Cristiano Caruso

Eosinophilic diseases comprise a heterogeneous spectrum of conditions characterized by increased eosinophil counts and tissue infiltration, ranging from organ-specific allergic disorders to systemic inflammatory, autoimmune, and hematologic diseases. Although traditionally classified according to the primary organ involved, increasing evidence indicates that eosinophilia often reflects a systemic immune dysregulation with shared pathogenic mechanisms and overlapping clinical phenotypes. This complexity challenges purely organ-based diagnostic and therapeutic approaches and underscores the need for biomarker-driven strategies. Eosinophils act as multifunctional effector cells bridging innate and adaptive immunity and contribute to tissue damage, vascular dysfunction, and thrombotic complications through the release of cytotoxic granule proteins, cytokines, and lipid mediators. In this context, circulating inflammatory and coagulation-related biomarkers provide a non-invasive window into disease activity, pathogenic pathways, and risk stratification. Peripheral blood eosinophil count remains a central marker, while markers of coagulation activation, mast cell–derived mediators, complement components, and type 2 inflammatory biomarkers capture complementary dimensions of eosinophilic inflammation. In airway diseases such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps, integration of cytokine biology with circulating and airway biomarkers has enabled biomarker-guided selection of biologic therapies targeting interleukin (IL)-5, IL-4/IL-13, and upstream epithelial alarmins. Conversely, in systemic eosinophilic syndromes, immune-mediated diseases, and eosinophilic gastrointestinal disorders, validated serum biomarkers capable of guiding diagnosis and monitoring remain limited, highlighting important unmet clinical needs. Among currently available markers, blood eosinophil count has the clearest established clinical utility in severe eosinophilic asthma and CRSwNP, whereas tryptase, ANCA, C-reactive protein, IgG4, D-dimer, fibrinogen, ECP, and EDN provide context-dependent adjunctive or investigational information in systemic disease and EGID. This review provides an integrated overview of inflammatory serum biomarkers across eosinophilic diseases, emphasizing their role in disease phenotyping, risk assessment, and precision medicine. By bridging perspectives from internal medicine, immunology, pulmonology, rheumatology, and gastroenterology, we propose a unified, biomarker-informed framework to support individualized management across the eosinophilic disease spectrum. No single serum biomarker reliably captures tissue activity across all eosinophilic disorders; longitudinal interpretation together with clinical phenotype, treatment exposure, and organ-specific assessment is therefore essential.

Background: Severe asthma treatment commonly entails progression from medium- to high-dose maintenance inhaled corticosteroids (mICS) before biologic therapies are considered. The objective of this post hoc analysis of REALITI-A was to assess the impact of mepolizumab on clinical outcomes when initiated in patients with severe asthma receiving either medium- or high-dose mICS at baseline. Methods: REALITI-A (GSK ID: 204710) was a 2-year, prospective observational cohort study enrolling adult patients with asthma receiving newly prescribed mepolizumab 100 mg subcutaneously (index). Data were collected for 12 months before and 24 months following mepolizumab initiation. Outcomes included rate of clinically significant exacerbations (CSEs) requiring systemic corticosteroids and/or emergency department visit/hospitalisation pre- and following mepolizumab, change from baseline (28 days before index) in daily maintenance oral corticosteroid (mOCS) dose to Week 101–104, and change from baseline (90 days before index) in Asthma Control Questionnaire (ACQ)-5 score at Month 24. Results: Baseline mICS dose data were available for 774/822 patients. Compared with pre-mepolizumab, the rate of CSEs following mepolizumab reduced by 80% and 73% in the medium- and high-dose mICS subgroups. For patients with baseline mOCS use, median mOCS dose also reduced by 85% and 100% for the medium- and high-dose mICS subgroups, with 45% and 58% of patients discontinuing mOCS. For the medium- and high-dose mICS subgroups, least squares mean ACQ-5 score improved from pre-mepolizumab by 1.57 and 1.55 points. Conclusions: Following mepolizumab treatment, patients with severe asthma had reduced CSEs and mOCS dose and improved symptom control, regardless of baseline mICS dose.

