Background
Allergy to natural rubber latex is common and serious in children and adults. Latex is the milky fluid derived from the lactiferous cells of the rubber tree, Hevea brasiliensis. It is composed primarily of cis -1,4-polyisoprene, a benign organic polymer that confers most of the strength and elasticity of latex. It also contains a large variety of sugars, lipids, nucleic acids, and highly allergenic proteins.
More than 200 polypeptides have been isolated from latex. Latex proteins vary in their allergenic potential. Protein content varies with harvest location and manufacturing process. Basic knowledge of the manufacturing processes aids in understanding the medical problems related to latex exposure. [1]
Freshly harvested latex from Malaysia, Indonesia, Thailand, and South America is treated with ammonia and other preservatives to prevent deterioration during transport to factories. Latex is treated with antioxidants and accelerators to strengthen the product during the manufacturing process, including carbamates, mercaptobenzothiazoles, and thiurams, which have allergenic potential of their own. [2, 3] It is then shaped into the desired object and vulcanized to produce disulfide cross-linking of latex molecules.
After being dried and rinsed to reduce proteins and impurities, the product frequently is dry-lubricated with cornstarch or talc powder. Powder particles rapidly adsorb residual latex proteins; other proteins remain in soluble form on the surface of finished products.
Latex is ubiquitous in modern society and particularly in health care. William Halstead first used latex surgical gloves in 1890. Latex has been used in a myriad of medical devices for decades. In the late 1980s, however, latex glove use in healthcare skyrocketed, driven by efforts to reduce occupational exposure to blood-borne pathogens, particularly human immunodeficiency virus (HIV). Billions of pairs of medical gloves are imported to the United States annually, often as powdered, nonsterile examination gloves.
In the 1980s and 1990s, heightened demand for latex to manufacture gloves and other objects resulted in hundreds of new, poorly regulated latex factories in tropical countries. The incidence of minor and serious allergic reactions to latex began to rise rapidly among patients and health care workers (HCWs) around the world. [4, 5, 6, 7, 8] Latex sensitization can occur after skin or mucosal contact, after peritoneal contact during surgery, and after inhalation of aerosolized particles with adsorbed latex on their surfaces.
See All About Allergies: Be Ready for Spring, a Critical Images slideshow, to help identify a variety of allergens and symptoms.
For related information, see Medscape's Allergy & Immunology Resource Center.
Pathophysiology
Latex exposure is associated with 3 clinical syndromes.
Irritant dermatitis results from mechanical disruption of the skin due to the rubbing of gloves and accounts for the majority of latex-induced local skin rashes. It is not immune mediated, is not associated with allergic complications, and is not the subject of this article. It may be confused with Type IV hypersensitivity. Any chronic hand dermatitis in HCWs raises the risk of nosocomial infections, including blood-borne pathogens, and should be addressed to identify and remove irritants.
The second syndrome is a delayed (type IV) hypersensitivity reaction, resulting in a typical allergic contact dermatitis. Symptoms usually develop within 24-48 hours of cutaneous or mucous membrane exposure to latex in a sensitized person. The primary allergens are residual accelerators and antioxidants left from the original manufacturing process. Langerhans cells process the antigens and present them to cutaneous T cells. Multiple objects can cause sensitization, but the most common sources in this country are probably nonsterile examination gloves for adults and shoe soles for children. Type IV hypersensitivity is more common in atopic individuals. The dermatitis may predispose patients to further sensitizations or infections.
The third, most serious, and least common syndrome is immediate (type I) hypersensitivity. It is mediated by an immunoglobulin E (IgE) response specific for latex proteins. As noted, latex proteins are highly allergenic, and they are variable between lots from different plantations, factories, and manufacturers. Cross-linking of IgE molecules on mast cell and basophil cell membranes by latex protein allergens triggers the release of histamine and other mediators of the systemic allergic cascade in sensitized individuals. [9]
Exposure can occur following skin, mucous membrane, or visceral/peritoneal contact. Powdered latex examination gloves have been the most frequent source of sensitization in adults, causing cutaneous and inhalational exposures, most often affecting the HCWs wearing them. (Fortunately, their use is decreasing as many hospitals move toward powder-free, "low-allergen," or nonlatex glove products.) [10]
It also can follow inhalation of latex-laden particles or bloodstream exposure to soluble latex proteins following intravascular access procedures. [11] Anaphylaxis during anesthesia and in the perioperative period is increasingly recognized as a manifestation of type I allergy to latex. [12, 13, 14] These events can occur intraoperatively during surgery childbirth, gynecologic or obstetrical procedures, and dental procedures as well. Anaphylaxis can also occur from contact with balloons, condoms, diaphragms, rubber-handled sports equipment, pacifiers, bottle nipples, and adhesives for hair extensions. [15] It can be fatal without emergency treatment. [16]
Sensitization is more common in atopic individuals. Symptoms generally begin within minutes of exposure. The spectrum of clinical manifestations includes localized or generalized urticaria, rhinitis, conjunctivitis, bronchospasm, laryngospasm, hypotension, and full-blown anaphylaxis.
