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Bladder cancer aggressiveness is correlated with abnormal N-cadherin transmembrane glycoprotein expression. This protein is cleaved by the metalloprotease ADAM10 and the γ-secretase complex releasing a pro-angiogenic N-terminal fragment (NTF) and a proliferation-activating soluble C-terminal fragment (CTF2). Tetraspanin 15 (Tspan15) is identified as an ADAM10-interacting protein to induce selective N-cadherin cleavage. We first demonstrated, in invasive T24 bladder cancer cells, that N-cadherin was cleaved by ADAM10 generating NTF in the extracellular environment and leaving a membrane-anchored CTF1 fragment and that Tspan15 is required for ADAM10 to induce the selective N-cadherin cleavage. Targeting N-cadherin function in cancer is relevant to preventing tumor progression and metastases. For antitumor molecules to inhibit N-cadherin function, they should be complete and not cleaved. We first showed that the GW501516, an agonist of the nuclear receptor PPARβ/δ, decreased Tspan15 and prevented N-cadherin cleavage thus decreasing NTF. Interestingly, the drug did not modify ADAM10 expression, which was important because it could limit side effects since ADAM10 cleaves numerous substrates. By targeting Tspan15 to block ADAM10 activity on N-cadherin, GW501516 could prevent NTF pro-tumoral effects and be a promising molecule to treat bladder cancer. More interestingly, it could optimize the effects of the N-cadherin antagonists those such as ADH-1 that target the N-cadherin ectodomain. [ABSTRACT FROM AUTHOR]

In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has become an important tool for adjusting the diagnostic strategy to the perceived risk, whilst still maintaining a high level of safety for the patient. Skin tests are recommended before DPT but may be omitted in low‐risk patients. The task force suggests a strict definition of such low‐risk patients in children and adults. Based on experience and evidence from studies of allergy to beta‐lactam antibiotics, an algorithm on how to adjust DPT to the risk, and when to omit skin tests before DPT, is presented. For other antibiotics, non‐steroidal anti‐inflammatory drugs and other drugs, skin tests are poorly validated and DPT is frequently necessary. We recommend performing DPT with chemotherapeutics and biologicals to avoid unnecessary desensitization procedures and DPT with skin tests negative contrast media. We suggest DPT with anesthetics only in highly specialized centers. Specifics of DPT to proton pump inhibitors, anticonvulsants and corticosteroids are discussed. This position paper provides general recommendations and guidance on optimizing use of DPT, whilst balancing benefits with patient safety and optimizing the use of the limited available resources. [ABSTRACT FROM AUTHOR]

Objective: To analyse the clinical characteristics and sensitivity of an essential oil patch test series (EOS) in patients sensitized to their own essential oils (EOs). Method: We analysed the clinical data and patch test results obtained with the European baseline series (BSE) and an EOS, as well as the mode of use of EOs, through a questionnaire included in the patient file. Results: The study included 42 patients (79% women, average age 50 years) with allergic contact dermatitis (ACD), 8 patients required hospitalization. All patients were sensitized to the EO they used, primarily lavender (Lavandula augustifolia, 8000‐28‐0), tea tree (Melaleuca alternifolia leaf oil, 68647‐73‐4), ravintsara (Cinnamomum camphora oil, 92201‐50‐8), and 2 cases were attributed to helichrysum (helichrysum italicum flower absolute, 90045‐56‐0). 71% had positive patch tests to fragrance mix I or II, 9 only to the EOS and 4 only with their personal EO. Interestingly, 40% of patients did not spontaneously mention the use of EOs, and only 33% received advice on their use at the time of purchase. Conclusion: Patch tests with the BSE, limonene and linalool HP, and oxidized tea tree oil is sufficient to detect most EO‐sensitized patients. The most important is to test the patient's own used EOs. [ABSTRACT FROM AUTHOR]

Background: Anaphylaxis, which is rare, has been reported after COVID‐19 vaccination, but its management is not standardized. Method: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre‐vaccination screening and management of allergic reactions to COVID‐19 vaccines, and literature was analysed. Results: No death due to anaphylaxis to COVID‐19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1—anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2—anaphylaxis to oral/topical PEG containing products; 3—recurrent anaphylaxis of unknown cause; 4—suspected or confirmed allergy to any mRNA vaccine; and 5—confirmed allergy to PEG or derivatives. We recommend a prick‐to‐prick skin test with the left‐over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. Conclusions: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID‐19 vaccines and enable more people with history of allergy to be vaccinated. [ABSTRACT FROM AUTHOR]

