The importance of nasal provocation test in the diagnosis of natural rubber latex allergy

Background:  Most studies regarding natural rubber latex (NRL) allergy have concentrated on the prevalance using skin prick test (SPT) and specific IgE assay. The objective of this study is to examine the target organ (skin, nasal mucosa) responses in patients with positive SPT to NRL using the nasal provacation test (NPT) and glove use test (GUT).
Methods:  Four thousand four hundred and twenty patients presented to our polyclinic between July 2003 and January 2007 were evaluated. One thousand six hundred and ninety-nine patients had positive SPT to one or more allergens (NRL and other inhaler allergens). Twenty-nine patients with positive SPT to NRL comprised the NRL sensitive group (group 1). Thirty-five randomized patients with positive SPT to an inhaler allergen other than NRL and negative NRL-specific IgE comprised atopic control group (group 2). Thirty healthy individuals who had no allergic diseases and had negative SPT and NRL-specific IgE comprised the healthy control group (group 3).
Results:  The lowest NRL allergen concentration leading to NPT positiveness was 0.05 μg/mL. NPT was negative in groups 2 and 3. NPT was found to have a sensitivity of 96%, specificity of 100%, negative predictive value of 98% and positive predictive value of 100%. GUT was found to have a sensitivity of 81%, specificity of 90%, negative predictive value of 75% and positive predictive value of 93%.
Conclusions:  Nasal provocation test was successfully used for the first time in the diagnosis of NRL allergy. NPT is a more sensitive method as compared to GUT.     

Frequency of natural rubber latex allergy in adults is increased after multiple operative procedures

BACKGROUND: It has been shown that immediate-type allergy to natural rubber latex (NRL) affects predominantly health-care workers and infants with malformations requiring repeated medical procedures. Adult patients with multiple invasive procedures are not thought to be at an increased risk of NRL allergy. METHODS: A total of 325 consecutive adult inpatients (54.4+/-15.6 years; 219 men, 106 women) awaiting surgical or urologic procedures were assessed by questionnaire-based history (atopic diseases, number of previous standard operative or endoscopic procedures, intolerance to rubber products, and adverse reactions during medical care), by skin prick tests with different NRL test solutions, by measurement of NRL-specific IgE in the serum, and, if sensitization to NRL was found, by cutaneous challenge tests with NRL-containing material. Subjects were classified as sensitized to NRL if skin prick test reactions to NRL were positive or if NRL-specific IgE antibodies were found. NRL allergy was defined as NRL sensitization and immediate-type symptoms to NRL. RESULTS: Thirty-one of 325 (9.5%) subjects were found to be sensitized to NRL, 14/285 (4.9%) by skin prick testing and 23/323 (7.1%) by NRL-specific IgE antibodies in the serum. Four individuals (1.2%) were diagnosed as having clinically manifest NRL allergy, and another 27 (8.3%) were sensitized to NRL without symptoms to date. The frequency of previous invasive procedures was zero in eight patients, up to 10 in 245, 11-20 in 52, 21-30 in seven, and over 30 (up to 83) in 13 patients. No association was found between the number of invasive procedures and NRL sensitization without clinical symptoms. However, 3/4 patients with NRL allergy had undergone more than 30 interventions, and 1/4 had had 11 operations. Frequent invasive procedures (more than 10) were significantly associated with NRL allergy (P<0.001). Allergy or sensitization to NRL was associated with atopy (21/31 vs 87/294) (P<0.001). CONCLUSIONS: A remarkable percentage of unselected adult patients undergoing surgical procedures have allergy or sensitization to NRL. Repeated invasive treatment appears to be a risk factor for NRL allergy.     

