Chapter 29
LATEX

Carol A. Epling*

OCCUPATIONAL SETTING

Contemporary awareness of the problem of occupational latex hypersensitivity (LH) began in 1979 with Nutter’s report of a case of contact urticaria produced by latex gloves.1 Over the next 10 years there were a few literature reports of occupational latex allergies, but the problem remained a minor curiosity to occupational physicians. About 1990, however, the trickle of reports expanded into a steady stream, and LH became recognized as a significant occupational problem, particularly for healthcare workers.

Various theories have been advanced to explain this phenomenon. Perhaps the most plausible is that occupational exposure to latex antigens was low until the implementation of universal precautions in the late 1980s prompted an increase of more than 10-fold in the use of powdered natural rubber latex gloves. As the usage increased, manufacturers reduced quality control in an attempt to keep pace with demand, and new manufacturers with little experience entered the market. This led to a marked rise in the antigen content of latex gloves. The juxtaposition of elevated antigen content and increased wear time probably increased the latex antigen exposure of the typical healthcare worker by more than an order of magnitude. Meanwhile, the prevalence of latex-related problems rose markedly throughout the 1990s. While case reporting may have increased somewhat due to greater physician awareness, there can be little doubt that there was a dramatic increase in both the prevalence and severity of latex-related occupational illness.

The occupational population at risk for latex allergy comprises primarily end users of latex gloves, predominantly healthcare workers. As a group, healthcare workers account for almost all the occupational epidemiology studies of latex allergy. However, numerous other groups have significant occupational exposure to latex. These include morticians, hairdressers, greenhouse workers, food handlers, and a variety of manufacturing workers. Interestingly, the literature contains few reports of latex allergy associated with the manufacture of latex products. This may be related to the movement of much of latex product manufacturing to overseas locations and to relatively low exposure to latex aerosols during production. As a result, this chapter will focus on latex allergy and latex glove dermatitis in healthcare workers. It should also be noted that persons with spina bifida also have a significant risk of latex allergy, attributed to repeated mucous membrane exposures to latex from operations early in life.

EXPOSURE (ROUTE)

Exposure to latex antigens typically occurs through skin contact and inhalation. Although ingestion is a theoretical possibility, there have been no reports of occupational exposure by this route. Skin exposure occurs primarily by direct contact with latex products such as gloves. Latex gloves contain highly variable amounts of extractable protein, which acts as the antigenic material. The wearer’s skin moisture provides an effective mechanism for extraction of these antigens. Glove powder also provides an effective vehicle for the transfer of latex antigen from the glove matrix to the wearer’s skin. Although the proteins that comprise the latex antigen are nonvolatile, they bind to glove powder. When the glove is donned or removed, a puff of glove powder with bound antigen is released into the air as an aerosol that can be inhaled by the wearer or nearby coworkers. When this process is extrapolated to an area such as an operating room or a laboratory, where dozens of workers may don and remove dozens of pairs of gloves each day, the potential for inhalation exposure can be magnified. Thus, glove powder can act as a classical vector. Latex antigen exposure can be estimated by the latex content of gloves, the duration of wear, the route of exposure (with mucosal and parenteral routes thought to be most significant), and the average daily number of glove pairs worn by the worker and coworkers. Considering these variables, the prevalence of LH in subsets of the population correlates roughly with the intensity of latex antigen exposure (Table 29.1).

TABLE 29.1 Prevalence of latex hypersensitivity according to exposure group.

Population Prevalence (%)
General population 0.5–1.0
Healthcare workers 3–15
Clinical laboratory workers 10–20
Spina bifida patients 35–65

Note that reported prevalence varies with measurement technique as well as population.

A meta-analysis of the evidence of LH among healthcare workers using powdered latex gloves found the prevalence of clinical allergy to latex confirmed by IgE diagnostic testing ranged between 4.01 and 4.63%.2 The study by Kelly et al.3 highlighted the importance of healthcare worker exposure to airborne latex antigen leading to the development of LH. The investigators measured airborne latex antigen levels in the workplace before and after replacing powdered latex gloves with nonpowdered latex gloves. Not only was there a quantitative relationship between the prevalence of LH and the concentration of latex antigen in air ducts, but also there was a significant reduction of new onset latex sensitization following glove substitution.

