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Disease Summaries

Latex Reactions: Allergic and Non-Allergic Hypersensitivity

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Posted: July 2004


Professor Connie Katelaris MB BS PhD FRACP (FAAAAI FACAAI)
Clinical Associate Professor, Dept of Clinical Immunology and Allergy
Westmead Medical Centre
Westmead, Australia

Latex

Latex that is used commercially is derived from the rubber tree (Hevea brasiliensis), one of the many worldwide lactifer plants, which include Ponsettia (Euphorbia pulcherrima) and Castor Bean (Ricinus communis).

Lactifer plants are unique in that they contain cells that secrete a milky substance - latex. Latex circulates in branched tubes throughout the plant tissues and is rich in hydrocarbon cis-1, 4 polyisoprene, which can cross-link to form a plug that can heal cuts in the surface of the plant, similar to the way a blood clot occurs in a human wound.

Latex allergens

Approximately 12% of harvested latex is treated either with 0.7% of ammonia alone (high ammoniated latex) or with 0.2% ammonia and thiuram (low ammoniated latex) and used in the production of "dipped" products such as condoms, balloons and gloves. These account for the majority of the reactions to latex. Most of the harvested latex is acid-coagulated to form dry sheets or crumb rubber and then "vulcanised" by treatment with sulfur at extremely high temperatures for prolonged periods of time, resulting in low-to-undetectable levels of allergenic proteins which render the particles non-allergenic. This explains why clinical reactions do not occur in latex allergic patients driving on or walking by roads where levels of latex particles are high.

The most important components of latex that cause clinical reactions are water-soluble membrane-bound proteins. There are at least 11 recognized latex allergens (molecular weight 4.7 to 57 kDa) of which Hev b 1 to Hev b 6 are considered of major importance as causes of clinical reactions, whilst Hev b 7 to Hev b 11 are considered to be of less (minor) significance. Hev b 1 - the rubber elongation factor - is involved in the biosynthesis of propylisoprene, while others such as Hev b 5 exhibit close homology to other plant and fruit allergens such as Kiwi fruit protein pKIWI501. Latex is frequently referred to as natural rubber latex or NRL. This convention is not universal, and therefore the term latex will be used in this educational module.

Allergic and Non-allergic Hypersensitivity

Non-allergic Hypersensitivity

Irritant Contact Dermatitis-ICD (non-allergic contact dermatitis) (see Contact Dermatitis): This example of non-allergic hypersensitivity is the most common clinical reaction to latex products. Dry, itchy, irritated lesions occur on the skin, usually of the hands, associated with heavy use of latex gloves. The sweating caused by wearing gloves may be sufficient to cause a reaction, but other factors include frequent hand washing, incomplete drying of the hands and the use of cleansing products and disinfectants. Cornstarch glove donning powder is an additional irritating factor by producing an alkaline pH (9) of the skin. Irritant contact dermatitis is an important risk factor for the development of latex protein allergy.

Allergic Hypersensitivity

Allergic Contact Dermatitis (ACD) (see Contact Dermatitis): This is a delayed allergic reaction (also referred to as a Type IV reaction) mediated by lymphocytes exposed to the chemicals added to raw latex during harvesting, processing and manufacturing, particularly rubber accelerators such as thiurams, carbamates and mercaptobenzothiazole, and the black dye paraphenylenediamine. Upon re-exposure, individuals already allergic to these chemicals develop the typical red raised blistering lesions characteristic of contact dermatitis within 48-72 hours. The lesions are usually confined to the area of contact but may spread more extensively. Allergic contact dermatitis is a risk factor for the development of latex protein allergy.

Latex Protein Allergy (LPA): This IgE-mediated allergic reaction, also referred to as a Type 1 reaction, began to be more widely recognized in the late 1970s. A typical reaction develops in minutes after contact with latex by those who have developed IgE-antibodies to latex proteins. Symptoms may include:

  1. Contact urticaria - localized or generalized.
  2. Rhinosinusitis and conjunctivitis.
  3. Asthma.
  4. Anaphylaxis - rarely.

Contact with latex in sufficient concentration can provoke chronic symptoms of the skin, eyes and respiratory tract due to sensitization to latex protein allergens. (See the modules in this series - rhinosinusitis, ocular allergy, urticaria, contact dermatitis and anaphylaxis.)

