Gordon L. Sussman

Latex allergy can induce clinical reactions to specific foods.

Objective The purpose of this study was to investigate crossreactivity between latex and foods, to identify crossreacting IgE binding proteins, and to assess the clinical significance.

Allergy to latex rubber.

Latex gloves are indispensable in todays health care practice. The comfort, barrier, and tactile properties of powdered latex gloves have been thought to be ideal. Between 1988 and 1992, an estimated 11.8 billion examination gloves and 1.8 billion surgical latex gloves were used in the United States. Recent reports of allergic responses to latex have led some authors to re-examine the safety of latex medical devices. Although many health care workers report allergic reactions to gloves, most are not serious. The predominant immunologic response (82%) to natural rubber latex is type IV delayed hypersensitivity to rubber additives, which presents clinically as contact dermatitis [1]. However, between 1988 and 1992, the FDA received reports of more than 1000 systemic allergic reactions to latex, 15 of which were fatal [2]. These systemic reactions are type I immunologic responses that are mediated by IgE antibody to residual rubber tree proteins in latex medical devices. Health care workers develop sensitization from regular latex exposure: wearing latex gloves or inhaling aerosolized latex in the workplace [3]. Re-exposure in a sensitized patient may result in contact urticaria, allergic rhinoconjunctivitis, asthma, or anaphylaxis [4]. Epidemiology There are several explanations for the recent epidemic of latex allergy. After the introduction of universal precautions for human immunodeficiency virus, use of natural rubber latex gloves increased. The increased demand for gloves may have temporarily changed manufacturing procedures, resulting in a poor-quality, highly allergenic product. Increased awareness of latex allergy has resulted in more numerous reports [5] of this allergy during the last 6 years. Presently, the incidence of latex sensitization is unknown. The prevalence of latex allergy in the general nonatopic population is believed to be less than 1%. Latex sensitivity has been reported in 1 of 800 patients (0.125%) before surgery [6]. However, the prevalence of latex allergy in children with spina bifida ranges from 28% to 67% [5]. Mucosal absorption of latex allergens during multiple surgical procedures done early in life may have sensitized these children. The prevalence of latex allergy in health care workers is between 7% and 10% [7, 8]. Health care workers with atopic allergy have been reported [8] to have a 24% prevalence of a positive result from latex skin-prick testing. Fifty percent (5 of 10) of patients in this study [8] were clinically asymptomatic. The risk for subsequent development of latex allergy in this group is unknown. Eczematous hand dermatitis disrupts the skin barrier and may predispose persons to latex allergy. A progression may occur from localized (hand) to generalized (anaphylactic) allergic responses [9]. Areas with significant airborne latex allergens (operating rooms, intensive care units, and dental suites) may sensitize health care workers who inhale allergenic proteins [10-12]. Clinical Latex Allergy Irritant contact dermatitis, the most common clinical manifestation of latex allergy, is a nonallergic cutaneous response that manifests as dry, crusted lesions in latex glove-exposed areas. Prolonged and repeated latex exposure is aggravated by sweating and rubbing under the glove, leading to papular and ulcerative lesions [1]. Allergic contact dermatitis is a delayed hypersensitivity reaction to rubber additives (thiurams, mercaptobenzothiazole, carbamates) [13]. The acute phase of the reaction occurs 48 to 96 hours after exposure, affects the dorsum of the hands, and is characterized by vesicular skin lesions. With continued latex exposure, these skin lesions develop a crusted, thickened appearance. Immunoglobulin E-mediated latex allergy may be locally visible as contact urticaria [14] or may present as occupational rhinoconjunctivitis or asthma [3, 12]. Anaphylactic reactions have most often been caused by exposure to the surgeons latex gloves during abdominal or genitourinary surgery or by other sources of mucosal exposure to latex (barium enema, dental procedures) [3-5]. Anaphylaxis has been reported less often from latex exposure that occurs when health care workers put on gloves or work in a latex-laden environment. Identification and Management of Latex Allergy The prevention of adverse latex reactions depends on identification of patients who are allergic. A careful and complete history will not identify all persons at risk for latex allergy. The latex skin-prick test is a sensitive indicator of IgE sensitization, but a standardized latex extract that can be used in this test is presently not available. Latex skin-prick testing of extremely allergic persons using commercially available extracts has been safe [3, 6-8]. However, five [15, 16] anaphylactic episodes occurring after the use of extracts prepared from latex gloves or after the use of certain skin test reagents have been reported. Extracts prepared from latex gloves have variable allergenic potency, and skin-prick testing appears to have an increased risk for adverse reactions. Latex skin-prick tests should therefore be done cautiously starting with very diluted (1:1 million) extracts of the stock testing solution. This should only be done in an allergy center familiar with the test. Full emergency equipment must be available to treat possible systemic reactions. In vitro testing for latex protein-specific IgE antibodies (using radioallergosorbent tests, enzyme-linked immunosorbent assays, and Western blots) reportedly identifies 50% to 60% of persons with IgE sensitivity [17]. The American Academy of Allergy and Immunology has published guidelines [18] for providing care to persons with latex allergy. A flow chart for management of latex aller-gy is shown in Figure 1. Key points include the following: 1. All persons at risk for latex allergy should have a careful history and should complete a standardized latex allergy questionnaire (Table 1). Table 1. Questionnaire for Identification of Possible Latex Allergy* Figure 1. Overview of the identification and management of persons with latex allergy. 2. High-risk patients should be offered clinical testing for latex allergy. This includes children with spina bifida and health care workers with atopy (type I allergic reactions) (Table 1). 3. A latex-free environment is defined as one in which there is no latex glove use by any personnel. In addition, no direct patient contact should occur with other latex devices (catheters, condoms, adhesives, tourniquets, and anesthetic equipment). 4. Procedures on children with spina bifida should be done in a latex-free environment (Table 2). Table 2. Nonlatex Alternatives for Patients Allergic to Latex* 5. Procedures on all patients with positive skin test results should be done in a latex-free environment. Treatment of Latex Allergy Patients with an irritant latex reaction should eliminate unnecessary glove use. Cotton liners or barrier creams can be effective treatments. Patients who have contact dermatitis (type IV delayed hypersensitivity reaction) to latex additives should be appropriately diagnosed by patch testing. The implicated allergen should be avoided by changing to a different glove [1]. Patients with a negative history for latex allergy but with a positive result from latex skin testing or radioallergosorbent testing (RAST) or both should have a latex glove challenge test called a use test [19]. Patients with a positive latex challenge result should wear nonlatex gloves (Table 2). Patients with a negative challenge test result who have a positive result from latex skin testing or radioallergosorbent testing may tolerate low-protein latex glove use, but these patients should not have mucosal latex exposure during surgery or medical procedures. Patients with symptomatic latex allergy often present with severe allergic rhinoconjunctivitis and asthma that require them to leave their workplace. Although it is known that latex proteins are the responsible allergens, cornstarch glove powder has an important role. Latex proteins are easily absorbed by glove powder and are aerosolized at levels similar to those of other occupational respiratory allergens [10-12]. Complete removal of powdered latex gloves has resulted in undetectable levels of airborne latex particles. When all their coworkers switch to using powder-free latex gloves, health care workers with latex allergies have been able to return to their workplace [12]. In 1991, latex and banana were reported to be cross-reactive. Patients with latex allergy have subsequently presented with allergies to avocado, kiwi, and chestnut [20]. Clinically, these patients often have perioral itching and local urticaria, and they occasionally have been reported to have life-threatening, food-induced anaphylactic shock. The observed cross-reactivity of latex with avocado, kiwi, and chestnut probably occurs because latex proteins are structurally homologous with other plant proteins. Latex is ubiquitous in the medical environment, and health care workers encounter these allergens by multiple routes, including compromised skin and mucous membranes of the respiratory tract. Once sensitized, these health care workers are at risk for severe systemic allergic reactions. The antigenic protein level on latex rubber devices should be reduced to prevent further sensitization and allergic reactions [21]. Low-allergen latex gloves are available [22], and most manufacturers are working to lower protein levels. As cleaner products are brought to market, the incidence of new sensitization and adverse reactions is expected to decrease.

