Latex immunotherapy: state of the art.

OBJECTIVE: Latex allergy remains a significant problem, especially among certain professional categories, and specific immunotherapy has been suggested as a suitable therapeutic option. The objective of the this article is to review the available literature on clinical trials of specific immunotherapy in latex allergy. DATA SOURCES: Literature databases (PubMed, Embase, Google Scholar) were searched for latex immunotherapy clinical trials. STUDY SELECTIONS: Clinical trials (either open or randomized controlled) using subcutaneous or sublingual immunotherapy with latex extracts were selected. Only articles published in English in peer-reviewed journals were considered. Case reports quoted in the clinical trials were also described, when pertinent. RESULTS: Eleven clinical trials (3 with subcutaneous and 8 with sublingual immunotherapy) were identified. Two of the 3 randomized trials of subcutaneous immunotherapy reported some benefit in adults but a remarkable occurrence of side effects. Concerning sublingual immunotherapy (SLIT), there were 6 randomized placebo-controlled (1 in children), 1 randomized open, and 1 open trials. All but 1 trial reported positive results, and the safety profile was overall superior to injection immunotherapy. The overall quality of the study was moderate, and the number of subjects studied was low. CONCLUSION: Although guidelines do not consider allergy to latex as an accepted indication to desensitization, SLIT can be offered, in addition to symptomatic treatment, to selected patients, when avoidance measures are not feasible or effective.

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

BACKGROUND: As 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. OBJECTIVE: To examine variations in immunologic parameters, clinical efficacy, and safety of NRL sublingual immunotherapy (SLIT). METHODS: This 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. RESULTS: Patients 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. CONCLUSION: NRL 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.

Latex allergy: Position Paper.

Correct management of latex allergy is essential to ensure adequate care of patients who are allergic to latex, which is ubiquitous in the health care setting. In this Position Paper, the Latex Committee of the Spanish Society of Allergology and Clinical Immunology provides guidelines for the management of latex allergy.

[Successful use of C1 esterase inhibitor in capillary leak syndrome]. / Erfolgreiche Anwendung von C1-Esterase-Inhibitor bei "capillary leak syndrome"

This article reports the successful use of C1 esterase inhibitor in the treatment of capillary leak syndrome. The coincidence of exposure to latex during surgery and medication with ramipril led to prolonged shock complicated by secondary hyperfibrinolysis, capillary leak syndrome and multiple organ failure. Initial treatment according to relevant guidelines failed to stabilize the condition. Treatment was only successful after administration of 1,500 IU of human C1 esterase inhibitor.

[Latex allergy: therapeutic options]. / Alergia al látex: opciones terapéuticas.

Latex allergy is a major problem worldwide due to both the severity of the symptomatology it produces and the risk groups that are exposed to it. Complete avoidance is difficult, if not impossible, due to its ubiquity. Natural rubber latex (NRL) is a natural polymer that is released by the Hevea brasiliensis (Hev b) tree, which functions as a protective sealant. It is currently used for the manufacture of health-care products such as tube caps, pistons, masks, and cannulas. The purpose of this review is to highlight the epidemiological, clinical, and diagnostic aspects of NRL allergy, and to conduct a review of the literature on its management through a bibliographic search of articles in databases such as PubMed, Cochrane, UpToDate, and Google Scholar, up to September 2021. About 121 articles were reviewed, of which 76 were used as a reference. We concluded that latex allergy is an entity for which its treatment, even nowadays, is avoidance, despite having a worldwide prevalence of 4.3 % and representing a surgical complication in about 20 % of surgeries with an anaphylactic reaction and a mortality rate that can reach 9 %. The only treatment that could modify the evolution of this disease is immunotherapy, but there are no standardized extracts yet and it has not been possible to determine the safest and most effective way to apply it.

