Profile Shift in Latex Sensitization over the Last 20 Years.

BACKGROUND: Natural rubber latex (NRL) allergy is commonly diagnosed according to medical history, skin allergy tests, and serological analyses. However, skin tests are increasingly being abandoned because of (i) their time-consuming nature, (ii) latex preparations for skin tests being not commercially available, and (iii) the use of in-house prepared test solutions is becoming ever more difficult due to increasing regulatory hurdles. In this light, we have evaluated differences in the profiles of current and former patients with suspected latex allergy. METHODS: Sera of skin test-positive patients from a historic cohort (1995-2001, n = 149 patients) and currently (2014-2015, n = 48 patients) were simultaneously analyzed for specific IgE to latex by ImmunoCAP. If the serological screening was positive (≥0.35 kU/L), component-resolved diagnostics including profilins and cross-reactive carbohydrate determinants (CCDs) were performed. RESULTS: In contrast to 88% (131/149) of the skin test-positive patients from the 1990s, only 51.1% (24/47) of the current cohort were found positive for specific IgE to latex. While 48.3% (72/149) of the patients had a convincing positive history in the 1990s, current skin test-positive patients rarely reported a relevant medical history (8.5%, 4/47). Specific IgE levels to latex were significantly higher in former patients with suspected latex allergy (p < 0.001) than in former sensitized individuals without allergy. However, this significant difference was lost in current allergic and sensitized patients with positive skin tests. CONCLUSION: Sensitization profiles in patients with latex allergy have changed significantly over the last 2 decades. Discrimination between NRL sensitization and clinical allergy remains a diagnostic challenge. Our data highlight the need for a combination of all 3 criteria, i.e., patient history, skin test, and analysis of specific IgE, for a correct diagnosis of latex allergy.

Performance of specific immunoglobulin E tests for diagnosing occupational asthma: a systematic review and meta-analysis.

OBJECTIVES: To determine the test performance parameters for the retrievable range of high-molecular-weight (HMW) and low-molecular-weight (LMW) occupational allergens and to evaluate the impact of allergenic components and the implementation of measures for test validation. METHODS: A protocol with predefined objectives and inclusion criteria was the basis of an electronic literature search of MEDLINE and EMBASE (time period 1967-2016). The specific inhalation challenge and serial peak flow measurements were the reference standards for the specific IgE (sIgE) test parameters. All of the review procedures were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Seventy-one studies were selected, and 62 entered meta-analysis. Pooled pairs analysis indicated a sensitivity of 0.74(95% CI 0.66 to 0.80) and specificity of 0.71(95% CI 0.63 to 0.77) for HMW allergens and a sensitivity of 0.28(95% CI 0.18 to 0.40) and specificity of 0.89(95% CI 0.77 to 0.95) for LMW allergens. Component-specific analysis improved the test parameters for some allergens. Test validation was handled heterogeneously among studies. CONCLUSION: sIgE test performance is rather satisfactory for a wide range of HMW allergens with the potential for component-specific approaches, whereas sensitivity for LMW allergens is considerably lower, indicating methodological complications and/or divergent pathomechanisms. A common standard for test validation is needed.

Allergy topics for dental practitioners.

Penicillin allergy, local anesthetic hypersensitivity, latex allergy, contact hypersensitivity, and anaphylaxis are among the allergic reactions encountered in dental practice. This article reviews the literature pertaining to these important areas of overlap between dentistry and allergy/immunology. The epidemiology, diagnosis, and management of penicillin allergy as it relates to dentistry are reviewed. The relevant literature regarding local anesthetic and latex hypersensitivity is discussed. In addition, the presentation, evaluation, and management of contact hypersensitivity, including that to metals, are addressed. Recognition and appropriate treatment of anaphylaxis also are reviewed. This article will help dentists understand potential areas of comanagement with allergists/immunologists to optimize patient care.

Misleading Allergens in the Diagnosis of Latex Allergy: Profilin and Cross-Reactive Carbohydrate Determinants.

