BACKGROUND:Hypersensitivity reactions to antineoplastic agents are an increasing clinical challenge due to their rising incidence and potential severity. Early allergological assessment and tailored drug re-exposure strategies may allow continuation of essential therapies, although real-world data remain limited. METHODS:We conducted a monocentric retrospective observational study including adult oncologic patients with suspected chemotherapy-induced hypersensitivity reactions. Clinical features, allergological work-up, and management strategies were analyzed. The primary outcome was the success rate of drug reintroduction using desensitization or enhanced premedication. Secondary outcomes included skin test positivity rates and the association between cumulative chemotherapy exposure and anaphylaxis. RESULTS:Forty-two patients were included (95% female; median age 57.5 years). Re-exposure was required in 18 patients, and was successful in all patients undergoing desensitization and in 92% of those managed with enhanced premedication. Skin testing was positive in 71% of suspected platinum reactions, 30% of taxanes, and 40% of biologic agent reactions. Anaphylaxis occurred in 26.2% of patients, and a trend toward an association with cumulative chemotherapy exposure was observed; each additional cycle was associated with a 28% increase in the odds of anaphylaxis (adjusted OR 1.28; 95% CI, 1.00-1.63). CONCLUSIONS:Desensitization and enhanced premedication allow safe reintroduction of antineoplastic agents. Cumulative chemotherapy exposure is associated with an increased risk of anaphylaxis.
PURPOSE OF REVIEW:Cutaneous adverse reactions are among the most frequent complications of anticancer therapies and a major cause of treatment interruption, dose reduction, or switching to alternative regimens. This review explores the complex interplay between direct tissue toxicity and immune-mediated mechanisms underlying chemotherapy-induced skin reactions. RECENT FINDINGS:Emerging evidence indicates that chemotherapy-induced skin reactions arise from dynamic interactions among keratinocyte injury, innate immune activation, cytokine-driven inflammation, and adaptive immune responses, resulting in overlapping clinical phenotypes rather than isolated pathogenic processes. This evolving concept is exemplified by common reactions such as maculopapular eruptions, toxic erythema of chemotherapy, hand-foot syndrome, acneiform rash, and radiation recall dermatitis, as well as by immune-mediated conditions including urticaria, fixed drug eruption, severe cutaneous adverse reactions, bullous pemphigoid, and lichenoid eruptions. The expanding use of targeted therapies and immune checkpoint inhibitors further broadened this spectrum and highlighted the complexity of the underlying mechanisms. SUMMARY:Recognizing the complex interplay between tissue toxicity and immune activation provides a more comprehensive framework for interpreting chemotherapy-induced skin reactions. Improved clinical phenotyping, integrated allergologic assessment, and close collaboration between oncologists and allergists are essential to optimize diagnosis, guide rechallenge or desensitization strategies and avoid unnecessary discontinuation of effective anticancer therapies.
Background: Adult parvovirus B19 (B19V) infection occurs with cyclic outbreaks and can be associated with inflammatory manifestations mimicking or heralding the onset of systemic autoimmune diseases. Little is known about clinical traits distinguishing patients with transient vs. persisting manifestations. Methods: Leveraging data from the 2024 B19V infection outbreak, we set up a retrospective, multicentre, observational study investigating the epidemiology and clinical phenotypes of patients with B19V infection presenting to tertiary care for immune-mediated manifestations, including patients with pre-existing autoimmunity. Results: A total of 39 B19V infections were identified, yielding an annual incidence of 1.78 cases/1000 patients. Autoimmune rheumatic diseases were pre-existing in 7/39 and newly diagnosed in 5/39. One patient was hospitalised. Arthritis was more frequent in new-onset (89%) than in pre-existing (14%; p = 0.010) or no autoimmunity (19%; p < 0.001). Anaemia was not found in patients with pre-existing autoimmunity in contrast to those with new autoimmune disease diagnoses (40%; p = 0.039) or transient manifestations (52%; p = 0.013). Skin manifestations were numerically less frequent in this latter group (56%) than in patients with pre-existing (100%) or newly onset autoimmunity (80%). Autoantibodies were detected in 44% of cases and were more frequent in patients with constitutional symptoms but were not confirmed in the long term in most cases. Glucocorticoids were more frequently employed in patients with new-onset rather than pre-existing autoimmune diseases (p = 0.006) or without chronic autoimmunity (p = 0.027). Conclusion: B19V-associated new-onset autoimmunity may occur in one in six cases observed in tertiary immunology care, show distinct clinical features, and require significant immunosuppression.