Control of airborne latex by use of powder-free latex gloves ☆ ☆☆ ★ ★★

OBJECTIVE Our objective was to assess airborne latex allergen exposure in the workplace of a hospital laboratory technician with occupational latex sensitization and repeated anaphylactic episodes from this. Her allergic manifestations had cleared only when coworkers changed to powder-free latex gloves. Therefore a laboratory still using powdered latex gloves was selected for comparative airborne latex sampling. DESIGN The design was a survey. SETTING We used a hospital hematology laboratory, and a biochemistry laboratory was used for comparison. PARTICIPANTS The index case with latex allergy is described. An average of 10 employees worked on the day shift in the same laboratory, and 10 employees worked in the biochemistry laboratory studied. MAIN OUTCOME MEASURE Airborne latex allergen levels obtained by high airflow area sampling were compared in the laboratory using powder-free latex gloves and in the laboratory using powdered latex gloves. RESULTS Levels were below the level of detection (< 0.02 ng/m3 of latex allergen) in the laboratory using powder-free latex gloves but ranged from 39 to 311 ng/m3 in the laboratory using powdered gloves. CONCLUSIONS Airborne latex allergen is produced with use of powdered latex gloves. Such usage by coworkers may provoke respiratory and anaphylactic response to latex in sensitized subjects. Use of powder-free gloves by coworkers may enable such patients to continue work in their trained profession and may prevent measurable airborne latex exposure. Affected patients, however, still need to avoid direct latex contact.

Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis.

BACKGROUND Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies. OBJECTIVES We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR (index of reactivity) 5-grass-pollen SLIT tablets (Oralair) compared with placebo assessed by using the average adjusted symptom score (AAdSS) at season 3 in adults with grass pollen-induced rhinoconjunctivitis. METHODS Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons. The primary outcome was the AAdSS, a symptom score adjusted for rescue medication use, after 3 consecutive treatment seasons. Secondary outcomes were symptoms and rescue medication score, quality-of-life, and safety assessments. RESULTS The mean AAdSS was reduced by 36.0% and 34.5% at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups, respectively, compared with that in the placebo group (P < .0001 for both). Reductions were observed in total symptom scores and ISSs and the medication score, with a marked improvement in quality of life for both active groups compared with the placebo group at season 3. Most treatment-emergent adverse events were local reactions expected with SLIT, decreasing in number and intensity in each treatment season. CONCLUSIONS Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated, with reduction in symptoms and rescue medication use. The treatment was well tolerated. Adverse events decreased in number and intensity over the 3 seasons.

Hypersensitivity to natural latex

Rubber hypersensitivity is well described but usually as a contact dermatitis caused by chemicals added during the process of making natural latex or synthetic rubber. IgE-mediated reactions, mainly contact urticaria, have rarely been reported in Europe. We report a case of immediate hypersensitivity to latex. A 34-year-old female operating room nurse developed hand eczema to natural latex. On two occasions, while she was gloving for surgery, she had the following reactions: flushing, tachycardia, urticaria, angioedema, wheezing, and light-headedness. Prick and patch testing to thiuram mix, mercaptobenzothiazole, phenylenediamine mix, and carbamate mix (common rubber additives) were negative. Prick tests to natural latex elicited a 4+ reaction associated with immediate flushing, tachycardia, urticaria, and light-headedness. Five control subjects did not react. IgE antibodies to latex by RAST demonstrated 17.7% binding (control, 4%). This case demonstrates that natural latex can cause IgE-mediated symptoms. The route of exposure was cutaneous absorption of relevant latex allergens. As the use of latex rubber products continues to escalate, more cases are likely to occur.

Latex sensitization: Occupational versus general population prevalence rates †

BACKGROUND Natural rubber latex (NRL) has become an important occupational health concern in recent years, particularly among health care workers. It has been suggested in some reports that the prevalence of latex sensitization among occupationally exposed groups is not different from that in the general population. METHODS The findings of prevalence studies conducted among occupationally-exposed and general population groups were reviewed to determine whether there is evidence to support this suggestion. RESULTS Numerous surveys of HCWs have demonstrated that the prevalence of sensitization to latex ranged in most studies from 5 to 12%; sensitization of HCWs may produce clinical effects including urticaria, rhinoconjunctivitis, occupational asthma, and potentially life-threatening anaphylactic shock. More than a decade ago, data from Finland indicated that the prevalence of latex allergy in the general population was less than 1%. Recent reports from Finland have confirmed this, with observations that 0.7-1.1% of large series of patients were NRL-allergic, while among 804 unselected patients, the prevalence of latex skin prick test (SPT) positivity was 0.12%. In contrast, other studies have suggested that from 4 to 6.4% of individuals tested were positive for serum latex-specific IgE antibodies. However, the specificity of these assays has been reported to be low. In three recent studies based on SPTs, published in 1997, the prevalence of positive reactions to latex was about 1% or less. The prevalence was 0.7% (95% CI 0.3-1.4) among 758 apprentices in Quebec, Canada; and 1.1% among more than 3,000 children tested in Finland (1.0% confirmed on latex use test). There were no first- and second-year dental students with positive latex SPTs in Ontario, Canada. CONCLUSIONS These recent investigations provide further evidence consistent with earlier studies based on skin testing that the prevalence of latex sensitization in occupationally-unexposed groups is quite low (< 1%). The marked differences in the findings based on serological assays may relate to the nonspecificity of these assays and deserve further investigation.

