2-Hydroxyethyl methacrylate (2-HEMA) sensitization, a global epidemic at its peak in Spain?

BACKGROUND: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. OBJECTIVES: To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. METHODS: From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. RESULTS: Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). CONCLUSION: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means.

Contact allergy caused by acrylates in nail cosmetics: A pilot study from Greece.

BACKGROUND: The growing popularity of nail techniques based on acrylates has led to a higher frequency of sensitization in both nail technicians and users. OBJECTIVES: The study aimed to assess cases of allergic contact dermatitis (ACD) caused by acrylates in individuals with occupational or non-occupational exposure to nail techniques. METHODS: A preliminary study was conducted on 30 patients with ACD caused by acrylates in nail techniques, who were patch tested from September 2022 to March 2023 at the First Department of Dermatology and Venereology of Andreas Syggros Hospital, Athens, Greece. RESULTS: Thirty female patients with ACD to acrylates were documented (15 users and 15 nail technicians and users). The most common allergens were: 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl methacrylate (HPMA) and ethyleneglycol dimethacrylate (EGDMA), which tested positive in all 30 patients (100.0%). Twenty patients (66.7%) had been exposed to dental procedures involving acrylates, before the onset of ACD. Nail technicians exhibited extensive skin lesions, 40.0% experienced ACD within the first year of work and 13.3% during their professional practice. Three of them (20.0%) had to discontinue their work. CONCLUSION: Acrylates have been identified as potent allergens, necessitating the implementation of safety measures for the use of these chemicals in nail techniques.

Contact allergy to acrylate-containing nail cosmetics: A retrospective 8-year study.

BACKGROUND: Over the last 10 years, allergic contact dermatitis (ACD) from acrylate-containing nail cosmetics (acrylic nails, gel nails, gel nail polish) has been reported repeatedly. OBJECTIVES: To investigate the frequency and clinical features of ACD in nail cosmetics in a university hospital in Amsterdam, The Netherlands. PATIENTS AND METHODS: A retrospective study in patients diagnosed with ACD from acrylate-containing nail cosmetics at the Amsterdam University Medical Centers between January 2015 and August 2023. RESULTS: Sixty-seven patients, all women, were diagnosed with ACD from nail cosmetics, representing 1.6% of all individuals and 2.3% of all women patch tested in this period. Sixty-five of sixty-seven (97%) subjects had a positive patch test to 2-hydroxyethyl methacrylate (HEMA). Forty-nine patients (73%) were consumers and 18 (27%) were professional nail stylists. The sites most frequently affected with dermatitis were the fingers (79%), hands (40%) and the head and/or neck. Avoidance of contact with acrylate-containing products resulted in complete clearing of dermatitis in 80% of patients. CONCLUSIONS: ACD from acrylate-containing nail cosmetics is frequent in women patch tested in Amsterdam. Nearly all were identified by a positive patch test to 2-hydroxyethyl methacrylate in the (meth)acrylate series or the European baseline series.

Contact allergies to dental materials in patients.

BACKGROUND: Concerns regarding contact allergies and intolerance reactions to dental materials are widespread among patients. Development of novel dental materials and less frequent amalgam use may alter sensitization profiles in patients with possible contact allergy. OBJECTIVES: To analyse current sensitization patterns to dental materials in patients with suspected contact allergy. METHODS: This retrospective, multicentre analysis from the Information Network of Departments of Dermatology (IVDK) selected participants from 169 834 people tested in 2005-2019 and registered with (i) an affected area of 'mouth' (and 'lips'/'perioral'), (ii) with the dental material in question belonging to one of three groups (dental filling materials, oral implants or dentures or equivalents) and (iii) with patch-testing done in parallel with the German baseline series, (dental) metal series and dental technician series. RESULTS: A total of 2730 of 169 834 tested patients met the inclusion criteria. The patients were predominantly women (81.2%) aged ≥ 40 years (92.8%). The sensitization rates with confirmed allergic contact stomatitis in women (n = 444) were highest for metals (nickel 28.6%, palladium 21.4%, amalgam 10.9%), (meth)acrylates [2-hydroxyethyl methacrylate (HEMA) 4.8%] and the substances propolis (6.8%) and 'balsam of Peru' (11.4%). The most relevant acrylates were HEMA, 2-hydroxypropyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate and pentaerythritol triacrylate. Few men were diagnosed with allergic contact stomatitis (n = 68); sensitization rates in men were highest for propolis (14.9%) and amalgam (13.6%). CONCLUSIONS: Allergic contact stomatitis to dental materials is rare. Patch testing should not only focus on metals such as nickel, palladium, amalgam and gold, but also (meth)acrylates and the natural substances propolis and 'balsam of Peru'.