Skin tests, including patch tests (PTs), prick tests, and intradermal tests (IDTs), are useful in identifying the culprits of cutaneous adverse drug reactions (CADRs), and determining safer, alternative drugs. PTs have a low sensitivity but are valuable in investigating maculopapular exanthema (MPE), as well as severe CADR, including toxic epidermal necrolysis (TEN), Stevens‐Johnson syndrome (SJS), and in particular, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). To ensure their specificity, at least 10 control tests should be performed. Prick tests are mainly used in the evaluation of immediate‐type hypersensitivity and can be performed with all drugs, except opiates. IDTs can be used to explore immediate and delayed‐type hypersensitivity, if an injectable form of the drug exists. Except for SJS/TEN, IDTs should be performed by injecting 0.02 mL of the drug. We here provide a practical, up‐to‐date review on the use of these skin tests in the work‐up of CADRs. Numerous negative controls for drug PTs, as well as criteria for the immediate and delayed positivity of prick tests and IDT, are included. It should be emphasized that a negative result never excludes the potential responsibility of a drug in a CADR. [ABSTRACT FROM AUTHOR]

ABSTRACT A number of works have been focused on the study of polymers microtacticity and the probability of iso-, syndio-, and atactic arrangement of monomers such as polypropylene and poly(methacrylic esters) before the 1980s. This type of study was fewer in the last four decades despite the importance of stereochemical knowledge of macromolecules in the biomedical field. NMR analysis was the invaluable tool for the study of stereochemistry. This work detailed the synthesis and the physicochemical and microtacticity characterizations of new semicrystalline and amorphous polyesters, poly(3-allyl-3-methylmalic acid) (PAlMMLA) derivatives which are part of the poly(malic acid) family. This polymer is biodegradable and biocompatible. It can also be chemically modified for a possible combination with bioactive molecules. It can be synthesized from chiral product leading a stereoregular and semicrystalline structure. In the case of a racemic starting product, the obtained macromolecular structure is amorphous. Semi-crystalline polyester presented a highly diisotactic structure. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2408-2418 [ABSTRACT FROM AUTHOR]

In order to reduce restenosis, the necessity to develop the appropriate coating material of metallic stent is a challenge for biomedicine and scientific research over the past decade. Therefore, biodegradable copolymers of poly(( R , S )-3,3 dimethylmalic acid) (PDMMLA) were prepared in order to develop a new coating exhibiting different custom groups in its side chain and being able to carry a drug. This material will be in direct contact with cells and blood. It consists of carboxylic acid and hexylic groups used for hydrophilic and hydrophobic character, respectively. The study of this material wettability and dynamic surface properties is of importance due to the influence of the chemistry and the potential motility of these chemical groups on cell adhesion and polymer kinetic hydrolysis. Cassie theory was used for the theoretical correction of contact angles of these chemical heterogeneous surfaces coatings. Dynamic Surface Analysis was used as practical homogenizer of chemical heterogeneous surfaces by cycling during many cycles in water. In this work, we confirmed that, unlike receding contact angle, advancing contact angle is influenced by the difference of only 10% of acidic groups (%A) in side-chain of polymers. It linearly decreases with increasing acidity percentage. Hysteresis ( H ) is also a sensitive parameter which is discussed in this paper. Finally, we conclude that cycling provides real information, thus avoiding theoretical Cassie correction. H 10 is the most sensible parameter to %A. [ABSTRACT FROM AUTHOR]

Background Few studies have been published on the histopathology of cutaneous adverse drug reactions ( CADR), and most of these lack information on skin allergological tests. The histopathology of drug reaction with eosinophilia and systemic symptoms ( DRESS) is also seldom described. The purpose of our study was to examine six types of well-documented CADR (maculopapular exanthema, DRESS, fixed drug eruption, Stevens-Johnson syndrome, toxic epidermal necrolysis [ TEN], and acute generalized exanthematous pustulosis) using histopathology and immunohistochemistry to evaluate the expression of granulysin, a key molecule in TEN. Methods We retrospectively included 106 skin biopsies performed in proven cases of CADR (by chronological investigation, single attributable drug, or/and skin tests). All slides were reviewed, and microscopic changes were analyzed using a standardized form. Granulysin expression was studied by immunohistochemistry. Results In DRESS, we observed spongiosis, edema, and basal vacuolization, with rare necrotic keratinocytes and constant lymphocytic infiltrate in the superficial dermis. Eosinophils were often present, and pustules were found in 15% of cases. Necrotic keratinocytes are often absent in maculopapular exanthema. Granulysin was expressed in six types of CADR with a trend toward more intense expression in DRESS and TEN. Conclusion We detailed further about the histopathology of DRESS. Granulysin expression was observed in all CADR with a marked overlap of expression pattern between the six types. [ABSTRACT FROM AUTHOR]

ABSTRACT Various optically active (4 R)-alkyloxycarbonyl-3,3-dialkyl-2-oxetanones as monomers were synthesized from L-( S)-malic acid in six steps to prepare a new family of stereopolyesters for biomedical applications. The synthesis began with an esterification followed of a dialkylation in the aim to introduce hydrophobic groups as methyl or reactive group as allyl. Then, a saponification has permitted to obtain the corresponding diacids that reacted with appropriate alcohols to furnish different monoesters. The last and most important step was activation of hydroxyl group of monoesters with the asymmetric carbon configuration inversion according to the Mitsunobu reaction. Thus, this reaction has provided lactones from monoesters with 100% enantiomeric excess which was confirmed by 1H NMR and by the synthesis of corresponding isotactic and semicrystalline homopolyesters. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2586-2597 [ABSTRACT FROM AUTHOR]

The article presents a case study of a 28-year-old woman who had history of pruritic erythematous scaly dermatitis on both hands and on the neck, after keeping a rabbit as pet. She fed her rabbit with chicory leaves, dandelion, hay, and dry food, and the dermatitis disappeared when the patient stopped feeding her rabbit with chicory.

