Latex Allergy Update
By Curtis P. Hamann, MD, Pamela A. Rodgers, PhD, and Kim Sullivan
Often thought of as a modern-day malady, allergic reactions to rubber gloves were first reported in the early 1930s. However, the number of reported reactions rapidly increased as the consumption of medical gloves rose after the implementation of Universal Precautions during the mid-1980s. The more common reactions--often referred to as allergic contact dermatitis--are caused by processing chemicals found in both natural and synthetic rubbers. However, the more serious and potentially life-threatening Type I latex allergy is due to proteins only found in natural rubber products. As of 1997, more than 2,300 allergic reactions associated with latex had been reported to the FDA's MedWatch Program. Over 200 of these reported cases were associated with anaphylaxis, and 17 were also fatal. Recent studies of healthcare workers have estimated the prevalence of Type I latex allergy to be as high as 17%.1 Assuming a conservative 10% prevalence, over 800,000 healthcare workers in the United States have a Type I allergy to latex and 2 million workers may experience allergic contact dermatitis (Type IV) to one of the many chemicals found in the healthcare environment today.
Latex Allergy Defined
Latex allergy is clinically defined as Type I (or Immediate) natural rubber latex (NRL) allergy (Table 1). It is an acquired immune reaction to one or more of the plant proteins inherent to NRL.
Individuals can become sensitized to NRL by constant exposure through the use of various NRL products including: gloves, condoms, balloons, pacifiers, and rubber toys. Exposure to NRL proteins often occurs through cutaneous or percutaneous contact; aerosolized contact (respiratory exposure), mucosal contact (exposure to eyes, nose, mouth, vagina, rectum); intraoperative exposure; and hematogenous exposure through stopcocks, rubber stoppers, and intravenous contact.
Type I symptoms can involve the skin, mucous membranes, respiratory tract, gastrointestinal tract, and/or the cardiovascular system (Table 1). Symptoms can develop rapidly but subside within hours. Because a significant number of individuals are apparently asymptomatic, a detailed medical history is essential to identify risk factors, previous unexplained allergic reactions, or any potentially related symptoms. Individuals who are potentially "at risk" for Type I latex allergy include those who are repeatedly exposed to NRL such as healthcare and latex industry workers, as well as patients with spina bifida, myelomeningocele, or urogenital defects. The presence of pre-existing allergies can be considered an additional risk factor, particularly allergies to kiwi, avocado, banana, chestnuts or stone fruits.
The diagnosis of a Type I latex allery in an individual should be based on symptom evaluation, medical history and the presence of circulating anti-NRL antibodies. These antibodies can be detected using one of three methods: 1) skin prick testing with a source of NRL, 2) serum immunoanalyses and/or 3) use testing with a NRL product (Table 2). Unfortunately, due to the lack of standardization of these methods, obtaining a definitive diagnosis of a Type I latex allergy can be challenging.
A skin prick test is currently considered the most accurate diagnostic method for Type I latex allergy. It is easy to perform, provides quick results (within 15 minutes) and is highly sensitive. Briefly, a patient's arm is pricked through drops of test solution (prepared from NRL gloves or a purified NRL source). A raised red welt at the prick site indicates that the patient is latex allergic. Unfortunately, the standardized test reagents available in Europe with known protein and antigen content are still not commercially available in the United States. For this reason, physicians often choose serologic testing such as the ImmunoCAP and AlaSTAT tests, which determine the amount of certain anti-NRL protein antibodies present in a patient's serum. For high-risk groups such as spina bifida patients, positive serologic test results are considered quite accurate. Unfortunately, serologic tests are not as sensitive and results can be falsely negative in 20-30% of the individuals tested3. Finally, in-use provocation testing may also be considered, where a patient is exposed to a NRL product for a specified time to measure their reaction. Because there is a greater risk of anaphylaxis with in-use testing, patients should be monitored closely.
Currently, Type I latex allergy is a complex problem with multiple allergens and poorly standardized test methods. Therefore, more recent diagnostic guidelines suggest combining one or more test methods. Multiple test methods are particularly recommended for individuals with symptoms inconsistent with serum test results. For example, combining serologic with skin prick testing, or using multiple serologic tests.3 In all cases, tests should be accompanied by an in-depth documentation of a patient's history and risk factors.