2-Hydroxyethyl methacrylate (HEMA): A clinical review of contact allergy and allergic contact dermatitis. Part 2. Cross- and co-sensitization, other skin reactions to HEMA, position of HEMA among (meth)acrylates, sensitivity as screening agent, presence of HEMA in commercial products and practical information on patch test procedures.

This is the second part of a literature review of the clinical aspects of contact allergy to and allergic contact dermatitis from 2-hydroxyethyl methacrylate (HEMA). Topics include cross- and co-sensitization, atypical manifestations of contact allergy, frequency of positive patch tests to HEMA compared with other (meth)acrylates, sensitivity of HEMA as a screening agent, the presence of HEMA in commercial products, and practical information on patch testing procedures. Primary sensitization to methacrylates including HEMA may result in methacrylate and acrylate cross-sensitization. There is a strong cross-allergy between HEMA, ethylene glycol dimethacrylate (EGDMA), and hydroxypropyl methacrylate; many reactions to EGDMA are cross-reactions to primary HEMA sensitization. Rare atypical manifestations of HEMA-allergy include lichen planus, lymphomatoid papulosis, systemic contact dermatitis, leukoderma after positive patch tests, and systemic side effects such as nausea, diarrhoea, malaise, and palpitations. The occurrence of respiratory disease caused by methacrylates such as asthma is not infrequent. HEMA is the most frequently patch test-positive methacrylate. It is a good screening agent for allergy to other (meth)acrylates. Patch test sensitization to HEMA 2% pet. is extremely rare. There are (some) indications that HEMA is frequently used in dental products and nail cosmetics.

Presence of 2-hydroxyethyl methacrylate (HEMA) and other (meth)acrylates in nail cosmetics, and compliance with EU legislation: An online market survey.

BACKGROUND: During the last 15-20 years, allergic contact dermatitis from acrylates-containing nail cosmetics (acrylic nails, gel nails, gel nail polish) has been increasingly reported. 2-Hydroxyethyl methacrylate (HEMA) is considered to be the major allergenic culprit; few data on its presence in nail cosmetics are available. OBJECTIVES: To investigate (1) the frequency in which HEMA and di-HEMA trimethylhexyl dicarbamate are present in nail cosmetics; (2) whether nail cosmetics comply with EU regulations; (3) which other (meth)acrylates are present in nail cosmetics and how often. METHODS: One-line market survey. RESULTS: HEMA was present in nearly 60% of 394 cosmetic nail products and di-HEMA trimethylhexyl dicarbamate in 34%. Mandatory warnings on the packages of products containing HEMA were absent in 35% ('For professional use only') resp. 55% ('Can cause an allergic reaction'). Forty-five other (meth)acrylates were identified, of which the most frequent were hydroxypropyl methacrylate (25%), isobornyl methacrylate (16%) and trimethylolpropane triacrylate (12%). Some ingredient lists mentioned non-INCI names or non-specific names. CONCLUSIONS: HEMA was by far the most common ingredient of nail cosmetics, being present in nearly 60% of the products. Violations of EU legislation occurred in >30% (mandatory warnings missing) resp. 10% (mislabelling) of nail cosmetics.

Results of patch testing 2-hydroxyethyl methacrylate (HEMA) in the European baseline series: A 4-year retrospective study.