Epidemiology
Frequency
Latex allergy is present in 1%–5% of the general population, with an increased prevalence in atopic individuals. Latex allergy is increased in populations with chronic occupational exposure to latex. [17] It is found in 8%–12% of healthcare workers (HCWs) [18] and in at least 10% of rubber industry workers. [19] Symptoms of latex allergy have been described in 14% of a group of EMS providers and in 54% of a pediatric ED staff. [20, 21, 22] Atopy raises the risk of occupational sensitization.
The highest prevalence of latex allergy (20%–68%) has been reported in patients with spina bifida or congenital urogenital abnormalities. Sensitization in these patients apparently follows multiple urinary tract, rectal, and thecal procedures, as well as multiple surgeries during early childhood. Children with spinal cord injuries also have increased incidence of latex allergy, [23] although children with spinal dysraphism in one study had a low prevalence. [24] Patients with spina bifida may have a genetic predisposition for latex sensitization. Patients with spina bifida and human leukocyte antigen (HLA) alleles DRB and DQB1 were more likely to have a specific IgE response to a common latex antigen. Again, within this risk group, atopic children are at increased risk.
Other patients with a history of multiple surgeries or other latex-exposing procedures are also at increased risk relative to the general population. Patients with cerebral palsy, intellectual disability, or paraplegia also appear to have increased risk of latex allergy, probably because of repeated medical exposures.
It is important to note that the degree of exposure is the most important factor that enhances a person's likelihood of being sensitized to latex allergens. Apprentices starting careers in animal health, pastry making, dental hygiene, and veterinary medicine had a 70% prevalence of skin sensitivity to latex. This is more common in students further along in their studies (e.g., third-year students) rather than those just beginning. The sensitizing dose with repeated exposure measured by inhibition immunoassay was 0.6 ng/cubic meter. [25]
Finally, the prevalence of latex allergy is increased in persons with allergies to avocado, banana, chestnut, kiwi, papaya, peach, or nectarine. Cross-reacting antigens have been found between these tropical fruits and latex.
The occupational and nonoccupational risk patterns described above are similar in other developed countries, documented in an extensive international literature now focused more on interventions to reduce latex allergy in HCWs and other populations than on simply describing their increased risk. [2, 26, 27] Workers with occupational exposure during harvesting and/or processing latex in developing countries where H brasiliensis is grown have an increased risk relative to the general populations. [17, 28]
Mortality/Morbidity
Patients with type I hypersensitivity are at risk of developing anaphylaxis and/or respiratory obstruction, which can be fatal.
Deaths have been reported following the intraoperative or procedural use of latex devices. Latex anaphylaxis has occurred after childbirth, instrumentation, intravenous injection, balloon blowing, condom use, and hyperbaric treatment. [16, 12, 14, 13, 29]
Although most patients can be treated effectively for type IV and type I reactions without clinical sequelae, major allergy may prevent them from pursuing certain careers, using many household and workplace objects, and seeking timely medical care due to justified fear of latex exposure.
Demographics
Incidence in males and females is equal. Latex allergy probably is more common in children and younger working adults because of the increased medical and/or occupational exposure over the past decades.
Prognosis
Most latex-allergic patients can function normally by avoiding significant latex exposure at home, at work, and in medical/dental situations.
Some patients will become more sensitized and have greater difficulty functioning.
A small percentage of patients with IgE-mediated allergy become so sensitized that inadvertent exposure to minute amounts of latex, either by contact or inhalation, causes frequent life-threatening episodes.
In the absence of effective immunomodulatory therapy, avoidance of latex and excellent ED care must be the patients' mainstays.
Patient Education
Patients can and should be referred to local or national support groups to stay abreast of new developments in latex-free devices that may make their lives safer and more convenient.
These groups frequently maintain lists of latex-safe medical and dental practices; many track regulatory and legislative developments.