Allergic Contact Dermatitis
Although often erroneously referred to as "latex allergy," allergic contact dermatitis (ACD) is a common response to the processing chemicals (i.e., thiurams, carbamates, thioureas, thiazoles) found in rubber products. These chemicals can be used in the production of nitrile, neoprene, and natural rubber medical gloves. Other chemicals commonly used in healthcare settings such as antiseptics, adhesives, disinfectants, and resins can also produce allergic reactions. Known as a Type IV (or delayed) allergy, ACD is an immune-mediated inflammation of the skin that can also involve the fingernails. In contrast to a Type I latex allergy, ACD is localized to the skin (Table 1). Symptoms can take anywhere from minutes to several hours to develop and can persist for weeks. Whether individuals develop ACD is dependent upon individual susceptibility, exposure history and the allergenic potential of the chemical(s). While not life-threatening, if left mismanaged or untreated, ACD reactions can cause permanent damage to the patient/user's skin. Therefore, an accurate and complete diagnosis is essential.
The diagnosis of ACD should be based on symptoms (Table 1), medical history, and a positive skin reaction to test chemicals (known as patch testing). The patch test is typically conducted by a qualified clinician using a standard series of test allergens on the upper back. The patches are applied for 24 to 48 hours, and the skin examined 24, 48, 72, and 96 hours after the patches are removed. Red and inflamed skin under the patch is indicative of an allergy to the applied chemical. While not a perfect method, patch testing is a valuable tool in identifying chemical allergies, particularly when combined with a detailed medical history and symptom survey.
Management of Latex Allergy
Individuals with a Type I latex allergy should use products made from non-latex alternatives which do not contain NRL proteins. Current choices include nitrile, neoprene, polyurethane and styrene-based rubber exam and surgical gloves as well as vinyl exam gloves. Each material is made from a different mixture of chemicals as well as different base polymers. Some of these materials--such as nitrile and neoprene--are vulcanized (heat-cured) much like natural rubber. Others--such as vinyl, polyurethane, and styrene-based rubbers--are created in solvent-based systems without vulcanization. In addition, a powder-free latex environment should be maintained for latex-allergic workers or patients to minimize aerosolized latex allergens. Such an atmosphere has been shown to reduce their symptoms.4
Institutions and individual practitioners can quickly address the problem of latex allergies by offering workers a combination of education, testing and alternative glove materials. The Occupational Safety and Health Administration (OSHA) requires that all employers provide non-latex alternatives to allergic staff, in addition to the safe working environment required by worker compensation laws. Furthermore, considering the significant liability that has arisen in association with a latex-induced anaphylaxis or fatality, it may no longer be cost effective to ignore the problem. In a recent study using conservative estimates of healthcare worker disability costs, implementation of latex alternatives were found to be cost saving, even in small clinics and hospitals.5
With respect to glove choices, cured plastic materials such as vinyl and thermoplastic elastomers are not considered "sensitizing" and do not contain the same rubber processing chemicals found in natural or synthetic rubber gloves. However, gloves made of vinyl or thermoplastic elastomers may contain additives in the form of plasticizers, stabilizers, UV absorbers, fungicides, bacteriocides, and colorants. For some individuals these additives (such as epoxy resins or phthalate plasticizers), can be allergenic.
Workers frequently report some type of occupational skin irritation, but these are not necessarily due to allergic reactions. Frequent hand washing is a common source of skin irritation in health care: in a recent study of over 400 nurses, the number of hand washings per shift ranged as high as 100, and averaged around 30.6 In addition, the skin on a healthcare worker's hand is exposed to hundreds of potential irritants throughout the day. Poor hand and skin care practices may be an initiating factor in occupational skin damage. A recent study also showed that latex allergens penetrated abraded skin more frequently and deeply than healthy, non-abraded skin.7
Latex Allergy Management Protocols and Procedures
Institutional policies should be developed that include identification of latex-allergic individuals, recognition of NRL-containing products and substitutions, coordination of procedures throughout the hospital or clinic, and education of staff and patients (Table 3). Development and implementation of these policies requires input from a multi-disciplinary task force with representatives from occupational safety and health, risk management, materials management, and all patient care departments including food service and housekeeping.9 The goal of these policies and procedures is to establish and maintain a "latex-safe" environment where a patient's or worker's exposure to NRL is eliminated or significantly reduced. An effective strategy involves coordination of NRL-allergic patient care throughout their stay.
Continuing education is a key element of a successful latex management policy. A recent study showed that even when non-latex alternatives were provided and policies established, 80% of healthcare workers with skin problems still chose latex gloves, including those with powder.9 The authors concluded that education was a missing but essential component, and recommended that this begin during preplacement evaluations and training. Ongoing education programs can train staff and patients to identify NRL products, recognize latex allergy symptoms, as well as initiate appropriate treatment.
