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.

Effects of titration speed, gender, obesity and concomitant medications on the risk and onset time of clozapine-associated fever among Japanese patients with schizophrenia: retrospective review of charts from 21 hospitals.

BACKGROUND: Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation. AIMS: We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date. METHOD: We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days. RESULTS: Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset. CONCLUSION: A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

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.

Antibiotic-induced severe cutaneous adverse reactions: a single-center retrospective study over ten years.

Objective: Severe cutaneous adverse reactions (SCARs) are rare but life-threatening, with antibiotics being the main cause. This retrospective study from a single center was designed to analyze the culprit drugs, clinical features and treatment outcomes of antibiotic-induced SCARs. Methods: We analyzed cases of antibiotic-induced SCARs in a tertiary hospital in China between January 2013 and January 2024, including Steven-Johnson syndrome (SJS) or Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Descriptive analysis of the demographic characteristics, clinical manifestations, treatment and prognosis were carried out. Results: Among 354 cases of SCARs, 63 validated antibiotic-related cases were included. Cephalosporins (31.7%), penicillins (25.4%), and quinolones (19.0%) were the most common triggers for SCARs. Overall, liver (50.8%), lungs (31.7%), and kidneys (23.8%) were the most frequently affected organ in SCARs cases. Eight patients (28.6%) in the SJS/SJS-TEN overlap group and 8 patients (80.0%) in the TEN group received combination therapy of corticosteroids and IVIG. Patients with SCARs caused by penicillins or cephalosporins could receive alternative treatments such as lincomamides, quinolones, and tetracyclines. The mortality rate in the TEN group was the highest at 20.0%, followed by the SJS/SJS-TEN overlap group (7.1%), and no deaths were observed in the DRESS and AGEP groups. Conclusion: The identification of the culprit antibiotics and the application of alternative antibiotic therapies are crucial for the management of antibiotic-induced SCARs. If complicated underlying conditions and complications like advanced age, cancer and pneumonia coexist with SCARs, patients might be more at risk for mortality.

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.

A Dermatological Dilemma: The Importance of Recognizing Dermatologic Manifestations of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in Skin of Color Patients.

Many dermatologic conditions that are seen in medical literature are typically on lighter skin tones making it easier to identify. This can pose a difficult problem in the care of skin of color patients. The purpose of this paper is to highlight the importance of dermatologic manifestations in skin of color patients and the disparities that exist in the medical field. Here, we present the case of a 51-year-old African American male who was hospitalized on a prolonged course of antibiotics found to have drug reaction with eosinophilia and systemic symptoms (DRESS). Although the initial diagnosis was not made at symptom onset due to the atypical presentation in darker skin tones, the patient improved when the diagnosis was eventually made with cessation of the offending agent and steroid therapy. There is a vital need for continued awareness of the disparities that exist within medical literature and the medical field in regard to skin of color patients.

Drug Rash With Eosinophilia and Systemic Symptoms (DRESS) Due to Multiple Anti-Epileptic Drug Hypersensitivity.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare type of hypersensitivity reaction with an incidence in the general population of one case per 10,000, which may lead to life-threatening complications with a mortality rate of 3.8% to 10%. This condition has been characterized by the following symptoms: skin rash, febrile episodes, lymph node enlargement, and involvement of internal organs, specifically the liver. Common medications associated with these reactions are aromatic anticonvulsants and antibiotics. In this paper, we report a case of a 41-year-old female presenting with head-turning to the right and stiffening of the right upper and lower extremities, with subsequent involvement of the left upper and lower extremities secondary to a left frontal lobe glioma. She had a hypersensitivity reaction to five anticonvulsant medications and was treated with prednisone pulse therapy. This case showed that DRESS syndrome may also manifest with newer non-aromatic anticonvulsants such as levetiracetam and that steroid pulse therapy is effective in resolving the elevated blood parameters as well as skin lesions of patients with DRESS syndrome. The patient's epilepsy responded well to gabapentin without any recurrence of seizure episodes or hypersensitivity reactions.

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 DRESS syndrome without eosinophilia.

Despite the name, eosinophilia is not essential for diagnosing drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Early recognition and stopping the offending drug are vital to managing this condition, as it can otherwise lead to high mortality rates.

