Latex Allergy

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.

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.

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, mental retardation, 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. 

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.

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.

Symptoms of delayed (type IV) hypersensitivity usually develop within 1-2 days of exposure. Immediate (type I) hypersensitivity causes symptoms within minutes of exposure. Immediate symptoms may include the following:

• Pruritus of exposed skin and mucous membranes

• Edema of the skin, mucous membranes, or subcutaneous tissues

• Hoarseness

• Tearing

• Rhinitis

• Dyspnea

• Lightheadedness, syncope

• Abdominal cramping

• Nausea, vomiting

• Diarrhea

See the list below:

• Rash

  • Erythema, edema, papules, and vesicles in areas of direct contact (type IV)

  • Erythema, thickening, and pigment changes with chronic exposure (type IV)

  • Urticaria, localized or generalized (type I)

• Angioedema

• Conjunctivitis

• Rhinitis

• Stridor

• Wheezing

• Hypotension, shock

The source of latex exposure may be obvious or occult. The history of latex allergy may be known or unknown. Individuals may be exposed to latex through their skin, mucous membranes, or airway (ie, oral, nasal, or endotracheal tissue). Medical procedures may cause reactions in sensitized providers or patients. Inadvertent inhalational exposure is frequent in medical settings where aerosolized latex-laden glove powder may remain airborne for hours; this risk is reduced when powder-free products are used. Inhalational exposure also may occur outside hospitals from use of powder-lubricated latex products or even tire particles in heavy traffic areas. Common sources of latex exposure include, but are not limited to, the following:

• Gloves (eg, examination, surgical, household)

• Tourniquets, blood pressure cuffs

• Stethoscopes

• Catheters

• Intravenous tubing, devices, and ports; syringe plungers

• Electrode pads

• Goggles

• Respirators

• Wound drains and tubes

• Multidose vial tops

• Dental dams

• Tires

• Handgrips

• Carpeting

• Shoe soles, elastic in clothing

• Condoms, diaphragms

• Balloons

• Pacifiers, baby bottle nipples

• Erasers, computer mouse pads, and rubber bands

ED diagnosis and management depends on the history and the physical examination.[30] Results of laboratory tests sent from the ED are not generally available in a useful time frame. Several types of diagnostic studies are useful in nonemergent evaluations.

Total serum IgE may be elevated in patients with type I allergy, but it is neither sensitive nor specific.

Radioimmunoassay test (RAST) results for latex-specific IgE range from 50-100% sensitive and 63-100% specific. Predictive value depends on the exact test used, the patient population, and the source of allergen. RAST can be a useful and safe confirmatory test in patients with suggestive clinical histories. The sensitivity and specificity are improving with newer-generation testing methods.[31]

Enzyme-linked assays of latex-specific IgE (ELISA) may serve the same purpose.[32]

Genomic profiling may become a useful tool for predicting risk, guiding therapy, and understanding pathophysiology in latex allergy.[33]

Skin patch testing is useful in identifying specific allergens in patients with type IV hypersensitivity to latex products.[34]

Skin prick testing (SPT) with latex extracts is sensitive, specific, and rapid; however, it carries the risk of anaphylaxis.[35] Significant variability in the allergen content of extracts continues to limit the reliability and reproducibility of this test. SPT is an important step in the diagnosis of IgE-mediated occupational allergic disease. It is utilized in latex allergy, however, the outcome is related to the quality of allergen extracts. Unfortunately, there are no standardized extracts commercially available in the United States. There are some standard extracts in Europe. These were developed with natural rubber protein latex for oral testing and the results show that both protein and antigen contents of the SPT solution varies remarkably depending upon the manufacturer.[36]

Testing with glove fingertips applied to the patient's skin is useful when the history is consistent with latex allergy but the blood tests are negative. It carries the risk of anaphylaxis in type I-sensitized patients.

