Natural Rubber Latex Proteins Research Articles

Latex allergy - from discovery to component-resolved diagnosis.

Latex allergy is a hypersensitivity response to natural rubber latex (NRL) proteins or rubber chemicals used in the manufacture of latex products. An accurate diagnosis is the first step in the effective management of individuals with latex allergy, especially in high-risk groups, such as healthcare workers and those affected by spina bifida. Diagnosis is based on the clinical history and an accurate allergological evaluation. In the case of type I IgE-mediated hypersensitivity re-actions, which can manifest urticaria, angioedema, rhinoconjunctivitis, asthma and anaphylaxis after latex exposure, skin prick tests or latex-specific IgE (sIgE) antibody detection using sero-logical assays can be performed to confirm sensitization. Instead, in the case of contact dermati-tis, a patch test can be applied to confirm the presence of a type IV T cell-mediated hypersensi-tivity reaction to rubber accelerators or additives. Basophils activation tests or challenge tests may be performed if there's an incongruity between the clinical history and the results of in vivo and in vitro tests. The aim of this review is to analyze the current state of the art of diagnostic techniques for latex allergy and algorithms employed in clinical practice and possible future de-velopments in this field.

A New Preparation Method for cis-1,4-polyisoprene/Na-montmorillonite Latex Composites by in situ Solution Emulsification

AbstractCis-1,4-polyisoprene latex (IRL) is the best alternative to natural rubber latex (NRL), and can help to avoid human allergic reactions caused by proteins in NRL. The mechanical properties of IRL are inferior to those of NRL, however. To address this issue, a novel strategy was developed using an in situ solution emulsification to prepare a latex composite incorporating sodium montmorillonite (Na-Mnt). The properties of the latex film prepared were investigated. The dispersion state of the Mnt in the latex composites and the morphology of the resulting composite films were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, the mechanism of Mnt reinforcement of IRL is described comprehensively. The results showed that the Mnt/IRL latex composites prepared were stable and excellent films were formed, similar to those of NRL. The current research provided an effective method for preparing high-performance composite films suitable for use in high-end medical applications.

Alergia ao Látex em Contexto Ocupacional

Introduction/framework/objectives Latex allergy is recognized as a widespread health problem that assumed serious proportions in the 1990s. Although preventive measures have markedly decreased its incidence, recent studies have shown that it remains an important health problem in certain population groups, particularly in developing countries. This work aims to provide a comprehensive review of the current status of occupational latex allergies. We summarize various aspects of this condition, such as prevalence, risk groups, latex allergens, the diagnostic approach, prevention, and treatment. Methodology A bibliographic review was carried out in January 2023 in the following databases: PubMed/Medline, Cochrane Library, Evidence-based Medicine, Canadian Medical Association, Practice Guidelines and National Guideline Clearinghouse. Content Repeated exposure to latex in an occupational context can lead to worker sensitivity, with a significant clinical and socio-economic impact. We summarize various aspects of this condition, such as prevalence, risk groups, latex allergens, the diagnostic approach, prevention and treatment. Discussion and Conclusions The history of latex allergies has demonstrated that potent allergens such as Natural Rubber Latex proteins can cause rapid immunoglobulin-E-mediated sensitization and clinical allergies, reaching serious proportions in highly exposed individuals. Occupational exposure has a decisive influence on the allergen sensitivity profile, with important clinical and therapeutic consequences. The effectiveness of secondary prevention measures is limited. Thus, it is essential to implement early primary prevention measures in individuals belonging to risk groups, to avoid or minimize exposure to latex allergens. KEYWORDS: Healthcare Professionals, Latex allergy, Latex gloves, Latex hypersensitivity, Natural rubber latex, Occupational diseases, Occupational health, Occupational Medicine.

