Drug Hypersensitivity Reactions Research Articles

In vitro diagnostics of drug allergies.

In vitro diagnostics for drug hypersensitivity reactions distinguish between serological and cellular-based tests. A serological test used for the diagnosis of immediate type reactions is the detection of specific IgE antibodies. The cellular tests include the basophil activation test for immediate type reactions and the lymphocyte transformation test, which is mainly used to detect delayed type hypersensitivity reactions. Further cellular-based tests are the CAST-ELISA and the mast cell activation test. None of the above-mentioned tests can definitively exclude an allergy if the result is negative. In addition, it is important to note that even a positive test result is not necessarily associated with an allergy but has to be interpreted in the clinical context.

Preventing Overrides of Severe Drug Allergy Alerts Initiative: an Implemented System Upgrade

Administering medications to patients with documented drug hypersensitivity reactions (DHR) poses a significant risk for adverse events, ranging from mild reactions to life-threatening incidents. Electronic healthcare systems have revolutionized the modern clinical decision-making process, with built in warnings. However, as these alerts become a routine part of healthcare provider’s workflow, alert fatigue becomes a challenge. This study was conducted within the Ministry of National Guard Health Affairs (MNGHA), a government healthcare system in Saudi Arabia. A taskforce of experts was formed to develop an electronic path that would prevent unintentional overrides of severe drug allergy alerts. The system underwent rigorous testing, and monitoring parameters were established. We outline the implementation of a system upgrade designed to trigger an alternative interruption in the computerized physician order entry (CPOE) process, distinct from the regular allergy pop-up alerts. The alternate path is activated upon a CPOE with a drug-to-drug match and a documented severe drug allergy symptom, necessitating co-signature form another prescriber before proceeding. The adopted upgrade is a proactive approach to enhance medication safety in electronic healthcare systems, ensuring that serious allergy-related warnings are not overridden, ultimately enhancing patient safety. Further monitoring will confirm the safety and effectiveness of this measure. This study provides a model for institutions seeking to prevent allergy-related harm within their patient population.

Retinal vasculopathy and choroiditis after pegcetacoplan injection: clinicopathologic support for a drug hypersensitivity reaction

PurposeTo report the detailed histopathology of two enucleated eyes from two patients who developed severe visual loss associated with retinal hemorrhages, vessel sheathing and vascular nonperfusion after administration of an initial dose of intravitreal pegcetacoplan, and to propose, with supportive histopathology, the pathogenesis of the clinical syndrome previously termed hemorrhagic occlusive retinal vasculitis (HORV). DesignCase series. SubjectsTwo enucleated eyes from two patients treated with intravitreal pegcetacoplan. MethodsRetrospective, multicenter consecutive clinical-pathologic analysis. Main Outcome MeasuresHistopathologic review and immunophenotypic characterization. ResultsBoth patients presented with inflammation and significant vision loss nine days following the initial injection of pegcetacoplan with no subsequent improvement and underwent enucleation for pain control. Histologic examination of the enucleated eyes (patient one at 4 months post-injection and patient two at 40 days) revealed extensive vascular thrombosis, retinal hemorrhages and necrosis, and a dense inflammatory infiltrate in the uvea and variably the optic nerve, episclera, and muscle tendons composed of predominantly of T-cells, macrophages, and eosinophils. Notably, the inflammatory infiltrate was absent from the retina. In addition, one eye demonstrated multiple foci of glomerular-like vascular proliferations in the uveal tract and thrombosis with focal recanalization of vessels in the optic nerve. ConclusionDrug-induced, immune-mediated, retinal vasculopathy and choroiditis (DIRVAC) is a rare complication following pegcetacoplan injection. Although some limitations arise in interpretation of histopathologic findings due to compensatory changes in the eyes over time (prior to enucleation), the authors propose that the combined clinical, histopathologic, and immunohistochemical findings suggest a mixed-type, delayed hypersensitivity reaction as mechanism of initial injury.

