Natural rubber latex allergy: Spectrum, diagnostic approach, and therapy

Natural rubber latex allergy: Spectrum, diagnostic approach, and therapy

The Journal of Emergency Medicine, VOI IS. No 1, pp 7 I-85. 1997 Copyright 0 1997 Elsevier Science Inc. Printed in the USA. All rights reserved 07?&46...

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The Journal of Emergency Medicine, VOI IS. No 1, pp 7 I-85. 1997 Copyright 0 1997 Elsevier Science Inc. Printed in the USA. All rights reserved 07?&4679,97

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NATURAL RUBBER LATEX ALLERGY: SPECTRUM, DIAGNOSTIC APPROACH, A#D THERAPY Julia A. Woods, BA, * Susan Lambert, RN, BSN , * Thomas A. E. Platts-Mills, David B. Drake, MD,* and Richard F. Edlich, MD, PhD*

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Departments of *Plastic Surgery and tlnternal Medicine/Allergy, University of Virginia School of Medicine, Charlottesville, Virginia Reprmt Address: Richard F. Edlich, MD, Pho, Department of Plastic Surgery, Box 332, University of Virginia School of Medicine, Charlottesville. VA 22908

J Abstract-Latex allergy has reached epidemic proportions in the United States and is increasingly recog nized as a significant contributor to morbidity and mortality during medical and surgical procedures. Ultimately, many of the affected patients with recognized latex sensitivity and those who are not yet diagnosed will receive treatment for their allergic reactions to latex in emergency departments. Consequently, emergency phy sicians must have a comprehensive understanding of the etiology, epidemiology, pathogenesis, treatment, and management of these challenging patients. Groups at high risk include spina billda cystica patients, health care workers, latex industry workers, specific food-allergy patients, aud patients with a history of atopy or multiple surgical procedures. Sensitization to latex antigens is commonly encountered in health care workers wearing latex gloves with high latex allergen concentrations and in workers using powdered latex surgical gloves. Exposure to air-borne allergens aad water-soluble IgE reactive latex antigens from natural rubber latex products in sensitized individuals can result in type I (immediate) hypersensitivity reactions. Clinical manifestations include contact urticaria, dermatitis, allergic rhinitis, conjunctivitis, asthma, angioedema, and anaphylaxis. Diagnostic t&s include serological assays and skin prick testing. At present, latex avoidance is the only available treatment and is the key to preventing allergic reactions in latex-sensitized individuals. Health care worker sensitization to latex antigens in natural rubber products is becomiq an increasing contributor to workers’ liability and disability claims. Specific action can be taken to reRECEIVED: ACCEPTED:

21 February 1996; FINAL 4 June 1996

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duce occupational and patient exposure to latex slltigens.

Copyright 0 1997Elsevier ScienceInc. q Keywords-latex allergy; natural rubber; laxis; hnmediate hypersensitivity; oceq&omd powdered latex gloves; spina biflda

amyallergy;

INTRODUCTION

During the last 100 years, latex products have become ubiquitous in our environment. The popularity of latex is attributed to its unique biomechanical performance characteristics, which include strength, elasticity, tear resistance, and superior barrier qualities ( 1) . Until recently, complications stemming from the use of latex products were thought to be limited to contact dermatitis. During the last decade, the prevalence of latex allergy has reached epidemic levels. This rapid increase in the prevalence of latex allergy has coincided with the implementation of universal precautions. The frequency of latex glove donning and removal by health care professionals is extremely high for those working in the emergency medical system. This high level of exposure to latex gloves and other latex medical products by emergency medical workers place them in a high-risk group for developing latex allergy. For this

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reason alone, emergency physicians should be knowledgeable about latex allergy. Another compelling reason for their interest in this subject is that they will be the cornerstone of treatment of life-threatening allergic reactions to latex in individuals with documented latex allergies and those without a previous history of latex allergy. This collective review of latex allergy highlights the etiology, epidemiology, pathogenesis, diagnosis, and management of this challenging clinical problem. LATEX MANUFACTURING

PROCESSES

Natural rubber latex is a cytoplasmic exudate derived from the cytosol, or latex, of the commercial rubber tree, Havea brasiliensis (2). The vast majority of H. brusiliensis cultivation occurs in Malaysia, Indonesia, and Thailand. After latex is harvested by sap collection from the rubber tree, ammonia is added immediately to prevent bacterial contamination and autocoagulation. Ammonia disrupts the collected sap, resulting in a twophase product that is later concentrated by centrifugation. The centrifuged sample is sold as either high ammonia latex concentrate (0.7% ammonia by weight) or low ammonia latex concentrate (0.2-0.3% ammonia by weight). Accelerators, antioxidants, and secondary preservatives are then added to these concentrated latex preparations. Approximately 90% of the harvested rubber is used in the manufacture of extruded rubber products (e.g., rubber thread), injection molded goods (e.g., rubber seals, diaphragms), or pneumatic tires for vehicles (3). The remaining 10% of the harvested rubber is used in the manufacture of dipped products including rubber gloves, condoms, and balloons. Dipped products are primarily responsible for most of the anaphylactic reactions to natural rubber latex. There are two basic dipping techniques used in the production of latex gloves and condoms. Surgical and industrial gloves are most often created by coagulant dipping, which involves the use of a salt or other ionic compound deposited on the dipping former. The former is then dipped in the latex compound and the product of these two steps is oven dried. Straight dipping techniques, used for the production of very thin films, such as condoms and examination gloves, involve the use of formers that are dipped directly into the latex compound. The thin latex film is then oven dried. Once the coagulant dipping or the straight dipping step is complete, the oven-dried gloves are passed through leaching tanks to remove water-soluble proteins and excess additives. The glove is then cured by vulcanization, a heat-catalyzed process in which the

latex molecules are cross linked in the presence of sulfur-containing accelerators. Some manufacturers use powder lubricants, which are applied after vulcanization. Powder-free gloves are processed separately by either coating their surface with a hydrogel polymer or passing the gloves through a chlorination wash that makes the glove surface more slippery. After these processing steps, the powdered and powder-free gloves are stripped from their formers and packaged for distribution. The essential structural functional unit in processed latex is spherical droplet cis- 1,Cpolyisoprene, which is coated with a layer of protein, lipid, and phospholipid. The protein content of rubber tree sap is approximately 15 mg/mL. Some protein is lost by hydrolysis when ammonia is added to the sap, and more is lost on centrifugation of raw latex. Many scientists agree that latex-specific allergens are present in raw rubber tree sap and persist in extracts of finished latex products ( 1). The protein components in latex have been blamed as the agentsresponsible for latex-specific allergy, with three exceptions. First, the accelerators and antioxidants used in glove processing are causative agents of type IV allergic reactions occurring with the use of latex gloves (i.e., dermatitis). Second, when casein is added to some brands of surgical and household gloves, it may be responsible for glove-related reactions in milk-sensitive individuals (4). Third, there are isolated reports of allergy to the bleached cornstarch powder lubricants used in most powdered latex gloves (5). In addition, cornstarch powders can adsorb allergenic latex proteins, thus promoting the development of respirable air-borne latex-sensitizing particles. Natural rubber latex is distinct from butyl rubber and from latex in paints, both of which present no danger to persons who are sensitized to natural rubber latex (hereafter referred to as latex). ETIOLOGY Latex proteins are potent allergens capable of inducing potentially fatal anaphylaxis. Accurate measurement of these proteins in latex medical products is very difficult. In addition, isolation and characterization have been complicated by variations in the manufacturing process. Ammoniation, centrifugation, pre- and postvulcanization, on-line leaching, dry-film washing, exposure to proteolytic enzymes during leaching, and chlorination can all have considerable impact on the protein fractions in latex. Latex proteins can be divided into three groups: water-soluble proteins, starch-bound proteins, and latex-bound proteins.