Latex Allergens in the Ear Straps of Face Coverings and Masks in the UK: Initial Findings

The SARS-CoV-2 pandemic led to an unprecedented demand for PPE and generated a small-scale industry making personalised face coverings. Concerns had been raised about the use of natural rubber latex (NRL) as an elastomeric material, with its health risks. We have investigated the levels of four NRL allergens and total protein in elastomeric ear-straps in manufactured face coverings and the material sold for their production, and a number of imported N95/KN95 PPE masks. None of the samples identified whether NRL was involved or not. NRL allergens levels in manufactured masks were low or not detectable; 3/10 of the N95/KN95 masks showed levels above the limit of detection, probably reflecting low-level cross-contamination during manufacture. Three batches of material sold for “the manufacture of ear straps for face coverings” had significant but variable levels of allergen (250–2526 ng/g of material). Historically, extractable protein measurements have been used as an indicator of possible NRL proteins. This study showed significant levels of apparent protein in sample extracts without measurable NRL allergens or confirmation by electrophoresis. Therefore, the immunochemical measurement of NRL allergens remains key to rule out elastomeric material with the potential to cause latex-related health problems.

Considering the switch to a latex-free glove policy to safeguard staff and patients.

While it is difficult to imagine that before the late 1800s, surgeons in the theatre environment operated on patients without gloves, gloves are now a clinical necessity. Their use has risen exponentially over the last 30 years, along with concerns over staff and patient allergy and sensitivity to the natural rubber latex proteins used in their manufacture. Having used latex gloves for the better part of 35 years, the author recently evaluated a latex-free alternative. In this article, which presents a rationale for the introduction of a latex-free glove policy across NHS departments and trusts, particularly in theatre settings, the author presents his experience, together with cases from four other surgeons, as well as evidence from the literature regarding potential clinical outcomes, quality of life and cost-effectiveness associated with latex-free gloves.

Studies on the effect of purified natural rubber latex and accelerators on rubber allergens in natural rubber dipping product

Natural rubber (NR) glove is a worldwide use product of NR latex, which is mainly used for protective purposes. However, allergic reactions to NR gloves causing by the residual proteins in NR latex and chemical used in the manufacturing process, which are called as rubber allergens, are still a significant concern. Thus, the present work is an attempt to minimize such the rubber allergens from NR dipping products, herewith, finger cot is used as a model for this study. Purified NR latices were prepared by an urea treatment and saponification method, called as deproteinized NR (DPNR) and saponified NR (SPNR), respectively. Both of DPNR and SPNR were found to have low nitrogen content. Fourier-transform infrared spectroscopy (FTIR) was used to identify functional groups as a result of the absence of the amine functional group, which can be referred to proteins. For a compounded NR, the various purified NR latices and rubber accelerators were used in the compounded formula. The existing and residual proteins of each sample were analysed by Bradford’s assay and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) method, respectively. The DPNR and SPNR were found to contain lower protein profiles. The residual rubber accelerators released into artificial sweat were extracted and analysed by high-performance liquid chromatography (HPLC) technique.

Natural rubber latex (NRL) waste protein purified at various pH condition and metal extraction studies

Purification of NRL protein was accompanied by extraction of waste proteins using salting out and multiple centrifugation methods. Both methods contributes to varying degree of yield and purified protein characteristics. However both methods produces protein that can bind metal efficiently. Conventionally, salting out method was used and it is uncommon to use multiple centrifuge to extract protein. The key aspects discussed here, were on how the pH condition exposed to the NRL waste leads to variation in hevea protein extracted amount and how metal binding featured in FTIR spectroscopy. The purified protein were reacted with metal solution of different strength to study the binding characteristics. Molecular weight cut-off (MWCO) size of dialyzing tube shows greater effect on the final protein extracted amount by about 50% when smaller size were used. Acidic condition favors part of proteins from waste in purification while some favors basic condition. Standard salting out method shows consistent profile in extracting metal compared to multiple centrifugation method from 30 to 80%.

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

Patch testing is mandatory for diagnosing contact dermatitis. It is, however, crucial that patients understand and remember the result of the test. 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. 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. 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. 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.

