REVIEW ARTICLE Latex Allergy: An Update David L. Hepner, MD*, and Mariana C. Castells, MD, PhD† Departments of *Anesthesiology, Perioperative, and Pain Medicine and †Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts he rate of latex sensitization has been increasing NRL: Description, Proteins, and since its first recognition in 1979, and anesthesi- Biochemistry T ologists encounter patients with a diagnosis of latex allergy more and more often (1). Latex is a ubiq- NRL (cis-1,4-polyisoprene) is a milky fluid obtained uitous material that is found in balloons, condoms, primarily from the Hevea brasiliensis tree (6). Latex and many surgical and nonsurgical products. Anes- and natural rubber by-products are substances found thesiologists, like many other types of physicians who in many products present in hospital and home envi- often wear latex gloves, may also become sensitized to ronments. Since the 1980s, the increase in the inci- latex (2,3), and there are cases of disability of health dence of latex anaphylaxis has been associated with care professionals because of latex allergy (4,5). Latex the increased use of latex gloves because of Universal anaphylaxis may lead to significant morbidity, and Precautions. The use of Universal Precautions pro- deaths have been reported (4,5). It is essential to rec- moted by the Centers for Disease Control and Preven- ognize which patients and colleagues are sensitized to tion to decrease the spread of the human immunode- latex to provide appropriate treatment and to establish ficiency virus and hepatitis B and C viruses has lead to adequate prevention. a 25-fold increase in the use of latex-containing surgi- The purpose of this article is to review recent find- cal gloves (7). Over the last two decades, latex has emerged as the second most common cause of ana- ings and developments on latex allergy. This article phylaxis in surgical suites (16.6% of cases) (8). How- reviews the general concepts of latex allergy in the ever, a recent French report (9) found that the inci- perioperative setting and specifically addresses natu- dence of cases of latex anaphylaxis is decreasing as a ral rubber latex (NRL) proteins, reactions associated result of the identification of at-risk patients, im- with NRL, and high-risk groups for developing latex proved testing, and preventive measures. In addition, allergy. In addition, we discuss the diagnosis, man- many manufacturers are decreasing latex in a variety agement, and prevention of latex allergy and conclude of products (10). There is currently no cure for latex with a discussion of future therapies. allergy, and avoidance of latex-containing products is The literature was searched using Medline from mandatory for affected individuals. 1966 until July 2002. A literature search with the key Latex gloves are the major source of latex proteins words anesthesia, anesthesiology, operating room and are implicated in most cases of latex-mediated (OR) or surgery, and latex, latex allergy, or latex hy- reactions (11,12). Latex gloves contain proteins that persensitivity produced 80 articles. The references of are subject to hydrolysis and denaturation during pro- these manuscripts were reviewed to identify other cessing. Latex particles are generally insoluble in wa- relevant articles. Finally, additional references were ter but are made more soluble in the presence of identified from reviews and abstracts on latex allergy ammonia, which is used to stabilize and preserve com- from the allergy and clinical immunology literature mercial latex. Ammonia has been implicated in the from the last 5 yr. 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 mo- lecular weight polypeptides (13). Hevea brasiliensis latex contains several well-characterized proteins (14– Accepted for publication November 21, 2002. 18). The rubber elongation factor of rubber trees (He- Address correspondence and reprint requests to David L. Hepner, MD, Department of Anesthesiology, Perioperative, and Pain Medicine, vea brasiliensis or Hev b) is the major allergen in latex Brigham and Women’s Hospital, Harvard Medical School, 75 Francis (18) and there are 11 Hev b proteins (Hevb1toHev St., Boston, MA 02115. Address e-mail to [email protected]. b 11) of which latex profilin (Hev b 5, 18–20 kd) and DOI: 10.1213/01.ANE.0000050768.04953.16 hevein (Hev b 6.02, 4.7 kd) are common examples ©2003 by the International Anesthesia Research Society 0003-2999/03 Anesth Analg 2003;96:1219–29 1219 1220 REVIEW ARTICLE HEPNER AND CASTELLS ANESTH ANALG LATEX ALLERGY 2003;96:1219–29 (14,18). In addition, others have reported a 14-kd com- and Type IV mediated hypersensitivity (24). Another ponent as being an important allergen in latex (15–17). reaction associated with latex, but not caused by latex Hev b 5 sensitization is common among health care itself, is irritant contact dermatitis. workers. Irritant Contact Dermatitis. The most common reac- The increased demand for gloves also led to a