Keywords: allergic contact dermatitis; CAS no. 78336-31-9; case report; copolymers; cosmetic products; PEG-22/dodecyl glycol copolymer; PEG-45/dodecyl glycol copolymer EN allergic contact dermatitis CAS no. 78336-31-9 case report copolymers cosmetic products PEG-22/dodecyl glycol copolymer PEG-45/dodecyl glycol copolymer 213 215 3 08/04/23 20230901 NES 230901 We report a case of allergic contact dermatitis (ACD) caused by PEG-22/dodecyl glycol copolymer and PEG-45/dodecyl glycol copolymer contained in two different "skin-repairing" creams. Allergic contact dermatitis, CAS no. 78336-31-9, case report, copolymers, cosmetic products, PEG-22/dodecyl glycol copolymer, PEG-45/dodecyl glycol copolymer Allergic contact dermatitis caused by PEG-22 and PEG-45 dodecyl glycol copolymers in two skin-repairing creams. [Extracted from the article]

The article discusses research which was conducted to measure the three dimensional similarity between carbamazepine and 40 psychotropic drugs with similar or adjacent indications. After evaluating the drugs the researchers concluded that their research results were not sufficient for clinical decision making in patients sensitized to carbamazepine and that the results should be considered as one line of evidence among others for benefit-risk assessment.

Background Polymorphisms of genes controlling cytokine production have not been studied in the genetic susceptibility to cutaneous adverse drug reactions ( CADR). Objectives The objective was to determine whether polymorphisms in nine cytokine genes were associated to the occurrence of drug reaction with eosinophilia and systemic symptoms ( DRESS) compared to drug-induced maculopapular eruption or urticaria and to controls without drug intolerance. Methods Results from 118 patients with a well-defined CADR were compared to 236 controls without drug intolerance living in the same area of France. We assessed nine polymorphisms: interleukin ( IL)1-alpha-889C>T (rs 1800587), IL1-beta-511C>T (rs 16944), IL1- RN intron-2- VNTR (rs2234663), IL2-330T>G (rs 2069762), IL4-33C>T (rs 2070874), IL5-745C>T (rs 2069812), IL10-592C>A (rs 1800872), IL16-295T>C (rs 4778889) and tumour necrosis factor-alpha-308G>A (rs 1800629). Results Three polymorphisms exhibited a significant association with CADR ( P < 0.05). The combination of the IL1- RN-A2 and IL1-beta-511C alleles was statistically different between cases and controls ( P = 0.007) and the A2C haplotype was associated with susceptibility to CADR, particularly in drug reaction with eosinophilia and systemic symptoms ( DRESS) patients (odds ratio = 3.22; 95% confidence interval = 1.23-8.41; P = 0.016). The frequency of the IL10-592A allele was higher in DRESS patients than in controls (dominant model CC vs. CA + AA: P = 0.035). These abnormalities were not evident in maculopapular eruptions or urticaria. Conclusions This is the first study showing that IL1-cluster polymorphisms and haplotypes and the IL10-592A allele (a low IL10 producer) are associated with DRESS. These gene variants may decrease drug tolerance and promote herpes virus reactivation. [ABSTRACT FROM AUTHOR]

The mixing of confined liquids is a central yet challenging operation in miniaturized devices. Microfluidic mixing is usually achieved with passive mixers that are robust but poorly flexible, or active mixers that offer dynamic control but mainly rely on electrical or mechanical transducers, which increase the fragility, cost, and complexity of the device. Here, we describe the first remote and reversible control of microfluidic mixing triggered by a light illumination simply provided by an external LED illumination device. The approach is based on the light-induced generation of water microdroplets acting as reversible stirrers of two continuous oil phase flows containing samples to be mixed. We demonstrate many cycles of reversible photoinduced transitions between a nonmixing behavior and full homogenization of the two oil phases. The method is cheap, portable, and adaptable to many device configurations, thus constituting an essential brick for the generation of future all-optofluidic chip. [ABSTRACT FROM AUTHOR]

The article presents a case study of several cases involving patients who experienced adverse drug reactions due to delayed sensitization to carboxymethylcellulose. Among the cases discussed include a 24-year-old man who had a drug reaction caused by Tegretol® and a 48-year-old man with rheumatism who developed rash after taking pills with piroxicam and carboxymethylcellulose. It discusses the contribution of carbomethylcellulose to these reactions and hypersensitivity among the patients.