Incidence of latex sensitization among latex glove users

BACKGROUND Although there are several reports of the prevalence of latex sensitization among health care workers, the incidence of sensitization is unknown. OBJECTIVE The objective of this study was to estimate the incidence of sensitization among latex glove users at a hospital in Hamilton, Ontario, Canada. METHODS Workers with negative results to the skin test at baseline were followed prospectively over 1 year, some wearing powdered gloves and others using powder-free gloves. They were reevaluated in 1995 with a questionnaire and skin prick test (SPT) sensitivity to latex reagents, three common inhalants, and six foods. A conversion was defined as a (new) latex SPT with wheal diameter at least 4 mm greater than saline control. Glove extracts were assayed for antigenic protein, and air samples were obtained to estimate exposure to airborne latex protein. RESULTS During powdered glove use, personal exposures ranged from 5 to 616 ng/m3, whereas during powder-free glove use, all but two results for air samples were below the limit of detection (about 0.1 ng/m3). During the study period, the protein concentration in the powdered gloves, initially mean 557 microg/gm of sample, declined at a rate of 295 microg/gm per year (p < 0.0001). Of the 1075 SPT-negative participants at baseline, 479 were working in eligible wards, and of these, 435 (91%) participated in follow-up, 227 using powder-free gloves and 208 using powdered gloves. We identified four conversions, two (1.0%) in the powdered glove group and two (0.9%) in the powder-free group. The two participants using powdered gloves were the only converters who were symptomatic. The significance of skin test conversions identified in the powder-free group, both asymptomatic patients, is unclear. The limitations of the study are discussed, including the limited power, the declines in latex protein concentrations, and the possibility of information (observer) bias. CONCLUSION To our knowledge, this represents the first reported estimate (about 1%) of incidence of sensitization in hospital personnel using latex gloves.

Identification of a 46-kD latex protein allergen in health care workers

Latex allergy is an occupational hazard for health care workers. Extractable latex proteins are known to be allergenic, but most latex allergens have not been specifically identified. The purpose of this study was to characterize the IgE response of latex‐allergic patients to latex proteins and to identify common protein allergens. Serum was obtained from 40 individuals who were skin test‐positive to latex; 85% were health care workers. Western blots for IgE reactivity were performed using both ammoniated (AL) and non‐ammoniated (NAL) latex proteins and IgE‐reactive NAL proteins were analysed by microsequence analysis. The patients were grouped according to common patterns of reactivity. Pattern 1, the most common pattern of reactivity (9/40 patients) recognized two protein bands in both NAL and AL at 46 and 110kD. A second, heterogeneous pattern of reactivity (pattern 2) recognized a diffuse pattern of polypeptides in the AL preparation. The n‐terminal amino acid sequences for allergens at 14, 18, 29, 46 and 110 kD were determined. Sequence analysis identified the 14‐kD and 18‐kD allergens as the hevein preprotein. The 46‐kD and 110‐kD had identical sequences which were unique from known latex proteins. We conclude that multiple latex proteins are allergens with hevein preprotein and a previously unidentified 46/110‐kD protein being commonly recognized in health care workers.

Skin Prick Test Reactivity to Recombinant Latex Allergens

Background: Allergy to latex has become a serious and increasingly common health problem, particularly for healthcare workers and patients who undergo frequent surgical procedures. Testing for latex allergy currently involves in vitro tests and skin prick testing using crude preparations of natural rubber latex (NRL). To date, 10 latex proteins have received designation as allergens (Hev b 1 to Hev b 10) and, except for Hev b 4, have been cloned as recombinant proteins. Our aim was to compare the skin prick test (SPT) reactivity of six recombinant latex allergens with SPT reactivity to natural rubber latex proteins in known latex-allergic individuals. Methods: Six recombinant proteins were expressed in Escherichia coli, and tested as the intact fusion proteins (Hev b 2, 5, 6, 8) or as purified proteins (Hev b 3 and 7). SPT with the six recombinant latex allergens was performed using 10-fold serial dilutions on 31 latex-allergic subjects to determine the level of reactivity to each recombinant allergen. Latex-specific IgE was determined using the AlaSTAT assay. Results: All six recombinant allergens were reactive by SPT in at least 1 latex-allergic patient but not in any of the control patients. The frequency of sensitization to the various recombinant allergens was similar to previous studies using the native proteins isolated from NRL. The minimal level of protein for a positive skin test was 70 pg/ml for NRL and 1 ng/ml for one recombinant allergen (Hev b 7). In our patients, the use of a combination of recombinant latex allergens Hev b 5, 6 and 7 diagnosed latex allergy with 93% sensitivity and 100% specificity. Conclusion: Recombinant latex allergens are clinically reactive, can be produced in a standardized manner, and could potentially provide safe, sensitive and specific reagents for the diagnosis of latex allergy.

Post‐treatment efficacy of discontinuous treatment with 300IR 5‐grass pollen sublingual tablet in adults with grass pollen‐induced allergic rhinoconjunctivitis

Sustained efficacy over three pollen seasons of pre‐ and co‐seasonal treatment with 300IR 5‐grass pollen sublingual tablet has been demonstrated in adults with moderate‐severe grass pollen‐associated allergic rhinoconjunctivitis.