Introduction
The challenges associated with latex and its effects on the human body represent a key concern in contemporary medicine and biotechnology. Given the extensive applications of latex, particularly in the production of medical devices such as gloves, catheters, and other personal protective equipment, its safety is of paramount importance.
Latex allergy is a complex and multifaceted phenomenon that raises concerns due to its potential to trigger severe immune reactions in a substantial proportion of individuals [1]. Current research trends exploring the causes and mechanisms of latex allergy contribute to a deeper understanding of this pathology and the effects of biologically active latex components on the human immune system.
Furthermore, advancements in diagnostic methods enable the timely identification of sensitised individuals, thereby reducing the risk of severe reactions upon exposure to allergens. Studies aimed at developing new approaches to the treatment and prevention of latex allergy, particularly by reducing the allergenic protein content in latex products, hold both practical and scientific value.
The issue of natural rubber latex allergy remains relevant due to the widespread use of latex in industry and medicine. Research in this area focuses on the immunological, epidemiological, and technological aspects of latex. The analysis of latex’s biological properties, the assessment of its health impacts, and the development of safer alternatives have also emerged as key subjects in the 2020s.
Jiménez-Carrillo et al. [2] investigated allergic reactions to latex, particularly within healthcare settings, where exposure to latex-containing products is exceptionally high. They emphasised that latex allergy is a potentially severe condition that may frequently lead to anaphylactic reactions, particularly in surgical departments [2]. The primary conclusion of their study was that avoiding latex products remains the only reliable preventive measure. However, they noted that the lack of standardisation in immunotherapy for latex allergy poses challenges to its clinical implementation, highlighting gaps in research concerning the optimisation of allergen extracts for therapeutic use. The study conducted by Vajrapatkul [3] focused on the economic and technological aspects of concentrated latex production in Thailand. Employing Bayesian analysis methods, the researcher assessed the impact of technological innovations on production, employment, and pricing within the industry. The findings indicated that technological advancements enhance productivity and reduce costs. Nevertheless, gaps include an insufficient analysis of the long-term consequences of external economic shocks on the sector.
Guerra et al. [4] investigated the biomedical applications of natural latex, particularly its capacity to stimulate angiogenesis and osteogenesis. They described the development of latex-based devices for controlled drug release, particularly in the treatment of chronic wounds. The principal conclusions of the study highlighted the material’s high biocompatibility; however, the issue of its slow biodegradation remains unresolved. Koyuncu et al. [5] examined the impact of the COVID-19 pandemic on the use of latex gloves among nurses. Their study discovered that the frequency of latex glove usage had doubled, leading to an increase in allergic symptoms among healthcare professionals. However, limited attention was given to the long-term health consequences, indicating the need for further research.
Peixe et al. [6] explored the issue of labelling medical products containing latex in their packaging. Their findings demonstrated that a substantial proportion of manufacturers fail to provide accurate information regarding latex content, thereby posing risks to patients with latex allergies. The authors emphasised the necessity of implementing stricter labelling standards. Cesar et al. [7] developed biomedical latex membranes incorporating polylactic acid, which demonstrated improved biodegradability and the absence of toxic effects. This innovation opens new possibilities for the use of latex in medical implants; however, the limited number of clinical trials remains a constraint. Benjamaa et al. [8] conducted a review of the phytochemical properties of latex from the Euphorbia genus. Their findings demonstrated potential for its use in medicine, particularly due to its antibacterial and antioxidant properties. Nevertheless, the authors highlighted a lack of understanding regarding the role of certain secondary metabolites in therapeutic effects, representing a gap in current research.
The issue of occupational allergies among healthcare professionals remains a pressing concern in Poland due to the high prevalence of sensitisation to various allergens, including latex. This is particularly relevant given the widespread use of latex gloves, which are an essential component of medical practice. Polish researchers indicated that latex remains one of the primary causes of contact dermatitis and allergic reactions among medical staff, despite its role often being underestimated in broader epidemiological studies.
In a study conducted by Stróżyk et al. [9], the adherence of medical professionals to allergy diagnosis protocols was examined. It was established that only a portion of physicians follow international guidelines for the diagnosis and prevention of allergies. The findings highlighted insufficient utilisation of sensitisation tests, such as skin prick tests or specific IgE assays, which could confirm latex allergy. Despite this, the majority of physicians recommended appropriate preventive measures, including the use of low-latex gloves or alternatives. However, a notable limitation of the study was the insufficient emphasis on occupational risks for professionals who frequently work with latex materials, such as surgeons and dentists.
Aim
Thus, the purpose of the study is to investigate the causes, clinical manifestations, and contemporary approaches to the diagnosis of latex allergy. To achieve this purpose, the following tasks are undertaken: analysis of scientific and clinical sources to determine the primary causes of latex allergy development and potential risk groups; synthesis of typical symptoms and the progression of allergic reactions to latex, considering individual patient characteristics; and assessment and comparison of current diagnostic methods for latex allergy, with particular attention to their accuracy, accessibility, and safety.
Methods
The study was designed as a systematic review, conducted between August and December 2024. The timeframe encompassed studies published between 2019 and 2024 to ensure the inclusion of the most up-to-date sources on latex allergy.
