Latex Allergy Update

March 1, 2001

Latex Allergy Update

Latex Allergy Update

By Curtis P. Hamann, MD, Pamela A. Rodgers,PhD, and Kim Sullivan

Oftenthought of as a modern-day malady, allergic reactions to rubber gloves werefirst reported in the early 1930s. However, the number of reported reactionsrapidly increased as the consumption of medical gloves rose after theimplementation of Universal Precautions during the mid-1980s. The more commonreactions--often referred to as allergic contact dermatitis--are caused byprocessing chemicals found in both natural and synthetic rubbers. However, themore serious and potentially life-threatening Type I latex allergy is due toproteins only found in natural rubber products. As of 1997, more than 2,300allergic reactions associated with latex had been reported to the FDA's MedWatchProgram. Over 200 of these reported cases were associated with anaphylaxis, and17 were also fatal. Recent studies of healthcare workers have estimated theprevalence of Type I latex allergy to be as high as 17%.1 Assuming aconservative 10% prevalence, over 800,000 healthcare workers in the UnitedStates have a Type I allergy to latex and 2 million workers may experienceallergic contact dermatitis (Type IV) to one of the many chemicals found in thehealthcare environment today.

Latex Allergy Defined

Latex allergy is clinically defined as Type I (or Immediate) natural rubberlatex (NRL) allergy (Table 1). It is an acquired immune reaction to one or moreof the plant proteins inherent to NRL.

Individuals can become sensitized to NRL by constant exposure through the useof various NRL products including: gloves, condoms, balloons, pacifiers, andrubber toys. Exposure to NRL proteins often occurs through cutaneous orpercutaneous contact; aerosolized contact (respiratory exposure), mucosalcontact (exposure to eyes, nose, mouth, vagina, rectum); intraoperativeexposure; and hematogenous exposure through stopcocks, rubber stoppers, andintravenous 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 significantnumber of individuals are apparently asymptomatic, a detailed medical history isessential to identify risk factors, previous unexplained allergic reactions, orany potentially related symptoms. Individuals who are potentially "atrisk" for Type I latex allergy include those who are repeatedly exposed toNRL such as healthcare and latex industry workers, as well as patients withspina bifida, myelomeningocele, or urogenital defects. The presence ofpre-existing allergies can be considered an additional risk factor, particularlyallergies to kiwi, avocado, banana, chestnuts or stone fruits.

The diagnosis of a Type I latex allery in an individual should be based onsymptom evaluation, medical history and the presence of circulating anti-NRLantibodies. These antibodies can be detected using one of three methods: 1) skinprick testing with a source of NRL, 2) serum immunoanalyses and/or 3) usetesting with a NRL product (Table 2). Unfortunately, due to the lack ofstandardization of these methods, obtaining a definitive diagnosis of a Type Ilatex allergy can be challenging.

A skin prick test is currently considered the most accurate diagnostic methodfor Type I latex allergy. It is easy to perform, provides quick results (within15 minutes) and is highly sensitive. Briefly, a patient's arm is pricked throughdrops of test solution (prepared from NRL gloves or a purified NRL source). Araised red welt at the prick site indicates that the patient is latex allergic.Unfortunately, the standardized test reagents available in Europe with knownprotein and antigen content are still not commercially available in the UnitedStates. For this reason, physicians often choose serologic testing such as theImmunoCAP and AlaSTAT tests, which determine the amount of certain anti-NRLprotein antibodies present in a patient's serum. For high-risk groups such asspina bifida patients, positive serologic test results are considered quiteaccurate. Unfortunately, serologic tests are not as sensitive and results can befalsely negative in 20-30% of the individuals tested3. Finally,in-use provocation testing may also be considered, where a patient is exposed toa NRL product for a specified time to measure their reaction. Because there is agreater risk of anaphylaxis with in-use testing, patients should be monitoredclosely.

Currently, Type I latex allergy is a complex problem with multiple allergensand poorly standardized test methods. Therefore, more recent diagnosticguidelines suggest combining one or more test methods. Multiple test methods areparticularly recommended for individuals with symptoms inconsistent with serumtest results. For example, combining serologic with skin prick testing, or usingmultiple serologic tests.3 In all cases, tests should be accompaniedby an in-depth documentation of a patient's history and risk factors.

