A case of latex allergy with bronchial asthma]

A 26-year-old nurse consulted our department because of shortness of breath, wheezing and skin eruption after eating lunch several days before. At the consultation, the symptoms had disappeared, pulmonary function showed no abnormality, and there were no abnormal findings on chest auscultation. Latex allergy was suspected because of a history of wheezing and skin eruption after wearing latex gloves and an elevated serum IgE level specific to latex antigen. After a usage test of medical latex gloves, wheezing, skin eruption, and a decrease of FEV1.0 on pulmonary function testing were observed. The case was therefore diagnosed as latex allergy with bronchial asthma. Her symptoms were not observed after polymer coated gloves were substituted. Latex allergy is apt to complicate food allergy, an initial symptom of the present case. Specific IgE for several kinds of food was also elevated.     

IGE-mediated natural rubber latex allergy: an update

In the past 2 decades, IgE-mediated NRL allergy has become a well-defined condition with recognised risk groups, established diagnostic tools, and adequate prevention strategies (1-3). Furthermore, molecular biology and biochemical techniques have significantly improved our knowledge of the proteins responsible to cause the disease. Clinical manifestations will not be addressed in this review, nor will broad preventive strategies be proposed; these have been discussed elsewhere (4, 5). After a brief introduction this review will focus on specific issues: (1) How do we estimate the prevalence of NRL allergy and who is at risk for clinical sensitisation? (2) What specific allergens cause NRL allergy? How does sensitisation for these allergens occur? Are all patients sensitised for the same allergens? Threshold allergen exposure levels. (4) What is the latex-fruit syndrome? What is the clinical relevance of a positive plant food specific IgE quantification in patients with NRL allergy? (5) How do we diagnose NRL allergy? What are the strengths and weaknesses of currently available diagnostic tools? (7) How do we manage NRL allergy? What is the role of medication and immunotherapy in the treatment of NRL allergy? How do we select an appropriate non-NRL alternative for NRL gloves? Which regulatory provisions have been implemented?     

Natural rubber latex allergy and asthma

Allergic responses to natural rubber latex (NRL) continue to be reported. In adults, the major exposure is in the occupational setting, especially in relation to NRL glove use by health care workers. Issues addressed over the past year include improving diagnostic methods for NRL allergy and characterization of NRL allergens relevant to various exposure groups and evaluating strategies for prevention and early detection of NRL allergy. Assessment of in vitro tests show good intertest correlation but lower sensitivity compared with skin test responses. NRL allergens have been further characterized as reported in the past year. Development of recombinant Hev b 3, a major NRL allergen relevant to children with spina bifida, enhances the likelihood for improved diagnostic reagents. Preliminary reports of primary preventive strategies suggest that avoidance of high-protein, powdered gloves in health care facilities can be cost-effective and is associated with a decline in sensitized workers.     

Prevalence of type I allergy to natural rubber latex and type IV allergy to latex and rubber additives in operating room staff with glove-related symptoms.

There is lack of data on the prevalence of latex allergy in the health care setting in Iran. This study was performed to determine the prevalence of type I latex allergy and type IV allergy to latex and rubber additives among the operating room staff with glove-related symptoms in 13 general hospitals in Tehran. Skin-prick tests with commercial latex extract, patch tests with latex and 25 rubber additive series, and total and latex-specific IgE detection were performed on the operating room staff who reported latex glove-related symptoms. Five hundred twelve self-administered questionnaires (100%) were completed by all operating room staff and latex glove-related symptoms were reported by 59 (11.5%) employees. Among all symptomatic operating room staff tested, the prevalence of type I latex allergy was 30.5% and the prevalence rates of type IV allergy to latex and rubber additives were 16.7 and 14.6%, respectively. The most positive patch test result with rubber additives was related to tetramethylthiuram monosulfide (38.5%). The risk factors for type I latex allergy were female sex (p = 0.009) and positive patch test with rubber additives (p = 0.012). Subjects who had positive patch test with latex were significantly more likely to have positive patch test with rubber additives (p < 0.0001). Our results showed a high prevalence of type I latex allergy and type IV allergy to latex and rubber additives. Based on this study, we recommend eliminating powdered latex gloves from the operating rooms of the 13 studied general hospitals and support the substitution of powder-free latex gloves.     