Data collection was performed using multiple scientometric platforms, including PubMed, Scopus, Web of Science, and Google Scholar, as well as Polish indexing resources (Index Copernicus, BazTech, BazHum, PSJD, and Biblioteka Nauki). Keyword searches were conducted using English terms (“latex allergy”, “latex allergy diagnosis”, “natural rubber latex AND allergenic proteins”) and Polish equivalents (“alergia na lateks”, “diagnostyka alergii na lateks”). Inclusion criteria encompassed peer-reviewed publications, availability of full texts, research on sensitisation mechanisms and latex allergy diagnosis, publication within the 2019–2024 period, and absence of major methodological flaws. Exclusion criteria included duplicate records across databases, studies lacking detailed information on Hev b allergenic proteins, publications without clinical data on latex allergy manifestations, and studies with inadequate statistical sample sizes. Initially, 112 sources were identified; however, after applying extended inclusion/exclusion criteria, 67 publications remained.
The study employed systematic review methods and comparative content analysis. Each source was first assessed for relevance, with a particular focus on data regarding latex allergenic proteins, IgE-mediated reactions, and diagnostic and preventive approaches. Subsequently, the results of the content analysis were systematically organised into tables based on several parameters: prevalence of occupational sensitisation, differences in latex allergy among children and adults, and the effectiveness of diagnostic methods. Moreover, available experimental data were reviewed, and descriptions of equipment for skin tests and laboratory analyses were included (such as standard prick test kits, skin test applicators for patch tests, and immunoassay systems for the detection of specific antibodies).
Considerable attention was given to the method of detecting specific IgE in serum, which was used to confirm or refute the clinical relevance of sensitisation to Hev b proteins. The potential of provocation tests was thoroughly examined, as these tests helped establish a connection between latex exposure and existing allergic symptoms. To analyse recommendations from different countries, data on standardised testing procedures and regulatory documents governing the labelling of latex-containing products were compared. Table 1 summarises the reported availability of major diagnostic methods for latex allergy (SPT, sIgE, CRD, provocation tests) across different countries and regions, based on the included studies.
Table 1
Availability of major diagnostic methods for latex allergy across regions/countries. Source: compiled by the author based on Giangrieco et al. [22], Sell and Visentainer [32], Mwanga et al. [33], Vajrapatkul [3], Rojruthai et al. [17], Stingeni et al. [59], Dickel and Mahler [60], Stróżyk et al. [9], and Malathy et al. [58]
| Region/country | SPT availability | sIgE availability | CRD availability | Provocation tests |
|---|---|---|---|---|
| Poland | Yes | Yes | Limited | Rare |
| Thailand | Yes | Yes | Limited | Rare |
| Africa | Limited | Limited | Rare | Rare |
| Italy | Yes | Yes | Yes | Occasional |
The collected publications were systematised and stored using Mendeley (version 2.108.0). Initially, all PDF files and full-text documents were uploaded to the Mendeley library, where metadata records were automatically generated. Manual editing of titles and annotations was then performed in cases where the software incorrectly identified information. Separate folders were created in Mendeley for specific thematic areas (e.g., “Occupational Sensitisation”, “Diagnosis”, “Cross-Reactivity”), allowing for efficient sorting and review of relevant articles. Finally, citations for the 67 selected sources, which met the research objectives, were generated using the built-in “Citations” function.
A problem-thematic approach was employed to interpret the results: central themes (Hev b allergens, risk groups, diagnostic algorithms) were first identified and subsequently compared and summarised in the form of a structured description, incorporating examples from different regions and methodological approaches. This analytical framework facilitated the identification of research gaps in latex allergy studies and enabled the formulation of generalised conclusions.
Furthermore, the limitations of the study must be acknowledged. This systematic review is subject to constraints such as the heterogeneity of the included studies, the absence of standardised diagnostic protocols, varying definitions of clinical outcomes, and disparities in access to diagnostic procedures across different locations. The difficulties arose directly from the study of the 67 included papers and offer significant context for evaluating the results and generalising the conclusions.
Results
Theoretical background on latex: definition and applications
Latex is a biological material produced by plants such as the rubber tree Hevea brasiliensis. It is a colloidal solution containing natural rubber particles (primarily composed of polyisoprene), proteins, lipids, carbohydrates, and minerals. Fresh latex consists of approximately 60% water, 35% polyisoprene, and around 5% other compounds. The structure of latex influences its properties, particularly the strength and stability of products made from natural rubber [10].
Natural rubber is a biopolymer composed predominantly of cis-1,4-polyisoprene [11]. Its chemical structure consists of approximately 97% cis-1,4 linkages, 1% trans-1,4 linkages, and 3% other structures. The primary component of latex is the polymer phase, which is surrounded by a layer of phospholipids and proteins that stabilise the colloidal system. These components also contribute to the superior mechanical properties of natural rubber compared to its synthetic counterparts [12].