de- tion associated with latex is an irritant contact derma- crease in processing time, and this in turn has led to an titis that may develop minutes to hours after exposure increase in latex proteins. Different manufacturers of to latex-powdered gloves or chemicals. It may occur gloves use different methods, standards, and process- on the first exposure, is usually benign, and not life ing times. There is a 3000-fold difference in latex con- threatening. It looks similar to a localized powder tents in 10 different brands of gloves (11). There are no abrasion with a loss of the epidermoid skin layer, government regulations that require glove companies eventually leading to soreness, pruritus, and redness. to label the protein content. Cornstarch, used as a The extent of the reaction depends on physical factors donning agent for gloves, acts as a carrier for latex such as the duration of exposure and skin tempera- allergens by binding to latex proteins. The cornstarch- ture. The alkaline pH of most powdered gloves is the latex particles are released into the air and inhaled and most likely cause of this reaction (25). may lead to respiratory symptoms (3). Allergic Contact Dermatitis or Type IV Cell-Mediated Frequently used products that contain latex include Hypersensitivity Reaction. This is a delayed onset im- urinary catheters, tourniquets, rubber plunger of sy- munologic reaction and results from T-cell-mediated ringes, IV tubing, tape, and electrocardiogram pads sensitization to the additives of latex. It is not life (Table 1). It is very difficult to predict which device threatening, and it is far more common than a Type I and brand may contain latex without appropriate la- reaction. This is usually secondary to a reaction to beling. Starting on September 30, 1998, the Food and antioxidants and rubber accelerators such as thiurams, Drug Administration (FDA) mandated that the prod- carbamates, and mercapto compounds. On a repeated ucts that contain latex be labeled as such, including exposure, a reaction begins within 48–72 h of expo- packaging devices containing NRL that require labels sure, often leading to erythema with vesicles and such as “Caution: The Packaging of this Product Con- scales. One can diagnose this type of reaction with a tains Natural Rubber Latex Which May Cause Allergic patch test to one of these antioxidants or accelerators Reactions” (19). Labeling statements relating to hy- (26). poallergenicity are prohibited because the FDA has Type I IgE-Mediated Hypersensitivity Reaction. This received several reports of allergic reactions to medi- is the most severe reaction and may lead to significant cal gloves labeled as hypoallergenic. morbidity and mortality. It requires sensitization and Natural rubber includes all materials made from or containing natural latex. The production of latex in- the production of IgE antibodies. On first exposure, patients are sensitized and produce IgE specific for volves the use of natural latex in a concentrated col- ϩ loidal suspension. In contrast, dry natural rubber pro- Hev b. Hev b proteins act as antigens, activate CD4 duction involves the use of coagulated natural latex T-helper cells Type II (Th2 cells), and induce B cells to dried or milled sheets. Dry natural rubber is less al- form specific Hev b IgE secreting plasma cells. The IgE lergenic than latex and carries a softer warning by the then binds to the surface of tissue mast cells and blood FDA as follows: “This Product Contains Dry Natural basophils. Upon reexposure, Hev b proteins cross-link Rubber” (19). However, dry natural rubber can cause membrane-bound IgE leading to degranulation of the allergic reactions and should not be used in a latex- sensitized mast cells and basophils. Preformed medi- allergic patient (20–23). It is of note that the FDA does ators, histamine, and proteases such as tryptase and not require manufacturers to recall nonlabeled devices newly generated arachidonic acid metabolites (prosta- already in interstate commerce before September 30, glandins and leukotrienes) are then released, leading 1998. to a reaction that ranges from local urticaria to a full-blown anaphylactic reaction. Latex proteins are absorbed slowly when the expo- sure is airborne, and symptoms usually develop ap- Reactions Associated with Latex proximately 30 min after exposure. Mild reactions in- Latex sensitization is defined as the presence of im- clude local urticaria, rhinitis, and conjunctivitis and munoglobulin (Ig)E antibodies to latex but without are more likely to result via airborne exposure or clinical manifestations. Latex sensitization does not direct contact with the skin. Powdered gloves may always lead to latex allergy, even if there is further release airborne particles (cornstarch) with latex pro- contact with latex products. Latex allergy refers to any tein, which can lead to symptoms such as bronchocon- immune-mediated reaction to latex associated with striction, rhinitis, and conjunctivitis.