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Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the management of type 2 diabetes and obesity. It was the first GLP-1 receptor agonist to be approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of obesity. To date, numerous skin adverse reactions to liraglutide have been reported, but data regarding hypersensitivity reactions are scarce, raising concerns about its safety and clinical management. We present the case of a 56-year-old female patient with class 3 obesity who was started on subcutaneous liraglutide (Saxenda) by her endocrinologist. One month after starting the aforementioned treatment, the patient presented well-defined, round, erythematous pruriginous plaques surrounding the injection site, around 24 hours after the drug administration. A liraglutide-induced, delayed-type hypersensitivity reaction was suspected, which could be subsequently confirmed by allergy testing and histopathological study. This paper explores the clinical use of liraglutide, the occurrence of hypersensitivity reactions, diagnosis, management, and implications for future research. Understanding and managing liraglutide hypersensitivity is crucial to ensuring the safety and efficacy of this medication. [ABSTRACT FROM AUTHOR]

Background: Professional ice hockey players may contract irritant and allergic contact dermatitis. Aims: To investigate the presence of contact allergy (CA) in professional ice hockey players in Sweden. Methods: Ten teams from the two top leagues were assessed for potential occupational exposure to sensitizers. Exactly 107 players were patch tested with an extended baseline series and a working series, in total 74 test preparations. The CA rates were compared between the ice hockey players and controls from the general population and dermatitis patients. Results: One out of 4 players had at least one contact allergy. The most common sensitizers were Amerchol L 101, nickel and oxidized limonene. CA was as common in the ice hockey players as in dermatitis patients and significantly more common than in the general population. Fragrances and combined sensitizers in cosmetic products (fragrances + preservatives + emulsifier) were significantly more common in ice hockey players compared with the general population. Conclusion: The possible relationship between CA to fragrances and cosmetic products on the one hand and the presence of dermatitis on the other should be explored further. [ABSTRACT FROM AUTHOR]

Modern neurosurgeons commonly rely on dural grafts to aid in obtaining watertight closures when the native dura itself cannot be approximated. We present a patient who developed a symptomatic, delayed hypersensitivity reaction to a cellulose-based synthetic dural graft, which resolved after reoperation and removal of the graft. Dural grafts are a safe and common implant utilized in neurosurgery. Nevertheless, as with all implanted material, there is a chance for symptomatic immune reactions to occur. This type of response is exceedingly uncommon, but recognition of this rare presentation may help other providers recognize it in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] • ABF1 is induced by ABA and promotes ABA repression on rice flowering. • SAPK8 phosphorylates ABF1 and strengthens the latter participating in ABA-mediated flowering inhibition. • ABA enhances the direct transcriptional repression of ABF1 on Ehd1 and Ehd2. • ABF1 recruits PRC2 complex to deposit H3K27me3 to suppress Ehd1 and Ehd2. Rice flowering is a major agronomic trait, determining yield and ecological adaptability in particular regions. ABA plays an essential role in rice flowering, but the underlying molecular mechanism remains largely elusive. In this study, we demonstrated a "SAPK8-ABF1- Ehd1/Ehd2 " pathway, through which exogenous ABA represses rice flowering in a photoperiod-independent manner. We generated abf1 and sapk8 mutants using the CRISPR-Cas9 method. Using yeast two-hybrid, Pull down, BiFC and kinase assays, SAPK8 interacted and phosphorylated ABF1. ABF1 directly bound to the promoters of Ehd1 and Ehd2 using ChIP-qPCR, EMSA, and LUC transient transcriptional activity assay, and suppressed the transcription of these genes. Under both long day and short day conditions, simultaneous knock-out of ABF1 and its homolog bZIP40 accelerated flowering, while SAPK8 and ABF1 over-expression lines exhibited delayed flowering and hypersensitivity to ABA-mediated flowering repression. After perceiving the ABA signal, SAPK8 physically binds to and phosphorylates ABF1 to enhance its binding to the promoters of master positive flowering regulators Ehd1 and Ehd2. Upon interacting with FIE2, ABF1 recruited PRC2 complex to deposit H3K27me3 suppressive histone modification on Ehd1 and Ehd2 to suppress these genes transcription, thereby leading to later flowering. Our work highlighted the biological functions of SAPK8 and ABF1 in ABA signaling, flowering control and the involvement of a PRC2-mediated epigenetic repression mechanism in the transcription regulation governed by ABF1 on ABA-mediated rice flowering repression. [ABSTRACT FROM AUTHOR]

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy presenting with delayed onset of projectile vomiting in the absence of cutaneous and respiratory symptoms. The pathophysiology of FPIES remains poorly characterized. The first international consensus guidelines for FPIES were published in 2017 and provided clinicians with parameters on the diagnosis and treatment of FPIES. The guidelines have served as a resource in the recognition and management of FPIES, contributing to an increased awareness of FPIES. Since then, new evidence has emerged, shedding light on adult-onset FPIES, the different phenotypes of FPIES, the recognition of new food triggers, center-specific food challenge protocols and management of acute FPIES. Emerging evidence indicates that FPIES impacts both pediatric and adult population. As a result, there is growing need to tailor the consensus guidelines to capture diagnoses in both patient groups. Furthermore, it is crucial to provide food challenge protocols that meet the needs of both pediatric and adult FPIES patients, as well as the subset of patients with atypical FPIES. This review highlights the evolving clinical evidence relating to FPIES diagnosis and management published since the 2017 International FPIES Guidelines. We will focus on areas where recent published evidence may support evolution or revision of the guidelines. [ABSTRACT FROM AUTHOR]

