Latex-induced allergic reactions, including anaphylaxis, have been increasingly recognized in surgical patients since Nutter's first report of latex induced contact urticaria in 1979 . In fact, Laxenaire and Monert-Vautrin  have suggested that 12% of intraoperative anaphylactic reactions can be attributed to latex allergy. Individuals with chronic latex exposure, atopy, specific food allergies, spina bifida, or congenital urologic defects have been identified as being at high risk . In addition, individuals with a history of symptoms on exposure to latex products (i.e., shortness of breath after blowing up balloons or playing with rubber balls, oral itching or swelling after dental examinations, etc.) are thought to be latex-sensitive. The broader use of latex as a body fluid barrier has increased the number of individuals exposed to latex, thereby potentially sensitizing more people. The Food and Drug Administration (FDA) recommends performing a preoperative latex-directed history to identify individuals at risk of latex allergic responses . Of great concern, however, is evidence that history alone may not identify many latex-sensitive individuals [5,6].
Increasing numbers of perioperative reactions to latex have suggested the need for a sensitive, specific, cost-effective method of identifying individuals at risk of latex hypersensitivity reactions. Skin and provocation testing have been used for this purpose, but these pose the risk of inducing allergic reactions, particularly anaphylaxis. Recently, in vitro testing technology has improved, and the sensitivity and specificity of newer assays are high . The AlaSTAT latex allergy test (an enzyme-linked immunoadsorbent assay for detecting the presence of immunoglobin E [IgE] antibodies against latex) is one low-risk standardized testing methodology that may prove valuable for screening patients.
Identification of individuals at risk of latex allergic responses is crucial, since the only reliable method of preventing allergic responses is to prevent exposure. Pretreatment with steroids, antihistamines, and/or type 2 histamine antagonists has been suggested; however, there have been case reports of allergic reactions despite pretreatment [8,9]. Therefore, characterizing the ambulatory surgical population, which constitutes more than 60% of surgical patients, would be of value in preventing latex allergic events. This study was undertaken to define the incidence of latex sensitivity and the ability of a questionnaire to identify individuals at risk of latex hypersensitivity reactions in an ambulatory surgical population.
After institutional review board approval, a random convenience sample of 996 patients scheduled for ambulatory surgery at the Henry Ford Hospital Detroit campus was enrolled. Exclusion criteria included age less than 18 yr, pregnancy, or failure to consent to the study.
After informed consent, patients completed a questionnaire covering demographic information, previous exposure or reactions to latex, history of atopy, asthma, food allergies, congenital neurologic abnormalities, urologic abnormalities or self catheterization; and number of surgical procedures (see Appendix Table 3). The responses to these questionnaires were not available to the anesthesiologist on the day of surgery. Blood samples were obtained and sent to the allergy research laboratory at Henry Ford Hospital for analysis. Samples were batch run, and results were not available at the time of surgery. The anesthesiologists managing the patients made the decision to use a latex-reduced environment based on the preoperative histories they obtained, the FDA's currently recommended standard. All persons with IgE antibodies against latex were notified of the results of their serum testing in writing and were advised to discuss it with their personal physician or call the anesthesiologists involved in the study.
Serum samples were tested for anti-latex IgE antibodies using the AlaSTAT test (Diagnostic Products, Inc., Los Angeles, CA). Significantly elevated antilatex IgE levels were defined as these >or=to0.35 IU/mL. Anti-latex IgE levels were graded as negative or Class 0 (0.00-0.29 IU/mL), equivocal or Class +/- (0.30-0.34 IU/mL), Class I (0.35-1.49 IU/mL), Class II (1.50-2.99 IU/mL), Class III (3.00-14.9 IU/mL), or Class IV (>or=to15.0 IU/mL). Individuals testing the serum samples were unaware of the answers on the questionnaire. Questionnaire and serum results were collated by a statistician not directly involved in the study. The independent variables in the questionnaire were assessed for association with the presence of elevated anti-latex IgE levels using Fisher's exact test for binary variables and the Wilcoxon rank sum test for continuous variables. For binary variables, odds ratios and associated 95% confidence intervals were estimated. The odds ratio represents the ratio of the odds of having high anti-latex IgE when the independent variable is present to the odds of having high anti-latex IgE when the independent variable is not present. If any of the cells in the 2 x 2 Table wereempty, a correction factor of 0.5 was used for estimation of the odds ratio.
