Facility Reporting

Issue No. 19 Spring 1997

A quarterly bulletin to assist hospitals, nursing homes, and other device user facilities

List of Articles in this Issue:
Adverse Reactions to Natural Rubber Latex
Natural Rubber Latex Allergy
How FDA Regulates Gloves
FDA Scientists Study QA Tests for Latex Gloves
FDA Clarifies Latex Terminology
Glove Quality And Selection Criteria
FDA Alerts Users of Reusable Medical Devices


By Vesna J. Tomazic, Ph.D.

In response to the highly infectious hepatitis B virus (HBV) and the appearance of the human immunodeficiency virus (HIV), the Occupational Safety and Health Administration (OSHA) issued a Universal Precautions Standard in the 1980s, requiring all health care workers to use protective equipment. Since then, medical gloves have been the primary source of barrier protection for healthcare workers and others such as those in the waste disposal industry, janitors, and police. When HIV became a serious health threat, there was a ten-fold increase in the number of gloves used in the United States. Most medical gloves are made of natural rubber latex (NRL).

With such a dramatic increase in the demand for medical gloves and the longer and more frequent use of gloves, the number and the severity of adverse reactions to NRL have increased greatly. In the past, occasional problems with NRL were reported to the Food and Drug Administration (FDA) and appeared in the scientific literature, but there was little public concern. After a decade of intensive use of NRL gloves, many of which are now supplied from new, less-controlled sources, adverse reactions to NRL are reaching almost epidemic proportions. To prevent or solve the problem, manufacturers and users will need extensive education in the new diagnostic testing and manufacturing technologies for NRL products.

What kinds of reactions are caused by NRL products?

Three types of adverse reactions may develop as a result of frequent and prolonged exposure to NRL: irritant contact dermatitis, allergic contact dermatitis, and urticaria/anaphylaxis.

Irritant Contact Dermatitis
is a direct injury to the skin caused by chemicals, added to NRL during manufacturing, that remain on the surface of finished products. These chemicals injure the skin and cause redness and swelling, sometimes accompanied by itching and a burning sensation. The first symptoms appear shortly after exposure, in the range of several minutes to 6 hours. If the source of irritation is eliminated, symptoms will clear in several hours. With chronic exposure, however, symptoms will worsen and the skin will become dry, thickened and cracked. The intensity of the reaction depends on the dose and duration of exposure and the skin condition at the time of exposure. There is no known genetic factor that links susceptibility to this type of irritation.

Allergic Contact Dermatitis
is an immunological response to chemicals on NRL products that penetrate the user’s skin and bind to the user’s own proteins. This is called delayed or Type IV hypersensitivity or chemical sensitivity. The dose of chemicals, frequency of exposure, and skin condition are among the most important factors in causing sensitization. The symptoms of Type IV hypersensitivity include redness and swelling, which can appear 1 to 3 days after exposure and can last for several days. With each exposure, the individual becomes more sensitized, and the reaction becomes more intense. In severe cases, the sensitivity reaction will include thickened skin, pimples, blisters, and other skin sores.

Two major characteristics distinguish ICD from ACD. ICD develops shortly after exposure, while ACD usually develops 1 to 3 days later and lasts longer than ICD. Second, ICD is always confined to the area of exposure; ACD may extend beyond the area of exposure, even on distant skin areas.

Urticaria and Anaphylaxis
are clinically dissimilar reactions, but both are manifestations of the same type of hypersensitivity referred to as Type I or Immediate. Type I hypersensitivity is also an immunological reaction; in contrast to contact dermatitis, it is caused by proteins present in raw NRL. Some of these NRL proteins remain on finished NRL products, regardless of the manufacturing processes. With use of the NRL products, the proteins may penetrate the user’s skin or any other body tissue that may be directly exposed. The proteins may cause antibody production that increases with each subsequent exposure. A number of exposures may occur before any clinical symptoms appear.

The type and severity of reaction depend on the level of sensitivity, the amount of allergen, and the site of exposure. If contact with the allergen is through the skin, urticaria can develop in 10 to 30 minutes after exposure. The appearance of the skin reaction differs clearly from the appearance of ACD or ICD. Urticaria is characterized by pink hives and swelling, often accompanied by itching and tingling. A respiratory exposure to the allergen could result in a runny nose, wheezing, and difficulty in breathing.

