Occupational exposure to natural rubber latex has led to sensitization of health-care workers. However, the prevalence of latex allergy among occupationally exposed workers in American hospitals has not been reproducibly determined. The objectives of the current study were to determine the prevalence of and risk factors for latex sensitization among a cohort of highly exposed health-care workers.
Participants were 168 of 171 eligible anesthesiologists and nurse anesthetists working in the Department of Anesthesiology and Critical Care Medicine. A clinical questionnaire was administered, and testing was performed using a characterized nonammoniated latex reagent for puncture skin testing, a Food and Drug Administration-approved assay to quantify latex-specific immunoglobulin E antibody in serum, and, when required for clarification, a validated two-stage (contact-inhalation) latex glove provocation procedure.
The prevalence of latex allergy with clinical symptoms and latex sensitization without clinical symptoms was 2.4% and 10.1%, respectively. The prevalence of irritant or contact dermatitis was 24%. The risk factors identified for latex sensitization were atopy (odds ratio, 14.1; 95% CI, 1.8-112.1; P = 0.012); history of allergy to selected fruits, such as bananas, avocados, or kiwis (odds ratio, 9.8; 95% CI, 1.6-61.9; P = 0.015); and history of skin symptoms with latex glove use (odds ratio, 4.6; 95% CI, 1.6-13.4; P = 0.006).
The prevalence of latex sensitization among anesthesiologists is high (12.5%). Of these, 10.1% had occult (asymptomatic) latex allergy. Hospital employees may be sensitized to latex even in the absence of perceived latex allergy symptoms. These data support the need to transform the health-care environment into a latex-safe one that minimizes latex exposure to patients and hospital staff.
This article is accompanied by an Editorial View. Please see: Holzman RS: Occupational latex allergy: The end of innocence. Anesthesiology 1998; 89:287–9.
IMMUNOGLOBULIN E (IgE) antibody-mediated hypersensitivity to natural rubber latex (latex) occurs in children with spina bifida who receive extensive latex exposure through surgery and in health-care workers who have long-term occupational exposure. [1,2]Because these groups appear to become sensitized to latex allergen in a hospital setting, the Centers for Disease Control and Prevention and the National Institute of Occupational Health and Safety [3–5]have encouraged the development of latex-safe policies in hospitals that minimize airborne and contact exposure to latex products of patients and hospital staff. Some hospital administrators, however, view latex allergy as an infrequent, minor problem because they rarely see latex-allergic staff in their employee health clinics. They also remain skeptical about published prevalence figures that are as high as 15.8%[6–13]because the questionnaire and in vivo and in vitro diagnostic tests used in these studies to identify cases have not readily been reproduced because of a lack of standardized and clinically validated reagents.
In designing this prevalence study, we selected reproducible diagnostic methods and reagents to determine the prevalence of latex allergy among a group of anesthesiologists and nurse anesthetists in an institution that used highly allergenic powdered latex gloves and other rubber medical products. To address any concern about the reproducibility of previous prevalence study methods, we adopted a frequently used questionnaire to take clinical histories, an immunochemically characterized nonammoniated latex reagent for puncture skin testing (PST), a Food and Drug Administration-approved serologic assay to quantify latex-specific IgE antibody (latex IgE) in serum, and a validated two-stage latex glove provocation procedure. We chose to evaluate clinical personnel in the Department of Anesthesiology and Critical Care Medicine because they represent a cohort with daily high-level exposure to latex allergens from powdered latex gloves.
All clinical faculty, fellows, residents, and nurse anesthetists in the Department of Anesthesiology and Critical Care Medicine at the Johns Hopkins Medical Institutions were asked to participate voluntarily in this study, which was approved by the Institutional Review Board of the Johns Hopkins Medical Institutions. Potential participants were excluded from skin testing and glove provocation testing if they had unstable asthma within the past 72 h, were pregnant, or had taken interfering medications (such as [small beta, Greek]-blockers, antihistamines, or tricyclic antidepressants) less than 1 week before the study.
