Fluoxetine is a widely prescribed selective serotonin reuptake inhibitor in children and adolescents. Hypersensitivity reactions are rare and poorly characterized in this population. We report the case of a 17-year-old female who developed acute throat tightness with perceived oropharyngeal swelling and respiratory symptoms within 30 minutes of the first dose of fluoxetine, in the absence of cutaneous manifestations. Symptoms improved with bronchodilator therapy. Basophil activation testing demonstrated drug-induced activation, and an oral drug provocation test reproduced symptoms, confirming hypersensitivity. Previously reported pediatric cases included delayed urticaria, angioedema, and drug rash with eosinophilia and systemic symptoms. In contrast, this case highlights an immediate reaction predominantly affecting the airway. This report expands the known clinical spectrum of fluoxetine hypersensitivity reactions and emphasizes that the absence of cutaneous manifestations does not exclude drug allergy.

Löffler endocarditis, an idiopathic hypereosinophilic syndrome, can present symptoms of heart failure and peripheral eosinophilia. We present the case of a 46-year-old woman with fatigue, shortness of breath, and edema, who was found to have thrombocytopenia, elevated cardiac biomarkers, and hypereosinophilia (2.96 k/uL). Cardiac MRI revealed hypertrophic cardiomyopathy, right ventricular hypertrophy, and a restrictive filling pattern, raising suspicion for Löffler endocarditis. Despite initial corticosteroid and diuretic treatment, she was readmitted with persistent symptoms. This case highlights the diagnostic imaging and treatment challenges with corticosteroid therapy, to control eosinophilic infiltration and prevent irreversible cardiac damage. Löffler endocarditis should be considered in the imaging differential diagnosis of unexplained heart failure.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly debilitating airway disease primarily characterized by type 2 inflammation and eosinophilic infiltration. Among the key cytokines involved, Interleukin-5 (IL-5) plays a relevant role in eosinophil biology and contributes, together with other mediators of type 2 inflammation, to epithelial barrier dysfunction, immune dysregulation, mucus hypersecretion, and tissue remodeling. Therapies targeting this cytokine have demonstrated both efficacy and safety in patients with CRSwNP. This narrative commentary summarizes current evidence in understanding IL-5's role in CRSwNP, integrating insights from an Italian otolaryngology expert panel, with a particular focus on the patient journey in Italy. Available evidence suggests that IL-5 is associated with disease severity and may contribute to multiple aspects of CRSwNP pathophysiology beyond eosinophilia. Targeting the IL-5 pathway has been shown to improve clinical outcomes, including nasal polyp burden, symptom control, olfactory function, and quality of life, in selected patients. From a clinical perspective, the expert panel highlighted several critical unmet needs in the Italian setting, including diagnostic delay, heterogeneous implementation of care pathways, suboptimal patient selection, and limited adherence to long-term management strategies. The importance of structured diagnostic work-up, endotyping, multidisciplinary management, and patient awareness was emphasized. The implementation of shared Diagnostic and Therapeutic Care Pathways (PDTA) and network-based models may support more standardized and timely management, although further evidence is needed to define their impact on clinical outcomes. Overall, improving the understanding of IL-5-driven mechanisms and addressing organizational gaps may contribute to optimizing the management of CRSwNP in clinical practice.

