Prevalence and Prevention of Contact Dermatitis Caused by FreeStyle Libre: A Monocentric Experience.

OBJECTIVE: Cutaneous adverse events (CAE) from FreeStyle Libre include allergic contact dermatitis (ACD) caused by the allergen isobornyl acrylate (IBOA). We aim to report CAE from this glucose sensor, ACD to IBOA in particular, and the outcome of using barrier films as a prevention. RESEARCH DESIGN AND METHODS: A monocentric, retrospective review of medical files from adult and pediatric patients with diabetes using Freestyle Libre, in the period between December 2016 and April 2019, was performed with a focus on CAE. RESULTS: Fifty-seven of 1,036 patients with diabetes (5.5%) were referred to our dermatology department because of CAE from FreeStyle Libre. Thirty-nine of 1,036 (3.8%) had ACD due to IBOA. Only two patients, of whom one sensitized to IBOA, had a benefit from using barrier films. CONCLUSIONS: CAE occurred in 5.5% of FreeStyle Libre users, and 3.8% suffered from ACD due to IBOA. Barrier films had limited value in the prevention.

Trends in nail services may cause dermatitis: not your mother's nail polish.

The advent of acrylate-based nail treatments-known as gels, dips, or shellac-has resulted in an uptick in nail-related acrylate allergy. Acrylate dermatitis related to nail services can affect both clients and technicians and can present on the hands, fingers, and wrists, as well as on the face and neck. Nail acrylate allergy occurs from sensitization to acrylate monomers; 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl methacrylate, ethyl cyanoacrylate, and others have been identified as relevant allergens. Patch testing with HEMA and ethyl cyanoacrylate can screen for nail acrylate allergy. Avoidance is key, and we recommend less-permanent, acrylate-free nail polishes as alternatives.

Recommendation to include hydroxyethyl (meth)acrylate in the British baseline patch test series.

BACKGROUND: (Meth)acrylates are potent sensitizers and a common cause of allergic contact dermatitis (ACD). The frequency of (meth)acrylate ACD has increased with soaring demand for acrylic nails. A preliminary audit has suggested a significant rate of positive patch tests to (meth)acrylates using aimed testing in patients providing a clear history of exposure. To date, (meth)acrylates have not been routinely tested in the baseline patch test series in the U.K. and Europe. OBJECTIVES: To determine whether inclusion of 2-hydroxyethyl methacrylate (2-HEMA) 2% in petrolatum (pet.) in the baseline series detects cases of treatable (meth)acrylate ACD. METHODS: During 2016-2017, 15 U.K. dermatology centres included 2-HEMA in the extended baseline patch test series. Patients with a history of (meth)acrylate exposure, or who tested positive to 2-HEMA, were selectively tested with a short series of eight (meth)acrylate allergens. RESULTS: In total 5920 patients were consecutively patch tested with the baseline series, of whom 669 were also tested with the (meth)acrylate series. Overall, 102 of 5920 (1·7%) tested positive to 2-HEMA and 140 (2·4%) to at least one (meth)acrylate. Had 2-HEMA been excluded from the baseline series, (meth)acrylate allergy would have been missed in 36 of 5920 (0·6% of all patients). The top (meth)acrylates eliciting a positive reaction were 2-HEMA (n = 102, 1·7%), 2-hydroxypropyl methacrylate (n = 61, 1·0%) and 2-hydroxyethyl acrylate (n = 57, 1·0%). CONCLUSIONS: We recommend that 2-HEMA 2% pet. be added to the British baseline patch test series. We also suggest a standardized short (meth)acrylate series, which is likely to detect most cases of (meth)acrylate allergy.

Selective Fishing for Peptides with Antibody-Immobilized Acrylate Monoliths, Coupled Online with NanoLC-MS.