Improved Deproteinization Process for Protein-Free Natural Rubber Latex

Hev b1-14 type proteins in natural rubber latex (NRL) have been identified as allergens in immunogenic responses. Several methods have been developed to reduce these proteins from NRL such as enzyme treatment, centrifugation, creaming, simple or ultrasonic leaching, and chlorination. In this work, the improvement of deproteinization of NRL was developed using the combination of enzyme treatment and leaching processes. The fresh NRL was incubated with 0.2 phr proteolytic alcalase enzyme, and preserved with 2%v/v paraben concentrate in the presence of a 2%v/v sodium lauryl ether sulfate (SLES) as a surfactant at 37°C for 24 hours, and then centrifuged. The upper rubber mass was then leached for three times with either distilled water, a 1%v/v SLES solution, or a mixture of 1%v/v SLES and 2.5%v/v ethanol, and then finally re-dispersed in distilled water. It was found that the increasing process of leaching with either 1%v/v SLES or a mixture of 1%v/v SLES and 2.5%v/v ethanol had the higher efficacy to reduce the remained protein in deproteinized NRL (DNRL). The best deproteinized process was the enzyme treatment and followed by the three times leaching process with a mixture of 1%v/v SLES and 2.5%v/v ethanol, that could completely reduce the proteins in DNRL to 0%. This DNRL had the pH value, viscosity, dry rubber content, and total solid content of 7.41, 13.82 cps, 42.57%, and 44.63%, respectively. Its particle size was 626.23 nm with low polydispersity index of 0.16. The negative charge of SLES could increase the higher negative charge of DNRL to-63.20 mV that exhibited very good physical stability during storage. In conclusions, the combination of enzyme treatment and leaching process with both SLES and ethanol was successful to produce the protein-free DNRL. This DNRL could be further used for several applications including medical skin products.

Cosmetic Pore Packs from Deproteinized Natural Rubber Latex

Natural rubber latex (NRL) from Hevea brasiliensis consists of cis-1,4-polyisoprene that have many excellent physical properties such as high elasticity, tensile strength, and easily film-forming. However, some proteins in NRL can cause allergy. Hence, this research aimed to prepare cosmetic pore packs from deproteinized NRL (DNRL) that was prepared in-house by enzyme treatment and centrifugation processes. The properties of DNRL were evaluated in terms of amount of remained protein, pH, particle size, polydispersity index, and zeta potential. This DNRL was then formulated the pore pack products by mixing with the other ingredients and casting to the film form. An appropriate pore pack formulation composed of sodium alginate and polyvinylpyrrolidone K30 mixed with DNRL to produce films with good properties. Hydroxypropylmethylcellulose was also added to another formulation for improving toughness of the films. Both products had similar appearance and physical properties such as thickness, uniformity of weight, pH, tensile strength, and elongation at break, but lower peel strength comparing with the commercial pore pack product. These films showed good flexibility, softness, and toughness. After storage at room temperature for a month, there were no different in appearance and pH that presented good stability. The obtained pore packs also exhibited desirable characteristics with acceptable volunteer satisfactions. However, they should be improved for more adhesiveness in further study. In conclusion, DNRL could be used as major component for cosmetic pore pack preparations.

Novel Process in Preparation of Deproteinized Natural Rubber Latex

Natural rubber latex (NRL) tapped from Hevea brasiliensis is composed of cis-1,4-polyisoprene as the major polymer which provides several desirable physical properties which make it to be interesting in pharmaceutical formulations. However, the International Union of Immunological Societies (IUIS) has reported about latex allergies caused by 14 NRL proteins (Hev b1-14). This problem can be coped with deproteinization of NRL in order to obtain deproteinized natural rubber latex (DNRL). This study aimed to prepare DNRL by novel process which was easy to perform and used pharmaceutical acceptable agents. The obtained DNRL was assayed for remained protein amount in form of nitrogen content by Kjeldahl method. Its physical properties were characterized. Its stability was also physically investigated. The DNRL was tested for the skin irritation in 3 rabbits. It was found that the protein amount of DNRL was 0.257% while the initial protein amount of fresh NRL was 1.531%. Hence, the protein was removed for 83.21%. DNRL had the average pH of 7.27. Both protein content and pH value implied that DNRL should be safe for skin application. DNRL possessed Newtonian flow with low viscosity which should be easy for mixing with other components in the further pharmaceutical formulations. The particle size, polydispersity index (PI), and zeta potential of DNRL were 441.0 nm, 0.240, and -42.53 mV, respectively, indicating narrow size distribution and physical stability. The dry rubber content and total solid content of DNRL were controlled as 39.55% and 40.72%, respectively. The suitable storage condition of DNRL was at 2-8°C in tight containers where DNRL could be kept for longer than 4 months. Very slightly irritation with no allergy caused by DNRL was observed in the tested rabbits. It could be concluded that this deproteinization process was easy and the prepared DNRL by this process was suitable and safe for using in further pharmaceutical and cosmetic formulations.