BACKGROUND: 2-Hydroxyethyl methacrylate (HEMA) was added to the European baseline series (EBS) in 2019. Few recent data are available on the frequency and relevance of positive reactions to this hapten. OBJECTIVES: To investigate the frequency and relevance of positive patch tests to HEMA in the EBS in a university hospital in Amsterdam, The Netherlands. PATIENTS AND METHODS: Retrospective study in patients with positive patch tests to HEMA investigated between June 2019 and August 2023. RESULTS: Of 2927 consecutive patients, 88 (79 women and 9 men; 3.0%) had a positive reaction to HEMA. The prevalence in women was 3.9%, in men 1.0%. Forty-three (49%) reactions were judged to be of current clinical relevance and 21 (24%) of past relevance. In this group of 64 patients with relevant reactions, 18 (28%) had occupational contact with (meth)acrylate-containing products, of who 11 (61%) were nail stylists. In 46 patients with non-occupational allergic contact dermatitis, 31 (67%) had allergic reactions to nail cosmetics. Glues and glue-containing products accounted for 22% of the materials causing allergic contact dermatitis and dental products for 8%. CONCLUSIONS: Allergic reactions to HEMA are very frequent in women investigated in Amsterdam. Nearly two thirds of cases were caused by nail cosmetics.

Increased Rates of Gold and Acrylate Allergy in Individuals with Fibromyalgia Tested with an Extended Dental Patch Test Series.

Fibromyalgia is a common chronic pain condition. Rates of contact allergy in individuals with fibromyalgia have not been widely studied. Systemic contact allergy can present with muscle and joint pain and general malaise. The aim of this study is to investigate contact allergy rates in individuals with fibromyalgia to the sensitizers in an extended dental series and compare with control groups. Contact allergy to gold was significantly more common in the fibromyalgia group than the dermatitis control group. When corrected for patch test system, contact allergy to gold was significantly more common in the fibromyalgia group than the dental control group. Contact allergy to hydroxyethyl methacrylate and grouped acrylates and methacrylates was significantly more common in the fibromyalgia group than the dental control group. In conclusion, individuals with fibromyalgia may have a propensity to sensitization to gold, either via an increased exposure or an alteration in the oral environment. Gold is also implicated in systemic contact dermatitis and may be a factor in elicitation of symptoms in individuals with fibromyalgia. Acrylate allergy is also common in the fibromyalgia population and may be a consequence of occupational exposure or dental treatment.

Prognosis and sequelae of meth(acrylate) sensitization in beauticians and consumers of manicure materials.

BACKGROUND: Allergic contact dermatitis from (meth)acrylic monomers (ACDMA) in manicure products is increasing. OBJECTIVE: To evaluate the prognosis, work performance impairment and sequelae of a cohort of beauticians and manicure consumers with ACDMA sensitized from the exposure to manicure products. METHODS: We conducted a telephone survey with patients diagnosed with ACDMA. RESULTS: One hundred and six patients were evaluated, including 75 (70.8%) beauticians and 31 (29.2%) consumers. All were women with a mean age of 39 (19-62). Thirty-seven of 75 beauticians (49.3%) continued to work. Twenty-seven of 106 (25.5%) patients continued to use manicure products with (meth)acrylates regularly. Seventeen of 51 (33.3%) patients who discontinued the exposure described ongoing nail/periungual changes. Nine of 58 (15.5%) patients who required dental restoration, orthodontic or occlusal splint materials recalled reactions from them; and, 25 of 96 (26%) who used sanitary napkins recalled intolerance to them starting after the diagnosis of ACDMA. Fifteen of 25 (60%) discontinued the use of sanitary napkins. CONCLUSION: 49.3% beauticians continued to work; most patients stopped wearing acrylic manicure materials; reactions from dental materials were not uncommon, however, removal of dental materials was never required; and, reactions to sanitary napkins developing after the diagnosis of ACDMA were common most leading to discontinuation of use.

A case report of allergic reaction with acute facial swelling: a rare complication of dental acrylic resin.

Resin components, such as methyl methacrylate (MMA) can cause allergic contact dermatitis (ACD). Allergic reactions to resin are usually delayed. Only a few studies have reported dental resin allergy with acute symptoms. Here, a case of ACD with acute facial swelling after dental treatment using resin material is reported. A 55-year-old woman with a history of periungual inflammation when using gel nail polish had repeated episodes of facial swelling after dental treatment with resin material. The resin temporary crown was removed, and symptoms were alleviated with antihistamines and corticosteroids. With the suspicion of resin allergy, skin tests were performed. Patch testing revealed positive reactions to self-adhesive resin cement (primer and polymerized), self-curing acrylic resin (liquid and polymerized), 2-hydroxyethyl methacrylate (2-HEMA), and ethylene glycol dimethacrylate (EGDMA), whereas the prick test was negative for all allergens. Complement C4 and C1 inhibitor activity were reference values in the tests for hereditary angioedema. Based on these findings, the patient was diagnosed with ACD to 2-HEMA and EGDMA. Since diagnosis, no similar symptoms have been observed in subsequent dental treatment with non-resin materials. The use of dental resin materials may cause ACD with an acute reaction. This report alerts dentists who routinely use resin materials.