After giving informed consent, each participant underwent an evaluation that involved a detailed clinical history, collection of blood, a puncture skin test, and, if required, a two-stage glove provocation test (Figure 1). Fourteen persons provided only a history and a blood specimen because they were taking antihistamines, were pregnant, or were fearful of the skin testing. All testing was completed during a 10-week period. Before and at the time of testing, powdered natural rubber latex examination and sterile surgical gloves were being used routinely in the operating rooms.
One of the investigators (R.H.B.) took a clinical history from each participant using a previously validated questionnaire. The questions focused on the participants' atopic history (seasonal rhinitis, childhood asthma, eczema, food allergies), the number of previous surgeries, symptoms associated with the use of latex gloves and other latex rubber-containing devices, the extent and type of gloves used (powdered latex, nonpowdered latex, or synthetic), and the consistency and frequency of any reactions. The duration of latex glove exposure was defined from the year beginning with the participants' anesthesiology residency or nurse-anesthesia education.
Whole blood (10 ml), collected by venipuncture using synthetic gloves and tourniquets, was clotted for 30 min and centrifuged. The serum was divided into aliquots, coded for masking purposes, and frozen at -20 [degree sign]C. Each specimen was analyzed for total serum IgE; IgE antibodies specific for natural rubber latex, kiwi, banana, and avocado; and a single multi-allergen test (Phadiatop, Pharmacia-Upjohn, Kalamazoo, MI) as a general screen for atopy. Total serum IgE was measured using the Abbott ImX (Abbott Park, IL). Latex and food allergen-specific IgE antibody levels were measured using the Pharmacia-Upjohn CAP System (Kalamazoo, MI), which uses allergens covalently attached to high-binding-capacity sponge matrices. Results are reported in kIUa/l of IgE, with a positive result indicated by >0.35 kIUa/l. All latex-specific IgE measurements were reconfirmed in a second masked analysis using coded sera. The diagnostic sensitivity and specificity of the latex CAP System assay have been reported at 74.8% and 93.8%, respectively. The multiallergen screen (Phadiatop) is a CAP System test that uses a single allergosorbent to which 15 of the clinically most important aeroallergens are covalently attached and that produce most aeroallergen-related allergic diseases. Results of the Phadiatop screen were reported as positive or negative, with a positive result indicated by >100% of the reference serum binding level.
Puncture skin testing was performed by a second investigator (R.G.H.), blinded to the clinical history, using three concentrations of a nonammoniated natural rubber latex reagent prepared by Greer Laboratories (Lenoir, NC). This is the candidate skin testing material being evaluated under IND 6365 in a multiple-center study for licensing by the Food and Drug Administration. Glycerinated saline, histamine (1.8 mg/ml), and nonammoniated latex (1,100, and 1,000 [micro sign]g/ml) were applied in duplicate to the volar aspect of the forearm, and a puncture was performed with a new bifurcated needle (Allergy Laboratories of Ohio, Columbus, OH). To maximize safety, the three nonammoniated natural rubber latex concentrations were applied sequentially every 15 min in persons with a history suggesting a latex allergy. All skin tests were read 15 min after application and were considered positive if there was a wheal and erythema, 2 mm and 5 mm, respectively, greater than those produced by the saline negative control.
Glove Provocation Test
A two-stage (contact-inhalation) glove provocation test was performed, as previously reported, in participants who had discordant skin test and serologic test results or when both tests were discordant with the clinical history. Peak flow measurements were performed before and after the skin and glove tests. Briefly, the stage 1 (contact) glove challenge involved puncturing the skin on the hand through saline and donning either a highly allergenic powdered latex (challenge) or nonallergenic vinyl (control) glove on different hands. After 15 min, if no adverse skin (wheal, erythema) reactions were observed, the participants were asked to blow up a highly allergenic latex glove like a balloon (three times) and release it into their faces to simulate a gross airborne allergen exposure. Upper and lower airway symptom scores and changes in peak flow measurements were used to define a positive glove challenge reaction.