Percutaneous reactivity to natural rubber latex proteins persists in health-care workers following avoidance of natural rubber latex

BACKGROUND: Long-term avoidance of natural rubber latex [Hevea brasiliensis (Hev b)] is currently recommended for health-care workers (HCWs) with established natural rubber latex (NRL) allergy. Percutaneous sensitivity to eight Hev b NRL allergens was evaluated in HCWs in 2000. To date, no studies have evaluated the longitudinal effects of NRL avoidance on percutaneous sensitivity to NRL allergens. OBJECTIVE: The aims of this study were to evaluate changes in percutaneous reactivity to non-ammoniated latex (NAL) and NRL allergens in HCWs 5 years after a recommendation to avoid NRL and to evaluate factors that predict the persistence of in vivo sensitivity to NAL and NRL allergens. METHODS: Skin prick testing was performed with NAL, seven NRL allergens (Hev b 1, 2, 3, 4, 6.01, 7.01, and 13), and recombinant Hev b 5 (rHev b 5) in 34 HCWs who were initially evaluated in 2000 for occupationally related NRL allergy. Serial 10-fold dilutions of NAL and NRL allergens were employed in skin testing. Sera from the HCWs were assayed for latex and enhanced latex (rHev b 5-enriched allergosorbent)-specific IgE antibodies using the ImmunoCAP assay. RESULTS: The prevalence of work-related symptoms significantly decreased between 2000 and 2005 with avoidance of NRL (P<0.05). A >/=100-fold reduction in percutaneous sensitivity to Hev b 2 and Hev b 7 was less likely in those with prior history of systemic reactions to NRL (P=0.0053), reported history of reaction to cross-reactive foods (P=0.014), continued local reactions to NRL gloves (P<0.0001), or high NRL glove exposure since the initial study (P=0.0075). The diagnostic sensitivity and specificity of the latex-specific IgE serology was 54% and 87.5%, respectively, in comparison with NAL skin tests. The addition of rHev b 5 to the ImmunoCAP (enhanced latex) allergosorbent altered the diagnostic sensitivity and specificity of the ImmunoCAP to 77% and 75%, respectively. CONCLUSION: While symptoms may resolve quickly with NRL avoidance therapy, detectable IgE indicating continued sensitization remains beyond 5 years, and thus continued avoidance of NRL should be recommended.     

Latex allergy diagnosis: in vivo and in vitro standardization of a natural rubber latex extract

For the diagnosis of IgE-mediated (immediate) hypersensitivity to natural rubber latex (NRL), skin prick testing with extracts of latex gloves has been widely used, but such extracts are difficult to standardize. The present study aimed to produce on an industrial scale an NRL extract from freshly collected NRL and to evaluate, calibrate, and standardize the extract by both in vivo and in vitro testing. The source material, latex of the rubber tree, Hevea brasiliensis (clone RRIM 600), was frozen immediately after collection in Malaysia and shipped in dry ice to Stallergènes SA, France. Protein and allergen profiles were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, isoelectric focusing (IEF), crossed immunoelectrophoresis (CIE), and crossed radioimmunoelectrophoresis (CRIE). Allergen quantification was effected by RAST inhibition. The capacity of the preparation to elicit immediate hypersensitivity reactions in vivo was measured by skin prick testing in 46 latex-allergic patients and 76 nonallergic control subjects. SDS-PAGE and immunoblot profiles of the extract and an NRL standard (E8) provided by the US Food and Drug Administration were almost identical, disclosing several distinct IgE-binding proteins with apparent molecular weights of 14, 20, 27, 30, and 45 kDa, conforming to reported molecular weights of several significant NRL allergens. An arbitrary index of reactivity (IR) of 100 was assigned to the extract at 1:200 dilution (w/v), having a protein content of 22 μg/ml. Skin prick testing of latex-allergic patients and controls using the extract at 100 IR revealed 93% sensitivity, 100% specificity, 100% negative predictive value, and 96% positive predictive value. In conclusion, a skin prick test reagent for diagnosis of type I NRL allergy was successfully standardized. The reagent was demonstrated to contain most, if not all, of the currently known clinically significant NRL allergens, and it showed high sensitivity and specificity.     