La alergia al látex es un problema importante en el mundo debido a la gravedad de la sintomatología que produce y a los grupos de riesgo expuestos. La evitación completa es difícil, casi imposible, dada su ubicuidad. El látex de caucho natural (LCN) es un polímero secretado por el árbol Hevea brasiliensis (Hev b), que funciona como sellador protector. Actualmente se usa para fabricar productos para el cuidado de la salud como tapones para tubos, pistones, mascarillas y cánulas. El objetivo de esta revisión es resaltar los aspectos epidemiológicos, clínicos y diagnósticos de la alergia al LCN, y realizar una revisión de la literatura sobre su manejo, mediante una búsqueda bibliográfica de artículos en bases de datos como PubMed, Cochrane, UpToDate y Google Académico, hasta septiembre del 2021. Se revisaron aproximadamente 121 artículos, de los cuales se utilizaron 76 como referencia. Concluimos que la alergia al látex es una entidad cuyo tratamiento aún hoy en día es la evitación, a pesar de tener una prevalencia mundial de 4.3 % y representar una complicación quirúrgica de cerca de 20 % de las cirugías con una reacción anafiláctica y una mortalidad que puede llegar a 9 %. El único tratamiento que podría modificar la evolución de esta enfermedad es la inmunoterapia, pero aún no se cuenta con extractos estandarizados y no se ha podido determinar la vía más segura y efectiva.

Clinical and quality of life assessment in patients with latex allergy during COVID-19 pandemic: Possible protective role of continuous latex immunotherapy.

Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 ± 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A (p < 0.001), respiratory symptoms (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients.

Perioperative latex allergy.

The prevalence of latex allergy varies greatly depending on the population studied and the methods used to detect sensitization. Subjects considered to be at high risk for latex allergy are rubber industry workers, children with spina bifida and urological abnormalities, children undergoing multiple surgical procedures and with urinary catheterization, health care workers and people with food allergy (latex fruit syndrome). In this paper we report a review of latex proteins, the symptoms of latex allergy, diagnosis and management in subjects with latex allergy.

[Novel type of vaccine with a combination of Toll like receptor agonists--TLR 1/2, 4, 5/6, 9].

AIM: Proof of therapeutic efficacy of a novel type of vaccine with a combination of natural Toll like receptor agonists (TLR) 1/2, 4, 5/6, 9 in infectious and noninfectious human pathology. MATERIALS AND METHODS: Immunovac-VP-4 vaccine, containing antigens of opportunistic microorganisms that are TLR 1/2, 4, 5/6, 9 ligands, was used for experiments and clinical trials. RESULTS: Immunovac-VP-4 activates innate immunity by inducing maturation of dendritic cells with expression of costimulating molecules on their membrane (CD40+, CD80+, CD86+), terminal differentiation molecules--CD83+ and antigen-presenting molecules (MHC class I and II); activates proinflammatory (TNFalpha, IL-6) and regulatory (IL-12, INFgamma) cytokine synthesis that programs T-lymphocyte differentiation by Th1 pathway; increases cytotoxic activity of natural killer cells, inhibits melanoma B16 growth and Lewis lung carcinoma metastasis. Therapeutic effect of Immunovac-VP-4 was evident regardless of pathology by a significant decrease of quantity and severity of recidives, improvement of all clinical parameters, reduction of quantity of administered pharmaceutical preparations including antibiotics and glucocorticosteroids. The rate of intercurrent acute respiratory viral illnesses and their bacterial complications decreased. Immunovac-VP-4 therapy modified course of illness from severe into milder forms. Positive therapeutic effect was 69.2 - 100%. CONCLUSION: High therapeutic effect of vaccine therapy is based on innate immunity activation by combining TLR agonists. Immunovac-VP-4 contains an optimal combination of natural TLR agonists that ensure high therapeutic effect in various nosological forms of infectious and noninfectious human pathology.

Pitfalls in the diagnosis of latex allergy.

BACKGROUND: Screening patients for latex allergy prior to surgery is an important but intensive procedure. The appropriate testing strategy for diagnosing latex (Hevea brasiliensis) allergy involves in-vitro specific IgE or skin prick testing. The sensitivity and specificity of both tests are influenced by patient-specific factors or manufacturing processes that alter the clinically relevant allergens in skin testing solutions. METHODS: Total IgE and latex-specific IgE testing was introduced as a screening test. Skin prick testing was done on patients with a high probability of latex allergy and negative specific IgE with total IgE <100 kU/L. SDS-PAGE was done on the non-ammoniated latex (NAL) and newly introduced ammoniated latex (AL) reagents for the clinically relevant allergens. RESULTS: 51 patients had a total IgE <100 (range, 2.8-99.0 kU/L), and 10% had a positive skin test. 60% of positive skin tests would have been missed with lower total IgE cut-offs of 50 kU/L (6% of referrals). SDS-PAGE of the NAL solution showed 3 prominent bands with molecular weights of approximately 20, 24 and 42 kDa that correlated with Hev b 6, Hev b 3 and Hev b 7/13, respectively. In contrast, the AL solution showed 3 very faint higher molecular weights bands that did not correlate with clinically relevant antigens. CONCLUSIONS: Increasing the cut-off value of total IgE for allergen-specific IgE testing increased the sensitivity of the specific IgE test. The NAL reagent had a greater number of clinically significant allergens at higher concentrations than AL, which may have implications for the clinical sensitivity of the newer AL reagent.