BACKGROUND: It has been suggested that latex-specific IgE analysis may lead to false-positive results, especially in patients with pollen allergy. In the present study, the reasons underlying clinically irrelevant latex-specific IgE positivity were investigated. METHODS: Thirty patients with latex allergy (group 1), 89 patients sensitised to aeroallergens (group 2a), and 98 healthy individuals without allergy (group 2b) were enrolled. Participants from all 3 groups were subjected to skin prick tests with aeroallergens including latex, latex-specific IgE analysis (ImmunoCAP), and nasal provocation test with latex. All cases demonstrating positive latex-specific IgE also underwent specific IgE tests (ImmunoCAP) with latex profilin, birch pollen profilin, peach lipid transfer protein, and pineapple bromelain as cross-reactive carbohydrate determinants. RESULTS: Comparison of the atopic and healthy control groups showed that the rate of positive latex-specific IgE was significantly higher in group 2a. Latex profilin-, birch pollen profilin-, and bromelain-specific IgE were remarkably higher in group 2a. CONCLUSION: False positivity to latex-specific IgE in ImmunoCAP analysis may be observed in approximately 19% of patients with pollen allergy. Profilins and bromelain are the main contributors to clinically irrelevant positive latex-specific IgE.

Latex sensitization in patients with myelomeningocele: contribution of microarray technique.

Summary: Background. Microarray technique employing molecular allergens is pointed out as a new method to evaluate allergic patients. Objective. To evaluate if microarray technique (ImmunoCAP-ISAC®; I-ISAC®) is similar to fluorescence enzyme immunoassay (FEIA; ImmunoCAP®) in the diagnosis of latex allergy (specific IgE to latex plus symptoms) and latex sensitization (only antibody) in pediatric (9-mo to 14-yrs) patients with myelomeningocele undergone to surgical repair. Methods. Patients underwent skin prick testing (SPT) to latex and food (prick to prick), and dosage of serum specific IgE to latex and recombinant latex allergens (rHev b 1, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9, and rHev b 11) by ImmunoCAP® and I-ISAC®. Results. The comparison between the two methods showed high level of concordance considering positive and negative results. A statistically significant correlation for rHev b 3 and rHev b 6.01 for the allergic patients, and for rHev b5 and rHev b6.01 for those sensitized to latex, was observed. I-ISAC® is limited to 5 recombinant latex allergens (rHev b 1, 3, 5, 6.01 and 8). Despite the presence of antibodies against pollens, LTP and profilins (I-ISAC®) in some patients, none of them reported symptoms related with intake of fruits and/or vegetables. Conclusion. Both methods are effective in assisting the diagnosis of latex allergy, but differ in the assessment of sensitized pediatric patients with myelomeningocele. The assessment of latex sensitized patients is more complete using the 8 recombinant latex fractions available for ImmunoCAP®, instead of I-ISAC®.

Atopic status and latex sensitization in a cohort of 1,628 students of health care faculties.

BACKGROUND: Atopic diseases have increased since the second half of the previous century. Atopic workers are at higher risk to be sensitized to latex, and the first years of exposure are supposed to be especially risky. OBJECTIVE: To assess atopic status and rate of latex sensitization in health care students starting their exposure to latex gloves. METHODS: We analyzed medical surveillance data from 1,628 health care students from 2010 to 2016. Students completed a questionnaire focused on their previous and current latex exposure and personal and family histories of allergic diseases; underwent skin prick testing with common allergens and latex extract (and/or total and latex-specific immunoglobulin E in serum); and underwent a medical examination. RESULTS: Skin prick test results for common inhalant allergens showed that 807 of 1,628 students (49.6%) had atopy. Atopy by skin prick testing was associated with male sex (odds ratio 1.49, 95% confidence interval 1.18-1.86), a personal history of oculorhinitis or asthma (odds ratio 10.22, 95% confidence interval 7.4-14.13), and atopic eczema (odds ratio 1.87, 95% confidence interval 1.05-3.36) at multivariate regression analysis. Eleven students (0.7% of total population) were found to be sensitized to latex and all had atopy. CONCLUSION: Despite the high prevalence of atopy in health care students of Trieste, the latex sensitization rate is very low and comparable to general population. This is reasonably due to the low exposure to latex gloves at the time of the evaluation and to low latex release from the gloves currently used in our hospital.

Patch testing with rubber series in Europe: a critical review and recommendation.