Type I allergy to natural rubber latex and type IV allergy to rubber chemicals in health care workers with glove-related skin symptoms

BACKGROUND: It has been established that there are type I and type IV allergens in latex gloves. OBJECTIVE: The purpose of the study was to establish the prevalence of rubber glove-induced skin symptoms among health care workers in one Italian hospital. METHODS: Health care workers (n = 1584) were evaluated using a written questionnaire and 295 respondents with glove-induced skin symptoms were tested. We performed: skin prick test with latex glove extract and commercial latex, and environmental and food allergens; glove use test; patch tests with a rubber additive series; and RASTs. RESULTS: Hospital employees who used or had used latex gloves at work were 1294. Three hundred and sixteen (24.4%) reported glove-induced symptoms, namely, cutaneous symptoms in all the cases and non-cutaneous symptoms in 105 subjects (8.1%). Twenty-seven of the 295 symptomatic employees tested (9.1%) were latex sensitive. Thirty-one patients (10.5%) exhibited positive patch test to rubber-related allergens. The most positive readings were obtained from the Thiuram mix and the Carba mix, with 12 and 9 positivities, respectively. The risk factors for latex skin sensitization were: a previous history of atopy and asthma; history of surgery; pre-existing hand dermatitis; work-related symptoms; and positive skin tests to common inhalant and certain foods (P < 0.05). Subjects who exhibited positive patch test were significantly more likely to have a prior hand dermatitis (P < 0.001). Of the 295 cases, 275 (93.2%) were contact dermatitis (CD), 13 (4.4%) contact urticaria (CU) (including protein CD) and 7 (2.4%) CD associated with CU. CONCLUSIONS: Our results show a high prevalence of rubber glove-induced dermatoses among the employees in one Italian hospital. The majority of skin complaints of latex gloves are related to skin irritation rather than to allergy. The immediate allergy to latex and the delayed allergy to rubber chemicals suggest that all the health care workers with glove-related dermatitis should undergo both skin prick test and glove use test to detect type I hypersensitivity to latex, and patch test to detect type IV hypersensitivity to rubber chemicals.     

Identification and practical management of latex allergy in occupational settings

Allergy to natural rubber latex (NRL) from Hevea brasiliensis is a relevant occupational health hazard. The use of gloves and products manufactured with latex and environmental allergen exposure in the work environment are risks factors for the development of occupational allergy among different job categories. Healthcare workers have been the most commonly affected, but other professions with exposure to latex products such as hairdressers, cleaners, food handlers and those making natural rubber latex (NRL) products are also at risk of developing occupational allergy. Clinical manifestations of IgE-mediated latex allergy can range from troublesome skin disorders to life-threatening systemic reactions. It is very important to identify the occupational allergic diseases in their early stages in order to implement avoidance strategies. For this purpose, the interventions for prevention should emphasize the importance of latex allergy awareness and surveillance among exposed workforces.     

Cross-reactivity between Ficus benjamina (weeping fig) and natural rubber latex

The importance of hypersensitivity to Ficiis allergens is reported, Cross-sensitization between fig (Ficus carica), weeping fig (F. benjamina [Fb]), and natural rubber latex (NRL) was confirmed by RAST inhibition. We performed skin prick tests with fresh Fb tree sap and NRL extracts in 346 consecutive patients and in 151 patients with immediate-type hypersensitivity to NRL, Total serum IgE and IgE antibodies to NRL and Ficus spp. were analyzed in sera. By the RAST-inhibition method, we studied cross-reactivity among latex, fig. and weeping fig, Sensitization to Fb was diagnosed in 23 of the 346 consecutive patients, and the simultaneous presence of latex-specific IgE was highly significant. Of 151 NRL-allergic patients, 35 were also sensitized to Fb. Cross-reacting IgE antibodies recognizing latex and Ficus allergens were demonstrated by RAST inhibition. The present study reinforces the importance of Fb as an indoor allergen. Cross-reacting IgE antibodies to NRL and Ficus spp, allergens frequently found in the sera of atopic patients. Development of commercially available standardized extracts for skin tests is urgently necessary.     