PATHOBIOLOGY

The raw material for natural rubber latex is the milky sap of the rubber tree Hevea brasiliensis (Hev b) grown in Africa and Southeast Asia. This sap is an aqueous emulsion of isoprene droplets (which polymerize to form natural rubber) and a variety of other substances, including over 250 distinct proteins, some 60 of which have been shown to be antigenic. Researchers have identified at least 14 Hev b latex allergens most commonly associated with clinical allergy. Hev b 5 and 6.02, found in dipped rubber products including gloves, are of major importance inducing allergy in latex glove users.4,5 As the sap is processed, various stabilizers and vulcanizing agents are added. These include thiurams, mercaptobenzothiazoles, carbamates, and phenol derivatives. When the emulsion is deposited on hand-shaped ceramic forms and polymerized to form a glove, some of the proteins are adsorbed and trapped in the matrix. Depending on the manufacturing process and the subsequent washing steps, the protein content of gloves can range from undetectable to over 1000 µg/g of finished glove.6

Latex gloves can produce three specific types of problems: irritant contact dermatitis, allergic contact dermatitis, and LH. In addition, all types of gloves can produce nonspecific irritation in the form of hyperhidrosis and maceration of the stratum corneum from accumulation of heat and moisture inside the glove. The vast majority of latex glove problems fall into the category of irritant contact dermatitis (ICD), which is produced by direct local tissue irritation without activation of the immune system. ICD may be immediate or slowly progressive and is characterized by erythema limited to skin areas in direct contact with gloves. It does not spread to noncontact areas or produce more serious sequelae.

Allergic contact dermatitis (ACD) is a Type IV (cell mediated) immune reaction and is typically characterized by a delay of one to several days between exposure and development of local erythema. With chronic glove wear, however, the delay may be less apparent. Although latex proteins may occasionally incite ACD, the antigens for this reaction are usually the low-molecular-weight additives such as thiurams and carbamates. ACD is usually limited to areas in direct contact with gloves, but the rash can occasionally generalize. Frequently, ACD and ICD are difficult to distinguish clinically.

LH is a Type I (IgE mediated) immune reaction and typically occurs as an immediate reaction (within minutes of exposure). LH may occur in a spectrum of presentations (listed in rough order of increasing severity):

  • Positive skin prick test in an asymptomatic patient
  • Contact urticaria
  • Rhinoconjunctivitis
  • Angioedema
  • Asthma
  • Anaphylaxis

Since it is somewhat unusual to see serious reactions such as asthma and anaphylaxis as the initial presentations of LH, some investigators believe that susceptible individuals who experience ongoing exposure to latex will tend to show a progression toward serious manifestations with time. In this respect, LH appears to act like other IgE-mediated responses to protein antigens.

While LH is the least common of latex glove problems, it is potentially the most serious and expensive. When LH is defined by positive skin prick testing, which is the current gold standard, the prevalence is between 3% and 15% for healthcare workers exposed to powdered latex gloves, in general, and possibly higher for laboratory workers. Unfortunately, skin prick testing simply identifies workers with sufficient latex-specific IgE to produce a skin reaction but does not provide a clear estimate of the prevalence of symptomatic disease. In a recent prospective cohort study of healthcare workers exposed to nonpowdered latex gloves, Filon et al.7 reported the incidence of latex sensitization, urticaria, rhinitis, and asthma as 1.0, 0.72, 0.12, and 0.21 per 1000 person-years, respectively. While prevalence of LH was 5.2% among a group using powdered latex gloves, it was 3.2% among newly hired workers exposed to nonpowdered latex gloves.

Several studies have detected a correlation between airborne latex antigen levels and measures of LH.8–10 The corollary of this is that the indices of LH appear to decrease when airborne latex antigen is reduced. These indices include severity of rhinoconjunctivitis, latex-specific IgE levels, and frequency of asthma attacks. Equally importantly, the study of Allmers et al. showed that removal of powdered latex gloves led to dramatic reduction of airborne latex antigen levels within a few days.10

An association between LH and allergies to certain foods has been observed by a number of investigators. The most prominent of these associations are listed in Table 29.2.11 The studies of Mikkola et al. and Posch et al. provide a biochemical model for such cross-reactions.12,13 Using sera from banana- and avocado-sensitized latex-hypersensitive patients, respectively, they identified 31–33 kDa proteins from banana and avocado that cross-react with hevein (one of the major latex antigens).

