While there have been sporadic reports of adverse reactions to latex products since the 1920’s, there has been an unprecedented increase in the prevalence of latex allergies since the late 1980’s. After the first North American reports of allergic reactions to latex in 1989, an alarming number of cases were reported to the Food & Drug Administration, including 15 deaths.
Explanations for this apparent epidemic have ranged from a failure to recognize previous allergic reactions to changes in the way latex products are manufactured. The most convincing epidemiological explanation, however, is that the sudden increase in sensitization resulted from greater exposure to latex following the adoption of universal precautions to prevent transmission of bloodborne pathogens in 1987.
The term “epidemic” is not an overstatement: there is no evidence for a significant number of former “missed” reactions, and the prevalence of latex allergy in certain populations is substantial and growing. The most important common denominator is frequent exposure to latex on an occupational or medical basis. Groups at increased risk therefore include physicians, nurses, dentists, and patients who have undergone multiple operations.
Once a latex allergy has developed, it can remain unchanged, evolve slowly, or progress rapidly from an annoying dermatitis to life-threatening anaphylaxis. The medical, vocational, and medicolegal implications of this growing problem are obvious. For that reason, it is essential for all healthcare providers to understand what causes latex allergy, how to recognize it, and how to manage it.
What Is Latex?
Latex (cis-1,4-polyisoprene) is not a substance that is synthesized in a laboratory. It is actually a natural product obtained from the Brazilian rubber tree, Hevea brasiliensis. Its biological function is to coagulate and seal any wounds to the plant. Latex-containing fluid (a cytosol) is collected from slits in the bark of the tree, much the way maple syrup is harvested. This milky fluid is pooled, treated with ammonia as a preservative and stabilizer, then centrifuged to concentrate the solids. Natural rubber latex then goes through additional processing steps such as heat-treatment with sulfur, a process called vulcanization, which gives rubber added elasticity, strength, stability, and heat-resistance. Various chemicals may also be added in order to accelerate the curing process or impart desired properties to the finished product (Table 1).
Latex can be used to make two kinds of products. One type is crepe or hardened rubber products, which are extruded or compression-molded to form objects like tires and toys. Dipped products like gloves and condoms, which retain more allergens, are formed on ceramic molds. After being coated with a coagulating salt to accelerate gelling, the mold is submerged in liquid latex, much like dipping a candle wick in melted wax. The emulsion-coated mold is then cured in an oven and the finished object removed. Some products, like latex gloves, may also be washed, chemically treated, or coated with cornstarch powder to permit easier donning and removal.
What Makes Latex Allergenic?
Latex allergens consist of a number of proteins and polypeptides. At least 250 polypeptides have been identified in natural rubber latex, and over sixty of them are potential allergens capable of binding IgE. Ten polypeptides (designated as Hev b 1 to Hev b 8) are especially frequent sensitizers, including a 14 kilodalton (kd) peptide known as rubber elongation factor (Hev b 1) and a 4.7 kd peptide called hevein (Hev b 6.02), and its precursor, a 20 kd peptide called pro-hevein (Hev b 6.01); the latter two have been implicated in healthcare workers’ latex allergies.
Latex-contaminated cornstarch lubricating powder allows these allergens to become airborne, exposing nearby individuals to latex without actual contact. The powder, which adsorbs latex proteins, is dispersed into the ambient air when gloves are removed.
Another source of allergens in latex products are the chemical additives used in processing. These chemicals, chiefly the accelerators used to speed the curing process, are responsible for most cases of contact dermatitis.
A common bacterial contaminant generated during the manufacturing process is also thought to contribute to the development of latex allergy. Latex (cis-1,4-polyisoprene) is not a substance that is synthesized in a laboratory. It is actually a natural product obtained from the Brazilian rubber tree, Hevea brasiliensis. Its biological function is to coagulate and seal any wounds to the plant. Latex-containing fluid (a cytosol) is collected from slits in the bark of the tree, much the way maple syrup is harvested. This milky fluid is pooled, treated with ammonia as a preservative and stabilizer, then centrifuged to concentrate the solids. Natural rubber latex then goes through additional processing steps such as heat-treatment with sulfur, a process called vulcanization, which gives rubber added elasticity, strength, stability, and heat-resistance. Various chemicals may also be added in order to accelerate the curing process or impart desired properties to the finished product (Table 1).
Who Is At Risk of Latex Allergy?
Like other allergies, the risk of sensitization to an allergen like latex increases under two circumstances: atopy (having other allergies or a tendency to produce IgE responses) and repeated exposure. All high-risk groups can be explained on the basis of one or both of these characteristics.