Prevalence

An increase in the incidence of latex protein allergy occurred in the late 1980s, most probably as a result of two factors:

  • The recommendations by lay and government agencies for prevention of HIV transmission in health care settings, commonly referred to as "universal precautions." These rules and regulations mandated that health care professionals use barrier protection, including latex gloves, to protect against transmission of infectious organisms.

  • Implementation of "universal precautions" caused a dramatic increase in the manufacturing of latex gloves, with changes in processing that decreased leaching of latex proteins, with a resultant increase in the allergenicity of latex products.

Approximately 50% of all cases of latex protein allergy have been reported in health care professionals, and the prevalence in this group ranges from 2% to 15%. The reasons for this wide range are unclear but could to some degree be explained by methodological differences in various studies, e.g., lack of standardized allergen preparations for testing to confirm IgE-sensitization to latex proteins, and differences in ascertainment of the study populations. Although there may be a higher incidence of clinical symptoms related to latex in healthcare professionals, because latex is used primarily in this area of work, epidemiological studies show that sensitization is the same in healthcare professionals as in the lay population.

Development of Latex Protein Allergy

Latex proteins can sensitize in the following manner:

  • Inhalation of powder particles to which latex allergens have been absorbed, when gloves are donned or discarded.
  • Absorption through the skin from latex products, when latex allergens are either solubilized by body secretions or pass through skin damaged by trauma, irritation or contact dermatitis.
  • Absorption through mucous membranes from condoms, the rubber tips of barium enema applicators, or during internal examinations with latex gloves. The allergenic protein content varies widely among various latex-containing medical devices and even between different batches of the same medical products.
  • Direct entry into the body, when latex protein is present in intravenous injection ports or during surgical procedures when the physician and/or other healthcare professional is using latex gloves.

Risk Factors

People at increased risk for the development of latex protein allergy include:

  • Physicians and other healthcare professionals
  • Other individuals who use latex gloves
  • Rubber industry workers
  • Patients undergoing multiple surgical operations
  • Condom users
  • Atopic individuals

Medical conditions associated with an increased risk of latex protein allergy:

  • Spina bifida
  • Urogenital abnormalities
  • Imperforate anus
  • Tracheo-oesophageal fistula
  • Multiple congenital deformities
  • Ventriculo-peritoneal shunt
  • Cerebral palsy
  • Quadriplegia
  • Pre-term infants

Symptoms and Signs

Symptoms and signs of latex protein allergy are more likely to occur in the following groups:

  • Health care professionals and individuals who work in rubber manufacturing and processing, food preparation, cleaning, gardening and housekeeping.
  • Infants and children undergoing multiple surgical procedures.
  • Children with severe allergic eczema.
  • Individuals with fruit allergy (mostly banana, melon, kiwi and peach)
  • Patients undergoing multiple dental, radiological or gynecological procedures.

The symptoms and signs of latex protein allergy depend upon the affected organ. (See the modules in this series - allergic rhinitis, ocular allergy, urticaria, contact dermatitis and anaphylaxis.)

Diagnosis

Skin Testing

A safe and approved testing solution for latex protein allergens is not available universally, but safe, reliable testing solutions are available in specialized centers. In Europe, ammoniated latex diagnostic allergens are commercially available. Skin prick testing (SPT) is the method of choice to demonstrate IgE-sensitization but should only be performed by specialists since systemic reactions to testing occur in 2% of subjects tested. Enzyme linked immunoassays are reliable alternatives when diagnostic allergens for latex are not readily available. SPT and serological tests are useful to help confirm a diagnosis of IgE-sensitization to latex. Even so, some patients with a strong clinical history of allergic symptoms related to latex can have negative test results, perhaps as a result of non-IgE mediated reactions, or poor quality testing materials.

Cross-reactivity of Latex Allergens

Latex proteins cross-react with a number of proteins from different fruits, vegetables and grains, probably because of common T- and B-cell epitopes.

