US Pharm. 2006;4:HS-5-HS-9.     

Natural latex has been used for over 100 years in food and rubber industries, hospitals, and homes. Following the report of a case of hypersensitivity to latex in England in 1979, 16 deaths occurred in association with the use of a latex barium enema tip. The first cases of latex allergy in the United States were reported in 1989, leading to the recall of the device by the Food and Drug Administration in 1991.1 FDA then warned of an increase of the risk of a life-threatening type I allergy associated with natural latex devices. With the advent of universal precautions in 1987 to prevent transmission of human immunodeficiency virus (HIV) and other bloodborne pathogens, the use of barrier protection such as latex gloves and latex condoms dramatically increased. In fact, the number of latex gloves imported into the United States in 1987 was one billion and in 1988 it was eight billion. This caused an increase in total exposure to latex and a true increase in the number of persons with latex sensitivity.

It is estimated that 17 million adults in the U.S. are affected by a type I latex allergy. Many health care workers and rubber industry employees have become sensitized, and some have developed occupational asthma as a result of latex exposure.2 Many who have been sensitized to latex do not know that their symptoms are caused by latex allergy. This is due to the nonspecific nature of symptoms and a lack of knowledge about latex allergy. Others at high risk of sensitization are those with prolonged exposure to latex, those who undergo repeated surgeries (especially newborns), and workers in the latex manufacturing industry such as latex-doll makers. As many as 65% of children with spina bifida have latex allergy.

Since latex-sensitive people may rapidly develop anaphylaxis, they should be educated about the latex content of common products. In people who have been sensitized, avoidance is the most important strategy in the treatment of latex allergy. This article briefly reviews the nature of latex allergy, its symptoms, diagnosis, and treatment.3

What is Latex?
Latex is a polymer of 1,3 cis-polyisoprene derived from Hevea brasiliensis rubber plant. Natural rubber latex consists of approximately 60% water, 35% rubber, and 5% protein and hydrocarbons. Protein antigens (2% to 3%) associated with the polymer are involved in the sensitization process leading to immediate hypersensitivity. This polymer is a long molecule composed of many repeating smaller molecular units. The basic unit of the polymer is called isoprene. Latex is derived from the latex sap of commercially grown rubber trees. The sap is extracted and heated while chemical preservatives, primarily ammonia, are added to enhance the rubber's structural qualities. Latex contains at least 10 different low-molecular-weight soluble proteins that cause IgE-mediated allergic reactions. Added stabilizers and antioxidants may also be significant mediators of allergic contact dermatitis and may cause or exacerbate irritant contact dermatitis.4

Commercial Latex Products
Natural rubber latex is processed into two types of commercial products. Approximately 90% is processed into dry products, which are then converted into molded rubber products such as tires and vial stoppers. The reminder is used for dipped rubber products such as gloves, diaphragms, balloons, and condoms. The dipped products are the primary sources of bioavailable latex allergens. Latex products are much stronger than vinyl products but appear to have the highest content of latex proteins and therefore have the greatest allergenic potential.

During the manufacturing process, cornstarch powder is applied to latex gloves to prevent stickiness and to make it easy to get them on and off. Latex protein particles have been shown to rest on the surface of these cornstarch particles and to aerosolize when the gloves are removed, especially when quickly snapped off.3,5 These airborne latex particles may result in sensitization. In areas where powdered gloves are used frequently, such as in operating rooms, labor and delivery units, and physician offices, sufficiently elevated concentrations of aerosolized latex may produce significant symptoms in sensitized persons.

There is much variation in the antigenicity of latex gloves because there are multiple manufacturers and different types of gloves. Slow removal of the gloves will reduce the potential for aerosolization of latex. Because latex proteins are water-soluble, glove manufacturers try to reduce these proteins by washing, chlorination, and other treatments to prevent latex protein antigenicity.  Low-protein, powder-free gloves have minimal potential for sensitization in those who have not yet become sensitized to latex.5

Other products that may sensitize patients include urinary catheters, face masks, tourniquets, adhesive tapes, medication vial stoppers, blood pressure cuff tubing, and PCA syringes. Household items such as clothing, racquet handles, tools, diapers, shoe soles, erasers, and toys may contain latex as well.