Summary of appropriate measures to prevent natural rubber latex allergy

This paper presents a short overview of the diagnostics and background of type I allergy to natural rubber latex proteins and makes recommendations for preventing corresponding allergic diseases in the future. These recommendations and prevention strategies are based on the current knowledge of latex allergy presented in the literature and are addressed to legislative bodies; manufacturers; directors of hospitals; those working at nursing facilities and physicians' and dentists' practices; as well as to other health service employees. Primary prevention is the focus but advice is also given on secondary prevention. The major preventive aim is the elimination of causative protein allergens in all latex devices and thus, the minimization of latex-related health problems.     

Recombinant latex allergens

In the last few years many efforts have been made to reduce the incidence of latex allergy. The identification of the major latex allergens and their recombinant production are useful steps towards the understanding of latex allergy and its management. A clear advantage of the recombinant proteins in general is the possibility to produce large-scale quantities at highly reproducible quality. Recombinant allergens also facilitate the study of the molecular bases of the immune reactivity of the proteins. Nevertheless, they have to be validated against native proteins for equivalence in allergenicity before they can be more widely adapted for clinical use. Currently 13 latex allergens have been included in the latest nomenclature list of the International Nomenclature Committee of Allergens and assigned the official names Hev b 1–13. With the use of single native and/or recombinant allergens the determination of specific sensitization profiles for different patient groups dependent on their various routes of exposure is possible. The specific IgE-diagnostic was further improved significantly by addition of recombinant Hev b 5 to natural latex extract, which was underrepresented in the initial test extract.     

Natural rubber latex allergy: a problem of interdisciplinary concern in medicine

In the past 10 years, IgE-mediated allergy to natural rubber latex has become a significant health problem in industrialized countries, especially among health care workers, patients with congenital malformations, and children with a history of multiple surgical interventions. Curative treatment inducing immunological tolerance in formerly sensitized patients is experimental and not yet generally available. Therefore, it is important to be aware of the seriousness of latex allergy and to understand the risk factors leading to this allergy. Preventive measures are needed to decrease the incidence of natural rubber latex sensitization. This article gives a brief review of the current state of knowledge concerning latex allergy, including a definition of latex, epidemiological data, identified allergens, the clinical spectrum, diagnostic procedures, cross-reactions, preventive measures, the legislative background, and economics.     

New insights on latex allergy diagnosis and treatment.

Because of widespread latex manufacturing in the last decades, exposure to latex has become ever greater, as has the incidence of latex allergy among the general population as well as the high-risk groups. Clinical manifestations range from local reactions (edema, itching, erythema, and papulae), rhino-conjunctivitis, asthma, pharyngeal edema, to severe systemic reactions such as anaphylactic shock (from parenteral exposure especially during medical examinations or surgical procedures). Diagnosis is formulated on the basis of the personal history and an accurate allergological evaluation. Patients usually have a history of food intolerance or adverse reactions during medical or surgical procedures, which are believed to be the result of anesthetics or other drugs. In vivo tests are prick and patch tests and challenge tests. Challenge tests (nasal, conjunctival, bronchial, intravaginal, sublingual, oral, and cutaneous tests) are important for confirming the diagnosis, for evaluating a patient's response to the different kinds of latex exposure, and for verifying the effects of desensitizing treatments on the various organs involved in latex allergy. The most important in vitro test is the specific anti-natural rubber latex IgE assay. The only effective resolution to the latex allergy problem seems to be desensitization. The criteria of effectiveness are the capability to use latex items, to undergo medical examinations (even invasive), and to remain in an environment where latex particles can be inhaled (such as surgical departments), without symptoms. The first attempts were performed by subcutaneous administration of latex, but this protocol seems to be delicate to perform because of the side effects. Two different alternative methods (percutaneous and sublingual) were successfully performed and proved to be safer and more effective, even though further studies on a larger group of patients are needed.     