A stepwise logistic regression routine was used to determine which set of independent variables best modeled the presence of high anti-latex IgE antibodies. A P value of 0.05 was used as the entry criterion for modeling. Screening parameters of sensitivity, specificity, predictive value positive, and predictive value negative were estimated from the multiple logistic regression model. For comparison purposes, the screening parameters for the prediction rule that predicted a high anti-latex IgE if any of the statistically significant (P < 0.05) independent variables were present were also computed.
At the end of the study, a retrospective chart review was performed for all individuals found latex sensitive by serum testing. The perioperative records of these patients were reviewed for evidence suggestive of allergic reactions.
Of the study population, 6.7% (n = 67) had IgE antibodies against latex. Of the men, 8.6% (37 of 430) were IgE-positive compared with 5.3% (30 of 566) of women, a statistically significant difference (P = 0.042, odds ratio 1.68, 95% confidence interval 1.0, 2.8). Of the individuals who identified themselves as non-Caucasian, 9.8% (42 of 429) had antibodies against latex, as opposed to 4.3% (24 of 563) of Caucasians (P = 0.001, odds ratio 2.44, 95% confidence interval 1.5, 4.1). In addition, a history of asthma, congenital spinal cord problems, allergy to any foods and to banana or kiwi specifically, history of latex allergy, or the allergic symptoms of rash, wheezing, watery eyes, or symptoms during dental examinations was a statistically significant predictor of the presence of IgE antibodies against latex (Table 1). In fact, individuals with allergic symptoms during dental examinations or when eating kiwi fruit were more than 14 times as likely to be latex-sensitive. The symptom of watery eyes on latex exposure was associated with a 9.5-fold increased risk. A rash with latex exposure or a history of latex allergy more than quadrupled the risk of having IgE antibodies against latex (Table 1). Age was also found to be a significant factor, with younger individuals being more likely to have antibodies against latex (mean age of 48.5 +/- 20 yr vs 55.8 +/- 17.4 yr, P = 0.0012). Histories of hay fever (P = 0.06) and of difficulty breathing when exposed to latex (P = 0.07) approached statistical significance. There was no significant relationship between the number of previous surgeries and the presence of latex sensitivity (mean number of surgeries for latex sensitive individuals was 3.5 +/- 3.1 vs 3.3 +/- 3.7 for non-latex-sensitive individuals, P = 0.2622). None of the other historical factors was associated with the presence of anti-latex IgE antibodies (Table 2). Using stepwise regression, male gender, non-Caucasian race, history of asthma, congenital spinal cord problems, allergy to bananas, rash on exposure to latex, and age were identified as the best historical predictors of seropositivity. The combined historical predictors had a sensitivity of 77%, a specificity of 46%, a positive predictive value of 9%, and a negative predictive value of 97%.
For comparison to the "best" statistical model generated by the stepwise logistic analysis, a prediction rule was generated using all of the variables listed in Table 1 as well as gender and race. A positive was defined as an individual who was positive on any of the 12 statistically significant variables from Table 1, including gender and race. This includes six additional variables when compared with the stepwise logistic model. With this approach, the sensitivity was 93%, the specificity was 26%, the positive predictive value was 8%, and the negative predictive value was 98%. The two approaches produced very similar results. The logistic model missed six latex-sensitive individuals (9%), while the all significant variables approach missed five (7.5%).
Eight hundred eighty-four individuals tested negative or equivocal for IgE antibodies against latex. Most positive reactions were Class I (n = 35), with decreasing numbers of Class II (n = 14), Class III (n = 15), and Class IV (n = 3) results noted.