A survey of anti-latex IgE antibodies in volunteer blood donors showed a prevalence of 6.4%; high levels of IgE were found in 2.3%. However, there is a difference between sensitization, reflected in IgE responses, and clinical sensitivity, reflected in observable adverse reactions, which is much lower. Estimates of clinical sensitivity in the general population are around 0.8%. This disparity between sensitization and clinical sensitivity is one reason why screening for antibodies has limited value; like many other diagnostic tests, testing for anti-latex antibodies is meaningful only in the context of the clinical history.
Since repeated exposure promotes sensitization, one of the highest-risk groups is healthcare workers. This is not surprising, since nine billion latex gloves are sold annually in the U.S. Estimates of sensitivity range from 7.4% of surgeons and operating room nurses and 10% of dentists . Rubber industry workers also have an increased prevalence of latex allergy, estimated at 5-10%. Since atopic or allergic individuals (those with allergic rhinitis, asthma, eczema, or food or drug allergies) are prone to making IgE responses, they are also at higher risk, estimated at 10%.
Another important high-risk group is patients who have been repeatedly exposed to latex during medical and surgical procedures such as multiple operations, frequent bladder catheterizations, and manual stool disimpaction. The highest-risk group of all is children with neural tube defects such as spina bifida and ventriculo-peritoneal shunts, and those with congenital urogenital abnormalities. Up to 65% of children with spina bifida develop latex allergies. They have a 500-fold increase in risk of intraoperative anaphylaxis, accounting for up to 80% of cases of intraoperative anaphylaxis in children. This prevalence is so overwhelming that many authorities recommend avoiding latex exposure from birth in this group of children.
One important caveat about risk groups: latex allergies may occur in individuals with no risk factors, so any patient with a suggestive history should be considered a potential candidate.
Clinical Manifestations of Latex Allergy
Reactions to latex can range from a rash to fatal anaphylaxis. The most common adverse reaction is irritant dermatitis, a non-immunologic condition similar to “dish-pan hands”. Caused by repeated hand-washing, harsh soaps, friction, and occlusion, irritant dermatitis typically has a dry, cracked appearance. One concern is that irritant dermatitis may predispose to development of latex allergy by facilitating passage of latex antigens into the circulation.
The second most common type of skin reaction is delayed hypersensitivity contact dermatitis. This is a delayed or Type IV immunologic reaction similar to poison ivy dermatitis. This inflammatory dermatitis is rarely caused by latex itself, but instead by chemical additives such as accelerators. The appearance, like poison ivy, is typically red and swollen, often with blistering, weeping, and crusting; the reaction is often intensely pruritic. Onset of the reaction is usually delayed for hours to days after contact, but may become chronic with repeated exposure. Since delayed hypersensitivity contact dermatitis is not a true IgE-mediated allergic reaction (it is mediated by T-cells), skin and blood tests for latex IgE antibodies will be negative, but delayed patch tests for additives will be positive.
The next step up the “ladder” of latex allergies is contact urticaria or localized hives. This is the first Type I or true IgE-mediated reaction to latex proteins. Onset is usually rapid (within twenty minutes) after contact and the dermatitis consists of localized red, raised, pruritic urticarial lesions at the site of contact.
The next, and more serious stage, is mucosal reactions. These reactions consist of conjunctivitis or rhinitis, similar to hay fever. Symptoms may include red, itchy, watery, swollen eyes; sneezing, nasal congestion, itchy nose, clear nasal discharge, or itchy throat. This type of IgE-mediated reaction can be caused either by contact with latex or exposure to airborne powder from latex gloves.
Further up the ladder of reactions is respiratory or bronchospastic reactions. Symptoms may include cough, wheezing, chest tightness, or shortness of breath.
The most severe reactions are systemic reactions. These explosive, potentially life-threatening allergic reactions include generalized urticaria, angioedema, and anaphylaxis.
While the severity of allergic reactions to latex is often gradually progressive, it is important to keep in mind that progression can be rapid, sometimes “skipping” steps from contact urticaria, for example, to full-blown anaphylaxis without warning. For that reason, even mild allergic symptoms can be a harbinger of anaphylaxis and should be taken seriously.
Latex allergies can manifest in one other unusual way: food allergies. A number of foods, especially bananas, chestnuts, and avocados, cause allergies in latex-allergic individuals (Table 2). This phenomenon is now thought to be attributable to plant enzymes called chitinases, which cross-react with the latex peptide hevein9. At present, it is not clear if latex-allergic patients should be routinely cautioned to avoid these foods in the absence of a history of prior reactions, or if patients with these food allergies should avoid latex exposure.
