce B cells to form specific Hev b IgE secreting plasma cells. The IgE then binds to the surface of tissue mast cells and blood basophils. Upon reexposure, Hev b proteins cross-link membrane-bound IgE leading to degranulation of the sensitized mast cells and basophils. Preformed mediators, histamine, and proteases such as tryptase and newly generated arachidonic acid metabolites (prostaglandins and leukotrienes) are then released, leading to a reaction that ranges from local urticaria to a full-blown anaphylactic reaction.

Latex proteins are absorbed slowly when the exposure is airborne, and symptoms usually develop approximately 30 min after exposure. Mild reactions include local urticaria, rhinitis, and conjunctivitis and are more likely to result via airborne exposure or direct contact with the skin. Powdered gloves may release airborne particles (cornstarch) with latex protein, which can lead to symptoms such as bronchoconstriction, rhinitis, and conjunctivitis. Occupational exposure to latex is strongly correlated with allergic asthma. Baur et al. (27) screened subjects working in hospitals and ORs with different latex aeroallergen levels and demonstrated that sensitization and respiratory symptoms were likely to develop if the level of latex aeroallergens was more than 0.6 ng/m3. Others have published data about aeroallergen levels in ORs depending on the use of the room, total number of gloves used, and type of gloves (28). Long OR time, large number of gloves used, and high-allergen-containing gloves are associated with large aeroallergen levels (28). There is a recent report of a parturient at 32-wk gestation who developed dyspnea, wheezing, hypotension, and an urticarial rash, as well as fetal bradycardia after the removal of latex powdered gloves by a nurse (29).

Severe reactions usually occur shortly after parenteral or mucous membrane exposure and include flushing, vasodilatation, severe bronchospasm, and increased vascular permeability with edema and cardiovascular collapse (9). A recent survey of anaphylaxis during anesthesia demonstrated that cardiovascular symptoms (73.6%), cutaneous symptoms (69.6%), and bronchospasm (44.2%) were the most common clinical features (9). Mild reactions such as urticaria and angioedema may be masked by the presence of surgical drapes, whereas mild bronchoconstriction or hypotension may be masked by the presence of other anesthetics or may be difficult to recognize because they may mimic physiological reactions happening during anesthesia. Therefore, only a severe reaction may be recognized, and the only presenting sign may be cardiovascular collapse.

Other conditions that may resemble anaphylaxis should be considered. Histamine release, with skin manifestations such as hives, may occur from frequently used medications such as morphine and some nondepolarizing muscle relaxants. Bronchospasm may be secondary to an asthmatic attack, right mainstem obstruction, inadequate anesthesia, pneumothorax, mechanical obstruction, endobronchial intubation, pulmonary aspiration, pulmonary edema, or pulmonary embolism. Sudden cardiovascular collapse may be the result of an acute myocardial infarction or a high spinal anesthetic. The medical history, the timing of the event, and the clinical presentation are essential to aid in the precise diagnosis.

Anaphylaxis caused by something other than latex should also be considered. Allergic reactions to anesthetic drugs, such as propofol (30), nondepolarizing muscle relaxants, such as vecuronium (31), and opioids, such as fentanyl (32), usually occur within 10 min of the drug exposure but can also occur later (30 min to several hours). In general, drugs that have been used for long, continuous periods of time before the onset of an anaphylactic reaction are less likely to be the causative drug as opposed to a medication that was recently given (33). Sometimes it may be difficult to pinpoint the exact cause of the anaphylactic reaction either because of multiple medications being used or because of the failure to consider a medication that could cause an allergic reaction. Because latex is often not considered a medication, it is often not considered in the differential diagnosis of anaphylaxis, and this may lead to an erroneous diagnosis (34,35). There are also reports of anaphylaxis where the practitioner was not aware that a device, such as a pulmonary artery catheter, was made out of latex (36). Latex should always be considered in the differential diagnosis when an episode of perioperative anaphylaxis occurs. Failure to do so may lead to the wrong diagnosis or to another life-threatening episode if another exposure to latex occurs.

Back to Top | Article Outline

High-Risk Groups

Health care workers, nonhealth care workers with occupational exposure to latex such as hairdressers, food-service workers, and police officers, patients with atopic backgrounds, and children with spina bifida or genitourinary abnormalities who have undergone multiple surgeries are at increased risk for latex sensitivity (37). Spina bifida, even in the absence of multiple surgical procedures, seems to be an independent risk factor for latex sensitization (38). Adult patients undergoing multiple surgeries have a less frequent incidence of latex sensitization than children with spina bifida, and latex-free precautions from birth in children with spina bifida are more effective in preventing latex sensitization than the same precautions instituted later in life (39). Hev b 1 is the major allergen for children with spina bifida (39).