Trichloroethylene-induced hypersensitivity dermatitis (TIHD) is a delayed hypersensitivity response that is affected by genetic and environmental factors. Occupational exposure to trichloroethylene (TCE) enhances antigen presentation, leading to hypersensitivity in workers with the HLA-B* 13:01 allele. Several studies have observed the activation of herpesviruses, such as Epstein Barr virus (EBV), in TIHD patients. However, the underlying mechanisms remain unclear. Toll-like receptors (TLRs) play a pivotal role in the pathogenesis of herpesvirus infection. This study aimed to explore whether TLRs serve as a shared mechanism for both herpesvirus and allergenic chemicals. In this study, HLA-B* 13:01-transfected Hmy2. A C1R cell model was constructed, and cells were treated with TCOH and EBV to explore the possible mechanisms. We established a mouse model of dermatitis and used a TLR4 agonist to verify the effect of herpesvirus on TIHD. The results showed that EBV and TCOH synergistically enhance antigen processing and presentation via the TLR2/NF-κB axis. Furthermore, TLR4 agonist further aggravated skin lesions and liver damage in TCE-sensitized mice through TLR4/NF-κB axis-mediated antigen processing and presentation. Together, this study indicates that viral infection further aggravates the inflammatory response in TIHD based on environment-gene interactions. • Trichloroethanol and EBV synergistically activated TLR2/NF-κB pathway. • Trichloroethanol and EBV promoted antigen processing and presentation. • TLR4 agonist aggravated trichloroethylene-induced antigen-presenting function. • TLR4 agonist potentiated the skin lesions of trichloroethylene-sensitized mice. [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. [ABSTRACT FROM AUTHOR]

This article provides an allergological reappraisal of the Annex to the European Commission guideline on excipients in medicinal products. The authors argue that the current guideline is outdated and fails to include excipients that have been reported to cause severe hypersensitivity reactions. They stress the importance of updating allergological information on excipients to ensure patient safety. The article includes tables summarizing excipients not included in the guideline and examples of reported hypersensitivity reactions. The document also provides a list of various substances and their associated adverse reactions, highlighting the need to update the allergological information of certain excipients in the Annex. The authors declare no conflicts of interest and received no funding for the study. [Extracted from the article]

Background: Contact allergy rates of linalool and limonene hydroperoxides (HPs) have increased. Objectives: To demonstrate the patterns of simultaneous positive patch test (PT) reactions and prevalences of multiple contact allergies (MCAs) in patients with contact allergy to linalool and/or limonene HPs. Methods: A retrospective analysis of consecutive dermatitis patients in 2015–2020 was performed. Results: Of all 4192 patients, 1851 had at least one positive PT reaction. Of these, 410 (22.2%) had MCAs, significantly related to a higher age (p‐value = 0.003). Patients with an exclusively positive reaction to linalool HPs but not limonene HPs were shown to have MCAs (p‐value <0.001, odds ratio (95% confidence interval) = 4.15 (3.01–5.73)). Patients with simultaneous contact allergies to both linalool and limonene HPs had contact allergies to many other screening and fragrance allergens. Conclusions: Simultaneous positive PT reactions to allergens in baseline series and fragrances are common in patients with the HPs contact allergy, especially linalool HPs. The pattern of simultaneous PT reactions principally suggested the co‐sensitization of the cosmetic allergens. [ABSTRACT FROM AUTHOR]

Objective. Fibroblast-like synoviocytes (FLSs) are critical for promoting joint damage in rheumatoid arthritis (RA). N6 -methyladenosine (m6 A) modification plays key roles in various diseases, but its role in the pathogenesis of RA is largely unknown. Here, we investigate increased demethylase ALKBH5 promotion of proliferation, migration, and invasion of RA FLSs via regulating JARID2 expression. Methods. ALKBH5 expression in FLSs was evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. 5-ethynyl-20-deoxyuridine, scratch wound healing, and transwell assays were implemented to determine the role of ALKBH5 on RA FLS proliferation, mobility, and migration. Then, m6 A sequencing combined with RNA sequencing was performed to identify the potential targets of ALKBH5. RNA immunoprecipitation and RNA pulldown were then used to validate the interaction between the protein and messenger RNA (mRNA). Collagen-induced arthritis (CIA) and delayed-type hypersensitivity arthritis (DTHA) models were further established to assess the therapeutic potency of ALKBH5 in vivo. Results. We demonstrated that ALKBH5 expression was increased in FLSs and synovium from RA. Functionally, ALKBH5 knockdown inhibited the proliferation, migration, and invasion of RA FLSs, whereas overexpression of ALKBH5 displayed the opposite effect. Mechanistically, ALKBH5 mediated m6 A modification in the JARID2 mRNA and enhanced its mRNA stability in cooperation with IGF2BP3. Intriguingly, the severity of arthritis was attenuated in mice with DTHA and ALKBH5 knockout or rats with CIA and intra-articular injection of ALKBH5 short hairpin RNA. Conclusion. Our findings suggest that ALKBH5-mediated m6 A modification is crucial for synovial hyperplasia and invasion in RA. ALKBH5 might be a potential therapeutic target for RA and even for dysregulated fibroblasts in a wide range of diseases. [ABSTRACT FROM AUTHOR]

The etiology and pathophysiology of delayed inflammatory reactions caused by hyaluronic acid fillers have not yet been elucidated. Previous studies have suggested that the etiology can be attributed to the hyaluronic acid filler itself, patient's immunological status, infection, and injection technique. Hyaluronic acid fillers are composed of high-molecular weight hyaluronic acids that are chemically cross-linked using substances such as 1,4-butanediol diglycidyl ether (BDDE). The mechanism by which BDDE cross-links the two hyaluronic acid disaccharides is still unclear and it may exist as a fully reacted cross-linker, pendant cross-linker, deactivated cross-linker, and residual cross-linker. The hyaluronic acid filler also contains impurities such as silicone oil and aluminum during the manufacturing process. Impurities can induce a foreign body reaction when the hyaluronic acid filler is injected into the body. Aseptic hyaluronic acid filler injections should be performed while considering the possibility of biofilm formation or delayed inflammatory reaction. Delayed inflammatory reactions tend to occur when patients experience flu-like illnesses; thus, the patient's immunological status plays an important role in delayed inflammatory reactions. Large-bolus hyaluronic acid filler injections can induce foreign body reactions and carry a relatively high risk of granuloma formation. [ABSTRACT FROM AUTHOR]