A diagnostic dilemma: distinguishing a sulfasalazine induced DRESS hypersensitivity syndrome from a CD30 + lymphoma in a young patient.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction characterized by cutaneous rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and life-threatening organ dysfunctions. We describe the case of a 26 year old patient admitted to the Emergency Department for DRESS syndrome after sulfasalazine treatment for rheumatoid arthritis in the right knee. Whole body computer tomography showed multiple neck, chest, and abdominal lymphadenopathy with splenomegaly, massive ascites and severe hepatic cytolysis. Serology results for Epstein-Barr Virus (EBV), influenza, measles, rubella, hepatitis A and B were negative. The histologic analysis of skin, lymph node and bone marrow biopsies could not indicate a classical Hodgkin's Disease or iatrogenic immunodeficiency/EBV-associated lymphoproliferative disorder (LPD), Hodgkin type. The relatively small caliber of the CD30 + immunoreactive blastoid cells in the lymph nodes suggested reactive immunoblasts rather than Hodgkin cells. The morphologic aspects of the lymph node biopsies with predominance of T-cells were compatible with the diagnosis of a sulfasalazine-induced DRESS syndrome as the patient had a high RegiSCAR score for DRESS. [DRESS Syndrome Foundation: Diagnosis and Treatment. (2023)] The patient's complex clinical course, marked by two hospital admissions, highlights the challenges in diagnosing and managing DRESS. This case underscores the need for individualized care, close patient monitoring, and further research to better understand DRESS's underlying mechanisms and optimal therapeutic strategies.

Delayed Skin Testing for Systemic Medications: Helpful or Not?

Cutaneous adverse drug reactions collectively are delayed drug reactions such as morbilliform drug eruption and severe cutaneous adverse reactions (SCARs). Morbilliform drug eruption may wane over time, be the result of drug viral interactions, and be amenable to slow reintroduction or rechallenge, whereas SCARs are HLA class I restricted, T-cell-mediated reactions that demonstrate durable immunity and warrant lifelong avoidance. SCARs such as drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption often occur in the setting of multiple drugs dosed together. Collectively, they lead to significant morbidity, mortality, and drug safety concerns that could severely limit future treatment options. Currently, no single or combination of diagnostic tests for SCARs such as ex vivo or in vitro testing, in vivo (skin) testing, or other adjunctive tests such as HLA typing have 100% negative predictive value. In this "Controversies in Allergy Review" article, we review the current literature on delayed skin testing (patch and delayed prick/intradermal test) and critically assess the evidence base of its utility across different drugs and clinical phenotypes of delayed hypersensitivity reactions.

Sildenafil-induced drug reaction with eosinophilia and systemic symptoms.

Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS) is a life-threatening, multi-organ adverse drug reaction with a mortality rate of approximately 10 %-20 %. The most common culprit drugs are anticonvulsants, some antibiotics such as dapsone and minocycline, salazosulfapyridine, allopurinol and some antiretroviral molecules such as abacavir and nevirapine. Only one case of DRESS induced by sildenafil has been reported in the literature. Here we report a new case.

Metronidazole-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome With Parvovirus B19 Reactivation: A Pediatric Case.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and rare syndrome that causes life-threatening organ dysfunctions. Here, we present the case of a 10-year-old child who developed a pruritic erythematous eruption, fever, facial edema, and lymphadenopathy seven days after receiving intravenous metronidazole (20 mg/kg/day), vancomycin (50 mg/kg/day), and cefotaxime (200 mg/kg/day). Laboratory tests showed eosinophilia and liver damage as well as positive parvovirus B19 IgM and IgG indicating viral reactivation. Vancomycin was initially discontinued and later reintroduced with no ill effects. The patient was managed with topical corticosteroid emollients and cetirizine and improved within seven days of metronidazole withdrawal. Treatment with cefotaxime was continued and showed no adverse effects.

Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: a disproportionality analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS. AIM: This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHOD: A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3. RESULTS: There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57). CONCLUSION: This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Advanced human immunodeficiency virus (HIV) does not affect ability to utilize lymphadenopathy in assessment of drug reaction with eosinophilia and systemic symptoms syndrome in HIV and tuberculosis: Prospective comparative study.

