Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome to Hemodialysis Polysulfone Membrane.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe and potentially life-threatening hypersensitivity reaction. Although commonly associated with specific drugs, there have been no reports of DRESS syndrome caused by medical devices. We report a unique case of DRESS syndrome linked to a particular hemodialysis membrane during treatment. An 83-year-old man on hemodialysis exhibited fever, rash, and elevated eosinophils. Despite medication changes and consultations with specialists, his condition persisted. A drug-induced lymphocyte stimulation test revealed a positive response to the dialysis membrane. His symptoms and lab results met DRESS syndrome diagnostic criteria. After substituting the membrane and administering glucocorticoids, the patient displayed early improvement. Diagnosing DRESS syndrome is complex due to its varied presentation and lack of specific benchmarks. This instance underscores the need to consider medical devices as potential DRESS syndrome triggers. Enhanced physician awareness can facilitate prompt detection and proper management, ultimately refining patient outcomes.

DRESS/DiHS syndrome induced by Propylthiouracil: a case report.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction. Propylthiouracil, a member of thiouracils group, is widely used in medical treatment of hyperthyroidism. Propylthiouracil is associated with multiple adverse effects such as rash, agranulocytosis hepatitis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but rarely triggers DRESS/DiHS syndrome. Here, we describe a severe case of propylthiouracil-induced DRESS/DiHS syndrome. CASE PRESENTATION: A 38-year-old female was treated with methimazole for hyperthyroidism at first. 4 weeks later, the patient developed elevated liver transaminase so methimazole was stopped. After liver function improved in 2 weeks, medication was switched to propylthiouracil therapy. The patient subsequently developed nausea and rash followed by a high fever, acute toxic hepatitis and multiple organ dysfunction (liver, lung and heart), which lasted for 1 month after propylthiouracil was started. According to the diagnostic criteria, the patient was diagnosed of DRESS/DiHS syndrome which was induced by propylthiouracil. As a result, propylthiouracil was immediately withdrawn. And patient was then treated with adalimumab, systematic corticosteroids and plasmapheresis in sequence. Symptoms were finally resolved 4 weeks later. CONCLUSIONS: Propylthiouracil is a rare cause of the DRESS/DiHS syndrome, which typically consists of severe dermatitis and various degrees of internal organ involvement. We want to emphasize through this severe case that DRESS/DiHS syndrome should be promptly recognized to hasten recovery.

Non-IgE-Mediated Drug Hypersensitivity Reactions.

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. 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.

The role of drug, dose, and the tolerance/intolerance of new drugs in multiple drug hypersensitivity syndrome.

BACKGROUND: Multiple drug hypersensitivity syndrome (MDH) is used to describe persons with a drug hypersensitivity reaction (DHR) to at least two chemically unrelated drugs, confirmed by skin test or in vitro assay. METHODS: Medical records of 25 patients with MDH, tested and confirmed at our allergy division, were retrospectively evaluated in terms of clinical course, involved drugs, daily drug dose, latency periods, test results of skin test and cellular assays, and tolerated drugs in subsequent pharmacological treatments. RESULTS: Multiple drug hypersensitivity syndrome almost exclusively appeared as a delayed, often severe DHR and started in 14/25 with a drug reaction with eosinophilia and systemic symptoms (DRESS). Penicillins (13/25, 52.0%) and cephalosporins (6/25, 24.0%), typical high-dose drugs, were most often identified as elicitors of MDH, especially at the first DHR, followed by aromatic antiepileptics (7/25, 28.0%), vancomycin (4/25, 16.0%), and antibiotic sulfonamides (4/25, 16.0%). Cephalosporins, clindamycin, and radio contrast media (RCM) were mainly involved in subsequent DHR. The median daily drug dose of all drug trigger was 1875.0 mg (662.5; 2100.0) at the first DHR and 600.0 mg (300.0; 1300.0) at subsequent DHR, P = .0420. CONCLUSION: High-dose drugs, especially beta-lactam antibiotics, RCM and clindamycin, are common elicitors of subsequent DHR in patients with MDH. Macrolides, quinolones, doxycycline, nonaromatic antiepileptics, and paracetamol were often tolerated. As the same drugs elicited both flare-up reactions and real DHR, drug-induced flare-up reactions may be precursors of a possible second DHR and MDH. The administration of highly dosed drugs should be avoided in patients at risk for MDH.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms severity score: A useful tool for assessing disease severity and predicting fatal cytomegalovirus disease.