The goal of this study was an evaluation of the immunomodulatory effect of polysaccharides isolated from the seeds of Brassica rapa. Apolysaccharide (BRP) consisting mainly of α-linked pyranose residues belonging to the arabinogalactan class was obtained. The number of antibody-forming cells (AFCs) per spleen increased to 9,160 ± 1477.06, 12,000 ± 3480.33, and 19,080 ± 12,391.6 [antibody-forming reaction index (ARI) = 1, 5, 2, and 3.2 times, respectively] in experimental mice treated with BRP at a dose of 0.05, 0.5, and 5 mg/kg, respectively. The number of AFCs was 70.8 ± 8.05, 73.17 ± 20.5, and 120.3 ± 83.7, respectively, when converted to one million spleen cells. Under the effect of BRP at all studied doses (0.05, 0.5, and 5 mg/kg), a dose-dependent decrease in the index of response to inflammation was observed and a significant trend toward a decrease in the development of hypersensitivity reactions of the delayed type was revealed, especially at doses of 0.5 and 5 mg/kg, as compared to a reference drug (Immunal) administered at a dose of 60 mg/kg. The results suggested that B. rapa polysaccharides had a stimulating effect on the humoral and cellular immune response. [ABSTRACT FROM AUTHOR]

Background: Simultaneous overrepresentations of contact allergies and photocontact allergies are common in individuals with photocontact allergy to ketoprofen. Aims: To investigate whether contact allergy to oxidised (ox.) geraniol, geraniol, geranial, neral and citral is overrepresented in individuals with photocontact allergy to ketoprofen. Methods: The contact allergy rates to ox. geraniol, geraniol, geranial, neral and citral in routinely patch tested dermatitis patients were compared with the corresponding rates in individuals with photocontact allergy to ketoprofen. Results: Allergic patch test reactions were noted to ox. geraniol 11% (n = 39, 5.8%), ox. geraniol 6% (n = 12, 1.8%), geraniol 6% (n = 2, 0.3%), geranial (n = 18, 2.7%), neral (n = 7, 1.0%) and citral (n = 15, 2.2%). In those four patients who were diagnosed with photocontact allergy to ketoprofen during the test period, a significant overrepresentation (p = 0.020) of simultaneous contact allergy to ox. geraniol 11% was demonstrated. Overrepresentation of simultaneous contact allergy to various combinations of ox. geraniol, ox. limonene and ox. linalool was also noted in ketoprofen‐photoallergic patients. Conclusions: Contact allergy to ox. geraniol, geranial and citral is common in routinely tested dermatitis patients. There is an overrepresentation of simultaneous contact allergy to ox. geraniol, ox. limonene and ox. linalool in patients with photocontact allergy to ketoprofen. [ABSTRACT FROM AUTHOR]

Introduction: Soft tissue fillers are widely used and are commonly considered to be safe. Nonetheless, adverse events such as late inflammatory reactions (LIRs) are reported for every type of filler. As of the start of the COVID-19 pandemic, LIRs have been reported after SARS-CoV infection or vaccination. In the past, we reviewed these adverse events; however, since then, we faced a wave with the Omicron, and the vaccination programs continued with booster vaccines. We therefore aimed to perform an up-to-date review of the literature on LIRs after COVID-19 infection and vaccination with additional learned lessons from this pandemic. Material and methods: We performed a systematic review on soft tissue filler-related LIRs after SARS-CoV-2 infection or vaccination in line with the PRISMA guidelines. Eligible studies were searched in the database PubMed from 1 August 2021 until 1 June 2023. Data on patient characteristics, filler characteristics, clinical findings, and treatment options were retrieved. Results: A total of 14 papers with in total 52 patients were reported, of which 16 had adverse events after a SARS-CoV-2 infection and 36 after SARS-CoV-2 vaccination. In most cases, it concerned females who had their (mostly temporary) fillers for cosmetic purposes. Symptoms were reported in a matter of hours up to weeks after SARS-CoV-2 vaccination (22 Pfizer, 7 Moderna, 3 AstraZeneca, 3 Sputnik V, and one after Siophram), mostly after the first or second dose but sporadically after a third dose. Most patients were treated in a conservative manner. Discussion: LIRs continue to be reported after SARS-CoV-2 infection and vaccination and are currently also reported for non-mRNA vaccines, for non-temporary fillers, and also after a third dose of the vaccine. Although there are more and more papers on this matter, they remain minor and self-limiting. We therefore still advise patients with soft tissue fillers to remain participated in vaccination programs when needed. Level of evidence: Not gradable. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: An 82-year-old woman presented with acute pyrexial illness and mesenteric panniculitis and developed biochemical aseptic meningitis (cerebrospinal fluid pleocytosis with no identifiable pathogen). Investigation determined her illness was likely a delayed hypersensitivity reaction caused by sulfasalazine. Sulfasalazine-induced aseptic meningitis is a rare condition often diagnosed late in a patient's admission owing to initial non-specific illness symptomatology requiring the exclusion of more common "red flag" etiologies, such as infection and malignancy. Case Report: An 82-year-old woman with a history of recurrent urinary tract infections and seronegative arthritis presented with a 3-day history of fatigue, headache, dyspnea, and lassitude. On admission, she was treated as presumed sepsis of uncertain source owing to pyrexia and tachycardia. Brain computer tomography (CT) revealed no acute intracranial abnormality. Furthermore, CT of the chest, abdomen, and pelvis did not reveal any source of sepsis or features of malignancy. After excluding infective etiologies with serological and cerebrospinal fluid testing, sulfasalazine-induced aseptic meningitis (SIAM) was diagnosed. The patient was then commenced on intravenous steroids, resulting in immediate defervescence and symptom resolution. Conclusions: SIAM remains a diagnostic challenge since patients present with non-specific signs and symptoms, such as pyrexia, headaches, and lassitude. These patients require a thorough investigative battery starting with anamnesis, physical examination, biochemical testing, and radiologic imaging. This case illustrates the need for a high suspicion index of drug-induced hypersensitivity reaction in a rheumatological patient with pyrexial illness where infective etiologies have been confidently excluded. Prompt initiation of intravenous steroids in SIAM provides a dramatic recovery and resolution of symptoms. [ABSTRACT FROM AUTHOR]

