LATEX HYPERSENSITIVITY: PERSONAL DATA AND REVIEW OF THE LITERATURE

ABSTRACT

Latex allergy is an increasingly common condition, because use of latex products is widespread. The reactions to latex manufactures can be classified as allergic and non-allergic, these are the most common. Latex proteins are responsible for immediate IgE-mediated hypersensitivity allergic reactions. Symptoms range from rhinitis, conjunctivitis and urticaria to anaphylactic shock. Chemical additives can cause allergic contact dermatitis. The clinical symptoms of latex allergy could arise from direct contact with latex products, but may also result from inhalation of airborne allergens. Subpopulations at particular risk include: atopics, children with spina bifida or individuals who required frequent surgical instrumentations, health care workers, and all persons who have regular contact with latex products. Diagnosis of allergy is based initially on history; search for specific serum IgE, skin prick test and provocation test may confirm the suspicion. The most effective strategy in the treatment of latex allergy is avoidance, however this is virtually impossible, given large number of latex products we encounter since childhood. In this paper we review the current state of knowledge concerning latex allergy, including the clinical spectrum, identified allergens, the cross-reactions regarding the latex-fruit syndrome, diagnostic procedures and preventive measures. Several personal data increase awareness on this issue.     

IDENTIFICATION OF ANTIGENIC AND ALLERGENIC NATURAL RUBBER LATEX PROTEINS BY IMMUNOBLOTTING1*

ABSTRACT

Quantitation of proteins in finished natural rubber latex (NRL) products is essential in predicting their allergenic potential. The ASTM standard Modified Lowry method for measuring total protein content has been used for several years. Most recently, ASTM published a standard for more sensitive and more specific enzyme immunoassay for quantitation of antigenic NRL proteins. It is an ELISA inhibition assay, using rabbit anti NRL sera. Since the measurement of proteins in this method depends on recognition capacity of rabbit antibodies, the selection of an appropriate protein source for rabbit immunization is crucial for the accuracy of such test. In this study, we evaluated the composition of NRL proteins from ammoniated (AL) and nonammoniated (NAL) raw latex and from finished NRL products, and compared the effectiveness of sera from rabbits immunized with NRL proteins, to react with those extracts. Immune rabbit sera were analyzed by immunoblotting against extracts of several samples of AL, NAL, and glove proteins. In the NAL extracts, we identified 26–28 protein bands by SDS-PAGE. AL samples had between 6 and 9 bands with a great variation in the band positions among the samples. The Western blot analysis showed that anti-AL rabbit serum reacted with 4–9 protein bands in various AL extracts. The highest intensity of reaction was observed with the extract used to immunize the rabbits. Similar reaction was observed with anti-NAL serum. However, when the antisera were blotted against NAL extracts, anti-NAL serum reacted more strongly and with a larger number of proteins than anti-AL serum. In summary, anti-NAL serum recognized an equal number of proteins in AL extract as anti-AL serum. However, anti-AL serum recognized fewer protein molecules in NAL extract than anti-NAL serum. Our findings suggest that NAL extract contains more individual proteins than other extracts, and sera from rabbits immunized with this antigen have a greater capacity to react with a wide spectrum of NRL proteins. This finding may be helpful in selecting the representative reference antigen and antiserum for further efforts in NRL protein quantitation.

     

A COMPARISON OF THE ROSE-WAALER,LATEX FIXATION, "RA-TEST," AND BENTONITE FLOCCULATION TESTS

The bentonite flocculation test of Bozicevich, Bunim, Freund, and Ward (1958), the latex fixation test of Singer and Plotz (1956), and the "RA-test" (a latex reagent for use as a slide test) of Hyland Laboratories have been compared with each other and with a modified Rose-Waaler test, the behaviour of which has been previously extensively investigated. In these tests sera from 2,250 patients were tested by two or more methods on 3,000 occasions. The findings of this trial are set out and the merits of the tests and reasons for disagreement among them are discussed. It is concluded that the most satisfactory means of testing rheumatoid sera is by the Rose-Waaler test and the "RA-test," or a satisfactory modification of it, in parallel.     

