Subspecialty Clinics: Allergic Diseases Allergic Reactions to Latex Among Health-Care Workers
MARK E. BUBAK, M.D.,* Division ofAllergic Diseases and Internal Medicine; CHARLES E. REED, M.D., Allergic Diseases Research Laboratory; ANTHONY F. FRANSWAY, M.D., Department ofDermatology; JOHN W. YUNGINGER, M.D., Section of General Pediatrics and Pediatric Allergy and Immunology; RICHARD T. JONES, B.S., Allergic Diseases Research Laboratory; CAROL A. CARLSON, M.D., Section of General Pediatrics and Pediatric Allergy and Immunology; LOREN W. HUNT, M.D., Division ofAllergic Diseases and Internal Medicine With the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic and the practice of protecting health-care workers from all body fluids, the use of rubber gloves has increased, as has occupational allergy to latex among health-care workers. During 1991, 49 Mayo Medical Center employees sought assessment and treatment of rhinitis, conjunctivitis, contact urticaria, contact dermatitis, asthma, or eczema thought to be related to exposure to latex. Most of these persons had a history of atopy and worked in areas where rubber gloves were used and changed frequently. Of the 49 subjects, 34 had positive results of skin tests to latex products, and the sera from 19 of 3S persons tested contained increased latex-specific IgE antibodies. Employees with sensitivity to latex (and co-workers in the immediate areas) should use vinyl gloves and should notify their own health-care providers of their sensitization. Changes in job assignment may be necessary for some persons.
The epidemic of the acquired immunodeficiency syndrome (AIDS) has resulted in drastic changes in the policies and procedures for both medical and paramedical personnel. Virtually all persons who work in medical laboratories, phlebotomy and intravenous services, nursing, respiratory therapy, radiology, and dental clinics as well as emergency medical, fire, and police personnel have been encouraged to wear protective gloves and eye protection when they perform venipunctures or attend trauma-injured patients or *Currentaddress: Central Plains Clinic, Sioux Falls, South Dakota. This study was supported in part by Grants AI 21255 and AI 72621 from the National Institutes of Health, Public Health Service, and by Mayo Foundation. Address reprint requests to Dr. L. W. Hunt, Division of Allergic Diseases, Mayo Clinic, Rochester, MN 55905. Mayo CIin Proc 67:1075-1079,1992
when they are exposed to soiled dressings, human blood, or tissue products. For many persons, this dramatic growth in the daily use of protective gloves and the frequent changing of these gloves may be resulting in an increased contact with or inhalant sensitization to latex products as well as an increasing incidence of occupational allergy to latex. Allergic contact dermatitis from rubber products has long been recognized, but natural latex is rarely the sensitizer; rather, the additives such as mercaptobenzothiazole and tetramethylthiuram disulfide are responsible.' Immediate hypersensitivity to latex was first noted in 1979.2 Since then, several reports have suggested that the frequency of latex allergy may be increasing. Immediate-type allergic reactions to latex, such as local urticarial lesions on the hands or face, rhinoconjunctivitis, asthma, or even anaphylaxis, have been recognized clinically>" The implications of allergy to latex extend considerably beyond the use of gloves and
1075
1076 LATEX ALLERGY AMONG HEALTH"CARE WORKERS
include condoms, balloons, and various catheters. A recent bulletin from the Food and Drug Administration? suggested that anaphylactic reactions to barium enemas may be due to the latex balloon-tipped catheter used to instill the barium," and it described the removal of these devices from the market by the manufacturer. Recently, numerous Mayo Medical Genter personnel who sought assessment and treatment of rhinoconjunctivitis, asthma, urticaria, and contact dermatitis had a possible allergy to latex. Thus, we developed and modified a skin testing procedure to confirm suspected IgE-mediated allergic reactions to latex. Herein we provide a clinical description of these patients and propose recommendations for management of their sensitivity.