Symptoms of Latex Allergy
Symptoms of latex allergy vary in different people. Allergic symptoms may present in the following ways:
• Delayed hypersensitivity (contact dermatitis): This is a cell-mediated response (type IV). It causes contact dermatitis in response to latex up to two days after exposure, with erythema, vesicles, papules, pruritus, blisters, and crusting in the areas where the skin has come into contact with the material. There are no systemic symptoms. This may also be caused by chemicals used in the manufacturing of the gloves.
• Immediate hypersensitivity: This is an immediate response (type I) occurring within minutes, in which two phases may be observed. The first involves sensitization to the latex allergens, with specific IgE release by plasma cells and its deposit in mast cells and basophils. In the second or exposure phase, the allergen interacts with the IgE on the surface of the mast cells and the basophils and triggers their degranulation, which then causes the release of the mediators of the allergic reaction in less than two hours.  The symptoms include local and generalized urticaria, angioedema, nausea, vomiting, rhinoconjunctivitis, bronchospasm, and anaphylactic shock.
• Anaphylactic reactions: Anaphylaxis to latex has also been reported due to increased latex protein absorption through the skin of persons who had previously experienced irritant or allergic contact dermatitis. It is possible to have used latex gloves for years and suddenly have a progression to systemic symptoms. Some people who are sensitive to latex, such as health care workers, may have a history of atopic disease and show a positive skin test in reaction to latex.3,6

Food–Latex Cross-Allergy
Food allergies to bananas, avocados, and chestnuts predispose individuals to latex allergy. People who have been sensitized to latex may also show cross-reactivity to certain fruits--such as bananas, chestnuts, kiwi, avocado, and tomato--due to proteins in them that are similar to latex protein. Certain other foods, including figs, apples, celery, melons, potatoes, papayas, and pitted fruits, such as cherries and peaches, have also caused dermal and oral itching in some people. People with a history of reactions to these foods are at increased risk of developing latex allergy upon latex contact, and those who are sensitive to latex should avoid foods to which they have had previous reactions. Consultation with a nutritionist or a dietary specialist will be very useful.7-9

Diagnosis of Latex Allergy
Diagnosis of latex allergy is made through a careful medical history and immunologic testing. The patient should be evaluated for all high-risk factors, background, and type of occupation. If the patient has had previous reactions, it is important to identify under what conditions those reactions occurred--e.g., following the use of rubber gloves, condom, or diaphragm, or during a pelvic examination in a medical clinic. All of these point to a possibility of latex sensitivity.

Sometimes, the respiratory symptoms (e.g., rhinoconjunctivitis or bronchospasm) in a sensitized person could be due to a latex exposure, but if the patient is not educated about latex allergy the patient will not attribute it to the latex exposure. It is critical to evaluate patients' medical history and latex exposure before they undergo any procedures that could trigger an allergic reaction. This important step could help reduce the chances of analphylactic reaction or death.

FDA-approved in vitro tests to measure latex-specific IgE are available from several companies. The ELISA (enzyme-linked immunosorbent assay) may be used to measure serum latex- specific IgE; it appears to be most sensitive in patients with a positive skin test with or without a history of allergy to latex. Also, negative serologic testing with a strongly positive history would suggest the value of skin testing to confirm the diagnosis.2,5

Management of Latex Allergy
The major approaches to the management of latex allergy are prevention and treatment of latex allergy in both health care personnel and the latex-allergic patient. Continual exposure to powdered gloves is likely to produce sensitization. Sensitized health care workers have to avoid using latex products (powdered gloves are one of the most sensitizing latex products) and must try to reduce airborne antigen exposure. To reduce cumulative exposure to latex, it is important to use nonpowdered, low-protein latex or nonlatex gloves; some newer latex glove products have very low levels of solubilized and aerosol proteins. For health care workers and patients who are allergic to latex, only nonlatex gloves must be used. The National Institute of Occupational Safety and Health (NIOSH) recommends nonlatex gloves for use in food preparation, routine housekeeping, maintenance work, and any other activities not likely to involve infectious materials. Vinyl gloves are comparable to latex in cost but are not as effective against viral penetration.10 Other nonlatex materials demonstrate excellent barrier integrity but generally are more expensive.