Regulatory agencies and professional organizations now recommend reductions in the protein content of NRL products to reduce the frequency and severity of latex allergy symptoms in allergic individuals, and to reduce the risk of sensitization in the future. Since their 1997 final rule on latex labeling in medical products, the Food and Drug Administration (FDA) has encouraged the American Society for Testing and Materials (ASTM) to revise and expand their protein and powder standards for medical grade gloves.
Glove protein level is usually determined using a modified Lowry assay (ASTM D5712). This assay measures the amount of total protein found in water used to "wash" sample gloves. Although widely used, the reliability of Lowry assay values can be limited by interfering compounds and its variable response to different proteins. Noting that results should be interpreted cautiously, ASTM recommends that the Lowry total protein content be less than 200 micrograms per decimeter squared.(a unit that reflects protein content per unit of surface area) for latex surgical and examination gloves.
NRL glove protein level can also be assessed using immunological assays such as the LEAP assay (ASTM D6499), RAST (radioallergosorbent test) inhibition assay or ELISA (enzyme-linked immunosorbent assay) inhibition assay.10 These assays use anti-NRL antibodies to detect the antigenic protein--not total protein--found in the water used to wash sample gloves. Unfortunately, because the character of anti-NRL antibodies is not yet well standardized, each assay may recognize different NRL proteins. Furthermore, assay results don't match the severity of symptoms in latex-allergic individuals. Unfortunately, none of the above assays demonstrates consistent quantification of known NRL allergens or total proteins. All have practical limitations in sensitivity, repeatability, and/or precision. Regardless, future ASTM standards are likely to include a maximum limit for antigenic protein in addition to the current total protein limit. Therefore, healthcare workers should interpret NRL protein values cautiously.
Some "low-protein" gloves can contain higher levels of NRL allergens than gloves with higher levels of total protein. As there is no clear relationship between protein level, sensitization, or the severity of allergic reactions, latex gloves with "low protein levels" could still cause reactions in latex-allergic workers and patient, and should therefore never be used by them.
Cornstarch powder on NRL gloves has been shown to attach and carry NRL proteins. When healthcare workers don or strip powdered NRL gloves, this powder becomes airborne and can then be inhaled, often provoking symptoms in latex-allergic individuals. In fact, studies have shown that respiratory symptoms decrease as the level of aerosolized powder and latex proteins decrease.4 For this reason (and its potential role in post-surgical adhesions), the FDA has encouraged the ASTM to reduce powder levels on all surgical and examination gloves. By 2002, acceptable powder levels on powdered surgical gloves must be reduced to 15 milligrams per decimeter squared. Similarly, powder levels on powdered exam gloves must be reduced to 10 milligrams per decimeter squared. Since 1999, ASTM standards have also reduced the level of acceptable residual powder on all powder free gloves by 50%. These changes apply regardless of the glove material (NRL or synthetics) or brand. Further changes in ASTM standards and FDA regulations are likely during the next few years in an attempt to increase glove product safety, reduce symptoms in allergic individuals and lower sensitization rates.
Symptom Management and Product Avoidance
Reporting of Type I latex allergy has increased dramatically over the last 20 years. Defined as an immune reaction to the plant proteins in natural rubber latex, a Type I allergy demands an active management and NRL-product avoidance strategy both at a personal and institutional level. Allergic contact dermatitis to one or more chemicals in the healthcare environment is more common, but less life-threatening than a Type I latex allergy. If untreated, the long-term effects of ACD on the skin can compromise a healthcare worker's career.
For both types of allergy, appropriate diagnosis and alternate product selection can be critical. Given the implications of these allergies, it is imperative that health care workers be educated in the risk factors and symptoms, and receive an accurate diagnosis. Furthermore, allergic individuals should be counseled with regard to appropriate product selection both at work and at home.
Changes in government regulations and industry standards may help lower symptom elicitation and sensitization rates. New polymer developments may also increase product choices for allergic individuals looking to substitute NRL with a synthetic rubber product. Research continues into the causes, improved diagnostic methods, and effective control measures for these allergies with the goal of reduced symptoms and sensitization rates.
Acknowledgements: The authors gratefully acknowledge the editorial assistance of Tina Evans in the preparation of this manuscript.