Latex allergy and latex sensitization in children and adolescents with meningomyelocele

Background: The high prevalence of clinical latex allergy and latex sensitization in children with meningomyelocele has been widely reported. It has also been noted that these same children have a higher than expected prevalence of atopic disease. It would be useful to have a safe, sensitive, and specific skin test to detect latex sensitivity and to know how well this test compares with available in vitro tests. It would likewise be helpful to know as fully as possible the characteristics of the individual and to evaluate the relative importance of factors suspected to contribute to clinical latex allergy and latex sensitization in this population. Methods: A group of 116 children and adolescents 1 to 20 years of age were recruited for the study. An extensive history of latex allergy, atopic diseases, and surgical procedures was taken on all subjects. Each subject had either a latex skin test or an in vitro study for latex-specific IgE, and 67 subjects had both tests simultaneously. Eighty-five subjects had epicutaneous skin tests to a panel of environmental allergens. Results: Overall, 25 of 116 (21.5%) subjects had a history of clinical latex allergy, and 51 of 116 (44%) were sensitized to latex. The sensitivity and specificity of skin tests for clinical latex allergy were slightly greater than for the in vitro test (100% vs 95.8% and 82.3% vs 68.9%, respectively). The positive predictive value and negative predictive value of skin testing for clinical latex allergy were also greater (67.6% vs 50% and 100% vs 98.1%, respectively). Age was found to be a significant variable for both latex allergy and latex sensitization. The number of surgical procedures undergone and the presence of positive skin test responses to environmental allergens were significantly correlated with latex sensitization but not with clinical allergy to latex. Conclusions: A sensitive, specific, and safe skin test for latex sensitivity appears superior to in vitro testing for latex allergy. Age, number of surgical procedures, and the presence of positive allergen skin test responses are significantly correlated with latex sensitization. Age alone is significantly correlated with clinical allergy to latex. (J Allergy Clin Immunol 1998;101:741-6.)     

The relationship between latex skin prick test responses and clinical allergic responses

BACKGROUND: Allergic responses to latex have been reported more frequently in the past 5 years. Although commercial skin prick test solutions are available and can be used in the diagnosis of latex allergy in some countries, the characteristics of patients sensitized to latex relative to their skin test responses have not been reported. OBJECTIVE: The purpose of this study is to relate the clinical characteristics of patients with latex sensitivity to the size of their latex skin prick test response. METHODS: A retrospective review of patients who were attending a hospital-based allergy and asthma clinic and who had positive skin test responses to a commercial latex skin test solution was undertaken. RESULTS: Of 47 patients who had skin test responses to latex, 36 had a mean wheal diameter at least 3 mm greater than the negative control (diluent). Sixty-eight percent were health care workers. There was a positive association between the size of skin test response and severity of latex-induced symptoms (p < 0.001). A history of banana sensitivity was also associated with larger skin test responses (p < 0.05). CONCLUSION: The size of the skin prick test response to latex solution that is commercially available in Canada reflects the severity of latex-induced clinical allergic responses. (J Allergy Clin Immunol 1996;97:1202-6.)     

Comparison of enzyme-linked immunosorbent assay with coagglutination and latex agglutination for rapid diagnosis of pneumococcal pneumonia by detecting antigen in sputa

A sandwich enzyme-linked immunosorbent assay detecting the species-specific pneumococcal C polysaccharide was compared to latex agglutination and a coagglutination test which detected capsular pnenmococcal antigens in sputum specimens with regard to specificity and sensitivity. Specimens from 52 patients with clinical and radiological evidence for pneumonia were tested. Twenty-one patients with Streptococcus pneumoniae isolated in sputum and 31 patients with a non-pneumococcal etiology were included. The predictive values for a positive test by enzyme-linked immunosorbent assay was 0.91 and for a negative test 0.97, by latex agglutination 0.90 and 0.91, and by coagglutination 0.84 and 0.85 respectively; these values did not show a statistically significant difference. Whereas agglutination tests are technically more simple and can be performed more rapidly, the enzymelinked immunosorbent assay has the advantage of detecting pneumococcal C polysaccharide, an antigen common to all pneumococci. Thus it provides an interesting alternative to tests based on serum containing antibodies to all 83 different capsular polysaccharides.     