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Latex Allergy

Water-Soluble Latex Antigens

Water-soluble proteins are easily extracted with saline solutions from latex gloves. Carrillo et al. (6) were the first to determine that a latex allergen responsible for immediate hypersensitivity was a water-soluble protein. They filtered the latex allergen from natural rubber into three fractions and demonstrated that it has a molecular weight over 30,000 kDa. Morales et al. (7 ) later isolated four soluble polypeptides from latex that seemed responsible for the hypersensitivity reactions. They showed that these four proteins bind to IgE in the serum of patients who have experienced anaphylactic reactions to latex products. Furthermore, these four proteins give positive skin prick tests in individuals sensitive to latex. Other soluble proteins isolated from latex gloves and chemical additives from latex processing did not elicit such a response in these patients. Research efforts directed at identifying IgEreactive latex antigens have demonstrated that crude ammoniated and nonammoniated latex extracts appeared to have similar antigenic proteins. Over 15 different latex antigens have been identified, all of which bind IgE antibodies in individual or pooled sera obtained from latex-sensitive individuals. Fortunately, these soluble proteins can be reduced or removed from gloves by repeated leaching and other manufacturing modifications by the industry. Starch Powder-Bound

Protein

Cornstarch powder used as a lubricant to easeremoval from the former in glove manufacture and to easedonning of surgical gloves servesas a vector for latex allergens. The possibility that powder lubricants on surgical gloves act ascarriers of latex antigenswas first suggested by Baur and Jaeger(8). This hypothesis was substantiated by Turjanmaa et al. (9), who demonstrated that patients with latex sensitivity have IgE present in their serum that interacts with glove extracts, crude latex extracts, and glove powder extracts. Beezhold and Beck ( 10) extended these observationsby using Western blot analysis and polyclonal rabbit IgG antiserum.They identified a significant interaction between latex proteins and cornstarch powders and suggestedthat the latex proteinstarch particle represents a potentially reactive antigen and an agentfor exposureand sensitizationof health care workers to latex proteins. Complex antigenshave long been recognized as having more immunogenic potential than smaller proteins or biochemically simple molecules ( 11). Furthermore, antigens that are composed of protein-polysaccharide complexes are strongly immunogenic ( 11) . The addition

of cornstarch as a lubricant during the manufacture of surgical and medical examination gloves may create a new set of antigens with high immunogenic potential. Becauseit is very difficult, costlyl and time consuming to remove cornstarch from surgical gloves by washing, these protein-coated starch particles may gain accessto the wound ( 10). Once in the body, Beezhuld ( 12) asserted, the protein-starch particles act as adjuvants that enhance immune recognition of the relatively small amounts of bound latex proteins and may favor the production of IgE antibodies. Studies were performed by Beezhold et al. ( 13) using a modified immunoblot technique with rabbit anti-latex-protein antiserum (to detect total latex antigen) and human serum from one latex-allergic subject who had experienced anaphylaxis from glove contact during surgery (to detect IgE-reactive latex allergens ) . These studies have demonstrated that latex protein from gloves was transferred to saline-moistened nitrocellulose membranes immediately upon contact and that washing powdered gloves prior to use had no effect on the amount of antigen transferred to the membrane. Furthermore, they found that powder-free gloves have much lower levels of transferred proteins. They also studied the latex protein transfer from surgical gloves to the hand of the glove wearer and demonstrated that immediately after glove removal considerable protein was left on the skin of the wearer. Protective hand creamsapplied before the donning of surgical gloves increased the amount of latex protein that was transferred from gloves to the hands of the wearers. There may be up to 700 mg of powder on a typical pair of sterile surgical gloves (14). Swanson et al. ( 1.5) quantified the occupational exposure of health care personnel to latex aeroallergens within a medical center by collecting air samples using area and personal breathing zone air samplers.They measuredlatex allergens with a radioallergosorbent (RAST) inhibition assay using IgE antibodies from latex-sensitive individuals. Latex aeroallergen concentrations were 13208 rig/m” in 11 areas where powdered gloves were frequently used. In four areas of the medical center. where powdered gloves were rarely or uever used or where vinyl or powder-free latex gloves were used. concentrations were 0.3- 1.8 ng/m3. Large quantities of allergen were recovered from swabs of laboratory surfaces and from used laboratory coats and surgical scrub suits. An amount in excess of 1 mg of allergen was recovered from one laboratory coat that had been in use for a week. They reported that exposure most likely occurred when gloves were frequently donned and removed and from resuspension of powder from reservoirs in the room and on clothing Swanson et al. ( 15) noted that latex aeroallergen lel:els were not

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significantly different in an operating room with high laminar flow air exchange rate (225 times/h) as compared with an operating room with conventional air exchange rate (25 times/h). They concluded that control of exposure by changing to powder-free and low allergen-containing gloves may be a more effective approach than air filtration or trying to contain airborne allergens within a glove-changing station.

Latex-Bound Proteins Insoluble latex proteins are incorporated in the polyisoprene matrix of the glove. These proteins may be physically trapped or noncovalently linked to the latex. Although the presence of these proteins has not been explicitly demonstrated, their presence was inferred by Beezhold (12) after demonstrating the reactivity to patch testing in latex-sensitized individuals with washed powder-free gloves. There are several methods to prevent the reactivity of these latex-bound proteins. During the formulation of latex, removal of all traces of protein from raw latex has been attempted but was unsuccessful. The use of a hydrogel coating of the latex that reduces direct contact of the hand to the latex has been achieved successfully.

Total Protein In quantifying exposure, there remains debate as to whether one should measure the total protein content of latex products or the fraction of proteins that have so far been identified to function as allergens. Because patients recognize many different proteins rather than a few allergens, measurement of total protein in latex products is now the accepted method of quantifying exposure ( 16).

EPIDEMIOLOGY General Population In 1994, Ownby et al. (17) measured latex-specific IgE in the serum from 1000 blood donors selected to minimize sampling of health care workers. Sixty-five (6.5%) were repeatedly positive for antilatex IgE antibodies. Prevalence of positive samples was not associated with age or race. Samples from men were more likely to be positive than samples from women (8.7% vs. 4.1%).

et al.