Latex glove allergy: The story behind the "invention" of the surgical glove and the emergence of latex allergy

Latex rubber gloves have become increasingly common over the last 30 years. This has led to an increase in allergy to natural rubber latex (NRL) proteins in health care professionals using protective gloves and/or in those exposed to products made of NRL. This has led to a growing need to monitor the allergenicity of gloves and other latex goods to prevent sensitization and clinical allergy. There is still considerable amount of misinformation regarding latex allergy. In this article, we examine the history behind the invention of the surgical glove, the emergence of latex allergy and the diagnostic tests available and possible remedies. We searched PubMed and MedLine using key words such as Latex allergy, surgical gloves, rubber, immunoglobulin E proteins, radioallergosorbent test. Recent and old papers on the subject were reviewed and analyzed. Surgical gloves were a huge milestone in the field of surgery as it allowed the development in the field of asepsis. It was instrumental in reducing the rates of infection and making health care professionals think about aseptic techniques. However, the emergence of latex allergy over the last few decades has proved a challenge in the perioperative setting. Surgical gloves are important tools in performing safe surgery. However, the increasing incidence of latex allergy and its effects on theatre personnel is of great concern.

Removal of water extractable proteins from concentrated natural rubber latex by eggshells

The protein allergy caused by latex products has become an acute problem to human and animals; sweat removes proteins, which then comes in contact with the skin causing the sensitization or allergic reactions. Eggshells from chickens, ducks, and birds are potential starting materials to be used in reducing the water extractable proteins in concentrated natural rubber latex (NRL). The pyrolysis of eggshells at 900°C for 2 h transforms the crystal structure of calcium carbonate into calcium oxide with a high purity, creates a small and uniform particle size, a suitable specific surface area, and an average pore diameter that is suitable for reacting with hydrochloric acid to obtain calcium chloride (CaCl2). The additions of CaCl2 solution and sodium dodecyl sulphate into concentrated NRL are shown and reported here to extract effectively the proteins from the NRL film.

Thermal and Thermo-Oxidative Degradations of Deproteinized Natural Rubber and Natural Rubber

Deproteinization of natural rubber was achieved in the latex stage. The structure of deproteinized natural rubber (DPNR) was characterized by fourier transform infrared spectroscopy (FTIR). The thermo degradation of DPNR was studied by thermogravimetry analysis (TG) under air atmosphere and nitrogen atmosphere. The kinetic parameters apparent activation energies (Ea) of the thermal decomposition reaction been calculated from the TG curves using the method described by Broido. And the results were compared with the thermo degradation of natural rubber (NR) under the same conditions. The effect of proteins in natural rubber latex on thermal/ thermo-oxidative stability of NR was discussed. The results show that: the absorptions of the proteins in DPNR at 1546 ㎝-1, compared to NR, become significantly weaker, nearly disappear, which indicates most of proteins has been removed from NR. The thermo degradation of DPNR in nitrogen atmosphere is a one-step reaction. The initial degradation temperature (T0) 、the maximum degradation temperature（Tp） and the final degradation temperature（Tf）as well as the Ea of DPNR are higher than those of NR, which indicates that DPNR represents a better thermal stability than NR under nitrogen atmosphere. Thermo-oxidative degradation of DPNR and NR are two-step reaction. The characteristic temperatures (T0, Tp and Tf) of DPNR are lower than those of NR. The Ea during the First Step of Thermooxidative Degradation of DPNR are also lower than those of NR. These results prove that the thermo-oxidative stability of DPNR is worse than that of NR. Protein is the key role to the thermal stability of natural rubber.