Univariate and multivariate analyses were performed using STATA 5.0 software (Stata Corp., College Station, TX). Initially, participants were categorized into four groups: latex allergic (Hx+, PST+, latex IgE+), latex sensitive but asymptomatic (Hx-, PST+ or latex IgE+ or both), contact dermatitis (Hx+ for contact dermatitis, PST-, latex IgE-), and controls (Hx-, PST-, latex IgE-). For all analyses, the control group was used as the reference for comparison. Unpaired Student's t tests were used to compare the continuous variables, and chi-squared tests were used to compare the categoric and binomial variables. Univariate analysis showed that the result for the allergic and the sensitized but asymptomatic groups were not significantly different (results not shown), therefore, the data from these two groups were combined. Similarly, univariate analysis showed that the results for the contact dermatitis and the control groups were not significantly different, except for a clinical history of skin symptoms in the former (results not shown), therefore, the data from these two groups were combined for further analysis. Univariate analyses were repeated with the participants divided into two groups: latex sensitized (allergic and sensitized but asymptomatic) and nonsensitized (contact dermatitis and control). All factors that were significant in the univariate analyses were incorporated into a multivariate backward stepwise logistic regression analysis. From the stepwise multivariate logistic regression, three significant factors were identified, and a multivariate logistic regression was constructed. The probability values reported from the final multivariate analysis may be smaller than the true probability values because they do not account for finding the best model using a univariate analysis followed by a stepwise backward multivariate regression analysis. All probability values were two tailed, and those <0.05 were considered significant.
Of the eligible 171 anesthesiologists, 168 (98%) completed the questionnaire and provided a blood specimen. Fourteen (8.4%) did not undergo skin testing because they were pregnant (n = 3), were taking antihistamines (n = 7), or refused (n = 4). Table 1summarizes the demographics of the entire study group. Eighty-seven (52%) of the participants gave an atopic history, and 84 (50%) of the participants had a positive Phadiatop result. Seven persons (4%) reported a specific history of food allergy to banana, avocado, or kiwi.
Of the 168 participants, 33 (19.6%) provided a history consistent with a delayed type IV hypersensitivity to the chemicals in natural rubber latex gloves and were classified as having contact dermatitis. Although the contact dermatitis was not confirmed with patch testing, the time course (24–48 h after exposure) and severity of the skin lesions were used to clinically distinguish between contact dermatitis and simple irritation. Four anesthesiologists (2.4%) provided a history consistent with a type 1 (immediate type) hypersensitivity to latex, and 131 (78%) participants had negative histories for any symptoms associated with powdered latex gloves. Notably, 14 (8%) of the anesthesiologists had a positive latex-specific IgE serology (0.41 to 7.53 kIUa/l;Table 2). Eleven of these 14 persons had a positive serum IgE antibody cross-reactive to banana, avocado, or kiwi (Table 2). Of the 154 participants who were skin tested, 17 (11%) were classified as PST positive at the 1,000 [micro sign]g/ml dose level (Table 2).
Twenty-one (12.5%) of the anesthesiologists were considered sensitized (IgE antibody positive) to natural rubber latex allergens (Table 2). Of these, 4 (2.4%) were both sensitized and symptomatic with rhinoconjunctivitis, hives, or asthma. Three had a concordant positive history, skin test, and serologic result. One anesthesiologist had a positive history and serologic result but could not be skin tested because of antihistamine use. The remaining 17 sensitized anesthesiologists had negative contact and inhalation glove provocation test results and were labeled as having an occult or presymptomatic sensitization (not clinically allergic to latex). Eight of these persons had both a positive latex specific IgE and puncture skin test result, three had only a positive latex specific IgE result, and six had only a positive puncture skin test result (Table 2). Finally, two (1%) persons were classified as not latex allergic but providing a false-positive history for latex allergy. They indicated allergy symptoms not limited to their hands after latex glove use and had both a negative PST and a latex-specific IgE result. One of these also had a negative glove provocation test result, whereas the other could not undergo glove provocation testing because of the initiation of systemic steroid therapy for asthma. From a safety perspective, no study participant exhibited any local or systemic adverse reactions as a result of the latex puncture skin testing. Peak flow measurements before and after skin testing showed no change in pulmonary function (data not shown).