Rapid Desensitization to Antitumoral Agents. Result from a Retrospective Study, DESARCh

Antitumoral drugs (ADs) can induce drug hypersensitivity reactions (DHRs). Rapid drug desensitization (RDD) protocols represent an important option to mitigate recurrent DHRs thus allowing the safe administration of ADs at therapeutic doses. The aim of this retrospective study was to assess the effectiveness of the RDD protocols performed at our institution. The “DESARCh” study was a retrospective, observational study that included consecutive patients who underwent RDD protocols from January 2011 to December 2022 at IRCCS Ospedale Sacro Cuore Don Calabria in Negrar di Valpolicella, Verona, Italy. The RDD protocol consisted of a 5-step protocol with 5 different concentrations of the drugs at 1:1, 1:10, 1:100, 1:1,000 and 1:10,000 dilution given intravenously over a 1-hour infusion each, with concentrations increasing from the most diluted to the most concentrated form, preceded by a 30-min premedication regimen. A total of 66 RDD protocols were administered to 25 female patients with ovarian (64%; n = 16/25), breast (12%; n = 3/25), endometrium (8%; n = 2/25), cervix (8%; n = 2/25), uterine (4%; n = 1/25) and fallopian tubes (4%; n = 1/25) cancers. A known history of atopy/allergy was reported by 36% (n = 9/25) of patients. Patients received RDD protocols because of DHRs to carboplatin (n = 23/66, 34.85%), paclitaxel (n = 18/66, 27.27%), pegylated liposomal doxorubicin (n = 3/66, 4.55%), and trastuzumab (n = 22/66, 33.33%). DHRs were mild-moderate, severe and life-threatening in 60.72%, 28.57% and 10.71% of cases, respectively. The success rate of RDD protocols, defined as the rate of complete administration of full target dose with no breakthrough reactions, was 81.82% (n = 54/66). Success rate was lower for carboplatin compared to other drugs (65.22% vs 90.7%; P = .017678). The RDD protocol used in our institution was found to be safe, with a meaningful success rate. However, further research is needed to better understand the underlying mechanisms of DHRs and to enhance effectiveness, particularly for patients experiencing DHRs to platinum compounds. This study was approved by the ethics committee of Verona and Rovigo (Italy) with approval number 15476 on 10/03/2023 and it was registered with the Register of Observational Studies of the Italian Medicines Agency (AIFA) (available since 31 January 2023), with ID n. 109, on 28/02/2023 ( https://www.aifa.gov.it/en/registro-studi-osservazionali ).

Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions

Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Various classes of oral antibiotics. Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

Drug fever-an immune-mediated delayed type hypersensitivity reaction to Vinca alkaloids in pediatric oncology patients, possibly mediated by cysteinyl leukotrienes.

Drug hypersensitivity reactions are common in pediatric hemato-oncology patients due to multiple factors including immune compromise and pharmacological complexities. Fever can signify severe delayed-type hypersensitivity reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The etiology of fever as an isolated hypersensitivity reaction to chemotherapeutic agents not fully understood. Here, we report three children with intracranial neoplasms experiencing recurrent febrile reactions following Vinca alkaloid-based chemotherapy, mitigated by cysteinyl leukotriene receptor antagonist therapy. We present a series of pediatric patients with diverse intracranial neoplasms who developed recurrent fever episodes after multiple courses of Vinca alkaloid-based chemotherapy. Treatment involved prophylactic and post-chemotherapy administration of a cysteinyl leukotriene receptor antagonist to prevent fever episodes and enable completion of chemotherapy regimens without protocol modifications or desensitization. All three patients experienced fever consistent with delayed-type hypersensitivity reactions to Vinca alkaloids. Prophylactic use of the leukotriene antagonist Montelukast successfully prevented fever recurrence, allowing uninterrupted completion of chemotherapy courses. Our findings suggest that Montelukast, a leukotriene antagonist, may be beneficial in managing fever as a delayed-type hypersensitivity reaction to Vinca alkaloids in pediatric patients. Further research is warranted to elucidate the underlying mechanisms and leukotriene pathways involved in drug-induced fever reactions.