Development of a rubber elongation factor, surface-imprinted polymer–quartz crystal microbalance sensor, for quantitative determination of Hev b1 rubber latex allergens present in natural rubber latex products

Molecularly imprinted polymers (MIPs) for screening to detect rubber latex allergens (Hev b1) in natural rubber based products were designed as artificial recognition polymeric materials coated onto a quartz crystal microbalance (QCM). The polymers were prepared using a stamp imprinting procedure after mixing optimum amounts of methacrylic acid–vinylpyrrolidone–dihydroxyethylene bisacrylamide and Hev b1 latex allergen proteins, obtained from rubber gloves. QCM measurements showed that the resulting polymer layers after removal of the proteins used in their preparation could incorporate structures and features down to nanometer scale of protein templates into the imprinted polymer much better than a non-specific control polymer under controlled sensor conditions and an optimized polymerization process. This selective polymer but not the non-selective polymer clearly distinguished between the latex allergen Hev b1 and proteins such as lysozyme, ovalbumin and bovine serum albumin, with a selectivity factor of from 2 to 4, and the response of the rubber elongation factors by an astonishing factor of 12. The imprinted cavities recognized specific binding sites and could distinguish among related hevein latex allergenic proteins isolated from fresh natural rubber latex; Hev b1, Hev b2, and Hev b3 with a selectivity factor of from 4 to 6. The different QCM measurements obtained presumably reflected slightly different conformations and affinities to the MIP binding sites. The sensor layers selectively adsorbed Hev b1 within minutes in amounts ranging from 10 to 1500 μg L −1 and with a detection limit of 1 μg L −1. This work has demonstrated that this new sensor provides a fast and reliable response to natural rubber latex protein, even after being extracted from the matrix of rubber gloves.

A Proteomic Investigation of B Lymphocytes in an Autistic Family: A Pilot Study of Exposure to Natural Rubber Latex (NRL) May Lead to Autism

Autism is a multi-factorial neurodevelopmental disorder. We have investigated the molecular mechanism involved in a Chinese family with autism by a proteomic approach. Antibody chips containing 500 spots of human protein antibodies were used to screen for differentially expressed proteins in the peripheral B lymphocytes between autistic and non-autistic siblings in this family. Four proteins relevant to immuno-pathway, including IKKα that was up-regulated and Tyk2, EIF4G1 and PRKCI that were down-regulated, were identified differentially expressed in autistic versus non-autistic siblings. Western blot analysis and reverse transcription quantitative polymerase chain reaction validated the differential expression of these four proteins. Based on the function of these differentially expressed proteins, relevant studies on immunoglobulin E (IgE) level, nuclear factor kappa B signaling activation and cell cycle were conducted in both autistic and non-autistic children of this family. Considering the fact that the family members were in close contact with natural rubber latex (NRL) and that IgE-mediated cross-reactions could be triggered by Hevea brasiliensis (Hev-b) proteins in NRL, we hypothesize that immune reactions triggered by close contact with NRL might influence the functions of B lymphocytes by altering expression of certain proteins identified in our experiments thus contributing to the occurrence of autism.