Studies using skin prick testing of latex protein positive subjects demonstrate that 53% have positive tests to avocado, 40% to potato, 38% to banana, 28% to tomato, 28% to chestnut and 17% to kiwi. The cross-reactivity among fruits, pollens and latex is attributable, to some degree, to the highly conserved plant allergen, profilin, present in all three. Most patients with IgE antibodies to these foods do not have clinical sensitivity to these foods, so a positive skin test does not necessarily mean the food cannot be eaten. Those who have allergic reactions to these cross-reactive foods most often develop the "oral allergy syndrome," i.e., develop oropharyngeal itching and/or facial angioedema. Patients clinically allergic to foods which are cross-reactive to latex should ideally be screened for individual risk for latex allergy with an appropriate history, physical examination and skin test (if available) and/or radioallergosorbent test to latex.

Management

Repeated exposure of latex protein allergic patients may lead to life threatening IgE-mediated reactions. Thus, the medical management of latex allergy is avoiding skin or mucous membrane contact with latex proteins.

1. Reduction in exposure to latex proteins in the workplace:

  • Where possible, latex gloves should be replaced with non-latex gloves, although latex gloves remain the best barrier against infectious organisms.
  • Latex gloves should be powder free and contain a low protein content.

These measures should help to reduce the overall prevalence of latex protein allergy.

2. Reduction to exposure to latex proteins in the home:

If a patient has a history of non-life-threatening reactions to latex, e.g., contact urticaria, mild asthma, rhinitis or conjunctivitis, advise a realistic and practical approach to latex avoidance; excessive latex avoidance is unnecessary, financially costly, and impacts on lifestyle. If there is a history of life-threatening reactions to latex, e.g., severe asthma, angioedema or anaphylaxis, closer vigilance is necessary. The most important products to avoid are latex gloves (either worn by the individual, or used during surgery), latex condoms, and latex-containing medical products such as catheters, and advise patients against blowing up latex balloons. Household items, clothing, and sports equipment containing latex are more likely to affect people who experience contact dermatitis if they come into contact with latex.

Where necessary, advise replacement of latex with non-latex products:

Latex Product Non-Latex Product
Balloons Synthetic latex balloons
Baby bath toys Plastic toys
Belts Leather
Condoms Sheep cecum condoms - for birth control only (if locally available). THESE ARE NOT GOOD BARRIERS FOR INFECTIOUS ORGANISMS. There are non-latex condoms, called deproteinized latex condoms, which are tolerated by latex-allergic patients.
Elastic bands/erasers Paper clips/non-rubber erasers
Feeding nipples Silicone nipples
Gloves Synthetic latex or cotton
Rubber boots Clear vinyl "rubbers"
Sports shoes Leather shoes
Shoes with rubber bottoms Synthetic or leather bottoms
Swim and goggle fins/rims Clear plastic fins/rims
Racquet handles Leather handles
Telephone cords Clear cords
Thong sandals Leather sandals
Other clothes and household items should be checked for the presence of latex Advise replacement with cotton, leather or synthetic materials

It is, however, important to stress that, because of the way latex is processed, many forms of rubber are not dangerous to latex protein allergic individuals, for example, rubber soles, basketballs, latex in tires, and many other products.

Managing the Patient with Latex Protein Allergy

Patients with latex protein allergy should:

  1. Wear a medic alert bracelet or necklace, especially if the allergy is severe and life threatening.
  2. Inform parents and family, employers, school personnel, care givers and healthcare professionals about their latex protein allergy.
  3. Be given a list of latex-containing products most likely to cause a reaction and use safe alternatives.
  4. As necessary, be prescribed an epinephrine auto-injector.

Medical sources of latex may include the following items. Where necessary, avoid the following:

  • Gloves
  • Blood pressure cuffs
  • Catheters
  • Dental devices
  • Face masks and straps
  • Tourniquets
  • Wound drains
  • Injection ports
  • Electrode pads
  • Bulb syringes
  • Bandages
  • Rubber in syringe stoppers
  • Stethoscope tubing

Communicate latex precautions to healthcare professionals:

  1. Alert healthcare professionals to the potential for latex protein allergy.
  2. Printed precautions and alternatives should be in place to care for latex protein allergic subjects.
  3. Latex protein allergy should be noted on the patient's chart/notes.
  4. A medical alert bracelet or necklace is useful for the severe allergic subject.
  5. Appropriate caution should be taken by physicians and other healthcare professionals in clinical settings.
  6. Health care professionals who use latex gloves should wash carefully and change their outer garments before they treat the highly latex protein allergic patient.