The principal source of natural rubber is the Hevea brasiliensis tree, cultivated in tropical regions. Latex extracted from this tree accounts for the majority of global natural rubber production. Other plants, such as Taraxacum kok-saghyz, are being investigated as alternative sources; however, they have yet to match Hevea brasiliensis in terms of production scale and economic efficiency [13]. Synthetic rubber, derived from petrochemical products, serves as an alternative but exhibits limited elasticity and mechanical properties in comparison to natural rubber. For instance, the cis-dominated polyisoprene in natural rubber provides exceptional elasticity and wear resistance, which are difficult to replicate synthetically [14].
Latex derived from Hevea brasiliensis has extensive applications in medicine, manufacture, and everyday life due to its physicochemical properties, including elasticity, biocompatibility, and protective characteristics. It is widely used in the manufacture of medical products such as gloves, catheters, tourniquets, airway tubes, and condoms. Natural rubber offers excellent microbial barrier properties, making it indispensable in infection prevention [15, 16]. Latex gloves remain the standard in surgical settings, although they require additional processing to reduce allergenicity due to the presence of proteins that may trigger allergic reactions [17]. Meanwhile, alternative materials, such as guayule latex-based, are being developed to eliminate allergy risks while providing improved mechanical stability [18].
In industry, latex is a key component in the production of tyres, adhesives, and coatings. Natural rubber is favoured for its elasticity and resistance to mechanical damage, which are critical for automotive tyre manufacturing. In the adhesives and coatings sector, innovative processes are being introduced to enhance environmental sustainability and reduce toxic additives, such as the incorporation of natural substances like cellulose and collagen [19]. In everyday life, latex is used in the manufacture of toys, balloons, hairbands, and condoms. Due to its flexibility and durability, latex ensures the comfort and longevity of these products. In the case of condoms, particular attention is given to biocompatibility and the reduction of allergic reactions through specialised material treatment [20]. Overall, latex remains a valuable material owing to its versatility. However, significant efforts are being directed towards the development of less allergenic and more environmentally friendly alternatives to meet contemporary demands. This ensures its continued relevance across various sectors, including medicine, manufacturing, and domestic applications.
Latex sensitisation is a complex process based on the interaction between latex proteins and the human immune system, as well as cross-reactivity with other allergens [21]. Latex contains a range of proteins, notably Hev b 1-13, which serve as key allergens. Upon contact with latex, these proteins activate the immune system via an IgE-mediated response, contributing to the onset of allergic symptoms. This process begins with sensitisation, wherein latex proteins are recognised by the immune system as foreign antigens. Subsequent exposure to the allergen can trigger immediate allergic reactions, including angioedema, bronchospasm, or anaphylaxis. For instance, Hev b 5, a latex protein, is a major allergen capable of interacting with IgE, thereby eliciting a strong immune response [22].
The latex-fruit syndrome represents a classic example of cross-reactivity. Latex allergens share structural epitopes with proteins found in certain fruits, including bananas, avocados, kiwis, pineapples, papayas, and others. For example, Hev b 8, a latex panallergen, exhibits structural similarity to profilins present in pollen and plant-derived products. As a result, individuals allergic to latex may also experience allergic reactions to these fruits [23]. Sensitisation to latex is frequently complicated by concurrent food allergies. In approximately 30–50% of cases, patients with latex-fruit syndrome exhibit allergic reactions to fruits such as bananas, avocados, kiwis, pineapples, papayas, and others. Studies demonstrated that cross-reactivity between latex proteins and fruit proteins can lead to both localised symptoms (e.g., itching, swelling) and systemic reactions (e.g., anaphylaxis) [24].
Biochemical studies identified shared epitopes between latex proteins, fruit allergens, and plant pollen proteins. This explains why sensitised individuals often experience a broad spectrum of allergic reactions. The diagnosis of latex allergy relies on specific IgE testing and methods for detecting cross-reactivity [25]. Thus, latex sensitisation and its cross-reactivity with other allergens are crucial considerations in the diagnosis and management of allergic reactions. Identifying the structural similarities of allergens is essential for the development of effective therapeutic strategies.
The main causes of latex allergy development and risk groups
Latex contains several key allergenic proteins that trigger an immune response, including Hev b 1, Hev b 3, Hev b 5, Hev b 6, Hev b 8, and others. These proteins activate IgE-mediated reactions, leading to allergic symptoms such as itching, swelling, and even anaphylaxis. Studies indicate that Hev b 8, a pan-allergen, can interact with the immune system due to its structural similarity to profilins found in fruits and pollen [26].
The specificity of the immune response to latex proteins depends on factors such as the frequency and intensity of exposure to latex, and genetic predisposition. For instance, healthcare workers are more likely to become sensitised to Hev b 5 and Hev b 6, while patients with concomitant fruit allergies (such as bananas, avocados, kiwis, pineapples, papayas, and others) typically show a reaction to Hev b 8 due to cross-reactivity with fruit proteins [24].
Patients with atopy (eczema, asthma) and those who have undergone multiple surgical procedures in childhood are at significantly higher risk of latex sensitisation [27–29]. For example, children with spina bifida have an increased risk of developing an allergy due to frequent exposure to medical devices containing latex. This group of patients often demonstrates sensitisation to proteins such as Hev b 1 and Hev b 3, which is confirmed by the detection of specific IgE to these allergens [30].