Delayed reactions to iodine contrast media (CM) account for 1-3% of patients with adverse reactions to iodine CM. The cellular and molecular mechanisms of these reactions remain poorly documented. Although most of these reactions are T cell mediated, the involvement of dendritic cells (DC) has not been investigated sufficiently. To determine whether the T cell response to iodixanol requires DC as antigen-presenting cell and, more particularly, to evaluate the changes induced by iodixanol on DC maturation and in vitro production of cytokines after drug stimulation in patients with maculopapular exanthema. Peripheral blood lymphocytes, immature monocyte-derived DC (imDC) and skin biopsies were obtained from patients with delayed reactions to iodixanol and tolerant subjects. We studied the consequences of the interaction between DC, lymphocytes and iodixanol by phenotype analysis, proliferation and cytokine production. A T-cell-mediated reaction was evidenced in patient biopsies, with a lymphocyte-rich, peri-vascular infiltrate. Iodixanol induced maturation of imDC from patients but not from controls, with expression of the co-stimulatory markers CD83, CD86 and CD40 and an increase in mean fluorescence intensity of CD80, CD86 and HLA-DR. In the absence of DC, positive cell proliferation to iodixanol was detected in only one patient while the addition of DC produced a positive test in five of the six patients. Similarly, the increase in cytokines (IFN-γ, IL-2, IL-6, IL-1b and TNF-α) was higher when imDC were introduced into the culture together with the culprit drug. These results provide evidence for a DC-mediated mechanism in delayed allergic reactions to CM, influencing T cell proliferation and cytokine production. These new insights will be helpful for designing immunotherapeutic strategies and in vitro diagnostic tests of CM-delayed reactions. Cite this as: C. Antunez, A. Barbaud, E. Gomez, S. Audonnet, S. Lopez, R.-M. Guéant-Rodriguez, I. Aimone- Gastin, F. Gomez, M. Blanca and J.-L. Guéant, Clinical & Experimental Allergy, 2011 (41) 657-664. [ABSTRACT FROM AUTHOR]

The article presents a study which examines whether there are any cross-reactivity between tetrazepam and other benzodiazepines in patients with a cutaneous adverse drug reaction. In this study, researchers conducted skin tests and oral provocation tests with other benzodiazepines. From the nine patients with confirmed sensitization to tetrazepam on patch testing, researchers found that there were no cross-reactions on patch testing or intradermal testing with other benzodiazepines.

Background: There is a lack of prospective studies investigating contact sensitization in patients with chronic leg ulcers. Objectives: To determine the frequency of contact sensitization in patients with chronic leg ulcers using a special series of patch tests and to determine whether the number of sensitizations was correlated with the duration of the chronic leg ulcers. Patients/methods: Multicentre study carried out in patients with chronic leg ulcers; patch tests with the European baseline series and with an additional 34 individual allergens or mixes and 3 commercial products. Results: Of the 423 patients (301 women, 122 men, mean age 68.5 years) with chronic leg ulcers, 308 (73%) had at least one positive patch test with 3.65 positive patch tests per patient. The main allergens were Myroxylon pereirae (41%), fragrance mix I (26.5%), antiseptics (20%), and corticosteroids (8%). The number of positive tests per patient was not correlated with the cause of ulcer but was increased with the duration of the ulcer with a statistical difference between the group of the <1 year compared with the group >10 years duration. Conclusions: From this large prospective multicentre study, polysensitization is frequent in patients with chronic leg ulcers, increasing with the duration of the ulcer. We propose avoidance of topical antiseptics and ointments containing perfumes in patients with chronic leg ulcers and an updated patch test series for investigating these patients. [ABSTRACT FROM AUTHOR]

Abstract: The rectal route is indicated to treat patients with rapidly evolving malaria who cannot take oral medication to prevent progression to severe forms of the disease. Improvement can be made in terms of rectal bioavailability and stability of current formulations. We studied a new two-compartment, muco-adhesive gel formulation of artesunate which is adapted for use in children and storage in tropical climates. The formulation contains 50mg of artesunate per gram of gel. Because of its instability in aqueous solutions, artesunate is in the dry component of the gel with Carbopol® and separate from the liquid phase until reconstitution. Artesunate is stable in the dry blend for 6 months at 45°C and 60% RH. The gel should be used between 1 and 72h after being reconstituted. Artesunate release was measured by with a rapid, simple and reliable HPLC-UV which allowed the analysis of artesunate and dihydroartemisinin with an analysis time at 3min. The amount of artesunate released over 6h was 56±0.97%. Compared to the reference suspension, total release and dissolution efficiency were lower and rate of release was slower (time to 50% dissolution 271±21min), probably because of the higher viscosity of the gel, but the drug release profiles were similar. The calculated in vitro release exponent (n) value suggested that artesunate is released from the gel by non-Fickian transport. [Copyright &y& Elsevier]