High-Risk Groups Spina bijida patients. Patients with spina bifida cystica form a population at highest risk for latex allergy. An epidemiologic study conducted by Kelly et al. (18) has indicated that spina bifida pediatric patients have a risk of latex-related anaphylaxis during operative procedures that is 500 times greater than that of the general pediatric population ( 12/ 152 vs. O/7684). Eight of 10 pediatric patients experiencing anaphylaxis during surgery were spina bifida cystica patients (19). Prevalence rates of latex sensitivity among the spina bifida cystica pediatric population was reportedly 40-65% (20). Meningocele, meningomyelocele, and myeloschisis are part of the anomaly referred to as spina bifida cystica, which is found with a frequency of 4.3 per 10,000 live births (21-23). Spina bifida cystica is frequently associated with severe neurologic defects that correlate to the level of the cerebrospinal defect. Thoracic lesions are associated with the most severe neurologic deficits and present with vertebral column instability. Most patients with these lesions have bowel and bladder dysfunction, The bladder dysfunction may manifest as repeated episodes of urinary tract infection, reflux neuropathy, or renal insufficiency. Meningomyelocele is also often associated with a caudal displacement of the medulla and of a portion of the cerebellum in the spinal canal, the Arnold-Chiari brainstem malformation (21) . Because the foramen magnum is obstructed by either the brainstem or the cerebellum, this defect almost invariably causes hydrocephalus, requiring early placement of a ventriculoperitoneal shunt. Management of infants with spina bifida cystica involves different procedures that include immediate operative skin closure of an open- or thin-walled defect, ventriculoperitoneal shunting of hydrocephalus, bracing of the lower extremities, and other surgical procedures to address sensory deficits, bowel and bladder dysfunction, pain elimination, orthopedic problems, and to minimize or prevent associated neurologic defects (22). In 1986, Lozynsky et al. (24) described six children with spina bifida who had adverse reactions following saline enema infusions; these children collectively experienced 13 cases of generalized hives and angioedema. In addition, in two cases anaphylactoid systemic reactions occurred. The enemas were administered using a kit comprised of a plastic bag, tubing, and a rectal endpiece. A third child developed a systemic reaction with insertion only of the rectal endpiece and without infusion of barium or any other fluid. An in-hospital challenge using

Latex Allergy

one endpiece in one patient, who was clinically the most sensitive, produced an acute anaphylactic reaction, implicating the latex endpiece as the most likely allergen source. The suggestion by Lozynsky et al. (24) that exposure to natural rubber products in children with spina bifida could elicit IgE-mediated anaphylactic reactions in children was confirmed by Slater (25) 4 yr later. Slater (25) described skin tests and histamine-release experiments in two children with spina bifida cystica who had anaphylactic episodes during surgery. Both children had a history of urticaria after exposure to rubber products. His investigation suggested that anaphylactic reactions in both children were due to IgE-mediated hypersensitivity to rubber. One of Slater’s (25) cases had a past history of asthma and an allergy to phenytoin. Although children with spina bifida were not specifically atopic or predisposed to developing drug allergies, Moneret-Vautrin et al. (26) in 1990 presented casesof three children with spina bifida who exhibited anaphylactic shock after exposure to latex and ethylene oxide during surgery. Two of their caseshad a past history of asthma; one was atopic and had different adverse drug reactions. On the basis of these cases, they recommended the avoidance of all latex products and other equipment sterilized with ethylene oxide for children with spina bifida. By 1991, there was a growing realization that pediatric patients with spina bifida cystica were at high risk for developing IgE-mediated reactions to latex. Gold et al. (27) identified a group a children with spina bifida cystica and other urologic abnormalities who experienced 19 intraoperative anaphylactic reactions. All patients had previous exposure to latex materials since infancy as part of their medical management. Seven of 15 patients had a previous history of local cutaneous reactions to rubber. Four of the 15 patients were atopic. In 1990, Kelly et al. ( 18) observedthat nine patients at one children’s hospital had onset of anaphylactic reactions within 30 min following the onset of general anesthesia; no patient had had a surgical incision at the time of the reaction. A retrospective epidemiologic investigation at this hospital demonstratedthat 11 patients had anaphylactic reactions during general anesthesiafrom January 1989 through January 1991. All were pediatric patients. Ten of these patients had a meningomyelocele, and one patient had a congenital urological abnormality. This investigation also included a case control study of the 11 casepatients and all noncasepatients with a meningomyelocele (n = 64) who had undergone general anesthesia.Casepatients were more likely to have a history of other allergies or of multiple surgical procedures. Ten of the 11 casepatientsreportedly had skin, KAST, or

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enzyme-linked imunosorbent tests (ELLS4 ) suggesting latex allergy. At that time, preliminary reports from a nationwide survey of children’s hospitals identified at least 25 other institutions that had reported similar reactions between January 1990 and January 1991, involving approximately 75 patients (range = l-6 patientsiinstitution) with a meningomyelocele or genitourinary dysplasias (18). Based on the results of their studies, Kelly et al. ( 18) concluded that patients with meningomyeolcele and genitourinary dysplasias undergoing multiple surgical procedures and requiring intermittent clean catheterizations may be at increased risk for developing latex sensitization. Therefore, they recommended that until the specific routes of IgE sensitization in this population were better characterized, postponement of elective surgical procedures should be considered. Since that comprehensive report ( 18) , there have been numerous additional studies evaluating the risk factors for latex allergy in the spina bifida cystica patient population (28-3 1) . All agree that the major risk factors for latex sensitization in spina b&da cystica children include atopy and exposure. Furthermore, in their prospective study of the risk factors for latex hypersensitivity, Moneret-Vautrin et al. (25 ) found that atopy and frequent exposure were in fact synergistic and independent risk factors. Health care workers. Nutter (32) was the first investi-

gator to describe contact urticaria to rubber gloves. The condition occurred in a 34-yr-old housewife with long-standing atopic dermatitis, which in recent years had involved mainly her hands. During an exacerbation of her hand eczema, she noted intense itching of her hands that occurred 5 min after donning a pair of rubber gloves. The contact urticaria was confirmed by a patch test using a small piece of the rubber gloves, which produced a wheal on unbroken skin. She also had a positive skin prick test with 5% natural rubber in distilled water. One year later, Forstrom (33 ) described the first case of contact urticaria from latex surgical gloves. He reported on a 24-yr-old operating room nurse with a history of atopic dermatitis and allergic rhinitis who, for a period of 5 months, had developed hand urticaria every time that she wore Triflex” surgical gloves (,Travenol Laboratories, England). Simultaneously, she exhibited symptoms of rhinitis and developed edema of her eyelids. A chamberlike scarification test with a piece of Triflex@ surgical gloves induced a strong urticarial reaction, with swelling of her face. Six years later, Wrangsjii et al. (34) presented a study of 15 patients with discomfort caused by rubber gloves and confirmed that contact urticaria was present

