Marc A. Riedel
Hypersensitivity reactions to latex are a significant concern among patients and health care providers. The apparent increased prevalence of latex allergy over the last few decades is believed in part to be due to the widespread use of latex gloves to prevent transmission of blood-borne pathogens such as HIV. The frequent use of latex-containing materials within the health care system thus generates a great deal of concern and anxiety among individuals who have adverse reactions to latex, and true latex allergy can cause serious complications, including death.
EPIDEMIOLOGY AND PATHOPHYSIOLOGY
Natural rubber is a highly processed plant product of the commercial rubber tree, Hevea brasiliensis. Most true allergic reactions to natural rubber latex occur with exposure to “dipped” products such as gloves or balloons. These products made from liquid latex rubber have a large number of soluble proteins capable of binding IgE.1
IgE-mediated allergic reactions to latex, while not common in the general population, are a leading cause of anaphylaxis in children, particularly for events that occur during hospitalization. Life-threatening allergic reactions may be the presenting factor of latex allergy in up to 30% of latex-sensitive children. The majority of latex-allergic individuals are highly atopic, with histories of allergic conditions such as rhinitis or asthma. The prevalence of clinical latex allergy in the general population has not been established. Studies have demonstrated that 3% to 9.5% of the general population is sensitized to latex as determined by skin or serum allergy testing; however, these numbers do not represent the prevalence of clinical reactions to latex exposure (ie, a positive allergy test does not mean a clinical allergy to latex). Studies have demonstrated a higher prevalence of latex sensitization in certain high-risk groups with frequent exposure to latex, including health care workers and children with spina bifida undergoing repeated urologic and neurologic surgical procedures. Children with spina bifida have the highest prevalence of latex sensitization, with reports ranging from 18% to 73%.2 Risk factors for sensitization in this population include more than 5 surgeries and a history of atopy. While these prevalence rates indicate the presence of latex-specific IgE by diagnostic testing rather than clinical allergic reactions, the high rate of sensitization and potential severity of reactions suggest that all spina bifida patients should be evaluated for their individual risk of latex allergy prior to surgical procedures to minimize complications as much as possible.
Interestingly, latex allergy has been associated with allergy to several fruits and vegetables, including avocado, kiwi, banana, potato, tomato, chestnut, and papaya. Termed the latex-fruit syndrome, this clinical observation has been traced to homology between major latex allergen proteins (Hev b 5, Hev b 6, Hev b 7) and various proteins found within these foods.3
True latex allergy is mediated by antigen-specific IgE, which triggers mast cell activation with latex exposure. Atopic individuals may potentially generate latex-specific IgE after an initial exposure to latex antigen. The sensitizing exposure is most commonly mucocutaneous (as with latex gloves or balloons) or intraoperative, as latex antigens are leached from rubber products by moisture. Latex antigen may also be adsorbed onto corn starch powder inside gloves, thereby facilitating respiratory exposure from airborne particles. Studies show strong associations between latex aeroallergen levels and the use of powdered latex gloves.4 With subsequent latex exposure, latex-specific IgE bound to mast cells and basophils is cross-linked by the antigen and mast cell activation occurs via high-affinity IgE receptor signaling. Activated mast cells release preformed histamine, tryptase, chymase, and heparin, as well as generate other inflammatory mediators, such as cysteinyl leukotrienes, prostaglandins, and inflammatory cytokines. This mediator release into tissues and circulation leads to the allergic signs and symptoms associated with allergic reactions to latex.
A detailed history of adverse reactions to latex product exposure is the most important initial step in properly assessing for latex allergy. IgE-mediated latex allergy may cause various symptoms consistent with a mast cell–mediated reaction. These may include urticaria, angioedema, acute rhinitis or conjunctivitis, bronchospasm, and anaphylaxis. As is typical of IgE-mediated reactions, symptoms generally appear with 15 minutes of exposure. Contact urticaria is the most common early manifestation of latex allergy. Generally, such symptoms result from physical contact with latex products either in the home setting (balloons, household rubber products) or the health care setting (gloves, blood pressure cuffs). Less commonly, symptoms of rhinitis and asthma may result from respiratory exposure to aerosolized latex particles adsorbed by cornstarch particles in powdered gloves. Latex-induced anaphylaxis is most commonly encountered during medical procedures such as bladder catheter placement, barium enemas, and surgical procedures. Latex allergy should always be considered in the differential diagnosis of causes for intraoperative anaphylaxis, as it is among the most common causes of this event.
