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Background: Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma concentration of benzylpenicillin and cloxacillin in patients with IE and explore associations between antibiotic concentrations and DHR. Methods: Plasma concentrations of benzylpenicillin and cloxacillin were measured as centre (midpoint concentrations between consecutive doses) and trough values during the first and third weeks of treatment in patients with IE. Patient characteristics and outcomes, including DHR, were documented. Results: A total of 55 patients were included, with 37 patients (67%) receiving benzylpenicillin and 18 (33%) receiving cloxacillin. The 90-day mortality rate was 3%. Both centre and trough concentration exhibited substantial interpatient variation for the two antibiotics, while intra-patient variability between weeks 1 and 3 remained low for most patients. Kidney function could explain, at best, 54% of the variation, and a multiple regression model including kidney function, body mass index, age, and albumin explained up to 68% of the variation for benzylpenicillin. There was no relation between high plasma concentration and the prevalence of DHR; conversely, we observed a tendency of low plasma concentrations in these patients. Conclusions: This study revealed significant interindividual variation in plasma concentrations for both studied penicillins. TDM might be useful in situations where concentrations are hard to predict, such as severe obesity or kidney failure. Additionally, we found no indication that high plasma concentrations are related to the prevalence of DHR. [ABSTRACT FROM AUTHOR]

Purpose: The occurrence of a hypersensitivity reaction with the injection of botulinum toxin type A (BTX-A) in cosmetic use is a rare complication. We report the largest case series of temporary delayed hypersensitivity reaction (DHR) with BTX-A following COVID-19 vaccination and the first cases to incobotulinum toxin A (incoBTX-A). Methods: A retrospective multicentric case series of patients who developed a DHR to BTX-A after COVID-19 vaccination. Results: Twelve patients were treated with BTX-A injections for the management of facial rhytids. The age range was between 29 and 45 years. Ten (83.3%) were female. Ten (83.3%) patients received incoBTX-A, and two received onabotulinum toxin A (onaBTX-A). All patients had COVID-19 vaccination (mRNA vaccine) between 1 and 7 months before. Within an average time of 24 h after BTX-A injection, all patients developed progressive facial swelling and erythema that were more prominent at the injection points. Intradermal allergic tests to BTX-A were performed in six (50%) patients, and the results were all negative. Adequate clinical control was achieved with systemic corticosteroids and antihistamines. After 1 year with no further vaccination, a new BTX-A treatment (provocation test) was performed in all patients with no secondary effects. Conclusion: Previous COVID-19 vaccination and the absence of new adverse events with further BTX-A injections suggest a temporary DHR. Clinicians should be aware of the importance of immunization history and its potential post-vaccine immunogenic effects with BTX-A. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authorswww.springer.com/00266. [ABSTRACT FROM AUTHOR]

Abstract Background To report a case of Bilateral Purtscher-like retinopathy associated with DRESS syndrome managed with ocular and systemic treatments. Case presentation A 29-year-old healthy female developed multi-organ (cutaneous, hematologic, renal and hepatic) disfunction and profound vision loss 1 month after Human papillomavirus vaccine injection. At the first presentation, her visual acuity was counting fingers in both eyes. Fundus exam showed remarkable cotton-wool spots, retinal hemorrhages and macular edema. She was diagnosed DRESS syndrome and Purtscher-like retinopathy and treated with intravitreal injection of ranibizumab, systemic steroids anticoagulants, and plasma exchange. The patient finally recovered from this life-threatening condition but left with permanent visual damage. Conclusion Purtscher-like retinopathy could be complicated by DRESS syndrome which is usually considered a type IV hypersensitivity reaction.

Background: To report a case of Bilateral Purtscher-like retinopathy associated with DRESS syndrome managed with ocular and systemic treatments. Case presentation: A 29-year-old healthy female developed multi-organ (cutaneous, hematologic, renal and hepatic) disfunction and profound vision loss 1 month after Human papillomavirus vaccine injection. At the first presentation, her visual acuity was counting fingers in both eyes. Fundus exam showed remarkable cotton-wool spots, retinal hemorrhages and macular edema. She was diagnosed DRESS syndrome and Purtscher-like retinopathy and treated with intravitreal injection of ranibizumab, systemic steroids anticoagulants, and plasma exchange. The patient finally recovered from this life-threatening condition but left with permanent visual damage. Conclusion: Purtscher-like retinopathy could be complicated by DRESS syndrome which is usually considered a type IV hypersensitivity reaction. [ABSTRACT FROM AUTHOR]

Background: Granulomatous inflammation is a persistent inflammatory reaction marked by the presence of aggregations of active histiocytes, epithelioid cells, and multinucleate giant cells. This phenomenon is reported in several viral and non-infectious diseases and is classified as a type IV delayed hypersensitivity response. Research Materials and Procedures: The present cross-sectional study was conducted in the histopathology section of the Department of Pathology, MMIMSR, Mullana, from October 2022 to October 2023. A total of 100 cases presenting with granulomatous lesions were analyzed. Detailed clinical data, including age, sex, site of the lesion, and duration of disease, were recorded. Histopathological examination was performed using Hematoxylin and Eosin (H&E) stain, with additional special stains like Ziehl-Neelsen and Periodic Acid-Schiff (PAS) applied where necessary. Materials and Methods: This investigation was conducted at the histology division of the Department of Pathology, MMIMSR, Mullana, between October 2022 and October 2023. The analysis included a total of 100 patients that had granulomatous lesions. Precise clinical information, such as age, gender, location of the lesion, and length of illness, was documented. The histological analysis was conducted using hematoxylin and eosin (H and E) stain, along with supplementary specific stains, such as Ziehl-Neelsen and periodic acid-Schiff (PAS) when needed. Results: Lesions of granulomatous nature were more common in individuals in their third and fourth decades of life, with a little higher occurrence in females (male: female ratio = 1:1.43). The primary location of infection was the gastrointestinal system, accounting for 16% of cases, followed by the urogenital tract at 15% and soft tissues at 13%. Granulomatous pathology-not otherwise specified (GP-NOS) was the most prevalent histological category, representing 52% of cases. It was followed by granulomatous pathology-tubercular (GP-TB) at 15%, granulomatous pathology-leprosy (GP-L) at 3%, and one case of granulomatous pathology-fungal (GP-F). The etiology of 25% of cases was attributed to tuberculosis, whereas in 3% of instances, it was diagnosed as leprosy. The main kind of neoplasms seen were epithelioid cell granulomas, with caseous necrosis being the most prevalent form of necrosis. About 10% of patients had fibrosis, and Langhans giant cells were often documented. Conclusion: Histopathology, with the use of certain stains, continues to be the most reliable method for identifying and classifying granulomatous lesions. Despite the broad use of Bacillus Calmette-Guerin (BCG) vaccine, infections, including tuberculosis (TB), remain the primary cause of granulomatous lesions in our community.