Treatment perspectives: immunotherapy with latex

Latex allergy currently constitutes a serious problem because of the severity of its symptoms and the at-risk groups it affects. Since complete avoidance of this substance is practically impossible, in the last few years intense efforts have been made to standardize a latex extract with the aim not only of improving clinical diagnosis but also of being able to offer other therapeutic alternatives, such as specific immunotherapy.Since 1998, reports of immunotherapy with oral (three patients) subcutaneous (one patient) and sublingual latex desensitization (one patient) have been published. In all cases, clinical improvement was evident. In 2000, Laynadier published the first pilot study, a phase IIB multicenter, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of specific immunotherapy with latex in patients with occupational allergy. Twenty health care workers without obvious latex exposure and with latex allergy-induced symptoms of rhinitis and/or asthma were included. Treatment started with a 2-day course of rush immunotherapy in hospital and maintenance therapy was continued for 1 year. Efficacy was assessed by symptom and medication scores and by variation in the conjunctival reactivity threshold. The safety of the extract was also evaluated. In the overall analysis of symptom score, the treated group showed a marked improvement and the medication score was significantly lower in patients in the active treatment group than in the placebo group. Concerning safety, almost half the patients receiving active treatment showed local reactions starting with the first injection and four of the nine patients in this group suffered moderate-to-severe systemic reactions. In view of this first clinical trial, it can be concluded that this treatment is effective but that its tolerance is low.A second clinical trial with the same characteristics and extract is currently underway. Its aim is to validate the previous protocol, confirm the efficacy of specific immunotherapy with latex, improve its safety and, if possible, determine the optimal dose.J. Sastre et al. have recently (Formigal 2002) presented the results of the first double-blind study with latex immunotherapy using an extract standardized by the ALK-Abelló-Espa?a group. The authors included 24 patients with latex sensitization and symptoms of occupational allergy. To diagnose respiratory allergy, an inhalation challenge was performed in a closed 7-m2 chamber and, in case of contact urticaria, glove-wearing and rubbing tests were performed, using a vinyl glove as negative control. Treatment consisted of a first phase of incremental doses for 14 weeks, with 18 injections, followed by maintenance doses for 6 months. Sixteen patients received active treatment and 8 received placebo. Of the 578 doses administered, adverse effects were observed in 41 (7.1 %). There were 21 immediate systemic reactions (5.7 % of the doses) and 10 delayed systemic reactions (2.6 % of the doses). Adverse effects were more frequent in patients with underlying respiratory disease (p < 0.05). After 6 months' treatment, a clear improvement in the cutaneous response index was found in the active treatment group and in the rubbing and glove-wearing tests. The authors conclude that the immunotherapy tested was a high-risk treatment and that the greatest clinical improvement was found in cutaneous symptoms.In conclusion, although effective, latex immunotherapy is currently a high-risk treatment.     

Diagnosis of latex hypersensitivity: comparison of different methods

A standardized diagnostic protocol for latex allergy is still lacking, although latex-related manifestations are a common health problem especially among health-care workers and patients with spina bifida. The present study was aimed to compare different in vivo (skin prick test, patch test, use test) and in vitro (specific IgE determination by CAP-Rast, basophil histamine release assay, immunoblot) methods to diagnose latex sensitization in 47 health care workers reporting latex-related manifestations. According to the established criteria, 20 subjects (42.5%) were considered as truly sensitized to latex, 18 with type I and 2 with type IV hypersensitivity. Skin prick test displayed the highest diagnostic efficiency, having higher sensitivity and specificity than specific IgE determination and use test. Patch test with rubber chemicals had a low sensitivity, but a good specificity. Basophil histamine release and immunoblot showed low sensitivity and specificity. A combination of clinical history and skin prick test should be used in order to diagnose latex allergy, except in those subjects reporting life-threatening reactions, in which in vitro specific IgE determination must be preferred. Patch testing with rubber chemicals should be reserved to selected cases. Basophil histamine release and immunoblotting can be performed for research purpose, but cannot be recommended for routine diagnostic use.     