Routes of Exposure
Latex can induce allergic reactions through several different routes. The first is cutaneous – direct skin contact, which can trigger either a local or systemic reaction. The second type of exposure is mucosal (oral, nasal, conjunctival, or genital membranes), either from direct contact with latex or airborne glove powder. The third type, percutaneous exposure, results from injection of latex-contaminated medications. Latex antigens from multi-dose rubber vial stoppers or latex injection ports are readily soluble in medications, especially after multiple punctures. While the amount of soluble latex antigen is small, it is sufficient to induce severe reactions in highly sensitive individuals. Parenteral exposure typically results from various medical and surgical procedures such as operations, urinary catheterizations, and endoscopic procedures.
While the more intimate the exposure, the more likely it is to provoke a severe reaction, it is important to remember that even casual contact can trigger anaphylaxis in a highly sensitive patient.
One other type of exposure can be misleading: indirect exposure. A typical example is a nurse who removes her latex gloves after leaving one patient’s room, then enters a latex-allergic patient’s room. Even the trace amounts of latex or powder on her skin and clothing can cause reactions. There have been reports of a surgeon’s wife who developed urticaria when her latex-contaminated husband came home from work, and of individuals who reacted to food contaminated by latex glove-wearing food workers.
Diagnosing Latex Allergy
The most important diagnostic test for latex allergies is the medical history. As with drug allergies, patients should be routinely questioned; a good screening question is: “Have you ever noticed any itching or congestion after exposure to latex or rubber products such as rubber gloves or balloons?”
It’s important in taking a history to have a high index of suspicion, especially in high-risk patients such as healthcare workers. If latex allergies are suspected, more detailed questions should be asked (Table 3).
One special case is latex anaphylaxis in surgery, which can be misleading. One reason is that reactions can be delayed in onset, sometimes from 15 minutes to two hours into the operation. Second, manifestations can be highly variable, ranging from flushing to cardiopulmonary arrest. Other potential symptoms of latex anaphylaxis in surgery include tachycardia, hypotension, urticaria, laryngeal or facial edema, and post-intubation bronchospasm. Wheezing or difficulty ventilating a patient may also be an indication of latex allergy, even in a known asthmatic – 60% of latex-allergic patients are also atopic.
To complicate matters further, intraoperative anaphylaxis due to latex can be mistakenly attributed to other causes, such as drug allergy, transfusion reaction, or reaction to a muscle relaxant or anesthetic. For that reason, any allergic or systemic reaction in the operating room should be considered a possible latex allergy.
After the history, the most important confirmatory tests for latex allergy are in vitro tests (RAST or ELISA) such as the AlaSTAT (Diagnostic Products Corporation, Los Angeles, CA) or ImmunoCap (Pharmacia & Upjohn Diagnostics Division, Kalamazoo, MI), or HY-TEC (Hycor Biomedical, Irvine, CA). Compared to the gold standard percutaneous skin tests, , these FDA-approved tests have somewhat limited sensitivity and specificity. About one-quarter of AlaSTAT and ImmunoCap tests are false-negative, and 27% of HY-TEC tests are false-positive11. However, high titers (> Class 3) are highly predictive of latex-induced asthma or urticaria.
Allergy skin tests, performed by some specialists, have even better sensitivity and specificity. However, no FDA-approved skin testing reagent is currently available in the U.S. Some allergists test with “home-made” aqueous latex extracts, but since these vary in potency and there have been reports of serious adverse reactions, this type of test should only be performed by experienced physicians.
For patients with chronic dermatitis, it may be necessary to refer them to a dermatologist for patch testing to diagnose delayed hypersensitivity contact dermatitis caused by chemical additives. Alternatively, a switch to a powder-free or non-latex glove may help both confirm the diagnosis and solve the problem.
For patients with bronchospastic symptoms in a health-care setting, a mini-peak flow meter is another diagnostic option that can help document airflow obstruction in the workplace.
Finally, “use” tests can help clarify latex allergy in ambiguous cases, chiefly in patients with a convincing history but a negative in vitro test. This two-stage test should be performed only if there are adequate facilities and expertise to treat a potential systemic reaction. In the “use” test, first a latex glove fingertip is placed on a patient’s wet finger for fifteen minutes. If there is no sign of reaction, an entire latex glove is placed on a wet hand for fifteen minutes. Additional steps include pricking the skin before donning the glove, pricking the skin through the glove once, then pricking the skin through the glove three times. Lack of a local or systemic reaction strongly argues against latex allergy. A neoprene or vinyl glove can be used on the other hand as a control.