ABSTRACT: Background: Granulomatous inflammation is a persistent inflammatory reaction marked by the presence of aggregations of active histiocytes, epithelioid cells, and multinucleate giant cells. This phenomenon is reported in several viral and non-infectious diseases and is classified as a type IV delayed hypersensitivity response. Research Materials and Procedures: The present cross-sectional study was conducted in the histopathology section of the Department of Pathology, MMIMSR, Mullana, from October 2022 to October 2023. A total of 100 cases presenting with granulomatous lesions were analyzed. Detailed clinical data, including age, sex, site of the lesion, and duration of disease, were recorded. Histopathological examination was performed using Hematoxylin and Eosin (H&E) stain, with additional special stains like Ziehl-Neelsen and Periodic Acid-Schiff (PAS) applied where necessary. Materials and Methods: This investigation was conducted at the histology division of the Department of Pathology, MMIMSR, Mullana, between October 2022 and October 2023. The analysis included a total of 100 patients that had granulomatous lesions. Precise clinical information, such as age, gender, location of the lesion, and length of illness, was documented. The histological analysis was conducted using hematoxylin and eosin (H and E) stain, along with supplementary specific stains, such as Ziehl-Neelsen and periodic acid-Schiff (PAS) when needed. Results: Lesions of granulomatous nature were more common in individuals in their third and fourth decades of life, with a little higher occurrence in females (male: female ratio = 1:1.43). The primary location of infection was the gastrointestinal system, accounting for 16% of cases, followed by the urogenital tract at 15% and soft tissues at 13%. Granulomatous pathology-not otherwise specified (GP-NOS) was the most prevalent histological category, representing 52% of cases. It was followed by granulomatous pathology-tubercular (GP-TB) at 15%, granulomatous pathology-leprosy (GP-L) at 3%, and one case of granulomatous pathology-fungal (GP-F). The etiology of 25% of cases was attributed to tuberculosis, whereas in 3% of instances, it was diagnosed as leprosy. The main kind of neoplasms seen were epithelioid cell granulomas, with caseous necrosis being the most prevalent form of necrosis. About 10% of patients had fibrosis, and Langhans giant cells were often documented. Conclusion: Histopathology, with the use of certain stains, continues to be the most reliable method for identifying and classifying granulomatous lesions. Despite the broad use of Bacillus Calmette-Guerin (BCG) vaccine, infections, including tuberculosis (TB), remain the primary cause of granulomatous lesions in our community. [ABSTRACT FROM AUTHOR]

Introduction Bupropion is an antidepressant approved for the treatment of major depressive disorder (MDD), seasonal affective disorder, and smoking cessation. Nausea, headache, tremor, and insomnia are well-known adverse effects of this medication. Less well-recognized adverse effects include delayed allergic reactions, which, in some cases, can appear 2 or more weeks after bupropion initiation. Case Report A 27-year-old male with recurrent MDD was referred for medication treatment at an outpatient mental health clinic and prescribed bupropion XL. On day 28 of treatment, he reported significant improvement in depressive symptoms and the development of itchiness and urticaria on his extremities and back. Bupropion was tapered over the course of 7 days, and he was given cetirizine 10 mg daily. He was transitioned to venlafaxine treatment and experienced complete resolution of hives and pruritus. Discussion Despite published reports on bupropion causing delayed hypersensitivity reactions, there remains limited clinical recognition of this side effect, and the risk of underrecognition may be greater when the onset of the reaction is more than 2 weeks after bupropion initiation. Conclusion Bupropion can cause delayed hypersensitivity reactions, including delayed pruritis and urticaria. The risk may be highest in males aged 17 to 40 years and those with a history of allergic reactions.

Background: Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma concentration of benzylpenicillin and cloxacillin in patients with IE and explore associations between antibiotic concentrations and DHR. Methods: Plasma concentrations of benzylpenicillin and cloxacillin were measured as centre (midpoint concentrations between consecutive doses) and trough values during the first and third weeks of treatment in patients with IE. Patient characteristics and outcomes, including DHR, were documented. Results: A total of 55 patients were included, with 37 patients (67%) receiving benzylpenicillin and 18 (33%) receiving cloxacillin. The 90-day mortality rate was 3%. Both centre and trough concentration exhibited substantial interpatient variation for the two antibiotics, while intra-patient variability between weeks 1 and 3 remained low for most patients. Kidney function could explain, at best, 54% of the variation, and a multiple regression model including kidney function, body mass index, age, and albumin explained up to 68% of the variation for benzylpenicillin. There was no relation between high plasma concentration and the prevalence of DHR; conversely, we observed a tendency of low plasma concentrations in these patients. Conclusions: This study revealed significant interindividual variation in plasma concentrations for both studied penicillins. TDM might be useful in situations where concentrations are hard to predict, such as severe obesity or kidney failure. Additionally, we found no indication that high plasma concentrations are related to the prevalence of DHR.

Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis. [ABSTRACT FROM AUTHOR]

Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment. [ABSTRACT FROM AUTHOR]

Summary: This case report describes a healthy 25-year-old woman who underwent lip filler augmentation and developed a delayed hypersensitivity reaction not once but four times. A Caucasian female with no medical history presented to the authors in March 2022 with diffuse painful swelling on the left upper lip. Upon examination, the affected area was soft and tender on palpation, with no palpable nodules or lumps. Five days later,the patient reported waking up with tenderness and swelling on her right upper lip this time. Two months after this incident the patient reported that she had experienced two similar incidents at the beginning of May. She again reported waking up with the same symptoms on her right upper lip, which spontaneously resolved within 48 h; and then four days later, she exhibited the same symptoms on her left upper lip. When questioned, she did not recall any flu-like symptoms or signs of COVID-19. She had been vaccinated against COVID-19, but this was long before she had lip fillers injected, namely, in 2020 (two years before the events described here). In this case, no obvious triggering factor was identified, apart from the fact that the patient had been stressed due to upcoming examination. Stress is known to cause flares of autoimmune or infectious diseases, such as herpes simplex virus, through complicated processes that influence immune function. Therefore, stress could have been the triggering factor in the current case.