Peculiarities of latex allergy and preventive measures in the pediatric age group

Latex allergy can be considered a problem of public health in at-risk populations. Although the figures on prevalence vary, approximately 1 % of the general population is sensitized to latex. To date, two determining factors for latex sensitization have been identified: an atopic predisposition and the number of operations. Among atopic patients or those at-risk for allergy, the prevalence of latex sensitization is between 3 and 20 times higher than that among the general population. Nevertheless, the effect of this factor seems to be modulatory and the determining factor seems to be the number of operations that children have undergone; the critical number is 5-6 interventions, after which the probability of sensitization increases considerably.All children who have undergone multiple operations should be considered as being at-risk. Children with spina bifida are especially at-risk. The reasons for this are still a matter of debate: the disease itself has been postulated as a specific risk factor, although other, possible associated factors could be determinant in triggering latex sensitization (the presence of a ventricular-peritoneal shunt, age at which surgery was performed, type of operation, etc.). Children with spina bifida and latex allergy show considerable differences in type of allergic sensitization; these differences seem to result from the different route of sensitization and could explain the variations observed in the clinical manifestations between children and adults: children become sensitized mainly by direct contact between latex particles and blood vessels and open mucosae while in adults the process takes place transcutaneously or by inhalation of aerosol particles. Consequently, the most frequent manifestation in children is urticaria while contact dermatitis and respiratory symptoms predominate in adults. Studies performed with immunoblotting have confirmed that children have IgE that almost constantly recognize low molecular weight latex proteins (14, 15 and 27 Kd) while this finding is less frequent in adults.The preventive measures in the pediatric population focus on avoidance of latex, especially in hospitals. Today, latex is ubiquitous, making complete avoidance difficult. When necessary, and whenever a latex-free environment cannot be guaranteed, presurgical medication can be used, although its utility is debatable. Although further studies are required, specific immunotherapy is one therapeutic possibility that may in future be used in children with latex allergy.     

Prevalence of latex allergy and evaluation of some risk factors in a population of atopic children.

The aims of our study were to evaluate (1) the prevalence of natural rubber latex (NRL) allergy in an unselected population of atopic children; (2) the diagnostic efficacy of skin prick tests (SPTs) with latex extracts; (3) the correlation between positive SPTs to latex and risk factors such as atopy, fruit allergy, history of surgery cares or dental cares. We randomly enrolled 151 unselected atopic and 59 nonatopic children who underwent SPTs with common inhalant and food allergens, and SPTs with two different latex extracts. A clinical history concerning allergic history, symptoms after contact with latex objects or after ingestion of fruits or vegetables, dental and surgical treatments was obtained. Six of the 151 atopic children were positive to latex SPTs, but only one out of 59 nonatopic children was positive to latex SPTs. Concerning risk factors, 86% of children with SPT positive to latex were atopic, 71.4% had a clinical history of surgery, and none of them had undergone dental or orthodontic treatments. The prevalence of NRL sensitization in our unselected population of atopic children was 3.9%, but the prevalence of NRL allergy was 2.6%. Concerning NRL allergy, the sensitivity and the specificity of SPTs with latex extracts are high (1.00 and 0.98, respectively), as well as negative predicting value (1.00); the positive predictive value is low (0.70). We conclude that atopy, surgical treatments, and sensitization to foods cross-reacting with NRL are important risk factors for NRL sensitization. We have no data concerning dental or orthodontic cares.     