Stevens–Johnson syndrome-toxic epidermal necrolysis overlap in a patient taking quetiapine and famotidine: a case report

BackgroundStevens–Johnson syndrome-toxic epidermal necrolysis (SJS-TNE) overlap is a rare skin disorder characterized by erythema, blisters, extensive exfoliation, epidermal detachment, the involvement of multiple mucosae, and positive Nikolsky’s sign. SJS-TEN has a high mortality rate. Our case involves a rare occurrence of drug-induced Stevens–Johnson syndrome-toxic epidermal necrolysis overlap with a delayed onset in the setting of quetiapine and famotidine therapy.Case presentationAn 82-year-old Taiwanese female was admitted to our hospital for decreased urine output, generalized edema, and multiple skin blisters and bedsores. With further spread of the lesions, multiple ruptured bullae with shallow erosions on the face, trunk, and limbs and mucosal involvement affected 20% of the total body surface area. Nikolsky’s sign was positive. A diagnosis of Steven–Johnson syndrome was highly suspected. One month prior, she had started famotidine and quetiapine. Intravenous methylprednisolone treatment was initiated, which ameliorated the skin lesions after 3 days. However, new lesions developed after only 1 day of methylprednisolone tapering. The patient died 12 days after admission.ConclusionStevens–Johnson syndrome-toxic epidermal necrolysis is a rare skin disorder. Although it is mainly acute and has a high mortality rate, delayed onset can still occur. Quetiapine and famotidine are generally safe and effective for treating geriatric and gastrointestinal problems, but rare drug hypersensitivity reactions can lead to debilitating consequences. Therefore, increased clinical awareness and the initiation of supportive care are imperative. Optimal management guidelines are still lacking, and confirmation of developed guidelines through randomized controlled trials is needed. Collaboration for better management strategies is warranted.

Systemic and skin-limited delayed-type drug hypersensitivity reactions associate with distinct resident and recruited T cell subsets.

Delayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype, and function of pathogenic T cells across the spectrum of severity require investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRMs) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), and skin-limited disease, morbilliform drug eruption (MDE). Microscopy, bulk transcriptional profiling, and single-cell RNA-sequencing (scRNA-Seq) plus cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) plus T cell receptor sequencing (TCR-Seq) supported clonal expansion and recruitment of cytotoxic CD8+ T cells from circulation into skin along with expanded and nonexpanded cytotoxic CD8+ skin TRM in SJS/TEN. Comparatively, MDE displayed a cytotoxic T cell profile in skin without appreciable expansion and recruitment of cytotoxic CD8+ T cells from circulation, implicating TRMs as potential protagonists in skin-limited disease. Mechanistic interrogation in patients unable to recruit T cells from circulation into skin and in a parallel mouse model supported that skin TRMs were sufficient to mediate MDE. Concomitantly, SJS/TEN displayed a reduced Treg signature compared with MDE. DRESS demonstrated recruitment of cytotoxic CD8+ T cells into skin as in SJS/TEN, yet a pro-Treg signature as in MDE. These findings have important implications for fundamental skin immunology and clinical care.

Early testing and grade of the reaction are affecting factors of skin test positivity in β-Lactam allergies.

Background: β-Lactams are the most widely used antibiotic family in the world. Nevertheless, they also stand out as the primary culprits for inducing drug hypersensitivity reactions (HSR). Methods: Between May 2018 and March 2023, patients with suspected HSRs to β-lactams, who underwent skin tests (ST), were retrospectively screened. The determinants of allergenic penicillin (DAP) tests, which include penicillin minor and major determinants, clavulanic acid, and amoxicillin, along with ampicillin, sulbactam, the identified culprit drugs, and alternative cephalosporins, which include cefuroxime, ceftriaxone prick and/or intradermal tests, were administered. The analysis focused on identifying positive ST results and determining the true HSRs rates in this patient cohort. Results: Of the 147 patients, 78.9% (n = 116) were women and the median (minimum-maximum) age was 41 years (18-71 years). Mild HSRs (grades 1-2) were observed in 72.78% (n = 107), whereas 24.4% (n = 36) had severe reactions (grades 3-4) and 2.7% (n = 4) had an unknown grade. Of the patients, 64% (n = 94) experienced HSRs within the first hour after the last dose of the identified culprit drug. The overall positivity rate for all STs was 26.5% (n = 39). ST positivity rates were notably higher in individuals who had experienced HSRs within the past 6 months (p = 0.02) and those with severe anaphylaxis (p < 0.001). Conclusion: β-Lactam ST positivity is higher, especially in those with grades 3-4 reactions and consulted a physician within the first 6 months after their HSRs.