TABLE 29.2 Major food allergies associated with latex hypersensitivity and their prevalence among latex-hypersensitive patients. Adapted from Kim and Hussain.11

Food Prevalence %
Banana 18
Avocado 16
Kiwi fruit 12
Shellfish 12
Fish 8
Tomato 6
Watermelon, peach, carrot (each) 4
Apple, chestnut, cherry, coconut, apricot, strawberry, loquat (each) 2

Amino acid sequencing revealed that these proteins (class I endochitinases) contain a domain of sequence homology with hevein, which explains the IgE cross-reactivity. Since endochitinases are common plant proteins, this type of cross-reactivity may offer a general explanation for associations between LH and allergies to fruits and vegetables. Other associations with LH include an atopic history, multiple operations, mucosal exposure to latex, and spina bifida.14

DIAGNOSIS

Nonspecific glove irritation is generally characterized by mild local itching or burning in the distribution of glove contact that resolves rapidly with cessation of glove wear. The skin appears normal or pale with possible mild edema and mild fissuring. Excoriation and lichenification are minimal. Usually this can be distinguished clinically from ICD or ACD.

Both ICD and ACD present with local itching, burning, and erythema in the glove distribution. Marked erythema, vesicles, and weeping may be present in severe cases. In chronic cases, fissuring and lichenification may be prominent. ICD and ACD can sometimes be distinguished on the basis of the history of an early reaction in the case of ICD and a delayed reaction for ACD. However, most workers are unable to give a sufficiently detailed history to allow the distinction to be made with confidence. Rashes that begin in the glove distribution but then generalize are not ICD. Both ACD and LH should be considered in such cases. Patch testing with a kit of typical latex additives may clarify the diagnosis by confirming ACD.

LH, like all allergic reactions, is primarily a clinical diagnosis. This is illustrated by analysis of the results of the Multi-Center Latex Skin Testing Study Task Force.15 These results show that a clinical evaluation provides about 90% sensitivity and specificity for diagnosis of LH (defined by subsequent positive skin prick test). In the evaluation, historical features of exposure, proximate symptoms, nature of symptoms, and family history are most important. Reported symptoms should fit into a recognizable pattern of Type I reactions (rhinoconjunctivitis, urticaria, angioedema, asthma, or anaphylaxis). A useful early sign of LH is development of a papular rash consistent with contact urticaria. Extension of the papular rash beyond the area of the glove is further evidence of LH. Physical examination should be used to provide objective confirmation of signs and symptoms but may be unremarkable in the asymptomatic patient. In the occupational setting, consistent provocation of typical symptoms by known work exposure to latex is frequently sufficient to make the diagnosis. In the case of latex-induced asthma, serial peak expiratory flow measurements are sometimes useful.

Laboratory testing is useful but primarily serves to confirm the clinical evaluation. Probably the ultimate diagnostic test is the wear and puff test.16 This involves starting with a finger cut from a high-antigen-content latex glove and wearing progressively larger portions until the entire glove is worn. Development of symptoms is assessed at each stage. If the glove can be worn without symptoms, a glove is inflated like a balloon, and the air inside (with suspended glove powder) is exhausted into the patient’s breathing zone. While highly sensitive, this test can provoke severe asthma or anaphylaxis in susceptible individuals and is not recommended except at specialized centers where occupational aerosol challenge testing is routinely performed.

Skin prick testing is a more practical confirmatory test. A standardized latex skin testing antigen manufactured by Greer Laboratories was evaluated by the Multi-Center Latex Skin Testing Study Task Force and found to be sensitive (sensitivity 95%), specific (specificity about 99%), and safe (no epinephrine-requiring reactions).15 Because the FDA has not licensed this antigen preparation, skin testing for LH in the United States is presently limited to either experimental or foreign (e.g., Canadian) antigen preparations.

In vitro testing for latex-specific IgE has also been used in evaluation of LH. Currently, three FDA-licensed test kits are commercially available in the United States. The characteristics of two of these kits (Diagnostic Products Corp. AlaSTAT and Pharmacia–Upjohn CAP) are comparable, with sensitivity in the range of 75% and specificity in the range of 97% in a population with more than 40% prevalence of LH.17 However, in a population with low prevalence of LH (5% by skin prick testing), the CAP assay demonstrated only 35% sensitivity and 98% specificity.18 Thus, serologic testing is recommended only for confirmation of a clinical suspicion of LH and not for screening in a population at low risk for LH.