Importance of recombinant k82 in the diagnosis of latex allergy

Measurement of IgEs keeps a predominant place in the diagnosis of allergy and in particular in certain pathologies such as those induced by dangerous allergens like, for example, latex. The contribution of recombinant allergens is a significant element in the measurement of IgEs and we have observed this for latex. Sensitivity of recombinant k82 is significantly greater than that of k82. It permits better detection of patients who are sensitised to latex and thus a better prevention by absence of frequent contact with latex gloves and detergents.     

Efficiency of diagnosis of latex allergy by the combined use of three latex materials for prick-tests

The diagnosis of latex allergy is mainly based on prick-tests. In order to improve the efficiency of the diagnosis, a comparative study of three latex materials is carried out in 64 controls and 29 patients allergic to latex = Stallergènes and Allerbio extracts, prepared from crude natural latex, and an ammoniated emulsion of rubber latex (AEL). No adverse reactions are recorded. The specificity is 100% for both extracts, 85% for AEL. Sensitivity is respectively 68%, 63%, 72%. The range of values of the wheal is significantly narrower for Stallergènes extract. 46% of allergic patients are reactive to the three materials. The combined use of three materials reaches an 80% efficiency similar to that of Rast Cap System and the addition of three prick-tests and Rast obtains an efficiency of 93.1%. Using several latex materials could increase the efficiency of the diagnosis, inasmuch as the extracts are generated from natural latex, whereas patients are sensitized to manufactured products originating from ammoniated latex.     

Allergy to cassava: a new allergenic food with cross-reactivity to latex.

Patients who are allergic to latex (Hevea brasiliensis) may exhibit cross-hypersensitivity with foods. We present a case of anaphylaxis due to cassava in a patient suffering from pollinosis, latex allergy, and latex-fruit syndrome. We performed sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with cassava, avocado, chestnut, banana, kiwi, and latex extracts in order to analyze the protein bands and their molecular weights, and identify immunoglobulin (Ig) E-binding bands. Immunoblot inhibition and enzyme-linked immunosorbent assay (ELISA) inhibition were performed with latex in order to assess cross-reactivity. Cassava exhibited numerous protein bands, 5 of which were IgE-binding (89.75, 46.28, 26.68, 21.38, and 19.49 kd). These cassava IgE-binding bands were 100% inhibited by preincubation of the patient's serum with latex extract. The ELISA inhibition between latex and cassava was 23%. Our results confirm cassava as another food with clinical cross-reactivity in patients suffering from latex allergy.     

Desensitization to latex by percutaneous route.

Latex allergy is a newly emerging problem. In the last decades its prevalence has increased progressively, especially among health care personnel and patients. Preventive measures have been suggested to reduce the risk of sensitization, but this is very difficult because of the ubiquity of latex products. Since only two clinical reports are available in the literature, suggesting that subcutaneous desensitizing treatments resulted in important side effects, we decided to attempt a desensitization through alternative routes. After having succeeded in carrying out sublingual desensitization, we report the case of a latex-allergic patient who successfully underwent percutaneous desensitization.     

Characterization of a mouse model of allergy to a major occupational latex glove allergen Hev b 5

Allergen-specific immunotherapy is a clinically proven effective treatment for many allergic diseases, including asthma; however, it is not currently available for latex allergy because of the high risk of anaphylaxis. There is, therefore, a crucial need for an animal model of latex allergy in which to develop effective immunotherapy. Previous mouse models of latex allergy either did not characterize the allergic pulmonary immune response or used crude latex extracts, making it difficult to quantify the contribution of individual proteins and limiting their usefulness for developing specific immunotherapy. We immunized mice with recombinant Hev b 5, a defined major latex allergen, or latex glove protein extract, representing the range of occupationally encountered processed latex allergens. The immune response was compared with that seen in ovalbumin-immunized mice. Immunization with Hev b 5 or glove extract elicits hallmarks of allergic pulmonary Th2-type immune responses, comparable to those for ovalbumin, including (1) serum antigen-specific IgE, (2) an eosinophilic inflammatory infiltrate in the lung, (3) increased interleukin-5 in lung bronchoalveolar lavage fluid, and (4) mucus hypersecretion by epithelial cells in the lung airways. This mouse model will aid the development of potentially curative treatments for latex-sensitized individuals, including those with occupational asthma.     