Allergic Contact Dermatitis

Although often erroneously referred to as "latex allergy," allergiccontact dermatitis (ACD) is a common response to the processing chemicals (i.e.,thiurams, carbamates, thioureas, thiazoles) found in rubber products. Thesechemicals can be used in the production of nitrile, neoprene, and natural rubbermedical gloves. Other chemicals commonly used in healthcare settings such asantiseptics, adhesives, disinfectants, and resins can also produce allergicreactions. Known as a Type IV (or delayed) allergy, ACD is an immune-mediatedinflammation of the skin that can also involve the fingernails. In contrast to aType I latex allergy, ACD is localized to the skin (Table 1). Symptomscan take anywhere from minutes to several hours to develop and can persist forweeks. Whether individuals develop ACD is dependent upon individualsusceptibility, exposure history and the allergenic potential of the chemical(s).While not life-threatening, if left mismanaged or untreated, ACD reactions cancause permanent damage to the patient/user's skin. Therefore, an accurate andcomplete diagnosis is essential.

The diagnosis of ACD should be based on symptoms (Table 1), medicalhistory, and a positive skin reaction to test chemicals (known as patchtesting). The patch test is typically conducted by a qualified clinician using astandard series of test allergens on the upper back. The patches are applied for24 to 48 hours, and the skin examined 24, 48, 72, and 96 hours after the patchesare removed. Red and inflamed skin under the patch is indicative of an allergyto the applied chemical. While not a perfect method, patch testing is a valuabletool in identifying chemical allergies, particularly when combined with adetailed medical history and symptom survey.

Management of Latex Allergy

Individuals with a Type I latex allergy should use products made fromnon-latex alternatives which do not contain NRL proteins. Current choicesinclude nitrile, neoprene, polyurethane and styrene-based rubber exam andsurgical gloves as well as vinyl exam gloves. Each material is made from adifferent mixture of chemicals as well as different base polymers. Some of thesematerials--such as nitrile and neoprene--are vulcanized (heat-cured) much likenatural rubber. Others--such as vinyl, polyurethane, and styrene-basedrubbers--are created in solvent-based systems without vulcanization. Inaddition, a powder-free latex environment should be maintained forlatex-allergic workers or patients to minimize aerosolized latex allergens. Suchan atmosphere has been shown to reduce their symptoms.4

Institutions and individual practitioners can quickly address the problem oflatex allergies by offering workers a combination of education, testing andalternative glove materials. The Occupational Safety and Health Administration (OSHA)requires that all employers provide non-latex alternatives to allergic staff, inaddition to the safe working environment required by worker compensation laws.Furthermore, considering the significant liability that has arisen inassociation with a latex-induced anaphylaxis or fatality, it may no longer becost effective to ignore the problem. In a recent study using conservativeestimates of healthcare worker disability costs, implementation of latexalternatives were found to be cost saving, even in small clinics and hospitals.5

With respect to glove choices, cured plastic materials such as vinyl andthermoplastic elastomers are not considered "sensitizing" and do notcontain the same rubber processing chemicals found in natural or syntheticrubber gloves. However, gloves made of vinyl or thermoplastic elastomers maycontain 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, butthese are not necessarily due to allergic reactions. Frequent hand washing is acommon source of skin irritation in health care: in a recent study of over 400nurses, the number of hand washings per shift ranged as high as 100, andaveraged around 30.6 In addition, the skin on a healthcare worker'shand is exposed to hundreds of potential irritants throughout the day. Poor handand skin care practices may be an initiating factor in occupational skin damage.A recent study also showed that latex allergens penetrated abraded skin morefrequently and deeply than healthy, non-abraded skin.7

Latex Allergy Management Protocols and Procedures

Institutional policies should be developed that include identification oflatex-allergic individuals, recognition of NRL-containing products andsubstitutions, coordination of procedures throughout the hospital or clinic, andeducation of staff and patients (Table 3). Development and implementationof these policies requires input from a multi-disciplinary task force withrepresentatives from occupational safety and health, risk management, materialsmanagement, and all patient care departments including food service andhousekeeping.9 The goal of these policies and procedures is toestablish and maintain a "latex-safe" environment where a patient's orworker's exposure to NRL is eliminated or significantly reduced. An effectivestrategy involves coordination of NRL-allergic patient care throughout theirstay.