The final test which is occasionally used when all other tests are negative is the inflate-deflate test, in which the subject blows up the glove like a balloon then allows it to deflate in his or her face.
In an emergent situation with no time for testing, a patient with any suggestive history should be considered latex-allergic until proven otherwise, much like a drug allergy.
Managing the Latex-Allergic Patient
As with any other allergy, the first principle of managing latex allergy is avoidance. Like drug allergies, the patient’s chart should be clearly labeled; for hospitalized patients, a warning sign should be placed outside the room, and relevant departments (Pharmacy, Central Supply, and Nutrition) notified of the admission.
Contamination of injected medications by latex should be avoided: latex IV injection ports should be covered with tape and a plastic stopcock used to inject all medications (IV tubing itself contains no latex). Tops of rubber-stopper multidose vials should be removed before drawing up injectable medications, and any vial with previous punctures should not be used. Single-dose glass ampules are preferred when available.
Latex medical products should not be taken into the patient’s room. Some latex items may not be immediately obvious (e.g. stethoscope tubing and tourniquets), so it is important to review potential sources of latex (Table 4). Many institutions avoid the uncertainty of this situation by forming multidisciplinary latex advisory committees to develop latex-free protocols, patient units, and crash carts (Table 5).
The operating room poses special challenges. Many surgical and anesthesia devices and products are made of latex, ranging from ventilator bellows to warming blankets. Consequently, many hospitals now designate at least one latex-free surgical suite.
One problem in operating rooms is residual airborne latex from powdered gloves used earlier in the day. This problem can be avoided by scheduling the latex-allergic patient as the first case of the day.
A severe acute reaction to latex should be treated as any other case of anaphylaxis. The first step is to check for and remove all sources of latex in the immediate vicinity. Next, secure the airway, provide oxygen, volume expansion, and treat with epinephrine. Second-line treatment options include H1 and H2 antihistamines, corticosteroids, bronchodilators, pressor agents, and intra-aortic balloon pumps in cases of refractory anaphylaxis.
Finally, all patients with documented latex allergy should be advised to:
- Notify all treating healthcare providers, including dentists
- Obtain a Medic-Alert pendant or bracelet (1-800-432-5378)
- Avoid exposure to latex-containing consumer products
- (Table 6)
- Carry an epinephrine-containing autoinjector (Epi-Pen, Ana-Kit, Ana-Guard)
- Keep a supply of non-latex gloves to take on visits to healthcare providers
Managing the Latex-Allergic Staff Member
In addition to all of the above measures, latex-allergic healthcare workers must avoid occupational exposure to latex.
For mild to moderate cutaneous reactions, simply switching to a powder-free or non-latex glove may be adequate. To prevent exposure to airborne latex, co-workers in the immediate area should switch to non-powdered gloves. One study showed that not only did eliminating powdered gloves from the workplace reduce airborne latex to undetectable levels within 24 hours, but new cases of sensitization in health care workers were prevented.
While the strategy of working in an “ALARA” (“as low as reasonably achievable”) environment is adequate for many healthcare workers, those with more severe or life-threatening allergies may require a 100% latex-free environment. If this is not possible, reassignment or vocational retraining may unfortunately be the only alternatives.
The epidemic of latex allergy is a new medical entity, and its prevalence is increasing. It poses a major problem for many patients, healthcare workers, and institutions, sometimes threatening both health and livelihood. Fortunately, as we become better informed, more accurate diagnostic tests become available, and a greater variety of non-latex products appear, latex allergy is usually a very manageable problem.
To prevent latex allergy from becoming a problem, it is important to keep six key strategic points in mind:
- Routinely ask patients (as for drug allergies)
- Identify high-risk patients
- Avoid latex exposure from birth in high-risk patients such as children with spina bifida
- Offer precautions to latex-allergic patients (e.g. MedicAlert, Epi-Pen)
- Offer latex-free units, operating rooms, and crash carts in hospitals
- Learn about latex allergies
Finally, remember four essential latex allergy warnings:
- Mucosal or parenteral exposure usually causes more severe reactions than cutaneous exposure
- The severity of previous reactions does not reliably predict the severity of future reactions
- Anaphylaxis may occur with any type of latex exposure
- Latex anaphylaxis may mimic a reaction to a drug, muscle relaxant, transfusion, or anesthetic.