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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]

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]

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]

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]

Copyright of Revista Alergia de Mexico is the property of Coleg. Mexicano de Inmunologia Clinica y Alergia A.C.; Soc. Lat. de Alergia, Asma e Inmunologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

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]

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]

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]

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]

Copyright of Revista de Investigaciones Veterinarias del Peru is the property of Universidad Nacional Mayor de San Marcos (UNMSM) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

The article describes the case of a 40-year-old female with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD). Topics discussed include the daily dose of riboflavin that should be given to MADD patients, the effectiveness of riboflavin in treating MADD, and the appearance of a diffuse cutaneous rash on the patient after 1 year of uninterrupted riboflavin supplementation.

We report a rare case of a delayed orbital inflammation with raised intraocular pressure as a result of hyluronidase allergy following sub-Tenon's anaesthesia. Here, we have shown evidence to prove the orbital inflammation to be an allergic response to hyluronidase with a skin patch test. This is the first case to our knowledge of a delayed hypersensitivity reaction to sub-Tenon's hyluronidase comprising of an initial exposure to hyluronidase in the fellow eye with no subsequent allergic response, but with a subsequent delayed reaction to hyluronidase during a second eye cataract surgery. This case demonstrates hyaluronidase allergy should be considered as a differential diagnosis among patients presenting with acute post-operative orbital inflammation, even if there is a history of previous exposure to hyaluronidase in the fellow eye with no subsequent allergic response. [ABSTRACT FROM AUTHOR]