Analysis of available diagnostic tests for latex sensitization in an at-risk population

BackgroundLack of a Food and Drug Administration (FDA)–approved skin testing reagent for latex allergy in the United States requires reliance on patient history and serologic assays for diagnosis.ObjectiveTo determine the diagnostic sensitivity, specificity, and predictive values of an FDA-cleared antilatex IgE serology test and an enzyme-linked immunosorbent assay (ELISA) with various sources of latex protein antigens in an at-risk but unselected population of health care workers.MethodsHealth care workers underwent duplicate latex and serologic testing for latex specific IgE with the CAP assay and ELISA from June 1, 1998, through December 31, 2002. Logistic regression with receiver operating characteristic curve analysis determined the values, resulting in 98% and 99% specificity for the CAP assay and ELISA, respectively.ResultsResults of paired skin and serologic tests were available for 792 participants. Forty duplicate skin test results (5%) were positive. For the CAP assay, sensitivity was 35%; specificity, 98%; positive predictive value, 48.3%; and negative predictive value, 96.6%. ELISA demonstrated similar results. Multivariable logistic regression yielding a 98% or 99% specificity for the various ELISAs demonstrated that the adjusted odds of a positive skin test result significantly increased with positive CAP assay and ELISA results using a powdered glove extract.ConclusionsThe performance of the FDA-cleared antilatex IgE serologic test for latex allergy has much lower sensitivity than previously reported. This finding confirms that this serologic test should be used only for patients with a history of latex allergy and not for screening the population with a low prevalence of latex sensitization.     

Component-resolved immunologic modifications, efficacy, and tolerance of latex sublingual immunotherapy in children

BackgroundAs the frequency of natural rubber latex (NRL) allergy has increased, attempts have been made to diminish exposure in high-risk patients. Despite some good results, complete NRL avoidance was not possible, so latex immunotherapy was developed.ObjectiveTo examine variations in immunologic parameters, clinical efficacy, and safety of NRL sublingual immunotherapy (SLIT).MethodsThis prospective, observational, open, case-control study included 23 patients (18 patients receiving NRL SLIT and 5 controls). Skin prick, conjunctival provocation, and in-use tests with NRL, specific IgE and specific IgG4 to NRL, specific IgE to recombinant NRL allergens, and basophil activation test (BAT) with whole latex, natural, and recombinant allergens were performed before immunotherapy (T0) and at 6 (T1) and 12 months (T2) of treatment.ResultsPatients were sensitized to Hev b 5, Hev b 6.01, and Hev b 6.02 proteins, optimal for SLIT. Changes in specific IgE were not significant. Increases in specific IgG4 between T1 and T2 were larger in the active group. BAT determinations showed significant decreases in recombinant Hev b 6.01 and natural Hev b 6.02 in the active group at T1 but not at T2. Both groups had new sensitizations at T1 but not at T2. The active group had significant increases in the response threshold in the in vivo tests at T1 and T2. Adverse effects were limited to local reactions.ConclusionNRL SLIT is effective and safe in children with latex allergy. Our results suggest that specific IgE determinations and BAT measurements to natural and recombinant latex allergens may allow obtaining an allergen-based diagnosis to help determine specific immunotherapy.     