TREATMENT

Nonspecific glove irritation usually responds to a glove holiday and/or use of glove liners made from materials such as white cotton or Dermapore.1 Liners should be changed whenever they become damp. ICD and ACD will sometimes respond to the same regimen, but the ultimate treatment is substituting a different glove material for the one that provokes the problem. In the acute phase, a glove holiday combined with treatment using a low- to medium-potency topical corticosteroid is beneficial. This may be combined with astringent soaks in the case of weeping lesions or emollient preparations in the case of dryness. The use of barrier creams is not a suitable alternative to removal from latex gloves, and some authors advise that creams may act as a vehicle for extraction of antigens from latex gloves.14

Symptomatic LH poses a special problem, since the definitive treatment is a complete removal from exposure to latex antigens. Sending a latex-hypersensitive worker back to work in a medical institution usually involves a degree of risk. As mentioned in the 1997 National Institute for Occupational Safety and Health (NIOSH) Alert, one of the most critical issues is whether the workplace is free of powdered latex gloves.19 Institution-wide substitution of powder-free latex gloves for powdered ones has been reported to reduce the level of airborne latex antigen to undetectable levels. Thus, it seems reasonably safe to send workers with LH back to work in institutions that have made this change. Care must still be exercised with activities that tend to release latex particles from reservoirs such as HVAC filters and plenums. The remaining issue is one of helping the worker avoid direct contact with latex. Given the variety of alternative glove materials, selecting alternative gloves need not be a problem. Avoiding contact with latex-containing supplies and equipment (Table 29.3), however, may require detailed examination of specifications for these items. In addition to these measures, LH workers should be educated to follow the recommendations in Table 29.4.

TABLE 29.3 Common items containing latex.

Hospital supplies:
Gloves, barium enema catheters, adhesive tape, EKG electrodes, blood pressure cuffs, stethoscopes, anesthesia masks, surgical masks, goggles, catheters, injection ports
Office supplies:
Rubber bands, erasers, adhesives
Household objects:
Automobile tires, elastic waistbands, dishwashing gloves, condoms, diaphragms, balloons, pacifiers, baby bottle nipples

TABLE 29.4 Recommendations for healthcare workers with latex hypersensitivity.

1. Inform employer, healthcare providers, and family members of latex allergy
2. Identify latex-containing products and avoid contact
3. Wear medical alert bracelet with latex allergy notation
4. Carry and understand the use of an epinephrine injector (e.g., EpiPen)
5. Notify employer’s occupational health service of changes in latex-related symptoms

MEDICAL SURVEILLANCE

Given the prevalence of LH, and that early diagnosis is almost certainly beneficial, LH is suitable for a medical surveillance program.20 Screening can be implemented with a simple symptom inventory for exposed workers, since history is the key feature in LH diagnosis. Workers classified as high risk by screening might undergo subsequent clinical history and physical examination, serial peak expiratory flow measurements, or nonspecific inhalation challenge testing for confirmation. Assuming the existence of an appropriate index of suspicion, clinical evaluation alone is probably sufficient to make the diagnosis in many cases. When a standardized skin testing antigen becomes available, skin prick testing will be the confirmatory test of choice in view of its sensitivity, specificity, and safety. For latex-hypersensitive workers who return to work with some degree of ongoing latex exposure, periodic follow-up in a medical surveillance program is indicated to detect development of new symptoms. If new symptoms occur, further intervention to eliminate latex exposure is vital.

PREVENTION

Primary prevention is aimed at avoidance of high-level and long-term latex exposure in all workers. Careful selection of barrier protection according to risk for contact with infectious materials may reduce the use of latex gloves among workers who are unlikely to encounter infectious substances (i.e., food services, maintenance, and housekeeping). Strict avoidance would mean eventually converting from latex to nonlatex gloves and perhaps making substitutions for latex articles such as Foley catheters and tourniquets that are routinely handled by workers. The cost of substituting nonlatex gloves can be substantial for medical institutions. In addition, wearer satisfaction and barrier properties of nonlatex gloves are significant issues for workers who wear gloves for prolonged periods during direct contact with blood.21 A compromise solution is to convert to low-antigen powder-free latex gloves as suggested by the NIOSH Alert.19 This provides a significant measure of protection from inhalational exposure for latex-hypersensitive individuals and decreases risk for new cases of sensitization.3,22,23

A powder-free latex workplace also affords a measure of secondary prevention for those who already have LH. In this situation, workers with LH, once identified, can return to work wearing nonlatex gloves while exercising caution in tasks that involve handling latex-containing supplies and equipment. One can be reasonably confident that these affected workers will have minimal latex aerosol exposure in this situation. Close medical follow-up, however, is indicated to monitor for possible progression of symptoms.