Occupational exposure to latex is common among health care workers such as nurses who work in the intensive care unit or postanesthesia care unit who change gloves approximately 50–100 times per day (personal communication between MCC and her latex-allergic nurses). A survey conducted among anesthesia faculty and residents at the Brigham and Women’s Hospital, Boston, MA, demonstrated that the average respondent changes their gloves approximately 15–20 times per day. The prevalence of latex sensitization is less than 1% in a nonatopic normal population, whereas the prevalence in health care workers ranges from 3%–12%(37). The incidence of latex sensitization, as measured by IgE levels, in ambulatory surgical patients at one institution was as frequent as 6.7%(1). Although sensitization does not always lead to an anaphylactic reaction, continued exposure to latex will increase the possibility of such a reaction. A health care worker who is atopic is at increased risk, and the risk is increased if they had a previous surgery (40). Anesthesiologists have a 12.5% and 2.4% prevalence of latex sensitization and allergy, respectively (2). Adult anesthesiologists change gloves more often than pediatric anesthesiologists and have been demonstrated to have an increased prevalence of latex sensitization (41). There is no increased risk of latex allergy with age, race, or sex, and exposure is the single most significant factor associated with latex allergy (2,42).

The use of powdered gloves in the United States has been significantly reduced in recent years. The removal of powder from gloves is important and is part of the continued evolution of improving the latex products that we use today. Latex sensitivity and latex-related symptoms such as urticaria, pruritus, asthma, and rhino-conjunctivitis have been shown to decrease in health care workers by changing from high-protein powdered gloves to low-protein, powder-free gloves (43). The American Academy of Allergy, Asthma, and Immunology and the American College of Allergy, Asthma, and Immunology recommend the use of powder-free latex gloves to decrease latex sensitivity among health care workers (44). A cost analysis of a conversion to a latex safe environment (no latex content at all) demonstrated that although there would be an initial increase in cost, it would be more than offset by the costs of diagnosis and disability because of latex sensitivity (45).

Back to Top | Article Outline

Latex-Fruit Syndrome

Some fruits, such as bananas and avocado pears, contain cross-reacting proteins with latex (46). In one study, fresh latex serum, latex gloves, avocado pears, and bananas shared a 30-kd epitope (46). An interesting finding from this study is that patients who were allergic to latex but not to fruits lacked the 30-kd protein band. In another study, IgE antibodies were detected for a 30-kd protein present in strawberries, bananas, guavas, citrus fruits, and peaches (47). Latex cross-sensitization with mangos is common in South Florida because of the ubiquity of mango trees in this area. Signs of allergic reactions to these fruits include pruritus, tightness in the throat, breathing difficulty, and hives. One study found that 21.1% (29 of 137) of patients with documented latex allergy had also food allergy. Fruits in that study included bananas, kiwis, watermelons, and peaches (48). In another study, 86% (49 of 57) of fruit-allergic patients were also allergic to latex compared with 4% (2 of 50) of controls (49). Allergies to melons, watermelons, peaches, bananas, cherries, and pears were common. Other foods often cited as being cross-reactive with latex include avocados, chestnuts, papains, potatoes, and tomatoes (50). Whereas patients allergic to fruits have an 11% risk of a latex reaction, patients allergic to latex have a 35% risk of a reaction to fruits (51).

Back to Top | Article Outline

Diagnosis

In the United States, the diagnosis of latex allergy is based on a focused history and physical examination followed by positive in vitro testing (52). A document released by the American Society of Anesthesiologists in 1999 states that a positive history or physical examination and a positive in vitro test establish the diagnosis of latex sensitivity (53). Standards for the diagnosis of latex allergy in the United States rely on in vitro serologic tests (Table 2). In vivo testing with ammoniated latex or from a nonammoniated source of latex is often used in Europe.

The diagnosis of anaphylaxis induced by latex is not different than that induced by other drugs or allergens. Table 3 outlines the components of the history and physical examination that should increase the index of suspicion for latex allergy. It is based on the presence of signs and symptoms suggestive of mast-cell activation and release of mediators. These include hypotension, bronchospasm, laryngeal edema, flushing, and urticaria. Other signs during an anesthetic include difficult hand ventilation, increased peak inspiratory pressure, expiratory wheezes, increased end-tidal carbon dioxide with an up-sloping of the tracing, tachycardia, and decreased blood pressure.

Back to Top | Article Outline

Blood Testing.

The retrospective diagnosis is based on serologic tests because skin testing is not currently approved in the United States. B-tryptase is a neutral protease stored in mast-cell secretory granules, which correlates with the level of hypotension, and an increased serum level demonstrates that mast-cell activation with mediator release has occurred (54,55). The level peaks at approximately 30 min and then gradually decreases (half-life is 2 h), but the more severe the reaction, the larger the B-tryptase level. The level may persist in the blood for many hours or even days after the episode (54,55). Levels of total tryptases more than 13 ng/mL or of β tryptase more than 1 ng/mL are specific for anaphylaxis because basophils possess minimal amounts of tryptase (56). Histamine is not measured routinely because of its short half-life of a few minutes. Urine histamine collections can be performed for 24 h after the anaphylactic episode and may be increased depending on the magnitude of anaphylaxis. Histamine is not specific for mast cells, and basophils have similar amounts (57).

Back to Top | Article Outline

Serologic Testing.