PURPOSE OF REVIEW:This review provides an updated overview of the association between chronic urticaria (CU) and autoinflammatory syndromes (AS), underlining the diagnostic and therapeutic implications of identifying CU as an initial manifestation of systemic autoinflammatory disorders. RECENT FINDINGS:emerging evidence has reinforced the role of innate immune dysregulation in the pathogenesis of CU associated with AS, with particular involvement of the pro-inflammatory cytokines such as interleukin (IL)-1β. Several monogenic and multifactorial autoinflammatory diseases, including cryopyrin-associated periodic syndromes (CAPS), Schnitzler syndrome (SchS), Still's disease (SD), and others, may present with CU. Neutrophilic urticarial dermatosis (NUD) has been recognized as a histopathological hallmark. Early diagnosis remains challenging but is crucial, as targeted therapies, especially IL-1 inhibitors, have demonstrated significant efficacy in controlling systemic inflammation and preventing disease progression. SUMMARY:CU refractory to conventional treatment, particularly when associated with systemic symptoms, should prompt suspicion of an underlying autoinflammatory syndrome. A comprehensive diagnostic approach, including clinical assessment, inflammatory markers evaluation, histopathological examination, and genetic testing, is essential. Recognition of the autoinflammatory nature of CU allows for timely initiation of personalized therapies, improving patient prognosis and reducing long-term morbidity.
Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age.
Background/Objectives: Hypersensitivity reactions (HSRs) to iodinated contrast media (ICM), both immediate and non-immediate, pose clinical challenges despite using low-osmolality agents. This review aims to summarize current diagnostic approaches, cross-reactivity patterns, and the debated role of premedication. Methods: A narrative review was conducted using PubMed (2014–2024), selecting studies on ICM-related HSRs, focusing on skin and in vitro testing, drug provocation tests (DPTs), cross-reactivity, and premedication. Results: Skin tests show limited sensitivity, especially for non-immediate reactions. Cross-reactivity among ICMs is common but unpredictable. DPTs are the diagnostic gold standard but lack standardized protocols. Premedication is frequently used, though its efficacy remains uncertain. Conclusions: The management of ICM hypersensitivity is limited by diagnostic gaps and insufficient evidence on premedication. Standardized protocols and prospective studies are needed to improve patient safety and guide clinical decisions.
Background A transient and usually asymptomatic increase in blood eosinophil count (BEC) associated with dupilumab treatment has been described. Predicting factors related to the increase in BEC and the occurrence of symptoms are still poorly investigated. Objective To investigate frequency, timing, duration, clinical relevance, and potential predictors of the increase in BEC in a real-life multicenter cohort of patients affected by asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab. Methods BEC and clinical conditions at baseline and every 3 months after the start of dupilumab treatment were assessed. Any adverse drug reaction was also recorded. Remission of dupilumab-associated eosinophilia was defined by follow-up BEC values <0.5 × 109 cells/L. Results Overall, 108 of 195 (55%) patients experienced an increased BEC after dupilumab initiation, but only 29 of 195 (14.9%) showed hypereosinophilia. BEC peak occurred 6 months after the start of treatment and resolved after 9 months (median time). The probability of developing hypereosinophilia was 3.3 times higher in patients with the baseline BEC between 0.5 × 109 and 1.5 × 109 cells/L. The occurrence of symptoms during BEC peak was higher in patients with comorbidities and in patients showing any increase in BEC. Conclusions In a real-life setting, dupilumab treatment in patients with asthma and/or CRSwNP was often associated with a transient increase in BEC, but hypereosinophilia rarely occurred. Onset of symptoms co-occurring with BEC peak was observed in a minority of subjects. BEC should not preclude dupilumab initiation or continuation but should be monitored for at least 8 months after treatment begins, particularly in the case of baseline eosinophilia/hypereosinophilia and/or comorbidities.