HLA-Related Drug Hypersensitivity Reactions

ÖZET İlaç reaksiyonları (İR) iki temel grupta sınıflandırılır. İlki, immünolojik mekanizma aracılı alerjik reaksiyonları; ikincisi, spesifik immünolojik mekanizmanın katılımı olmadan gelişen ilaç aşırı duyarlılık reaksiyonlarıdır (İADR). Morbidite ve mortalite prevalansı İADR’de yüksektir. Bu şiddetli reaksiyonların bazıları spesifik insan lokosit antijen (HLA) alelleri ile bağlantılıdır. Çünkü, HLA genleri genomun en yüksek oranda polimorfik lokuslarını barındırır. Dolayısıyla, İADR etyolojisinde farmakolojik doz etkisinden ziyade genetik yatkınlık farmokogenetik araştırmaların son dönem merak uyandıran alanlarından birini oluşturmaktadır. İADR ile spesifik HLA ilişkileri coğrafi bölgeler ve etnik gruplar arasında farklılık gösterebilir. Aynı populasyonun bireyleri arasında dahi HLA allellerine göre ilaç yanıtı ve duyarlılığı farklılık teşkil edebilir. Çok sayıda çalışma, spesifik HLA alellerinin İADR geliştirme riskini artırdığına dair kanıtlar sağlamıştır. Çünkü, ilaca yanıt veren T hücresi aktivasyonunda HLA, ilaçlar ve T hücresi reseptörleri arasındaki etkileşim HLA allellerine göre değişebilmektedir. Allel türüne göre, T hücresinin aktivasyonu, antijen ile etkileşimi doğurduğu immün cevap farklılığı doğuran en önemli moleküler sistemdir. Bu özellikler HLA allerinin İADR üzerinden farmakogenetik ilişkisini ortaya koyarken, farmakokinetik etki içinde HLA allel çeşitlerine göre ilacı hızlı metabolize eden veya hiç metabolize etmeden toksik yanıt geliştiren bireyler de olabilir. Bu doğrultuda, toplumlarda farmakogenomik ilişkilerin incelenmesi, HLA alleleri ile ilaç duyarlılığı için yeni verilerin keşfedilmesi, kanıt oranıyla bulunanların doğrulanması hem ilaç yararlanımı için sağlık kalitesi üzerinden hem de maliyet etkinliği üzerinden büyük fayda sağlayacaktır. İlaç kullanımından önce HLA kimliklendirmesi ile kişiye özel farmakolojik tedavi, gelişen toplumlarda güncel tedavi hedeflerinin başında gelmektedir. Bu derlemede, ilaç aşırı duyarlılık reaksiyonlarına yol açan modeller, en sık reaksiyon veren ilaçlar, ilişkili HLA alleleri ve izlenen klinik tablolar araştırılmıştır. Anahtar Kelimeler: HLA, ilaç, aşırı duyarlılık reaksiyonları

Cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs, manifested as urticaria and/or angioedema, anaphylaxis