The retrospective review of charts for the individuals with IgE antibodies against latex revealed no significant perioperative allergic events. None of the seropositive individuals in this study were treated in a latex-reduced environment.
The present study is the first large-scale prospective analysis to document the incidence of latex sensitivity in an ambulatory surgical population and to evaluate the efficacy of a standardized history for determining latex sensitivity. Previous studies of surgical populations have primarily been retrospective and have focused on the postoperative evaluation of individuals manifesting allergic responses under anesthesia. Despite hundreds of published reports of latex allergy, the incidence in the general population was previously unknown. The 6.7% incidence of latex sensitivity found in this study suggests that latex sensitivity in ambulatory surgical populations may be more of a problem than was previously recognized. These data are very similar to those of Ownby et al. , who found a 6.4% incidence in volunteer blood donors. Of great concern is the finding that younger individuals are more likely to be sensitive to latex. This clustering of latex sensitivity in a younger portion of the population is consistent with the findings of other investigators  and suggests that physicians will increasingly be caring for latex-sensitive individuals. Along with the broader recognition of latex as an allergen, this may account for the continued increase in the number of reports of perioperative latex allergic events.
The presence of latex-specific IgE antibodies in 67 surgical patients treated without avoidance precautions initially suggests that all 67 of the patients should have had allergic reactions perioperatively. As noted in allergy textbooks, the presence of specific IgE antibodies only demonstrates that sensitization has occurred and does not indicate which sensitized individuals will react to latex exposure . There is little information in the literature concerning the risk of allergic reactions in sensitized individuals, but a few studies suggest that severe reactions are relatively uncommon. Stuckey et al.  measured anti-honey bee venom IgE antibodies in 3439 adults and found a 15.8% prevalence of seropositivity. Of the 542 seropositive individuals, only 46 (8.5%) had histories of systemic reactions to stings. In a study of anaphylactic reactions during barium enemas, Ownby et al.  estimated that there was approximately 1 reaction per 1000 procedures. Presumably, the prevalence of latex sensitivity among patients undergoing barium enemas would have been similar to the prevalence in our presurgical population. Based on these considerations, the absence of any recognized allergic reactions among the 67 seropositive individuals in this study is not improbable based on chance alone.
Many approaches have been used to determine the presence of latex sensitivity; however, the lack of reliable, standardized testing methodologies has made diagnosis difficult . There is no diagnostic method that identifies 100% of latex-sensitive patients. At least one report has suggested that skin-prick testing (SPT) with appropriate extracts is highly predictive of latex allergy , but the safety and reliability of SPT have been questioned . Presently, there is no FDA-approved standardized latex extract available for skin testing, and as a result, clinicians have frequently resorted to office extraction of latex. This has contributed to inconsistent test solutions. Further, investigators have reported severe allergic reactions with SPT .
In vitro testing has the advantages of being safe, providing reproducible results, and being more practical for screening. The principal risk is failing to identify a latex-sensitive individual. Most immunoassays have demonstrated sensitivities of 50%-70% and specificities of more than 95% when compared with history or skin testing . The AlaSTAT test, however, has been shown to be highly sensitive (>90%) and specific (>90%)  and has been approved by the FDA for the diagnosis of latex sensitivity.
Currently, a preoperative latex-directed history is the primary method of identifying latex-sensitive patients. This is consistent with the recommendations of both the FDA  and the American Academy of Allergy and Immunology  and is similar to current recommendations for the performance of other preoperative tests. Unfortunately, despite the identification of many high-risk groups, there is inconsistency in the literature as to the historical and demographic factors that increase risk. In addition, as the reports on latex allergy increase, so do the historical variables linked to the presence of anti-latex antibodies, with a resultant decrease in the specificity of history. The present study has demonstrated that history as obtained by a questionnaire is an ineffective tool for identifying individuals with anti-latex antibodies. While the sensitivity was reasonably high (77%-93%), the specificity (26%-46%) and positive predictive value (8%-9%) of history were extremely low. Even the most liberal historical criteria failed to identify 9% of latex-sensitive individuals in the study. This finding is supported by studies of other populations that found that questionnaires were unreliable in predicting latex sensitization [3,6], which suggests that the historical factors critical for identifying latex-sensitive individuals, if they exist, have yet to be determined.