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in 6 of the 15 cases.Thirteen of these 15 patients had a history of preexisting hand eczema, and 14 of them were female. They concluded that these findings may indicate that the development of this type of localized contact urticaria was a complication in patients with active eczema who were exposed to rubber gloves. Although rubber gloves were increasingly implicated as causal agents of contact dermatitis and urticaria, Seaton et al. (35) were the first to describe a patient in whom asthma attacks were associated with and provoked by the use of powdered laboratory latex gloves. The patient, a 36-yr-old male laboratory technician, noted onset of bronchospasm within 10 min of donning each new pair of general purpose latex gloves, resulting in symptoms of coughing and wheezing. In 1987, Turjanmaa (36) was the first to examine the frequency of latex glove allergy among health care workers. In that study, 512 hospital employees were screened by using a latex-glove scratch-chamber test; those employees with a positive scratch chamber test were then subjected to skin prick tests. Twenty-three (4.5%) of the 512 employees had positive scratchchamber tests. Skin prick tests confirmed latex allergy in 15 of these 23 patients. Ten (67%) of the 15 latexallergic employees had a personal history of atopy (3, asthma; 8, allergic rhinitis; 7, atopic eczema). All latex allergic personnel could continue their routine work by using a pair of cotton or vinyl liners or less-irritating latex gloves. Latex glove allergy was significantly more common in operating room personnel than in hospital employees working in examination units and laboratories (p < 0.01). Nine (6.2%) of the 145 employees in the operating room units had latex sensitivities in contrast to 6 (1.6%) of 367 employees in nonoperating units. The allergy prevalence in operating units was 7.4% in physicians, 5.6% in nurses, and 5.0% in other employees. One year later, Turjanmaa et al. (37) described unusual obstetric complications in health care workers during delivery. The nurse experienced anaphylaxis during delivery. A female surgeon and dentist both exhibited local allergic reactions after closure of their episiotomy wounds. In 1991, Sussmanet al. (38) presenteda spectrumof IgE-mediated allergic reactions to latex in 14 patients, including health care workers sensitized by exposure. Symptoms often occurred immediately after exposure to latex, and manifestationsdiffered according to the route of latex antigen presentation. Skin exposure usually causedcontact urticaria. Exposureto latex via the respiratory epithelium elicited allergic rhinitis, conjunctivitis, and asthma. Systemic effects from latex were encountered intraoperatively due to contact with the surgeon’s latex gloves or other latex biomedical devices.Manifesta-

J. A. Woods et al.

tions of anaphylactic shock included the abovesymptoms and tachycardia and hypotension. All patients had positive latex skin prick tests. In all but one patient, serum IgE to latex was found with a latex RAST test. Many episodesof life-threatening anaphylaxis have now been documentedduring dental and medical procedures,during which the latex antigen is absorbedacrossoral, vaginal, or peritoneal membranesat the time of the procedure. Arellano et al. (39) were the first to report the prevalence of latex sensitization among physicians using latex gloves in a North American hospital setting. Using a latex skin prick test, they determined the prevalence of latex sensitization among 101 staff anesthesiologists,radiologists, and surgeonswho regularly used latex gloves and among 100 atopic controls who were not occupationally exposedto latex gloves. Latex skin prick tests were positive in 10 of 101 physicians and in 3 of 100 atopic controls. Latex skin prick tests were positive in 9 of the 38 atopic physicians and in only 1 of 63 nonatopic physicians. Thus, atopic physicians were more likely than nonatopic physicians to be skin prick test positive to latex antigens.This prevalence of latex allergy in North American physicians (9.9%) was remarkably similar to prevalence of latex allergy in the Finnish physicians reported by Turjanmaa (7.4%) (36). By 1992, there was a growing emergenceof allergic reactions to latex among health care workers. During 1991, 49 Mayo Clinic medical center employees sought evaluation of rhinitis, conjunctivitis, contact urticaria, contact dermatitis, asthma, or eczema that was attributed to exposure to latex (40). Almost all of the 49 individuals had a history of atopy (asthma, allergic rhinitis, or eczema) and worked in an area in the hospital where latex gloves were used and changed frequently. Of the subjects tested, 34 had positive results with skin prick tests to latex. Latex-specific IgE antibodies were increased in 19 of the 35 subjects (54%) in whom they were measured, and each of these 19 subjects had positive skin prick tests. The Occupational Safety and Health Administration (OSHA) have reported that more than 5 million American health care and other workers use latex gloves regularly, with an estimated 7 billion pairs of gloves used in the United States each year (41) . A number of recent Food and Drug Administration (FDA) reports of severe IgE-mediated anaphylactic reactions to latex included an estimate of more than 1800 serious, life-threatening reactions. These cases have been reported in a variety of situations, including surgical procedures, vaginal examination, and rectal manometry (25, 42-46).

Charous et al. (47) believe that these statistics radically underestimatedthe number of patients and workers affected by latex allergy because of underreporting of

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latex-associatedreactions.They noted that latex sensitization has becomea common illness in workers with occupational latex exposure.In their study of 47 symptomatic workers with occupational exposure to latex, review of the medical histories suggestedthat the number of patients reporting the onset of latex-induced contact dermatitis had remained relatively constant, whereasthe number of patients with contact urticaria and systemic reactions had markedly increasedover the previous few years. Furthermore, systemicreactions in workers with occupational latex exposurewas commonly precededby contact dermatitis or contact urticaria. In the 24 workers with histories of systemic allergic reactions to latex, all but 5 had prior local allergic reactions. In the 23 patients without systemic reactions, 15 had a history of preexisting nonspecific dermatitis. Among the 47 subjects,there was a high frequency of atopy (30 patients), food allergy ( I5 patients), and medication allergy ( 14 patents). Only 3 of the 24 patients with systemic allergic reactionsto latex reported no prior local latex allergic reactions. Latex industry workers. Rubber workers have an increased prevalence of chronic respiratory symptoms and reduced lung function. In 1976, McMichael et al. (48) studied the association between chronic respiratory symptoms and an individual’s job type within the rubber industry. They identified four job types as those most clearly associated with respiratory symptoms: milling, calendering, tube curing, and tube inspection. Of special interest was the high prevalence of symptoms in personnel involved in tube curing and inspection but not in tire curing and inspection. They identified four factors that might account for these findings. First, dust levels, primarily talc dusts, were generally much higher in the tube production area than in the tire production area. Second, the chemical composition of the tire and tube curing fumes differed and may contribute to this discrepancy. Third, tube curing and inspection within the plant was located in a more confined physical space than was tire curing and inspection. Fourth, the curing and inspection production-line moved faster for tubes than for tires, resulting in a greater amount of curing fumes in tube manufacture. They also demonstrated a synergistic effect between cigarette smoking and occupational exposure in the production of chronic respiratory disability. This synergistic effect was found for all job types except employees in the tire and tube curing areas. In these sites, employees with the greatest occupational respiratory disability were nonsmoking individuals. Two years later, Lednar et al. (49) provided additional information on the occupational determinants on chronic disabling respiratory disease in rubber workers. They examined 73 rubber industry workers who