Serology involves the quantitative measurement of serum-specific IgE antibodies to latex. Serologic tests can be performed while the patient has extensive skin lesions, is on medications such as antihistamines, or has presented with a recent episode of anaphylaxis. The FDA has approved three different serum tests that use the RAST technique and include the Pharmacia ImmunoCAP (Pharmacia AB, Uppsala, Sweden), the HY-TEC EIA system (HYOCOR Biomedical, Irvine, CA), and the AlaSTAT (Diagnostic Product, Inc, Los Angeles, CA) (58). RAST tests are highly specific, but their sensitivity is low. The ImmunoCAP and AlaSTAT tests have specificities that range from 80%–87% and sensitivities that range from 50%–90%(53). The results of these tests are divided into seven classes and range from Class 0 to Class VI. Class 0 demonstrates the absence of IgE antibodies, and Classes I to VI demonstrate the presence of serum-specific IgE antibodies to latex. Whereas Classes I and II demonstrate a significant increase, Classes V and VI demonstrate a very large increase of IgE antibodies. The rate of false-positive tests is mostly because of antibodies against carbohydrates that cross-react with IgE antibodies to latex (59,60). The rate of false negative is frequent (25%), and negative IgE antibody results should be interpreted with caution, especially in the setting of a positive history for latex sensitivity. The HY-TEC assay has a less frequent false-negative rate but at the expense of a 25% false-positive rate. The HY-TEC assay has increased sensitivity (close to 10% more than the other two tests) at the cost of a decreased specificity. Recent work demonstrated that these FDA-approved serologic tests failed in some cases to identify common allergenic latex epitopes such as Hev b 2, 4, 5, 6, and 7b, furthermore demonstrating the small diagnostic sensitivity of these tests (61). It is not currently recommended to screen patients for latex allergy before a surgical procedure in the absence of a suggestive history. Doing so may significantly overestimate the incidence of latex sensitization because of the poor sensitivity of the RAST tests and the small prevalence of latex sensitization (<1%) in the general population (62).

Back to Top | Article Outline

Skin Testing.

Skin testing should be performed 4–6 wk after the anaphylactic episode because of mast-cell mediator depletion. There is the risk of inducing systemic anaphylaxis, and therefore, these tests should only be performed by physicians with adequate resuscitative equipment and training. There are no commercially available latex extract skin testing reagents in the United States, but there are reports of the use of minute extracts of latex gloves (37). The problem is that different types of latex gloves contain different amounts of proteins (63). Even the same type of gloves may contain different amounts of latex proteins because of different storage conditions. Skin testing reagents in Europe are made from ammoniated latex, used in the manufacturing of latex gloves, or from a nonammoniated source of latex (64).

Hamilton and Adkinson (65) compared nonammoniated latex, ammoniated latex, and rubber glove extracts as skin testing reagents in nonlatex-allergic and latex-allergic volunteers. They demonstrated that as long as equivalent total protein amounts were used, equivalent diagnostic sensitivity and specificity were observed in all groups. The authors concluded that nonammoniated latex might be considered the reagent of choice on the basis of practical quality control and reproducibility considerations (65). The same authors went on to document the safety and diagnostic sensitivity of a nonammoniated latex extract in 358 adults (66). The participants underwent serologic testing for the presence of latex-specific IgE (Pharmacia Cap) and skin testing. The skin-prick test was very sensitive and specific, and none of the participants with a history of latex allergy developed an episode of systemic anaphylaxis. Some of these patients did develop signs of mild systemic reactions such as pruritus, rash, rhinitis, ocular itch, or urticaria after skin testing (66). More recently, Biagini et al. (67) performed skin testing of health care workers with native forms of the Hev b allergens. Whereas skin testing with these allergens identified most latex-allergic health care workers, it was not as sensitive or as specific as the nonammoniated latex.

Back to Top | Article Outline

Management

Discontinuation of the potential trigger and of the anesthetic drug is very important in the treatment of anaphylaxis. Gloves should be changed to nonlatex if anaphylaxis is suspected and latex gloves are being used. Special attention should be given to a recent medication or blood product that was given, and their administration should be discontinued. No further medications, other than those required for the treatment of anaphylaxis, should be given.

Therapeutic options include airway maintenance with 100% oxygen, IV fluids to sustain the blood pressure (25–50 mL/kg), and resuscitation medications. Epinephrine is the most important medication for the treatment of anaphylaxis. Its α-agonist properties help sustain the blood pressure, whereas its β2 effect is effective in relieving bronchoconstriction. The dose and route used depends on the severity of the episode. Whereas the allergy literature recommends initial doses of 0.2–0.5 mg subcutaneously or IM (54), the presence of an IV catheter during an anesthetic and the faster systemic absorption via the parenteral route suggest that an IV administration is preferred during anesthesia. The recommended dose is 5–10 μg IV (0.l μg/kg) as the initial bolus in the presence of severe hypotension, followed by a titration to maintain systolic blood pressure (68). In the presence of cardiovascular collapse, 0.1–0.5 mg IV of epinephrine should be promptly administered (68). The experience of one of the authors (DH) suggests that the cardiovascular collapse may be severe enough to warrant repeated doses of epinephrine and that an infusion may be required (69).

Other useful medications include antihistamines (diphenhydramine 0.5–1 mg/kg IV or IM), bronchodilators (albuterol and ipratropium bromide via nebulization), H-2 blockers (ranitidine 150-mg IV bolus or cimetidine 400-mg IV bolus), and corticosteroids (methylprednisolone 0.5 mg/kg). Corticosteroids are not the first line of treatment because of their prolonged onset but are beneficial for delayed and late reactions. Once the initial event is treated and the patient is medically stable, a serum tryptase should be drawn, and an allergy consultation should be obtained.