An online microfluidics-mass spectrometry platform was developed for determining proteotypic peptides from in-solution digested samples. Accelerated and selective sample cleanup was achieved by integrating proteotypic epitope peptide immunoextraction with nano liquid chromatography-tandem mass spectrometry (online IE-nanoLC-MS/MS). Ten individually prepared 180 µm inner diameter capillaries with ethylene glycol dimethacrylate- co-vinyl azlactone (EDMA- co-VDM) monoliths were immobilized with anti-protein antibodies that are used in routine immunoassays of the intact small cell lung cancer biomarker ProGRP. The resulting AB columns provided linearity correlation coefficients of 0.96-0.99 for protein amounts and concentrations of 10 pg to 5 ng and 0.5-250 ng/mL, respectively. The columns/platform gave relative peak area RSDs below 15%. The IE-nanoLC-MS/MS platform provided a limit of detection (LOD) of 520 pg/mL of ProGRP in human serum. The approach was applicable for other matrixes and proteins, i.e., primary glioblastoma cells and endogenous αV integrin chain. Thus, EDMA- co-VDM monoliths immobilized with antibodies are suited for automated peptide capture in microfluidic formats.

Poly(propylacrylic acid)-peptide nanoplexes as a platform for enhancing the immunogenicity of neoantigen cancer vaccines.

Cancer vaccines targeting patient-specific tumor neoantigens have recently emerged as a promising component of the rapidly expanding immunotherapeutic armamentarium. However, neoantigenic peptides typically elicit weak CD8+ T cell responses, and so there is a need for universally applicable vaccine delivery strategies to enhance the immunogenicity of these peptides. Ideally, such vaccines could also be rapidly fabricated using chemically synthesized peptide antigens customized to an individual patient. Here, we describe a strategy for simple and rapid packaging of peptide antigens into pH-responsive nanoparticles with endosomal escape activity. Electrostatically-stabilized polyplex nanoparticles (nanoplexes) can be assembled instantaneously by mixing decalysine-modified antigenic peptides and poly(propylacrylic acid) (pPAA), a polyanion with pH-dependent, membrane destabilizing activity. These nanoplexes increase and prolong antigen uptake and presentation on MHC-I (major histocompatibility complex class I) molecules expressed by dendritic cells, resulting in enhanced activation of CD8+ T cells. Using an intranasal immunization route, nanoplex vaccines inhibit formation of lung metastases in a murine melanoma model. Additionally, nanoplex vaccines strongly synergize with the adjuvant α-galactosylceramide (α-GalCer) in stimulating robust CD8+ T cell responses, significantly increasing survival time in mice with established melanoma tumors. Collectively, these findings demonstrate that peptide/pPAA nanoplexes offer a facile and versatile platform for enhancing CD8+ T cell responses to peptide antigens, with potential to complement ongoing advancements in the development of neoantigen-targeted cancer vaccines.

Wearable health device dermatitis: a case of acrylate-related contact allergy.

The popularity of mobile wearable health devices has skyrocketed. Some of these devices are worn on the wrist and have been associated with the development of allergic contact dermatitis. Although nickel has been the suspected culprit in cases reported by the media for consumers, we present a rare report of a patient who developed a localized contact dermatitis that was linked to acrylate allergy on epicutaneous patch testing. We surmise that the source of this acrylate might derive from leaching of this compound from the rechargeable battery housing given its correspondence to where the rash arose.

Competitive and noncompetitive phage immunoassays for the determination of benzothiostrobin.

Twenty-three phage-displayed peptides that specifically bind to an anti-benzothiostrobin monoclonal antibody (mAb) in the absence or presence of benzothiostrobin were isolated from a cyclic 8-residue peptide phage library. Competitive and noncompetitive phage enzyme linked immunosorbent assays (ELISAs) for benzothiostrobin were developed by using a clone C3-3 specific to the benzothiostrobin-free mAb and a clone N6-18 specific to the benzothiostrobin immunocomplex, respectively. Under the optimal conditions, the half maximal inhibition concentration (IC50) of the competitive phage ELISA and the concentration of analyte producing 50% saturation of the signal (SC50) of the noncompetitive phage ELISA for benzothiostrobin were 0.94 and 2.27 ng mL(-1), respectively. The noncompetitive phage ELISA showed higher selectivity compared to the competitive. Recoveries of the competitive and the noncompetitive phage ELISAs for benzothiostrobin in cucumber, tomato, pear and rice samples were 67.6-119.6% and 70.4-125.0%, respectively. The amounts of benzothiostrobin in the containing incurred residues samples detected by the two types of phage ELISAs were significantly correlated with that detected by high-performance liquid chromatography (HPLC).