This article discusses the use of upadacitinib, a Janus kinase inhibitor (JAKi), as a potential treatment for chronic actinic dermatitis (CAD). CAD is a rare immunologically mediated photodermatosis that causes pruritic, eczematous, and lichenified plaques on sun-exposed areas of the skin. Current treatment options for CAD include topical therapy with corticosteroids and calcineurin inhibitors, as well as oral corticosteroids and immunosuppressive drugs. However, some patients do not respond to these treatments, highlighting the need for novel therapeutic approaches. Upadacitinib has shown promise in treating other dermatoses and has been successful in treating a 75-year-old man with refractory CAD. Further investigation is needed to determine the efficacy of JAKi as a treatment option for CAD. [Extracted from the article]

Anaphylaxis, a type 1 hypersensitivity reaction, is a feared but uncommon complication of medications administered in the perioperative period. The incidence of perioperative hypersensitivity reactions has been reported to range from 1 in 20,000 to 1 in 1,361. Anesthesiologists are well aware of common causes of hypersensitivity such as paralytics and antibiotics; however, less common triggers of anaphylaxis need to be considered as well. Midazolam, a short acting benzodiazepine metabolized by cytochrome P450 enzymes, is considered very safe with a minimal risk profile. Previous reports have described adverse reactions to occur within seconds to minutes following the administration of midazolam. We describe a patient with no known history of asthma or allergies who underwent elective hydrocelectomy with spinal analgesia without incident until 42 minutes later at the conclusion of the procedure, when they experienced circulatory collapse necessitating immediate emergency treatment. This case emphasizes the necessity to improve knowledge and awareness of delayed hypersensitivity reactions following the administration of perioperative medications such as midazolam. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for allergy work-up. In recent years, some in vitro markers have been proposed and used for delayed reactions, such as contact dermatitis. Primary strategy: Avoidance is difficult to achieve, especially for COVID-19 vaccinations, when immunity against infection is extremely important. The aim of our study was to evaluate the application of in vitro delayed hypersensitivity tests in COVID-19 vaccines. Seven patients with a positive history of severe delayed drug allergy were enrolled. Vein blood was collected to stimulate cells with the tested vaccines (Comirnaty, Janssen, Spikevax) and excipients with the assessment of CD40L, CD69, IL-2, IL-4, IL-6, IL-10, IFNgamma, TNFalfa, and intracellular markers: granulysin and INFgamma. In addition, basophile activation tests, patch tests, skin prick tests, and intradermal tests were performed with the tested vaccine. Finally, the decision was made to either administer a vaccine or resign. Two out of seven patients were considered positive for drug hypersensitivity in the in vitro test according to the high vaccine stimulation index measured with CD69 (6.91 and 12.18) and CD40L (5.38 and 15.91). All patch tests, BATs, and skin tests were negative. Serum interleukin measurements were inconclusive as the impact of the vaccine itself on the immunity system was high. Intracellular markers gave uncertain results due to the lack of stimulation on the positive control. CD69 and CD40L could be reliable in vitro markers for delayed hypersensitivity to COVID-19 vaccines. Patch tests, skin tests, BATs, and serum interleukins did not confirm their usefulness in our study. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Alpha‐gal syndrome is an immunoglobulin E‐mediated hypersensitivity characterized by delayed allergic reactions to ingested products containing alpha‐gal carbohydrate. We present a patient with recurrent urticaria and suspected repaglinide hypersensitivity, who was eventually diagnosed with alpha‐gal syndrome, wanting to emphasize possible drug allergy misdiagnosis and required caution with the medication choice. [ABSTRACT FROM AUTHOR]

Background: Eugenol is a known contact sensitiser included in fragrance mix I. Objective: To assess the allergic reactivity to eugenol in different concentrations using patch test as well as repeated open application test (ROAT). Methods: Overall 67 subjects from 6 European dermatology clinics participated in the study. The ROAT was performed for 21 days twice a day, applying 3 dilutions of eugenol (2.7%–0.5%) and a control. Before and after the ROAT, patch testing with 17 dilutions of eugenol (2.0%–0.00006%) and controls was performed. Results: Out of the 34 subjects with contact allergy to eugenol, 21 (61.8%) showed a positive patch test before ROAT was performed, the lowest positive concentration was 0.031%. The ROAT was positive in 19 (55.9%) of the 34 subjects, the time until a positive reaction occurred was negatively associated with the concentration of the ROAT solution, as well as with the allergic reactivity of the subjects as defined by patch testing. In the patch test after ROAT, 20 of the 34 test subjects (58.8%) showed a positive reaction. In 13 (38.2%) of the 34 test subjects, the patch test result was not reproduceable, still 4 (31.0%) of these 13 subjects developed a positive ROAT. Conclusion: Eugenol can provoke a positive patch test reaction in a very low dose; besides, this hypersensitivity may persist even if a former positive patch test is not reproduceable. [ABSTRACT FROM AUTHOR]

Skin rejuvenation procedures have increasingly flooded the aesthetic market, one of which includes microneedling. In microneedling, multiple fine punctures of the skin are performed with a needle to induce neocollagenesis. Microneedling has increasingly been used to treat inflammatory acne, acne scarring, photodamaged skin, and even radiation dermatitis. We present a patient with a stable history of liquid injectable silicone (LIS) given 20 years prior who developed chronic periocular and facial hypersensitivity after undergoing microneedling at a medi-spa. Long-term steroids and immunosuppressants were needed for control. The patient's severe reaction and resistance to treatment highlights the potential complications of microneedling administered by a non-medical professional in the setting of prior injectable silicone. [ABSTRACT FROM AUTHOR]