Acute Management, Diagnosis, and Follow-Up of Suspected Perioperative Hypersensitivity Reactions in Flanders 2001-2018.

BACKGROUND: Despite numerous efforts to describe the clinical manifestations and the epidemiology of perioperative hypersensitivity (POH), there remains room to increase awareness among anesthetists and immunologists/allergists. OBJECTIVE: To report the findings of a 17-year survey of suspected POH in Antwerp, Belgium. METHODS: We analyzed clinical and diagnostic data from 715 patients referred because of a suspected POH reaction, between January 1, 2001, and May 31, 2018. A total of 456 patients demonstrating a POH could be queried about subsequent anesthesia. RESULTS: A total of 608 cases formed the final dataset; 208 had a non-life-threatening reaction and 400 a life-threatening reaction. In life-threatening reactions, hypotension was predominating. In the non-life-threatening reactions, 83.9% of the patients displayed cutaneous manifestations. In life-threatening reactions, intravenous adrenaline and fluids were administered in 75.7% and 31%, respectively, and 41.3% had their intervention abandoned. Mast cell activation (MCA) was mainly, but not exclusively, observed in severe grades but did not predict the mechanistic process nor the culprit. A cause was identified in 77.8% of severe and 48.6% of milder cases. Main culprits were neuromuscular blocking agents, latex, cefazolin, and dyes. A total of 156 cases had uneventful anesthesia, except 1 patient who was inadvertently re-exposed to hidden chlorhexidine. CONCLUSIONS: This study highlights that there is room for an improved acute management and an optimized diagnostic workup that should not be restricted to patients with severe reactions and/or showing MCA.

Latex allergy: a model for therapy.

Allergy to natural rubber latex products emerged as an important clinical condition following an increase in the use of latex gloves for barrier protection in the early 1980s. In addition to latex glove users, other high-risk groups with different latex exposure include spina bifida patients and others with multiple surgical procedures. Subjects with fruit and vegetable allergy are also at risk due to cross-reactive allergens. Following the significant advances in the identification and characterization of common aeroallergens, latex allergy was well placed to become an excellent model of therapy. Awareness of latex allergy and modes of sensitization enabled epidemiological studies to inform allergen avoidance initiatives, substantially reducing inadvertent exposure in major hospitals in Western countries. Spina bifida is often identified in utero or soon after birth, allowing vigorous latex allergen avoidance with enhanced efficacy of primary prevention. However, changing demographics of latex allergy and technological revolution in countries such as China and India are predicted to unleash a second wave of latex allergy reemphasizing the incentive for improved manufacturing procedures for latex products. The desirable high tensile strength and elasticity of natural rubber latex have made the commercial identification of good alternatives very difficult but this would also be attractive for primary prevention. In addition, an effective specific immunotherapy regimen would be valuable for selected high-risk atopic individuals. Current subcutaneous and sublingual immunotherapy schedules have been tested for treatment of latex allergy with evidence of efficacy but the risks of adverse events are high. For such potent allergens as latex, hypoallergenic but T cell-reactive preparations are required for clinical use. Identification of allergenic components of latex products, with generation of monoclonal antibodies and recombinant allergens, allowed sequence determination and mapping of T cell and B cell epitopes. Together, these reagents and data facilitated improved diagnostics and investigation of novel-specific therapeutics. Potential hypoallergenic latex preparations identified include modified non-IgE-reactive allergen molecules and short T cell epitope peptides. The co-administration of adjunct therapies such as anti-IgE or corticosteroids and of appropriate adjuvants for induction of regulatory T cell response offers promise for clinically effective, safe latex-specific vaccines.

Latex allergy: two educational cases.