Occupational contact dermatitis to acrylates in a manicurist.

We report the case of a manicurist who developed an allergic skin reaction to acrylates, manifested by bullous lesions on fingertips and eczema of the hands and ears. Patch tests showed positive reactions to 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, ethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate, 1,6-hexandiol diacrylate, 2-hydroxyethyl acrylate and triethyleneglycol diacrylate. Because of her skin disorder, she had to give up her job. She was not correctly advised on retraining and started to work as a dental nurse. Soon after re-exposure to acrylates in dental materials, she experienced recurrence of the skin symptoms.

Cell-penetrating peptide-linked polymers as carriers for mucosal vaccine delivery.

We evaluated the potential of poly(N-vinylacetamide-co-acrylic acid) modified with d-octaarginine, which is a typical cell-penetrating peptide, as a carrier for mucosal vaccine delivery. Mice were nasally inoculated four times every seventh day with PBS containing ovalbumin with or without the d-octaarginine-linked polymer. The polymer enhanced the production of ovalbumin-specific immunoglobulin G (IgG) and secreted immunoglobulin A (IgA) in the serum and the nasal cavity, respectively. Ovalbumin internalized into nasal epithelial cells appeared to stimulate IgA production. Ovalbumin transferred to systemic circulation possibly enhanced IgG production. An equivalent dose of the cholera toxin B subunit (CTB), which was used as a positive control, was superior to the polymer in enhancing antibody production; however, dose escalation of the polymer overcame this disadvantage. A similar immunization profile was also observed when ovalbumin was replaced with influenza virus HA vaccines. The polymer induced a vaccine-specific immune response identical to that induced by CTB, irrespective of the antibody type, when its dose was 10 times that of CTB. Our cell-penetrating peptide-linked polymer is a potential candidate for antigen carriers that induce humoral immunity on the mucosal surface and in systemic circulation when nasally coadministered with antigens.

Acrylates in contact dermatitis.

Acrylates are plastic materials that are formed by the polymerization of monomers derived from acrylic or methacrylic acid. They have found numerous applications in paints, varnishes and adhesives, in the printing industry, in the medical and dental professions, and in artificial nails. Beginning in the 1950s, many reports of occupational and nonoccupational allergic contact dermatitis to (meth)acrylate monomers have been published. These molecules are strong irritants, and patch testing can induce active sensitization. When patch tested, acrylate-allergic patients often display multiple positive tests. These reactions may represent cross-reactions, or concomitant reactions due to the presence, in the products responsible for sensitization, of impurities not disclosed in material safety data sheets. (Meth)acrylates are volatile and unstable chemicals, as demonstrated by their rapid disappearance from commercially available patch test allergens when exposed to air for more than a few hours.

Immuno-compatibility of soft hydrophobic poly (n-butyl acrylate) networks with elastic moduli for regeneration of functional tissues.

The need for engineered devices to treat cardiovascular diseases is increasing due to an aging population and a changing lifestyle. Soft poly(n-butyl acrylate) (cPnBA) networks were recently described as polymer networks with adjustable mechanical properties and suggested as soft substrates for cells, which could potentially be used for cardiovascular implants. Vascular prostheses designed to be implanted in arteries should have an elasticity similar to blood vessels (elastic modulus at body temperature between 100 and 1200 kPa). Therefore, cPnBA networks with E-moduli of 250 kPa (cPnBA0250) and 1100 kPa (cPnBA1100) were developed. Recently, it was shown that both materials were non-cytotoxic for murin fibroblasts, human primary endothelial cells and human monocytes. However, before such newly developed polymers can be used in vivo, it has to be assured that the sterilized materials have a very low endotoxin load to avoid an unspecific activation of the immune system, which otherwise might cause local or systemic inflammatory responses and could lead to severe pathologies. In this study we investigated the immuno-compatibility of sterilized cPnBA0250 and cPnBA1100 with the help of an immuno-competent macrophage cell line as well as with whole human blood.