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease of the esophagus within the type 2 inflammatory spectrum, characterized by progressive tissue remodeling driven by uncontrolled inflammation. Its incidence and prevalence are rising sharply, likely reflecting environmental triggers acting on genetic and epigenetic susceptibility. Therapeutic options have expanded rapidly, with recent approvals of new topical steroidal formulations together with biologic compounds. Proton pump inhibitors (PPIs), older swallowed topical corticosteroid (STC), and dietary interventions remain in use but are limited by suboptimal adherence and treatment discontinuation. This has driven a shift toward advanced orally dispersible STCs formulations—most notably budesonide orally dispersible tablets (BOT), budesonide oral suspension (BOS), and fluticasone orally dispersible tablets (FOT). BOT, the most extensively studied, achieves high rates of histologic and clinical remission, with favorable safety and superior adherence compared to earlier STCs formulations. This comprehensive overview focuses on following key research findings and novelty aspects of new treatments: (a) optimized esophageal targeting through orally dispersible or viscous formulations of STC, enhancing mucosal contact time and improving drug delivery to affected tissues compared to older formulations; (b) robust evidence for both induction and maintenance rates of remission, with data extending up to nearly 2 years and showing stable efficacy across clinical, histologic, and endoscopic endpoints; (c) effectiveness in STC-refractory patients, with BOT showing benefit even in those previously unresponsive to older STC formulations. This review synthesizes evidence of steroid therapy in EoE, from pharmacological aspects to clinical efficacy from randomized trials and emerging real-world studies, highlighting its impact on EoE management and outlining future therapeutic directions.
Purpose Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a common disease, which was previously approached with sinus surgery or systemic corticosteroids. The advent of biological therapies radically changed the approach to this disease. On the other hand, there is scarce scientific evidence of how specific subsets of patients respond to this treatment.Methods this is a monocentric, prospective study investigating the long-term efficacy on biweekly 300 mg dupilumab therapy in CRSwNP, prescribed to 61 patients. Patients were evaluated at baseline and every 2 months for the first 6 months, then at 9, 12, 16, 20 and 24 months.Results dupilumab proved to be an effective treatment, neatly improving both subjective and objective measurements in CRSwNP. The main finding of the study is the difference between specific subgroups of patients: while the overall response is similar, patients with Th2 comorbidities such as asthma and atopy tend to reach a stable response later, with the improvement ongoing even after 6 months of therapy, while non-asthmatic, non-atopic patients attain an earlier stability in response.Conclusions dupilumab provides an excellent long-term control of CRSwNP, but the response in asthmatic and atopic patients appears to be different and delayed when compared to non asthmatic and non atopic ones.
Increasing evidence suggests an association between atopic dermatitis, the most chronic inflammatory disease of the skin, and autism spectrum disorders, which are a group of neurodevelopmental diseases. Inflammation and immune dysregulation associated with genetic and environmental factors seem to characterize the pathophysiological mechanisms of both conditions. We conducted a literature review of the PubMed database aimed at identifying the clinical features and alleged risk factors that could be used in clinical practice to predict the onset of ASD and/or AD or worsen their prognosis in the context of comorbidities.