The prevalence of anti-latex IgE antibodies in 1000 volunteer blood donors

BACKGROUND: Latex allergy has been recognized as a medical problem with increasing frequency since the mid 1980s. Although certain groups of individuals, such as health care workers, have been recognized as having increased risk for latex allergy, little is known about the prevalence of latex allergy in the general population. METHODS: To estimate the prevalence of latex allergy among healthy adults, we measured anti-latex IgE antibodies in residual serum samples from 1000 volunteer Red Cross blood donors. The 1000 samples were from a sample of blood units collected from workplace mobile sites throughout Southeastern Michigan. Samples collected from mobile sites operating at health care institutions were excluded to minimize sampling of health care workers. Anti-latex IgE antibodies were measured by using the AlaSTAT assay (Diagnostic Products Corp., Los Angeles, Calif.) according to the manufacturer’s directions. Samples with anti-latex IgE concentrations of 0.35 IU/ml or greater were classified as positive and samples with IgE concentrations of 1.50 IU/ml or greater were classified as strongly positive. All positive samples were assayed a second time to confirm the result. All positive samples were also measured with the CAP assay (Pharmacia Diagnostics, Dublin, Ohio). RESULTS: The samples tested were from donors with a mean age of 37.8 years, and 47% were women. Sixty-four (6.4%, 95% confidence interval = 4.9-8.1%) of the samples were confirmed as repeatedly positive for anti-latex IgE, and 23 of the 64 positive samples were strongly positive (2.3% of the 1000). Sixty-one percent of the samples positive as determined by the AlaSTAT assay were also positive as determined by the CAP assay. Samples from male donors were more likely to be positive than those from female donors (8.7% vs 4.1%, p = 0.003). Prevalence of positive samples was not related to age or race. CONCLUSIONS: We conclude that the prevalence of detectable anti-latex IgE antibodies, in a large and relatively unselected adult population, is higher than previous estimates have suggested. Although the clinical significance of these observations needs further evaluation, the data suggest that latex allergy is not confined to individuals in previously recognized high-risk groups. (J Allergy Clin Immunol 1996;97:1188-92.)     

Effects of latex membrane on guided regeneration of long bones

Abstract

Natural latex extracted from Hevea brasiliensis is one of the materials pointed out as potential tissue regenerators. The use of latex-based membranes in bone regeneration might be an alternative to stimulate bone formation. The aim of this study was to evaluate the effects of latex membranes in guided bone regeneration of defects produced in long bones of rats. Sixty rats were equally divided into latex and control groups, and each group was subdivided into two subgroups according to treatment duration of 1 and 4 weeks. Bone defects with 2.5?mm in diameter were surgically made in the left tibia. In the animals of the latex group, a latex membrane was placed over the bone defect. The samples underwent quantitative histological analysis of bone formation and collagen matrix, immunohistochemical analysis of osteogenic protein markers, assessment of bone mechanical properties and bone densitometry, and radiological assessment. The osteocalcin immunostaining data were submitted to the generalized linear model test with two independent factors. For the other data, the multivariate ANOVA with two independent factors was performed. The use of the latex membrane significantly improved (p?<?0.005) the volume of newly formed bone, collagen type I matrix, expression of osteopontin, and bone stiffness, both in the early and late stages of regeneration. In conclusion, the latex membrane was able to promote bone regeneration in long bones.     

Latex immunoassays: Comparative studies on covalent and physical immobilization of antibodies. I. F(ab')2 fragments

Colloidal particles coated with antibodies are currently used in diagnostic test systems for the detection of antigens in biological fluids. Immobilization is usually carried out by physical adsorption. Covalent coupling of antibodies to particles, however, offers certain advantages. The present research deals with the study of these possible advantages. A sulphonated polystyrene latex has been used to prepare an immunolatex with physically adsorbed antibodies, while a functionalized latex with chloromethyl groups on the surface has been used for the partly covalent coupling of the antibody (F(ab')₂ fragments). The immunoreactivity was studied by measuring the variations in scattered light intensity after mixing a solution of CRP antigen and the sensitized latex. The influence on the immunoresponse of the scattering angle (5, 10, and 20 deg), protein coverage and storage time have been studied for both systems.     

THE LATEX SLIDE TEST IN RHEUMATIC DISORDERS

The latex slide test (L.S.T.) has been shown to be simple to perform and easy to read. It gives results comparable with the more complicated serological procedures used in the diagnosis of rheumatoid arthritis.     