Exploring alternative hapten tethering sites for high-affinity anti-picoxystrobin antibody generation.

The relevance of the linker tethering site in haptens was investigated for antibody generation and immunoassay development. Three derivatives of the strobilurin fungicide picoxystrobin were synthesized with the same functionalized spacer arm located at three different positions. Protein conjugates of those haptens were employed as immunogens, and novel polyclonal antibodies were produced and characterized. All haptens afforded highly specific antibodies, but different affinities to the free analyte were observed among the obtained antisera. Next, competitive enzyme-linked immunosorbent assays were studied in several formats, and site heterology was confirmed as an effective strategy for detectability improvement. An indirect heterologous immunoassay was eventually selected and optimized, showing a limit of detection for picoxystrobin of 0.02 µg/L and a working range between 0.03 and 1.30 µg/L. Finally, the developed extraction and analytical procedures revealed a practical limit of quantification of 5 µg/kg for this fungicide in soybean sprouts, well below the maximum residue limits in the European Union.

Biocompatibility and pathways of initial complement pathway activation with Phisio- and PMEA-coated cardiopulmonary bypass circuits during open-heart surgery.

A randomized open-heart surgery study comprising 30 patients was undertaken to compare the biocompatibility of Phisio-(phosphorylcholine) and PMEA-(poly-2-methoxyethyl acrylate) coated cardiopulmonary bypass (CPB) circuits and to assess the initial complement pathway activation during open-heart surgery. Blood samples were obtained at five time points, from the start of surgery to 24 hours postoperatively. The following analyses were performed: haemoglobin, lactate dehydrogenase, leukocyte and platelet counts, myeloperoxidase and neutrophil-activating peptide-2, thrombin-anti-thrombin complexes, syndecan-1 and the complement activation products C1rs-C1-inhibitor complexes, C4bc, C3bc, C3bBbP and the terminal complement complex (TCC). No significant inter-group difference was found in any parameters, except for the concentration of TCC which was moderately lower in the PMEA group at termination of CPB. Complement activation during open-heart surgery was mainly mediated through the alternative pathway. In conclusion, PMEA- and Phisio-coated circuits displayed similar biocompatibility with respect to inflammatory and haemostatic responses during and after open-heart surgery.

Screening for acrylate/methacrylate allergy in the baseline series: our experience in Sweden and Singapore.

BACKGROUND: No studies to specifically determine the prevalence of contact allergy to acrylates/methacrylates in patch tested populations have been published. OBJECTIVES: To determine the prevalence of acrylate/methacrylate allergy in all patients tested to the baseline patch test series. METHODS: Five acrylate/methacrylate allergens (2-hydroxyethyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate, triethylene glycol diacrylate, and 2-hydroxypropyl acrylate) were included in the baseline series for at least 2 years in Malmö and Singapore. RESULTS: Thirty-eight patients in total had reacted to acrylate/methacrylate allergens in the baseline series during the study period in both populations. In Malmö, there were 26 (1.4%) patients with positive patch tests to acrylate/methacrylate allergens, 14 of whom had relevant reactions. In Singapore, there were 12 (1.0%) patients with positive patch tests to acrylate/methacrylate allergens, but only 1 had relevant reactions. If we had not added acrylate/methacrylate allergens to the baseline series, we would not have patch tested 13/26 (50%) of the positive reactors in Malmö and 11/12 (92%) of the positive reactors in Singapore. The overall proportion of missed positive reactors would have been 24/38 (63%). CONCLUSIONS: The prevalence of acrylate/methacrylate allergy in our patch tested dermatitis populations is 1.4% in Malmö and 1.0% in Singapore.