Drug Rash With Eosinophilia And Systemic Symptoms Research Articles

Pharmacokinetic Simulation Study: Exploring the Impact of Clinical Parameters on Lamotrigine for Different Patient Populations with Implications for Liver Function Assessment and Therapeutic Drug Monitoring

Lamotrigine, widely used for managing epilepsy and bipolar disorder, carries potential side effects, including severe anticonvulsant hypersensitivity syndrome (AHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which may lead to hepatotoxicity. Patients with Type 2 Diabetes (TD2) and Non-Alcoholic Fatty Liver Disease (NAFLD) are identified as more susceptible to these adverse reactions. This exploratory analysis aims to identify clinical parameters influencing lamotrigine pharmacokinetics across diverse populations, shedding light on toxicity and therapeutic drug monitoring (TDM) considerations. Starting with a retrospective analysis of 41 lamotrigine-treated patients at Hospital Santo António reveals changes or deviations from normal levels in various blood parameters and significant correlations between these parameters. Serum level changes, including creatinine, albumin, gamma-glutamyl transferase, total bilirubin, and Vitamin B12, are observed, with strong negative correlations between Vitamin B12 and creatinine. Then, we used GastroPlus and DILIsym to explore the impact of clinical parameters on lamotrigine for different patient populations. We constructed a Physiologically Based Pharmacokinetic (PBPK) model for lamotrigine in GastroPlus, based on ADMET predictions and data from the literature, to simulate the pharmacokinetic variability of lamotrigine in different populations, and we visualized the impact of increasing lamotrigine dose on its plasma concentration–time profiles (200 mg, 400 mg, 600 mg, 1200 mg) and reduced bioavailability. At higher doses, it is possible that the saturation of metabolic pathways leads to the formation of toxic metabolites or intermediates. These metabolites may exert inhibitory effects on drug-metabolizing enzymes or disrupt normal physiological processes, thereby impeding the drug’s clearance and potentially lowering its bioavailability. In DILIsym, we investigated lamotrigine’s DILI potential for individuals with diabetes and NAFLD. The results demonstrated an increased risk, emphasizing the need for careful monitoring. This study underscores the importance of understanding lamotrigine’s pharmacokinetics for tailored treatment decisions, improved outcomes, and minimized adverse reactions.

Adverse events of biological agents in pediatric rheumatologic diseases

ABSTRACT Objectives To evaluate adverse events (AEs) in pediatric patients with rheumatologic diseases being treated with approved or off-label biologic agents (BAs). Methods This observational, retrospective, multicenter study was conducted from 2010 to 2022 in patients under 18 years of age with rheumatic diseases who were receiving interleukin-1 antibodies (Anti-IL1), interleukin-6 antibodies (Anti-IL6), and tumor necrosis factor alpha inhibitors (anti-TNF). Efficacy, AEs, and timing of AEs were collected from electronic medical records. Results Three hundred and fifteen BAs were prescribed to 237 patients. Fifty AEs occurred in 44 patients (18.6%). Anti-TNF exposure was present in 8 (72.2%) of 11 patients with latent tuberculosis (TB) and in all 7 patients with herpes infections. Four of 6 patients (66.7%) with recurrent upper respiratory tract infections and 7 of 8 patients (87.5%) with local skin reactions were on Anti-IL1. The cutoff value for latent TB development was determined as 23.5 months by ROC analysis (AUC: 0.684 ± 0.072, p = 0.038, 95% CI: 0.54–0.82). In patients who used BA for 23.5 months or more, the risk of latent TB was 5.94-fold (p = 0.024, 95% CI: 1.26–27.97). Drug rash with eosinophilia and systemic symptoms (DRESS) occurred in 2 patients on anakinra, and anaphylaxis occurred in 1 patient on anti-IL6. There were no cases of malignancy or death in any patient. Conclusion The physician should be vigilant for latent TB in patients exposed to BA for more than 2 years. While local skin reactions are more prevalent in patients receiving anti-IL1, severe skin reactions such as DRESS may also occur.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome following Ticagrelor administration leading to serious complications.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is rarely reported with administration of Ticagrelor. We report a case, where such complication developed after 7 days of Ticagrelor administration, leading to acute severe complications requiring hospitalization. There was airway and renal involvement with elevated inflammatory markers. On withdrawing Ticagrelor, there was rapid resolution of symptoms.