Eosinophilic Gastrointestinal Disorders (EGIDs) are a group of conditions characterized by abnormal eosinophil accumulation in the gastrointestinal tract. Among these EGIDs, Eosinophilic Esophagitis (EoE) is the most well documented, while less is known about Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), and Eosinophilic Colitis (EoC). The role of endoscopy in EGIDs is pivotal, with applications in diagnosis, disease monitoring, and therapeutic intervention. In EoE, the endoscopic reference score (EREFS) has been shown to be accurate in raising diagnostic suspicion and effective in monitoring therapeutic responses. Additionally, endoscopic dilation is the first-line treatment for esophageal strictures. For EoG and EoN, while the literature is more limited, common endoscopic findings include erythema, nodules, and ulcerations. Histology remains the gold standard for diagnosing EGIDs, as it quantifies eosinophilic infiltration. In recent years, there have been significant advancements in the histological understanding of EoE, leading to the development of diagnostic scores and the identification of specific microscopic features associated with the disease. However, for EoG, EoN, and EoC, precise eosinophil count thresholds for diagnosis have not yet been established. This review aims to elucidate the role of endoscopy and histology in the diagnosis and management of the three main EGIDs and to analyze their strengths and limitations, their interconnection, and future research directions.
To resume the current literature about vaccination and the onset of chronic urticaria. The recent large-scale vaccination against SARS-CoV-2 targeting elderly, adult and children, has highlighted how vaccines can trigger onset or exacerbation of chronic urticaria. COVID-19 vaccines may act as triggers in the development of chronic spontaneous urticaria. More data regarding the other vaccines are necessary to evaluate a similar potential role. Proper education of patients with vaccine-induced chronic urticaria is essential to avoid vaccination hesitancy.
Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. EoE shares a common pathogenetic mechanism with other chronic disorders pertaining to the type 2 inflammatory spectrum, such as atopic dermatitis (AD), allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). The recent advancements in EoE pathogenesis understanding have unveiled new molecular targets implied within the “atopic march” picture as well as specific to EoE. These discoveries have led to the clinical evaluation of several novel drugs (monoclonal antibodies and immune modulators), specifically aimed at the modulation of Th2 inflammation. In this comprehensive review, we have focused on the subtle mechanisms of type 2 inflammatory disorders, highlighting the similarities and differences with EoE, taking a deeper look into the evolving field of biologic therapies, already approved or under current investigation.
Background and aim Our aim was to evaluate outcomes of maintenance treatments for EoE among observational studies (OSs) and randomized controlled trials (RCTs). Materials and methods Studies reporting histological success of maintenance therapy ≥ 48 weeks were included. Primary outcome was histological success rate (defined as <15/<6 eos/HPF). Risk Ratios (RR) for histological success of maintenance therapy versus placebo or induction and drug safety were also assessed. Random effects meta-analyses with heterogeneity measured with I2 were performed. RCTs and OSs were analyzed separately. Results In RCTs, histological < 15 eos/HPF rates were 86% (95%CI, 71%-96%) for corticosteroids and 79% (95%CI, 69%-87%) for biologics. Dupilumab alone accounted for 82% (95%CI, 72%-89%) while small molecules yielded 28%. Biologics showed higher <6 eos/HPF rates compared to corticosteroids (70% vs 59%). Clinical success was 58% (95%CI, 31%-83%) for corticosteroids and 59% (95%CI, 34%-82%) for biologics. Budesonide showed common-effect-adjusted RR of 7.87 (95%CI, 4.19-14.77) of maintaining histological remission over therapy discontinuation. In OSs, proton pump inhibitors showed 64% (95%CI, 43%-83%) histological and 80% (95%CI, 53%-97%) clinical success, while corticosteroids achieved 49% (95%CI, 30%-68%) and 51% (95%CI, 18%-83%) rates, respectively. Therapy de-escalation was not associated with histological relapse (RR 1.04, 95%CI 0.72-1.51). Long-term safety was confirmed with 3% (95%CI, 1%-6%) severe adverse events in RCTs and 5% (95%CI, 2%-9%) in OSs. Treatment withdrawal rates were low (10% for RCTs, 4% for OSs). Moderate to substantial heterogeneity was observed for most outcomes. Conclusions Maintenance therapies prevent histological relapse in the long term, without clear disadvantage of dose de-escalation from induction to maintenance phase. Low adverse events and withdrawal rates confirm long-term treatment is well tolerated.