Specific IgE measurement through ImmunoCAP and the Immuno Solid-phase Allergen Chip (ISAC) has also been utilized. The ImmunoCAP system has the following eight single recombinant latex allergens available: rHev b 1, 3, 5, 6.01, 6.02, 8, 9, and 11. 

The ISAC test includes less antigens and relies on immunofluorescence anti-IgE. It includes rHev b 1, 3, 5, 6.01, and 8. These tests in general are very specific but not as sensitive. The most important selective allergen is Hev b 8, which is common between these two tests. ImmunoCAP is a more sensitive test, however. This has to be correlated with occupational exposure.

Flow cytometry to determine basophil activation is another alternative method to diagnose latex allergy. It is based on the determination of activated basophils expressing CD 63. The combination of flow cytometry and ImmunoCAP has been shown to be associated with accurate identification of natural rubber allergy to latex in patients.

The blood use test has also been utilized. It is highly sensitive when used with vinyl or nitrile gloves on one hand as a negative control. Finally, the latex allergy challenge test has been used on patients with respiratory symptoms and has shown high sensitivity. Mucus and cutaneous tests are the most reliable, with specificity of almost 100%. The conjunctival allergen challenge showed sensitivity and specificity of 92%–100%.

Latex allergens can be recovered from environmental air, laboratory colds, and subtle dust on the surface of laboratories where powdered rubber latex gloves are used. Samples can be obtained from air conditioning units, but have to be collected on a special filter for adequate analysis.[36]

Diagnosis of latex allergy continues to be challenging. SPT may achieve 62% sensitivity with a homemade solution. Skin tests specific for Hev protein b, 2, 5, 6.01, and 13  have 60% reactivity. In a murine model, contact dermatitis was the striking feature and it is associated with an increase in IgE. This suggests that latex sensitivity in humans can be a combination of type I and type IV reactions in some situations.[37]

If type I latex allergy is suspected, all procedures should be performed with latex-free instruments, devices, and protective clothing.

Preprocedure screening by history should include risk factors such as occupational and nonoccupational risk groups, tropical fruit allergy, and atopy as well as documented latex allergy.

Treatment consists of oral immunotherapy with useful results, but subcutaneous immunotherapy appears to be more successful. Unfortunately, this only applies in case reports. It is also specific to patients who have rhinitis and conjunctivitis from latex. Avoidance is the mainstay of treatment for type I and type IV reactions. The extract that was used in some studies contained 5 HEP/mL manufactured by ALK.  Average maximum tolerated dose was 11.1; this seems to be more effective.[36]

In the presence of viral epidemics and pandemics such as Covid, wearing gloves has become an important barrier. Reactions due to latex and additives continue to be a challenge. Education, avoidance, and vigilance are important.[38]

Prehospital providers should be aware of the risk of latex allergy in patients and providers.

Search for and read MedicAlert-type bracelets.

Note the patient's history of relevant allergies to medical devices or fruits.

To rule out latex allergy that could worsen with further medical exposure, review the patient's history of activities/exposures immediately preceding any systemic allergic reaction.

Use powder-free latex gloves or, ideally, high-quality nonlatex gloves to minimize risk to patients and providers in all circumstances. Latex-free resuscitation and intravenous (IV) access equipment should be available for high-risk patients. Do not give medication from rubber-topped multidose vials or through latex IV ports in latex-allergic patients.

Patients with known or suspected latex allergy who seek care for unrelated medical conditions or injuries must be kept within a latex-safe environment to prevent serious complications. This includes all patients with spina bifida.

Patients presenting with frank symptoms of type I latex allergy are treated as any other patients with systemic allergic reactions, except they must be protected from further latex contact to avoid clinical deterioration. Many EDs, hospitals, and medical offices represent very high-risk environments for latex-sensitive patients, particularly if powdered latex gloves are still in use.

• Latex-free resuscitation equipment must be available. This frequently is accomplished with a mobile, latex-free cart carrying non-latex intubation and ventilation equipment, IV tubing, syringes, tourniquets, electrode pads, gloves, masks, and medication vials.