Abstract: The management of patients who have developed a contact dermatitis due to topical drugs requires to stop the suspected drug application, to declare, if severe, the adverse drug reaction to a center for drug safety, to treat the patient with corticosteroid ointments, to perform dermatoallergological investigations e.g. drug patch tests in case of contact eczema and diluted prick tests in case of contact urticaria in order to determine whether the adverse drug reaction was due to excipients or to the drug itself. It is also absolutely necessary to advise the patient concerning the avoidance of topical but also systemic readministration of the responsible molecule. An excipient responsible in inducing a contact sensitization to a topical drug can also be found in cosmetics, the name of the responsible excipient has to be given to the patient under the common name but also under the INCI and/or CFTA name. When the drug itself is responsible in inducing a contact allergy it is necessary to determine if cross reactions with other drugs can occur and if the responsible molecule can induce systemic cutaneous adverse drug reactions if the drug is systemically readministred. Among NSAID there is no cross reactions between bufexamac and diclofenac, between salicylamide, glycol salicylate, salicylic acid and acetylsalicylic acid. In case of photosensitization 1) to ketoprofen or 2) piroxicam the topical and/or systemic administration of the following molecules are contraindicated with respectively 1) ketoprofen, tiaprofenic acid, fenofibrate, oxybenzone or 2) piroxicam, thimerosal. A patient sensitized to corticosteroid ointment has to be tested in order to determine which corticosteroid classes are sensitizing. The topical and systemic administrations of molecules belonging to the sensitizing classes (A, B, C, D1 or D2) have to be forbidden. In general, a contact dermatitis due to an antimicrobial drug induces a contraindication in further topical or systemic uses of the drug and to all the molecules belonging to the same class. In most of the cases there is no risk in systemically administering iodine, sulfites or excipients in a sensitized patient who had developed a contact dermatitis to topical medications. [Copyright &y& Elsevier]

Abstract: Patch testing with the suspected compound has been reported to be helpful in determining the cause of a cutaneous adverse drug reaction (CADR) and in studying the pathophysiological mechanisms involved. The main advantages of drug patch tests are that they can be done with no hospital surveillance because they induce only rarely adverse reactions and that any commercialized form of a drug can be used. In contrast, intradermal tests can be performed only with injectable forms or with a pure and sterile form of the drug. It is advised to perform drug patch tests during the 6 months following the CADR as we do not know whether positive results will persist. Due to the possibility that a low concentration might yield false negative results, drug patch tests have to be performed with rather high concentrations of the commercialized form of the drug, mostly diluted at 30% in petrolatum and/or in water. For some drugs and severe CADR, it is necessary to tests with lower concentrations or in other vehicles. Drug patch tests are positive in ca. 32–50% of patients who have developed a CADR. The clinical relevance of drug patch tests depends on the clinical features of the CADR (valuable in testing generalized eczema, systemic contact dermatitis, maculopapular rash, acute generalized exanthematous pustulosis, fixed drug eruption) and on the involved drug. As false positive results can be observed, it is always necessary to consider the relevance of any positive drug patch test. Their specificity and their negative predictive value have not been yet determined. [Copyright &y& Elsevier]

Abstract: Occupational dermatitis (irritant dermatitis, contact urticaria and contact eczema) is frequent among healthcare workers. Irritant hand dermatitis, the most common occupational dermatitis, occurs often in individual who work in a humid environment, who handle disinfectants, and who are required to wash their hands frequently; atopic dermatitis is a risk factor for this condition. Natural rubber latex present in rubber gloves is the most common cause of contact urticaria. Contact eczema can be induced by rubber accelerators (for example, thiurams) present in gloves, and also by disinfectants (glutaraldehyde, dodecyldimethylammonium), disinfectants and detergents, hand creams, acrylates (in dentists), and echography gels. Nurses sometimes develop contact dermatitis to drugs they handle; these allergies should be diagnosed by appropriate skin testing because sensitized individuals may develop a severe, generalized cutaneous adverse reaction if they are subsequently exposed systemically to the sensitizing drug. [Copyright &y& Elsevier]

The present study was made to determine the value of drug skin tests in patients with cutaneous adverse drug reactions (CADRs) due to a synergistin (pristinamycin) and to determine the frequency of cross-reactions between synergistins. 29 patients were referred during the onset of the CADR due to pristinamycin: 18 with maculopapular rash, 9 erythrodermas, 1 angioedema and 1 Stevens–Johnson syndrome. They all had patch tests with pristinamycin and, in most cases, with other synergistins [virginiamycin and dalfopristin–quinupristin (DQ)], prick tests (10 cases) and intradermal tests (IDT) (5 cases). Skin tests with synergistins were positive in 27 cases, patch tests with pristinamycin in 20/29 cases (69%), prick tests with pristinamycin in 3/9 cases on immediate (1 case) or on delayed (2 cases) readings, and IDT with DQ in 4/5 cases. Cross-reactions between synergistins occurred in 9/22 with virginiamycin and in 7/8 cases with DQ. Skin tests with synergistins are useful in investigating CADR due to pristinamycin. Synergistins are composed of 2 chains (1 depsipeptide and 1 macrocyclic lactone) with many structural analogies between all synergistins. According to the chemical structures and our results, it seems advisable to avoid all synergistins in patients with CADR due to pristinamycin. [ABSTRACT FROM AUTHOR]

Novel α, α′, β-trisubstituted β-lactones have been prepared by a concise and efficient synthesis in five steps from commercial racemic diethyl oxalpropionate. These lactones with different lateral groups can be polymerized or co-polymerized for obtaining polyesters with high molecular weight. Chemical modification of these functionalized hydrolyzable polymers will be used to adjust their properties to the selected temporary applications. [ABSTRACT FROM AUTHOR]