terminated gainful employment with a pulmonary disability retirement at a large rubber plant in Akron, Ohio. These individuals spent significantly more time employed in the curing preparation, curing, finishing, and inspection work areas. Each of these areas provided for significant employee exposure to particulate materials or solvents. The most important risk factors for developing a pulmonary disability were smoking and exposure to dust and fumes, especially exposure to talc and carbon black. Becauseof these predisposing factors to lung disease, it was difficult to determine the role of latex allergies on pulmonary disability. In 1988, Bascom et al. (50) described a spectrum of respiratory illnesses associated with eosinophilia that occurred in a group of rubber workers exposed to fumes from a synthetic rubber-based curing operation. Respiratory symptoms differed, from an acute illness with dyspnea and wheezing to pulmonary infiltrates and eosinophilia and chronic obstruction of the airway with recurrent bronchitic illness. Employees demonstrating this wide diversity of respiratory illnesses had a high prevalence of peripheral eosinophilia. After Tar10 et al. (5 1) identified a 33-yr-old latex glove inspector with occupational asthma and latex sensitivity by skin prick testing, they undertook a survey of her workplace. Of the 81 other workers evaluated in this survey, 7 had spirometric changes consistent with asthma. Two of these workers had positive skin prick test to latex. Fruit allergy patients. Axelsson et al. (52) were one of the first to describe an association between latex allergy and food. They described a 12-yr-old girl who developed rhinoconjunctivitis and itching in the throat after eating stone fruits. Subsequently, she developed angioedema after inflating a rubber balloon. In 1992, Ross et al. (53) demonstrated a cross reactivity between latex and banana allergens. The 16 sera used in the study included 10 banana-ELISA-positive sera that were also latex-ELISA positive and 6 latexRAST-positive sera that were inhibited by banana extract. They noted that all banana-positive sera had detectable latex-specific IgE, whereas none of the latexpositive sera had detectable banana-specific IgE. They concluded that, with the increasing concern about latex-induced anaphylaxis, the cross reactivity between banana and latex may have clinical significance. In the same year, Ceuppens et al. (54) described four patients who developed generalized anaphylaxis shortly after ingestion of bananas or chestnuts. Their histories and RAST assays revealed immediate latex allergy in all four cases.Two of these individuals were female nurses with a history of contact urticaria to rubber gloves at work. The other two individuals, a

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39-yr-old man and a lZyr-old boy, developed allergic reactions after inflating rubber balloons. In 1994, Blanc0 et al. (55) determined the clinical features of latex allergic patients and latex-associated food hypersensitivities. Twenty-five patients, 9 greenhouse workers and 6 hospital workers, with latex allergy (including 9 patients with anaphylactic reactions; mean age = 33 + 9 yr ) and a female predominance (23) were included. Skin sensitivity to foods was demonstrated in 13 patients: avocado (9), chestnut (9)) banana (7)) kiwi (5)) and papaya (3). These results supported the existence of a “latex-fruit syndrome” that predominantly affected adult women (56). In 1995, Lavaud et al. (57) performed immunoblot analysis and inhibition of immunoblot to investigate allergenic components further in natural latex from rubber tree sap, latex gloves, banana, and avocado pear. Their studiesof the crossinhibition of immunoblot assaysconfirmed that a main allergen was linked to a common epitope present in both latex and fruit. Today, epitopes or proteins that cross react with latex must be widespread in fruits, correlating with clinical observations. Latex allergy has now been associated with many fruit allergies, including tomato (44), grape (44), pineapple (44), nuts (52), figs (55), passion fruit (54)) celery (54)) kiwi (55)) citrus fruits (56), banana (56-59), chestnut (59-61), avocado (57,66), and peach (63). Other high-risk groups. The two other groups of individuals at high risk for developing latex allergy include individuals with a personal or family history of atopy and individuals who have undergone multiple operations. In this latter group, patients with genitourinary tract anomalies requiring early and multiple operations are particularly at risk. Atopy is used to designate a group of individuals who have a personal or a family history of one or more of the following diseases:hay fever, asthma, dry skin, and eczema. The incidence of atopy in the general population approaches20% (64). In 1992, Shield and Blaiss (65) reported that 6.8% of atopic children without other risk factors (3 /44) had positive skin tests to latex. However, their data base was small, and these data may not represent the true prevalence. Moneret-Vautrin et al. (28), in their 1993 prospective study of risk factors for latex allergy, identified a 9.4% prevalence of latex sensitization by skin prick tests in a group of 180 atopic subjects without other risk factors. Inclusion in this group of atopic individuals was based on the diagnosis of at least one atopic disease confirmed by skin prick testing or by at least one positive skin prick test confirmed by RAST. Instrumented patients and patients with a past medi-

cal history significant for multiple operations seem to be at higher risk for latex sensitization. Only one study has specifically addressed the isolated risk factor of multiple surgeries (28). This study had shown that multiply operated patients were sensitized to latex at a rate of 6.5% and that individuals without operative contacts or other risk factors were sensitized at a rate of only 0.37%. Patients with ventriculoperitoneal shunts, cloaca1 anomalies, or bladder extrophy who did not have other risk factors also seemed to be predisposed to latex allergy. PATHOGENESIS The immune system responds to the presence of foreign antigens with a three-phase host response. In the first phase, specific and nonspecific recognition of foreign antigenic moieties are mediated by T and B lymphocytes, macrophages, and other antigen-presenting cells. Activation of T cells and B cells leads to the production of T-effector cells and stimulates B cells to produce specific antibodies. The second phase consists of amplification of the inflammatory responses and involves recruitment of specific and nonspecific effector cells by complement components, lymphokines and monokines, kinins, arachidonic acid derivatives, and mast cell-basophil products. The third phase is associatedwith antigen destruction by macrophages, neutrophils, and lymphocytes and ends with direct cytotoxicity or phagocytosis of antigen particles by macrophages, neutrophils, or lymphocytes. Under normal circumstances, this three-phase immune response serves to protect the individual from the foreign antigen with a well-controlled immune and inflammatory response. However, damage to host tissues and clinically apparent disease can result from regulatory dysfunction of any of the components of the host defense system. The type of immunologic response (e.g., IgE vs. TgG) induced by a foreign antigen depends in part on the route of exposure to that antigen ( 10). Latex absorption through the skin is postulated as the major route of sensitization in health care workers (12,66). Beezhold et al. ( 13) suggested that body sweat inside latex gloves may make latex proteins soluble; the solubilized proteins were then absorbed through the skin, sensitizing the wearer to the latex antigen. Friction, pressure, heat, and perspiration are among the nonspecific factors that influence the occurrence, severity, and sites of involvement of hypersensitivity contact dermatitis. In addition, certain clinical statesare often associated with an increased incidence of allergic contact sensitization. Included among these are eczematous