BACKGROUND: The main mechanism of drug hypersensitivity to non-steroidal anti-inflammatory drugs is associated with inhibition of cyclooxygenase type 1, which leads to cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs from various subgroups of different chemical structures. Clinically, cross-hypersensitivity usually manifests in the form of urticaria and/or angioedema. AIM: To characterize a group of patients with cross-hypersensitivity to non-steroidal anti-inflammatory drugs manifesting as urticaria / angioedema / anaphylaxis. MATERIALS AND METHODS: To achieve this aim a prospective single-center study was conducted. Patients with a presumptive diagnosis of drug hypersensitivity to non-steroidal anti-inflammatory drugs (n=307) were consulted. A group of patients (n=237) with high probability of such reactions was identified, of which cross-hypersensitivity manifested as urticaria / angioedema / anaphylaxis was observed in 127 patients. This group was divided into 2 phenotypes: a group with concomitant chronic urticaria (n=67) and without it (n=60). We assessed demographic data, drug triggers, clinical manifestations, concomitant atopy, and compared these indicators between both groups. Selected patients underwent a drug provocation test with selective or predominantly selective non-steroidal anti-inflammatory drugs and paracetamol. RESULTS: Cross-hypersensitivity reactions manifested as urticaria / angioedema / anaphylaxis is the most common phenotype of immediate-type drug cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs (75.6%). Women develop this condition 2.5 times more frequently than men, and are more likely to develop cross-drug hypersensitivity with concomitant chronic urticaria with the onset of approximately 16 years later than men. Mild manifestations of cross-hypersensitivity (urticaria/angioedema) develop more frequently than severe ones (anaphylaxis). Angioedema in children, urticaria in adults with concomitant chronic urticaria and angioedema in adults without concomitant chronic urticaria are it's main manifestations. The most frequent non-steroidal anti-inflammatory drugs triggers are metamizole, acetylsalicylic acid and propionic acid derivatives. Non-steroidal anti-inflammatory drugs with the lowest risk of developing drug hypersensitivity are coxibs, paracetamol, and to a lesser extent ― meloxicam, nimesulide. CONCLUSION: The data obtained allowed us to expand our understanding of cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs presenting as urticaria/angioedema or anaphylaxis. Selective cyclooxygenase type 2 inhibitors and paracetamol are drugs with the highest safety profile.

Characteristics of Drug Hypersensitivity Reactions in Children: A Retrospective Analysis in an Allergy Outpatient Clinic

Objective: Confirmation of drug hypersensitivity reactions (DHRs) is crucial—as various nonallergic reactions, such as viral infections, in children can mimic such reactions. This study aimed to evaluate the characteristics of children with suspected DHRs applying to an allergy outpatient clinic. Material and Methods: This study involved children who visited our hospital’s pediatric allergy outpatient clinic between April 1 and December 31, 2023, with suspected DHRs . The data of patients analyzed retrospectively. Patient demographics, reaction characteristics, culprit drugs, diagnostic procedures (including skin and/or provocation tests), and final diagnoses were recorded. Results: The study included 163 reactions of 140 patients with 176 suspected drugs. The median age was 7.7 years (interquartile range [IQR]; 5.1–12 years), with an equal gender distribution. Notably, 27.1% of the patients presented with concurrent atopic diseases. The median age at the onset of reaction was 72 months (IQR; 34.5–108 months), with 16% of reactions occurring within hospital settings and the remainder at home. Oral administration accounted for 84.7% of the reactions, with antibiotics being the most common culprit drug group (75.5%). Immediate reactions constituted 41.1% (n = 67) of reactions, while delayed reactions accounted for 58.9% (n = 96). Skin symptoms were predominant (97.5%). DHRs were excluded in 75.5% (n = 123) of reactions but confirmed by diagnostic drug allergy tests in 4.9% (n = 8). Conclusion: A through evaluation of suspected DHRs in children is essential. Despite high suspicion rates, confirmation via diagnostic tests was low, emphasizing the need for referral to specialized clinics and appropriate diagnostics for accurate management.

Mast cell conditions and drug allergy: when to suspect and how to manage.

Patients with mast cell disorders frequently experience symptoms from excessive mediator release like histamine and tryptase, ranging from mild flushing to severe anaphylactic responses. Hypersensitivity reactions (HRs) to drugs are a major cause of anaphylaxis in these patients, who often worry about triggering mast cell degranulation when taking medications. The aim of this review is to explore the complex interactions between mast cell disorders and drug HRs, focusing on the clinical challenges of managing these conditions effectively to enhance understanding and guide safer clinical practices. Among the drugs most commonly associated with hypersensitivity reactions in patients with mast cell disorders are non-steroidal anti-inflammatory drugs, antibiotics, and perioperative agents. Recent studies have highlighted the role of Mas-related G-protein coupled receptor member X2 (MRGPRX2) - a receptor involved in non-immunoglobulin E mediated mast cell degranulation - in exacerbating HRs. Investigations reveal varied drug tolerance among patients, underscoring the need for individual risk assessments. Tailored diagnostic approaches are crucial for confirming drug allergies and assessing tolerance in patients with mastocytosis, preventing unnecessary medication avoidance and ensuring safety before acute situations arise.