Insights into Mefenamic Acid-Induced Allergic Reactions: A Comprehensive Clinical and Research Review

This study investigates the incidence of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome associated with the over-the-counter non-steroidal anti-inflammatory drug (NSAID) mefenamic acid. Approximately 10% of individuals exposed to mefenamic acid experience DRESS syndrome, a severe and potentially fatal allergic reaction characterized by fever, skin rash, lymphadenopathy, hematological abnormalities, and internal organ involvement. Leukocytosis with eosinophilia (90%) and mononucleosis (40%) has been linked to certain cases, emphasizing the diversity of clinical presentations. The causative medication must be promptly discontinued upon identification of DRESS syndrome, with documented evidence indicating improved prognosis with early drug removal. Despite the severity of these reactions, the study sheds light on the alarming accessibility of mefenamic acid and other banned medications in developing nations, particularly exemplified by the Indian Pharmacopoeia Commission’s alert on mefenamic acid issued on December 7, 2023. The lack of effective law enforcement and medical awareness poses significant challenges, allowing banned drugs, including Nimesulide and Rofecoxib, to persist in the market despite being banned by the USFDA. This research underscores the critical need for global collaboration to address regulatory gaps, enhance medical awareness, and enforce stringent measures to restrict the availability of harmful medications in developing nations. Urgent attention to these issues is imperative to safeguard public health and ensure the effective implementation of drug regulations on a global scale.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome in childhood: a narrative review.

Despite being rare, the Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a serious, possibly fatal condition that may affect both adults and children who may be also burdened by delayed sequelae. It is an adverse drug reaction characterized by widespread skin involvement, fever, lymphadenopathy, visceral involvement, and laboratory abnormalities (eosinophilia, mononucleosis-like atypical lymphocytes). It is more frequently triggered by anticonvulsants, sulphonamides, or antibiotics, the latter being responsible for up to 30% of pediatric cases. The disease typically develops 2-8 weeks after exposure to the culprit medication, with fever and widespread skin eruption; mild viral prodromes are possible. Unfortunately, diagnosis is challenging due to the absence of a reliable test; however, a score by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) allows to classify suspect patients into no, possible, probable, or definite DRESS cases. Moreover, rapid-onset DRESS syndrome has been described in recent years. It affects children more often than adults and differs from the most common form because it appears ≤15 days vs. >15 days after starting the drug, it is usually triggered by antibiotics or iodinated contrast media rather than by anticonvulsants and has a higher presence of lymphadenopathy. Differential diagnosis between rapid-onset antibiotic-driven DRESS syndrome, viral exanthems, or other drug eruptions may be challenging, but it is mandatory to define it as early as possible to start adequate treatment and monitor possible complications. The present review reports the latest evidence about the diagnosis and treatment of pediatric DRESS syndrome.

Herpes Simplex Virus Type 2 (HSV-2) Infection

More than 90% of people worldwide are seropositive for herpes simplex virus (HSV) by the fourth decade of their lives. HSV is usually asymptomatic or follows a mild, self-limited course in healthy individuals. In severely immunocompromised hosts or in patients with underlying inflammatory bowel disease (IBD) treated with immunomodulators, HSV can cause significant morbidity and mortality, including mucocutaneous ulcerations, esophagitis, hepatitis, and encephalitis. This is a rare case of HSV-2 causing necrotizing ischemic colitis, toxic megacolon, and necroinflammation of the liver in the absence of transaminitis in a patient who received steroids for drug rash with eosinophilia and systemic symptoms (DRESS) syndrome.

