ARTICLE
Latex allergy is important for three reasons; firstly, it is potentially
fatal if the patient is not properly managed [1]; secondly, it is common
in healthcare workers as an occupational disease [2]; and thirdly, it
has been increasing in incidence [3] probably due to increased use of
latex gloves as a barrier against viral infections. Therefore, a guidelines
document for the care of latex-allergic patients should be a risk management
priority for every hospital and health care centre.
It was first reported by Stern in 1927 [4] who described a severe generalised
urticaria to a dental prosthesis made of latex. Almost 50 years later,
contact urticaria to latex gloves was reported by Nutter in 1979 [5].
Since then the prevalence and incidence of latex allergy has increased
almost exponentially and does not show any signs of abating. Akasawa et
al. [6] in 1993 reported a prevalence rate of 2% latex
allergy in health care workers. In a similar study in 1997 this had risen
by over 10 fold to 21% [7].
Definition of latex allergy
Latex allergy is characterised by the presence of latex specific IgE
antibody associated with symptoms consistent with IgE mediated reactions
to latex-containing devices. Either of these criteria alone is not sufficient
to diagnose latex allergy. Patients who have latex reactive antibody may
harbour cross-reactive antibodies of no clinical significance. Similarly,
those with type I hypersensitive reactions associated with latex-containing
devices may be reacting to other concomitant environmental allergens [8].
Latex allergens
Raw latex is a milky sap harvested from the rubber (Hevea brasiliensis)
tree. It is subsequently vulcanised into elastic rubber with which we
are all familiar. Rubber is extensively distributed in the environment
and we are in contact with it virtually all the time. The allergen, that
is the actual substance which induces the allergy, is a protein constituent
of the latex. Several allergens have been cloned and others partially
characterised. (Hev b1-10) It has been suggested that Hev bI and Hev b3
are major allergens in children with spina bifida and urological congenital
anomalies [9, 10] whereas Hev b2 and Hev b4 are more important
for health care workers with latex allergy [11].
Routes of exposure
The induction of allergy to latex is particularly likely to occur after
exposure of mucous membranes to latex, e.g. the mouth, vagina or
rectum [12, 13], but sensitization can occur through the skin
[14], by inhalation [15] or by internal exposure [16]. Medical
devices can induce allergy and then subsequently cause an allergy to develop
on re-exposure (Table 1).
These devices include anaesthetic masks, condom catheters, ileostomy bags,
balloon catheters used for enemas and latex gloves. Latex gloves are particularly
prone to induce allergy when they contain starch powder, which has the
effect of concentrating the protein [15]. Most latex allergy falls into
the category of immediate (type I) hypersensitivity, that is, it is IgE
mediated and comes on within minutes of exposure to the latex protein.
The allergic reaction is mediated by the release of inflammatory substances
from dermal mast cells triggered by the linking of IgE molecules on the
surface of the cells.
Clinical manifestations
Latex hypersensitivity reactions can affect the skin, eyes and lungs.
The skin manifestations include itching, swelling, redness and later,
an eczema [5] (Fig. 1). Respiratory involvement consists
of sneezing and wheezing [17]. The eyes may water and itch.
It may be serious and give rise to a generalised shock-like reaction known
as anaphylaxis which may include all of these symptoms with cardiogenic
shock and this is potentially fatal if not treated correctly and swiftly
[12].
Some patients with latex allergy also develop allergic symptoms with
certain foods. The reason for this is a similarity of epitopes (cross-reactivity)
between the food protein and the latex protein. Offending foods include
avocado, kiwi fruit, banana, mango, melon and chestnut. [18, 19]. The
history of food allergy may not be forthcoming without specific enquiry.
A type IV or delayed (cell mediated) hypersensitivity reaction to latex
can also occur with latex gloves. Typically this occurs in health care
workers as an allergic contact dermatitis of the hands. It was recently
confirmed in a series of 117 consecutive patients who were patch tested
with latex protein out of which 7 subjects (6%) were patch test positive
[20]. However, it is much more common to find that allergens, such as
tetramethylthiram (added to latex as an accelerator) and mercaptobenzothiazole
(added as an antioxidant) [21], cause type IV hypersensitivity than latex.
Some researchers have shown that endotoxins found in powdered gloves
due to bacterial contamination can lead to various clinical features ranging
from skin erythema and asthma to fever, malaise and shock [22]. In this
situation, subjects may have significant clinical symptoms in the presence
of negative serological tests for latex or skin prick test. This occurs
particularly in nonsterile latex gloves which are contaminated with high
amounts of endotoxins and proteins.