Aims: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, drug‐induced severe adverse reaction that usually occurs 3–6 weeks after initial exposure to certain drugs. It affects mainly adults and children to a lesser extent. Clinical features include fever, facial oedema, generalized skin rash, lymphadenopathy, haematological abnormalities and internal organ involvement. The objective was to investigate the clinical and laboratory features of patients with DRESS in our centre. Methods: We retrospectively describe and analyse 19 cases of DRESS whose diagnosis was based on the RegiSCAR criteria (≥6 points) that occurred from January 2009 to December 2019. Results: Patient age ranged from 4 to 76 years (4 children/15 adults); 10 were female (52.3%). The most common culprit drugs were antibiotics (74%) and anticonvulsants (21%). The most common comorbidities were epilepsy (26%) and hypertension (26%). All patients developed cutaneous manifestations and of those, 58% presented facial oedema. Liver function tests, urea/creatinine and troponin elevation were present in 74, 32 and 42%, respectively. The median time to develop the skin rash after the drug exposure was 3.7 weeks (interquartile range 2.4–4.2 wk). Eosinophilia (≥0.7 × 109/L) was present in 95% of the patients and peaked around 10 days after the skin manifestations. Leucocytosis and reactive lymphocytes were reported in 84% and 26% of all patients respectively. Treatment with systemic steroids was reported in 16 patients. The mean recovery time was 2 weeks (interquartile range 2–3.5 wk) and mortality was 5%. Conclusion: DRESS is a serious condition with significant morbidity and mortality, which requires more research for a better understanding. [ABSTRACT FROM AUTHOR]

Delayed drug T-cell immune-mediated hypersensitivity reactions have a large clinical heterogeneity varying from mild maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and severe skin necrosis and blistering as seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Given the knowledge gaps related to the immunopathogenesis of these conditions, the absence of validated diagnostic tools and the significant associated morbidity and mortality, patients with SCARs often have limited drug choices. We performed a comprehensive review aiming to evaluate in vivo diagnostic tools such as delayed intradermal skin and patch testing and ex vivo/in vitro research assays such as the lymphocyte transformation test (LTT) and the enzyme-linked ImmunoSpot (ELISpot) assay. We searched through PubMed using the terms “drug allergy,” “in vivo” and “ex vivo” for original papers in the last 10 years. A detailed meticulous approach adapted to the various clinical phenotypes is recommended for the diagnostic and management of delayed drug hypersensitivity reactions. This review highlights the current diagnostic tools for the delayed drug hypersensitivity phenotypes.

Introduction: Multiform exudative erythema is a rare delayed hypersensitivity reaction associated with medications. The manifestations caused by hydroxychloroquine are exceptional; however, due to the increase in its prescription due to the recent SARS-CoV-2 pandemic, adverse reactions have been exacerbated. Case report: A 60-year-old female patient, who attended the Emergency Department for a picture of erythematous rash of one week of evolution, with involvement of the trunk, face and palms of the hands. Laboratory studies reported: leukocytosis with neutrophilia and lymphopenia, without eosinophilia or abnormal liver enzymes. The lesions continued to descend towards her extremities, with subsequent desquamation. She was prescribed prednisone 15 mg/24 h for three days, tapering to 10 mg/24 h, until her new assessment, in addition to antihistamines. Two days later, new macular lesions appeared in the presternal area and on the oral mucosa. Control laboratory studies did not show alterations. Skin biopsy reported: vacuolar interface dermatitis with spongiosis and parakeratosis, compatible with erythema multiforme. Epicutaneous tests were carried out with meloxicam and 30% hydroxychloroquine in water and vaseline, occluded for two days and interpreted at 48 and 96 hours, with a positive result for the latter. The diagnosis of multiform exudative erythema due to hydroxychloroquine was established. Conclusion: This study confirms the efficacy of patch tests in patients with delayed hypersensitivity reactions to hydroxychloroquine. [ABSTRACT FROM AUTHOR]

Because of the increasing emergence of cutaneous reactions from COVID-19 vaccines worldwide, we investigated the published reports of these complications. We searched the PubMed, Google Scholar, and Scopus databases and the preprint server bioRxiv for articles on cutaneous complications linked to mRNA-1273 (Moderna), BNT162b2 (Pfizer–BioNTech), and AZD1222 (AstraZeneca–Oxford University) vaccines published until 30 September 2021. Eighty studies describing a total of 1415 reactions were included. Cutaneous reactions were more prevalent in females (81.6%). Delayed large local reactions were the most common complication (40.4%), followed by local injection site reactions (16.5%), zoster (9.5%), and urticarial eruptions (9.0%). Injection site and delayed large local reactions were predominantly caused by the mRNA-1273 vaccine (79.5% and 72.0%, respectively). BNT162b2 vaccination was more closely linked to distant reactions (50.1%) than mRNA-1273 (30.0%). Zoster was the most common distant reaction. Of reactions with adequate information for both vaccine doses, 58.3% occurred after the first dose only, 26.9% after the second dose only, and 14.8% after both doses. Overall, a large spectrum of cutaneous reaction patterns occurred following the COVID-19 vaccination. Most were mild and without long-term health implications. Therefore, the occurrence of such dermatologic complications does not contraindicate subsequent vaccination. [ABSTRACT FROM AUTHOR]

Abstract Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that has been known since the early 1990s. Swallowed topical corticosteroids (STC) belong to the therapeutic cornerstones. We describe a delayed hypersensitivity reaction to Jorveza®, a newly developed orodispersible budesonide tablet licensed for the treatment of eosinophilic esophagitis. Case presentation A 32-year-old Caucasian woman with EoE was newly treated with Jorveza®. Hours after the first intake, she felt a “strange pruritus” in the throat. This sensation worsened with each subsequent intake. On day 4 she developed oral mucosal symptoms (paresthesia of the tongue, sore and an itchy throat). Intraoral, throat and facial swellings, but no systemic reaction were observed. Patch testing using two commercial test series as well as the orodispersible budesonide tablet revealed a strong sensitization, proving a T cell mediated allergy to budesonide. Conclusions Orodispersible budesonide is increasingly prescribed for the treatment of eosinophilic esophagitis. The development of oropharyngeal symptoms after initiating should alert the treating physician to the possibility of a hypersensitivity reaction.