Occupational hand dermatitis secondary to methacrylates-The 'manual tray' sign.

A case report of a dentist presenting with allergic contact dermatitis to methacrylates present in dental bonding agent applied on the dorsum of a gloved hand. The patient presented with a localized dermatitis to the dorsum of the non-dominant hand which can be described as a 'manual tray sign'.

Allergic contact dermatitis caused by 2-hydroxyethyl methacrylate and ethyl cyanoacrylate contained in cosmetic glues among hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications: A systematic review.

Current cosmetic regulations primarily focus on protecting consumers, not the professional user who is subjected to a partly different, and certainly more intense exposure to hazardous substances. Against this background, this systematic review aims to compile and appraise evidence regarding skin toxicity of 2-hydroxyethyl methacrylate (HEMA; CAS no. 212-782-2) and ethyl cyanoacrylate (ECA; CAS no. 7085-85-0) contained in cosmetic glues used among hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications. This systematic review followed the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) 2020 recommendations for reporting systematic reviews and meta-analysis. In total, six publications from six countries were eligible for this systematic review. A meta-analysis revealed that hairdressers and beauticians have a ninefold increased risk of developing contact allergy to HEMA compared with controls who are not hairdressers and beauticians. Results for ECA are lacking. The results of this systematic review clearly show that-regarding contact allergy to acrylates-it is not appropriate to apply risk assessment for consumers to hairdressers and beauticians who occupationally handle cosmetic glues. The regulations in existence do not adequately address occupational risks for hairdressers and beauticians connected with the use of acrylate-containing cosmetic substances and need reconsideration.

The COlorectal NEoplasia Endoscopic Classification to Choose the Treatment classification for identification of large laterally spreading lesions lacking submucosal carcinomas: A prospective study of 663 lesions.

INTRODUCTION: Optical diagnosis is necessary when selecting the resection modality for large superficial colorectal lesions. The COlorectal NEoplasia Endoscopic Classification to Choose the Treatment (CONECCT) encompasses overt (irregular pit or vascular pattern) and covert (macroscopic features) signs of carcinoma in an all-in-one classification using validated criteria. The CONECCT IIC subtype corresponds to adenomas with a high risk of superficial carcinoma that should be resected en bloc with free margins. METHODS: This prospective multicentre study investigated the diagnostic accuracy of the CONECCT classification for predicting submucosal invasion in colorectal lesions >20 mm. Optical diagnosis before en bloc resection by endoscopic submucosal dissection (ESD) was compared with the final histological diagnosis. Diagnostic accuracy for the CONECCT IIC subtype was compared with literature-validated features of concern considered to be risk factors for submucosal invasion (non-granular large spreading tumour [NG LST], macronodule >1 cm, SANO IIIA area, and Paris 0-IIC area). RESULTS: Six hundred 63 lesions removed by ESD were assessed. The en bloc, R0, and curative resection rates were respectively 96%, 85%, and 81%. The CONECCT classification had a sensitivity (Se) of 100%, specificity (Sp) of 26.2%, positive predictive value of 11.6%, and negative predictive value (NPV) of 100% for predicting at least submucosal adenocarcinoma. The sensitivity of CONECCT IIC (100%) to predict submucosal cancer was superior to all other criteria evaluated. COlorectal NEoplasia Endoscopic Classification to Choose the Treatment IIC lesions constituted 11.5% of all submucosal carcinomas. CONCLUSION: The CONECCT classification, which combines covert and overt signs of carcinoma, identifies with very perfect sensitivity (Se 100%, NPV 100%) the 30% of low-risk adenomas in large laterally spreading lesions treatable by piecemeal endoscopic mucosal resection or ESD according to expertise without undertreatment. However, the low specificity of CONECCT leads to a large number of potentially not indicated ESDs for suspected high-risk lesions.