MATERIAL AND METHODS Study Subjects.-All 49 study subjects (45 women and 4 men) were Mayo Medical Center employees and were referred to the Division of Allergic Diseases and Internal Medicine or the Department of Dermatology during the calendar year 1991. In all subjects, data on age, sex, description of personal atopy, occupational background, and current symptoms suggestive of an allergic reaction to latex were elicited, and skin testing was performed. Skin Tests.-Extracts oflatex gloves (Bodyguards, T. K. Glove Products; Pharmsal-Flexam, Baxter Corporation; and Safeskin, Safeskin Corp.), vinyl gloves (Tru-Touch, Becton Dickinson), and cornstarch (two types-cross-linked cornstarch from Baxter and locally purchased Argo cornstarch) were prepared 1:5 (weightvolume) in phosphate-buffered saline that contained 0.5% human serum albumin. Skin tests with histamine phosphate and buffer controls were performed by the prick method. Patients assessed during the first 4 months were also tested by using a skin prick through diluent over which a piece of washed or unwashed glove had been placed, a modification of the method described by Turjanmaa and associates," Some patients were also tested with a 1:10 dilution of white or brown latex compound solution (provided by Baxter), from which their gloves had been made. Skin responses greater than 3 mm in diameter were considered positive. Latex-Specific IgE Antibodies.-We extracted latex gloves (Bodyguards) 1:5 (weight:volume) in phosphatebuffered saline alone and concentrated the extract 20-fold by pressure filtration through Amicon YM-lO membranes. The concentrated extract was reacted with derivitized polyacrylamide beads that contained N-hydroxysuccinimide carboxylate ester groups (Matrex Pel 102, Amicon Corp.); extract components that have free amino-groups are covalently coupled to the derivitized beads.'? The solid-phase allergen thus produced was used in subsequent radioimmunoassays to measure latex-specific IgE antibodies in some serum
Mayo eIin Proc, November 1992, Vol 67
samples from the subjects.'? Results were expressed as percent negative control-for example, the percentage of radioactive binding produced by the test sera, divided by the percentage of radioactive binding produced by serum from a normal, nonallergic person, times 100. Values greater than 250% negative control were considered increased.
RESULTS The demographic data of the 49 Mayo employees who underwent skin tests are summarized in Table 1. Almost all the persons had a history of atopy-asthma, allergic rhinitis, or eczema or some combination of these conditions. For most of these persons, their jobs involved exposure to latex gloves, and they often changed gloves numerous times during the day. Almost all the study subjects were laboratory or operating room technicians, nurses, phlebotomists, dental technicians, or physicians (one orthopedist and one anesthesiologist). The most frequent symptoms associated with exposure to latex were rhinoconjunctivitis, contact urticaria, contact dermatitis, and asthma. Of the 49 study subjects, results of skin tests to one or more latex products were positive in 34; in almost all cases, all latex products tested had concordant positive results (Table 2). In five persons, skin test reactivity to vinyl glove extracts was slight; results of all skin tests to cornstarch were negative. Of interest, results of skin tests with washed glove patches were positive less often than were those with unwashed patches (28% and 60%, respectively); this finding suggests that the latex allergen content on the glove surface can be decreased with careful washing. Latex-specific IgE antibodies were increased in 19 of the 35 persons (54%) in whom they were measured, and all 19 had positive results of latex skin tests. The magnitude of the IgE antibody increase was not associated with patient age, occupation, or symptom complex. DISCUSSION Latex is the milky sap of the tree Hevea brasiliensis, to which preservatives, accelerators, and antioxidants are added. Latex gloves are generally manufactured over a heated, powdered mold that passes through a slurry of this latex compound at room temperature. The web of latex that makes the glove forms over the heated mold, and this mold is then baked at high temperature; the glove is later removed and can be further powdered.':" Although cornstarch is used to powder gloves, it is rarely the primary allergen.I-" In our study subjects, no skin tests to commercial or industrial cornstarch had positive results. Recently, investigators showed that latex allergens adsorb to cornstarch particles inside the gloves and that starch particles from latex gloves (but not from vinyl gloves) could evoke positive results to inhalation challenge tests in latex-sensitive persons. 14 In our
Mayo Clin Proc, November 1992,Vol 67
LATEX ALLERGY AMONG HEALTH-CARE WORKERS
Table I.-Demographic Data and Allergic Symptoms of 49 Mayo Employees Who Underwent Skin Tests for Allergy to Latex Subjects* Factor
No.