Pharmacological prophylaxis in the acute setting with H-1 blockers (e.g., diphenhydramine), H-2 blockers (e.g., ranitidine), and steroids (e.g., methylprednisolone) is currently not recommended for patients with a documented latex allergy undergoing a surgical procedure. These medications do not produce any changes in the sensitized mast cells and basophils. Prophylaxis can diminish the early immune response, may blunt the early signs of anaphylaxis, and occasionally a very severe response such as cardiovascular collapse may be the only presenting sign (70,71).

Back to Top | Article Outline

Prevention

Prevention is the cornerstone in the management of latex sensitization. Patients should be educated regarding their condition and the means to protect themselves from future reactions by avoiding latex, wearing a Medic-Alert bracelet that identifies latex allergy for emergency situations, and carrying an Epi-Pen at all times. Table 4 identifies latex-free products available in the community. A recent follow-up study (72) on latex allergy in health care workers demonstrated that although the skin-prick test remained positive 2 yr after latex avoidance, latex specific IgE levels decreased in most patients. In addition, allergic symptoms decreased in most patients.

Dakin and Yentis (73) developed a strategy for management of latex allergic patients that consists of a collection of information of medical equipment including latex-free and latex-containing items and latex containing items that could be used with modification. These authors contacted the technical support division of the different manufacturers of medical equipment and posted these lists together with a protocol to manage latex-allergic patients in a latex-free box in the OR and labor and delivery floor (73). A protocol to manage latex-allergic patients consists of identification of at-risk groups, latex-free environment, and close coordination between all health care personnel involved in the management of these patients.

The American Society of Anesthesiologists Task Force of Latex Sensitivity recommends that patients who are latex allergic have a surgical procedure performed as the first case in the morning, when the levels of latex aeroallergens are the smallest (53). If it is not possible to do the case first, it is recommended to wash hands especially thoroughly to remove any traces of powder or latex. It is best to use nonpowdered gloves to avoid all latex aeroallergens (74). The OR should be latex safe, and all medical products should be made of nonlatex materials. A resuscitation cart should be next to the OR, and the room should be labeled (in a visible place) as a latex-free OR. Holzman (75) demonstrated that a latex-safe protocol was effective in preventing anaphylaxis in latex-allergic children. No prophylaxis was used in 267 anesthetics, and there was only one episode of anaphylaxis. This episode occurred in close temporal relation to the injection of a local anesthetic-opioid mixture from a syringe with a latex stopper. The mixture was prepared 1.5 wk before the injection, and the patient tolerated the same mixture when prepared from a latex-free syringe (75).

Although glass syringes or syringes with latex-free plungers (e.g., Becton Dickinson syringes, Becton Dickinson, Franklin Lakes, NJ) are the ideal approach, drawing the medication immediately before use into a syringe with a rubber-tipped plunger has been reported without complications (76). However, there is a report of an allergic reaction to latex in a patient who received morphine that was drawn immediately before the administration in a syringe with a rubber-tipped plunger (77). The bottom line is that it is safer to use glass syringes or those with latex-free plungers, especially in patients with known episodes of latex anaphylaxis. If a syringe with a rubber tip plunger is used, the contents of the syringe should be injected immediately after filling to decrease antigen release from the plunger. Premixed syringes of drugs should be avoided except in an emergency where the benefits of rapid treatment would outweigh the risk of additional latex exposure. However, it is best to notify the pharmacy in high-risk cases so that freshly prepared syringes with emergency medications are available, ideally prepared in latex-free syringes.

It is best to use medications from glass ampoules if available. If the formulation comes only in vials with stoppers, it is best to use those not made of latex. However, it is our experience that it is very difficult to know and keep track of which stopper is made out of latex. Furthermore, most stoppers contain latex. It has been recommended to avoid instrumentation of the rubber stopper with a syringe but instead to remove the stopper and then to draw up the medication (76–78). Because there is a report of an allergic reaction to latex from a vial stopper that was not punctured with a needle, the vial should be kept upright and not shaken (78). This case involved the use of a methylprednisolone vial that contained two rubber stoppers and required the displacement of one of the stoppers to mix the solid and liquid parts of the medication (78).

Although it is safest to use IV tubing, fluids, and injection ports that are latex-free, such as the Walrus anesthesia sets, latex-containing anesthesia sets have been used and recommended in patients with known latex sensitivity as long as the latex injection ports are not instrumented (76,78). Medications should be injected IV with the use of a stopcock, and all injection ports, including Y-sites, rubber boots, and T-pieces, should be covered with tape to prevent the accidental puncturing of these sites. Penetrating these sites may lead to liberation of latex particles into the IV fluid stream. Most injection sites are now latex free.

It is important that hospitals purchase nonpowdered surgical and examination gloves with small latex protein content to prevent the sensitization of health care workers and of patients requiring multiple surgical or nonsurgical procedures. Most reports of positive skin-prick responses to latex glove extracts in latex sensitized individuals occur when the protein content is more than 100 μg/g, as measured by the modified Lowry method (79). Smaller levels of protein exposure will reduce the risk for sensitization and elicitation of symptoms. The European Commission’s Scientific Committee on Medicinal Products and Medical Devices’ opinion of NRL allergy (80) was that the modified Lowry method is useful to distinguish between gloves containing small, moderate, and large protein levels, is simple to perform, and can be used as a routine method for monitoring production. However, because the limit of sensitization is likely to be close to or less than the quantification limit of the assay, there are concerns about whether it can be used to define a safe protein level (80). It is of note that the FDA allows manufacturers of latex gloves to have a 50 μg/g detection limit (81). There are concerted efforts by glove manufacturers in Malaysia to reduce the protein content of latex gloves to less than 100 μg/g. Although the threshold latex protein level for sensitization is unknown, the potential for allergenicity is markedly decreased when the level is <100 μg/g.