Diagnosis of latex allergy
The diagnosis is made from the patient's history supported by a either
a positive skin prick test or a blood test. The blood test (the radio-allergosorbant
test or RAST) relies on identification of antibodies (IgE) to latex proteins
in the laboratory. The IgE level is a marker of exposure and IgE response
but does not correlate with symptoms. In patients with atopy who frequently
have very high levels of total IgE, non-specific binding to the allergen
can cause false positive results. However, unlike skin tests they are
not influenced by concurrent treatment. Various immunoassays are currently
available such as, CAP RAST FIEA (Pharmacia UpJohn), microplate AlaSTAT
(Diagnostics Products), and HY-TEC-EIA (HYTEC). Their specificities (i.e.
rate of true negative) range from 80% [23] - 87%
[24] and the sensitivities (i.e. rate of true positive) from
53% [25] - 97% [26].
In the skin prick test, very small amounts of a latex protein solution
are pricked into forearm skin and an itchy weal develops within 15 min.
Latex protein solution can be obtained from natural latex (ammoniated
extract), commercially prepared skin test reagent such as, Bencard (Canada),
Stallergenes (France), Lofarma (Italy), ALK-Abello S.A. (Spain) and in-house
preparation of latex-glove allergen-test solution. In a study performed
by Blanco et al. the diagnostic sensitivity ranged from 98% for
ammoniated natural latex extract to 90-98% for commercial latex extracts.
However, glove extracts showed lower diagnostic sensitivity ranging from
64-96%. Diagnostic specificity for all skin prick tests was 100% [25-27].
Although skin prick tests are more accurate than blood tests, it carries
with it a small risk of inducing an anaphylactic reaction [28] (Fig.
2). A 5 year retrospective study from the Mayo clinic reported a systemic
reaction rate of 152 to 200/10,000 skin tests [29]. However, skin tests
should not be done whilst patients are on drugs such as antihistamines
and steroids, because this can result in false negative results. In patients
who exhibit dermographism, skin tests may be difficult to interpret because
any minor injury can provoke a wheal. The use test, rub test and scratch
chamber test involve direct application of rubber products to the skin.
As they are not reproducible and can induce anaphylaxis, they are no longer
recommended. Patients who have negative serologic tests and skin prick
tests in the presence of convincing histories of allergic reactions may
be challenged with a confirmatory test. However, there are many challenge
protocols with varying methods of evaluating skin and respiratory symptoms.
These tests do not employ a common source of powdered latex gloves with
a known allergen content. Consequently, latex glove provocation procedures
are generally considered unsafe and of variable diagnostic significance.
The following challenge tests are currently in practice: modified glove
provocational protocol [30]; two-stage latex provocation test [31]; glove
use with laminar flow helmet and inhalation chamber [32]; hooded exposure
chamber [33]. A negative test in this situation may suggest that there
is no evidence of latex allergy and allow subjects to return to their
workplace.
Intradermal tests involve injecting diluted antigenic solution directly
under the skin. It is more painful and exposes the patients to far higher
antigen load (100-1,000 fold) than skin prick tests. The commercial extract
is not available and due to an increased rate of side-effects compared
to skin prick tests, including anaphylaxis [34], it is rarely performed
nowadays.
The basophil histamine test is an in vitro test with a sensitivity
rate comparable to skin prick test. Although there is no risk of anaphylaxis
it is time-consuming, expensive and is not readily available [35].
Population at risk
People who are atopics, that is to say have a history of childhood eczema,
hay fever or asthma, are at greater risk (about two-fold) of developing
latex allergy than the non-atopic population [36]. Certain patient groups
are also at higher risk of developing allergy to latex, e.g. children
with spina bifida [37] or urological abnormalities. This is thought to
be because of exposure to urinary catheters and multiple episodes of surgery.
Occupational latex allergy is found in between 5% and 21% [38] of all
healthcare workers. Those most at risk are staff who wear powdered latex
gloves, or work in areas with high latex aeroallergen levels, e.g.
operating room technicians, other theatre staff (nurses, anaesthetists,
surgeons), dentists and dental nurses, ward nurses, and other nurses and
support workers who perform procedures requiring gloves to be worn.
Latex allergy is also commoner in patients with food allergies. An epidemiologic
study performed in France revealed that amongst subjects who used gloves,
latex intolerance was found in 10.4% of subjects with food allergy (vs
5.6% of subjects without food allergy). However, the overall prevalence
of glove intolerance in the general population was 0.7% [39].
Management
There are two facets to management, that for staff and that for patients.