Cross-reactivity between latex proteins and fruits depends on their amino acid composition and shared epitopes. For example, the protein Hev b 8, a pan-allergen, shares structural similarities with the proteins in bananas, avocados, kiwis, pineapples, papayas, and others, leading to cross-reactions in patients with latex allergy. Studies also show that patients allergic to latex often exhibit increased sensitivity to several tropical fruits, such as kiwis, avocados, and papayas [31]. This further enhances the understanding of the relationship between latex sensitisation and food allergies, emphasising the need for accurate diagnosis and a comprehensive approach to patients with these conditions. The main causes of latex allergy are outlined in Table 2 [22, 32, 33].
Table 2
Key causes and risk factors for latex allergy development. Source: compiled by the author based on Giangrieco et al. [22], Sell and Visentainer [32], and Mwanga et al. [33]
The processing and vulcanisation of natural rubber significantly affect its allergenic profile [34]. High temperatures during vulcanisation promote modifications of Hev b proteins, particularly through denaturation or the creation of new epitopes that may enhance the allergenicity of the material. Studies show that chemical accelerators, such as zinc compounds used in glove manufacturing, can intensify sensitisation by affecting proteins or creating conditions for type IV hypersensitivity reactions. Modern latex purification methods, such as saponification and deproteinisation, aim to reduce the content of allergenic proteins. These measures decrease the risk of sensitisation among users, especially in the medical field. Studies demonstrate that these technologies can reduce Hev b protein levels to concentrations that do not provoke clinical allergy symptoms [17].
The type of occupational contact with latex also influences the risk of sensitisation. Healthcare workers who use gloves and other latex products have a higher risk of sensitisation to Hev b proteins due to prolonged contact and inhalation of latex particles [35, 36]. Studies among healthcare professionals show that 5–17% of workers experience allergic reactions, while industrial workers who come into contact with raw latex may experience sensitisation rates of up to 12% due to direct contact with unprocessed material [37].
In medical institutions, the risk of sensitisation decreases after switching to gloves made from purified latex or synthetic materials. However, in industrial settings, where products with high protein content are used, the risk remains elevated, particularly in the absence of personal protective equipment [38].
Geographical factors and the specifics of latex production play a substantial role in shaping the allergenic profile and health risks. Climatic conditions, soil types, and the methods of latex harvesting and processing affect its chemical composition and the content of allergenic proteins [39]. For instance, studies show that the level of Hev b allergenic proteins varies depending on the geographical region of production, influencing risks for workers and users of latex products. Furthermore, various production methods, such as vulcanisation, can either reduce or increase the allergenicity of latex by modifying protein structures. Purification and processing methods, such as saponification, aimed at reducing the allergenic profile, are important in decreasing the sensitisation of users [38].
The geographical distribution of latex production, particularly in Asian countries (Malaysia, Thailand), which are major producers of natural latex, requires consideration of risks associated with local conditions. For example, the use of pesticides or additives in different regions may further impact the chemical composition of latex. Geographical variation also affects the availability of modern purification methods and regulations governing latex quality [40]. In a global context, the increased demand for latex in the medical field during the COVID-19 pandemic emphasised the importance of geographical factors. Changes in production processes and increased allergenicity of latex in certain countries highlight the importance of regional studies to mitigate risks.
Genetic factors play a key role in the development of latex allergy, influencing the immune system and predisposition to hypersensitivity [41]. Studies identified several genetic variants associated with an increased risk of allergic diseases, including latex allergy. Polygenic risk scores (PRS) allow for the identification of susceptibility to allergy through a combination of genetic variants. PRS for conditions such as asthma and allergic rhinitis show a correlation with the severity of allergic diseases, including reactions to latex. In studies of patients with elevated IgE levels, an enhanced immune response to latex was noted in those with a high PRS for allergic conditions. This suggests that genetic factors not only increase the risk but also affect the severity of the allergy [42].
Genome studies uncovered several key genes that influence the risk of developing allergic diseases. For example, the filaggrin (FLG) gene is responsible for maintaining the skin’s barrier function. Mutations in FLG disrupt the skin’s protective barrier, facilitating the penetration of allergens, including latex. Meanwhile, the NOD2 and PRKCQ genes influence the immune response, particularly T-cell activation, which plays a key role in allergy development. Importantly, combinations of mutations in these genes are associated with high IgE levels and increased sensitivity to latex proteins [43].
Children with a family history of allergies have an increased risk of developing a latex allergy. For instance, studies on children genetically predisposed to atopy showed that they are more likely to become sensitised to latex proteins due to the activation of immune cells. Genetic markers that regulate IgE levels have also been linked to an increased risk of allergic sensitisation [44]. Genetic predisposition to allergies may be modulated by maternal factors during pregnancy. Elevated maternal IgE levels, along with factors affecting the foetal epithelial barrier, may contribute to the development of allergic predispositions, including latex allergy. Epigenetic modifications induced by environmental factors, such as smoking, pesticides, and poor nutrition during pregnancy, also play an important role [45].
Genetic factors, including mutations in genes regulating the epithelial barrier and immune response, increase the risk of developing latex allergy. Research into these mechanisms opens up new possibilities for personalised medicine aimed at the prevention and management of allergic reactions.