For a complete list of references, visit: www.infectioncontroltoday.com
Curtis P. Hamann, M.D. is the CEO and medical director of SmartHealth in Phoenix, Ariz. and has been a member of the Health Industry Manufacturer's Association (HIMA) Latex Task Force. Pamela A. Rodgers, PhD, is a clinical research associate at SmartHealth and has specialized in liver disease studies at Stanford Medical Center. Kim M. Sullivan is Vice President of Research and Development/Regulatory Affairs at SmartHealth, and is currently working on two studies with the American Dental Association in collaboration with Hamann.
Table 1: Characteristics of Rubber-Based Allergies
|Allergic Contact Dermatitis||NRL Allergy|
|Type||Type IV (Delayed)||Type I (Immediate)|
|Source of Allergic Reaction||Skin (Cellular)||Systemic (humoral)|
|Antigen||Processing chemicals: in natural and synthetic rubbers (low molecular compounds).||NRL proteins: only in natural rubber high molecular weight compounds).|
|Circulating Antibody||None||IgE or IgG|
|Sources of Exposure||Skin||Skin, mucous membranes, injections, inhalation.|
|Onset of Symptoms||Less than 1 hour to several days.||Within a few minutes or hours.|
|Skin Symptoms||Sorness, pruritus, cracking, peeling, scabbing, crusting, swelling, papules, drying, swelling, skin thickening, redness, scaling, fissures, and vesicles usually limited to contact area.*||Urticaria (hives), tightness, itching, redness, tingling.|
|Respiratory Symptoms||None||Asthma, wheezing, throat constriction, coughing, sneezing, rhinitis, angioedema.|
|Gastrointestinal Symptoms||None||Nausea, vomiting, diarrhea, cramps.|
Hypotension, tachcardia, shock.
|Symptoms Subside||Within weeks||Within hours|
|Diagnosis||Based on medical history and patch testing with chemicals.||Based on medical history and skin prick testing, in vitro serologic testing, or in-use provocation testing.|
|*Although uncommon, widespread skin symptoms may occur if the allergen is ingested or inhaled.|
|Table 2: Diagnostic Test Methods for Rubber-Based Allergies|
|Diagnose Allergy Type||Test Reagents or Kits||Test Description||Results||Method Limitations|
|Skin Prick Test (SPT)||1) Type I NRL
4) Glove wash solutions3
|1) Stallergenes2 pricks skin through solution containing NRL protein and the reaction is referenced against that of positive and negative controls||Allergist or
immunologist pricks skin on arm. Raised
welt at site indicates positive reaction.
|Postive or negative||1) Limited test
2) Possible reactions
|RAST or EAST1
|Type I NRL||1) CAP4
|Physician collects serum for analysis of anti-NRL antibodies and results are referenced against positives controls||Ranked multiple grades of positive||1) False negative rate as high as 30%|
|In-Use Provocation||Type I NRL||None-uses finger of latex glove||Allergist of immunologist places latex on finger; reaction is compared to that of vinyl on another finger||Positive or negative||1) Difficult to
2) Possible reactions
|Patch Test||Allergic contact dermatitis||1) T.R.U.E. Test
2) Finn chambers With Trolab or chemotechnique reagents
|Dermatologist places patches containing suspect allergens (chemicals) placed on back for 1-3 days; results read for several days after patch removal||Positive or negative||Requires physician physician training|
Test; EAST=Enzymeallergosorbent Test
2Manufactured test standards available in Europe; not available in the US
but often freshly prepared by testing physicians
4CAP RAST FEIA (Pharmacia UpJohn), AlaSTAT (Diagnostic Products) and HY-TEC-EIA (HYTEC).
|Table 3. Critical Components of Latex Allergy Management|
|Protocol and policy Elements||Description||Involves Patients?||Involves Workers?|
|Task Force Development||Multidisciplinary group to develop and maintain NRL management protocols||No||Yes|
|Education||Train staff to recognize NRL products and allergy symptoms and to follow appropriate procedures||No||Yes|
|NRL Products||Identify products that contain NRL and obtain substitutes||Yes||Yes|
|Risk Assessment||Screening to identify high and medium risk individuals||Yes||Yes|
|Diagnostic Protocols||Procedures for diagnosing latex allergy based on symptoms, medical history and/or testing by qualified physican||Yes||Yes|
|Perioperative Management||Procedures for handling latex allergic patients, including premedication protocols||No||Yes|
|Emergency Treatment Protocols||Procedures for emergency treatment of latex-allergic patients, including anaphylactic shock||No||Yes|
|Ongoing Evaluation||Annual or semi-annual review of all procedures and protocols||No||Yes|
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