Natural rubber latex (NRL) allergy is a significant problem both for health care workers and for children with complex medical and surgical conditions that require multiple surgical interventions. Primary and secondary prophylaxis are effective measures in identified high risk groups, such as spina bifida (SB). It is therefore likely that with proper attention to prevention and secondary prophylaxis in the highest risk groups that the numbers of paediatric SB patients with NRL allergy will continue to decrease. In contrast medical awareness of established latex allergy needs to be maintained. The issue of latex sensitisation via fruit and food allergy will also remain, so some of the attention that SB patients have received in the past may need to be refocussed onto other emerging high risk groups. Innovative immunomodulatory approaches may soon translate to the clinic for latex sensitised or allergic subjects.

Adverse reactions to latex occurring in an outpatient dialysis access center.

Latex allergies have been reported to be present in 1-5% of the general population. Patients with multiple surgeries and frequent exposure have a significant increase in the risk of a serious latex allergy. Reports of latex allergy in dialysis patients who need interventional procedures, however, have been limited. In this analysis, two patients treated at an outpatient dialysis access center are presented with presumed latex allergies. This report reviews the mechanism of latex allergy and provides important considerations regarding latex allergy. In addition, it calls for heightened awareness of this uncommon but potentially dangerous condition.

Natural rubber latex allergy in children: clinical and immunological effects of 3-years sublingual immunotherapy.

BACKGROUND: We previously demonstrated that one year of sublingual immunotherapy (SLIT) with natural rubber latex (NRL) was safe and efficacious in paediatric patients with NRL allergy. RESEARCH DESIGN AND METHODS: We studied 12 NRL-allergic children (age 4-15), previously assigned to the treated arm of a double-blind placebo controlled study, who received a commercial latex SLIT for three years. Adverse reactions were monitored. The primary end-point was the NRL glove-use test. As secondary end-points, skin prick test with NRL and NRL serum specific IgE were used. MAIN OUTCOMES MEASURES: No SLIT-related side effects were observed. A significant reduction of the glove-use score was observed after one-year treatment (5.1 +/- 4.2 vs. 14.8 +/- 5.7, p=0.0031). This parameter was further reduced in the second year since SLIT start (2.0 +/- 2.7, p=000007). After 3 years of SLIT all patients had a negative glove-use test (p<0.0001). Baseline wheal areas of skin prick test (6.8 +/- 2.5 mm2) were significantly reduced after 2 (5.3 +/- 1.8 mm2) and 3 years (4.0 +/- 1.8 mm2) of SLIT (p=0.039 and 0.027, respectively). Baseline values of serum specific IgE (23 +/- 34 KU/l) were significantly reduced after 3 years since SLIT start (6.4 +/- 5.0, p=0.0371). CONCLUSIONS: Three years of latex SLIT is safe and consolidates the efficacy previously observed after one year of treatment in paediatric patients.

[Natural latex allergy. Patient management: from clinic to prevention. A review]. / Allergia a latice naturale. Gestione del paziente: dalla clinica alla prevenzione. Rassegna critica.

The widespread use of latex devices has been followed, in the last 25 years, by an increase in IgE mediated sensitization. The clinical manifestations of latex allergy affect the skin (urticaria and angioneurotic oedema), the lower and the upper respiratory tracts (rhinoconjunctivitis, asthma and glottis oedema), and the cardiovascular system (anaphylaxis). There is also an anaphylactic risk during surgery and invasive diagnostic procedures. Vegetable food cross-reacts with latex so that more than half of the patients show specific IgE against some food. Further than traditional groups at risk, as health care workers, other work categories have to be protected, because of the inappropriate use of latex gloves (food or drug industry workers, mechanics, panel beaters and so on). Recently the latex most important allergenic fractions have been characterized and recombinant allergens are now available. The recombinant allergens allow a better standardization of the extracts for diagnostic use, the production of safer extracts for immunotherapy as well as a more accurate evaluation of food cross-reactions. The recombinant allergens will allow a more accurate dosage of latex concentrations in air and in objects and, in future, to establish threshold limit values. The main aims of prevention are the replacement of latex with alternative elastomers, the reduction of work and extra work exposure and an efficient health survey in working environment. The use of latex gloves and devices among general population has to be discouraged. Specific immunotherapy has to be considered a second choice and restricted to highly qualified workers in order to realize a rehabilitation to their previous jobs. The actually obtained protection must be verified.

[Consensus Document. Update on latex exposure and use of gloves in Italian health care settings]. / Documento di Consenso. Aggiornamenti in tema di esposizione a latice e impiego di guanti in ambito sanitario.