Asthma-chronic obstructive pulmonary disease (COPD) overlap is a heterogeneous clinical descriptor applied to patients with persistent airflow limitation who exhibit features of both asthma and chronic obstructive pulmonary disease. Diagnostic uncertainty is common, particularly when smoking-related emphysema coexists with asthma-associated traits such as bronchodilator reversibility, allergic rhinitis or atopy, eosinophilia, and elevated immunoglobulin E. We report four adults with chronic obstructive physiology and overlapping clinical, radiographic, physiologic, and inflammatory features. Two patients had persistent symptoms despite guideline-directed inhaled therapy and were treated with add-on biologic therapy targeting type 2 inflammation using benralizumab or dupilumab. The dupilumab-treated case demonstrated symptomatic and spirometric improvement over three months, whereas the benralizumab-treated case illustrates phenotype-guided biologic selection in eosinophilic asthma with coexisting COPD features and persistent severe obstruction on verified follow-up spirometry. The remaining cases illustrate practical diagnostic challenges, including the interpretation of serial spirometry, the recognition of bronchodilator responsiveness, and the reconciliation of radiographic emphysema with asthma-like variability and allergic sensitization. This case series highlights the clinical heterogeneity of asthma-chronic obstructive pulmonary disease overlap and supports a phenotype-informed approach incorporating spirometry, imaging, allergic evaluation, and accessible type 2 inflammatory biomarkers. Further prospective studies are needed to define which overlap phenotypes are most likely to benefit from biologic therapy.

Eosinophilia is commonly associated with parasitic infections, allergic disorders and haematological conditions. Although bleeding in patients with eosinophilia is rare, platelet dysfunction may contribute, even when platelet counts are normal. We report the case of a 7-year-old boy with glucose-6-phosphate dehydrogenase deficiency who presented with recurrent spontaneous bruising over 6 months. Physical examination revealed multiple ecchymoses over the lower limbs, with no organomegaly or lymphadenopathy. Laboratory investigations revealed a normal platelet count, marked eosinophilia and prolonged bleeding time. Platelet function testing using whole blood impedance aggregometry (Chrono-Log) demonstrated reduced aggregation in response to multiple agonists, consistent with a selective impairment of aggregation to adenosine diphosphate and collagen. The patient was treated with anthelminthics, resulting in a significant reduction in the eosinophil count and resolution of bleeding symptoms. This case highlights that eosinophilia may be associated with acquired platelet dysfunction, even in the presence of normal platelet counts. Clinicians should consider platelet function testing in patients with unexplained bleeding and eosinophilia, as timely treatment of the underlying cause can lead to clinical improvement.

Hyperuricemia is a major risk factor of gout and other metabolic diseases. Allopurinol, febuxostat, dotinurad, and benzbromarone are commonly used clinically as uric acid-lowering drugs. Real-world pharmacovigilance studies of four drug-related adverse drug reactions (ADRs) were conducted in the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Database of Adverse Reactions (JADER) to provide a reference for the safe clinical use of drugs. Adverse reaction data (Q1 2004 through Q3 2024) for data pertaining to the four drugs were retrieved from the FAERS and JADER databases. Four disproportionality analysis algorithms, including proportional reporting ratio (PRR), reporting ratio of ratios (ROR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM) methods, were used to analyze the signals of ADRs. A total of 14,125 ADR reports were included. Patients aged ≥ 65 years constituted the largest age group, and the proportion of reports was higher in males than in females. At the system organ class (SOC) level, positive signals for hepatobiliary disorders and renal and urinary disorders were detected for all four drugs. The predominant ADRs associated with allopurinol were drug reaction with eosinophilia and systemic symptoms and acute kidney injury, whereas those associated with febuxostat were primarily rash and nausea. Abnormal liver function and acute kidney injury were the main ADRs reported for benzbromarone and dotinurad. Several unexpected signals not previously documented in the literature were also identified, including allopurinol-associated sepsis, multiple organ dysfunction syndrome, and tubulointerstitial nephritis. Most ADRs associated with the four drugs occurred during the early stage of treatment, particularly within the first 30 days, although some were reported more than 1 year after treatment initiation. External validation using the JADER database showed that disproportionality analyses of allopurinol and febuxostat supported the findings obtained from the FAERS database. Sensitivity analyses further confirmed the robustness of the main results. This study compares ADR signaling differences between two XOD and two URAT1 inhibitors as well as high-risk signals, providing evidence for clinical monitoring of drug safety. However, large-scale prospective studies are still needed for future validation.