Background: RegiSCAR validation criteria for drug reaction with eosinophilia and systemic symptoms (DRESS) includes lymphadenopathy, a frequent feature of both tuberculosis (TB) and human immunodeficiency virus (HIV). TB is the most common HIV-associated coinfection. Advanced HIV is associated with lymph node (LN) fibrosis. It is not clear if this negatively affects case validation in HIV-associated DRESS. To answer this question, we designed a prospective descriptive study to assess lymphadenopathy in various combinations of comorbid HIV, TB, and DRESS. Objectives: We sought to describe the prevalence of DRESS-associated lymphadenopathy and characterize LN quality, size, and distribution in a high HIV-TB burden setting over time. Methods: We prospectively and systematically examined LN in 25 consecutive acute DRESS cases hospitalized at a South African tertiary-care center and 10 hospitalized non-DRESS HIV-TB coinfected controls. Results: Fourteen (56%) of 25 patients were HIV infected, with a median (interquartile range) CD4 count of 254 (66-478) cells/mm³, and 7 of 14 were coinfected with TB. Using RegiSCAR criteria, 12 (46%) of 25 were definite DRESS cases, 8 (31%) of 25 probable, and 5 (23%) of 25 possible. Possible cases were excluded in the analysis. Fifteen (75%) of 20 subjects had LN in ≥2 anatomic sites, including all 7 patients with HIV-TB coinfection. In contrast, 1 (20%) of 5 hospitalized non-DRESS HIV-TB coinfected controls had LN. Cervical LN, in 15 (88%) of 17, was most common, followed by axillary (76%) and inguinal (59%). Cervical LN ranged between 1 and 2 cm in size. Among the 8 (32%) of 25 subjects with follow-up data, LN had regressed in all within 6 weeks of stopping the offending drug and initiating TB treatment. There was no correlation with CD4 cell count and LN. Conclusion: Lymphadenopathy is a common feature of acute DRESS, even among HIV-TB-coinfected patients with advanced immunosuppression.

Operating Room Airborne Microbial Load: Nonscrubbed Staff Apparel Matters.

BACKGROUND: Infection is a leading cause of total joint arthroplasty failure. In previous studies, we found correlations between the level of contamination, concentrations of airborne particles, and the number of staff present. In this study, we focused on the apparel of nonscrubbed operating room (OR) staff to elucidate their contribution to the airborne microbial load. METHODS: We compared hospital-laundered scrubs to disposable coveralls using 2 methods. (1) Participants entered an isolation chamber with a controlled environment and completed tasks for 1 hour wearing both the approved and alternative OR attire. Settle plates collected viable contaminants that were shed by the participants during testing. (2) Lab members conducted standardized maneuvers in a functional OR that simulated typical movements of the nurse, anesthesiologist, implant representative, and entering/exiting staff. An airborne particle counter and settle plates were positioned throughout the OR. After 1 hour, the staff changed apparel and repeated the test. Each session of both phases consisted of 2 tests by the same individuals on the same day. RESULTS: There was approximately a 10-fold difference in the settlement rate of viable particles between groups when employing the isolation chamber. The settle rate for scrubs was 5,519 ± 1,381 colony forming units (CFUs)/m2/h, while the settle rate for coveralls was 505 ± 55 CFUs/m2/h (P = .008). During testing in the OR, 218.7 ± 35 CFUs/m2/h were captured for scrubs, compared with 50.5 ± 13 CFUs/m2/h for the coverall (P < .01). The concentration of airborne particles collected for scrubs was 4,952.1 ± 495 particles/m3 and 1,065 ± 53 particles/m3 for the coveralls (P < .01). This was a 77% and 79% reduction for both measures, respectively. CONCLUSIONS: The open nature of standard scrubs allows contaminated particles to escape into the OR environment, whereas the one-piece design of the coveralls restricts pathways of escape. The results of this study may be helpful when developing hospital infection prevention policies.

Management of acute coronary syndromes requiring coronary angiography in patients with drug reaction with eosinophilia and systemic symptoms syndrome induced by iodinated contrast media: two case reports and narrative review.

Background: Hypersensitivity reactions to iodinated contrast media (ICM) are frequently encountered in clinical practice. Severe manifestations, despite being infrequent, can be life-threatening and represent an issue when re-administration of ICM is required. Clear recommendations on prevention and management of relapses are still lacking. Case summary: We present the cases of two patients presenting with acute coronary syndrome requiring urgent coronary angiography, with an anamnesis of ICM-induced drug reaction with eosinophilia and systemic symptoms syndrome. Both patients safely underwent a coronary angiography with the use of a different ICM (iobitridol) to the one linked to hypersensitivity manifestations, after premedication with corticosteroids and H1 antagonists. Discussion: Our experience highlights that in clinical situations in which the use of ICM is urgently needed, premedication with corticosteroids and H1 antagonists together with the choice of an alternative contrast agent (when the culprit is known) represents an effective strategy to perform a potentially life-saving procedure while avoiding serious systemic allergic reactions.