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Acute generalized exanthematous pustulosis (AGEP) is a rare, usually drug-induced, acute pustular rash. Despite the lack of strong data supporting the effectiveness of topical or systemic corticosteroids in this drug reaction, they are widely used. More generally, there is no consensus on the diagnostic modalities and the management of patients with AGEP. We aimed to provide European expert recommendations for the diagnosis and management or patients with AGEP. Members of the ToxiTEN group of the European Reference Network (ERN)-skin, all dermatologists and/or allergologists with expertise in drug reactions, elaborated these recommendations based on their own experience and on a review of the literature. Recommendations were separated into the following categories: professionals involved, assessment of the diagnosis of AGEP, management of the patient and allergological work-up after the acute phase. Consensus was obtained among experts for the list of professionals involved for the diagnosis and management of AGEP, including the minimum diagnostic work-up, the setting of management, the treatments, the modalities and the timing of allergological work-up and follow-up. European experts in drug allergies propose herein consensus on the diagnosis and management of patients with AGEP. A multidisciplinary approach is warranted, including dermatologists, allergologists and pharmacovigilance services., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

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.

COVAX, the international initiative supporting COVID-19 vaccination campaigns globally, is budgeted to be the costliest public health initiative in low- and middle-income countries, with over 16 billion US dollars already committed. While some claim that the target of vaccinating 70% of people worldwide is justified on equity grounds, we argue that this rationale is wrong for two reasons. First, mass COVID-19 vaccination campaigns do not meet standard public health requirements for clear expected benefit, based on costs, disease burden and intervention effectiveness. Second, it constitutes a diversion of resources from more cost-effective and impactful public health programmes, thus reducing health equity. We conclude that the COVAX initiative warrants urgent review.

IntroductionApproximately 10% of individuals report a suspected allergy to penicillin, but according to allergy work-ups, only 10%–15% of them are truly allergic. A clinical decision score, the PEN-FAST, was developed and validated to identify adults with low-risk penicillin allergy.ObjectivesThe objective of this study was to improve the performance of the PEN-FAST score, particularly for those with delayed hypersensitivity (HS), by improving the negative predictive value.MethodsSTEP 1: Retrospective evaluation of the PEN-FAST score in patients with proven immediate and delayed penicillin allergy. STEP 2: Identification of additional criteria among Step 1 patients misclassified by PEN-FAST score. Development of the PEN-FAST+ score using multivariable logistic regression in a prospective cohort of patients with a suspicion of HS to penicillin. STEP 3: Comparison of diagnostic performances of PEN-FAST and PEN-FAST+ scores.ResultsThe PEN-FAST score showed limitations in predicting the relapse of immediate skin HS or delayed maculopapular exanthema, with 28.6% and 38.4% of patients misclassified, respectively. We identified two potential additional criteria: skin rash lasting more than 7 days and immediate reaction occurring in less than 1 h (generalized or localized on palmoplantar area or scalp itching/heat feeling). A total of 32/252 (12.7%) patients were confirmed to be allergic to penicillin. With PEN-FAST, 37% of patients (n = 10) with delayed allergic penicillin HS were misclassified. With PEN-FAST+, 3 patients with delayed HS confirmed by a ST (11.1%) were misclassified. The AUC was significantly higher for PEN-FAST+ than PEN-FAST (85% vs. 72%, p = 0.03).

Biocompatible and biodegradable polymers are widely used in the medical field. In some cases, the biopolymer is accompanied by an active drug, which is delivered locally in a controlled manner in order to improve the healing conditions. Poly([R,S]-3,3-dimethylmalic acid) (PDMMLA) is a synthetic amphiphilic biodegradable polymer, which unlike PLA, can be chemically modified to adapt hydrophilic/hydrophobic balance, degradation kinetics, and physicochemical and biological properties. It may contain a lateral alkyl group or a functional group for coupling bioactive molecules to release during its degradation. In this work, we realized the chemical grafting of paclitaxel (PTX), a microtubule stabilizing anti-cancer agent on PDMMLA derivatives bio-polyesters following a Steglich esterification protocol. 1D and 2D NMR analyses validated the reaction with 10% (using 0.1 equivalent) of PTX on the copolymer PDMMLAH40-co-Hex60 (PDMMLA 40/60) and a maximal PTX grafting rate of 55% on the homopolymer PDMMLAH (PDMMLA 100/0). In vitro adhesion and cytotoxicity assays were carried out on HUVEC cells with PDMMLA 40/60, PDMMLA-PTX 30/10/60 and PLA.

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]

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., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Abstract Background and Aims Vitamins are bioactive compounds naturally found in many different types of food and required by the human body for many biological functions and enzymatic activities. Due to their antioxidant properties, certain vitamin derivatives have been synthesized for inclusion in many cosmetics, thus leading to an increasing incidence of allergic contact dermatitis (ACD) cases. Therefore, the present review may be helpful to provide an insight into the sensitizing role of at least certain vitamins and may also offer possible patch test alternatives for definitive diagnosis. Methods This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Literature search regarding ACD cases to vitamins was performed using the Medline, PubMed, Scopus, EMBASE, and Google Scholar databases from January 1940 up to June 2021. Results A total of 4494 articles matched the keywords used for the researched. Records removed before screening included 15 duplicate articles and 3429 not eligible articles (e.g., not written in English, studies on animals, not relevant to the topic). A total of 1050 articles underwent the screening phase and 258 were therefore excluded as they were not primary studies. Subsequentially, 792 articles were considered eligible for the review and 688 of them were finally excluded as they did not report the outcome of interest. Therefore, 104 articles were definitely included in the present review. Conclusion ACD to vitamins is still probably an underestimated issue in cosmetology, as many vitamins are considered “natural” and therefore “safe” ingredients. On the contrary, according to current literature, almost all vitamins contained in topical products are able to induce allergic reactions, with the exception of vitamin B2 and vitamin B9. Patch tests are not standardized, thus leading to difficulties in diagnosis.