Latex Allergy

and burned skin, the skin of varicose eczema, and skin simultaneously undergoing nonspecific primary irritation. Because penetration of the allergen below the horny layer is essential for allergenic activity, breaking of the normally existing skin barrier by trauma favors sensitization. Nevertheless, in sensitized individuals, allergen absorption can occur through intact skin. Cutaneous exposure is usually associatedwith local reactions limited to the area of contact but may progress to systemic reactions. In addition to direct cutaneous contact, inhalation and mucosal (e.g., oral, visceral, etc.) and parenteral (e.g., intravenous, intrathecal, etc.) exposure to latex have also been suggested as possible routes of latex sensitization. Although exposure to latex aeroallergens in a hospital setting has been well characterized, new data suggest that the risk of inhalational sensitization may be more widespread. In a disturbing report by Williams et al. ( 67 ), investigators observed irregularshaped respirable black particles that appeared to represent air-borne tire fragments in an urban setting. Their observations indicated that latex tire fragments containing latex antigens were abundant in urban air and suggested that these particles can contribute to latex sensitization and allergy. Anaphylactic response to latex exposure occurs most commonly intraoperatively (38 ) . Genitourinary, abdominal, and cesarean sections were the surgical procedures most often associated with exposure. In these situations, the skin barrier was bypassedand latex allergen absorption occurred through the mucosa. The mechanisms of immunologically mediated inflammation have been categorized into four types. Two of these hypersensitivity reactions play roles in latex allergy. Latex glove use has also been associated with nonallergic or irritant contact dermatitis. Most allergic reactions to natural rubber latex gloves are type IV (delayed type) hypersensitivity reactions, primarily related to mercaptobenzothiazole and tetramethyl thiuram accelerators in latex products and to excessive exposure to several other chemical irritants (20), including soaps and cleansers. Delayed type allergies have been found in 84% of patients with occupationally acquired allergic reactions to latex products. Studies conducted by Heese et al. (68) have indicated that thiuram accelerators in rubber gloves were the sensitizing agents in 72% of patients with occupationally induced type IV latex-associated skin reactions, carba-mix accelerators were the sensitizing agent in 25%, and mercapto-mix accelerators were the sensitizer in 3%. The phenylenediamine group is the marker allergen for industrial products. Patients typically present with hand dermatitis (68 ) , The type IV hypersensitivity re-

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action is a T-cell-induced mononuclear cell accumulation of regulatory and effector T cells and macrophages. Lymphokines and monokines are released. In contrast, latex proteins cause IgE-mediated allergic reactions (type I hypersensitivity). Mast cells and basophils have receptors for the Fc portion of IgE; antigen binding to cell-bound IgE at thesehigh-afhnity Fc receptors induces mast cell and basophil degranulation and mediator release.IgE molecules bound to the surface of mast cells and basophils serve as the recognition site for antigenic binding. Nearly 500,000 IgE molecules are located on each mast cell, and these serve as a bridge to engageallergens. The bridging of two IgE molecules by an antigen initiates the biochemical cascadeleading to the activation of a cell-membrane-associatedprocessthat releaseshistamine, leukotrienes,and other mediators.The symptomselicited dependon the tissuesinto which mediators are released.

CLINICAL Irritant

MANIFESTATIONS

Contact Dermatitis

Nonallergic irritant contact dermatitis accounts for 80% of all casesof contact dermatitis (69) and occurs when an exogenous substancewithout previous sensitization causesdirect damage to the skin. Chapped skin from hand washing with detergents is a typical example of a situation capable of producing irritant contact dermatitis. Just as with allergic contact dermatitis, presentation can be acute, subacute, or chronic. Itching is the most common symptom with either allergic or irritant contact dermatitis. Because the morphologic features (dry, crusted lesions in areas exposed to latex gloves) may be similar in allergic and irritant contact dermatitis, the emergency physician must have an understanding of the exogenous substance exposure to allow formulation of a diagnostic plan to differentiate the two entities.

Type IV Hypersensitivi~v

Contact dermatitis is one form of eczematous dermatitis, based on specific allergic sensitization that principally is causedby cutaneous contact with the offending agent. The term ‘ ‘eczematous’’ indicates an eruption that in its acute and subacute phasesis clinically characterized by papulovesiculation and erythema, often associated with edema. In chronic contact dermatitis, the skin becomeserythematous, thickened, and lichenified and at times either hyper- or hypopigmented. The scalp, palms, and soles have a greater resistance to

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contact allergic and irritant reactions than do other skin areas. Because of this resistance, an eruption subsequent to allergen contact that occurs primarily on the palms is likely to manifest in the web spaces of the fingers and on the dorsa of the hands. The scalp will rarely show vesiculation, and the eyelids, penis, and scrotum often show pronounced erythema and edema rather than vesiculation. The primary reaction is usually several (at least 4) days after contact, but subsequent reactions can develop sooner. These clinical findings are localized initially and can persist for weeks but ultimately spread peripherally. The patient will remain sensitized, and a reaction will recur if the individual comes into contact with products containing the same chemical. The development of a type IV hypersensitivity allergic response may occur after years of contact with a substance ( 69).

Anaphylaxis. Anaphylaxis has been most commonly encountered intraoperatively. There also have been 15 reported latex-allergy-associated deaths during barium enema examinations from exposure to the latex enema tips (70). However, anaphylactic reactions have been encountered during gloving, exposure to dental dams, condom use, and even after indirect exposure by contact with individuals who use latex gloves. The life-threatening anaphylactic response appears within minutes of administration of the specific antigen and is accompanied by respiratory distress, followed by vascular collapse or shock. Cutaneous symptoms often occur with anaphylaxis and include pruritis and urticaria with or without angioedema. Gastrointestinal manifestations involve nausea, vomiting, crampy abdominal pain, and diarrhea. DIAGNOSIS

Type I Hypersensitivity The route of latex antigen presentation will usually dictate the attendant clinical manifestations. A patient with cutaneous exposure to the latex allergen will most often present with dermatitis or urticaria but in some cases may present with angioedema or anaphylaxis. Inhalant exposure to latex allergens in sensitized individuals results in severe occupational rhinoconjunctivitis and asthma. A mucosal route of exposure to latex allergens is the route most often associated with anaphylactic reactions. Generalized urticaria and angioedema also have been noted to occur with mucosal antigen exposure. Contact urticaria. Contact urticaria is the most common early manifestation of rubber allergy, particularly in latex-sensitive health care workers (47 ) . Symptoms appear within lo-15 min after donning gloves. Urticarial eruptions are distinctly pruritic. No residual discoloration occurs after resolution of the urticaria. Rhinitis and asthma. Episodic rhinorrhea, sneezing, and obstruction of the nasal passageswith lacrimation and pruritis of the conjunctiva, nasal mucosa, and oral pharynx are the cardinal features of allergic rhinitis. Asthma is characterized by bronchial obstruction, with marked hyperinflation of the lung parenchyma. The bronchi have luminal secretions, peribronchial congestion, submucosal edema, and eosinophilic infiltration. In long-standing cases, the patient may develop emphysema attributed to intractable bronchospasm.

In 1991, the FDA ( 18) recommended that all patients be questioned for potential latex allergy, particularly those with spina bifida cystica or any patient scheduled for diagnostic or surgical procedures. All physicians are requested to report all episodes of anaphylaxis during procedures requiring general anesthesia through state health departments to the epidemiology branch of the hospital infections program at the Center for Disease Control’s National Center for Infectious Disease. History and Physical Examination Central to the diagnosis of latex allergy is a reliable clinical history. The medical history is often similar among individuals affected by latex allergies. Onset is often insidious, with dermatitis of the hands, which the patient initially attributes to frequent hand washing and irritation. After a short period of time (less than a year), erythema, papulovesiculation, induration, and pruritis emerge within l-3 h after onset of glove use. For patients presenting with contact dermatitis or urticaria, the physician should ask about location and time of onset of the eruption, morphology, nature of progression, and recurrence or periodicity. Among affected health care workers, one may often elicit a history of respiratory symptoms including rhinitis, recurrent sinusitis, and asthma, which are pronounced while at work but improve while at home. The patient should be questioned about response to therapy, a history of atopic disease such as asthma, food allergy, and anaphylaxis, and about u&aria related to latex contact in the home or community. These questions will help the

Latex Allergy

81

emergency physician to identify patients in high-risk groups for latex-related anaphylaxis. It is important to remember that the majority of reported latex-allergic health care workers are employed as physicians, dentists, dental hygienists, and operating room nurses and have prior histories of contact dermatitis or contact urticaria when using latex gloves.

