Products containing natural or synthetic rubber are ubiquitous in our
environment. These substances can be manufactured into a variety of
useful items to improve our quality of life and in many cases make it
safer. Over the years, as these products have proliferated, an increasing
number of clinical problems have been associated with their use. The
derivation and evolution of these problems is complex and unclear. They
include: direct irritant effects from simple occlusion of the skin; irritant
effects from chemicals and possibly other biologics contained in the final
product; and the development of cellular immunological or humoral
immunological reactivity to various components. Clinically, these
problems range from direct irritation to a number of allergic sensitization
phenomena such as contact dermatitis, conjunctivitis, rhinitis, acute
urticaria, asthma, and even anaphylactic shock. The marked increase in
the cumulative prevalence of these problems has focused intense research
into defining their origin and eliminating their occurrence.
The research findings on these problems can be separated into three
groups. The furst deals with the irritant effects, the second with the
chemicals involved in the manufacturing process, and the third with the
proteins and haptenated polymers which stimulate the production of
specific IgE antibodies. It should be stressed that these phenomena are
not mutually exclusive and could contribute in combination to the natural
history of the various pathologies.
It is difficult to assess the irritating effects of wearing rubber gloves. A
study of dental surgeons revealed 29% of respondents had experienced
hand irritation, with females having the highest occurrence (38% vs.
27%). This may reflect their recognized preponderance of hand
dermatitis. The majority presented as irritant contact dermatitis; however
this is difficult to distinguish from allergic contact dermatitis. A strong
association was found between the pattern of glove wearing and skin
irritation with those who routinely wear gloves experiencing more
irritation than those who did not. Some evidence indicates that washing
hands with detergents and disinfectants before donning gloves could
increase the incidence of irritation. Surprisingly, individuals who wore
vinyl gloves reported an increased incidence of skin irritation; however
this finding could be biased in that vinyl gloves were most likely worn by
respondents who had experienced irritation with other glove types. In this
study no difference was noted between gloves with or without
cornstarch. The authors of the above referenced study proposed that
occlusion of the skin, which can create a moist environment for bacteria
or elution of substances from the gloves, may be one of the largest factors
determining skin irritation. Additionally, confined sweat can also be
irritating. This may be why more irritant effects are seen the longer the
same gloves are worn. Further studies are needed on this subject.
A variety of chemicals are utilized in the manufacture of rubber products
to give the final product the desired properties for its intended use. For
example, latex glove products utilize coagulants, accelerators,
antioxidants, emulsifiers, stabilizers, extenders, colorants, stiffeners,
biocides, ultraviolent absorbers, fragrances, etc. Reportedly, up to 5% of
the final product can be a complex composite of these chemicals. It is
unknown what new substances may be created through these processes.
Procedures are available to measure chemicals contained in the final
products, but most of these are experimental and include extractions of
rubber products in anything from universal solvents to artificial sweat
formulas. Liquid chromatography is the most commonly used method to
measure the chemicals in these extractions, but this can also be done by
gas chromatography coupled to mass spectrometry. Attempts at
quantitating the various chemicals elutable from rubber products are not
satisfying, probably due to lack of agreement on a standard method.
Efforts are underway with the FDA and ASTM to resolve this dilemma.
When evaluating direct cause and effect sequalae of contact with rubber
products and the chemicals contained therein, it should also be noted that
these same chemicals are present in many non-rubber products. This
possibility of exposure from other sources confounds efforts to identify
specific sources of sensitization.
Besides the possible irritant effects of wearing gloves, gloves and other
rubber products contain several chemicals demonstrated to be potent
sensitizers of human skin. Resulting symptoms are generally classified
as allergic contact demmatitis or eczema and can usually be verified by
patch testing. Two well studied groups of these chemicals include
carbamates (and their corresponding amine derivatives) and thiurarns.
Other groups of chemicals such as the thioureas thiazoles have
also been implicated, but we will discuss the carbamates and thiurams
as representative examples of chemicals capable of inducing this type
of disease.
As for pathogenic mechanisms of carbamates and thiurams, these
accelerators are believed to be absorbed through or onto the skin
they can interact with native proteins. When this occurs they usually
become covalently bound to the protein resulting in the protein being
recognized as foreign to the immune system. When small chemicals
modify native proteins the process is called haptenization. The
haptenated protein can now be recognized by T-cells which can
proliferate and induce inflammatory foci upon encountering the same.
These inflammatory foci can be puritic and often disrupt normal skin
functions. Although these same chemicals are present in numerous
products such as paints, drugs, clothing, insecticides, etc., the fact that
gloves confine them in a warm moist environment probably enhances the
elution of the chemicals and possibly the sensitization process.
There are a variety of proteins derived from natural latex in final products
when used as a source of polymer. These proteins can be antigenic under
the appropriate circumstances. That many individuals who are
continually exposed to these proteins in a variety of different products
rarely make specific IgE responses indicates that somehow wearing latex
gloves creates more appropriate circumstances for this type of
sensitization. Hypotheses put forward are multiple and some evidence for
each has been advanced, e.g., individuals who are atopic and already
make specific IgE to environmental exposures are more likely to become
sensitized to these proteins, and this increases the more frequently they
are exposed. These products however, have been in our environment for
a long period of time without much evidence of sensitization until the
late 1980s when several, well detailed, changes occurred in frequency of
glove usage.
Research has confirmed that IgE antibodies reactive to latex proteins
often cross-react with proteins derived from different foods. It is
believed that many of the same chemicals used in the manufacture of
rubber products are also used as plant extenders, insecticides, foilants,
etc. These substances induce the overproduction of wound and stress
proteins which among different species of plants serve similar functions
and may have similar structures. While this remains to be proven it does
explain the widespread cross reactivities seen among generally unrelated
plant sources.
Since the mid-eighties most latex rubber gloves have been treated with
cornstarch powder to facilitate donning and absorb some of the moisture
resulting from perspiration. The manufacturing process usually involves
dipping molded gloves through a bath of constarch particles. These
baths may be heavily contaminated with bacteria resulting in significant
amounts of endotoxin, a very potent irritant and stimulant of the immune
system, on the particles. When dry, these particles are very buoyant and
can easily become airbome. Thus, in high-powdered latex glove use
areas, airbome particles containing latex proteins along with a very
potent immunological stimulus can be respired, which could explain
asthmatic symptoms and also be responsible for inducing IgE responses
through the respiratory route.
In summary, a number of problems have been documented which deal
with the use of rubber products. These are not exclusive to latex gloves
but are more easily identified from this source. The irritation of the skin
from occlusion and chemicals are clearly problems encountered when
wearing gloves and other protective gear. While we do not completely
understand the mechanism, the development of contact sensitivity due to
these chemicals has been documented. The sensitization to various
proteins caught up in the manufacturing process is also clear in
individuals in whom IgE antibodies have been induced. One might well
ask the question, are these processes related? Since there seems to be a
high number of individuals who have experienced irritation while a
lesser number experience contact demmatitis, and a smaller number still
experience specific IgE related phenomena, one could postulate a
natural history to these problems with a similar progressing. This would
be affected by a number of factors from amount of exposure and perhaps
individual genetic susceptibility.
Whatever the mechanism, problems with rubber products have become
commonplace. Further research will allow us to understand how these
problems have arisen and give us methods of reducing their source. At
this point, we must admit the irony that products designed to make our
life easier and safer are making a number of us ill.