%
Women Men Personal history of atopy] Occupation Laboratory technician Nurse Operating room technician Phlebotomist Dental technician Physician Administrative services Record clerk Dietary worker Environmental services Symptoms:j: Rhinoconjunctivitis Contact urticaria Contact dermatitis Asthma Conjunctivitis only Pruritus Eczema
45 4 32
92 8 65
16 14 6 4 3 2 I 1 1 I
33 29 12
36 25 14 13 1 1 1
73 51 29 27 2 2 2
8
6 4 2 2 2 2
*The subjects ranged in age from 22 to 50 years. t Allergic rhinitis, asthma, or eczema or a combination of these conditions. :j:Some patients had multiple symptoms after exposure to latex.
study, the positive results of skin tests to the vinyl gloves were minimal and occurred only in subjects with highly positive results of latex skin tests. The clinical significance of these weak positive reactions is questionable because none of the patients had clinical symptoms with use of vinyl gloves. Latex allergens are incompletely characterized. Immunoblots from polyacrylamide gel electrophoresis of latex in sodium dodecyl sulfate that were probed with sera from latex-sensitized persons revealed IgE-binding bands with apparentmolecular weights of 14 kd, 28 kd, or 66 kd. 1s- 18 Of interest, in the current study, we found that the subjects with a highclinical sensitivity had positive reactions to the liquid latex compound mixture used to manufacture the gloves as well as to the glove extracts; this finding is consistent with the allergens arising from the latex itself and not being "neoantigens" formed by the heating or the manufacturing process. This relationship had been shown earlier by Turjanmaa and colleagues? and-Slater," who noted positive results of skin tests to latex obtained directly from the rubber tree. Our initial testing included skin prick tests with washed and unwashed gloves; the reactions to the skin test with
1077
washed gloves were smaller and less frequent than those with unwashed gloves. The amount of allergen in latex products such as gloves and condoms varies from manufacturer to manufacturer.P?' All the latex-allergic study subjects reported frequent exposure to latex products at work, and latex gloves were the main offending source. Children at risk of latex sensitization include those with myelodysplasia and those who have undergone multiple previous operations or repeated urinary catheterizations.S'
MARK E. BUBAK, M.D.,* Division ofAllergic Diseases and Internal Medicine; CHARLES E. REED, M.D., Allergic Diseases Research Laboratory; ANTHONY F. FRANSWAY, M.D., Department ofDermatology; JOHN W. YUNGINGER, M.D., Section of General Pediatrics and Pediatric Allergy and Immunology; RICHARD T. JONES, B.S., Allergic Diseases Research Laboratory; CAROL A. CARLSON, M.D., Section of General Pediatrics and Pediatric Allergy and Immunology; LOREN W. HUNT, M.D., Division ofAllergic Diseases and Internal Medicine With the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic and the practice of protecting health-care workers from all body fluids, the use of rubber gloves has increased, as has occupational allergy to latex among health-care workers. During 1991, 49 Mayo Medical Center employees sought assessment and treatment of rhinitis, conjunctivitis, contact urticaria, contact dermatitis, asthma, or eczema thought to be related to exposure to latex. Most of these persons had a history of atopy and worked in areas where rubber gloves were used and changed frequently. Of the 49 subjects, 34 had positive results of skin tests to latex products, and the sera from 19 of 3S persons tested contained increased latex-specific IgE antibodies. Employees with sensitivity to latex (and co-workers in the immediate areas) should use vinyl gloves and should notify their own health-care providers of their sensitization. Changes in job assignment may be necessary for some persons.