• Routine care of high-risk patients should use non-latex supplies. Major reactions in sensitized patients have been precipitated with pelvic and rectal exams using latex gloves, urinary catheterization with latex catheters, IV medication given through latex ports, and inhalation of aerosolized latex glove powder.

• Consultants must be aware of the need to completely avoid latex exposure to the patient during examinations and procedures.

• Patients needing studies in other hospital areas, such as radiology, must be transported without risking latex exposure.

• Identification of latex versus non-latex medical devices traditionally has required laborious contacts with individual manufacturers. Since 1999, the US Food and Drug Administration has required all manufacturers to apply warning labels to medical devices containing natural rubber latex.[39] This regulation has helped to facilitate safe care of patients who are allergic to latex. In addition, medical device manufacturers have developed many latex-free alternatives for routine care and invasive procedures. However, providers should be aware that package labeling for latex content may not be clear, and that latex-containing medications and devices can be mistaken for latex-free products in busy clinical settings.

Consultants must be aware of the need to scrupulously avoid exposing the patient to latex during exams and procedures.

Latex allergies are best treated with patient education to avoid further exposure. Even HCWs may be poorly informed about latex allergy risk factors, clinical syndromes, and preventive approaches.[26] Type I reactions are treated as any other systemic allergic reaction. The cornerstones of treatment are epinephrine and H1 antihistamines. Systemic corticosteroids and H2 blockers may be useful. Please see articles on Anaphylaxis, Angioedema, and Asthma for details of therapy. No specific immunotherapy has been shown to be effective.

Type IV reactions (localized contact dermatitis) are unlikely to require ED treatment. They can be treated with topical steroids and patient education to avoid further exposures.

All patients with type I latex allergy should carry a subcutaneous epinephrine kit at all times.

Patients and their families should be educated to identify and avoid latex in home, work, and medical/dental settings.

Patients should be referred to an allergist or primary care provider for follow-up.

Patients should be aware of the life-threatening complications of anaphylaxis, bronchospasm, and laryngospasm.

Patients with type I hypersensitivity should carry subcutaneous epinephrine kits at all times.

Patients should obtain and wear a MedicAlert-type bracelet identifying their allergy.

Patients should be aware of the risk of cross-reacting fruit allergies.

Patients with major latex allergies who are admitted for allergic complications or unrelated conditions must be moved to latex-safe rooms with clear warnings on doors and charts.

All examinations and care must be done without use of latex-containing devices or equipment.

All providers should be educated to avoid inadvertent exposure.

Latex is the second most common cause of intraoperative anaphylaxis, which can be difficult to diagnose because of infrequent cutaneous signs and patients' inability to express symptoms.[16, 14] Known latex allergy or a history suggestive of major latex allergy should trigger the use of latex-free operating rooms and postoperative care.

Hospitals should make policy and purchasing decisions to minimize latex exposure in the institution, with the goal being to protect sensitized patients and employees as well as to reduce the risk of primary sensitization. Several cost analyses have found that becoming latex-safe is cost-effective for health care facilities.[40, 41]

Minimally, this requires reducing or eliminating powdered latex examination gloves and substituting less allergenic latex gloves or, ideally, high-quality nonlatex gloves. This strategy has been shown to reduce natural rubber latex aeroallergen, sensitization of exposed HCWs, and incidence of asthma in HCWs.[42, 43] Follow-up studies of latex allergic HCWs have shown a reduction in latex-specific IgE antibodies after latex use is substantially reduced in the healthcare workplace.[44, 45, 46, 27]

It also requires clear guidelines for the safe treatment of sensitized patients and for the accommodation of sensitized employees.

Multidisciplinary hospital committees can be effective in accomplishing these goals.

Non-healthcare workplaces should address the risk of workplace anaphylaxis.[47]