BACKGROUND: The prognosis of drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is highly unpredictable. Severe complications, either related or unrelated to cytomegalovirus (CMV) reactivation, are a highly probable cause of death. OBJECTIVES: The aim was to establish a scoring system for DiHS/DRESS that can be used to monitor severity, predict prognosis, and stratify the risk of developing CMV disease and complications. METHODS: A retrospective analysis of 55 patients with DiHS/DRESS was performed. A composite score was created using clinical data. DiHS/DRESS patients were also stratified into 3 groups based on the scores to predict the risk of CMV reactivation and complications. RESULTS: This scoring system made it possible to predict CMV disease and complications. Scores ≥4 were associated with the later development of CMV disease and complications, while no patients with scores <4 developed complications. LIMITATIONS: This was a single-institution study with a relatively small patient cohort that lacked a validation cohort. CONCLUSIONS: Our scoring system may be useful for predicting CMV-related complications, and early intervention with anti-CMV agents should be considered in patients with scores ≥4 or with evidence of CMV reactivation.

Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): An update in 2019.

The aim of this review was to provide an updated overview of drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS). Several new insights have been made, particularly with regards to the diagnosis, pathogenesis and care of some important complications and sequelae. The indication of herpesvirus reactivations in diagnosis in the assessment of disease severity is now better specified. Nevertheless, because fatal complications and autoimmune sequelae have been under-recognized, there is a clear need to identify effective parameters for assessing disease severity and predicting prognosis of the disease in the early phase. In this regard, we have established a scoring system that can be used to monitor severity, predict prognosis and stratify the risk of developing severe complications including fatal cytomegalovirus (CMV) disease. Regulatory T cells are likely to be central to the mechanism and would represent potential targets for therapeutic approaches that can ameliorate inflammatory responses occurring at the acute phase while preventing the subsequent development of harmful outcomes, such as CMV disease and autoimmune diseases.

Severe Cutaneous Adverse Drug Reactions: Presentation, Risk Factors, and Management.

PURPOSE OF STUDY: Immune-mediated adverse drug reactions occur commonly in clinical practice and include mild, self-limited cutaneous eruptions, IgE-mediated hypersensitivity, and severe cutaneous adverse drug reactions (SCAR). SCARs represent an uncommon but potentially life-threatening form of delayed T cell-mediated reaction. The spectrum of illness ranges from acute generalized exanthematous pustulosis (AGEP) to drug reaction with eosinophilia with systemic symptoms (DRESS), to the most severe form of illness, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). RECENT FINDINGS: There is emerging literature on the efficacy of cyclosporine in decreasing mortality in SJS/TEN. The purpose of our review is to discuss the typical presentations of these conditions, with a special focus on identifying the culprit medication. We review risk factors for developing SCAR, including HLA alleles strongly associated with drug hypersensitivity. We conclude by discussing current strategies for the management of these conditions.

Serum TARC levels are strongly correlated with blood eosinophil count in patients with drug eruptions.