Back to Top | Article Outline

Future Therapies

Many patients who have latex allergy may be forced to quit their jobs, and complete avoidance of latex is difficult. Latex is found in many surgical products because it is relatively cheap, durable, and resistant (53). The tactile properties of latex are hard to replace, especially for surgeons performing fine surgeries. Vinyl gloves can be used as an alternative to latex, but durability and barrier properties have been of concern (82,83). Latex-sensitive individuals may develop symptoms of rhinitis and conjunctivitis when exposed to areas with increased levels of latex aeroallergens. This is of particular concern to health care workers, and it may be difficult to modify the working environment. Recent work has demonstrated that aerosol or particulate face masks were effective in reducing occupational exposure to latex (84). The use of powder-free gloves throughout the working environment is a much easier and effective alternative than wearing masks.

Immunotherapy, the controlled, standardized administration of an allergen to a sensitive patient, has proven effective in protecting patients with insect venom allergy and anaphylaxis. Immunotherapy has been considered in the setting of latex allergic health care workers. There is a report of subcutaneous desensitization treatment with standardized latex extract in a radiology technician with occupational latex allergy that was successful in minimizing respiratory and cutaneous symptoms (85). The patient was given incremental injections of latex extract subcutaneously until a local or systemic reaction was demonstrated. A maximum tolerated dose was calculated by the patient’s response and was given weekly to build up tolerance. Although there was an improvement in clinical symptoms, there was no significant change in the patient’s serum levels of IgE to latex, except for a mild increase at the end of the immunotherapy (85). Another randomized, double-blinded, placebo-controlled trial study conducted in Europe with a standardized latex extract on latex-allergic health care workers demonstrated improvements in the incidence and severity of rhinitis, conjunctivitis, and cutaneous symptoms (86). However, severe side effects including hypotension, bronchospasm, and pharyngeal edema developed in some patients. The authors acknowledged that further clinical trials with a smaller maintenance dose of latex extract are required before recommending this therapy (86). In addition, the authors caution that immunotherapy with latex allergen should be performed by experts in the field of allergy in a center with resuscitation equipment.

More recently, five cases of desensitization to latex were successfully performed by means of an original contact exposure protocol (87). Five health care workers with proven IgE-mediated latex allergy progressively increased their exposure to latex first by wearing latex gloves for 10 s/d on one hand. The goal was to reach a final exposure of 1 h in both hands twice a day at the end of a 1-yr period. All five subjects completed the protocol, no subject experienced side effects, the cutaneous reaction to latex was markedly decreased, and the latex-specific IgE levels decreased after the desensitization. The authors caution that these are preliminary reports and that future studies with a larger number of patients are required before recommending this treatment (87).

Recently, Hev b 5, a major latex allergen, has been modified at critical amino acid residues by site directed mutagenesis (88). This modification has resulted in decreased IgE binding activity, and new recombinant Hev b 5 proteins are being considered as candidates for immunotherapy (88). Modified latex proteins would induce little IgE binding on mast cells and few or no adverse reactions upon exposure. In addition, hevein (Hev b 6.02) has been well characterized as a three-dimensional structure and is considered as a good candidate for allergen specific immunotherapy (89). Its terminal regions were modified with single-point mutations that caused a decrease in IgE binding capacity.

Humanized anti-IgE monoclonal antibodies have been produced with a potential role in latex allergy and anaphylaxis. Patients with asthma and allergies treated with anti-IgE have shown a dramatic response, reducing symptoms and the need for medication (90).

In summary, awareness of latex allergy is essential to avoid an unnecessary increase in the morbidity and mortality of a growing population of patients. It is also essential that anesthesia practitioners, as well as other health care workers, use latex-free gloves or nonpowdered gloves with small latex protein count to prevent the sensitization of patients and health care workers. Although sensitization does not always lead to latex allergy, more frequent and prolonged exposure to latex is likely to increase the number of cases of latex allergy and anaphylaxis.

Recent developments in the fields of allergy and immunology are aiming to desensitize health care providers that are severely allergic to latex. Although these treatment modalities are currently experimental, they hold some promise for patients who have a severe latex allergy and for health care providers who have been forced to quit their jobs. Currently, avoidance of latex containing surgical products and a latex-free environment are mandatory in the care of sensitized patients.