Recent studies have emphasized the value of drug patch tests, in addition to, prick and intradermal tests to determine the molecule responsible for cutaneous adverse drug reactions (CADR), also known as drug eruptions. The value of drug patch tests depends on the clinical features of the CADR, and they are valuable in the investigation of drug reactions, such as generalized eczema, systemic contact dermatitis, maculopapular rashes, toxic epidermal necrolysis, and fixed drug eruptions. Their sensitivity also depends on the particular drug involved. Guidelines for performing prick, ID and patch tests, published in 2001, are analyzed in the present article. We also report on the information published more recently on how to perform the tests, how to interpret them, new drugs reported to yield positive reactions and, finally, how to define the relevance and the specificity of drug patch tests in the workup of cutaneous drug allergies. [Copyright &y& Elsevier]

Skin testing with a suspected drug has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADR). Many isolated reports of positive drug skin tests are published, but without detailed information concerning the clinical features of the CADR and the method used in performing drug skin tests, such data are not very informative. A working party of the European Society of Contact Dermatitis (ESCD) for the study of skin testing in investigating cutaneous adverse drug reactions, has proposed the herein-reported guidelines for performing skin testing in CADR in order to standardize these procedures. In each reported case, the imputability of each drug taken at the onset of the CADR and a highly detailed description and characterization of the dermatitis need to be given. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed according to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested diluted at 30% pet. (pet.) and/or water (aq.). The pure drug is tested diluted at 10% in pet. or aq. In severe CADR, drug patch tests are performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR. Drug prick tests are performed on the volar forearm skin with the commercialized form of the drug, but with sequential dilutions in cases of urticaria. Intradermal tests (IDT) are performed with sterile sequential dilutions (10–4, 10–3, 10–2, 10–1) of a pure sterile or an injectable form of the suspected drug with a small volume of 0.04 ml. Drug skin tests need to be read at 20 min and also later at D2 and D4 for patch tests, at D1 for prick tests and IDT. All these tests also need to be read at 1 week. The success of skin tests varies with the drug tested, with a high % of positive results, for example, with betalactam antibiotics,... [ABSTRACT FROM AUTHOR]

Skin tests with drugs can be of value in investigating patients who have developed cutaneous adverse drug reactions (CADR), but their specificity and relevance remain to be determined. A false-positive result on skin testing can happen if it is not compared to results in control subjects. When performing intradermal tests (IDT), we have determined the lowest concentrations that induce false-positive results for many drugs, including betalactam antibiotics, cephalosporins, other antibiotics or non-steroidal anti-inflammatory drugs. Some drugs in their commercialized form contain sodium lauryl sulfate and can induce irritation when patch tested as such. When patch tested with colchicine at 10% in pet. or with a Cytotec® pill (containing misoprostol) at 30% in pet., respectively, 80% of the 29 and 9 of the 10 negative controls developed false-positive results. Lastly, positive results of patch tests with drugs can be related to contact allergy to one of the components of the commercialized form of the drug, without any relevance to the investigation of a CADR, as observed in 2 cases with iodine or avocado oil. [ABSTRACT FROM AUTHOR]

Provides information on a study which examined the role of the phenothiazine component of the Neuriplege ointment in contact dermatitis. Information on patients; Results of the patch tests and photopatch tests with chlorproethazine.

Reports on the medical case of a 46-year-old woman with a maculopapular rash while taking Panos which contained tetrazepam. Patch test results; Usefulness of patch testing on the previously most severely affected site in a cutaneous adverse drug reaction to tetrazepam.

Background: An aqueous antiseptic containing "chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol" (CBB) is widely used in France. The only previous documented study dealing with allergic contact dermatitis (ACD) to this antiseptic is one small case series in children. The French Vigilance Network for Dermatology and Allergy (REVIDAL‐GERDA) has collected many cases in the last few years. Objectives: To evaluate the clinical and sensitization profiles of patients diagnosed with ACD to CBB. Methods: We performed a retrospective study of patients with contact dermatitis to CBB and positive tests to CBB and/or at least one of its components. All patients had to be tested with all components of CBB. Results: A total of 102 patients (71 adults and 31 children) were included. The lesions were extensive in 63% of patients and 55% had delayed time to diagnosis. CBB patch tests were positive in 93.8% of cases. The allergen was identified in 97% of patients, mainly benzyl alcohol in adults (81.7%) and chlorhexidine digluconate in children (54.8%). About 32.4% of the patients were sensitized to several components. Conclusion: CBB is a cause of ACD at all ages. The components of the antiseptic should be tested. The sensitization profile seems to be different between adults and children. [ABSTRACT FROM AUTHOR]