Evaluation of recombinant leptospiral surface antigen (Lsa27) lipoprotein for serodiagnosis of human leptospirosis by latex agglutination test

PurposeLeptospirosis has wide clinical presentations often mimicking other illnesses, thus rapid and simple diagnostics will have facilitated the initial patient management and therapy compared to other inaccessible and laborious tests/assays.MethodIn this study, the sensitized latex beads coated with purified recombinant outer membrane (OM)-leptospiral surface antigen (Lsa27) lipoprotein of pathogenic Leptospira was evaluated as a diagnostic antigen in latex agglutination test (LAT) for the detection of anti-leptospiral antibodies in the human sera. The prepared rLsa27 latex beads were evaluated with the confirmed microscopic agglutination test (MAT) reactive (at 1:50) Leptospira-specific positive (n = 42) and non-reactive negative (n = 80) sera from human cases suspected of leptospirosis with the history of pyrexia of unknown origin.ResultThe results revealed the relative diagnostic sensitivity of 90.48 % (confidence interval (CI) at 95 % : 77.4–97.3 %) and diagnostic specificity of 91.35 % (CI at 95 %: 82.8–96.4 %), with an accuracy of 90.98 % (CI at 95 %: 84.44–95.41 %), and the kappa value of 0.8036 ± 0.056 SE (CI at 95 %: 0.69–0.91) with a substantial agreement against gold standard serological MAT.ConclusionThe findings suggest that the rLsa27 protein-based LAT can be useful as a simple rapid screening diagnostic test for the detection of anti-leptospiral antibodies in the sera of humans. This rapid test can be complemented by other confirmatory diagnostics for the early detection of Leptospira antibodies which may in turn help in the prompt treatment and mitigates the public health problem at primary health care level.     

Serum reactivities to latex proteins (Hevea brasiliensis)

Background: In recent years there has been an increasing incidence of allergy to latex among health care workers and children with spina bifida. The allergic response in these individuals can be severe and occasionally fatal. Several allergens have been identified with the use of sera from different patient groups. In our effort to identify reagents for in vitro testing and clinical use, we investigated the reactivities of latex proteins to sera collected from a wide range of patients with latex allergy. Methods: Twenty-six serum samples were obtained from adult patients with latex allergy, both hospital workers and non-hospital workers. Serum pools were made either from sera of children with spina bifida or sera of adult patients with latex allergy. Proteins from C-serum and latex particles of latex sap (nonammoniated) were separated by different gel electrophoresis techniques and evaluated for specific IgE binding by immunoblotting. Results: More than 50% of the sera tested reacted to an 18 kd protein, a 25.6 kd acidic protein with an isoelectric point of 3.5, or to both proteins; whereas only 23% of the individual serum samples tested reacted to the rubber elongation factor, which has been reported to be a major latex allergen. The immunoreactive patterns of children's and adults' serum pools were similar but not identical. Conclusions: With the use of gel electrophoresis and immunoblotting techniques, different immunoreactive proteins were identified in C-serum and particles of latex. Rubber elongation factor, which reacted to only 23% of sera tested, did not appear to cross-react immunologically with other latex allergens. (J ALLERGY CLIN IMMUNOL 1995;95:1196-1205.)     

Gentamicin encapsulated within a biopolymer for the treatment of Staphylococcus aureus and Escherichia coli infected skin ulcers