Evaluation of acoustic rhinometry in a nasal provocation test with allergen

BACKGROUND: The objective was to validate acoustic rhinometry (AR) in a nasal challenge with allergen. METHODS: Nasal response to allergen provocation was based on clinical and symptom scores, cross-sectional changes of the nasal mucosa as measured by AR with the Rhinoklack system, and peak nasal inspiratory flow (PNIF), in atopic and nonatopic volunteers. RESULTS: After allergen challenge, mean variation in minimal cross-sectional area (deltaMCA), as measured by AR, or in peak nasal inspiratory flow (deltaPNIF) in nonatopic volunteers, was -0.4+/-14.3% and 5.2+/-15.7%, respectively, compared to baseline. This allowed the determination of a reaction threshold of -29% for deltaMCA and of -26% for deltaPNIF. All but one of the 30 atopic patients reached the AR reaction threshold, whereas all patients reached the PNIF reaction threshold. AR and PNIF closely correlated with clinical and symptom scores for nasal congestion, since there was no significant difference at reaction threshold between both methods. CONCLUSIONS: In an allergen provocation test, AR appears to be as specific and sensitive as peak nasal inspiratory flow, with the advantage of being independent of the patient's active cooperation. Discrepancies between both methods emphasize the role of nasal cavity anatomy in measuring nasal congestion by AR.     

Nasal eosinophilia in children: its use in the nasal allergen provocation test

This pediatric cytological and clinical study aimed at assessing the value of nasal eosinophilia during nasal provocation tests for identifying an offending allergen. The population studied comprised 50 children aged from 4 to 18 yr; 39 of these had well-characterized allergic rhinitis, which in 21 cases was combined with asthma, and the remaining 11 had nonatopic chronic rhinitis. Nasal secretions, collected by nose blowing, were stained with May-Grünwald-Giemsa or Wright stain. The percentage of nasal eosinophils was obtained by examining the cells in the whole slides. Counts were carried out on secretions collected before challenge, after insufflation of saline solution (for verification), and 40 min after insufflation into each nostril of an allergen (housedust mite extract). The nasal provocation test was considered positive when insufflation of the allergen increased nasal eosinophilia by more than 10%, provided that the prechallenge proportion of eosinophils was less than 50%. No increase in specific bronchial resistance was noted. These results indicate that nasal provocation tests are safe, even in asthmatic children.     

Crossreactivity between allergens in natural rubber latex and banana studied by immunoblot inhibition

Background An association between allergic reactions to natural rubber latex and to banana has been reported but the immunochemical properties of the putative crossreacting allergens remain unknown. Obfective To study extracts of banana and natural rubber latex and sera from latex-allergic patients for possible crossreacting allergens and IgE antibodies. Methods Sera from 22 latex-allergic patients and 22 control subjects with no evidence of allergy to latex or to banana were studied. All patients had positive and controls negative reactions in skin-prick testing using an eluate of latex gloves. IgE antibodies to natural rubber latex and to banana were evaluated by immunoblotting and by radioailergosorbent test (RAST) and crossreactivity between allergens in banana and natural rubber latex by immunoblot inhibition. Skin-prick testing was used to examine in vivo reactivity to banana. Results Ten of the 22 (45%) latex-allergic patients sera recognized altogether 14 allergens in banana by immunoblotting. The most frequently identified banana allergens were 23, 32, 36, 39 and 47kDa proteins. The banana skin-prick test was positive in 14 of 18 (78%) latex-allergic patients studied and banana RAST in 12 of 14 patient sera tested. Fourteen of 21 interviewed patients reported symptoms from eating or handling bananas. In immunoblot inhibition studies a dose-dependent inhibition of IgE binding to banana extract with natural rubber latex proteins was observed in all five patient sera tested and, likewise, the binding of IgE to natural rubber latex extract was inhibited with banana proteins in four of the five patient sera. Conclusions The present results confirm the existence of crossreacting allergens in natural rubber latex and banana and provide new information on the immunochemical nature and heterogeneity of these allergens.     