Clinical manifestations and pathogenetic mechanisms of latex allergy
Skin symptoms of latex allergy are among the most common manifestations of this hypersensitivity. These can range from mild, localised reactions to severe systemic conditions that require emergency medical attention. The most common symptoms include urticaria, itching, redness, erythema, and swelling. In some cases, symptoms may be complicated by the formation of blisters or cracks on the skin. These manifestations often occur upon direct contact with latex products, such as gloves, balloons, or catheters, but can also be triggered by inhalation of latex aerosol.
Latex-induced contact dermatitis is a type IV reaction characterised by a delayed onset. It is caused by chemicals added to latex during the manufacturing process, particularly vulcanisation accelerators. Symptoms include itching, peeling, skin redness, dryness, and cracks. This type of reactions typically develops 24–48 h after contact with the allergen. Treatment usually involves avoiding contact with latex and using topical corticosteroids to reduce inflammation [46].
IgE-mediated reactions, also known as immediate-type reactions, occur in response to latex proteins and result from the binding of IgE to receptors on mast cells. This leads to the release of histamine and other inflammatory mediators, causing symptoms such as urticaria, angioedema, and itching. In severe cases, such reactions may progress to anaphylaxis, which includes difficulty breathing, low blood pressure, and a life-threatening risk. These reactions occur rapidly, often within minutes of contact with latex [47].
In children, latex allergy symptoms can be particularly acute due to several factors. The immaturity of the skin barrier and immune system makes children’s skin more permeable to allergens. For example, in children with atopic dermatitis, the skin’s protective barrier is often impaired, allowing allergens to penetrate more easily and trigger sensitisation. Elevated IgE levels in children with a genetic predisposition to allergies contribute to rapid and severe allergic reactions. In such children, the risk of acute symptoms is higher, and allergic manifestations may appear within minutes of contact [48].
Pro-inflammatory cytokines are of particular importance, as they promote the intensification of allergic reactions in children. In addition, children sensitised to latex often exhibit polyallergy to other substances, such as pollen allergens or food products. This further increases the risk of rapid symptom development [49].
Thus, skin manifestations of latex allergy, regardless of the mechanism of their onset, require an accurate diagnosis for timely treatment. It is crucial to distinguish between contact dermatitis and IgE-mediated reactions to determine the most effective therapeutic approach, especially in children, whose reactions can be particularly severe and transient.
Respiratory symptoms, such as rhinitis, sneezing, and difficulty breathing, are common manifestations of latex allergy [50]. These symptoms arise due to an IgE-mediated reaction, in which latex proteins stimulate the production of specific IgE antibodies. Upon subsequent exposure, the allergen binds to IgE on mast cells and basophils, triggering their degranulation and the release of histamine, leukotrienes, and other mediators. This results in inflammation of the mucous membranes of the respiratory tract, manifesting as rhinitis, sneezing, and nasal congestion. In severe cases, these reactions can progress to bronchospasm, characterised by bronchial constriction and difficulty breathing [51].
The progression of latex allergy to anaphylaxis is possible, particularly in patients with high levels of sensitisation. Anaphylactic shock is the most severe manifestation of the allergy, arising from massive histamine release and other mediators, causing a sharp drop in blood pressure, generalised swelling, bronchospasm, and potentially life-threatening breathing difficulties [52]. Warning signs of allergy progression may include the onset of generalised urticaria, intense itching, nasal congestion, difficulty breathing, or coughing following latex exposure. In some patients, initial symptoms may be minimal but rapidly progress to severe reactions. In addition, a history of previous allergic reactions to latex or a predisposition to atopic diseases such as asthma or allergic rhinitis increases the risk of developing severe conditions [31].
In children, these symptoms can be particularly acute due to the immaturity of their immune system and the smaller diameter of their airways. These patients often experience relapses of bronchospasm or asthmatic symptoms in response to inhalation of latex protein aerosol [53]. Early recognition of warning signals such as severe itching, nasal congestion, and difficulty breathing, along with proper diagnosis (skin tests, specific IgE), is crucial to prevent the progression of allergies to bronchospasm or anaphylaxis. This highlights the need for patients and healthcare professionals to be aware of the risks associated with latex allergies.
Clinical cases of latex allergy show a wide range of manifestations – from mild local reactions to severe anaphylaxis. Mild manifestations, such as urticaria, pruritus, and erythema, most commonly occur at the site of latex contact and generally subside once exposure to the allergen ceases. However, in some patients, latex allergy may progress to systemic manifestations.
Typical moderate allergic reactions include mucosal oedema, rhinitis, and conjunctivitis, which present with nasal congestion, sneezing, and excessive lacrimation. These symptoms are often triggered by inhalation of airborne latex proteins, particularly in hospital settings or industrial environments [51].
Atopic status and comorbid chronic conditions, such as bronchial asthma and atopic dermatitis, influence the course of latex allergy, increasing the risk of systemic reactions and associated complications. Patients with atopic conditions frequently exhibit heightened immune activity, which exacerbates allergic responses, including those triggered by latex. Bronchial asthma, in particular, increases the likelihood of respiratory symptoms, such as bronchospasm, upon exposure to airborne latex proteins. Asthmatic patients have heightened airway hyperreactivity, rendering them more susceptible to aerosolised latex allergens [54].