Scleral necrosis following ocular surgery can lead to significant ocular and systemic complications. The two most prevalent procedures associated with surgically-induced scleral necrosis are pterygium excision and cataract surgery. This condition represents a rare delayed hypersensitivity reaction. We present a case of a male patient in his late 60s from India who experienced progressive scleral necrosis in his right eye six months after undergoing small-incision cataract surgery (SICS). The patient exhibited pain and redness without any decline in vision, and all systemic evaluations returned normal results. Ultimately, he was scheduled for a scleral patch graft. This case emphasizes the necessity for rapid diagnosis of surgically-induced necrotizing scleritis (SINS) and timely intervention., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vatkar et al.)

Introduction:Ex vivo and in vitro diagnostics, such as interferon-γ (IFN-γ) release enzyme linked ImmunoSpot (ELISpot) and flow cytometry, are increasingly employed in the research and diagnostic setting for severe T-cell mediated hypersensitivity. Despite an increasing use of IFN-γ release ELISpot for drug causality assessment and utilization of a range of antimicrobial concentrations ex vivo, data regarding antimicrobial-associated cellular cytotoxicity and implications for assay performance remain scarcely described in the literature. Using the measurement of lactate dehydrogenase (LDH) and the 7-AAD cell viability staining, we aimed via an exploratory study, to determine the maximal antimicrobial concentrations required to preserve cell viability for commonly implicated antimicrobials in severe T-cell mediated hypersensitivity.Method: After an 18-h incubation of patient peripheral blood monocytes (PBMCs) and antimicrobials at varying drug concentrations, the cell cytotoxicity was measured in two ways. A colorimetric based assay that detects LDH activity and by flow cytometry using the 7-AAD cell viability staining. We used the PBMCs collected from three healthy control participants with no known history of adverse drug reaction and two patients with a rifampicin-associated drug reaction with eosinophilia and systemic symptoms (DRESS), confirmed on IFN-γ ELISpot assay. The PBMCs were stimulated for the investigated drugs at the previously published drug maximum concentration (Cmax), and concentrations 10- and 100-fold above.Results: In a human immunodeficiency virus (HIV) negative and a positive rifampicin-associated DRESS with positive ex vivo IFN-γ ELISpot assay, use of 10- and 100-fold Cmax drug concentrations decreased spot forming units/million cells by 32–100%, and this corresponded to cell cytotoxicity of more than 40 and 20% using an LDH assay and 7-AAD cell viability staining, respectively. The other antimicrobials (ceftriaxone, flucloxacillin, piperacillin/tazobactam, and isoniazid) tested in healthy controls showed similar dose-dependent increased cytotoxicity using the LDH assay, but cytotoxicity remained lower than 40% for all Cmax and 10-fold Cmax drug concentrations except flucloxacillin. All 100-fold Cmax concentrations resulted in cell death >40% (median 57%), except for isoniazid. 7-AAD cell viability staining also confirmed an increase in lymphocyte death in PBMCs incubated with 10-fold and 100-fold above Cmax for ceftriaxone, and flucloxacillin; however, piperacillin/tazobactam and isoniazid indicated no differences in percentages of viable lymphocytes across concentrations tested.Conclusion: The LDH cytotoxicity and 7-AAD cell viability staining techniques both demonstrate increased cell death corresponding to a loss in ELISpot sensitivity, with use of higher antimicrobial drug concentrations for ex vivo diagnostic IFN-γ ELISpot assays. For all the antimicrobials evaluated, the use of Cmax and 10-fold Cmax concentrations impacts cell viability and potentially affects ELISpot performance. These findings inform future approaches for ex vivo diagnostics such as IFN-γ release ELISpot.

Background: Multiple drug hypersensitivity syndrome (MDHS) results in treatment delay or failure and often results in severe drug hypersensitivity reactions. There are few reports of MDHS in response to anti-tuberculosis drugs; however, clinical information is scarce. Understanding the frequency and clinical characteristics of simultaneous MDHS against first-line anti-tuberculosis drugs in patients with non-severe drug hypersensitivity reactions is necessary. Methods: We reviewed 27 patients with drug fever or maculopapular exanthem in response to first-line anti-tuberculosis drugs between January 2010 and June 2019. Drug fever or maculopapular exanthem occurred when isoniazid, rifampin, ethambutol, and pyrazinamide were administered simultaneously. Drug provocation tests for the 4 drugs were performed to identify the culprit drugs. Results: All patients showed positive reactions to 1 or more drugs. MDHS was diagnosed in 13 (48%) patients, of whom 11 and 2 patients reacted to 2 and 3 drugs, respectively. In comparison to the patients with single-drug hypersensitivity, the patients with MDHS did not exhibit any differences in characteristics. Ethambutol and rifampin were the common drugs that induced a reaction, and the combination of these 2 drugs induced MDHS most frequently. Among the patients with MDHS, there were no differences between the drugs that caused drug fever and maculopapular exanthem. All patients with MDHS were successfully treated with alternative drugs. Conclusions: Simultaneous MDHS may occur frequently in patients with drug fever or maculopapular exanthem caused by first-line anti-tuberculosis drugs, indicating the need to evaluate the allergy responses for all 4 drugs, even in patients without severe drug hypersensitivity. The combination of ethambutol and rifampin was the most common trigger that induced MDHS.