Minimum prevalence of latex hypersensitivity in health care workers.

Health care workers (HCW) have been shown to be at significant risk for developing latex allergy. Natural rubber latex hypersensitivity has been reported in 2.9 to 17% of health care workers in previously published studies. This study describes the prevalence of latex hypersensitivity in a large cohort of medical center employees. A screening questionnaire was distributed to 1967 employees in six job categories exposed to latex, and 1331 questionnaires were returned (68%) between March and November 1995. Skin and serologic testing was performed on 156 volunteers. Of the 1331 HCWs who completed the screening questionnaire, 290 (21.8%) self-reported contact dermatitis to latex, 67 (5.0%) self-reported urticaria to latex, 163 (12.2%) self-reported rhinoconjunctivitis to latex, and 17 (1.3%) self-reported asthmatic symptoms to latex. Of the total population of 1967 employees, 38 (1.9%) were either skin test or blood test positive and 30 (1.5%) of these 38 were symptomatic around latex. This study suggests a minimum prevalence of IgE-mediated hypersensitivity to latex of 1.5% among medical center employees. Our reported prevalence figures are lower than previously reported, reflecting, in part, reporting methods using a denominator more consistent with the total population at risk. Our study also illustrates the pitfall of relying on self-reporting in making the diagnosis of latex allergy.     

Atopy and risk factors for latex sensitization in a selected population.

The value of recommending latex allergy screening in allergy departments of the Army's Hospital was studied. The purpose of the study was to evaluate whether atopy was a risk factor for latex sensitization in a specific population such as the young male soldiers of the Italian Army. The study was also aimed to assess the role of other risk factors. One thousand five hundred male subjects (1000 subjects who were atopic and 500 subjects who were nonatopic), visiting the Department of Allergology and Respiratory Physiopathology of the Army's Hospital in Bari, Italy, were enrolled into the study. The protocol included a questionnaire (symptoms of atopy, use of latex gloves and condoms and possible reactions previous surgical procedures), a clinical examination, a skin-prick test to latex and common allergens to evaluate atopy, and in part a latex challenge. Among the 1000 subjects who were atopic, 2.8% had evidence for sensitization to latex compared with 1.2% in the 500 subjects in the nonatopic group. The risk of latex sensitization was 19 times higher for subjects with a history of reactions to latex exposure and had a twofold increase for each surgical procedure and for each skin test positivity for inhalant allergens. Another risk factor was positivity to skin-prick tests for Artemisia vulgaris, cypress, and molds. Atopy significantly relates to an increased risk of latex sensitization. Screening is recommended in the Army's Hospital to identify latex-sensitized subjects and inform them about the risks connected with this condition.     

Episodic stridor with latex nipple use in a 2-month-old infant

Latex allergy in the pediatric population is most commonly identified in patients who have undergone multiple operations for neural tube defects or exstrophic genitourinary anomalies. However, there are a significant number of children who, without the usual risk factors, clinically and/or serologically appear to be latex allergic. There is sporadic information in the medical literature regarding reactions to latex allergens in household items, especially in patients younger than 1 year old. Several recent reports even support the existence of reactions to latex pacifiers. We report a case of an atopic 2-month-old infant who experienced the previously unreported reaction of repeated stridor on exposure to a latex nipple while feeding. It is important that clinicians recognize stridor as a potential reaction to latex in infants.