Atopic dermatitis predisposes individuals to contact dermatitis following latex exposure, as a compromised skin barrier facilitates allergen penetration. Moreover, such patients often exhibit elevated levels of IgE, thereby increasing their susceptibility to systemic manifestations, including urticaria and, in severe cases, anaphylaxis [55].
The comorbidity of asthma, atopic dermatitis, and allergic rhinitis – commonly referred to as the “atopic march” – predisposes individuals to a higher frequency and severity of allergic reactions. Patients presenting with this triad are at an increased risk of severe complications, including anaphylaxis. A study demonstrated that individuals with both atopic dermatitis and asthma have a heightened risk of myocardial infarction and cardiovascular-related mortality, underscoring the multisystemic impact of these conditions [56]. Furthermore, atopic patients tend to exhibit a heightened propensity for recurrent allergic reactions upon repeated exposure to latex. Timely diagnosis, avoidance of latex exposure, and effective management of comorbid conditions are paramount in mitigating the risk of complications.
Skin moisture, microlesions, and excessive perspiration are critical factors influencing the onset and severity of allergic reactions to latex, particularly in occupational settings. These factors enhance skin contact with allergens and facilitate their penetration into the body, thereby increasing the likelihood of sensitisation and exacerbation of symptoms.
Moist skin, whether due to perspiration or the prolonged use of damp gloves, creates an environment that enhances the absorption of latex proteins. This is a common concern among healthcare workers who frequently wear latex gloves for extended periods [57]. Microlesions resulting from mechanical friction or pre-existing dermatological conditions, such as atopic dermatitis, further elevate the risk of allergic reactions. A compromised skin barrier permits deeper penetration of latex proteins into the epidermis, where they interact with the immune system, triggering sensitisation responses.
Sweat levels also play a noteworthy role in the development of allergic reactions. Perspiration can enhance the adhesion of latex proteins to the skin, increasing their bioavailability. Furthermore, prolonged use of latex gloves may lead to skin maceration, rendering it even more vulnerable to allergens [58]. To mitigate these risks, it is recommended to use powder-free gloves or those with a low latex protein content, as well as to ensure proper skin care and moisture control. Educating workers on the correct use of protective equipment and monitoring their condition are crucial for preventing allergic reactions in occupational settings.
Efficacy and safety of primary diagnostic methods for latex allergy
Skin tests, such as the prick and patch tests, are the principal diagnostic methods for detecting latex allergy. They offer high sensitivity and specificity, allowing the identification of immediate IgE-mediated reactions and delayed-type reactions associated with contact dermatitis. The prick test is used to diagnose immediate hypersensitivity (Type I) caused by latex proteins.
This procedure involves applying a drop of latex extract to the skin, followed by a small puncture using a specialised lancet. The results are assessed within 15–20 min, with the appearance of a wheal or erythema indicating sensitisation. To minimise false results, it is essential to use standardised extracts and conduct the test in a clinical setting, particularly for patients at high risk of anaphylaxis [47].
Conversely, the patch test is used to diagnose delayed hypersensitivity reactions (Type IV) related to contact dermatitis. This method involves applying adhesive patches containing allergens to the skin, which are left in place for 48 h. The results are evaluated after 48–72 h and, if necessary, again after 7 days. To prevent false-negative outcomes, it is important to consider regional variations in the extracts and allergens used [59].
The conditions under which these tests are performed are critical for minimising the risk of complications. The prick test should be conducted with immediate access to emergency medical care in case of anaphylaxis, while the patch test requires strict adherence to timing intervals to ensure delayed reactions are accurately recorded. Antihistamines should be temporarily discontinued before conducting both tests to avoid suppression of allergic responses [60]. A detailed analysis of the most commonly used diagnostic methods is presented in Table 3.
Table 3
Comparative characteristics of modern diagnostic methods for latex allergy. Source: compiled by the author based on Giangrieco et al. [22], Sell and Visentainer [32], and Mwanga et al. [33]
Modern laboratory techniques for detecting specific IgE to latex proteins, including molecular diagnostics, enhanced the accuracy of latex allergy diagnosis. The use of component-resolved diagnostics (CRD) enables the identification of individual protein components of latex, such as Hev b 1-13, which play a crucial role in allergic reactions.
Molecular diagnostics are based on the detection of IgE antibodies to specific latex proteins. For instance, Hev b 5 and Hev b 6 are among the most clinically relevant allergens responsible for IgE-mediated reactions in latex-allergic individuals. Multiplex assays, such as ALEX2, facilitate the simultaneous assessment of specific IgE to a broad spectrum of allergens, including latex proteins, thereby enabling a personalised diagnostic approach. Multiplex platforms such as ALEX2 (Allergy Explorer) allow for the simultaneous analysis of up to 295 allergens, including 178 molecular components. These methods enable the identification of specific IgE to key latex proteins, such as Hev b 2, Hev b 5, and Hev b 8, offering high sensitivity and specificity while also mitigating the risk of cross-reactivity between latex and other allergens, such as certain fruits [25].