Back to Top | Article Outline

References

1. Lebenbom-Mansour M, Oesterle JR, Ownby DR, et al. The incidence of latex sensitivity in ambulatory surgical patients: a correlation of historical factors with positive serum immunoglobin E levels. Anesth Analg 1997; 85: 44–9.
2. Brown RH, Schauble JF, Hamilton RG. Prevalence of latex allergy among anesthesiologists: identification of sensitized but asymptomatic individuals. Anesthesiology 1998; 89: 287–9.
3. Konrad C, Fieber T, Gerber H, et al. The prevalence of latex sensitivity among anesthesiology staff. Anesth Analg 1997; 84: 629–33.
4. Kelly KJ, Walsh-Kelly CM. Latex allergy: a patient and health care system emergency. Ann Emerg Med 1998; 32: 723–9.
5. Petsonk EL. Couriers of asthma: antigenic proteins in natural rubber latex. Occup Med 2000; 15: 421–30.
6. Slater JE. Allergic reactions to natural rubber. Ann Allergy 1992; 68: 203–11.
7. Centers for Disease Control. Recommendations for prevention of HIV transmission in health-care settings. Morb Mortal Wkly Rep 1987; Suppl 2: 3–18.
8. Vervloet D, Magnan A, Birnbaum J, Pradal M. Allergic emergencies seen in surgical suites. Clin Rev Allergy Immunol 1999; 17: 459–67.
9. Laxenaire MC, Mertes PM, Benabes B, et al. Anaphylaxis during anaesthesia: results of a two-year survey in France. Br J Anaesth 2001; 87: 549–58.
10. Palosuo T, Turjanmaa K, Ovod V, et al. Concentrations of natural rubber latex (NRL) allergens Hev b1, 3, 5 and 602 in NRL gloves capable of causing positive skin prick test reactions in NRL-allergic subjects (abstract). J Allergy Clin Immunol 2002; 109: S332.
11. Yunginger JW, Jones RT, Fransway AF, et al. Extractable latex allergens and proteins in disposable medical gloves and other rubber products. J Allergy Clin Immunol 1994; 93: 836–42.
12. Zucker-Pinchoff B, Stadtmauer GJ. Latex allergy. M Sinai J Med 2002; 69: 88–95.
13. Yeang HY, Cheong KF, Sunderasan E, et al. The 14.6 kd rubber elongation factor (Hev b 1) and 24 kd (Hev b 3) rubber particle proteins are recognized by IgE from patients with spina bifida and latex allergy. J Allergy Clin Immunol 1996; 98: 628–39.
14. Vallier P, Balland S, Harf R, et al. Identification of profilin as an IgE-binding component in latex from Hevea brasiliensis: clinical implications. Clin Exp Allergy 1995; 25: 332–9.
15. Alenius H, Turjanmaa K, Palosuo T, et al. Surgical latex gloves allergy: characterization of rubber protein allergens by immunoblotting. Int Arch Allergy Appl Immunol 1991; 96: 376–80.
16. Jaeger D, Kleinhans D, Czuppon AB, Baur X. Latex-specific proteins causing immediate-type cutaneous, nasal, bronchial, and systemic reactions. J Allergy Clin Immunol 1992; 89: 759–68.
17. Slater JE, Chabra SK. Latex antigens. J Allergy Clin Immunol 1992; 89: 673–80.
18. Czuppon AB, Chen Z, Rennert S, et al. The rubber elongation factor of rubber trees (Hevea brasiliensis) is the major allergen in latex. J Allergy Clin Immunol 1993; 92: 690–7.
19. Hubbard WK, Department of Health and Human Services. Food and Drug Administration: natural rubber-containing medical devices—user labeling. Federal Register 1997; 62: 189.
20. Lear JT, English JS. Anaphylaxis after hepatitis B vaccination. Lancet 1995; 345: 1249.
21. Towse A, O’Brien M, Twarog FJ, et al. Local reaction secondary to insulin injection. Diabetes Care 1995; 18: 1195–7.
22. MacCracken J, Stenger P, Jackson T. Latex allergy in diabetic patients: a call for latex-free insulin tops. Diabetes Care 1996; 19: 184.
23. Jones JM, Sussman GL, Beezhold DH. Latex allergen levels of injectable collagen stored in syringes with rubber plungers. Urology 1996; 47: 898–902.
24. Sussman G, Talo S, Dolovich J. The spectrum of IgE-mediated responses to latex. JAMA 1991; 265: 2844–7.
25. Brehler R, Kutting B. Natural rubber latex allergy: a problem of interdisciplinary concern in medicine. Arch Intern Med 2001; 161: 1057–64.
26. Cohen DE, Scheman A, Stewart L, et al. American academy of dermatology’s position paper on latex allergy. J Am Acad Dermatol 1998; 39: 98–106.
27. Baur X, Chen Z, Allmers H. Can a threshold limit value for natural rubber latex airborne allergens be defined? J Allergy Clin Immunol 1998; 101: 24–7.
28. Heilman DK, Jones RT, Swanson MC, Yunginger JW. A prospective, controlled study showing that rubber gloves are the major contributor to latex aeroallergen levels in the operating room. J Allergy Clin Immunol 1996; 98: 325–30.
29. Eckhout GV, Ayad S. Anaphylaxis due to airborne exposure to latex in a primigravida. Anesthesiology 2001; 95: 1034–5.