For staff known to be latex-allergic, the most important aspect is the
provision of non-latex gloves and avoidance of latex-containing materials
in the workplace environment. Nonlatex gloves made of vinyl, stretch vinyl,
thermoplastic elastomer and nitrile are now available. A study comparing
the barrier function and handling characteristics of these gloves demonstrated
that nitrile may be the most suitable alternative to latex [40]. Conversely,
Yunginger et al. have suggested that substitution of non-latex
gloves will in all probability involve some loss of barrier function [41].
Latex gloves with polytetrafluorethylene liners have been shown to prevent
the transfer of allergen from gloves onto the skin [31] but their handling
characteristics have not yet been studied.
For patients, and staff when they become patients, the situation is
more complicated, because during ward management or particularly during
surgery, they are likely to be exposed to latex-containing materials from
virtually every side and often through many orifices. It is therefore
important to identify patients at high risk of developing serious reactions
to latex especially during operative procedures. Kelly et al. showed
that amongst children with spina bifida undergoing operation, factors
such as, atopy, medical history of immediate contact allergy to latex,
non-white race, food allergy, IgE greater than 84 IU, or nine or more
prior surgical procedures can identify those with highest risk of anaphylactic
reactions [42]. The list of medical devices that contain latex used in
the modern operating theatre is very extensive [43] (Table
I). Most hospitals place a high priority on risk management and have
already devised their own guidelines for the care of latex allergic patients.
It is important that these are understood and followed by every member
of staff. This requires all staff to know about the problem of latex allergy
and be alert to suspect the diagnosis. Any patient in whom the diagnosis
is known needs to be managed using a latex-free protocol. If latex allergy
is suspected, e.g. by the admitting nurse or doctor, and there
is time the patient can be investigated (by RAST or skin prick test),
but if there is no time because the patient needs emergency surgery, then
a latex-free protocol should be followed.
Immunotherapy: As latex allergy is an IgE mediated disease various
desensitisation regimes have been tried with moderate success. Both oral
[44] and subcutaneous [45] desensitisation with latex allergen have been
reported to be successful in patients with clinical latex allergy. These
claims would need to be confirmed by controlled trials. Animal experiments
have shown that vaccines with cloned Hev b5 DNA sequences inhibited IgE
responses to Hev b5 in mice sensitised to this antigen [46]. At present
the role of immunotherapy in the management of latex allergy remains investigational.
Prevention
Corn-starch powder which is used as a dry lubricant has a strong propensity
to bind proteins when it comes in contact with natural latex. Airborne
particles from latex gloves can result in serious allergic reactions [15].
Therefore, for healthcare staff, the most important preventive measure
is the provision of good quality powder-free disposable latex gloves.
For patients with diagnosed latex allergy, Medi-Alert bracelets are useful.
As contact with latex is generally easily avoided, self-injectable adrenaline
syringe is not routinely prescribed. It should be recommended only to
patients at high risk of anaphylaxis when eating small amounts of latex
proteins or with cross reacted food anaphylaxis [47]. Hospitals and health
centres, should ensure the education of staff and the provision of a latex-free
protocol. For pre-employment medicals, applicants for work (especially
atopics) in the healthcare professions should be questioned about a history
which might suggest latex allergy. In children with spina bifida and others
who need repeated urological surgery, consideration should be given to
using latex free protocol especially for their first surgery.
It has been shown that substitution of non-powdered gloves resulted
in reduction of latex aeroallergens and significant decrease in latex
specific IgE antibody concentration. Various studies have documented reduction
in allergic symptoms after removal of powdered natural latex gloves from
hospitals [48]. This might allow latex sensitive individuals to go back
to their workplace. There is also data suggesting that powder use may
increase bacterial environmental contamination and promote wound infection
[49].
An extra wash with chlorine removes much of the powder and protein from
the glove but it makes the gloves more expensive and also accelerates
their deterioration [50]. During the process of manufacturing almost 90%
of extractable protein can be removed by combining the two processes of
wet gel leaching and dry film leaching [51].
CONCLUSION
Latex allergy has become a problem of epidemic proportion caused in part
by the adoption of "universal precaution" primarily against viral infections
such as hepatitis and HIV. This was compounded by the supply of sub-standard
latex gloves. One of the problems in combating latex allergy has been
the difficulty in standardising the quality of latex gloves. Not only
does this vary between different geographical regions but it also depends
on the season when latex is harvested. As more rigorous quality control
measures are being adopted a reduction in this epidemic can be hoped for.
This is essential because of the potential for extreme consequences of
mismanagement.
Article accepted on 26/2/02
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