In order to confirm the mechanism of skin sensitization to propacetamol, a pro-drug of acetaminophen, 3 patients with allergic contact dermatitis from propacetamol were patch tested with N,Ndiethylglycine phenyl ester, an activated form of N,N-diethylglycine. Positive patch tests were observed in all the patients at 10% in pet., while 20 control patients remained negative. This strongly suggests that propacetamol is acting as an activated form of N,N-diethylglycine, transferring this part of the molecule to nucleophilic residues of proteins. This also explains why reactions to acetaminophen have never been observed in patients sensitized to propacetamol. [ABSTRACT FROM AUTHOR]

The occurrence of a new AEs with neurological involvement during the reintroduction of an anti-CD25, in a patient who previously would have had a DRESS, has nothing to do with our study involving DRESS induced by xenobiotics. Finally, any side-effects occurring during slow drug re-introductions in our patients were scrupulously recorded and described, and no patient had neurological involvement. The discussion of a relapse of a DRESS due to an anti-CD25 with neurological involvement without liver or renal involvement is purely hypothetical and has no relation to our study. [Extracted from the article]

Allergic contact dermatitis caused by acyclovir is rare. We report the 5th case of systemic acyclovir reaction subsequent to acyclovir contact dermatitis, with investigations made to determine an alternative antiviral treatment. A 23-year-old woman, after dermatitis while using Zovirax® cream, went on to develop urticaria after oral acyclovir. Patch tests were performed with the components of Zovirax® cream (acyclovir, propylene glycol and sodium lauryl sulfate) and with other antiviral drugs. Patch tests were positive to Zovirax® cream, acyclovir, valacyclovir and propylene glycol. Patch and prick tests with famciclovir were negative, but its oral administration caused an itchy erythematous dermatitis on the trunk and extremities. Our patient developed a systemic acyclovir reaction subsequent to acyclovir allergic contact dermatitis, with cross-reactions to valacyclovir and famciclovir. Their common chemical structure is the 2-aminopurine nucleus. It is probably this part of the molecule that provokes both contact allergy and systemic reactions. The only antiviral drugs not having this core are foscarnet and cidofovir, and these could therefore be alternatives. [ABSTRACT FROM AUTHOR]

A concise and efficient synthesis of α,α′,β-trisubstituted β-lactones is presented. These novel lactones are easily obtained in five steps and will be dedicated to anionic ring opening polymerization. [Copyright &y& Elsevier]

Provides information on a medical case on improvement in essential tremor after pure sensory stroke due to thalamic infarction. Findings of neurological examination and computed tomography scan; Overview of the distal sensory syndrome of the fingers; Health implications of somatosensory feedback loops.

Reports on the case of a ten-year-old girl in whom Stevens-Johnson syndrome was associated with a pustular eruption due to Mycoplasma pneumoniae infection. Clinical manifestations; Results of diagnostic procedures; Etiopathogenesis of the condition.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well‐known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%–3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence‐based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in‐depth investigations in the topic. [ABSTRACT FROM AUTHOR]

Diagnosing immediate drug hypersensitivity reactions (IDHRs) can pose a significant challenge and there is an urgent need for safe and reliable tests. Evidence has emerged that the basophil activation test (BAT), an in vitro assay that mirrors the in vivo response, can be a complementary test for many drugs. In this position paper, members of Task Force (TF) "Basophil activation test in the evaluation of Drug Hypersensitivity Reactions" from the European Academy of Allergy and Clinical Immunology (EAACI) present the data from a survey about the use and utility of BAT in IDHRs in Europe. The survey results indicate that there is a great interest for using BAT especially for diagnosing IDHRs. However, there are still main needs, mainly in the standardization of the protocols. Subsequently consensus‐based recommendations were formulated for: (i) Technical aspects of BAT in IDHRs including type of sample, management of drugs, flow cytometry protocols, interpretation of the results; and (ii) Drug‐specific aspects that should be taken into account when performing BAT in relation to betalactams, neuromuscular blocking agents, fluoroquinolones, chlorhexidine, opioids, radio contrast media, chemotherapeutics, biological agents, nonsteroidal anti‐inflammatory drugs, COVID vaccine, and excipients. Moreover, aspects in the evaluation of pediatric population have also been considered. All this indicates that BAT offers the clinician and laboratory a complementary tool for a safe diagnostic for IDHRs, although its place in the diagnostic algorithm depends on the drug class and patient population (phenotype, geography, and age). The standardization of BAT is important for generalizing this method beyond the individual laboratory. [ABSTRACT FROM AUTHOR]

Background: Differential diagnosis between cutaneous lupus erythematosus (CLE) and dermatomyositis (DM) may be challenging if digital lesions occur. Objectives: To compare nailfold capillaroscopy (NFC) findings in CLE patients with or without digital involvement, and to compare capillaroscopic findings between CLE patients with digital lesions and DM patients. Methods: Prospective monocentric study including CLE and DM patients. NFC was performed and standardized items were recorded. Results: Fifty-one CLE patients and 10 DM patients with digital lesions were included. A scleroderma pattern was found in 6 patients (12%): in 5 out of 17 patients with digital lesions, compared with only 1 out of 34 patients without digital lesions (p = 0.01). In multivariate analysis, CLE digital lesions and digital ulcerations were statistically associated with scleroderma pattern. CLE digital lesions were significantly associated with architectural disorganization (p = 0.0003) and capillary rarefaction (p = 0.0038). A scleroderma pattern was significantly more frequent in DM patients (80%) than in CLE patients with digital lesions (30%, p = 0.018). Capillaroscopic findings were not significantly different between CLE patients with digital lesions and DM patients. Conclusion: Although scleroderma pattern is more frequent in DM patients than in CLE patients with digital lesions, NFC cannot formally distinguish CLE from DM. [ABSTRACT FROM AUTHOR]