Measurement of natural rubber latex allergen levels in medical gloves by allergen-specific IgE-ELISA inhibition, RAST inhibition, and skin prick test

Exposure to natural rubber latex (NRL) medical gloves poses risks to patients sensitized to NRL and to users of protective gloves. Previous studies have shown that extractable allergen levels of the gloves vary widely. Since most of the available laboratory methods of NRL allergen measurement lack adequate validation, we wanted to evaluate the performance of a recently developed competitive IgE-ELISA-inhibition method in relation to the skin prick test (SPT) and RAST inhibition, as well as to extractable protein quantification and an immunochemical latex antigen assay (LEAP). Twenty samples of surgical (n = l4) and examination gloves (n=6), covering >90% of medical gloves marketed in Finland in 1994–5. were collected by the Finnish National Research and Development Centre for Welfare and Health, coded, extracted, and analyzed by the five methods. The IgE-ELISA inhibition correlated highly significantly with SPT (r=0.94) and RAST inhibition (r=0.96). Likewise, ELISA inhibition and RAST inhibition showed highly significant correlation (P=0.96, P<0.0001 in all three instances). Protein quantification by a modified Lowry method also correlated highly significantly with SPT (r=0.80). RAST inhibition (r=0.82), and ELISA inhibition (r=0.81. P100 AU/ml) in seven of the 20 glove brands analyzed. In conclusion, the results of a novel IgE-ELISA-inhibition method of measuring NRL allergen levels in medical gloves correlated highly significantly with those of SPT TTie ELISA method was found to be sensitive, reproducible, technically easy, inexpensive, and suitable for the analysis of large numbers of NRL products. The results of extensive market surveys in 1994 and 1995, communicated to the medical community in Finland, appear to have had a clear effect in moving glove purchasing policies toward the use of low-allergen gloves.     

Bacterial protease treatment of natural rubber latex alters its primary immunogenicity in a mouse model of sensitization

The purpose of the present investigation was to determine whether enzyme-treated (ET)-NRL is less immunogenic than untreated NRL in a BALB/c mouse model of primary in vivo sensitization following repeated subcutaneous injections with the aqueous phase of ammoniated NRL or ET-NRL. Mice immunized with NRL produced IgE against NRL and ET-NRL, indicating that protease treatment did not completely destroy IgE antibody epitopes. In contrast, ET-NRL-immunized mice did not produce IgE against either NRL or ET-NRL, suggesting that enzyme treatment reduced the number of antigenic polypeptides associated with NRL below the threshold for sensitization. Thelper-lymphocytes from NRL-immunized mice proliferated and produced IL-4 when stimulated in vitro with polypeptides from NRL, but not ET-NRL. In contrast, Thelper-lymphocytes from ET-NRL-immunized mice were nonresponsive to ET-NRL or NRL. We conclude that lack of IgE production by ET-NRL-immunized mice is likely related to a lack of T-cell help in the form of IL-4, rather than enzyme digestion of IgE antibody epitopes. These data indicate that there is an immunologic rationale for production of enzyme-treated NRL-containing medical devices.     

Lower airway inflammatory responses to repeated very-low-dose allergen challenge in allergic rhinitis and asthma

BACKGROUND: Low-dose allergen challenge (LDAC) may be a useful tool for studying the capacity of allergens to induce airway inflammation in atopic subjects. OBJECTIVE: To evaluate lower airway inflammatory changes following repeated inhalation of very low doses of allergen (VLDAC) in non-asthmatic subjects with allergic rhinitis (NAAR) compared with mild allergic asthmatic subjects (AA). METHODS: Fourteen NAAR and 11 AA were seen out of the pollen season and had skin prick tests with common aeroallergens. Baseline spirometry (S) and methacholine challenge (MC) were done and blood and induced sputum (IS) differential cell counts were obtained. Each subject underwent VLDAC on four consecutive mornings with a relevant allergen. S, MC, and blood and IS samplings were repeated 6 h after the second and fourth VLDAC and one week later. RESULTS: Although there were, as expected, no changes in FEV1 or PC20 in either group, mean percentage eosinophils on IS were significantly increased in NAAR on day 2 of VLDAC and decreased in all but one subject on day 4, with a tendency to return to baseline levels one week later. In AA, there was a non-significant trend for sputum eosinophils to increase on day 2; four subjects showed a decrease of eosinophils on day 4 of VLDAC. There was a correlation between eosinophil cationic protein (ECP) levels and eosinophil counts in NAAR throughout the study. There were no variations in other sputum cells or blood inflammatory cells. CONCLUSION: VLDAC can increase the percentage of eosinophils in IS of NAAR subjects without associated respiratory symptoms nor physiological modifications. A reduction in eosinophilic response despite repeated exposure, more common in NAAR subjects, suggests an adaptation process that needs to be further evaluated.     