Abstract

Skin wound infection requires carefully long-term treatment with an immense financial burden to healthcare systems worldwide. Various strategies such as drug delivery systems using polymer matrix from natural source have been used to enhance wound healing. Natural rubber latex (NRL) from Hevea brasiliensis has shown angiogenic and tissue repair properties. Gentamicin sulfate (GS) is a broad-spectrum antibiotic which inhibits the growth of a wide variety of microorganisms and, because of this, it has also been applied topically for treatment of local infections. The aim of this study was to develop a GS release system using NRL as matrix for Staphylococcus aureus and Escherichia coli infected skin ulcers treatment, without changing drug antibiotic properties. The matrix did not change the GS antimicrobial activity against S. aureus and E. coli strains. Moreover, the NRL-GS biomembrane did not exhibit hemolytic activity, being non-toxic to red blood cells. The eluates of NRL-GS biomembranes and GS solutions did not significantly reduce the survival of Caenorhabditis elegans worms for 24?h at any of the tested concentrations. Thus, these results emphasize that the NRL-GS biomembrane proved to be a promising biomaterial for future studies on the development of dressings for topical uses, inexpensive and practicable, keeping drug antibiotic properties against pathogens and to reduce the side effects.     

A novel genetic variant of Streptococcus pneumoniae serotype 11A discovered in Fiji

ObjectivesAs part of annual cross-sectional Streptococcus pneumoniae carriage surveys in Fiji (2012–2015), we detected pneumococci in over 100 nasopharyngeal swabs that serotyped as ‘11F-like’ by microarray. We examined the genetic basis of this divergence in the 11F-like capsular polysaccharide (cps) locus compared to the reference 11F cps sequence. The impact of this diversity on capsule phenotype, and serotype results using genetic and serologic methods were determined.MethodsGenomic DNA from representative 11F-like S. pneumoniae isolates obtained from the nasopharynx of Fijian children was extracted and subject to whole genome sequencing. Genetic and phylogenetic analyses were used to identify genetic changes in the cps locus. Capsular phenotypes were evaluated using the Quellung reaction and latex agglutination.ResultsCompared to published 11F sequences, the wcwC and wcrL genes of the 11F-like cps locus are phylogenetically divergent, and the gct gene contains a single nucleotide insertion within a homopolymeric region. These changes within the DNA sequence of the 11F-like cps locus have modified the antigenic properties of the capsule, such that 11F-like isolates serotype as 11A by Quellung reaction and latex agglutination.ConclusionsThis study demonstrates the ability of molecular serotyping by microarray to identify genetic variants of S. pneumoniae and highlights the potential for discrepant results between phenotypic and genotypic serotyping methods. We propose that 11F-like isolates are not a new serotype but rather are a novel genetic variant of serotype 11A. These findings have implications for invasive pneumococcal disease surveillance as well as studies investigating vaccine impact.     

Anaphylaxis in a tertiary adult allergy clinic: a retrospective review of 516 patients

BackgroundAnaphylaxis is a life-threatening acute allergic reaction that can occur at any age.ObjectiveTo determine the frequency, triggering factors, and clinical features of anaphylaxis among adult patients who were referred to a tertiary health care facility.MethodsA retrospective medical chart review was performed including all patients referred to the outpatient clinic of the adult allergy department in our university hospital between January 1, 2008 and December 30, 2011 to determine cases involving anaphylaxis.ResultsA total of 516 (2.11%) patients among 24,443 admissions were diagnosed with anaphylaxis. Although the second highest frequency of anaphylaxis cases took place in 2008, a gradual rise in the frequency was determined from 2009 to 2011. Drugs (90.7%) were the most frequent cause, followed by Hymenoptera stings (5.4%), foods (1.6%), latex (0.4%), and exercise (0.2%) respectively. The clinical manifestations during anaphylaxis reported by patients were cutaneous (n = 292, 56.6%), respiratory (n = 253, 49%), cardiovascular (n = 212, 41%), neuropsychiatric (n = 60, 11.6%), and gastrointestinal (n = 52, 10.1%), respectively. Approximately one fifth of the patients received epinephrine, whereas 43% of patients did not receive epinephrine during their treatment in the emergency room. An epinephrine auto-injector was prescribed to 42 patients (8.1%).ConclusionIn this study, the second pattern of National Institute of Allergy and Infectious Disease (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN) diagnostic criteria for anaphylaxis predominated among adult patients. Drugs were the leading triggering factor, followed by Hymenoptera stings, foods, latex, and exercise, respectively. Atopy, asthma, and allergic rhinitis were rarely detected.