When IgE-mediated latex allergy is suspected based on the clinical history and symptoms, diagnostic testing for latex-specific IgE should be pursued. Such confirmatory testing is important in order to avoid misdiagnosis of patients as latex allergic if this is not true. Inappropriately classifying patients in this manner leads to a great deal of anxiety, difficulty, and cost in navigating the health care system due to unnecessary avoidance measures. Specific-IgE testing for latex can be accomplished by allergy skin testing or serum radioallergosorbent testing. At present in the United States, there is no commercially available standardized latex reagent for skin testing, making latex allergy skin testing a challenging endeavor. Historically, some specialists have performed skin testing using solutions extracted from latex rubber gloves. Such an approach is complicated by variability in the concentration of specific latex allergens, and the sensitivity and specificity of such testing has not been established. Skin testing for latex should only be performed and interpreted by an experienced specialist. Serum testing for latex-specific IgE is commercially available with immunoassays licensed by the US FDA. While some variability exists in the sensitivity and specificity of these assays, it is reasonable to expect a sensitivity of 70% and a specificity of 90% from the FDA-licensed tests.5
IgE-mediated latex allergy should be distinguished from dermatitis that occurs with rubber glove exposure. Latex rubber products can induce both irritant and allergic contact dermatitis. Allergic contact dermatitis, appearing days after cutaneous exposure, is a delayed-type inflammatory cutaneous reaction caused by specific T-cell activation. This type IV immunological reaction may be caused by a variety of chemical accelerators and antioxidants added to the rubber mixture during glove production. Thus, while this form of dermatitis may be a risk factor for IgE sensitization to latex, presumably due to compromised skin barrier function, this delayed dermatitis is generally not due to IgE-sensitization to latex and therefore does not confer the potential associated risks of acute, immediate life-threatening reactions with latex exposure. In the setting of rubber-induced dermatitis, it is important to distinguish latex allergy from sensitization to low-molecular-weight chemicals in rubber products. Allergy patch testing to these compounds may be helpful in establishing a diagnosis.
Acute allergic reactions to latex are managed in the same manner as other IgE-mediated reactions based on specific symptoms. The patient should be removed from the source of the latex exposure to prevent further exacerbations of the allergic reaction. Urticaria or angioedema should be treated with oral antihistamines, and rhinitis and conjunctivitis may be treated symptomatically with oral antihistamines or topically with ocular and nasal antihistamines. Inhaled bronchodilators are indicated for bronchospasm. Anaphylaxis is treated primarily with epinephrine, though corticosteroids, IV fluids, and other supportive care may be required. Once a diagnosis of latex allergy has been established and documented, the long-term management of such patients requires latex avoidance and education of the patient. Minimization of exposure to dipped rubber products such as gloves, balloons, and condoms is of primary importance. Patients should inform all health care providers of the latex allergy and consider medical alert identification indicating the allergy. Even though the health care system is often equipped with appropriate alternative rubber-free products, it is advisable for patients to have a personal supply of nonlatex gloves for use when they require medical or dental care and to carry self-injectable epinephrine. Medical procedures on latex allergic patients should be conducted in a latex-free environment where nonlatex gloves are worn by medical providers and no latex accessories come in direct contact with the patient.5,6 Anecdotal reports have described latex allergic patients developing reactions from the injection of medications through latex ports in IV tubing. However, the dry rubber products used in such closures generally have low levels of extractable protein compared to dipped products (gloves) made from liquid latex. Thus, the need to eliminate latex in IV tubing and medication vial closures is controversial. An updated list of non-latex alternative medical supplies available in the United States is provided by the American Latex Allergy Association.7 Patients diagnosed with latex allergy should also be asked about allergic signs or symptoms when they eat the foods included in the “latex-fruit” syndrome as listed above. If patients tolerate these foods without symptoms, there is no compelling reason to avoid them; however, latex-allergic individuals should be cautious when eating these foods for the first time. A variety of latex immunotherapies are under investigation but none are yet adequate for routine use.8