Factors predisposing these high-risk health-care workers to latex sensitization were identified by comparing the sensitized to the nonsensitized participants initially using univariate analysis (Table 3). Latex-sensitized persons were more likely to be atopic with a positive Phadiatop screen (P < 0.0001) and a higher total serum IgE (P < 0.0001) level than were nonsensitized persons. More latex-sensitized participants also had a history of atopy (95%) than the nonsensitized group (46%; P < 0.001). A history of seasonal rhinitis (P = 0.001), asthma (P = 0.026), food allergies (P < 0.0001), and a specific allergy to bananas, avocados, or kiwis (P < 0.0001) were all significantly more common in the latex-sensitized participants than in the nonsensitized group (Table 3). Latex-sensitized persons also described more symptoms of skin (P < 0.0001), eyes (P < 0.0001), and upper airway (P < 0.0001) associated with the use of latex gloves than nonsensitized persons.
Multivariate analyses identified persons with atopy as having >14-fold increased odds of becoming sensitized to latex (odds ratio, = 14.1; 95% CI, 1.8–112.1; P = 0.012). Persons with a history of food allergies to bananas, avocados, or kiwis had a nearly 10-fold increased odds of latex sensitization (odds ratio, 9.8; 95% CI, 1.6–61.9; P = 0.015). In addition, persons with a history of skin symptoms with latex glove use exhibited approximately a fivefold increased odds of latex sensitization (odds ratio, 4.6; 95% CI, 1.6–13.4; P = 0.006). If the persons with contact dermatitis were removed from the nonsensitized comparison group, then the odds of latex sensitization in persons who had skin symptoms with latex glove use increased markedly (odds ratio, = 24.2; 95% CI, 5.8–100.8; P < 0.0001).
Allergen exposure in a person allergic to natural rubber latex can produce a spectrum of symptoms ranging from mild rhinoconjunctivitis and hives to life-threatening asthma and anaphylaxis. Although the problem of latex allergy has been established, the actual prevalence of latex allergy among health-care workers in American hospitals has remained unclear, despite previous epidemiologic studies. [7–13,18–21]These past studies have not had the benefit of a reproducible diagnostic skin test procedure because of the absence of a safe and immunochemically well-characterized latex skin testing reagent in the United States. Furthermore, they did not use a validated glove provocation procedure to clarify mismatches between the clinical history and the diagnostic confirmatory tests. In the current study, we used a reproducible, well-characterized nonammoniated latex reagent to perform puncture skin testing. The diagnosis was further clarified using a latex-specific IgE antibody analysis on masked sera. Finally, a two-stage latex glove provocation procedure was performed if there was discordance between the history and the puncture skin test result, the latex-specific IgE test results, or both.
In our study, 12.5% of anesthesiologists (Table 2) were identified as sensitized (IgE antibody positive) to natural rubber latex. Of these, 2.4% had overt clinical symptoms that required them to take medication before work and to avoid using powdered and nonpowdered latex gloves. The remaining 10.1% of the sensitized anesthesiologists were considered occult or presymptomatic cases with no clinical symptoms after exposure of their skin or upper and lower airways to latex allergens presented during a two-stage glove provocation test. Because both the skin test and the serology results were reconfirmed in repeated tests, technical errors are considered unlikely as a cause of these results. We believe that these persons are in the early stages of sensitization, and perhaps by avoiding latex exposure, they can prevent progression to symptomatic disease. A longitudinal natural history is planned to follow this group at yearly intervals for the next 3 yr to examine this issue directly. Our ongoing natural history study of latex-allergic persons has shown that prolonged avoidance of latex exposure is effective in reducing skin reactivity and serum levels of latex-specific IgE. However, no latex-allergic health-care worker has completely lost his or her skin reactivity to latex. Therefore, we believe that identification of persons early in the sensitization process can facilitate avoidance practices that many minimize any progression to clinical symptoms. The prevalence rates in our study group compare favorably with those obtained in a Finnish population with a 6.2% rate of latex sensitization in highly exposed operating unit personnel in Finnish hospitals. 