• Vaccine excipient-positive BAT associates with delayed hypersensitivity manifestations. • DMG-PEG 2000 reactivity is frequent in patients with anti-SARS-CoV-2 vaccine hypersensitivity. • DMG-PEG 2000 reactivity associates with vaccination. Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Alpha-gal syndrome is an immunoglobulin E (IgE)-mediated delayed hypersensitivity reaction to nonprimate mammalian products, which has a newly established gastrointestinal (GI) phenotype in adults. We assessed the GI presentation and treatment response in children. METHODS: This is a retrospective study of patients presenting in a pediatric gastroenterology clinic tested for alpha-gal IgE. RESULTS: Forty of199patients (20%) tested had apositive alpha-gal-specific IgE,with77.5%reportingGIsymptomsin isolation. Of the 30 that attempted dietary elimination, 8 (27%) experienced full resolution of symptoms. DISCUSSION: Alpha-gal syndrome can present with isolated GI symptoms in children. [ABSTRACT FROM AUTHOR]

2012; 14 (3): R134. doi: 10.1186/ar3867 5 Atkinson SM, Nansen A. Pharmacological value of murine delayed-type hypersensitivity arthritis: a robust mouse model of rheumatoid arthritis in C57BL/6 mice. As blood sampling could only be performed once a week, mice in each intervention group were randomized to either blood sampling just before mBSA injection (baseline) or blood sampling 24 h after mBSA injections (at assumed peak inflammation). Keywords: animal models; arthritis; inflammation; mouse model; rheumatoid arthritis EN animal models arthritis inflammation mouse model rheumatoid arthritis 551 555 5 05/15/23 20230601 NES 230601 INTRODUCTION AND BACKGROUND Rheumatoid arthritis (RA) is the most prevalent autoimmune disease with an incidence of about 0.5%-1% of the general population.[1] Several experimental mouse models mimicking RA exist.[2] All these models harbour various experimental features ranging from specific pathophysiological mechanisms, as well as degree and durability of inflammation. Animal models, arthritis, inflammation, mouse model, rheumatoid arthritis. [Extracted from the article]

We report a case of a 15-year-old atopic patient presenting with delayed, severe ulcerative hypertrophic gingivitis after placement of orthodontic braces, which required removal of braces and restorative laser surgical procedures. Patch testing to multiple metals and chemicals showed weak positive reactions to steel bands and formaldehyde. The patient experienced urticarial, gingivitis, and other intraoral symptoms after patch testing and re-exposure to nickel-containing products. In contrast, nickel, cobalt, and cobalt-chromium (Co-Cr) bracket patch testing sites were negative. Nickel-caused contact dermatitis is Type IV delayed hypersensitivity reaction occurring at least 24 h after exposure. This reaction can result in intraoral blisters, ulcerations, eczematous and urticarial reactions of the face and more distant skin areas. This case illustrates the intraoral delayed response, symptom resolution after removing the braces, and brackets and local reactions upon subsequent nickel exposure, despite negative patch testing and lymphocyte stimulation test to nickel. This case further illustrates the difficulty associated with diagnosing nickel allergy. [ABSTRACT FROM AUTHOR]

Background: The two dialkylthiocarbamyl benzothiazole sulphides, dimethyl‐thiocarbamylbenzothiazole sulphide (DMTBS) and diethylthio‐carbamylbenzothiazole sulphide (DETBS) were shown to be good markers of both thiuram and mercaptobenzothiazole sensitivity. Objectives: To investigate if DMTBS and/or DETBS could be better markers of contact allergy to common rubber additives than the ones currently used. Methods: Sixty‐eight dermatitis patients were patch tested with DMTBS and DETBS, both at 1% in petrolatum (pet). Because of late reactions in 10 patients, these were retested to DMTBS and DETBS in serial dilutions. Tetramethylthiuram monosulphide (TMTM) 1.0% pet was also tested. Results: At the initial reading Days 3 and 7, no reactions were noted to DMTBS or DETBS. At retesting, 10 of the 68 (15%) patients reacted positively to lower concentrations of DMTBS than the initial test concentration. Seven of 8 also reacted to TMTM. Three of them had positive reactions to DEBTS. All 10 patients had reactions to more diluted solutions to DMBTS than to DEBTS (p = 0.0077; Mc‐Nemar test, two‐sided). Conclusions: Results speak for patch test sensitization to DMTBS with cross‐reactivity to TMTM and also DEBTS. DMTBS and DEBTS could be new markers of rubber allergy but a safe test concentration must be found. [ABSTRACT FROM AUTHOR]

Therefore, patch test should always be performed in non-immediate cephalosporin ADRs before proceeding with challenge test in order to find an alternative cephalosporin. Keywords: adverse drug reaction; case report; ceftazidime; cephalosporins; delayed hypersensitivity; patch test EN adverse drug reaction case report ceftazidime cephalosporins delayed hypersensitivity patch test 487 490 4 05/09/23 20230601 NES 230601 Cephalosporins are antibiotics frequently used both in hospitalized patients and outpatients due to their efficacy in several infectious diseases.[1] Early generation cephalosporins are mainly used for surgical site infection prophylaxis with good activity against gram-positive bacteria and a very limited activity against gram-negative, while late generation products have better pharmacokinetic and pharmacodynamic profiles with an increasing activity against gram-negative bacteria in severe and resistant infections. [Extracted from the article]