Sophie Seité,1 Charles Taieb,2 Nhân Pham-Thi,3,4 Annick Barbaud5,6 1La Roche-Posay Dermatological Laboratories, Levallois-Perret, France; 2European Market Maintenance Assessment, Fontenay-sous-Bois, France; 3Ecole Polytechnique, Economics, Palaiseau, France; 4Institut Pasteur Paris, Allergology, Paris, France; 5Dermatology and Allergy Department, Tenon Hospital, Medicine Sorbonne University, Paris, France; 6Assistance Publique-Hôpitaux de Paris, Paris, FranceCorrespondence: Sophie Seit&#x00E9La Roche-Posay Dermatological Laboratories, 62 Quai Charles Pasqua, Levallois-Perret, 92300, FranceTel +33 1 49 64 33 40Email sophie.seite@loreal.comBackground: Increased allergy frequency may have a significant impact on the skin, one of the largest targeted organs for allergic and immunological responses.Methods: An online survey of 2036 adults as a representative sample of the French general population was conducted to evaluate the prevalence of self-reported allergies, the populations who report allergies and the skin conditions related to allergies.Results: In general, 20.2% of French adults (average age 45 ± 15.8 years) reported allergies. These allergies were respiratory allergies (55.3%), skin allergies (48.8%) and food allergies (27.9%), and 78.9% indicated that their reported allergies were diagnosed by a doctor. In addition, 53.2% of individuals reporting an allergy also indicated that they experienced associated skin reactions. In comparison to those who did not report an allergy, these individuals were 1.5 to 4 times more likely to have a skin disease and 3 times more likely to have sensitive skin or skin reactions when using skincare products.Conclusion: It is estimated that over 10 million French adults have allergies. These data will help increase awareness among the allergic population and healthcare professionals about the burden associated with allergies and the need for management to reduce their health impact.Keywords: allergies, food allergy, skin allergy, respiratory allergy, prevalence, skin side effects

Acquired cold contact urticaria (ACU) is a putatively serious condition, because of the risk of anaphylactic shock whenever patients are massively exposed to cold atmosphere/water, raising the question of the prescription of an “emergency kit” with oral antihistamines and epinephrine auto-injector. We performed an online survey to evaluate how French-speaking urticaria experts manage ACU. According to the 2016 consensus recommendations on chronic inducible urticarias, all the participants perform at least 1 of the available provocation tests and 84.2%, 77.8%, and 88.9% prescribe on-label use of second generation anti-H1 antihistamines (2GAH1) as a first line treatment, updosed 2GAH1 as a second line treatment, and omalizumab as a third line treatment, respectively. Interestingly, 44.4% of the practitioners always prescribe a continuous background treatment, versus 11.1% prescribing only on-demand therapy. Also, 11.7% of participants always prescribe an epinephrine auto-injector, 70.6% sometimes do, and 17.6% never do. Finally, 89.5% authorize swimming under strict conditions but 36.8% and 68.4% contra-indicate other water sports and occupational cold exposure, respectively.

Soon after the release of the new anti-COVID mRNA vaccines, reports came in from the US and the UK of anaphylactic reactions. Fueled by the necessary caution toward these new vaccine platforms, these reports had a great impact and were largely commented upon in the scientific literature and global media. The current estimated frequency is of 5 cases per million doses. Very little biological data are presented in the literature to support the anaphylaxis diagnosis in these patients in addition to skin tests. Allergic reactions to vaccines are rare and mostly due to vaccine excipient. Therefore, the poly-ethylene-glycol (PEG) present in both mRNA formulation, and already known to be immunogenic, was soon suspected to be the potential culprit. Several hypersensitivity mechanisms to PEG or to other vaccine components can be suspected, even if the classical IgE-dependent anaphylaxis seems to be one of the most plausible candidates. In the early 2022, the international guidelines recommended to perform skin prick tests and basophil activation tests (BAT) in people experiencing allergic reaction to the first dose of COVID-19 vaccine or with a history of PEG allergy. The aim of this review is to discuss the main potential mechanisms of immediate allergy to COVID19 vaccines based on published data, together with the various techniques used to confirm or not sensitization to one component.

Linear Immunoglobulin A Bullous Disease (LABD) is a rare dermatosis whose pathomechanisms are not yet completely understood. LABD has different features characterizing adults and children in terms of potential triggers, clinical manifestations, and prognosis. The aim of the present study is to review all neonatal and pediatric cases of LABD and summarize the major characteristics. Childhood LABD is mainly idiopathic with a benign prognosis. Neonatal cases are difficult to differentiate from infectious diseases and usually have a poor prognosis. Drugs are one of the possible triggers that can activate autoimmune responses through antigen mimicry and epitope spreading as well as different stimuli (e.g., infections, inflammatory diseases, trauma). The gold standard for the diagnosis is based on direct immunofluorescence. Prognosis is generally favorable but often depends on the prompt dermatological diagnosis, treatment and follow-up guaranteed by a multidisciplinary team, including pediatricians for this group of age.

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]