Hospital Management Protocols
Protocols to prevent patient contact with latex should be established for the emergency department, operating room, and other areas.

At the time of admission, the patient should be questioned about latex allergy status. If the patient is admitted, status should be documented and immediately displayed at the door and the bedside and on wristbands.

Emergency department, operating room, and crash cart supplies should include nonlatex products.

Latex-sensitive patients undergoing surgery should be scheduled as the first case of the day, when aerosolized latex particles are at a low level.

If blood pressure cuffs and tubing are made of latex, the patient's extremities should be wrapped to prevent contact.

Syringes that contain latex rubber and latex ports should not be used for intravenous injections.

Hospitals must follow FDA rules for labeling all medical devices that contain natural rubber latex.

Staff should study a list of latex products and latex-free substitutes in both community and hospital settings, available from The Spina Bifida Association of America.11,12

Latex Allergy Treatment
Treatment of latex allergy is mainly symptomatic, with administration of fluids and epinephrine 0.5 to 5 mcg/min intravenously to control hypotension. To control bronchospasm, methylprednisolone 50 mg IV every six hours and nebulized metaproterenol 0.3 mL (5% solution) in 2.3 mL normal saline or IV aminophylline with loading dose of 6 mg/kg/h over 30 minutes followed by a continuous infusion of 0.3 to 0.9 mg/kg/h as a maintenance dose may be administered. Antihistamines such as diphenhydramine 25 to 50 mg every six to eight hours and cimetidine 300 mg every six hours may be given to control urticaria, erythema, and histamine release. Acute systemic reactions to latex should be treated in the same manner as any anaphylactic reaction. The airway, breathing, and circulation are assessed, oxygen is provided, and epinephrine and steroids are also administered. Treatment should be continued with monitoring after symptoms resolve. Pharmacists are in an excellent position to alert the public about the magnitude of health risk posed by latex allergy and to assist in improving and preventing this growing problem.13

 

REFERENCES
1. Ownby DR, Tomlanovich M, Sammons N, McCullough J. Anaphylaxis associated with latex allergy during barium enema examinations. Am J Roentgenol 1991;156:903-908.
2. Product approvals: latex sensitivity test. FDA Med Bull 1995;25:2-3
3. Hepner DL and Castells MC: Latex Allegy: an Update. Anesth Analg 2003; 96:1219-1229.
4. Zucker-Pinchoff B and Stadtmaur GJ: Latex Allergy. Mt Sinai J Med 2002; 69:88-95.
5. Landwehr LP and Boguniewicz M: Current perspectives on latex allergy. J Pediatr 1996;128(3):305-312.
6. Kwittken PL, Becker J, Oyefara B, Danziger R, Pawlowski N, Sweinberg S. Latex hypersensitivity reactions despite prophylaxis. Allergy Proc 1992; 13:123-127.
7. Lavaud F: Latex allergy in patients with allergy to fruits. Lancet 1992;339;492-493
8. Blanco C, Carrillo T, Castillo R, Quiralte J, Cuevas M. Latex allergy: clinical features and cross-reactivity with fruits. Ann Allergy 1994;73:309-314.
9. Beezhold DH, Sussman GL, Liss GM, Chang NS. Latex allergy can induce clinical reactions to specific foods. Clin Exp Allergy 1996;26:416-422.
10. Bernstein DI: Management of natural rubber latex allergy. J Allergy Clin Immunol. 2002;110: S111-S116.
11. United States Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Preventing allergic reactions to natural rubber latex in the workplace. Cincinnati: Government Printing Office, 1997; NIOSH publication no. 97-135.
12. Beezhold D, Beck WC. Surgical glove powders bind latex antigens. Arch Surg 1992;127:1354-1357.
13. Micromedex Health Series. 2005.


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