Acute hepatic failure in trimethoprim-induced drug rash with eosinophilia and systemic symptoms (DRESS).

In this paper, we describe four cases of drug rash with eosinophilia and systemic symptoms (DRESS) caused by trimethoprim administered for the treatment of acne. All cases were complicated by acute hepatic failure.

An Unusual Case of Hemophagocytic Lymphohistiocytosis Associated with Mycobacterium chimaera or Large-Cell Neuroendocrine Carcinoma

Hemophagocytic lymphohistiocytosis (HLH) is a rare and very dangerous condition characterized by abnormal activation of the immune system, causing hemophagocytosis, inflammation, and potentially widespread organ damage. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity, is most commonly seen in children. Secondary HLH is commonly associated with infections, malignancies, and rheumatologic disorders. Most current information on diagnosis and treatment is based on pediatric populations. HLH is a disease that should be diagnosed and treated promptly, otherwise it is fatal. Treatment is directed at treating the triggering disorder, along with symptomatic treatment with dexamethasone and etoposide. We present a 56-year-old patient who was admitted with worsening weakness, exertional dyspnea, dry and nonproductive cough, and a 5-pound weight loss associated with loss of appetite. This is among the rare disorders that are not commonly encountered in day-to-day practice. Our differential diagnoses were broad, including infection, such as visceral leishmaniasis, atypical/tuberculous mycobacteria, histoplasmosis, Ehrlichia, Bartonella, Brucella, Adenovirus, disseminated herpes simplex virus (HSV), hematological-like Langerhans cell histiocytosis, or multicentric Castleman disease; drug reaction, such as drug rash with eosinophilia and systemic symptoms (DRESS); and metabolic disorder, including Wolman's disease (infantile lysosomal acid lipase deficiency) or Gaucher's disease. Based on our investigations as described in our case report, it was narrowed down to hemophagocytic lymphohistiocytosis and COVID-19. Two COVID-19 tests were negative. His lab abnormalities and diagnostic testing revealed hemophagocytic lymphohistiocytosis. He was empirically started on antibiotics and dexamethasone, to be continued for 2 weeks then tapered if the patient showed continued improvement. Dexamethasone was tapered over 8 weeks. He improved on just one of the Food and Drug Administration (FDA)-approved medications, proving that treatment should be tailored to the patient. In addition, in this case study, we included the background, etiology, pathogenesis, diagnosis, management, and prognosis of HLH.

Drug rash with eosinophilia and systemic symptoms (DRESS): A report of two cases

Abstract Drug Rash with Eosinophilia and Systemic Systems (DRESS) is an idiosyncratic severe cutaneous adverse reaction characterised by a skin rash with systemic involvement. DRESS syndrome can be caused by several drugs. We report two patients who presented with DRESS syndrome caused by anti-epileptic drugs lamotrigine and oxcarbazepine. Based on clinical presentation, laboratory testing and imaging findings, the patients were diagnosed to have DRESS syndrome. In both the patients, offending drugs were stopped and patients were treated with iv corticosteroids, and symptomatic treatment and had recovered.

Time is skin: What does the emergency physician need to know about DRESS?

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, also known as Drug Induced Hypersensitivity Syndrome (DIHS), is an acute drug-induced hypersensitivity reaction. The pathogenesis of this syndrome, which can develop due to many drugs, especially antiepileptic agents, is not known exactly. This syndrome, which was denominated “hydantoin hypersensitivity” in 1950, was renamed as “DRESS syndrome” by Bocquet and his colleagues in 1996 and the first diagnostic criteria were determined. Unlike syndromes that may develop due to other drugs, DRESS syndrome customarily commences 2-8 weeks after the commencement of the drug, and symptoms perpetuate to progress after discontinuation of the responsible drug. Symptoms such as fever, lymphadenopathy, hematological disorders, maculopapular rash and internal organ involvement are common in this syndrome. Diagnosis of DRESS syndrome is often difficult, as the clinical manifestations are varied and the latent period after the initiation of drug use can be up to 3 months. Thus, it is thought that the diagnosis of DRESS should be in the minds of all doctors, especially emergency physicians.