Lazarine leprosy is an unusual expression of usually borderline tuberculoid (BT) form characterized by spontaneous ulceration of skin lesions. This is presumably the result of an exaggerated type 1 reaction. It commonly occurs in the BT, borderline lepromatous forms and rarely in the lepromatous forms of leprosy. We report two cases of lazarine leprosy in the BT and BT downgrading to borderline lepromatous spectrum in healthy and immunocompetent males. [ABSTRACT FROM AUTHOR]

Background: Five workers from an industry manufacturing various articles from carbon fibre reinforced epoxy plastics were referred to our department because of suspected occupational allergic contact dermatitis (OACD). When patch tested, four of them had positive reactions to components of epoxy resin systems (ERSs) that could explain their current skin problems. All of them had been working at the same workstation at a specially designed pressing machine, with operations including manually mixing epoxy resin with hardener. Multiple cases of OACD in the plant prompted an investigation including all workers with possible risk exposures at the plant. Objectives: To investigate the prevalence of occupational dermatoses and contact allergies among the workers at the plant. Materials and Methods: Totally 25 workers underwent investigation that included a brief consultation with a standardized anamnesis and clinical examination followed by patch testing. Results: ERSs‐related reactions were found in 7 of the 25 investigated workers. None of the seven had a history of previous exposure to ERSs and they are regarded as sensitized through work. Conclusions: Twenty‐eight percent of investigated workers showed reactions to ERSs. Of these the majority would have been missed if supplementary testing would not have been added to testing with the Swedish base line series. [ABSTRACT FROM AUTHOR]

In patients undergoing percutaneous coronary intervention, the second-generation drug-eluting stents (DES) are considered the gold standard of care for revascularization. By reducing neointimal hyperplasia, drug-eluting coronary stents decrease the need for repeat revascularizations compared with conventional coronary stents without an antiproliferative drug coating. It is important to note that early-generation DESs were associated with an increased risk of very late stent thrombosis, most likely due to delayed endothelialization or a delayed hypersensitivity reaction to the polymer. Studies have shown a lower risk of very late stent thrombosis with developing second-generation DESs with biocompatible and biodegradable polymers or without polymers altogether. In addition, research has indicated that thinner struts are associated with a reduced risk of intrastent restenosis and angiographic and clinical results. A DES with ultrathin struts (strut thickness of 70 µm) is more flexible, facilitates better tracking, and is more crossable than a conventional second-generation DES. The question is whether ultrathin eluting drug stents suit all kinds of lesions. Several authors have reported that improved coverage with less thrombus protrusion reduced the risk of distal embolization in patients with ST-elevation myocardial infarction (STEMI). Others have described that an ultrathin stent might recoil due to low radial strength. This could lead to residual stenosis and repeated revascularization of the artery. In CTO patients, the ultrathin stent failed to prove non-inferiority regarding in-segment late lumen loss and showed statistically higher rates of restenosis. Ultrathin-strut DESs with biodegradable polymers have limitations when treating calcified (or ostial) lesions and CTOs. However, they also possess certain advantages regarding deliverability (tight stenosis, tortuous lesions, high angulation, etc.), ease of use in bifurcation lesions, better endothelialization and vascular healing, and reducing stent thrombosis risk. In light of this, ultrathin-strut stents present a promising alternative to existing DESs of the second and third generation. The aims of the study are to compare ultrathin eluting stents with second- and third-generation conventional stents regarding procedural performance and outcomes based on different lesion types and specific populations. [ABSTRACT FROM AUTHOR]

T cell-and non T cell-mediated delayed hypersensitivity to dupilumab We hypothesize that Patient 1 was sensitized to T-cell epitopes in the tralokinumab primary sequence with cross-reactivity with dupilumab[6]; (ii) an Arthus-like reaction, that is, an immune complex-mediated reaction produced under conditions of excess antigens, for the second patient. We report the cases of a 52-year-old (Patient 1) and a 56-year-old (Patient 2) female patients, followed for severe AD with multiple previous treatment failures. [Extracted from the article]

In this paper, we explain why late-appearing patch test reactions to carvone followed by a positive retest within 3 days, do not need to be equivalent with active sensitization. Late-appearing patch test reactions to carvone do not need to be signs of active sensitization Keywords: allergic contact dermatitis; CAS 6485-40-1; contact allergy; delayed hypersensitivity; dilutions; mint-tasting flavor; retest EN allergic contact dermatitis CAS 6485-40-1 contact allergy delayed hypersensitivity dilutions mint-tasting flavor retest 207 209 3 08/04/23 20230901 NES 230901 A controlled and randomized use test with l-carvone in a toothpaste on individuals with or without contact allergy to carvone was performed.[1] One week before the use test, a patch test with l-carvone was performed in 37 volunteers. [Extracted from the article]

Cystic fibrosis is a life-shortening disease characterized by the mutation of the salt transporter cystic fibrosis transmembrane conductance regulator (CFTR) protein. Elexacaftor/tezacaftor/ivacaftor treatment, which has been used since 2019, has had effects such as improving the quality of life, improving respiratory functions, and reducing the rate of pulmonary exacerbations. The real-life side effects of the drug are still emerging due to the new use of modulator therapies and their new spread around the world. There are no proven protocols regarding these side effects yet. Strategies for managing adverse drug reactions to these drugs are important to ensure that as many patients as possible benefit from them. [ABSTRACT FROM AUTHOR]

Background: With ongoing COVID-19 vaccination schedules and the popularity of cosmetic fillers, it is important to examine and record associated adverse reactions to a more general audience of health care professionals. Case reports exist in subspecialty journals outlining reactions after SARS-CoV-2 infection and vaccination. This is one of the first cases published in Canada, and it highlights priorities and challenges faced by physicians in assessing and managing patients presenting with adverse reactions post vaccination. Case Presentation: We present a case of a 43 -year-old women with delayed type 4 hypersensitivity reaction to hyaluronic acid cosmetic filler triggered by COVID-19 mRNA vaccination. We outline the clinical presentation, diagnosis, complications, and treatment of a late inflammatory reaction to hyaluronic acid filler and highlight the treatment priorities for clinicians faced with similar presentations. Conclusion: The differential diagnosis of delayed onset nodules formation post filler injection is broad and includes redistribution of fillers, inflammatory reaction to biofilm, and delayed hypersensitivity reaction. As result, in order to make the right diagnosis, administer the appropriate treatment and achieve great cosmetic results, we highly recommend seeking expert opinion from dermatologist, plastic surgeon and allergist immunologist in a timely manner. [ABSTRACT FROM AUTHOR]