The use of monoclonal antibodies in the investigation of protein epitopes, such as Hev b 8, provides highly accurate diagnostic outcomes. These antibodies facilitate the detection of panallergens that trigger cross-reactivity between latex and food products. This method enables a more precise understanding of the molecular mechanisms underlying sensitisation [26]. Furthermore, nanomaterial-based diagnostic methods, including Fe3O4@SiO2-NTA, were developed. This approach involves the specific immobilisation of recombinant latex proteins onto magnetic nanoparticles, enabling the rapid and highly precise detection of IgE in serum. The method demonstrates a sensitivity threshold of 0.35 ng/ml and reduces diagnostic time, making it suitable for large-scale screening [61].
New ELISA systems utilise recombinant latex proteins, such as Hev b 6.02, to enhance sensitivity and specificity. Specifically, methods that capture IgE antibodies help reduce the influence of IgG and improve test accuracy in patients with low IgE levels [62]. Epitope profiling enables the identification of both linear and conformational epitopes of latex proteins, such as Hev b 5 or Hev b 6. This approach not only confirms allergenicity but also allows for an assessment of the risk of severe reactions. The use of this method is crucial for predicting the clinical significance of sensitisation.
Microfluidic systems incorporating technologies such as Rolling Circle Amplification facilitate the quantitative detection of specific IgE to latex proteins in ultra-small blood samples. These platforms enable rapid diagnostics with high precision and minimal costs [63]. The identification of protein components, such as Hev b 1-13, allows for a clear distinction between sensitisation and clinically significant allergy. Understanding cross-reactivities (e.g., between Hev b 8 and fruit profilin) helps prevent false-positive diagnoses and enables personalised treatment approaches.
The latex provocation test is considered the “gold standard” in allergy diagnostics due to its ability to confirm the clinical relevance of sensitisation to latex. This method involves the controlled administration of latex (via skin contact, inhalation, or another monitored exposure) followed by symptom monitoring in the patient. It provides definitive evidence of whether sensitisation is associated with clinical symptoms, which cannot be determined using other diagnostic methods, such as skin or laboratory tests.
This test is particularly valuable in cases where results from other methods, such as skin prick tests or specific IgE assays, do not correlate with the clinical presentation. The provocation test enables diagnostic confirmation, especially in complex cases such as latex-fruit syndrome or conflicting test outcomes [64]. By directly assessing the patient’s response to the allergen under controlled conditions, this method ensures the highest diagnostic accuracy by establishing a direct link between allergen exposure and clinical symptoms. This is particularly important in cases of sensitisation, where the mere presence of specific IgE does not necessarily indicate clinical allergy.
The safety of this method is ensured through strict adherence to protocols and careful patient monitoring. The test should only be conducted in specialised clinical settings by trained medical personnel with access to resuscitation equipment, due to the risk of severe reactions, including anaphylaxis. Prior to testing, a thorough medical history should be taken, antihistamines should be discontinued, and the allergen should be administered in minimal doses with gradual increments. These precautions reduce the risk of complications and enhance the reliability of results [65].
The provocation test is particularly appropriate in cases where it is necessary to confirm discrepancies between laboratory test results and clinical presentation and assess tolerance to alternative materials such as latex substitutes. It may also be used to determine cross-reactivities, for instance, between latex and certain foods (e.g., bananas, avocados, kiwis, pineapples, papayas, and others) in patients with latex-fruit syndrome [66]. The provocation test remains an indispensable tool for the accurate diagnosis of latex allergy, offering high precision and assisting clinicians in making optimal treatment decisions.
The availability of diagnostic methods for latex allergy varies between countries due to economic, technological, and political factors. These disparities influence the quality and speed of diagnosis, potentially leading to delayed detection of the condition and an increased risk of complications. In countries such as Germany and the United States, access to advanced diagnostic techniques, including specific IgE testing and molecular allergology (such as component-resolved diagnostics), is considerably broader. This enables early detection of latex allergy, even in complex cases such as latex-fruit syndrome. However, regulatory constraints may limit the use of skin tests due to the lack of commercially available extracts, which remains a challenge even in developed countries [67].
In the United States and Canada, provocation tests continue to be the gold standard for complex cases. Nevertheless, due to the high risk of anaphylaxis, these tests are only conducted in specialised centres equipped with resuscitation facilities. While this approach improves diagnostic accuracy, the high cost of such tests remains a barrier for some patients.
In countries such as Poland, access to diagnostic services varies by region. In major cities, basic methods such as specific IgE testing and skin prick tests are available; however, more advanced approaches, including component-resolved diagnostics, remain less widespread. This situation is largely due to financial constraints and limited dissemination of new technologies. For example, molecular approaches for the precise diagnosis of latex allergy are underutilised in Polish clinics. This limitation frequently results in delayed diagnoses, particularly among healthcare workers, who are at increased risk due to regular exposure to latex. Improvements in this area could be achieved through state-funded support for component-resolved diagnostics, the expansion of screening programmes, and enhanced training for medical professionals.