References

  1. 1. Nutter AF. Contact urticaria to rubber. Br J Dermatol 1979; 101:597–8.
  2. 2. Bousquet J, Flahault A, Vandenplas O, et al. Natural rubber latex allergy among health care workers: a systematic review of the evidence. J Allergy Clin Immunol 2006; 118:447–54.
  3. 3. Kelly KJ, Wang ML, Klancnik M, et al. Prevention of IgE sensitization to latex in health care workers after reduction of antigen exposures. J Occ Environ Med 2011; 53:934–40.
  4. 4. Rolland JM, O’Hehir RE. Latex allergy: a model for therapy. Clin Exp Allergy 2008; 38:898–912.
  5. 5. Yagami A, Suzuki K, Saito H, et al. Hev b 6.02 is the most important allergen in health care workers sensitized occupationally by natural rubber latex gloves. Allergol Int 2009; 58:347–55.
  6. 6. Williams PB, Halsey JF. Endotoxin as a factor in adverse reactions to latex gloves. Ann Allergy Asthma Immunol 1997; 79:303–10.
  7. 7. Filon FL, Bochdanovits L, Capuzzo C, et al. Ten years incidence of natural rubber sensitization and symptoms in a prospective cohort of health care workers using non-powdered latex gloves 2000–2009. Int Arch Environ Health 2014; 87:463–9.
  8. 8. Swanson MC, Bubak ME, Hunt LW, et al. Quantification of occupational latex aeroallergens in a medical center. J Allergy Clin Immunol 1994; 94:445–51.
  9. 9. Tarlo SM, Sussman G, Contala A, et al. Control of airborne latex by use of powder-free latex gloves. J Allergy Clin Immunol 1994; 93:985–9.
  10. 10. Allmers H, Brehler R, Chen Z, et al. Reduction of latex aero-allergens and latex-specific IgE antibodies in sensitized workers after removal of powdered natural rubber latex gloves in a hospital. J Allergy Clin Immunol 1998; 102: 841–5.
  11. 11. Kim KT, Hussain H. Prevalence of food allergy in 137 latex-allergic patients. Allergy Asthma Proc 1999; 20:95–7.
  12. 12. Mikkola JH, Alenius H, Kalkkinen N, et al. Hevein-like protein domains as a possible cause for allergen cross-reactivity between latex and banana. J Allergy Clin Immunol 1998; 102:1005–12.
  13. 13. Posch A, Wheeler CH, Chen Z, et al. Class 1 endochitinase containing a hevein domain is the causative allergen in latex-associated avocado allergy. Clin Exp Allergy 1999; 29:667–72.
  14. 14. Taylor JS, Erkek E. Latex allergy: diagnosis and management. Derm Therapy 2004; 17:289–301.
  15. 15. Hamilton RG, Adkinson NF Jr. Diagnosis of natural rubber latex allergy: multi-center latex skin testing efficacy study. The Multi-Center Latex Skin Testing Study Task Force. J Allergy Clin Immunol 1998; 102:482–90.
  16. 16. Hamilton RG, Adkinson NF Jr. Validation of the latex glove provocation procedure in latex-allergic subjects. Ann Allergy Asthma Immunol 1997; 79:266–72.
  17. 17. Hamilton RG, Biagini RE, Krieg EF. Diagnostic performance of food and drug administration-cleared serologic assays for natural rubber latex-specific IgE antibody. The multi-center latex skin testing study task force. J Allergy Clin Immunol 1999; 103:925–30.
  18. 18. Accetta Pedersen DJ, Klancnik M, Elms N, et al. Analysis of available diagnostic tests for latex sensitization in an at-risk population. Ann Allergy Asthma Immunol 2012; 108:94–7.
  19. 19. National Institute for Occupational Safety and Health. Preventing allergic reactions to natural rubber latex in the workplace. NIOSH publication no. 97-135. Cincinnati: Government Printing Office, 1997.
  20. 20. Epling C, Duncan J, Archibong E, et al. Latex allergy symptoms among health care workers: results from a university health and safety surveillance system. Int J Occup Environ Health 2011; 17:17–23.
  21. 21. Aldlyami E, Kulkarni A, Reed MR, et al. Latex-free gloves. Safer for whom? J Arthroplasty 2010; 25(1):27–30.
  22. 22. Allmers H, Schmengler J, John SM. Decreasing incidence of occupational contact urticaria caused by natural rubber latex allergy in German health care workers. J Allergy Clin Immunol 2004; 114:347–51.
  23. 23. LaMontagne AD, Radi S, Elder DS, et al. Primary prevention of latex related sensitization and occupational asthma: a systematic review. Occup Environ Med 2006;63:359–64.

Note

..................Content has been hidden....................

You can't read the all page of ebook, please click here login for view all page.
Reset
3.94.102.228