Staphylococcus aureus frequently colonizes the skin and upper airways and produces a broad repertoire of immunomodulatory molecules. In asthma, the most consistent evidence concerns staphylococcal enterotoxins (SEs), which can act both as superantigens and as allergens, and IgE sensitization to SEs (SE-sIgE). SE-sIgE is associated with severe asthma, type 2 inflammation, chronic rhinosinusitis with nasal polyps (CRSwNP), exacerbations, and, in some longitudinal studies, persistent airflow obstruction. However, this relationship is not necessarily causal: SE-sIgE may reflect exposure, an immune response, or a biologically active endotype, whereas colonization, local toxin production, and systemic sensitization are not equivalent. SEs simultaneously bind class II MHC molecules and Vbeta regions of the T-cell receptor, activating large fractions of T lymphocytes; they also promote IL-4, IL-5, and IL-13 production, polyclonal B-cell activation, local IgE synthesis, mast-cell degranulation, eosinophilia, and IL-8/neutrophil circuits. Alpha-toxin (Hla) and SEB can damage the epithelial barrier, facilitating allergen penetration and alarmin signalling. These observations support an interaction model in which dysbiosis, barrier dysfunction, and type 2 immunity mutually reinforce one another along the nasobronchial axis. Corticosteroids and antibiotics may modify selected nodes in this circuit, but current evidence is insufficient to recommend decolonization or antitoxin therapy in stable asthma. Biologics interrupt downstream pathways potentially fuelled by toxins: omalizumab neutralizes free IgE; mepolizumab and benralizumab reduce the eosinophilic axis; dupilumab blocks IL-4/IL-13 signalling; and tezepelumab acts upstream on TSLP. Nevertheless, randomized trials stratified by SE-sIgE are lacking, and no evidence demonstrates that these treatments eliminate colonization or toxin production. SE-sIgE therefore appears to be a promising biomarker, particularly in severe asthma with CRSwNP, but it is not yet an autonomous criterion for biologic selection. A broader barrier-organ analysis also identifies nasal, cutaneous, and intestinal colonization as distinct ecological states; atopic dermatitis as a complementary model of toxin-amplified type 2 inflammation; and biofilms and extracellular vesicles as candidate mechanisms of persistent toxin delivery. These data increase biological plausibility but remain indirect for asthma.

Background: Precision medicine targets clinical remission, but traditional symptom-based frameworks often ignore the biological pathways driving the disease. Adequate T2 biomarker interpretation is crucial to identify phenotypes where FeNO reflects epithelial barrier distress. We investigated the “clinical-biological gap” through the analysis of six groups to distinguish profiles of symptomatic resilience from biological insensitivity to corticosteroids. Methods: Real-world study of 292 patients stratified into six groups based on BEC (≥250 cells/microL), FeNO (≥25 ppb), and IgE (≥100 kU/L). ACT, BMI, FEV1, comorbidities, and therapeutic burden were analyzed. Results: The EoS+ IgE+ group showed “symptomatic resilience”: apparent clinical control (54.5% ACT ≥ 20) supported by a critical pharmacological burden (90% salbutamol, 80% OCS ≥ 7.5 mg). The Triple Positive and EoS+ FeNO+ groups depicted “Maximum Steroid Insensitivity,” characterized by poor control despite maximal ICS/OCS regimens. FeNO could appear like the primary driver of instability, reflecting a trajectory of oxidative stress not altered by steroids. Conclusions: T2 biomarkers provide a unique prognostic value unidentifiable by standard clinical assessment. FeNO monitoring unmasks silent distress in resilient patients and identifies the “therapeutic wall” in refractory profiles. Therefore biological remission could represents the only effective target to modify the natural history of the disease.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis with heterogeneous clinical manifestations. Identifying reliable biomarkers is crucial to predicting disease evolution and guiding therapy. We analyzed clinical, biological, and functional data from 33 patients with EGPA in the vasculitic phase. Blood eosinophil count (BEC), eosinophilic cationic protein (ECP), antineutrophil cytoplasmic antibodies (ANCAs), specific IgE to staphylococcal enterotoxins (SE-IgE), and serum free light chains (FLCs) were evaluated. Severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNPs) were present in 100% and 88.5% of patients, respectively. Median BEC was 1950 cells/mm3, with elevated ECP (60.0 µg/L). SE-IgE was detected in 54.2% of patients. A significant negative correlation emerged between λ FLCs and oral corticosteroid (OCS) dose (r = –0.58, p = 0.009). Forced expiratory volume in 1 second (FEV1) was significantly lower in C-ANCA+ patients (p = 0.006). ECP and SE-IgE may serve as markers of eosinophilic activity and epithelial barrier damage in EGPA. λ FLCs might be a useful indicator of OCS exposure and treatment response. These biomarkers could support the evaluation of disease evolution and treatment response.

Atopic dermatitis (AD) is a common inflammatory skin disorder which presents with recurrent eczematous lesions and itching. Its pathophysiology is complex and multifactorial. Alterations in cell-mediated immune responses, barrier dysfunction, environmental aspects and IgE-mediated hypersensitivity are all involved. This review aims to provide the clinician with an update on the impact that Th2 inflammation can have on growth and osteoimmunology. The potential adverse or protective effects brought on by the many therapies administered in this condition are also considered. Moreover, through this analysis, we aim to show how, by inhibiting the IL-4 and IL-13 signaling pathways—fundamental in the T helper 2 (Th2) immune axis and in AD pathogenesis—dupilumab may exert a protective role on growth and osteoimmunology in moderate-to-severe AD, particularly in young patients. This focus is essential for the correct, safe management of patients with Th2 inflammation.