Continuing education is a key element of a successful latex managementpolicy. A recent study showed that even when non-latex alternatives wereprovided and policies established, 80% of healthcare workers with skin problemsstill chose latex gloves, including those with powder.9 The authorsconcluded that education was a missing but essential component, and recommendedthat this begin during preplacement evaluations and training. Ongoing educationprograms can train staff and patients to identify NRL products, recognize latexallergy symptoms, as well as initiate appropriate treatment.

Regulatory agencies and professional organizations now recommend reductionsin the protein content of NRL products to reduce the frequency and severity oflatex allergy symptoms in allergic individuals, and to reduce the risk ofsensitization in the future. Since their 1997 final rule on latex labeling inmedical products, the Food and Drug Administration (FDA) has encouraged theAmerican Society for Testing and Materials (ASTM) to revise and expand theirprotein and powder standards for medical grade gloves.

Glove protein level is usually determined using a modified Lowry assay (ASTMD5712). This assay measures the amount of total protein found in water used to"wash" sample gloves. Although widely used, the reliability of Lowryassay values can be limited by interfering compounds and its variable responseto different proteins. Noting that results should be interpreted cautiously,ASTM recommends that the Lowry total protein content be less than 200 microgramsper decimeter squared.(a unit that reflects protein content per unit of surfacearea) for latex surgical and examination gloves.

NRL glove protein level can also be assessed using immunological assays suchas the LEAP assay (ASTM D6499), RAST (radioallergosorbent test) inhibition assayor ELISA (enzyme-linked immunosorbent assay) inhibition assay.10These assays use anti-NRL antibodies to detect the antigenic protein--not totalprotein--found in the water used to wash sample gloves. Unfortunately, becausethe character of anti-NRL antibodies is not yet well standardized, each assaymay recognize different NRL proteins. Furthermore, assay results don't match theseverity of symptoms in latex-allergic individuals. Unfortunately, none of theabove assays demonstrates consistent quantification of known NRL allergens ortotal proteins. All have practical limitations in sensitivity, repeatability,and/or precision. Regardless, future ASTM standards are likely to include amaximum limit for antigenic protein in addition to the current total proteinlimit. Therefore, healthcare workers should interpret NRL protein valuescautiously.

Some "low-protein" gloves can contain higher levels of NRLallergens than gloves with higher levels of total protein. As there is no clearrelationship between protein level, sensitization, or the severity of allergicreactions, latex gloves with "low protein levels" could still causereactions in latex-allergic workers and patient, and should therefore never beused by them.

Cornstarch powder on NRL gloves has been shown to attach and carry NRLproteins. When healthcare workers don or strip powdered NRL gloves, this powderbecomes airborne and can then be inhaled, often provoking symptoms inlatex-allergic individuals. In fact, studies have shown that respiratorysymptoms decrease as the level of aerosolized powder and latex proteinsdecrease.4 For this reason (and its potential role in post-surgicaladhesions), the FDA has encouraged the ASTM to reduce powder levels on allsurgical and examination gloves. By 2002, acceptable powder levels on powderedsurgical gloves must be reduced to 15 milligrams per decimeter squared.Similarly, powder levels on powdered exam gloves must be reduced to 10milligrams per decimeter squared. Since 1999, ASTM standards have also reducedthe level of acceptable residual powder on all powder free gloves by 50%. Thesechanges apply regardless of the glove material (NRL or synthetics) or brand.Further changes in ASTM standards and FDA regulations are likely during the nextfew years in an attempt to increase glove product safety, reduce symptoms inallergic individuals and lower sensitization rates.

Symptom Management and Product Avoidance

Reporting of Type I latex allergy has increased dramatically over the last 20years. Defined as an immune reaction to the plant proteins in natural rubberlatex, a Type I allergy demands an active management and NRL-product avoidancestrategy both at a personal and institutional level. Allergic contact dermatitisto one or more chemicals in the healthcare environment is more common, but lesslife-threatening than a Type I latex allergy. If untreated, the long-termeffects of ACD on the skin can compromise a healthcare worker's career.

For both types of allergy, appropriate diagnosis and alternate productselection can be critical. Given the implications of these allergies, it isimperative that health care workers be educated in the risk factors andsymptoms, and receive an accurate diagnosis. Furthermore, allergic individualsshould be counseled with regard to appropriate product selection both at workand at home.

