A variety of adverse reactions has been attributed to natural rubber latex (NRL) glove use. These include nonspecific skin irritation, contact dermatitis, and allergic problems such as rhinitis, urticaria, asthma, and even anaphylaxis. Contact dermatitis, the most common of these adverse health reactions, has been recognized for several decades and has been linked to chemicals inherent to the gloves. The allergic problems have been linked to proteins derived from raw latex and have only been recognized over the past decade. Given the nearly century long use of latex in the medical field, it is certainly unclear why these allergic reactions are only now emerging as a health concern.
Various explanations for the apparent increase in allergic reactions to NRL gloves include the dramatic increase in NRL glove use following the issuance of Universal Precautions by the Centers for Disease Control in 1987. This measure recommended that all healthcare workers wear gloves to protect themselves (and patients) from HIV and other infectious diseases. Speculation regarding possible manufacturing changes to meet that demand has also been proposed. These include changes in glove powdering processes, more rapid use of raw latex than before, a change to local production sites, production of larger lots, and the use of yield enhancers. Studies on these and other hypotheses have failed to produce any convincing evidence to explain the apparent increase in allergic reactions to these products. It has also been argued that the increase in case reports may be due in part to enhanced physician and patient awareness of NRL allergy. Here the potential for under-reporting of a previously unrecognized clinical entity coupled to the over-reporting of a now well publicized health issue could create a diagnostic bias. The degree to which this has influenced our estimates of the incidence of latex allergy is difficult to judge.
In a review of the literature on this subject a recurrent theme is that individuals with atopy are more at risk of becoming sensitized to latex proteins and of reacting to them clinically than the general population. A high proportion but not all of the patients identified with latex allergy symptoms are atopic. Patients undergoing repeated surgeries, particularly spina bifida patients, constitute another group frequently reporting allergic responses to NRL related products. As an occupational group, healthcare workers seem to have the highest reported frequency of NRL use related problems but food workers, janitors, and industrial workers have also been identified.
The conclusions from various epidemiological studies vary greatly regarding the incidence of NRL related allergic problems in healthcare workers and in the general population. A major problem in many of these studies is the nonrandom selection of study subjects. Most studies have enlisted volunteers without a comparable control group. Because individuals with symptoms are more likely to volunteer, this bias tends to overestimate incidence rates. Another problem is the lack of a definitive accepted method of diagnosing latex allergies. Several tools are available for this but different investigators have utilized these in different manners. For example, skin testing with different procedures, different allergen extracts, and different interpretations makes these studies incomparable. A similar situation exists when different serological tests for latex specific IgE antibodies are utilized. In allergy, the clinical history is often used as the "gold standard." A recent study indicates that even when strict entrance criteria are used to select latex positive patients, over 15% of these turned out to be false positive by history. This should not be surprising given that the history is a largely subjective process. It is interesting to note that surveys with self-reporting symptoms report out roughly 10-fold higher incidences than those derived from diagnosis. There are a variety of challenge test procedures that have been developed to determine the presence or absence of allergy to latex. These procedures create variable conclusions because patient reactivity varies with time and the procedures are rarely conducted with the patient or the physician in a blinded manner. As a result, these challenge procedures are typically biased, not particularly sensitive and cannot be said to be specific due to lack of characterization of the challenge materials. These factors and others make it difficult to judge the merit of various epidemioiogical studies utilizing these tools.
The skin and serological test data give rates of sensitization and not clinical disease but have revealed some interesting results. In two large studies with skin testing the incidence of positives was 0.7% (unselected schoolchildren) and 0.12% (pre-operative adult surgical patients). In three different groups of unselected patients (two from blood donors and one from a health-check) the incidence of latex specific IgE antibodies was between 6% to 7%. All three of these latter studies utilized the same serological test procedure, which is not without its critics. Unfortunately, none of these results were analyzed for specificity but the similarity in their findings was striking.
Estimates of atopic individuals in our population are around 15% to 20% and this seems to be increasing with time. Atopic individuals by definition are predisposed to make IgE antibodies to a variety of allergens. Since the allergens identified in latex seem to be identical or similar to those from a large number of other sources (many foods, pollens, and some molds) the finding of a population prevalence of IgE antibodies of around 6% to 7% may not be so surprising. It is interesting that these allergens seem to be most prevalent in certain foods, particularly those that have been treated with plant hormone to increase yield and ripening. This has led several investigators to suggest that latex allergies have arisen due to cross-sensitization. Evidence for this has come from one study where all subjects that were sensitive to a birch pollen protein had reactivity to latex, grass, olive tree pollen, and mugwort allergens.
Recently a large study by the Centers for Disease Control and Prevention analyzed 5,524 randomly selected adult samples from a cross section of 20,000 volunteers throughout the U.S. for IgE antibodies to latex allergens. The results indicated that the sensitization rates in healthcare workers and nonhealthcare workers were roughly the same. The incidence of sensitization in this study was surprisingly high; however, certain elements of the study design were attractive. These include the large number of participants, the relatively unselected population, and the fact that the investigators were blinded to the participants' status. The high incidence (19%) of positives could be a reflection of the test device but when the cutoff for positive results was raised, the conclusion regarding healthcare and nonhealthcare workers remained the same. This high rate could also represent the percent of atopic individuals with broad sensitization to pollens and plant derived foods as noted above.
Arguably the most definitive study published on this subject comes from a recent NIOSH (National Institute of Occupational Safety and Health) study. This study featured high participation from both the control group (hospital administrative staff) and the exposed group (nurses, physicians, etc.). They found that the sensitization rate for workers highly exposed to latex was 6. 1 % compared to 6.3% for workers who had no exposure to latex gloves. Again, sensitization rates were determined by the same assay as those above with similar findings. They did find that latex sensitization was significantly associated with atopy. Levels of airborne latex allergens were also measured with the conclusion that latex allergens were higher in the work areas of employees who were not sensitized. The conclusion from this study was that neither current nor past occupational latex glove use was a significant risk factor for the development of latex sensitization.
So, is the prevalence of latex allergy really higher in healthcare workers than the general population? We really don't know. From some of the more rigorous studies it seems reasonable to conclude that many of the published claims on this subject are not definitive and could be misleading. As for sensitization rates, although practically all of these data are derived from a single version of specific IgE testing, we do know that a significant number of individuals are sensitized to proteins derived from a diverse number of sources including latex.
Allergy to NRL and cross-reacting allergens is real but our knowledge and the issues surrounding it remain controversial. Thus, it is important to move beyond the simplistic anecdotal case reporting that has dominated the literature over the past few years. To enhance our knowledge of this subject it is critical that we adopt a consistent case definition of this disease. In addition, all possible efforts should be made to standardize and validate the diagnostic tools used in determining latex allergies. These measures would certainly allow for more comparable studies on this subject. Epidemiological studies should use unbiased random or consecutive selection of test and control populations and assure similar percentages of atopic individuals in both. Furthermore, participants should be blinded to the study objectives and the diagnosing physician blinded to participant status. In this way we may gain a clearer understanding of what is causing these allergic symptoms and then hopefully be in a better position to develop intervention strategies to decrease its occurrence.
