THE SCIENTIFIC DISCUSSION OF KEY ISSUE ASPECTS OF IMMUNOPATHOGENESIS AND PHARMACOLOGICAL PROPERTIES AND PROFILES IN RELATION TO ADVERSE DRUG REACTIONS CHALLENGES, FOCUS ON MULTIDIMENSIONAL DRUG-INDUCED EOSINOPHILIA AND SYSTEMIC SYNDROME

Drug-induced eosinophilia and systemic symptoms (DIES) represent a complex and potentially life-threatening spectrum of adverse drug reactions characterized by eosinophilic infiltration and multiorgan involvement. This review synthesizes current knowledge on the pharmacological, immunological, and clinical aspects of these reactions, with particular emphasis on severe manifestations such as drug reaction with eosinophilia and systemic symptoms (DRESS). We examine the mechanisms by which specific drug classes—including aromatic antiepileptics, antibiotics, and novel biologics—trigger eosinophil activation through hapten formation, direct T-cell stimulation, and cytokine release. Genetic predispositions, particularly HLA associations, and viral interactions (e.g., HHV-6 reactivation) are discussed as critical modulators of individual susceptibility and clinical severity. Recent advances in biomarker discovery (e.g., serum Siglec-8, eosinophil-derived extracellular traps) and imaging modalities (e.g., 68Ga-FAPI PET/CT) are evaluated for their diagnostic and prognostic utility. The review highlights emerging therapeutic strategies, including targeted biologics against IL-5/IL-33 and pharmacogenomic approaches to prevention, while underscoring persistent challenges in management, such as corticosteroid dependence and long-term sequelae. By integrating mechanistic insights with clinical observations, this work aims to refine diagnostic criteria, optimize therapeutic decision-making, and identify future research directions to mitigate the burden of these iatrogenic complications. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is an uncommon yet serious adverse drug reaction that presents with delayed systemic inflammation and multiple organ involvement. It is a member of the spectrum of severe cutaneous adverse reactions (SCAR), usually presenting 2–8 weeks post initiation of the culprit drug. Nonspecific symptoms, latency, and overlapping clinical findings with infections, autoimmune diseases, and other hypersensitivity reactions contribute to a failure to diagnose syndrome and worsening morbidity. The objective of this thesis is to conduct a comprehensive systematic review with emphasis on the pharmacological characteristics, clinical presentation, and genetic risk factors of DRESS syndrome, as well as a range of pathological drug classes, including anticonvulsants, antibiotics, allopurinol, and nonsteroidal anti-inflammatories (NSAIDs). The article also discusses treatment, long-term prognosis and research directions. The leading alternative agents were anticonvulsants (e.g., carbamazepine, phenytoin, lamotrigine), antibiotics (e.g., vancomycin, minocycline), allopurinol, and NSAIDs including mefenamic acid and ibuprofen. More than 60 % of cases had hepatic involvement; involvement of the kidneys (25 %) and the lungs (10–15 %) were also important. Nearly all patients presented with cutaneous findings, most commonly a diffuse morbilliform rash and facial edema, and frequently had fever and eosinophilia. Genetic predisposition is an important factor, with HLA-B58:01 allele in the context of allopurinol-induced DRESS, and HLA-A31:01 in the case of carbamazepine. These results emphasize the value of pharmacogenetic screening in high-risk population groups. Viral reactivation, including human herpesvirus-6 (HHV-6), had been observed in multiple patients and has contributed to overall disease severity and duration. Therapy consisted mainly in early discontinuation of the inducing agent and systemic corticosteroids. Although the majority of patients responded to corticosteroids, some became steroid resistant and were treated with medications such as cyclosporine, IVIG, and plasmapheresis. There is a lack of standardized treatment protocols, and randomized controlled trials are highly desired. Relapses during corticosteroid reduction or autoimmunity (type 1 diabetes, thyroiditis, lupus-like syndromes) occurred in some, but not in all patients.  Multisystem DRESS syndrome mandates a high degree of clinical suspicion for early diagnosis and treatment. The underestimation of NSAID-induced DRESS emphasises the necessity for better pharmacovigilance tools and public awareness on OTC drug safety.  Future advances would need to focus on the creation of general diagnostic criteria, useful biomarkers for early diagnosis, and the use of evidence-based algorithms for treatment.