Changes in government regulations and industry standards may help lowersymptom elicitation and sensitization rates. New polymer developments may alsoincrease product choices for allergic individuals looking to substitute NRL witha synthetic rubber product. Research continues into the causes, improveddiagnostic methods, and effective control measures for these allergies with thegoal of reduced symptoms and sensitization rates.

Acknowledgements: The authors gratefully acknowledge the editorial assistanceof Tina Evans in the preparation of this manuscript.

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Curtis P. Hamann, M.D. is the CEO and medical director of SmartHealth inPhoenix, Ariz. and has been a member of the Health Industry Manufacturer'sAssociation (HIMA) Latex Task Force. Pamela A. Rodgers, PhD, is a clinicalresearch associate at SmartHealth and has specialized in liver disease studiesat Stanford Medical Center. Kim M. Sullivan is Vice President of Research andDevelopment/Regulatory Affairs at SmartHealth, and is currently working on twostudies with the American Dental Association in collaboration with Hamann.

Table 1: Characteristics of Rubber-Based Allergies

Allergic Contact DermatitisNRL Allergy
TypeType IV (Delayed)Type I (Immediate)
Source of Allergic ReactionSkin (Cellular)Systemic (humoral)
AntigenProcessing chemicals: in natural and synthetic rubbers (low molecular compounds).NRL proteins: only in natural rubber high molecular weight compounds).
Circulating AntibodyNoneIgE or IgG
Sources of ExposureSkinSkin, mucous membranes, injections, inhalation.
Onset of SymptomsLess than 1 hour to several days.Within a few minutes or hours.
Skin SymptomsSorness, 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 SymptomsNoneAsthma, wheezing, throat constriction, coughing, sneezing, rhinitis, angioedema.
Gastrointestinal SymptomsNoneNausea, vomiting, diarrhea, cramps.
Cardiovascular SymptomsNone Hypotension, tachcardia, shock.
Symptoms SubsideWithin weeksWithin hours
DiagnosisBased 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.

 Diagnose Allergy TypeTest Reagents or KitsTest DescriptionResultsMethod Limitations
Skin Prick Test (SPT)1) Type I NRL 2) ALK-Abello1) StallergenesAllergist or immunologist pricks skin on arm. Raised welt at site indicates positive reaction.Postive or negative1) Limited test standardization 2) Possible reactions
RAST or EAST1 EAST1Type I NRL1) CAPPhysician collects serum for analysis of anti-NRL antibodies and results are referenced against positives controlsRanked multiple grades of positive1) False negative rate as high as 30%
In-Use ProvocationType I NRLNone-uses finger of latex gloveAllergist of immunologist places latex on finger; reaction is compared to that of vinyl on another fingerPositive or negative1) Difficult to standardize 2) Possible reactions
Patch TestAllergic contact dermatitis1) T.R.U.E. Test 2) Finn chambers With Trolab or chemotechnique reagentsDermatologist places patches containing suspect allergens (chemicals) placed on back for 1-3 days; results read for several days after patch removalPositive or negativeRequires physician physician training
1RAST=Radioallergosorbent Test; EAST=Enzymeallergosorbent Test 2Manufactured test standards available in Europe; not available in the US3Unstandardized but often freshly prepared by testing physicians 4CAP RAST FEIA (Pharmacia UpJohn), AlaSTAT (Diagnostic Products) and HY-TEC-EIA (HYTEC).

Protocol and policy ElementsDescriptionInvolves Patients?Involves Workers?
Task Force DevelopmentMultidisciplinary group to develop and maintain NRL management protocolsNoYes
EducationTrain staff to recognize NRL products and allergy symptoms and to follow appropriate proceduresNoYes
NRL ProductsIdentify products that contain NRL and obtain substitutesYesYes
Risk AssessmentScreening to identify high and medium risk individualsYesYes
Diagnostic ProtocolsProcedures for diagnosing latex allergy based on symptoms, medical history and/or testing by qualified physicanYesYes
Perioperative ManagementProcedures for handling latex allergic patients, including premedication protocolsNoYes
Emergency Treatment ProtocolsProcedures for emergency treatment of latex-allergic patients, including anaphylactic shockNoYes
Ongoing EvaluationAnnual or semi-annual review of all procedures and protocolsNoYes

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