A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta‐lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost‐effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross‐reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, and diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (ie, occurring within 1‐6 hours after the last administered dose) or nonimmediate (ie, occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low‐risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus. [ABSTRACT FROM AUTHOR]

Here we report a solution-processing strategy to stabilize the perovskite-based heterostructure. Strong Pb–Cl and Pb–O bonds formed between a [CH(NH2)2]x[CH3NH3]1−xPb1+yI3 film with a Pb-rich surface and a chlorinated graphene oxide layer. The constructed heterostructure can selectively extract photogenerated charge carriers and impede the loss of decomposed components from soft perovskites, thereby reducing damage to the organic charge-transporting semiconductors. Perovskite solar cells with an aperture area of 1.02 square centimeters maintained 90% of their initial efficiency of 21% after operation at the maximum power point under AM1.5G solar light (100 milliwatts per square centimeter) at 60°C for 1000 hours. The stabilized output efficiency of the aged device was further certified by an accredited test center. [ABSTRACT FROM AUTHOR]

In 145 patients, revaccination was performed with the culprit vaccine, which was well tolerated in 126 of the patients, and 15 of the patients had an alternative COVID-19 vaccine (other mRNA vaccine for 12), which was well tolerated in 13 of the patients (Figure 1). Keywords: allergy; anaphylaxis; COVID-19-mRNA vaccines EN allergy anaphylaxis COVID-19-mRNA vaccines 2320 2323 4 08/02/23 20230801 NES 230801 To the Editor, The mechanisms of allergic reactions to COVID-19-mRNA vaccines have not been elucidated. One hundred and sixty patients (84%) were revaccinated (122 under antihistamine premedication), 139 patients (87%) had good tolerance, and 30 patients refused further COVID-19 vaccination. [Extracted from the article]

A letter to the editor is presented about a patient who had developed a generalized eczema while taking desloratadine.

A letter to the editor is presented that discusses the nicorandil and ulcerations, a nicotinamide adenine dinucleotide/phosphate (NAD/NADP) and nicotinic acid-dependent side-effect.

Presents correspondence on the association of basal and squamous cell carcinoma with chronic venous leg ulcer. Disease backgrounds; Risk of developing carcinoma from leg ulcers.

Presents case studies on allergic contact dermatitis from surgical paints. Components of paints and adhesive tapes; Results of skin patch testing; Comparison of the different brands of surgical paints.

Objectives To describe the clinical and pathological features of biopsy-proven cutaneous vasculitis (CV) associated with SLE, focusing on diagnosis classification and impact on overall SLE activity. Methods Retrospective multicentric cohort study including SLE patients with biopsy-proven CV identified by (i) data from pathology departments of three university hospitals and (ii) a national call for cases. SLE was defined according to 1997 revised ACR and/or 2019 ACR/EULAR criteria. CV diagnosis was confirmed histologically and classified by using the dermatological addendum of the Chapel Hill classification. SLE activity and flare severity at the time of CV diagnosis were assessed independently of vasculitis items with the SELENA-SLEDAI and SELENA-SLEDAI Flare Index. Results Overall, 39 patients were included; 35 (90%) were female. Cutaneous manifestations included mostly palpable purpura (n  = 21; 54%) and urticarial lesions (n  = 18; 46%); lower limbs were the most common location (n  = 33; 85%). Eleven (28%) patients exhibited extracutaneous vasculitis. A higher prevalence of Sjögren's syndrome (51%) was found compared with SLE patients without CV from the French referral centre group (12%, P  < 0.0001) and the Swiss SLE Cohort (11%, P  < 0.0001). CV was mostly classified as urticarial vasculitis (n  = 14, 36%) and cryoglobulinaemia (n  = 13, 33%). Only 2 (5%) patients had no other cause than SLE to explain the CV. Sixty-one percent of patients had inactive SLE. Conclusion SLE-related vasculitis seems very rare and other causes of vasculitis should be ruled out before considering this diagnosis. Moreover, in more than half of patients, CV was not associated with another sign of active SLE. [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis, case report, cosmetics, patch tests A 53-year-old woman experienced a widespread eczema after application of two Tamanu oils on insect bites, with positive patch test results to the two Tamanu oils at 1% in olive oil. Keywords: allergic contact dermatitis; case report; cosmetics; patch tests EN allergic contact dermatitis case report cosmetics patch tests 99 100 2 06/14/22 20220701 NES 220701 Allergic contact dermatitis (ACD) to Tamanu oil is rare, but two recent cases underline that an increase in frequency of use could bring out more cases of ACD to this vegetable oil. [Extracted from the article]