BACKGROUND: Rubber additives constitute an important group of contact allergens, particularly in certain occupations. OBJECTIVES: To collect information regarding the current practice of using a 'rubber series' in Europe, and discuss this against the background of evidence concerning the prevalence of allergy in order to derive a recommendation for a 'European rubber series'. METHODS: The following were performed: (i) a survey targeting all members of the COST action 'StanDerm' consortium, (ii) analysis of rubber contact allergy data in the database of the European Surveillance System on Contact Allergies, and (iii) a literature review. RESULTS: Information from 13 countries was available, from one or several departments of dermatology, and occasionally occupational health. Apart from some substances tested only in single departments, a broad overlap regarding important allergens was evident, but considerable variation existed between departments. CONCLUSIONS: An up-to-date 'European rubber series' is recommended, with the exclusion of substances only of historical concern. A 'supplementary rubber series' containing allergens of less proven importance, requiring further analysis, is recommended for departments specializing in occupational contact allergy. These should be continually updated as new evidence emerges.

Patch test results with rubber series in the European Surveillance System on Contact Allergies (ESSCA), 2013/14.

BACKGROUND: Contact allergy to rubber additives is common, particularly in patients with occupational dermatitis. OBJECTIVES: To descriptively analyse and compare patch test reactions in patients patch tested both with the baseline series and with an additional 'rubber series' as used in the department. METHODS: Patch test data from those members of the European Surveillance System on Contact Allergies (ESSCA) network (www.essca-dc.org) who also contributed data on rubber series patch test results were retrospectively analysed. RESULTS: Among 29 522 patients patch tested, 2870 were eligible, that is, patch tested both with the baseline series and with a special rubber series. Of these, 8.8% had positive reaction(s) to one of the baseline screening rubber allergens (as compared with 4.2% in all patients), most often to carba mix, 12.3% had positive reaction(s) to allergens from an additional rubber series, and 6.4% had positive reaction(s) to both. CONCLUSIONS: Additional testing with a dedicated rubber series, containing break-down single ingredients of mixes from the baseline series and additional rubber allergens, is warranted in patients with suspected contact allergy to rubber, to avoid false-negative results.

Occupational allergic contact dermatitis in a 2-year follow-up study: how well does the patient remember the result of patch testing?

BACKGROUND: Patch testing is mandatory for diagnosing contact dermatitis. It is, however, crucial that patients understand and remember the result of the test. OBJECTIVES: The aim of our study was to evaluate the impact of patch testing with respect to patients' ability to remember patch test results and the results of natural rubber latex protein allergy after 2 years. METHODS: One hundred and ninety-nine patients diagnosed with relevant occupational epoxy or rubber chemical contact allergy, or allergy to natural rubber latex protein, were invited to participate in a questionnaire study about their knowledge of contact allergies after 2 years. RESULTS: The response rate was 75%. Of the respondents, 13% did not remember their occupational contact allergy to rubber chemicals or epoxy. Ability to remember was not significantly influenced by sex or Dermatology Life Quality Index, but was decreased by age >60 years (p < 0.01). Of patients with an additional contact allergy, <36% remembered this correctly. Of patients allergic to natural rubber latex proteins, 50% remembered this correctly. CONCLUSIONS: The impact of patch testing depends on the patients' ability to understand and remember the results of the test. Attention should be drawn to the importance of this, and patients with increased need for information should be identified.

Patterns of simultaneous patch test reactions to thiurams and dithiocarbamates in 164 patients.

BACKGROUND: Thiurams and dithiocarbamates are structurally related sensitizing rubber accelerators. OBJECTIVES: To study patterns of simultaneous patch test reactions to thiurams and dithiocarbamates at the Finnish Institute of Occupational Health in 1991-2015. METHODS: We searched the patch test files for patients with allergic reactions to thiuram mix, its four components, and three dithiocarbamates, and analysed patterns of simultaneous reactions to these test substances. RESULTS: We found 155 patients who reacted positively to at least one thiuram or dithiocarbamate in the rubber chemical series. Thirty-four (22%) of these patients reacted positively to some dithiocarbamate derivatives. Twenty-one reacted positively to zinc dimethyldithiocarbamate, 20 to zinc diethyldithiocarbamate, and 1 to zinc dibutyldithiocarbamate. All dithiocarbamate-allergic patients reacted positively to some thiurams, and their thiuram reactions were often strong or extreme positive. Nine thiuram mix reactions turned out to be false-positive reactions, without reactions to the constituents, and 24 patients showed false-negative reactions to thiuram mix during the same time period. CONCLUSIONS: Dithiocarbamate contact allergy was always connected to thiuram allergy. Screening dithiocarbamate allergy with carba mix thus appears to be unnecessary, but ways to improve the present thiuram mix should be investigated. Meanwhile, individual thiurams are best for diagnosing contact allergy to these accelerators.