Diagnostic

Testing

There is currently no available gold standard for the diagnosis of type I latex allergy. Kelly et al. (7 1) recently introduced guidelines that are useful in the clinical evaluation of latex allergy. They recommended sequential use of serologic, use, and skin prick tests to optimize safety, diagnostic sensitivity, and specificity. They also suggested that physicians offer serologic testing at a reputable laboratory to symptomatic patients with a possible latex allergy. If serologic testing is positive, latex allergy is confirmed and no further testing is necessary; if serologic testing is negative in a symptomatic patient, a use test should be performed. If the use test is positive, latex allergy is confirmed; if the use test is negative, a skin prick test is performed as the final diagnostic tool offered. They noted that negative prick or serologic testsperformed shortly after an acute latex response might reflect a false negative because of an immunologic refractory period similar to that encountered after a bee sting. Skin prick testing. Of the currently available tests, skin prick testing is the most reliable. This test has the advantagesof being sensitive, rapid, and cost effective. Reports of anaphylaxis during skin prick testing for latex allergy emphasize the need for safe testing methods for diagnosis (72,73). Skin prick testing should be done by trained allergists in a hospital setting with adequate resuscitation and medical support services and with an intravenous infusion readily available to provide epinephrine, volume expanders, and other vasopressor agents rapidly in the event of a reaction. Although available abroad, there is no commercially available, FDA-approved latex skin extract in the United States. Consequently, American allergists who wish to perform latex skin prick testing should follow experimental protocols (20). Outside of the United States, commercial nonstandardized extracts have proven effective for skin prick testing and are considered safe when initial testing is performed with a loor 1W-fold dilution to yield an extract with a < 1 ng/ mL concentration.

In vitro assays for latex-specijic IgE. Sensitive and specific commercial in vitro serologic assaysthat have been developed for the diagnosis of IgE-mediated latex allergy include an immunoflouro assay, Pharmacia CAP (Pharmacia Diagnostics, Piscataway, NJ), and an ELISA assay, AlaSTAT (AlaSTAT Diagnostic Products Corporation, Los Angeles, CA ,t The differencesin latex sourcematerials usedin latex exposure and the existenceof possible cross-reactingantibodies contribute to variance in the accuracy of these tests. If the latex antigens in the sensitizing product are different from the epitopes used in the assay. a falsenegative result may occur. In atopic individuals. especially in patients with allergies to fruits or vegetables, these serologic tests can produce false-positive results. All serological testing for latex allergy should be carried out by experienced laboratories.

Use test. The use test described by Kelly et al. (72 ) is useful in patients with a compelling history but a negative serologic assay. The use test should be preceded by an explanation of the attendant risks and benefits. The use test is performed with a fingertip cut from a sterile surgical glove, moistened with saline, and applied to the skin of the patient for a IS-mm period. Urticarial pruritis or erythema are indicative of a positive result. If no reaction is noted, an entire saline-moistened surgical glove then can be placed on the hand of the patient until a reaction ensues or for a maximum of 1.5min. However, patient safety during full-glove use testing is ill-defined and depends on the allergenicity of latex proteins in the surgical glove used for the test. Patch testing. Patch testing is helpful in differentiating

irritant contact dermatitis from allergic contact dermatitis mediated by type IV hypersensitivity reactions. The patch test is the definitive test for diagnosis of patients with type IV hypersensitivity to latex products. For patients presenting with only contact dermatitis or urticaria, diagnosis may be facilitated with patch testing using a standard battery of rubber additives. Accelerators evoke positive patch tests in 32 of 39 patients (82%) with occupationally induced contact dermatitis associated with glove use (68 ) . The allergen is applied on normal skin, usually on the patient’s back or arms, under a small semiocclusive dressing.When testing for allergic hypersensitivity, avoid applying test substancesin concentrations that have the inherent capacity to cause visible changeseven on nonsensitized normal skin. The standard screening tray of the North American Contact Dermatitis Group contains a seriesof common contact allergens, which include those found in surgical gloves and which are useful for patch

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testing; this battery includes 1%p -phenylenediamine,1% mercaptobenzothiazole,1% mercapto-mix, 1% thiurammix, and 3% carba-mix. Patch tests are left in place for 24-48 h. The results are first read about 30 min after removing the patches and again 24 or 48 h later. Before a substancethat has elicited a positive reaction can be acceptedas the cause of the presenting eruption, the result of each patch test must be associated with the history of allergenic exposures and with clinical findings. There is a risk of inducing contact sensitization by exposures involved in patch tests; however, this risk should not interfere with the judicious use of this form of testing. MANAGEMENT Acute Management Latex avoidance. Managementof a latex-allergic patient in an ambulance or in the emergency department can be very difficult becauselatex is ubiquitous in medical environments.Emergencymedical techniciansshould examine Medic-Alert? (Turlock, CA) braceletsand should use latex-free gloves when treating a patient with latex allergy. Ideally, the ambulance should carry sterile glass medication vials without rubber stoppers. Lyophilized drugs need to be reconstituted in a glass syringe and not in multidose vials. If theseprecautions are not taken, the emergency physician will be exposing a latex sensitive patient to additional latex antigens. A comprehensive protocol for the management of latex-allergic patients should be developed for each emergency department. In some hospitals, a latex-free emergency cart has been developed for use throughout the hospital. In the emergency department, the patient should be positioned on a mattress that has no latex mattress cover. A stockinet should always be wrapped around the extremity beneath the blood pressure cuff. Cover the patient’s finger with either a plastic baggy or Saran Wrap@ before applying a pulse oximeter. Medications should not be injected through latex intravenous ports. Covering the latex ports with colored tapes or caps is a helpful warning to hospital personnel. Management of type I allergic reactions. Antihistamines of the HI class and sympathomimetic agents often provide symptomatic relief for urticaria and angioedema.Cyproheptadine, hydroxyzine, and a combination of Hl and H2 antihistamines are another important therapeutic consideration for the treatment of angioedema and urticaria. Prolonged treatment with topically applied corticosteroids is not recommended in the management of type I allergic reactions. Antihistamines are the best specific end-organ an-