BACKGROUND: This study aims to evaluate the relationship between serum thymus and activation-regulated chemokine (TARC) levels with various clinicopathological conditions in patients with drug eruptions. The value of TARC in diagnosing drug-induced hypersensitivity syndrome (DIHS) was also examined. METHODS: Study participants included 84 patients who presented with generalized eruptions suspected to be drug-related, including DIHS, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), maculopapular exanthema (MPE), erythema multiforme (EM), erythroderma, and toxicoderma. The correlation coefficients between serum TARC levels and clinical parameters in peripheral blood samples were calculated. RESULTS: Serum TARC levels in patients with DIHS were higher than those found in patients with SJS/TEN, MPE, EM, and toxicoderma. TARC levels had 100% sensitivity and 92.3% specificity in diagnosing DIHS, with a threshold value of 13,900 pg/mL. Serum TARC levels positively correlated with age, white blood cell (WBC) count, neutrophil count, eosinophil count, monocyte count, atypical lymphocyte (Aty-ly) count, serum blood urea nitrogen (BUN) levels, and creatinine (Cr) levels. It negatively correlated with serum total protein (TP), albumin (Alb), and estimated glomerular filtration rate (eGFR). Among these clinical parameters, blood eosinophil counts were most strongly correlated with serum TARC levels, with a correlation coefficient of 0.53. CONCLUSIONS: Serum TARC levels are well correlated with blood eosinophil counts in patients with generalized drug eruptions, indicating that Th2-type immune reactions underlie TARC production. Serum TARC measurements also have potent diagnostic value for DIHS, with high sensitivity and specificity.

Clinical Presentation and Diagnosis of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review.

Effective treatment of drug reactions with eosinophilia and systemic symptoms (DReSS) requires early diagnosis and close monitoring. Diagnosing DReSS is especially challenging in children due to a low incidence rate, heterogeneous clinical presentation, and a lack of (pediatric) diagnostic criteria and clinical practice guidelines. We performed a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the clinical presentation and diagnostic process of DReSS in children (aged 0-18 years). Data from 644 individuals showed that DReSS manifests differently in children compared to adults. Children have a higher number of organs involved, including higher rates of cardiac and respiratory involvement compared to adults. Children < 6 years of age appear more prone to develop neurologic symptoms. Conversely, eosinophilia, edema, and kidney involvement are less frequently observed in children. Anti-seizure medications are by far the most common causative drug class, but the range of implicated drugs increases as children get older. This study highlights that children with DReSS not only differ from adults but also that differences exist between children of different ages. As such, there is a need to establish pediatric-specific diagnostic criteria. These efforts will promote earlier diagnosis of DReSS and likely lead to improved clinical care offered to children and their families.

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.

Case Report: Minocycline-induced drug reaction with eosinophilia and systemic symptoms syndrome: a case report and literature review.

Minocycline is a tetracycline commonly used for several dermatological diseases. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but severe adverse event which can be caused by minocycline. An 18-year-old male patient developed fever, acute rash, pharyngeal pain, lymphadenopathy, hematologic abnormalities, increased creatinine level, elevated liver enzyme levels, and splenomegaly 4 weeks after the oral treatment of minocycline, 100 mg daily, for acne. Once diagnosed with DRESS syndrome, intravenous methylprednisolone was applied and his clinical manifestations and laboratory results remarkably improved. Then, a total of 13 DRESS syndrome cases induced by minocycline were reviewed and their clinical characteristics were summarized. In these cases, only two patient (15.4%) was present with pharynx involved. In conclusion, we reported a rare minocycline-induced DRESS syndrome who developed fever, eosinophilia, acute rash, pharyngitis, lymphadenopathy, acute kidney injury, hepatitis, and splenomegaly. Our report provides detailed clinical features of minocycline-induced DRESS syndrome, which helps us further understand this severe adverse event.

Atypical Presentation of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in a Patient on Pembrolizumab: A Case Report.