High-resolution melting effectively pre-screens for TP53 mutations before direct sequencing in patients with diffuse glioma.

TP53 mutations are important molecular markers in diffuse astrocytic tumors and medulloblastomas. We examined the efficacy of a pre-screening method for high-resolution melting (HRM) analysis of TP53 mutation before direct sequencing using samples from patients with diffuse glioma. Surgical samples from 64 diffuse gliomas were classified based on the 2016 World Health Organization (WHO) histopathological grading system and the cIMPACT-NOW (consortium to inform molecular and practical approaches to CNS tumor taxonomy-not official WHO) update. TP53 mutations from exon 5 to exon 8 were assessed by direct sequencing. The results of HRM and p53 immunohistochemistry (IHC) analysis were compared by recording the sensitivity, specificity, and false negative and false positive rates. Direct sequencing detected TP53 mutations in 18 of 64 samples (28.1%): diffuse astrocytoma, IDH-mutant (n = 3); diffuse astrocytoma, IDH-wild type (n = 1); anaplastic astrocytoma, IDH-mutant (n = 3); anaplastic astrocytoma, IDH-wild type (n = 4); and glioblastoma, IDH-wild type (n = 7). A total of 22 mutations was detected in the 18 samples; 4 samples exhibited duplicate missense mutations. Sensitivity and specificity were 0.96 and 0.96, respectively, for HRM analysis; they were 0.89 and 0.52, respectively, for p53 IHC. Overall accuracy was 0.98 for HRM and 0.63 for IHC. HRM analysis is a good pre-screening method for the detection of TP53 mutation before direct sequencing.

Dental resin monomers induce early and potent oxidative damage on human odontoblast-like cells.

Resin-based dental materials consist of filler particles and different monomers that are light cured in situ to re-establish dental function and aesthetics. Due to the degree of conversion of adhesive polymers, the monomers triethyleneglycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) are released in relatively high amounts and are susceptible to degradation, acting as bioactive compounds and affecting cell and tissues. This study aimed to assess the effect of HEMA and TEGDMA exposure on metabolic activity, membrane integrity, and cell survival of human odontoblast-like cell (hOLCs). Exposure to resin monomers for 24 h induced major changes in cell membrane integrity, metabolic activity, and survival, which were measured by the calcein method and lactate dehydrogenase release. Increased and early reactive oxygen species (ROS) production was observed leading to degradative oxidation of membrane lipids identified as malondialdehyde production. Severe alteration in mitochondria occurred due to transmembrane mitochondrial potential collapse, possibly inducing activation of apoptotic cell death. hOLCs exposure to resin monomers modified the cell redox potential, with consequences on membrane permeability and integrity, including mitochondrial function. Lipid peroxidation appears to be a key phenomenon for the membrane structures oxidation after HEMA and TEGDMA exposure, leading to cell death and cytotoxicity. hOLCs respond early by differential induction of adaptive mechanisms to maintain cell homeostasis. Modulation of oxidative stress-induced response involves the regulation of genes that encode for antioxidant proteins such as catalase and heme oxygenase-1; regulation that functions as a critical protection mechanism against oxidative cell damage induced by HEMA and TEGDMA. Ascorbic acid as an antioxidant substance mitigates the oxidative damage associated with exposure to monomers.

Allergic Contact Dermatitis due to Methacrylates in a Dental Technician - a Clinical Case.

INTRODUCTION: Methacrylate-based materials are used daily in dental practice. Specialized publications report these materials as allergens with a high sensitizing potential. AIM: To draw the attention of dental doctors and personnel to risk factors of developing occupational allergies. MATERIALS AND METHODS: History and dermatological status of the patient were taken and he was given an epicutaneous test. RESULTS: The allergy testing revealed a strong positive allergic reaction to methacrylates which persisted and was observed at 72 hours as well as on day 7. A diagnosis of allergic contact dermatitis was made on the basis of the patient's history, the clinical examination and the results of the epicutaneous test. CONCLUSION: The presented clinical case shows that early identification of the specific causative agents allows clinicians to take adequate measures and achieve results without having to use a medicine, and stop the progression of the occupational disease and the development of complications.