Anaphylaxis, the most severe Type I allergy reaction that may appear in individuals sensitive to NRL proteins, occurs if the allergen is introduced directly into the blood. Anaphylaxis is a potentially life-threatening reaction characterized by facial swelling, difficulty in breathing, rapid heart rate, and a severe drop in blood pressure. Rapid intervention with antihistamine drugs will relieve the symptoms relatively quickly. If the appropriate therapy is not given, anaphylaxis may be fatal.

Type I allergy is also linked to genetic factors, making some individuals more sensitive than others. Therefore, individuals who have other allergies and are frequently exposed to NRL proteins would be at the highest risk to develop an allergy to NRL, usually after multiple exposures. Only about 1% of the general population is affected by this problem. However, the highest prevalence of Type I latex allergy (5% to 15%) is found in occupationally exposed individuals, such as healthcare providers and hospital personnel. It is also known that allergens in NRL have some similarity to those in chestnuts and some tropical fruits such as kiwi, avocado, and bananas. Therefore, individuals with fruit allergies may react to NRL products without ever having a previous reaction to NRL. Likewise, allergic reaction in NRL-sensitive individuals may be triggered by fruit consumption.

Which diagnostic tests are available and appropriate?

Identification and proper diagnosis of adverse reactions to NRL is an essential step for determining proper medical treatment and proper behavioral patterns to prevent further reactions. A review of the medical history and an accurate description of the symptoms may pinpoint the specific type of allergy and indicate appropriate testing. In some cases, frequently exposed individuals with a diagnosed Type IV allergy may also subsequently develop a Type I allergy.

Patch Test.   When irritant or allergic contact dermatitis is suspected, the patch test is a common diagnostic tool. Shielded application of the test material to intact skin will identify sensitized individuals. Irritant contact dermatitis can be distinguished from allergic contact dermatitis by the time of onset and duration of the skin reaction.

Skin Prick Test.   This is the preferred test method in the diagnosis of Type I allergy to latex proteins. NRL proteins are introduced through the skin by skin puncture. If an individual is sensitized, a reaction will develop in 15 to 20 minutes and is graded according to the diameter of redness and the swelling at the test site.

RAST Test.   This is an in vitro test for detection of allergen-specific antibodies in a patient’s blood (Type I). Recent technical improvements have increased the sensitivity of the test, making it a simple and reliable test for detection of sensitized individuals. The advantage of this in vitro test is that it can identify sensitization before the appearance of clinical symptoms. However, if the RAST test is positive, it should be followed by the skin test to confirm and to grade the level of sensitivity. Healthcare workers and other individuals frequently exposed to NRL products are encouraged to be tested regularly.

How can reactions be prevented?

In the case of irritant contact dermatitis, it may be helpful to identify different types of gloves and switch from one to another. A similar approach may be used for allergic contact dermatitis. Manufacturers, aware of this problem, have manufactured products with reduced amounts of residual chemicals and labeled them “Hypoallergenic.” In general, such gloves are an improvement and can be used by individuals who have had reactions to other gloves. However, to avoid possible confusion with protein allergy, the label “Hypoallergenic” will soon be replaced with a statement that clearly indicates a reduced content of sensitizing chemicals.

Type I allergy to NRL proteins is complicated. Severely sensitized individuals may develop a reaction to minute amounts of allergen. Manufacturers are making efforts to reduce the protein levels on their NRL products; but, it is not presently possible to make a “protein-free” latex product, or to measure extremely small amounts of protein on the products. With presently available methodology, reliable measurement cannot be made below 50 ug protein/g of NRL, an amount that may still cause a reaction. Therefore, for highly sensitized individuals, avoidance of NRL products is presently the only safe measure. Considering the wide use of rubber in medical and consumer products, this may be an extremely difficult task. FDA is issuing a rule requiring manufacturers of NRL medical devices to label all their products accordingly.

For other frequent users of NRL devices, a careful selection of low protein products is very important to prevent further sensitization. FDA has recently cleared for marketing a number of gloves that claim a minimum measurable level of protein (less than 50 ug/g of NRL). These gloves would be less likely to sensitize individuals but may still cause a reaction in those already sensitized. Both the American College of Allergy and Immunology and the American Academy of Allergy and Immunology have issued recommendations for diagnosis of NRL allergy and prevention procedures for hospitals and healthcare settings. Many hospitals have already developed specific procedures for NRL-sensitive patients and hospital personnel.

Vesna J. Tomazic is a Biologist/Immunologist in CDRH’s Office of Science and Technology.

Although it is important for FDA to learn of adverse incidents caused by medical devices, only a written report is necessary. We do NOT need to receive and inspect the device.

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