Introduction: Ex vivo and in vitro diagnostics, such as interferon-γ (IFN-γ) release enzyme linked ImmunoSpot (ELISpot) and flow cytometry, are increasingly employed in the research and diagnostic setting for severe T-cell mediated hypersensitivity. Despite an increasing use of IFN-γ release ELISpot for drug causality assessment and utilization of a range of antimicrobial concentrations ex vivo , data regarding antimicrobial-associated cellular cytotoxicity and implications for assay performance remain scarcely described in the literature. Using the measurement of lactate dehydrogenase (LDH) and the 7-AAD cell viability staining, we aimed via an exploratory study, to determine the maximal antimicrobial concentrations required to preserve cell viability for commonly implicated antimicrobials in severe T-cell mediated hypersensitivity. Method: After an 18-h incubation of patient peripheral blood monocytes (PBMCs) and antimicrobials at varying drug concentrations, the cell cytotoxicity was measured in two ways. A colorimetric based assay that detects LDH activity and by flow cytometry using the 7-AAD cell viability staining. We used the PBMCs collected from three healthy control participants with no known history of adverse drug reaction and two patients with a rifampicin-associated drug reaction with eosinophilia and systemic symptoms (DRESS), confirmed on IFN-γ ELISpot assay. The PBMCs were stimulated for the investigated drugs at the previously published drug maximum concentration (Cmax), and concentrations 10- and 100-fold above. Results: In a human immunodeficiency virus (HIV) negative and a positive rifampicin-associated DRESS with positive ex vivo IFN-γ ELISpot assay, use of 10- and 100-fold Cmax drug concentrations decreased spot forming units/million cells by 32–100%, and this corresponded to cell cytotoxicity of more than 40 and 20% using an LDH assay and 7-AAD cell viability staining, respectively. The other antimicrobials (ceftriaxone, flucloxacillin, piperacillin/tazobactam, and isoniazid) tested in healthy controls showed similar dose-dependent increased cytotoxicity using the LDH assay, but cytotoxicity remained lower than 40% for all Cmax and 10-fold Cmax drug concentrations except flucloxacillin. All 100-fold Cmax concentrations resulted in cell death >40% (median 57%), except for isoniazid. 7-AAD cell viability staining also confirmed an increase in lymphocyte death in PBMCs incubated with 10-fold and 100-fold above Cmax for ceftriaxone, and flucloxacillin; however, piperacillin/tazobactam and isoniazid indicated no differences in percentages of viable lymphocytes across concentrations tested. Conclusion: The LDH cytotoxicity and 7-AAD cell viability staining techniques both demonstrate increased cell death corresponding to a loss in ELISpot sensitivity, with use of higher antimicrobial drug concentrations for ex vivo diagnostic IFN-γ ELISpot assays. For all the antimicrobials evaluated, the use of Cmax and 10-fold Cmax concentrations impacts cell viability and potentially affects ELISpot performance. These findings inform future approaches for ex vivo diagnostics such as IFN-γ release ELISpot. [ABSTRACT FROM AUTHOR]

Delayed-onset nodules (DONs) represent a poorly understood and generally neglected group of complications. It is not a diagnosis. The underlying pathologies and their incidences are largely unknown due to the lack of specificity in clinical signs and the challenges in accessing diagnostic tests, cost implications, or reluctance from patients to undergo them. A lack of presumptive clinical diagnosis, coupled with management ranging from "scatter-gun" polypharmacy to clinical inertia, is believed to result in chronicity and increased morbidity. This paper provides guidance on the identification and understanding of the underlying pathologies and encourages the increased utilization of a medical model of care. The more routine adoption of histopathology, inflammatory markers, and ultrasound will permit a more targeted management and a greater understanding of the incidences and evolution of the pathologies. [ABSTRACT FROM AUTHOR]

Purpose of Review: Non-IgE-mediated drug reactions have traditionally been poorly defined and studied, though they are the most common form of hypersensitivity. Their presentations are highly variable and can range in severity from mild, cutaneous-only reactions to severe systemic disease. Recent Findings: The most notable advance in non-IgE-mediated hypersensitivity reactions is in diagnostics. HLA alleles have traditionally been used for identifying certain patients at risk for abacavir hypersensitivity syndrome, but more recent studies have shown several other HLA alleles associated with severe cutaneous adverse reactions with various medications. This article also highlights the use of delayed intradermal testing for radiocontrast media and patch testing for delayed antibiotic reactions. Summary: Drug reactions remain a major cause of morbidity and reason for treatment changes. Non-IgE-mediated reactions have had an increase in research interest over the past decade with an increased emphasis on better understanding the clinical presentation and underlying pathophysiology. [ABSTRACT FROM AUTHOR]

Delayed drug hypersensitivity reactions are clinically diverse reactions that vary from isolated benign skin conditions that remit quickly with no or symptomatic treatment, drug discontinuation or even continued drug treatment, to the other extreme of severe cutaneous adverse reactions (SCARs) that are associated with presumed life-long memory T-cell responses, significant acute and long-term morbidity and mortality. Diagnostic “in clinic” approaches to delayed hypersensitivity reactions have included patch testing (PT), delayed intradermal testing (IDT) and drug challenges for milder reactions. Patch and IDT are, in general, performed no sooner than 4–6 weeks after resolution of the acute reaction at the maximum non-irritating concentrations. Functional in vitro and ex vivo assays have largely remained the province of research laboratories and include lymphocyte transformation test (LTT) and cytokine release enzyme linked ImmunoSpot (ELISpot) assay, an emerging diagnostic tool which uses cytokine release, typically IFN-γ, after the patient’s peripheral blood mononuclear cells are stimulated with the suspected drug(s). Genetic markers such as human leukocyte antigen have shown recent promise for both pre-prescription screening as well as pre-emptive and diagnostic testing strategies.

Because of the increasing emergence of cutaneous reactions from COVID-19 vaccines worldwide, we investigated the published reports of these complications. We searched the PubMed, Google Scholar, and Scopus databases and the preprint server bioRxiv for articles on cutaneous complications linked to mRNA-1273 (Moderna), BNT162b2 (Pfizer–BioNTech), and AZD1222 (AstraZeneca–Oxford University) vaccines published until 30 September 2021. Eighty studies describing a total of 1415 reactions were included. Cutaneous reactions were more prevalent in females (81.6%). Delayed large local reactions were the most common complication (40.4%), followed by local injection site reactions (16.5%), zoster (9.5%), and urticarial eruptions (9.0%). Injection site and delayed large local reactions were predominantly caused by the mRNA-1273 vaccine (79.5% and 72.0%, respectively). BNT162b2 vaccination was more closely linked to distant reactions (50.1%) than mRNA-1273 (30.0%). Zoster was the most common distant reaction. Of reactions with adequate information for both vaccine doses, 58.3% occurred after the first dose only, 26.9% after the second dose only, and 14.8% after both doses. Overall, a large spectrum of cutaneous reaction patterns occurred following the COVID-19 vaccination. Most were mild and without long-term health implications. Therefore, the occurrence of such dermatologic complications does not contraindicate subsequent vaccination.

Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that has been known since the early 1990s. Swallowed topical corticosteroids (STC) belong to the therapeutic cornerstones. We describe a delayed hypersensitivity reaction to Jorveza®, a newly developed orodispersible budesonide tablet licensed for the treatment of eosinophilic esophagitis.Case Presentation: A 32-year-old Caucasian woman with EoE was newly treated with Jorveza®. Hours after the first intake, she felt a "strange pruritus" in the throat. This sensation worsened with each subsequent intake. On day 4 she developed oral mucosal symptoms (paresthesia of the tongue, sore and an itchy throat). Intraoral, throat and facial swellings, but no systemic reaction were observed. Patch testing using two commercial test series as well as the orodispersible budesonide tablet revealed a strong sensitization, proving a T cell mediated allergy to budesonide.Conclusions: Orodispersible budesonide is increasingly prescribed for the treatment of eosinophilic esophagitis. The development of oropharyngeal symptoms after initiating should alert the treating physician to the possibility of a hypersensitivity reaction. [ABSTRACT FROM AUTHOR]

Les héparines sont des anticoagulants utilisés dans la prévention des accidents thromboemboliques. Parmi les effets indésirables recensés pour cette classe médicamenteuse, on retrouve notamment des cas d'allergies. Celles-ci peuvent revêtir différentes formes et impliquent, quand elles se rencontrent chez un patient, une prise en charge adaptée. Nous rapportons le cas d'un patient opéré pour une reprise de prothèse totale de hanche (PTH) avec comme antécédent une allergie à l'héparine. Devant l'urgence de l'opération, aucune investigation clinique ou biologique n'a pu être faite afin de vérifier l'allergie. Le patient a donc été mis sous danaparoïde sodique en post-chirurgie et un relais par apixaban en prévention du risque thromboembolique a été réalisé, bien qu'il ne s'agisse pas du traitement de référence en cas d'antécédent d'allergie à l'héparine. Heparins are anticoagulants used in the prevention of thromboembolic events. Adverse reactions identified for this drug class include allergies. These can take different forms and involve, when they occur in a patient, appropriate management. We report the case of a patient operated on for a revision of a total hip replacement with a history of allergy to heparin. Given the urgency of the operation, no clinical or biological investigation could be carried out to verify the allergy. The patient was therefore placed on danaparoid sodic and apixaban has been introduced to prevent thromboembolic risk, although this is not the standard treatment for patients with a history of allergy to heparin. [ABSTRACT FROM AUTHOR]

Context: The seeds of Buchholzia coriacea Engler (Capparaceae) are used in Eastern Nigeria to treat feverish conditions, and to treat malaria and sleeping sickness that cause fever. Objective: The current study assesses the immunomodulatory activity of Buchholzia coriacea seed extract on Trypanosoma brucei brucei infected mice. Materials and methods: Delayed hypersensitivity reaction, humoral antibody response and in-vivo leucocyte mobilization tests were assessed in three different experiments to determine the effect of the extract on immune response. Seventy-five (75) mice (25 mice per experiment) were used for the study and were each infected with 1.00 × 106 trypanosomes intra-peritoneally. Groups A, B and C were given 250, 500 and 1000 mg/kg of the extract, respectively, group D received 7.5 mg/kg body weight of levamisole and group E was the control. Sheep RBCs were used as antigen. Results: The acute toxicity tests did not cause clinical signs or death within 24 h post treatment at all the doses tested. The extract inhibited delayed hypersensitivity reaction by 20.9 and 20.8% at 250 and 500 mg/kg, respectively, while at 1000 mg/kg, the paw size increased (−101.9%) when compared with the control. The extract elevated the antibody titre from 1.60 ± 0.40 for control to 8.00 ± 3.58 for 500 mg/kg group. The extract increased in total leucocytes counts. Discussion and conclusion: The extract has a very wide safety margin and was able to improve immune response. The results of the present study showed that Buchholzia coriacea seed methanol extract possesses immunostimulatory activity on trypanosome-infected mice.

Context:The seeds ofBuchholzia coriaceaEngler (Capparaceae) are used in Eastern Nigeria to treat feverish conditions, and to treat malaria and sleeping sickness that cause fever. Objective:The current study assesses the immunomodulatory activity ofBuchholzia coriaceaseed extract onTrypanosoma brucei bruceiinfected mice. Materials and methods:Delayed hypersensitivity reaction, humoral antibody response andin-vivoleucocyte mobilization tests were assessed in three different experiments to determine the effect of the extract on immune response. Seventy-five (75) mice (25 mice per experiment) were used for the study and were each infected with 1.00 × 106trypanosomes intra-peritoneally. Groups A, B and C were given 250, 500 and 1000 mg/kg of the extract, respectively, group D received 7.5 mg/kg body weight of levamisole and group E was the control. Sheep RBCs were used as antigen. Results:The acute toxicity tests did not cause clinical signs or death within 24 h post treatment at all the doses tested. The extract inhibited delayed hypersensitivity reaction by 20.9 and 20.8% at 250 and 500 mg/kg, respectively, while at 1000 mg/kg, the paw size increased (−101.9%) when compared with the control. The extract elevated the antibody titre from 1.60 ± 0.40 for control to 8.00 ± 3.58 for 500 mg/kg group. The extract increased in total leucocytes counts. Discussion and conclusion:The extract has a very wide safety margin and was able to improve immune response. The results of the present study showed thatBuchholzia coriaceaseed methanol extract possesses immunostimulatory activity on trypanosome-infected mice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the antitrypanosomal activity of Malva sylvestris (MS) extract in a Trypanosoma brucei brucei-infected mouse model of sleeping sickness. Methods: Sleeping sickness was induced by the intraperitoneal injection of Trypanosoma brucei bruceiinfected blood in mice. Confirmation of parasitaemia was performed by estimating the parasite count in the plasma on the 12th day after inoculation. All the mice were divided into five groups: control group that received neither infection nor treatment; negative control that was infected with the parasite but did not receive treatment; MS-treated group that receive MS extract (250 and 500 mg/kg, ip) and standard (STD) group that received levamisole (7.5 mg/kg, ip) for 7 days after the development of parasitaemia. A further parasite count was performed in the blood and cerebrospinal fluid (CSF) after the treatment period. Humoral antibody response, delayed hypersensitivity reaction, and mobilization of leucocytes were determined after the treatment period in SRBC-sensitized mice. Results: The results indicate that treatment with MS significantly decreased body weight and parasite count in the blood and CSF of mice with Trypanosoma brucei brucei-induced sleeping sickness compared with that in the negative control group. There was a significant increase in paw swelling and decrease in secondary antibody in the MS-treated group compared with that in the negative control group. However, treatment with MS extract also enhanced the mobilization of the total leucocyte count compared with that in the negative control group. Conclusion: The results demonstrate the anti-trypanosomal activity of Malva sylvestris extract via immunomodulation in a Trypanosoma brucei brucei-infected mouse model of sleeping sickness. [ABSTRACT FROM AUTHOR]