Purpose: Speed of clinical response to a new therapeutic intervention is a critical determinant of the overall treatment outcomes, but tools focused on asthma response speed are currently unavailable. This study aimed to validate the psychometric properties of a new questionnaire initially written in Italian, the Speed of Change in Feeling of Health (SCFH), in patients with asthma. Patients and Methods: Two hundred and seventy subjects with not-well- or poorly controlled asthma, enrolled in the Italian sites of the NEWTON real-world study, were asked to complete the provisional version of SCFH and three validated questionnaires, the Stanford Expectation of Treatment Scale (SETS), the 5-item version of the Asthma Control Questionnaire (ACQ-5), and the Global Rating Scale (GRS). Internal consistency and validity were determined. Moreover, we assessed the minimal clinically important difference (MCID) using anchor-based method. Results: One hundred and ninety-six patients completed the questionnaire at least once at 7 (± 1), 14 (± 2), or 30 (± 3) days after starting BDP/FF NEXThaler^® 100/6 μg treatment. We started from SCFH provisional questionnaire of 30 items, the internal consistency of which revealed a high redundancy (Cronbach’s alpha of 0.98), prompting its reduction to an 8-item questionnaire (SCFH-8; Cronbach’s alpha = 0.90). Known-group validity indicated significant differences in SCFH-8 scores (p = 0.0003) at 30 (± 3) days after enrollment between improved and non-improved subjects, as defined by changes in ACQ-5 scores. The study confirmed the convergent validity through comparisons with the SETS and the ACQ-5 questionnaires. A clinically relevant change in feeling of health was observed in 43.3% of participants at 7 days, while the cumulative frequency of patients reporting a clinically relevant change in their feeling of health at 30 days after enrollment was 70.4%. Conclusion: The Italian version of SCFH-8 is a valid, short tool with good psychometric properties for determining the speed of change in health perception after starting treatment.

Purpose of Review: To review current evidence on biologic therapies targeting type 2 inflammation in patients with eosinophilic COPD and respiratory comorbidities who remain uncontrolled despite optimized triple inhaled therapy. Recent Findings: Recent phase 3 trials have shown that dupilumab provides the most consistent benefit in eosinophilic COPD, reducing exacerbations and improving lung function and quality of life. Mepolizumab has shown a more limited effect, mainly on exacerbation reduction, whereas benralizumab has not demonstrated clear clinical benefit. Blood eosinophil count remains the main biomarker for treatment selection. Summary: Biologic therapies are advancing precision medicine in COPD, with dupilumab currently showing the strongest overall evidence. Careful patient selection is essential. Broader phenotyping may further improve management, as comorbidities such as chronic rhinosinusitis may contribute to symptom burden and support a multidisciplinary approach. Future studies should clarify long-term outcomes and optimal biologic selection.

Background: Urticaria, particularly chronic urticaria (CU), is a highly prevalent inflammatory skin disorder characterized by recurrent wheals and/or angioedema with a fluctuating and unpredictable course that significantly impairs quality of life and requires long-term monitoring. Despite established therapeutic guidelines, disease control remains suboptimal in a considerable proportion of patients. Telemedicine has emerged as a promising adjunctive strategy for chronic disease management. This review aims to critically evaluate the role, applications, benefits, and limitations of telemedicine and digital health interventions in urticaria management. Methods: A scoping review of the literature was conducted focusing on studies addressing telemedicine, digital patient-reported outcomes, mobile health applications, and remote monitoring strategies in urticaria. Evidence from pandemic and post-pandemic telemedicine models was also analyzed to identify transferable approaches. Results: Telemedicine demonstrates significant potential in urticaria management by enabling structured symptom monitoring, facilitating remote follow-up during therapeutic escalation (including biologic therapies), improving patient empowerment and adherence, and reducing healthcare utilization and indirect costs. Digital tools such as electronic diaries and validated PRO-based applications support continuous disease assessment. However, telemedicine cannot replace direct clinical examination, and limitations include diagnostic uncertainty, digital inequalities, data privacy concerns, and lack of large disease specific trials. Conclusions: Telemedicine represents a valuable complementary and integrative model for urticaria care, particularly suited for chronic disease monitoring. Hybrid care pathways combining remote and in-person management appear to be the most effective and sustainable strategy. Further high-quality urticaria-specific studies and standardized digital frameworks are required to optimize its clinical implementation.