Soluble ICAM-1 as a regulator of nasal allergic reaction under natural allergen provocation

Background: Intercellular adhesion molecule-1 (ICAM-1) plays a key role in the early stage of the signal cascade leading to cellular extravasation and the development of an inflammatory response. Recently, it has been reported that the soluble form of this adhesion molecule is present in human sera, possibly mediating biological actions.
Objective: The purpose of this study was to investigate levels of soluble ICAM-1 (sICAM-1) and its receptors in patients with allergic rhinitis, and to discuss sICAM-1's biological function.
Methods: The levels of sICAM-1 in sera and nasal epithelial lining fluids (ELF), the percentage of CD11a-positive lymphocytes in the peripheral blood, and scores of subjective symptoms from 14 patients with pollinosis (allergic group) were measured from pre- to post-season, results were compared with those from 10 non-allergic subjects (control group).
Results: The levels of sICAM-1 in sera and ELF were upregulated, and CD11a-positive lymphocytes were downregulatcd during the in-season in the allergic group. In addition, levels of sICAM-1 in sera from the allergic group remained high during the post-season, when levels of other parameters (symptoms, blood eosinophil counts, sICAM-1 in ELF and CD11a-positive lymphocytes) had roughly returned to the initial pre-season levels.
Conclusions: We demonstrate systemic and local upregulation of sICAM-1 and systemic downregulation of LFA-1 positive lymphocytes in patients with seasonal allergic rhinitis under natural allergen provocation, suggesting that sICAM-1 plays a role in regulating seasonal allergic inflammation.     

Banana allergy in patients with immediate-type hypersensitivity to natural rubber latex: Characterization of cross-reacting antibodies and allergens

Background: An association between allergy to latex and banana has been reported. Even though cross-reacting IgE antibodies have been demonstrated, in no study has the existence of structurally similar allergens been confirmed. In the present study banana allergy was studied in a large series of patients with latex allergy. Specific IgE antibodies were characterized for cross-reactivity and compared with pollen RAST results. Latex and banana extracts were investigated for common antigens and allergens. Methods: Latex-, banana-, and pollen-specific (birch, timothy, mugwort) IgE were measured in 47 sera from patients with latex allergy. Thirty-one patients were skin prick tested with banana and questioned for possible reactions after eating bananas. Several RAST inhibition and immunospot inhibition studies were used to characterize cross-reacting IgE antibodies. Structurally similar antigens and allergens were evaluated with crossed-line immunoelectrophoresis and crossed-line radioimmunoelectrophoresis, respectively. Results: Latex RAST results were positive in 31 (66%) and banana RAST results were positive in 26 (55%) of the 47 sera. Of the 31 latex RAST–positive sera, 25 (81%) were also banana RAST–positive. Results from latex RAST correlated significantly with results from banana RAST (p < 0.001), but not with those from pollen RAST (p > 0.05). Banana skin prick test results were positive in 11 (35%) of the 31 patients tested. Symptoms after eating bananas were reported by 16 (52%) of the 31 patients. In inhibition studies the binding of IgE antibodies to solid-phase banana and to several latex preparations was inhibited by latex and banana, respectively. In crossed-line immunoelectrophoresis at least one antigen from banana fused with an antigen from latex, which also bound IgE antibodies in autoradiography (crossed-line radioimmunoelectrophoresis). Conclusions: Patients with latex allergy have symptoms caused by banana and show positive skin test and specific IgE test results. Cross-reacting IgE antibodies were confirmed by several inhibition techniques. For the first time, a structurally similar antigen/allergen was demonstrated. (J ALLERGY CLIN IMMUNOL 1994;93:990-6.)