The epidemic of the acquired immunodeficiency syndrome (AIDS) has resulted in drastic changes in the policies and procedures for both medical and paramedical personnel. Virtually all persons who work in medical laboratories, phlebotomy and intravenous services, nursing, respiratory therapy, radiology, and dental clinics as well as emergency medical, fire, and police personnel have been encouraged to wear protective gloves and eye protection when they perform venipunctures or attend trauma-injured patients or *Currentaddress: Central Plains Clinic, Sioux Falls, South Dakota. This study was supported in part by Grants AI 21255 and AI 72621 from the National Institutes of Health, Public Health Service, and by Mayo Foundation. Address reprint requests to Dr. L. W. Hunt, Division of Allergic Diseases, Mayo Clinic, Rochester, MN 55905. Mayo CIin Proc 67:1075-1079,1992
when they are exposed to soiled dressings, human blood, or tissue products. For many persons, this dramatic growth in the daily use of protective gloves and the frequent changing of these gloves may be resulting in an increased contact with or inhalant sensitization to latex products as well as an increasing incidence of occupational allergy to latex. Allergic contact dermatitis from rubber products has long been recognized, but natural latex is rarely the sensitizer; rather, the additives such as mercaptobenzothiazole and tetramethylthiuram disulfide are responsible.' Immediate hypersensitivity to latex was first noted in 1979.2 Since then, several reports have suggested that the frequency of latex allergy may be increasing. Immediate-type allergic reactions to latex, such as local urticarial lesions on the hands or face, rhinoconjunctivitis, asthma, or even anaphylaxis, have been recognized clinically>" The implications of allergy to latex extend considerably beyond the use of gloves and
1075
1076 LATEX ALLERGY AMONG HEALTH"CARE WORKERS
include condoms, balloons, and various catheters. A recent bulletin from the Food and Drug Administration? suggested that anaphylactic reactions to barium enemas may be due to the latex balloon-tipped catheter used to instill the barium," and it described the removal of these devices from the market by the manufacturer. Recently, numerous Mayo Medical Genter personnel who sought assessment and treatment of rhinoconjunctivitis, asthma, urticaria, and contact dermatitis had a possible allergy to latex. Thus, we developed and modified a skin testing procedure to confirm suspected IgE-mediated allergic reactions to latex. Herein we provide a clinical description of these patients and propose recommendations for management of their sensitivity.
MATERIAL AND METHODS Study Subjects.-All 49 study subjects (45 women and 4 men) were Mayo Medical Center employees and were referred to the Division of Allergic Diseases and Internal Medicine or the Department of Dermatology during the calendar year 1991. In all subjects, data on age, sex, description of personal atopy, occupational background, and current symptoms suggestive of an allergic reaction to latex were elicited, and skin testing was performed. Skin Tests.-Extracts oflatex gloves (Bodyguards, T. K. Glove Products; Pharmsal-Flexam, Baxter Corporation; and Safeskin, Safeskin Corp.), vinyl gloves (Tru-Touch, Becton Dickinson), and cornstarch (two types-cross-linked cornstarch from Baxter and locally purchased Argo cornstarch) were prepared 1:5 (weightvolume) in phosphate-buffered saline that contained 0.5% human serum albumin. Skin tests with histamine phosphate and buffer controls were performed by the prick method. Patients assessed during the first 4 months were also tested by using a skin prick through diluent over which a piece of washed or unwashed glove had been placed, a modification of the method described by Turjanmaa and associates," Some patients were also tested with a 1:10 dilution of white or brown latex compound solution (provided by Baxter), from which their gloves had been made. Skin responses greater than 3 mm in diameter were considered positive. Latex-Specific IgE Antibodies.-We extracted latex gloves (Bodyguards) 1:5 (weight:volume) in phosphatebuffered saline alone and concentrated the extract 20-fold by pressure filtration through Amicon YM-lO membranes. The concentrated extract was reacted with derivitized polyacrylamide beads that contained N-hydroxysuccinimide carboxylate ester groups (Matrex Pel 102, Amicon Corp.); extract components that have free amino-groups are covalently coupled to the derivitized beads.'? The solid-phase allergen thus produced was used in subsequent radioimmunoassays to measure latex-specific IgE antibodies in some serum
Mayo eIin Proc, November 1992, Vol 67
samples from the subjects.'? Results were expressed as percent negative control-for example, the percentage of radioactive binding produced by the test sera, divided by the percentage of radioactive binding produced by serum from a normal, nonallergic person, times 100. Values greater than 250% negative control were considered increased.