54-Year-Old Man With Acute Dyspnea on Exertion

54-Year-Old Man With Acute Dyspnea on Exertion

An Eleven Year Old Boy with Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

Introduction: The prospective studies have estimated that the DRESS syndrome incidence rate is about 1 per 1000 to 10,000 with the mortality rate is to be around 10% to 20%.
 Case: We have been reported a case of DRESS in an eleven-year-old boy who came to the emergency room with the chief complaint of maculopapular rash in the body that had been happened for three days. The rash was first appeared in the arms area and thus spread to the trunk, abdomen, and lower extremities. The erythema was well-demarcated, purplish in color. There was a history of fever a week before admission which reached 40 0 Celcius. There are multiple histories of drug administration, either orally or intravenously to this patient, and made the diagnosis of drug reaction is highly possible. The management of these patients consists of suspending suspected drugs and implementing supportive measures.
 Conclusion: Regarding pharmacological treatment, the use of systemic corticosteroids for a prolonged period with a gradual decrease is suggested, to avoid relapses.

Histopathological Characterization of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Comparison with Maculopapular Drug Rash (MPDR).

Introduction:Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction (cADR) associated with significant systemic involvement and greater mortality. Variable patterns of inflammation are reported in the histopathology of DRESS. However, the role of histopathology in predicting systemic involvement and thus final outcome remains elusive. In the present study, we aim to review clinical and histopathological characteristics of patients with DRESS and compare their histopathology with that of maculopapular drug rash.Materials and Methods:A retrospective analysis of cases of cADRs diagnosed from July 2014 to July 2020 at a single tertiary care institute was performed. A RegiSCAR score of ≥4 was used to recruit patients as DRESS. Patients with a probable/definite diagnosis of cADR on the basis of Naranjo criteria and presenting with exanthem attaining a RegiSCAR score of ≤3 were categorized as MPDR. Correlation of histopathology characteristics with the investigative profile of patients with DRESS was done. MPDR and DRESS were also compared for histopathological characteristics using Chi-square test. Further histopathology of patients with drug rash (both DRESS and MPDR) having systemic involvement was compared with those without systemic involvement to identify specific predictors.Results:Eighteen patients of DRESS and 20 of MPDR fulfilled the inclusion criteria. Most common drugs implicated were anticonvulsants (27.8%). Characteristic findings seen on histopathology in patients with DRESS were epidermal spongiosis (94.5%), epidermal dyskeratosis (33.3%), lymphocytic exocytosis (88.9%), interface vacuolization (77.8%), papillary dermal edema (100%). and perivascular lymphocytic infiltrate (100%). Findings in favor of DRESS compared to MPDR were lymphocytic exocytosis (P < 0.001), interface vacuolization (P = 0.002), severe spongiosis (P = 0.046), severe papillary dermal edema (P = 0.018), and higher density of dermal infiltrate (P = 0.005). Lymphocyte exocytosis and distribution and density of dermal inflammatory infiltrate correlated significantly with deranged kidney function.Conclusion:Histopathology revealing prominent basal vacuolization, spongiosis, and dense dermal infiltrate suggests DRESS. Lymphocyte exocytosis and distribution and density of dermal inflammatory infiltrate predict renal involvement.

Fever with pancytopenia in a patient with lamotrigin induced DRESS syndrome: a case-based review

Background: Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare idiosyncratic and unpredictable drug reaction most commonly attributed to anticonvulsants, allopurinol, and antibiotics. Fever in combination with cutaneous manifestations and eosinophilia are the cardinal clinical findings, while organ involvement and very rarely pancytopenia can be present. Case presentation: We describe a 26-year-old female patient with pancytopenia in the context of lamotrigine-induced DRESS and we summarize this as a potentially life-threatening hypersensitivity reaction. Conclusion: DRESS should be suspected in patients presenting with fever, eosinophilia, skin involvement, and/or visceral organ involvement, who have started a new drug during the past 2 to 6 weeks, as early recognition of this syndrome with subsequent discontinuation of the offending drug could be lifesaving.