Occupational skin disease among Australian healthcare workers: a retrospective analysis from an occupational dermatology clinic, 1993-2014.

BACKGROUND: Healthcare workers (HCWs) are at risk of developing occupational skin disease (OSD). OBJECTIVES: To ascertain the causes of OSD in Australian HCWs in a tertiary referral clinic. METHODS: A retrospective review was performed of patients assessed at the Occupational Dermatology Clinic in Melbourne from 1993 to 2014. RESULTS: Of 685 HCWs assessed in the clinic over a period of 22 years, 555 (81.0%) were diagnosed with OSD. The most common diagnosis was irritant contact dermatitis (ICD) (79.1%), followed by allergic contact dermatitis (ACD) (49.7%). Natural rubber latex allergy was also relatively frequent (13.0%). The major substances causing ACD were rubber glove chemicals (thiuram mix and tetraethylthiuram disulfide), preservatives (formaldehyde, formaldehyde releasers, and isothiazolinones), excipients in hand cleansers, which are hard-to-avoid weak allergens, and antiseptics. ACD caused by commercial hand cleansers occurred more frequently than ACD caused by alcohol-based hand rubs (ABHRs). Occupational ICD was mostly caused by water/wet work and hand cleansers, and environmental irritants such as heat and sweating. CONCLUSIONS: Understanding the causes of OSD in HCWs is important in order to develop strategies for prevention. We suggest that skin care advice should be incorporated into hand hygiene education. The use of ABHRs should be encouraged, weak allergens in skin cleansers should be substituted, and accelerator-free gloves should be recommended for HCWs with OSD.

Content of Asthmagen Natural Rubber Latex Allergens in Commercial Disposable Gloves.

The use of natural rubber latex (NRL) gloves in many occupations may lead to latex sensitization, allergic asthma, and skin reactions. Due to their good properties and environmental safety NRL gloves are still being used in the healthcare setting, but also in the food industry, by hairdressers, cleaners, etc. The aim of our study was to assess the protein and NRL allergen content in commercial gloves by different methods, including a new assay. Twenty commercially available NRL gloves were analyzed. Protein extraction was performed according to the international standard ASTM D-5712. Total protein content was measured with a modified Lowry method, NRL content with the CAP Inhibition Assay, the Beezhold ELISA Inhibition Assay, and an innovative ELISA with IgY-antibodies extracted from eggs of NRL-immunized hens (IgY Inhibition Assay). We found a high protein content in a range of 215.0-1304.7 µg/g in 8 out of the 20 NRL gloves. Seven of the 20 gloves were powdered, four of them with a high protein content. In gloves with high protein content, the immunological tests detected congruently high levels of NRL allergen. We conclude that a high percentage of commercially available NRL gloves still represent a risk for NRL allergy, including asthma. The modified Lowry Method allows to infer on the latex allergen content.

[Latex allergy in a paediatric hospital. Characteristics and risk factors]. / Alergia al látex en un hospital pediátrico. Caracterización y factores de riesgo.

INTRODUCTION: The prevalence of latex sensitisation varies according to the population studied. There are various risk factors that increase latex sensitisation, such as genetic risk, atopy, and multiple surgeries. OBJECTIVE: To characterise patients referred to an Immunology Unit with suspected latex allergy, and to analyse their clinical features and risk factors. PATIENTS AND METHOD: A retrospective, descriptive study was conducted on children suspected of latex allergy. Their medical records were reviewed in order to assess symptoms with contact or exposure to latex materials. Known risk factors to latex sensitisation, such as pathologies requiring repeated surgery (spina bifida, myelomeningocele, scoliosis and nephro-urological alterations), atopy (rhinitis, asthma, atopic dermatitis) were investigated. A prick test and/or specific IgE to latex were also performed. A multivariate logistic regression model was performed to find associations between symptoms triggered by exposure to latex with underlying diseases and other risk conditions. RESULTS: A total of 106 patients were enrolled in the study, of whom 50 were evaluable. At diagnosis 96% of patients were older than five years. Most of the risk factors described were observable in these patients, such as multiple surgeries, neurological and nephro-urological malformations, surgery before one year-old, and repeated bladder catheterisation. After latex exposure, mucous cutaneous manifestations were the most common (52%), followed by respiratory symptoms (36%). All patients were sensitised and allergic to latex. CONCLUSION: Latex allergy is a significant problem in children with risk factors. The results shown in this study raise important challenges for preventive measures and awareness.