Résumé La pustulose exanthématique aiguë généralisée (PEAG) est une toxidermie sévère le plus souvent d'origine médicamenteuse. Nous rapportons un cas rare de PEAG survenue au décours d'un traitement au phénobarbital. Une patiente âgée de 22 et suivie pour une tuberculose pulmonaire sous traitement, développait un tableau de pustulose exanthématique fébrile après la prise de phénobarbital pour un tuberculome cérébrale. Le diagnostic de PEAG secondaire au phénobarbital était confirmé par la biopsie cutanée des lésions pustuleuses et un score d'imputabilité intrinsèque vraisemblable I3 (C2 S3). L'évolution était marquée par la régression complète des lésions cutanées après l'arrêt du phénobarbital. Abstract Acute generalized exanthematous pustulosis (AGEP) is a severe eruption chiefly induced by drugs. We report a rare case of AGEP occurring after treatment with phenobarbital. A 22-year-old woman developed febrile exanthematous pustulosis eruption after treatment with phenobarbital for cerebral tuberculoma. A diagnosis of phenobarbital-induced AGEP was made on the basis of a skin biopsy and of likely intrinsic imputability of I3 (C3 S3). Complete regression of lesions was obtained after withdrawal of the phenobarbital. [ABSTRACT FROM AUTHOR]

Following vaccination, patients can develop symptoms of eczema flare, which could range from mild skin irritation and urticaria to diffuse skin involvement. Delayed immunologic reactions have been described in association with the novel mRNA COVID-19 vaccines and boosters. We report the case of an 83-year-old female who presented with widespread pruritic urticarial indurated papules on the arms, legs, and palms, sparing the face six months following the booster vaccine. She denied constitutional symptoms, new medications, recent illnesses, or new personal care products. Punch biopsy demonstrated acanthosis, spongiosis, and superficial and mild dermal perivascular lymphocytic infiltration with occasional eosinophils compatible with a dermal hypersensitivity reaction. The patient was admitted to the hospital due to the need for systemic steroids as well as IV antibiotics secondary to a superimposed bacterial skin infection in the setting of severe itching and skin injury; she was discharged on oral steroids with follow-up to dermatology and rheumatology. Delayed hypersensitivity reactions typically peak within four days following vaccination and may be observed with COVID-19 vaccines or boosters. However, reports remain limited, and people's history of eczema should not preclude them from receiving a COVID-19 vaccine that is both safe and effective., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hanoodi et al.)

The article presents the case of an 82-year old woman, who was readmitted with chronic diarrhea of 8-month duration and weight loss of 20 kg. Duodenal biopsies have revealed subtotal villous atrophy with crypt hyperplasia and increased intraepithelial lymphocytes. The tissue transglutaminase antibodies and serum anti-endomysial antibodies were negative.

Delayed, or type IV, hypersensitivity reactions are a useful model to study the effects of new substances on the immune system. In this study, the experimental model of the delayed type hypersensitivity (DTH) reaction to ovalbumin (OVA) was used to evaluate the immunomodulating effects of low-level laser therapy (LLLT), which is used as an adjuvant therapy in medicine, dentistry, and physical therapy because of its potential anti-inflammatory and analgesic effects observed in several studies. The effects of LLLT (λ 780 nm, 0.06 W/cm of radiation, and fluency of 3.8 J/cm) in reaction to ovalbumin in Balb/C mice were examined after the induction phase of the hypersensitivity reaction. The animals treated with azathioprine (AZA), the animals that received a vehicle instead of ovalbumin, and those not immunized served as controls ( n = 6 for each group). Footpad thickness measurements and hematoxylin-eosin histopathological exams were performed. Proliferation tests were also performed (spontaneous, in the presence of concanavalin A and ovalbumin) to determine the production in mononuclear cells cultures of tumor necrosis factor-alpha (TNF-α), INF-γ, and IL-10. In the group of animals irradiated with lasers and in the group treated with AZA, footpad thickness measurements were significantly reduced in comparison to the control group ( p < 0.05). This reduction was accompanied by a very significant reduction in the density of the inflammatory infiltrate and by a significant reduction in the levels of TNF-α, INF-γ, and IL-10. LLLT radiation was shown to have an immunomodulating effect on DTH to OVA in Balb/C mice. [ABSTRACT FROM AUTHOR]

The effect of the methanolic extract of Mucuna pruriens seed was evaluated in mice with regards to delayed hypersensitivity reaction (DTR), primary and secondary antibody response and in vivo inflammatory leucocyte mobilization. The extract at 250 and 500 mg/kg produced significant ( p < 0.05) inhibition of DTR in mice by 33.33% and 28.89%, respectively. The extract caused elevation of secondary SRBCs-specific antibody titre with antibody response being significantly ( p < 0.05) increased at 250 and 500 mg/kg when compared with control. The extract at 250 and 500 mg/kg increased leucocyte mobilization significantly ( p < 0.05) when compared with the control and levamisole-treated groups. At 100 mg/kg, the mobilization did not differ with the levamisole-treated group but was significantly ( p < 0.05) higher than the control. The leucocyte mobilization was more of neutrophils than lymphocytes. The ability of the extract to inhibit the DTR, increase secondary antibody response and in vivo leucocyte mobilization was an indication that the extract probably influenced immune response in mice. [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: The leaves and rhizomes of Sansevieria trifasciata are used in folk medicine for treating bronchitis, asthma, cough, snake bite and insect bite etc. The ethanolic extract elicited analgesic, anti-inflammatory and antipyretic activity. Hence, it was decided to study the antiallergic activity of ethanolic extract of S. trifasciata (EEST) on various animal models as well as in vitro conditions, and also to understand possible mechanism of action. Materials and methods: Ethanolic extract of S. trifasciata leaves (EEST) were prepared by cold maceration followed by concentration and evaporation under reduced pressure on a rotary evaporator to obtain semisolid mass. The various phytoconstituents were analyzed. The acute toxicity study of EEST was carried out in mice. The antiallergic and anaphylactic activities were evaluated using animal models viz. milk induced eosinophilia and leukocytosis, compound 48/80 induced mast cell degranulation, active and passive cutaneous anaphylaxis and histamine induced pedal edema. In addition, EEST effect on Shultz–Dale reaction in sensitized guinea pig ileum in ex vivo and antioxidant activity by free radical scavenging by DPPH method (in vitro) were also studied. Results: EEST treatment at 100mg/kg and 200mg/kg p.o inhibited (a) milk-induced increased eosinophilia, leukocytosis, monocytes and neutrophils. (b) Prevented passive cutaneous and active anaphylactoid reactions. (c) Prevented compound 48/80 induced degranulation of sensitized mesenteric mast cells. (d) Inhibited histamine induced pedal edema formation significantly. EEST pretreatment inhibited Shultz–Dale reaction in guinea pig ileum and also elicited potent antioxidant activity. Conclusion: Experimental findings demonstrate promising antiallergic and anti-anaphylactic activity of EEST and also elicited potent antioxidant activity. The antiallergic and anti-anphylactic activity might be due to inhibition of release of chemical mediators from mast cells largely by phytoconstituents like steroidal saponins, triterpenoids and flavonoids present in EEST. [Copyright &y& Elsevier]