The present study did find some historical factors that increased the risk of having anti-latex antibodies. For example, a history of spinal cord abnormalities was associated with an increased likelihood of anti-latex IgE. This is consistent with the findings of other investigators [18,19]. The development of latex sensitivity in this population has been attributed to its increased exposure to latex as a result of multiple surgical procedures and the frequent need for urinary tract catheterization. However, the present study failed to show a relationship between urinary tract abnormalities, self-catheterization, number of surgical procedures, or on-the-job exposure to latex and the development of sensitization. These findings are surprising and suggest that additional research is warranted to better understand the role of chronic exposure in the development of latex sensitivity.
A history of atopy (asthma, allergic rhinitis, eczema, and hay fever) has been associated with latex sensitization [13,20]. The present study demonstrates that a history of asthma more than doubles the risk of having anti-latex antibodies. A history of hay fever approached statistical significance, but none of the other elements of atopy was significantly related to an increased risk of IgE antibodies against latex. While this finding appears to contradict data from other investigators, studies have demonstrated that the incidence of latex allergy in atopic controls is only 3% [21,22]. Rather than being an independent risk factor, atopy may be a predisposing factor to the development of latex sensitization. This has been demonstrated in physicians  and nurses [3,6] in whom the combination of atopy and latex exposure increased the incidence of latex sensitivity. It seems prudent to consider a history of atopy as increasing the level of concern for latex sensitivity, even though it may not be highly suggestive on its own. A history of asthma should be considered as a risk factor given that it more than doubled the risk of having anti-latex antibodies.
The present study's finding that a history of food allergy significantly increases the risk of latex sensitization is similar to the findings of other authors. Wrangsjo et al , in a study of 30 patients with contact urticaria to rubber products, found an association between food intolerance and latex sensitivity. General allergic phenomena, including food allergies, were shown by Kelly et al.  to be independent risk factors identifying spina bifida patients with the highest risk of latex-induced anaphylactic reactions. Studies have also found relationships between latex sensitivity and allergies to banana, avocado, peach, and passion fruit, among others [24,25]. This suggests that a history of food allergy should be sought preoperatively, and its presence should increase concern for latex sensitivity. A history of banana or kiwi allergy should raise particular concern and provoke more thorough questioning for evidence of latex sensitivity.
In summary, the present study is the first to demonstrate the incidence of latex sensitivity in an ambulatory surgical population. The 6.7% incidence found was higher than previously suspected. Several historical factors were associated with an increased risk of latex sensitivity; however, the questionnaire history was not effective in determining the presence of latex sensitization. In fact, 9% of latex-sensitive individuals in this study responded negatively to all questions. Since the first sign of latex sensitivity may be intraoperative anaphylaxis, preoperative identification of latex-sensitive individuals is crucial if morbidity and mortality are to be minimized. Despite the limitations identified, a thorough latex-directed history remains the first step, as there is no other reasonable, cost-effective alternative. For those patients with a suggestive history having elective surgery, preoperative consultation with an allergist, in vitro testing, and/or SPT should be considered. If surgery is urgent or emergent, consideration should be given to using a latex-reduced environment, and at the very minimum, there should be a heightened awareness of the possibility of systemic reaction on exposure to latex. The incidence of latex sensitivity justifies greater attention to its presence in ambulatory surgical patients.
The authors gratefully acknowledge the help of the phlebotomy team in Central Testing (the preoperative testing clinic). We also gratefully acknowledge Ed Peterson, PhD, and Michelle Jankowski, PhD, Department of Biostatistics, Henry Ford Hospital, for their help with data entry and statistical analysis.