Perioperative anaphylactic reactions: Review and procedure protocol in paediatrics.

Perioperative anaphylactic reactions are immediate, hypersensitive reactions that are potentially life-threatening resulting from a sudden release of mediators from mast cells and basophiles, due to either immune (IgE or non-IgE mediated) or non-immune mechanisms. The most frequent causing agents are neuromuscular blocking agents (NMBAs), latex and antibiotics, with latex being the first cause in paediatrics. With regard to perioperative anaphylactic reactions, the usual early signs and symptoms of an anaphylactic reaction could be overlooked or erroneously interpreted and non-severe anaphylaxis could go undetected, with a risk of more severe reactions in the future. Using the data registered on the anaesthesia sheet, it is essential to establish a chronological relationship between drugs and/or substances administered and the reaction observed. An elevated level of tryptase confirms an anaphylactic reaction, but this does not usually increase in the absence of compromised circulation. An allergy study should be carried out preferably between 4 and 6 weeks after the reaction, using a combination of specific IgE, skin and controlled exposure tests (if indicated). Test sensitivity is good for NMBAs, latex, antibiotics, chlorhexidine, gelatine and povidone, and poor for barbiturates, opiates (these can give false positives since they are histamine releasers) and benzodiazepines. Special preventive measures should be taken, especially in the case of latex. We present the maximum concentrations recommended for skin tests, the recommended dosage to treat anaphylactic reactions in paediatrics and a procedure algorithm for the allergological study of these reactions.

[Application of recombinant latex allergens in diagnostics of occupational latex allergy]. / Zastosowanie alergenów rekombinowanych w diagnostyce zawodowej alergii na lateks.

Over many years, allergy to natural rubber latex has been a major problem among health care workers (HCW). The diagnosis of occupational allergy requires methods of high diagnostic accuracy in view of certification implications (e.g., a sick worker quits a job). With the development of molecular methods, the frequency of application of recombinant allergens it the diagnostics of allergic diseases continues to increase. This paper reviews the applicability of laboratory tests which use recombinant allergens in the diagnostics of occupational allergy. The diagnosis of latex allergy is based on the presence of clinical symptoms linked with exposure to latex allergens, positive skin prick tests and detection of specific IgE antibodies to latex in serun. Moreover, in some cases specific challenge tests are conducted. The analysis of literature indicates that applying the panel of recombinant latex allergens in diagnostic tests, cross-reactivity can very likely be excluded and/or sensitization can be confirmed without the need for specific challenge tests, which in case of latex allergens carries a potential risk of aeneralized reactions.

Diagnostic value of the ISAC(®) allergy chip in detecting latex sensitizations.

PURPOSE: Latex allergy can be diagnosed by different test methods such as IgE quantification, Western blot, cellular antigen stimulation test (CAST), and in vivo methods [e.g. skin prick test (SPT)]. Phadia provides two modern methods using recombinant latex allergens: ImmunoCAP(®) and the Immuno Solid-phase Allergen Chip (ISAC(®)), which enables simultaneous determination of specific IgE against five latex allergens. We compared the diagnostic sensitivity of the ISAC(®) test kit and the conventional Hev b 5-spiked ImmunoCAP(®) latex extract. METHODS: Forty sera were sampled from subjects with suspected natural rubber latex (NRL) allergy. These patients had positive SPT to NRL extract, positive NRL Western blots, and positive results in the CAST. All sera were analysed using the ISAC(®) and recombinant NRL ImmunoCAP(®) allergens and compared to the results of 20 negative control sera. RESULTS: Only 22 of the 40 subjects (55 %) showed positivity to at least one latex allergen on the ISAC(®) (sensitivity ISAC(®) 55 %). The sensitivity of the ImmunoCAP(®) latex extract was 70 %. The most frequently detected sensitization was against Hev b 6.01 (n = 12). When the serum samples were tested with all recombinant ImmunoCAP(®) allergens, three additional sensitizations against latex could be detected compared to the ISAC(®). CONCLUSIONS: Microarrays do offer many potential benefits such as elegant simultaneous determination of sensitizations against different NRL allergens with minimal amounts of serum. However, a negative NRL test result should be regarded with caution and at least be confirmed by other in vitro methods.