tagonists for allergic rhinitis. The side effects, which include drowsiness and gastrointestinal distress, following administration of these agents may limit the dosageof the prescribed antihistamine. Topical administration of alpha-adrenergic agents may be helpful to treat upper respiratory symptoms, but it is accompanied by rebound vasodilatation after prolonged usage. Because episodes of urticaria, angioedema, rhinitis, and asthma may progress to anaphylaxis, the emergency physician must be prepared to treat this lifethreatening condition. Mild initial symptoms may be controlled by the administration of 0.2-0.5 mL of 1:1000 epinephrine subcutaneously, with repeated doses as required at 3-min intervals. In severe cases, an intravenous infusion should be initiated to provide a route for administration of epinephrine diluted 1:50,000. If significant hypotension persists, vasopressors, fluids, and volume expanders also must be administered. Oxygen via a nasal catheter may be initially helpful, but endotracheal intubation is mandatory if progressive hypoxia exists. Antihistamines such as diphenhydramine (50-80 mg intramuscularly or intravenously) are valuable for treating urticaria, angioedema, and bronchospasm. If persistent bronchospasm and hypotension occurs, intravenous corticosteroids, although delayed in onset of activity, may be useful. Long-Term Management Education on latex avoidance is mandatory to prevent allergic reactions in latex-sensitized patients. The patient must learn the long list of medical and consumer products that contain latex. Patients should be provided with a list of latex-free products for daily or occupational use. They should carry rubber-free examination gloves when seeking medical or dental care. Because there is cross reactivity between latex and fruit antigens, patients should use care when first consuming these fruits after diagnosis. All latex-allergic patients should wear a Medic-Alert@ bracelet and carry an emergency epinephrine kit at all times. Latex-safe environment. The Task Force on Allergic Reactionsto Latex of the American Academy of Allergy and Immunology has recommendedthat medical proceduresperformed on latex-sensitivepatients should be performed in a latex-safe environment (74). A latex-safe environment is one in which no latex gloves are used by any personnel. In addition, there should be no latex accessories(catheters,adhesives,tourniquets, anesthesia equipment, etc.) that come into direct contact with the patient. Detailed perioperative treatmentplans should be published for hospital personnelmanaginglatex-sensitive

Latex Allergy

patients. These protocols recommend preoperative prophylactic administration of glucocorticoids and both Hland H2-class antihistaminesto latex-sensitive individuals undergoing surgery. Surgical and medical examination gloves. With the institution of universal precautions in 1987, OSHA recommended that gloves be used in all situations when contact with blood or body fluids is anticipated. In addition, the American Association of Orthopaedic Surgeons has devised specific recommendations for double-gloving. These decisions have increased demands on the industry for greater production. Increaseddemand in the late 1980sand early 1990shave led some manufacturers to import gloves from Third World countries to improve supply. The inability of medical distributors to meet the precipitous increasein demand for medical examination and surgical gloves in the late 1980s was compounded by the removal of a major supplier, Liberia, becauseof internal conflicts in that nation (20). However, moldcontaminated glove lots and increased reports of pin holes and glove failure have led the FDA to investigate the quality of gloves and to devise improved qualityassurance protocols and tests for glove manufacturers to ensure user safety (75). The FDA has recently established more stringent guidelines for the industry regarding the overall quality of surgical and medical examination gloves. Surgical and medical examination gloves are classified by the FDA as class I medical devices. This classification is reserved for medical products that pose minimal risk to the user or patient. Only general regulatory controls are placed on class I devices, which are not subject to performance standards. Prior to 1989, manufacturers of medical examination gloves were exempt from premarket notification applications and from most good manufacturing practices. Manufacturers of surgical gloves prior to 1988, had only to show equivalence to other products. Today, the FDA has revised the examination and surgical glove classification. In addition, all glove manufacturers are subject to premarket notification applications and must also adhere to good manufacturing practices and to certain quality-assurance practices (76). The FDA has also investigated and revised past glove-testing methods; a regulatory change was instituted after the FDA developed a new test method, which allows a maximum 2.5% failure rate for surgical latex gloves and a 4% failure rate for latex examination gloves and incorporates multiple sequential testing ( 77 ) . Glove lubricants, such as surgical glove powder, are class III devices. As such, they are subject to more rigorous regulation than are class I devices. Because of the known tissue reactivity and potential dangers of

83 cornstarch glove lubricants, the FDA requires placement of a warning notice on the exterior glove packaging of sterile surgical gloves to advise wearers of the hazards and the need for removing powder after donning. Numerous studies have shown that starch glove powder present in a surgical wound acts as a foreign body and incites an inflammatory response, delays healing, serves as a carrier of latex allergens, and promotes the development of wound infection ( 14). Starch glove lubricants are increasingly implicated as the cause of iatrogenic disease and contribute signiticantly to patient morbidity and mortality. Nonetheless, clinical studies by Fay and Dooher (78 ) indicate low levels of compliance with glove-washing requirements. They noted that compliance differed widely among staff members in the operating room, with a 21% rate for nurses (164 of 781) and a 17% rate ( 140 of 827) for surgeons. The increasinguseof disposablelatex gloves by medical personnel subsequentto the recommendationfor universal precautions and the corresponding increase in the number of reports of contact or inhalant sensitization to latex among health care workers has led the Center for Devices and Radiological Health of the FDA to encourage rubber-medical-devicemanufacturersto collect data on the extractable proteins in their products. Reflecting these concerns, some medical gloves are now labeled hypoallergenic. Recent investigations have found the allergen content of disposablelatex gloves to vary by more than 3000-fold among different manufacturers (79,80). In general, significantly less allergen and protein can be extracted from powder-free examination and surgical gloves than from powdered examination and surgical gloves. In addition, the extractable allergen and protein levels are significantly higher in medical examination gloves than in surgical gloves. Overall, gloves labeled hypoallergenic tend to have less extractable allergen than do gloves without the hypoallergenic designation. However, 11 of the 24 measuredlots of hypoallergenic gloves had measurableamounts of latex allergens. The manufacturersof surgical gloves and the manufacturers of examination gloves employ different processes: similarly, the processesused to manufacturepowder-free gloves differ from the processesused to make powdered gloves. The specific processesused by glove manufacturers are consideredproprietary. The FDA has recently informed manufacturersof its intent to require aI.I medical devices that contain natural rubber latex and that come into contactwith the body to have this noteon the principal display panel: “This product contains natural rubber latex.” In addition, the FDA intends to prohibit the use of terms such as “hypoahergenic” on latex-containing gloves. The FDA has not as yet releaseda scheduk for the institution of theseregulatory changes(80 ‘i

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Gloves containing high levels of latex allergens are avoided by our medical center. A variety of low allergen powder-free latex gloves and synthetic gloves have been stocked to permit glove users a choice of brands and compositions. This decision was initially expected to be costly to the hospital because some powder-free and synthetic gloves are individually more expensive than are most high allergen powdered gloves. By decreasing the number of vendors from whom the hospital purchased gloves and by consolidating orders, our hospital will attempt to save a substantial amount of money each year. The selection of powder-free gloves in high glove-use areas in our hospital should also reduce latex aeroallergen levels. HEALTH

treatment may seek worker’s compensation or disability. Ideally, the best solution to this problem is to make the work place environment safe for the employee and allow the employee to continue to work after diagnosis of latex allergy. This appears to be an attainable goal, which is not cost prohibitive for an educated hospital administration. At present, however, health care workers with persistent respiratory symptoms or a history of latex-associated anaphylaxis may not be able to continue working. Consequently, documentation of the patient’s history, physical examination, confirmatory diagnostic tests, and measurements of disability, such as pulmonary function studies, may be requested. Worker’s compensation and disability claims are subject to different criteria and processes from state to state.

CARE WORKER DISABILITY

Health care workers with severe persistent allergic symptoms despite avoidance and pharmacological

researchwas supportedby a generous gift from ChristopherHenderson,New York, NY.

Acknowledgment-This

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