RESULTS The demographic data of the 49 Mayo employees who underwent skin tests are summarized in Table 1. Almost all the persons had a history of atopy-asthma, allergic rhinitis, or eczema or some combination of these conditions. For most of these persons, their jobs involved exposure to latex gloves, and they often changed gloves numerous times during the day. Almost all the study subjects were laboratory or operating room technicians, nurses, phlebotomists, dental technicians, or physicians (one orthopedist and one anesthesiologist). The most frequent symptoms associated with exposure to latex were rhinoconjunctivitis, contact urticaria, contact dermatitis, and asthma. Of the 49 study subjects, results of skin tests to one or more latex products were positive in 34; in almost all cases, all latex products tested had concordant positive results (Table 2). In five persons, skin test reactivity to vinyl glove extracts was slight; results of all skin tests to cornstarch were negative. Of interest, results of skin tests with washed glove patches were positive less often than were those with unwashed patches (28% and 60%, respectively); this finding suggests that the latex allergen content on the glove surface can be decreased with careful washing. Latex-specific IgE antibodies were increased in 19 of the 35 persons (54%) in whom they were measured, and all 19 had positive results of latex skin tests. The magnitude of the IgE antibody increase was not associated with patient age, occupation, or symptom complex. DISCUSSION Latex is the milky sap of the tree Hevea brasiliensis, to which preservatives, accelerators, and antioxidants are added. Latex gloves are generally manufactured over a heated, powdered mold that passes through a slurry of this latex compound at room temperature. The web of latex that makes the glove forms over the heated mold, and this mold is then baked at high temperature; the glove is later removed and can be further powdered.':" Although cornstarch is used to powder gloves, it is rarely the primary allergen.I-" In our study subjects, no skin tests to commercial or industrial cornstarch had positive results. Recently, investigators showed that latex allergens adsorb to cornstarch particles inside the gloves and that starch particles from latex gloves (but not from vinyl gloves) could evoke positive results to inhalation challenge tests in latex-sensitive persons. 14 In our
Mayo Clin Proc, November 1992,Vol 67
LATEX ALLERGY AMONG HEALTH-CARE WORKERS
Table I.-Demographic Data and Allergic Symptoms of 49 Mayo Employees Who Underwent Skin Tests for Allergy to Latex Subjects* Factor
No.
%
Women Men Personal history of atopy] Occupation Laboratory technician Nurse Operating room technician Phlebotomist Dental technician Physician Administrative services Record clerk Dietary worker Environmental services Symptoms:j: Rhinoconjunctivitis Contact urticaria Contact dermatitis Asthma Conjunctivitis only Pruritus Eczema
45 4 32
92 8 65
16 14 6 4 3 2 I 1 1 I
33 29 12
36 25 14 13 1 1 1
73 51 29 27 2 2 2
8
6 4 2 2 2 2
*The subjects ranged in age from 22 to 50 years. t Allergic rhinitis, asthma, or eczema or a combination of these conditions. :j:Some patients had multiple symptoms after exposure to latex.
study, the positive results of skin tests to the vinyl gloves were minimal and occurred only in subjects with highly positive results of latex skin tests. The clinical significance of these weak positive reactions is questionable because none of the patients had clinical symptoms with use of vinyl gloves. Latex allergens are incompletely characterized. Immunoblots from polyacrylamide gel electrophoresis of latex in sodium dodecyl sulfate that were probed with sera from latex-sensitized persons revealed IgE-binding bands with apparentmolecular weights of 14 kd, 28 kd, or 66 kd. 1s- 18 Of interest, in the current study, we found that the subjects with a highclinical sensitivity had positive reactions to the liquid latex compound mixture used to manufacture the gloves as well as to the glove extracts; this finding is consistent with the allergens arising from the latex itself and not being "neoantigens" formed by the heating or the manufacturing process. This relationship had been shown earlier by Turjanmaa and colleagues? and-Slater," who noted positive results of skin tests to latex obtained directly from the rubber tree. Our initial testing included skin prick tests with washed and unwashed gloves; the reactions to the skin test with
1077
washed gloves were smaller and less frequent than those with unwashed gloves. The amount of allergen in latex products such as gloves and condoms varies from manufacturer to manufacturer.P?' All the latex-allergic study subjects reported frequent exposure to latex products at work, and latex gloves were the main offending source. Children at risk of latex sensitization include those with myelodysplasia and those who have undergone multiple previous operations or repeated urinary catheterizations.S'