Quetiapine-induced drug rash with eosinophilia and systemic symptom syndrome

Drug rash with eosinophilia and systemic symptoms (DRESSs) syndrome is an adverse cutaneous reaction characterized by fever, skin eruption, hematological abnormalities, and internal organ involvement. Although many drugs are known to cause DRESS syndrome, quetiapine-induced DRESS syndrome case is rare. We report a case of a 78-year-old male who developed DRESS syndrome presented with rashes, eosinophilia after taking quetiapine for 2 weeks.

M050 IMATINIB-INDUCED DRESS/DIHS

Drug rash with eosinophilia and systemic symptoms (DRESS), or drug-induced hypersensitivity syndrome (DiHS), is a rare, but severe adverse drug reaction. Rapid diagnosis and removal of the causative drug are critical to treatment. With the increasing use of targeted therapies, it is important to be aware of these drugs as potential causes of DRESS/DiHS. Imatinib is a tyrosine kinase inhibitor used in the treatment of various malignancies, hypereosinophilic syndrome (HES), and other eosinophilic disorders. We report a rare case of imatinib-induced DRESS/DiHS.

P6‐6: Anti tuberculosis treatment induced drug rash with eosinophilia and systemic symptoms (DRESS) mimicking meningitis

P6‐6: Anti tuberculosis treatment induced drug rash with eosinophilia and systemic symptoms (DRESS) mimicking meningitis

M007 DRESS REACTION TO ANAKINRA IN A PATIENT WITH SEVERE SYSTEMIC JUVENILE ARTHRITIS (SJIA)

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is a life-threatening delayed drug hypersensitivity with rash, eosinophilia, and systemic symptoms with end organ damage. Cessation of the offending drug, supportive care, and immunosuppression are mainstays of treatment. This becomes challenging when the offending drug is critical for treating the underlying disease. We present a case of a patient with systemic juvenile arthritis (sJIA) developing DRESS to anakinra (IL-1 receptor antagonist).

Dapsone Induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome - A Case Report

A 50-year-old male Sudanese patient presented with a three-week history of jaundice, high-grade fever, and mucocutaneous eruption. For last months he was on compound therapy for leprosy, which had been confirmed recently. The patient’s face was prominent, along with the erythematous dusky morbilliform rash covering all the body. On examination, we detected hepatosplenomegaly and generalized lymphadenopathy. Laboratory investigations revealed hepatorenal impairment, and hematological analysis revealed leukocytosis mainly due to eosinophilia. The clinical and laboratory findings interpretation ranked DRESS or Drug-Induced Hypersensitivity Syndrome (DIHS) on top of possible causes before Dapsone Hypersensitivity Syndrome (DHS) and lepra reactions. We promptly discontinued MDT, admitted him to the dermatological ward. Two skin biopsies were sent to two different histopathologists, MF was suggested by one and Sezary syndrome by the other one. Besides the general conservative measures and vital functions monitoring, he received systemic and topical steroids. However, unfortunately, within the next three weeks, his condition deteriorated, and passed away from multi-systems failure.

26416 Is it really DRESS? A retrospective descriptive study

Background: There is limited information regarding patients with drug rash with eosinophilia and systemic symptoms (DRESS) in the Latin American population. We evaluated patients consulted to the Department of Dermatology service with a suspected diagnosis of DRESS from hospitals affiliated to the University of Puerto Rico School of Medicine. Our study aimed to characterize clinical, histopathologic, and/or laboratory findings significantly correlated with a final diagnosis of DRESS.