Background: Hyaluronic acid fillers have been increasingly used throughout the world in the management of aging skin in the periocular region and other areas. Objective: To evaluate very late‐term orbital mass formation secondary to Hyaluronic acid filler injection into the inferior eyelid. Methods: We report two cases that presented with a subcutaneous palpable mass localized at the right medial lower infraorbital area. Following clinical and radiological examination, surgical excision was required for the differential diagnosis of tumor. Results: After pathologic examination and the finding of a foreign‐body granulomatous reaction, both patients recalled that hyaluronic acid filler had once been injected into their lower eyelids approximately 10 years prior. This is consistent with the fact that dermal‐filler‐related granuloma formation may occur even years later in the differential diagnosis of mass lesions. Conclusion: It is suggested that patients be informed about the possible but rare mass effect in the infraorbital region. Clinicians should also attend to delayed hypersensitivity reactions, since patients may not recall details due to the length of time since injection. [ABSTRACT FROM AUTHOR]

To our knowledge, sweet bullous syndrome has been associated with contrast media only once in the literature, which makes our case very rare. Our patient developed, 48h after the realization of an injected scanner, a bullous eruption, cocardoides lesions and a fronto-malar erythema. The skin biopsy concluded to a bullous Sweet syndrome. The patient was treated with topical corticosteroids and the lesions disappeared after 7 days. Drug-induced sweet syndrome can mimic several other diagnoses. In our case, the malar erythema is reminiscent of lupus. Drug-induced sweet is a drug hypersensitivity reaction characterized by the following clinical signs: chronological development of a skin lesion following drug exposure, fever of 38.4°C, neutrophil infiltration in the dermis without vasculitis, and resolution of symptoms following steroid use, all of which were present in our case. We report a case of bullous sweet syndrome, an aggressive form which resolved with steroids. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) vaccines have long been suggested as encouraging candidates for widespread vaccination since they are manufactured rapidly and induce both humoral and cellular immune system components against pathogens. Available data on the efficacy and safety of these vaccines are relatively limited and the spectrum of skin reactions is still unclear. We would like to contribute to the literature by presenting a rare case with cutaneous reactions and discussing the skin complications of these kinds of vaccines. Our patient was a 17-year-old healthy female patient who applied to the pediatric emergency department with urticarial plaques that started from the legs and spread to the trunk nearly 80 hours after the second dose of the BioNTech-Pfizer COVID-19 vaccine was applied. The patient, whose skin lesions recurred more severely within 24 hours at home, and who noticed mild swelling in the fingers of the right hand and on the lip, was brought to the emergency service for the second time. Patients and physicians should be aware of the risk of delayed adverse skin reactions as well as the development of immediate hypersensitivity reactions such as urticaria and angioedema after administration of an mRNA COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Lenalidomide is considered a standard of care in multiple myeloma (MM) Some MM patients will develop delayed hypersensitivity to lenalidomide, which can lead to treatment discontinuation. Desensitization to lenalidomide can help these patients to complete treatment courses. Here, we aimed to review lenalidomide‐treated MM patients who developed delayed hypersensitivity‐induced rash and were treated with desensitization. Methods: A retrospective analysis of medical files of MM patients, who were desensitized to lenalidomide due to delayed hypersensitivity rash. Patients were treated between 2018 and 2022 at Hadassah Medical Center, Jerusalem, Israel. Results: Search of patients yielded 16 patients that underwent desensitization to lenalidomide within the study period. The desensitization protocol consisted of a slow, 3‐week‐long protocol with lenalidomide's target doses of 10, 15, and 25 mg/day. Of the 16 patients, 10 (62.5%) succeeded to complete the protocol and thus were able to complete lenalidomide treatment cycles. One patient with unsuccessful desensitization was subsequently treated with first‐generation IMiD thalidomide, with no rash appearing. None of the patients that were treated with desensitization had severe immune‐mediated or non‐dermatological adverse reactions. Conclusions: Desensitization to lenalidomide is safe and effective. Discontinuation of lenalidomide in MM patients with delayed hypersensitivity and no contraindication to desensitization should be discouraged. Collaboration between hematologists and allergists is needed. [ABSTRACT FROM AUTHOR]

Experimental exposure of healthy volunteers to the T‐cell dependent neoantigen keyhole limpet hemocyanin (KLH) permits the evaluation of immunomodulatory investigational medicinal product (IMP) pharmacology prior to the recruitment of patient populations. Despite widespread use, no standardized approach to the design and conduct of such studies has been agreed. The objective of this systematic review was to survey the published literature where KLH was used as a challenge agent, describing methodology, therapeutic targets addressed, and pharmacodynamic outcome measures. We searched MEDLINE, EMBASE, clinicaltrials.gov, and Cochrane CENTRAL for studies using KLH challenge in humans between January 1, 1994, and April 1, 2022. We described key study features, including KLH formulation, dose, use of adjuvants, route of administration, co‐administered IMPs, and end points. Of 2421 titles and abstracts screened, 46 met the inclusion criteria, including 14 (31%) early phase trials of IMP, of which 10 (71%) targeted T‐cell co‐stimulation. IMPs with diverse mechanisms demonstrated modulation of the humoral response to KLH, suggesting limited specificity of this end point. Two early phase IMP studies (14%) described the response to intradermal re‐challenge (delayed type hypersensitivity). Challenge regimens for IMP assessment were often incompletely described, and exhibited marked heterogeneity, including primary KLH dose (25‐fold variation: 100–2500 mcg), KLH formulation, and co‐administration with adjuvants. Methodological heterogeneity and failure to exploit the access to tissue‐level mechanism‐relevant end points afforded by KLH challenge has impaired the translational utility of this paradigm to date. Future standardization, characterization, and methodological development is required to permit tailored, appropriately powered, mechanism‐dependent study design to optimize drug development decisions. [ABSTRACT FROM AUTHOR]