1. Nutter AF. Contact urticaria to rubber. Br J Dermatol 1979;101:597-8.
2. Laxenaire MC, Moneret-Vautrin DA. Nouveautes en allergo anesthesie. Ann Fr Anesth Reanim 1993;12:89-90.
3. Levy DA, Charpin D, Pecquet C, et al. Allergy to latex. Allergy 1992;47:579-87.
4. FDA Medical Alert. Allergic reactions to latex-containing medical devices. MDA91-1, March 29, 1991.
5. Sussman GL, Beezhold DH. Allergy to latex rubber. Ann Intern Med 1995;122:43-6.
6. Lagier F, Vervoet D, Lhermet I, et al. Prevalence of latex allergy in operating room nurses. J Allergy Clin Immunol 1992;90:319-22.
7. Ownby DR, McCullough J. Testing for latex allergy. J. Clin Immunoassay 1993;16:109-13.
8. Kwitten PL, Becker J, Oyefara B, et al. Latex hypersensitivity reactions despite prophylaxis. Allergy Proc 1992;13:123-7.
9. Gold M, Swartz JS, Braude BM, et al. Intraoperative anaphylaxis: an association with latex sensitivity. J Clin Immunol 1991;87:662-6.
10. Ownby DR, Ownby HE, McCullough J, Shafer AW. The prevalence of anti-latex IgE antibodies in 1000 volunteer blood donors. J Allergy Clin Immunol 1996;97:1188-92.
11. Ownby DR. Tests for IgE antibody. In: Bierman CW, Pearlman DS, Shapiro GG, Busse WW, eds. Allergy, asthma, and immunology from infancy to adulthood. 3rd ed. Philadelphia: WB Saunders, 1996:144-56.
12. Stuckey M, Cobain M, Sears M, et al. Bee venom hypersensitivity in Busselton. Lancet 1982;2:41.
13. Ownby DR, Tomlanovich M, Sammons N, et al. Anaphylaxis associated with latex allergy during barium enema examinations. AJR Am J Roentgenol 1991;156:903-8.
14. Turjanmaa K. Allergy to natural rubber latex: a growing problem. Ann Med 1994;26:297-300.
15. Turjanmaa K, Revnala T, Rasanen L. Comparison of diagnostic methods in latex surgical glove contact urticaria. Contact Dermatitis 1988;19:241-7.
16. Kelly KJ, Kurup VP, Reijula KE, et al. The diagnosis of natural rubber latex allergy. J Allergy Clin Immunol 1994;93:813-6.
17. Kelly KJ, Kurup VP, Zacharism M, et al. Skin and serologic testing in the diagnosis of latex allergy. J Allergy Clin Immunol 1993;91:1140-5.
18. Kelly KJ, Pearson ML, Kurup VP, et al. A cluster of anaphylactic reactions in children with spina bifida during general anesthesia: epidemiologic features, risk factors, and latex hypersensitivity. J Allergy Clin Immunol 1994;94:53-61.
19. Yassin MS, Sanyurah S, Lierl MB, et al. Evaluation of latex allergy in patients with meningomyelocele. Ann Allergy 1992;69:207-11.
20. Lahti A, Turjanmaa K. Prick and use tests with 6 glove brands in patients with immediate allergy to rubber proteins. Contact Dermatitis 1992;26:259-62.
21. Sussman GL. Latex allergy: its importance in clinical practice. Allergy Proc 1992;13:67-9.
22. Arellano R, Bradley J, Sussman G, et al. Prevalence of latex sensitization among hospital physicians occupationally exposed to latex gloves. Anesthesiology 1992;77:905-8.
23. Wrangsjo K, Wahlberg JE, Axelsson IG. IgE-mediated allergy to natural rubber in 30 patients with contact urticaria. Contact Dermatitis 1988;19:264-71.
24. Crisi G, Belsito DV. Contact urticaria from latex in a patient with immediate hypersensitivity to banana, avocado and peach. Contact Dermatitis 1993;28:247-8.
25. Leynadier F, Pecquet C, Dry J. Anaphylaxis to latex during surgery. Anaesthesia 1989;44:547-50.