Latex Allergy Update

March 1, 2001

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.
Cardiovascular
Symptoms
None
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
2) ALK-Abello2
3) Lofarma2
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
standardization
2) Possible reactions
RAST or EAST1
EAST1
Type I NRL 1) CAP4
2) AlaSTAT4
3) HY-TEC-EIA4
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
standardize
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
1RAST=Radioallergosorbent
Test; EAST=Enzymeallergosorbent Test
2Manufactured test standards available in Europe; not available in the US
3Unstandardized
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

For a complete list of references click here