Amikacin induced Stevens Johnson syndrome and toxic epidermal necrolysis overlap: a rare case report

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe adverse drug reactions. They are characterized by necrosis and epidermal release in vesicobulosa skin, mucous orifice, and eyes, with more severe general symptoms. SJS/TEN-overlap syndrome is the term used to characterize situations where 10–30% of the body skin area is detached. TEN or SJS is one of the deadliest dermatological catastrophes. Despite being a rare condition, it frequently has a high death rate. Different types of purpuric macules or rounded patches with mucosal lesions are characteristic features of these type 3 hypersensitivity reactions. We are presenting a case of 50-year-old female patient brought to hospital on account of multiple black to red coloured raised lesions over body in the last 8 days. Patient was asymptomatic in the last 8 days after that patient noted red coloured lesions first over face followed by lower back, upper limb, lower limb followed by itching and Jiburning sensation all over the body. The patient had symptoms such as redness of eyes in the last 3-4 days, burning sensation and ulcers in mouth in the last 3-4 days. These symptoms developed day after she received amikacin. She was diagnosed with SJS-TEN overlap. This case highlights the precipitant of antibiotics for SJS. She was recovered completely after stopping the causative drug and treatment with Immunoglobulin with other symptomatic measures. The causative drug was found to be Amikacin and medicine taken for comorbid conditions like epilepsy, hypothyroidism and hypertension. Rarely, amikacin has been linked to a range of drug hypersensitivity reactions, including toxic epidermal necrolysis, Stevens-Johnson syndrome, and overlap between the two conditions.

ALDRESS: A Retrospective Pilot Study to Develop a Pharmacological Causality Algorithm for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe form of drug hypersensitivity reaction characterized by significant morbidity, mortality, and long-term sequelae, coupled with limited therapeutic avenues. Accurate identification of the causative drug(s) is paramount for acute management, exploration of safe therapeutic alternatives, and prevention of future occurrences. However, the absence of a standardized diagnostic test and a specific causality algorithm tailored to DRESS poses a significant challenge in its clinical management. Methods: We conducted a retrospective case-control study involving 37 DRESS patients to validate a novel causality algorithm, the ALDRESS, designed explicitly for this syndrome, comparing it against the current standard algorithm, SEFV. Results: The ALDRESS algorithm showcased superior performance, exhibiting an 85.7% sensitivity and 93% specificity with comparable negative predictive values (80.6% vs. 97%). Notably, the ALDRESS algorithm yielded a substantially higher positive predictive value (75%) compared to SEFV (51.40%), achieving an overall accuracy rate of 92%. Conclusions: Our findings underscore the efficacy of the ALDRESS algorithm in accurately attributing causality to drugs implicated in DRESS syndrome. However, further validation studies involving larger, diverse cohorts are warranted to consolidate its clinical utility and broaden its applicability. This study lays the groundwork for a refined causality assessment tool, promising advancements in the diagnosis and management of DRESS syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) caused by sulfasalazine: a case report and literature review

Drug-induced hypersensitivity syndrome (DIHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially fatal systemic reaction characterized by multiorgan damage involving the liver, hematopoietic system and skin, and heterogeneous manifestations of fever, rash, lymphadenopathy and eosinophilia with unpredictable course.We describe a 41-year-old female patient who developed DRESS syndrome after taking sulfasalazine prescribed for non-radiographic axial spondyloarthritis. Treatment with intravenous and then oral glucocorticoids was effective. A review of the literature on this topic is presented.

Drug hypersensitivity reactions: review of the state of the science for prediction and diagnosis.

Drug hypersensitivity reactions (DHRs) are a type of adverse drug reaction that can occur with different classes of drugs and affect multiple organ systems and patient populations. DHRs can be classified as allergic or non-allergic based on the cellular mechanisms involved. Whereas nonallergic reactions rely mainly on the innate immune system, allergic reactions involve the generation of an adaptive immune response. Consequently, drug allergies are DHRs for which an immunological mechanism, with antibody and/or T cell, is demonstrated. Despite decades of research, methods to predict the potential for a new chemical entity to cause DHRs or to correctly attribute DHRs to a specific mechanism and a specific molecule are not well-established. This review will focus on allergic reactions induced by systemically administered low-molecular weight drugs with an emphasis on drug- and patient-specific factors that could influence the development of DHRs. Strategies for predicting and diagnosing DHRs, including potential tools based on the current state of the science, will also be discussed.

Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons.

Iatrogenesis is an inevitable global threat to healthcare that drastically increases morbidity and mortality. Cancer is a fatal pathological condition that affects people of different ages, sexes, and races around the world. In addition to the detrimental cancer pathology, one of the most common contraindications and challenges observed in cancer patients is severe adverse drug effects and hypersensitivity reactions induced by chemotherapy. Chemotherapy-induced cognitive neurotoxicity is clinically referred to as Chemotherapy-induced cognitive impairment (CICI), chemobrain, or chemofog. In addition to CICI, chemotherapy also causes neuropsychiatric issues, mental disorders, hyperarousal states, and movement disorders. A synergistic chemotherapy regimen of Doxorubicin (Anthracycline-DOX) and Cyclophosphamide (Alkylating Cytophosphane-CPS) is indicated for the management of various cancers (breast cancer, lymphoma, and leukemia). Nevertheless, there are limited research studies on Doxorubicin and Cyclophosphamide's pharmacodynamic and toxicological effects on dopaminergic neuronal function. This study evaluated the dopaminergic neurotoxic effects of Doxorubicin and Cyclophosphamide. Doxorubicin and Cyclophosphamide were incubated with dopaminergic (N27) neurons. Neuronal viability was assessed using an MTT assay. The effect of Doxorubicin and Cyclophosphamide on various prooxidants, antioxidants, mitochondrial Complex-I & IV activities, and BAX expression were evaluated by Spectroscopic, Fluorometric, and RT-PCR methods, respectively. Prism-V software (La Jolla, CA, USA) was used for statistical analysis. Chemotherapeutics dose-dependently inhibited the proliferation of the dopaminergic neurons. The dopaminergic neurotoxic mechanism of Doxorubicin and Cyclophosphamide was attributed to a significant increase in prooxidants, a decrease in antioxidants, and augmented apoptosis without affecting mitochondrial function. This is one of the first reports that reveal Doxorubicin and Cyclophosphamide induce significant dopaminergic neurotoxicity. Thus, Chemotherapy-induced adverse drug reaction issues substantially persist during and after treatment and sometimes never be completely resolved clinically. Consequently, failure to adopt adequate patient care measures for cancer patients treated with certain chemotherapeutics might substantially raise the incidence of numerous movement disorders.

Cutaneous Adverse Drug Reactions on application of Nagaradi Lepa - A Retrospective analysis

Introduction: Cutaneous adverse drug reactions are among the most common types of drug hypersensitivity reactions. Although considered natural and safe, Ayurveda medicines can cause adverse reactions. This article highlights the cases of cutaneous adverse drug reactions possibly due to external application of Nagaradi lepa. Materials and Methods: This is an observational, retrospective and record based study conducted by analyzing the spontaneous reported ADR forms, caused by the external application of Nagaradi lepa, collected over a period of 12 months (April 2022 to March 2023) at Peripheral Pharmacovigilance Centre, VPSV Ayurveda College Kottakkal, Kerala. Results: During the period of one year, 3 cutaneous ADRs were reported due to external application of Nagaradi lepa. All the 3 cases fall under the category of Probable according to Naranjo’s ADR Probability scale. 2 cases were mild and 1 case was moderate in severity. All the 3 cases were recovered from ADR. Conclusion: Though under reporting, we may have to consider the possibility of Ayurvedic drugs to cause adverse drug reactions. Pharmacovigilance is an ongoing and continuous process. Reporting of ADR to Pharmacovigilance centers help to generate information on ADR related Ayurvedic formulations and also to prevent its recurrence.

Gradual drug provocation tests in the evaluation of suspected delayed drug hypersensitivity reactions

Gradual drug provocation tests in the evaluation of suspected delayed drug hypersensitivity reactions