Pembrolizumab is an immune checkpoint inhibitor that has been associated with numerous immune-mediated adverse effects. Several of these cutaneous side effects may include bullous pemphigoid, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS). Other case reports have reported DRESS as a rare side effect of immune checkpoint inhibitors but due to its variable presentation and similarities with other cutaneous diseases, it has proven to be a diagnostic challenge. In addition, no effective methods have been developed to monitor for such adverse skin reactions in patients on immunotherapy. Here, we report a diagnostic challenging case of pembrolizumab-induced blistering lesions that were initially treated as suspected Herpes zoster and/or bullous pemphigoid but further pathology was consistent with DRESS.

Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Preceding Toxic Epidermal Necrolysis Secondary to Sildenafil: A Case Report.

Drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome and Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) are reactive entities of aberrant cytotoxic immunologic reactions to exogenous medications. While they are conventionally seen as distinct, separate conditions, we present a case of a rare evolution of DRESS syndrome into SJS-TEN in the setting of simultaneous amoxicillin-clavulanate initiation and long-term sildenafil use in a 66-year-old South Asian female with a known history of prior DRESS syndrome and pulmonary arterial hypertension. We discuss the conditions leading to her unique clinical presentation and provide considerations for future clinical encounters.

Fatal Myocarditis in Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Without Mortality-Related Risk Factors: A Case Report and Literature Review.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction characterized by skin rash, organ involvement, lymph node swelling, eosinophilia, and atypical lymphocytosis, with myocarditis being a rare but potentially fatal complication. It has been reported that in patients with cardiac involvement due to DRESS, older age and shorter periods between offending drug exposure and symptom onset are associated with mortality. We report a case of fatal DRESS-associated myocarditis in a young woman, occurring one month after drug exposure, despite intensive immunosuppressive therapy. This case report highlights the risk of mortality from DRESS-associated myocarditis even in patients lacking known risk factors.

Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Case Report From South India.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome usually presents two to six weeks after treatment with a drug implicated in this disorder. However, in some cases, it can present more than eight weeks after the initiation of an implicated medication. This is a type 4 drug hypersensitivity reaction in which any internal organ may be involved. While the liver is commonly involved, cardiac involvement is not unheard of. Comorbidities and multiorgan involvement may obscure the diagnosis, and Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria are a useful diagnostic aid. It is best treated by withdrawing the offending agent and administering systemic steroids. Oxidative stress is high in DRESS syndrome. Hepatoprotection is a priority in all patients and yields a better prognosis.

Case report: Drug reaction with eosinophilia and systemic symptoms (DRESS) induced by ceftazidime in a connective tissue disease (CTD) patient.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe cutaneous adverse drug reactions (SCARs) with high mortality. Antibiotics are the most frequent causative agents related to DRESS. However, it is rarely reported in cephalosporins, especially for ceftazidime. Here, we reported a case of ceftazidime-induced DRESS with HLA genotypic polymorphism as a risk factor. A 58-year-old woman with connective tissue disease was intravenously infused with ceftazidime for the treatment of pneumonia and intestinal infection, followed by the presence of fever, rash, and hematologic and hepatic laboratory abnormalities. DRESS was diagnosed and the positive polymorphism in HLA-B*15:02 was found. Our case illustrated the necessity to clarify the patho-mechanism and the use of pretreatment HLA analysis to prevent ceftazidime-related DRESS may be a valuable option soon.

Amoxicillin-Induced Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome With Acute Onset of Diffuse Rash and Acute Kidney Injury (AKI).

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon and potentially fatal adverse drug reaction that can affect individuals with immunosuppression, viral reactivation, pharmacogenetic susceptibility, and recent exposures to new medications. Due to the ambiguous symptomology of DRESS syndrome along with a lack of diagnosis and treatment criteria, there can be delays in diagnosis and management. Here, we present a case of a 60-year-old female with an uncommon presentation of DRESS syndrome due to a less commonly implicated drug. We aim to bring awareness to the various presentations associated with DRESS syndrome and inform readers about current diagnostic and treatment modalities used today. In addition, this case serves to provide insights that further evidence is needed to have standardized guidelines in place to effectively diagnose and manage affected patients.