Hypereosinophilia may be the presenting feature of various conditions, including myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-eo-TK). We report the case of a 22-year-old male presenting with chest pain and severe cardiac involvement in the setting of marked hypereosinophilia. Laboratory findings revealed marked leukocytosis with hypereosinophilia, mild anemia, elevated NT-proBNP, impaired renal function, and elevated vitamin B12 levels. Imaging showed cardiomegaly and severe mitral regurgitation. Eosinophilia persisted despite corticosteroid and antiparasitic therapy. Bone marrow analysis revealed hypercellularity with eosinophilia, and karyotyping identified a t(5, 16) chromosomal translocation. RNA sequencing revealed a novel KCTD5::PDGFRB fusion transcript, establishing the diagnosis of MLN-eo-TK with cardiac involvement. Imatinib (400 mg daily) induced complete hematological remission within 24 hours; however, severe mitral regurgitation persisted, requiring valve replacement. To our knowledge, this is the first reported case of MLN-eo-TK associated with a KCTD5::PDGFRB fusion. This case highlights the importance of comprehensive cytogenetic and molecular testing in unexplained hypereosinophilia, particularly in corticosteroid-refractory patients, and demonstrates a rapid and marked response to imatinib.

The purpose was to investigate whether the eosinophil biomarker EMR1, ectopically expressed in colon cancer tumor cells, could be used to identify patients at risk for relapse after curative surgery. EMR1 mRNA levels were determined in primary tumors (n = 66) and lymph nodes (LNs; n = 377) from 121 colon cancer patients. Controls were resection margins of colon cancer tumors and LNs from patients with inflammatory bowel disease. Primary read-out was recurrency evaluated as disease-free survival time in the Kaplan-Meier survival model and hazard ratio calculation by uni- and multivariate Cox regression. High EMR1 levels in the regional LNs were associated with poor prognosis [hazard ratio 3.1 (1.2-8.0) at 5-year follow-up, p = 0.02]. Patients with a very poor prognosis were identified by combining EMR1 with CXCL17 analysis of LNs [hazard ratio 4.6 (1.1-19.7), p = 0.04]. High EMR1 levels in the primary tumor were associated with a good prognosis [hazard ratio 0.1 (0.02-0.9), p = 0.04]. Multivariate analysis strengthened the result for LNs but weakened the result for the primary tumor. These contradictory prognostic results probably relate to the prominent eosinophilia in the primary tumor, essentially lacking in LNs, where ectopically expressed EMR1 in tumor cells dominates. Thus, EMR1 expressed in tumor cells probably promotes tumor growth.

Hypereosinophilia (HE), defined as an absolute eosinophil count (AEC) exceeding 1,500/µL, is an uncommon finding with heterogeneous etiologies, including neoplastic causes. When associated with organ damage, it is defined as hypereosinophilic syndrome. Although hematological malignancies more frequently drive hypereosinophilia, it can rarely occur as a paraneoplastic phenomenon in solid tumors. Crucially, peripheral eosinophil counts do not reliably correlate with the severity of tissue injury, and significant organ dysfunction may arise even with mild-to-moderate eosinophilia. We report the case of a 66-year-old man, an active smoker, who presented with retrosternal chest pain, elevated high-sensitivity troponin, and markedly increased D-dimer levels. Initial chest computed tomography (CT) angiography revealed a solid pulmonary nodule. The patient was admitted under a diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI). During hospitalization, peripheral AEC peaked at 2,900 cells/μL. A paraneoplastic aetiology was established after ruling out secondary and clonal causes. Clinical course was marked by rapidly progressive multiorgan complications, including cerebral ischemia, splenic and renal infarctions, cutaneous embolic phenomena, and severe eosinophilic endomyocarditis. Although diagnosis of metastatic lung adenocarcinoma was confirmed by cervical lymph node biopsy, the patient suffered rapid deterioration and died before tumour-directed therapy could be initiated. Paraneoplastic hypereosinophilia in lung adenocarcinoma is an exceptionally rare manifestation associated with an aggressive tumor biology and poor prognosis. This case highlights its potential for devastating multiorgan involvement despite non-extreme peripheral eosinophilia, underscoring the vital need for early etiological recognition to prevent irreversible clinical deterioration.