The presence of skin symptoms (hives, rash, swelling, itching, redness, irritation) associated with latex glove use was the strongest risk factors (odds ratio, 24.2; 95% CI, 5.8–100.8 with the contact dermatitis group excluded from the control group; odds ratio, 4.6; 95% CI. 1.6–13.4 with the contact dermatitis group included in the control group). These data support a popular hypothesis that adsorption of allergen through skin on the hands that have been injured by irritation or type 4 (delayed-type) hypersensitivity to chemical additives in rubber gloves cab facilitate the induction of latex-specific IgE antibodies. Although it is unlikely that type 1 hypersensitivity will develop in all persons with hand lesions related to type 4 hypersensitivity symptoms, preventive measures would be prudent to eliminate type 4-related lesions to minimize allergen adsorption. Persons with a contact dermatitis might also consider diagnostic testing for latex-specific IgE before symptoms of type 1 hypersensitivity appear.
The IgE antibody cross-reactivity to specific foods such as bananas, avocados, and kiwis has been reported. [23,24]In agreement with other studies, we identified a history of allergy to bananas, avocados, or kiwis as a risk factor for the development of latex allergy (odds ratio, 9.8; CI, 1.6 - 61.9). Grzybowski et al. also reported an increased odds ratio in latex-sensitized nurses, from 1.5 to 10.9, when the nurse had evidence of an allergy to kiwi and avocado, respectively. Similarly, Lebenbom-Mansour et al. reported an increased odds of latex allergy in patients with kiwi and banana allergy (odds ratios, 4.92 and 14.22, respectively). Finally, consistent with other reports, [7,8,10,19,26]we found that a history of atopy is a third significant factor for latex sensitization. In the current study, persons with an atopic history had the greatest increase in risk for latex allergy (odds ratio, 14.1; 95% CI, 1.8 - 112.1).
Factors not shown to increase the risk for latex sensitization in health-care workers included duration of exposure to latex gloves either by age or by years of work as an anesthesiologist. This reinforces the idea that extended or massive exposure in and of itself may be neither necessary nor sufficient to cause sensitization if the person is not genetically predisposed to allergic disease. Furthermore, we identified persons still in residency training with limited exposure to latex who had become sensitized. Heese et al. also reported sensitization to latex during residency training in dental students. In contrast to our results, they found an increasing prevalence of latex sensitization in dental students with increasing time in residency. Contrary to previous reports, [10,25]we found neither sex nor racial differences in the prevalence of latex sensitization among white persons compared with African-Americans, Asian-Americans, or Hispanic-Americans. The greater prevalence of latex sensitization among men compared with women and among white persons shown by Lebenbom-Mansour et al. may have resulted from selections bias because they studied volunteers from an ambulatory surgery patient population on the day of surgery. Grzybowski et al. reported racial but not sex differences for latex sensitization among nurses. The voluntary nature and incomplete ascertainment of that study may also have led to selection bias that could account for their findings.
In conclusions, we studied a cohort of high-risk health-care workers for latex allergy. We used four independent tests to maximize the accuracy of diagnosis: a clinical history questionnaire, a characterized reproducible nonammoniated latex reagent to perform puncture skin testing, a Food and Drug Administration-approved serologic assay to quantify latex-specific IgE antibody in serum, and, when required for clarification, a validated two-stage latex glove provocation procedure. Using these methods, we determined that the prevalence of latex sensitization within this cohort of anesthesiologists in 12.5%, with overt symptoms appearing in 2.4%. Significant risk factors for latex sensitization included a history of atopy; history of allergy to bananas, avocados, or kiwis; and skin symptoms with the use of powdered latex gloves. These data support the need to transform the health-care environment into a latex-safe one that minimizes latex exposure to patients and hospital staff.