In African and South Asian countries, access to modern diagnostic methods is restricted, and most cases of latex allergy are diagnosed based on clinical history or basic tests. This leads to a high likelihood of underestimation or misdiagnosis. In resource-limited settings, patients often experience severe complications due to delayed treatment. One of the key challenges in these regions is the cost of diagnostic tests, such as specific IgE assays or provocation tests, which require expensive equipment and highly trained personnel. In addition, a lack of awareness among healthcare providers regarding contemporary diagnostic approaches further exacerbates the issue. The introduction of international initiatives to subsidise diagnostic services could help address these disparities.
Thus, within the European Union, overall access to diagnostic methods – including specific IgE testing, component-resolved diagnostics, and provocation tests – remains high. However, the complex regulatory framework and stringent bureaucratic requirements may hinder the implementation of new diagnostic technologies, affecting the speed of their integration into clinical practice. The introduction of unified EU-wide standards could optimise access to diagnostic tools, streamline logistical processes, and reduce costs for public and private healthcare institutions. Regulatory harmonisation would help lower barriers to innovative solutions, ensuring more equitable access to modern diagnostic methods across all member states.
In Africa, access to diagnostic services is considerably more challenging. The primary issue lies in the limited funding for healthcare, which restricts the acquisition of modern equipment and essential consumables. A substantial proportion of diagnostic kits are imported, rendering them unaffordable for many medical facilities due to their high cost. The development of local production of diagnostic materials could help address this issue by reducing reliance on imports and lowering the overall cost of testing. Moreover, training healthcare professionals and implementing international initiatives to subsidise diagnostic services are crucial steps towards improving access to allergy diagnostics in the region.
In Poland, the implementation of advanced molecular approaches, such as component-resolved diagnostics, remains limited. This is largely due to inadequate funding within the public healthcare system and uneven access to innovative technologies across different regions. To improve this situation, it is essential to integrate modern diagnostic methods into national healthcare programmes, ensure their funding, and make them widely available in public medical institutions. Introducing subsidies for diagnostic testing, along with training programmes for healthcare professionals, would enhance diagnostic accuracy and reduce the number of undiagnosed or misdiagnosed cases of latex allergy. These measures would help alleviate the burden on the healthcare system while improving the quality of life for allergy sufferers.
The availability of latex allergy diagnostic methods is highly dependent on a country’s economic status, regional healthcare policies, and the level of awareness among medical professionals. It is essential to implement subsidy programmes, standardise diagnostic methods, and enhance awareness among the general population and healthcare practitioners to reduce the frequency of delayed diagnoses. In Poland, particular attention should be given to advancing molecular approaches and ensuring state support for component-resolved diagnostics.
Conclusions
The scientific literature analysed in this study demonstrated that latex derived from Hevea brasiliensis is a complex colloidal system, in which structural proteins (such as Hev b 1, 3, 5, 6, and 8) act as key triggers of immune responses. It was established that fresh latex consists of approximately 60% water, 35% polyisoprene, and up to 5% lipids and proteins, including potentially allergenic fractions. Studies examining the theoretical foundations of latex also explored the impact of processing methods and additives (vulcanisation accelerators, stabilisers) on the development or enhancement of its allergenic properties. A notable finding was the confirmation that genetic predisposition and comorbid conditions (such as atopic dermatitis and asthma) can intensify allergic reactions. The role of external factors was also examined: skin humidity and repeated exposure to latex products were found to increase the likelihood of sensitisation, particularly when latex had not undergone the deproteinisation process. Furthermore, studies confirmed the importance of cross-reactivity with fruit proteins (such as those in bananas, avocados, kiwis, pineapples, papayas, and others), further complicating the clinical presentation and necessitating differential diagnosis.
Theoretically grounded approaches contributed to a deeper understanding of the pathogenesis and mechanisms underlying latex-fruit syndrome. A comprehensive analysis of molecular, immunological, and technological aspects enabled the identification of key risks of sensitisation for various population groups, including medical personnel and patients with congenital disorders. Another outcome was the synthesis of modern diagnostic methods, with a prominent focus on skin tests (prick test and patch test), molecular allergology with component-based analyses, and the determination of specific IgE. It was discovered that provocation tests remain the “gold standard” for confirming the clinical significance of allergies, although they require strict adherence to safety protocols due to the high risk of anaphylaxis. Several publications highlighted the limitations in testing accessibility: in developed countries, molecular allergology technologies are more widely implemented, while in resource-limited countries, only basic methods predominate. Moreover, it was established that deproteinisation and saponification of latex could reduce the levels of key Hev b proteins, and consequently, the risks of sensitisation. A noteworthy practical contribution came from the data on the need to standardise testing protocols and guidelines to enhance the accuracy of latex allergy detection and implement global preventive measures. The synthesis of epidemiological studies also confirmed the elevated risk of allergic reactions among surgeons and nurses who regularly use latex gloves.
The results underscored the importance of developing unified diagnostic programmes and providing medical personnel with specialised training on the risks of latex allergy. An important step was also the improvement of latex product labelling standards to prevent accidental use by patients with high sensitivity. Future research should focus on implementing comprehensive screening programmes for at-risk groups and expanding molecular diagnostic methods, which will enhance the accuracy and personalisation of latex allergy prevention and treatment. A limitation of the study was the limited number of randomised clinical trials conducted across different population groups.