Background: Renal complications have previously been reported with various vaccinations, including those for influenza and hepatitis. On a similar note, a spectrum of nephrological complications, both de novo, and flare-ups, were reported after immunization with various coronavirus disease 2019 (COVID-19) vaccines, causing concerns among patients as well as physicians. Materials and Methods: A systematic search of the literature published on renal complications seen post-COVID-19 vaccination was performed up to April 2022 using electronic databases such as PubMed and Google Scholar. Result: Immunoglobulin A (IgA) nephropathy, minimal change disease, glomerulonephritis, acute kidney injury, nephrotic syndrome, and anti-neutrophil cytoplasmic antibody-associated vasculitis were some of the renal complications reported upon administration of COVID-19 vaccines. The causality and underlying pathogenic mechanisms linking these complications and COVID-19 vaccination remain unclear. Nonetheless, a temporal relationship has been established with dysregulated T-cell response, transient systemic pro-inflammatory cytokine response, molecular mimicry, delayed hypersensitivity reaction to the vaccine, and other mechanisms such as hyperresponsive IgA, dysregulation of neutrophil extracellular traps were hypothesized as the possible mechanisms linking renal complications and COVID-19 vaccination. Conclusion: This review emphasizes the need for rigorous surveillance and reporting of the adverse events following COVID-19 vaccination and explores the underlying mechanisms instigating these renal complications in individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). [ABSTRACT FROM AUTHOR]

Introduction: Oral Lichen Planus (OLP) is a chronic disorder and its aetiology is multifactorial. Factors like local and systemic inducers of cell-mediated hypersensitivity, stress, autoimmune response and viral infection play a major role. Due to the varying aetiological factors, there are varying treatment modalities. With systemic medication, remission of the lesion is the most common side-effect. Aim: To determine the efficacy of carbon dioxide laser in treating OLP. Materials and Methods: In this systematic review, the study was done between January 2022 to April 2022 at Rajas Dental College and Hospital, Tamil Nadu. Search categories were specifically followed to databases like PubMed, PubMed Central, Cochrane, Medline, Embase and in Google Scholar. MeSH terms like CO2 Laser, OLP, Carbondioxide Laser and Oral Premalignant Condition were used for searching the articles. Results: A total of 942 articles had been collected. But after analysing the articles, only 16 articles based on the preformed inclusion and exclusion criteria had been selected. Out of these three were retrospective studies, five were prospective studies, one clinical trial, one observational study and one study was a Randomised Control Trial (RCT), one was a non RCT, one was a structured abstract, one was a single arm intervention study, one was a case series, and one was a case report. Conclusion: Carbon dioxide laser was very efficient in treating larger size lesions. Recurrence rate of the lesions was very less when treated at an early stage. [ABSTRACT FROM AUTHOR]

• Vero cell culture-derived Japanese encephalitis vaccine (JE-VC; Ixiaro) was approved for adults in 2009. • We retrospectively evaluated adverse events of special interest following JE-VC, including hypersensitivity and neurologic events. • Data from U.S. military personnel who received JE-VC were compared to data from recipients of Vi capsular polysaccharide typhoid vaccine, a vaccine with a favorable safety profile. • The risk of adverse events of special interest was similar between groups, supporting the safety of JE-VC. Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC; Ixiaro) was approved in the United States in 2009. The previous JE vaccine, an inactivated mouse brain-derived vaccine, had been associated with rare, but serious, allergic and neurologic adverse events (AE). Studies and AE surveillance have supported JE-VC's safety, but one evaluation among military personnel found elevated hypersensitivity and neurologic AE rates. However, co-administration of multiple vaccines to some personnel might have affected results. We retrospectively compared rates of hypersensitivity and neurologic AEs within 28 days following vaccination of military personnel with JE-VC or parenteral Vi capsular polysaccharide typhoid vaccine administered without other vaccines from July 1, 2011, through August 31, 2019. Rates of most events were similar between the vaccines. Only delayed hypersensitivity reactions occurred more frequently following JE-VC (rate ratio: 4.2, 95 % CI 1.2–15.3; p = 0.03), but rates were low for both vaccines. These results support JE-VC's safety. [ABSTRACT FROM AUTHOR]

Heat shock protein 70 (HSP70) production is a stress-generated cellular response with high interspecies homology. HSP70 has both chaperone and cytokine functions and may induce, depending on the context, tolerogenic anti-inflammatory reactivity or immunogenic and autoimmune reactivity. Intracellular (chaperoning transit of antigens to MHC in antigen-presenting cells) and extracellular HSP70-related effects are associated with hypertension, which is an inflammatory condition recognized as the most important risk factor for cardiovascular disease mortality. Here, we review (a) the relationship between HSP70, inflammation and immune reactivity, (b) clinical evidence relating to stress, HSP70 and anti-HSP70 reactivity with primary hypertension and (c) experimental data showing that salt-sensitive hypertension is associated with delayed hypersensitivity to HSP70. This is a consequence of anti-HSP70 reactivity in the kidneys and may be prevented and corrected by the T-cell-driven inhibition of kidney inflammation triggered by specific epitopes of HSP70. Finally, we discuss our postulate that lifelong stress signals and danger-associated molecular patterns stimulate HSP-70 and individual genetic and epigenetic characteristics determine whether the HSP70 response would drive inflammatory immune reactivity causing hypertension or, alternatively, would drive immunomodulatory responses that protect against hypertension. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]