Effect of Deproteinized Methods on the Proteins and Properties of Natural Rubber Latex during Storage

AbstractSummary: Three different methods of deproteinization, i.e. saponification, surfactant washing and enzymatic treatment were employed to unravel the effect of deproteinized on the properties of natural rubber (NR) latex. The cleavage of proteins in NR latex was found to proceed with concomitant formation of low molecular weight polypeptides. This results in a lowering in gel formation of the enzyme‐treated latex, indicating modification of the remaining proteins at the rubber chain‐end. Washing NR latex with surfactant would efficiently reduce and remove proteins from NR latex particles through denaturation and transferring them to the serum phase. The relatively stable gel formed during storage of surfactant‐washed NR latex is an indication of the absence of branch formation of proteins at the rubber molecule terminal. Saponification by strong alkali would hydrolyze the proteins and phospholipids adsorbed on the latex particle surface. The reason of the significantly higher gel formed in saponified NR latex is still not clear. The present study shows that deproteinization treatments result in modification of the proteins at the surface of NR latex particles and also those freely‐suspended in the serum. The cleavage or the denaturation of the rubber proteins during purification by washing has a profound effect on the properties of the deproteinized NR latex upon storage, in particular the thermal oxidative aging properties of the rubber obtained.

Natural Rubber Latex Allergy in Pediatric Patients

During the last fifteen years better hygienic standards led to an increased consumption of natural rubber latex (NRL) gloves for the protection of medical staff. At the same time case reports about an IgE-mediated allergy to NRL sometimes causing life-threatening anaphylactic reactions came up. This allergy was different from the well-known type IV reactions caused by latex additives. Health care workers and patients with multiple surgery surgeries were identified as high risk groups. For unknown reasons patients with spina bifida (SB) showed the highest prevalence of NRL-specific IgE-antibodies. A pre-existing atopy increased the risk of latex sensitization. Allergic reactions were caused mainly by medical procedures, especially surgeries, if latex gloves and other latex containing devices were used. Meanwhile some allergenic proteins in NRL (named Hev b in accordance with the rubber tree Hevea brasiliensis) could be identified. Patients in different risk groups showed distinct prevalences of sensitization to these allergens. The way of the allergen uptake (aerogen or by direct mucosal contact during surgeries) played an important role in the sensitization to different allergens. Most of the latex allergens like Hev b 1, Hev b 3, Hev b 6.02 have been totally sequenced. Since the sequence of all registrated allergens (Hev b 1 - Hev b 13) is known, it was possible to localize in Hev b 1, Hev b 5 and Hev b 6.01 several IgE binding sites as well as T cell epitopes. Cross-reacting antibodies between NRL and numerous fruit were described and for some proteins structural homologies were well characterized. For the in vitro diagnosis of NRL allergy serologic tests with improved extracts and recombinant allergens (for instance ImmunoCAPTM system) are available. NRL protein extracts for skin prick tests were difficult to standardize. The use of natural extracts in combination with recombinant latex allergens could be one possible future perspective for skin testing. The problem of NRL allergy is still not resolved but significant progress has been made in its prevention. In high risk patients like persons with spina bifida a primary prophylaxis was performed with success, but also secondary or tertiary prophylaxis allows safe operations without symptoms of NRL allergy.

Glove-Derived Foreign Proteins Induce Allergen-Specific IgE in a Mouse Model

Currently, most medical gloves are produced with a low content of natural rubber latex (NRL) protein. However, they may be substituted by proteins of foreign origin to maintain specific properties of the material. The aim of this study was to investigate the allergenicity and immunogenicity of unexpected proteins (i.e., soy and casein) compared with NRL proteins in a murine model in BALB/c mice. All respective allergen sources (extracts from three brands of NRL gloves, soy, and casein) were able to induce significant allergen-specific IgE and IgG(1) responses. On average, the highest IgE induction occurred after immunization with NRL, followed by soy and casein. Certain individuals from each treatment group exhibited levels of specific IgE as high as due to NRL. To analyze further specific IgE responses on a single allergen level, we established a microarray based on recombinant allergens for allergen-specific murine IgE detection. Besides specific IgE against rHev b 3, -6, -7, -8, and -11, specific IgE against kappa-casein could be detected in mice immunized with NRL glove extract, indicating a sensitization potential of the contained foreign protein. The substitution of genuine latex proteins by proteins of foreign origin may lead to a shift and de novo increase in sensitization to the finished products.

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

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. 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. 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. 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. 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.