This consensus document was prepared by an Italian working group including occupational health professionals involved for many years in the management of glove- and latex-related problems in health care settings. The aim of this document was to address the most significant technical, epidemiological, clinical, environmental and prevention problems related to the use of gloves and latex. The group's recommendations are based on scientific evidence and practical experience but they cannot be considered as final. These topics need to be periodically revised. The following points should be taken into account: glove quality seems to have improved considerably but the information on glove features provided by the manufacturers is often still inaccurate or incomplete; the regulations in force provide that the manufacturers perform tests to supply evidence for the quality of the products but they do not indicate which analytical method should be used and they do not require that the results be reported in the technical data sheets. Thus the manufacturers have only to declare that their products are "in accordance with the rules"; therefore, purchasers should require the manufacturing companies to supply detailed information and verify their reliability. Moreover, the rules should be adapted to higher quality standards; occupational physicians must be involved for the correct choice and purchase of protective gloves; the use of gloves (in particular latex gloves) and latex devices in health care settings should be based on specific criteria: procedures must be available stating which kind of gloves are suitable for specific tasks. When exposure to latex cannot be avoided it is necessary to choose products that have good biocompatibility (e.g., powder free-gloves with low allergen content); once and for all latex powdered gloves should no longer be commercially available! labels for latex devices (including gloves) should report the extractable latex allergen content. Limit values for extractable latex allergens should be established; the use of synthetic rubber gloves should be encouraged since some materials (e.g., neoprene and nitrile rubber) appear to have physical properties and protective efficacy similar to latex, plus good biocompatibility; more studies should be promoted to verify the protective efficacy of new synthetic materials; health care workers should be informed about the advisability and usefulness of using materials other than latex; health care services should not cause additional risks but rather highlight the advantages for workers and patients if the use of latex gloves and devices is minimized.

[Latex sensitization and allergy in Hospital General de Mexico surgery residents]. / Sensibilización y alergia a látex en residentes quirúrgicos del Hospital General de México.

BACKGROUND: The prevalence of latex allergy ranges from 0.8 to 6.5% and is the second cause of perioperative anaphylaxis. The main risk factors are being a health worker or latex producer, hours of latex gloves or products usage, exposure to other hand irritants, history of atopy, neural tube closure defects or numerous surgeries at early age. OBJECTIVE: To determine the frequency of latex sensitization in resident physicians of the Hospital General de México surgical area. METHODS: Prospective, cross-sectional, descriptive study where skin prick tests were applied to residents of the surgical area of the Hospital General de México, which depends on the Ministry of Health and is located in Mexico City. RESULTS: Ninety-two subjects were included and had skin tests practiced, with 11 surgical specialties participating. Latex sensitization in this population was 11.9%, whereas the presence of latex allergy was 10.8%. CONCLUSIONS: A high frequency of latex sensitization and allergy was demonstrated in Hospital General de Mexico surgery residents, which indicates the need for policies and procedures to be developed for health workers with latex allergy, as well as continuous training of employees on latex allergy.

Antecedentes: La prevalencia de alergia al látex oscila entre 0.8 y 6.5 % y es la segunda causa de anafilaxia perioperatoria. Los principales factores de riesgo son ser trabajador de la salud o productor de látex, horas de utilización de guantes o productos de látex, exposición a otros irritantes de manos, antecedente de atopia, defectos del cierre del tubo neural o numerosas cirugías a edad temprana. Objetivo: Determinar la frecuencia de sensibilización al látex en médicos residentes del área quirúrgica del Hospital General de México. Métodos: Estudio clínico prospectivo, transversal, descriptivo, mediante la realización de prueba de punción cutánea a residentes del área quirúrgica del Hospital General de México, Secretaría de Salud, Ciudad de México. Resultados: Se incluyeron 92 sujetos a los cuales se les realizó pruebas cutáneas, participando 11 especialidades quirúrgicas. La sensibilización al látex en esta población fue de 11.9 % y la presencia de alergia al látex de 10.8 %. Conclusiones: Se demuestró alta frecuencia de sensibilización y alergia al látex en los residentes quirúrgicos del Hospital General de México, lo que indica la necesidad de desarrollar políticas y procedimientos para los trabajadores de salud con alergia al látex y la capacitación continua de empleados sobre alergia al látex.