30. Laxenaire MC, Mata-Bermejo E, Moneret-Vautrin DA, Gueant JL. Life-threatening anaphylactoid reactions to propofol (Diprivan). Anesthesiology 1992; 77: 275–80.
31. Harle DG, Baldo BA, Fisher MM. Cross reactivity of metocurine, atracurium, vecuronium and fazadinium with IgE antibodies from patients unexposed to these drugs but allergic to other myoneural blocking drugs. Br J Anaesth 1985; 57: 1073–6.
32. Bennett MJ, Anderson LK, McMillan JC, et al. Anaphylactic reaction during anesthesia associated with positive intradermal skin test to fentanyl. Can Anaesth Soc J 1986; 33: 75–8.
33. Weiss ME, Adkinson NF Jr, Hirshman CA. Evaluation of allergic drug reactions in the perioperative period. Anesthesiology 1989; 71: 483–6.
34. Zucker-Pinchoff B, Ramanathan S. Anaphylactic reaction to epidural fentanyl. Anesthesiology 1989; 71: 599–601.
35. Zucker-Pinchoff B, Chandler MJ. Latex anaphylaxis masquerading as fentanyl anaphylaxis: retraction of a case report. Anesthesiology 1993; 79: 1152–3.
36. Gosgnach M, Bourel LM, Ducart A, et al. Pulmonary artery catheter balloon: an unusual cause of severe anaphylactic reaction. Anesthesiology 1995; 83: 220–1.
37. Kurup VP, Fink JN. The spectrum of immunologic sensitization in latex allergy. Allergy 2001; 56: 2–12.
38. Hochleitner BW, Menardi G, Haussler B, et al. Spina bifida as an independent risk factor for sensitization to latex. J Urol 2001; 166: 2370–3.
39. Nieto A, Mazon A, Pamies R, et al. Efficacy of latex avoidance for primary prevention of latex sensitization in children with spina bifida. J Pediatr 2002; 140: 370–2.
40. Zak HN, Kaste LM, Schwarzenberger K, et al. Health-care workers and latex allergy. Arch Environ Health 2000; 55: 336–46.
41. Greenberg RS, Hamilton RG, Brown RH. Differential latex allergy prevalence in anesthesiology subspecialties (letter). Anesthesiology 1999; 90: 1238.
42. Poley GE, Slater JE. Latex allergy. J Allergy Clin Immunol 2000; 105: 1054–62.
43. Saary MJ, Kanani A, Alghadeer H, et al. Changes in rates of natural rubber latex sensitivity among dental school students and staff members after changes in latex gloves. J Allergy Clin Immunol 2002; 109: 131–5.
44. AAAAI and ACAAI joint statement concerning the use of powdered and non-powdered natural rubber latex gloves. Ann Allergy Asthma Immunol 1997; 79: 487.
45. Phillips VL, Goodrich MA, Sullivan TJ. Health care worker disability due to latex allergy and asthma: a cost analysis. Am J Public Health 1999; 89: 1024–8.
46. Lavaud F, Prevost A, Cossart C, et al. Allergy to latex, avocado pear, and banana: evidence for a 30 kd antigen in immunoblotting. J Allergy Clin Immunol 1995; 95: 557–64.
47. Wadee AA, Boting LA, Rabson AR. Fruit allergy: demonstration of IgE antibodies to a 30 kDa protein present in several fruits. J Allergy Clin Immunol 1990; 85: 801–7.
48. Kim KT, Hussain H. Prevalence of food allergy in 137 latex-allergic patients. Allergy Asthma Proc 1999; 20: 95–7.
49. Garcia Ortiz JC, Moyano JC, Alvarez M, Bellido J. Latex allergy in fruit allergic patients. Allergy 1998; 53: 532–6.
50. Perkin JE. The latex and food allergy connection. J Am Diet Assoc 2000; 100: 1381–4.
51. Sicherer SH. Clinical implications of cross-reactive food allergens. J Allergy Clin Immunol 2001; 108: 881–90.
52. Warshaw EM. Latex allergy. J Am Acad Dermatol 1998; 39: 1–24.
53. Berry AJ, Katz JD, Brown RH, et al. Natural rubber latex allergy: consideration for anesthesiologists. Park Ridge, IL: American Society of Anesthesiologists, 1999: 1–34.
54. Supplement to the journal of allergy and clinical immunology. J Allergy Clin Immunol 1998; 101: S465–528.
55. Schwartz LB, Bradford TR, Rouse C, et al. Development of a new, more sensitive immunoassay for human tryptase: use in systemic anaphylaxis. J Clin Immunol 1994; 14: 190–204.
56. Castells MC, Irani A-M, Schwartz LB. Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol 1987; 138: 2184–9.
57. Schwartz LB, Irani A-M, Roller K, et al. Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. J Immunol 1987; 138: 2611–5.
58. Biagini RE, Krieg EF, Pinkerton LE, Hamilton RG. Receiver operating characteristics analyses of Food and Drug Administration-cleared serological assays for natural rubber latex-specific immunoglobulin E antibody. Clin Diagn Lab Immunol 2001; 8: 1145–9.
59. Mari A, Iacovacci P, Afferni C, et al. Specific IgE to cross-reactive carbohydrate determinants strongly affect the in vitro diagnosis of allergic diseases. J Allergy Clin Immunol 1999; 103: 1005–11.
60. Van Ree R, Aalbertese RC. Specific IgE without clinical allergy. J Allergy Clin Immunol 1999; 103: 1000–1.