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In-stent restenosis is a complication which impairs the success of coronary stenting. Recently, it was supposed that a delayed hypersensitivity reaction to nickel and molybdenum might be one of the triggering factors in in-stent restenosis. We have analyzed the data collected in our centre with respect to this hypothesis. Altogether, 34 patients were investigated (24 male, 10 female). Patch tests were performed with the standard series of the German Contact Dermatitis Research Group and a metal series containing the metal components of 316 L stainless steel. A positive patch test reaction to nickel was observed in 4 (11.8%) patients. None of the patients showed sensitization to the other metals. Retrospective analysis was performed in 20 patients: 2 of these patients had a positive patch test reaction to nickel, one of whom had an in-stent restenosis, and the other not. Restenoses were predominantly observed in patients with negative patch test reactions to nickel (6/18 patients). Out of the patients who were investigated prospectively only one showed sensitization to nickel. Restenosis was observed in 2 patients: neither patient had nickel allergy. Although it still cannot be excluded that metal allergy may play a role in the restenosis process in coronary stenting, there is at present little evidence for it. [ABSTRACT FROM AUTHOR]

Keywords: delayed hypersensitivity reaction; drug allergy; severe cutaneous adverse reaction; t-cell; enzyme link immunospot; cytotoxicity; flow cytoametry; lactate dehydrogenase EN delayed hypersensitivity reaction drug allergy severe cutaneous adverse reaction t-cell enzyme link immunospot cytotoxicity flow cytoametry lactate dehydrogenase 1 1 1 09/06/21 20210902 NES 210902 In the original article, we mistakenly omitted a statement from the Funding section. Delayed hypersensitivity reaction, drug allergy, severe cutaneous adverse reaction, t-cell, enzyme link immunospot, cytotoxicity, flow cytoametry, lactate dehydrogenase The statement reads as follows: "JP receives financial support from National Institutes of Health, award K43TW011178-02; the EDCTP2 programme supported by the European Union, grant number TMA2017SF-1981 and the South African National Research Foundation (NRF). [Extracted from the article]

The effects of butylated hydroxyanisole and butylated hydroxytoluene on the immune status in normal male mice were evaluated. They exhibited the significant decrease in the circulating leukocyte counts. Relative spleen and thymus weights were slightly decreased, but not statistically significant. There were, however, significant liver hypertrophies in their exposed mice. Splenic IgM PFCs per one million cells in 1/20 LD50 BHA and BHT exposed mice were significantly reduced. IgM PFCs per spleen were similar to those of control, except in 1/20 LD50 BHA exposed mice, where they were significantly suppressed. The precise nature of the inhibition is not clear. Direct cytotoxicity is not responsible for the depressed antibody response, even following relatively high doses of them, because the changes in spleen cellularity are not significant. Both substances, however, did not show any effects on the arthus reaction and delayed hypersensitivity reaction induced by heat-aggregated bovine serum albumin, and in vivo phagocytosis of colloidal carbon. In the light of the present results, in vivo antibody response as well as in vitro, may be sensitive to BHA and BHT. Further elucidation of the precise nature of antibody suppression in their exposed mice, is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Amalgam has been the restoration of choice for years, but its popularity has declined due to concerns about aesthetics, mercury toxicity and lichenoid lesions associated with it. Lichenoid reaction is considered to be a delayed hypersensitivity type of reaction and it has been associated with dental materials in general and amalgam in particular., Materials and Methodology: Two thousand patients having at least one amalgam restoration were examined for signs of lichenoid lesions when visiting the OPD of Conservative Dentistry and Endodontics at the Nair Hospital Dental College in Mumbai, India. Indirect spatial correlation to the amalgam restoration and the same were recorded. Descriptive analysis was used., Results: Three (0.15%) out of 2000 patients with amalgam-associated lichenoid lesions showed complete resolution of lesions after the replacement of the restorations., Conclusion: Amalgam associated lichenoid lesions have a low prevalence and should not be a contraindication to its use in routine restorative dental practice. Patch tests and biopsies have questionable diagnostic and prognostic value. Identification of the lesions should be made after the elimination of all other causative factors for the presenting symptoms. A close spatial association of the lesion to amalgam and the regression of symptoms after its removal should be considered as confirming the diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Gupta et al.)

Delayed drug hypersensitivity reactions are clinically diverse reactions that vary from isolated benign skin conditions that remit quickly with no or symptomatic treatment, drug discontinuation or even continued drug treatment, to the other extreme of severe cutaneous adverse reactions (SCARs) that are associated with presumed life-long memory T-cell responses, significant acute and long-term morbidity and mortality. Diagnostic "in clinic" approaches to delayed hypersensitivity reactions have included patch testing (PT), delayed intradermal testing (IDT) and drug challenges for milder reactions. Patch and IDT are, in general, performed no sooner than 4–6 weeks after resolution of the acute reaction at the maximum non-irritating concentrations. Functional in vitro and ex vivo assays have largely remained the province of research laboratories and include lymphocyte transformation test (LTT) and cytokine release enzyme linked ImmunoSpot (ELISpot) assay, an emerging diagnostic tool which uses cytokine release, typically IFN-γ, after the patient's peripheral blood mononuclear cells are stimulated with the suspected drug(s). Genetic markers such as human leukocyte antigen have shown recent promise for both pre-prescription screening as well as pre-emptive and diagnostic testing strategies. [ABSTRACT FROM AUTHOR]