Hypersensitivity reactions (HRs) to contrast media (CM) can be distinguished in immune-mediated (including allergic reactions) and non-immune-mediated reactions, even if clinical manifestations could be similar. Such manifestations range from mild skin eruptions to severe anaphylaxis, making it important for radiologists to know how to identify and manage them. A panel of experts from the Società Italiana di Radiologia Medica e Interventistica (SIRM) and the Società Italiana di Allergologia, Asma e Immunologia Clinica (SIAAIC) provided a consensus document on the management of patients who must undergo radiological investigations with CM. Consensus topics included: the risk stratification of patients, the identification of the culprit CM and of a safe alternative by an allergy workup, as well as the use of premedication and the correct procedure to safely perform an elective (i.e., scheduled) or urgent examination. The most important recommendations are: (1) in all patients, a thorough medical history must be taken by the prescribing physician and/or the radiologist to identify at-risk patients; (2) in patients with hypersensitivity reactions to CM, the radiologist must consider an alternative, non-contrast imaging study with a comparable diagnostic value, or prescribe a different investigation with another class of CM; (3) if such options are not feasible, the radiologist must address at-risk patients to a reference centre for an allergy evaluation; (4) if timely referral to an allergist is not viable, it is recommended to use a CM other than the responsible one, taking into account cross-reactivity patterns; in the case of patients with histories of severe reactions, the presence of an anesthesiologist is also recommended and a premedication is suggested.
Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.
Summary:Background. Food allergy can range from mild to severe, life-threatening reactions with various symptoms and organ involvement. The impact of asthma on severe food-induced allergic reactions is not completely understood. In the hypothesis that asthma increases the risk of severe food-induced allergic reactions, the aim of this study is to compare the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. Methods. We performed a systematic research on electronic databases, including PubMed, Scopus and Web of Science. Observational studies, studies reporting medical characteristics of patients diagnosed with food allergy and studies reporting medical history of patients with allergic reactions were included. The primary outcome was the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. Results. Eight studies with a total of 90,367 patients met the inclusion criteria and were included, with a total population of 28,166 of patients with food allergy. The incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma was increased (OR 1.28; 95%CI 1.03-1.59; p = 0.03; I2 = 59%). Conclusions. Individuals with both food allergy and asthma are at high risk of severe, potentially fatal allergic reactions. Healthcare professionals should prioritize prevention and management strategies for these subjects. Patients with asthma and food allergy are at increased risk of potentially fatal food-induced allergic reactions. Optimal management of both diseases is nec-essary to prevent potentially life-threatening events. Study registration. The protocol of this review was registered in PROSPERO (CRD42023448293).
The role of type 2 inflammation has been progressively associated with many diseases, including severe asthma, atopic dermatitis, nasal polyposis, eosinophilic granulomatosis with polyangiitis, and, recently, eosinophilic esophagitis. Despite this, the association between asthma and esophagitis is still poorly known, and this is probably because of the low prevalence of each disease and the even lower association between them. Nonetheless, observations in clinical trials and, subsequently, in real life, have allowed researchers to observe how drugs acting on type 2 inflammation, initially developed and marketed for severe asthma, could be effective also in treating eosinophilic esophagitis. For this reason, clinical trials specifically designed for the use of drugs targeted to type 2 inflammation were also developed for eosinophilic esophagitis. The results of clinical trials are presently promising and envisage the use of biologicals that are also likely to be employed in the field of gastroenterology in the near future. This review focuses on the use of biologicals for type 2 inflammation in cases of combined severe asthma and eosinophilic esophagitis.