61. Hamilton RG, Biagini R, Mackenzie B, et al. FDA-cleared immunoassays for latex-specific IgE are missing allergenic epitopes from multiple hev b allergens (abstract). J Allergy Clin Immunol 2002; 109: S259.
62. Charous BL, Blanco C, Tarlo S, et al. Natural rubber latex allergy after 12 years: recommendations and perspectives. J Allergy Clin Immunol 2002; 109: 31–4.
63. Alenius H, Makinen-Kiljunen S, Turjanmaa K, et al. Allergen and protein content of latex gloves. Ann Allergy 1994; 73: 315–20.
64. Akasawa A, Hsieh LS, Lin Y. Comparison of latex-specific IgE binding among nonammoniated latex, ammoniated latex, and latex glove allergenic extracts by ELISA and immunoblot inhibition. J Allergy Clin Immunol 1996; 97: 1116–20.
65. Hamilton RG, Adkinson NF Jr. Natural rubber latex skin testing reagents: safety and diagnostic accuracy of nonammoniated latex, ammoniated latex, and latex rubber glove extracts. J Allergy Clin Immunol 1996; 98: 872–83.
66. Hamilton RG, Adkinson NF Jr. Diagnosis of natural rubber latex allergy: multicenter latex skin testing efficacy study—multicenter latex skin testing study task force. J Allergy Clin Immunol 1998; 102: 482–90.
67. Biagini R, Bernstein DI, Karnani R, et al. Diagnostic sensitivity of puncture skin testing (PST) with isolated native and recombinant proteins from Hevea Brasiliensis (Hev b) for the diagnosis of latex hypersensitivity in health care workers (abstract). J Allergy Clin Immunol 2002; 109: S257(783).
68. Levy JH. Allergy and adverse drug reactions. Am Soc Anesth Ann Meet Refresher Course Lec 2000; 162: 1–7.
69. Hepner DL. Sudden bronchospasm on intubation: latex anaphylaxis? J Clin Anesth 2000; 12: 162–6.
70. Weiss ME, Hirshman CA. Latex allergy. Can J Anaesth 1992; 39: 528–32.
71. Setlock MA, Cotter TP, Rosner D. Latex allergy: failure of prophylaxis to prevent a severe reaction. Anesth Analg 1993; 76: 650–2.
72. Palczynski CM, Walusiak JM, Wittczak TA, et al. Follow-up study on latex allergy in health care workers (abstract). J Allergy Clin Immunol 2002; 109: S258.
73. Dakin MJ, Yentis SM. Latex allergy: a strategy for management. Anaesthesia 1998; 53: 774–81.
74. Jackson EM, Arnette JA, Martin ML, et al. A global inventory of hospitals using powder-free gloves: a search for principled medical leadership. J Emerg Med 2000; 18: 241–6.
75. Holzman RS. Clinical management of latex-allergic children. Anesth Analg 1997; 85: 529–33.
76. Holzman RS. Latex allergy: an emerging operating room problem. Anesth Analg 1993; 76: 635–41.
77. Kearns CF, Norris A. Latex allergy and plastic syringes. Anesth Analg 1996; 82: 429.
78. Vassallo SA, Thurston TA, Kim SH, Todres DI. Allergic reaction to latex from stopper of a medication vial. Anesth Analg 1995; 80: 1057–8.
79. Turjanmaa K, Lauren K, Makinen-Kiljunen S, Reunala T. Rubber contact urticaria: allergenic properties of 19 brands of latex gloves. Contact Dermatitis 1988; 19: 362–7.
80. Scientific Committee on Medicinal Products and Medical Devices. Opinion on natural rubber latex allergy. Eur Commission, June 2000.
81. Beezhold D, Pugh B, Liss G, Sussman G. Correlation of protein levels with skin prick test reactions in patients allergic to latex. J Allergy Clin Immunol 1996; 98: 1097–102.
82. Olsen RJ, Lynch P, Coyle MB, et al. Examination gloves as barriers to hand contamination in clinical practice. JAMA 1993; 270: 350–3.
83. Rego A, Roley L. In-use barrier integrity of gloves: latex and nitrile superior to vinyl. Am J Infect Control 1999; 27: 405–10.
84. Mitakakis TZ, Tovey ER, Yates D, et al. Interventions of latex allergen inhaled by health care workers through use of breathing masks or non-powdered gloves (abstract). J Allergy Clin Immunol 2002; 109: S257(785).
85. Pereira C, Rico P, Lourenco M, et al. Specific immunotherapy for occupational latex allergy. Allergy 1999; 54: 291–3.
86. Leynadier F, Herman D, Vervloet D, Andre C. Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers. J Allergy Clin Immunol 2000; 106: 585–90.
87. Patriarca G, Nucera E, Buonomo A, et al. Latex allergy desensitization by exposure protocol: five case reports. Anesth Analg 2002; 94: 754–8.
88. Beezhold DH, Hickey VL, Sussman GL. Mutational analysis of the IgE epitopes in the latex allergen Hev b 5. J Allergy Clin Immunol 2001; 107: 1069–76.
89. Karisola P, Mikkola J, Reunala T, et al. Identification of IgE-binding aminoacids on the conformational epitopes of hevein (Hev b 6.02) (abstract). J Allergy Clin Immunol 2002; 109: S1030.
90. Milgrom H, Fick RB Jr, Su JQ, et al. Treatment of allergic asthma with monoclonal anti-IgE antibody. N Engl J Med 1999; 341: 1966–73.
© 2003 International Anesthesia Research Society