Search Results (427)

Background: Food protein-induced allergic proctocolitis (FPIAP) is generally considered a benign and self-limited condition; however, both its natural course and the impact of management strategies on prognosis remain controversial. Data on modifiable factors influencing tolerance acquisition are limited. Methods: We conducted a retrospective cohort study including 180 infants with cow’s milk-induced FPIAP. Clinical characteristics, management strategies, and outcomes were analysed. Logistic regression was used to identify factors associated with delayed tolerance, and Kaplan–Meier and Cox regression analyses were performed to evaluate time to tolerance. Results: Tolerance was achieved in 91.2% of infants, with a median time from diagnosis to tolerance of 31.1 weeks. In multivariable logistic regression, multi-food elimination at presentation (OR, 2.58; 95% CI, 1.02–6.54; p = 0.046) and a longer interval from diagnosis to reintroduction (OR per week, 1.08; 95% CI, 1.02–1.14; p = 0.022) were independently associated with delayed tolerance. Exclusive breastfeeding was associated with lower odds of delayed tolerance in univariable analysis but not after adjustment. In unadjusted time-to-event analyses, observation-first management was associated with earlier tolerance acquisition (HR, 0.37; 95% CI, 0.22–0.62; p < 0.001), whereas multiple food allergy was associated with a lower probability of tolerance acquisition over time (HR, 0.60; 95% CI, 0.41–0.88; p = 0.009). Feeding modality also showed an unadjusted temporal association with tolerance acquisition, with exclusively breastfed infants demonstrating a more favorable pattern than formula-fed infants. Conclusions: The course of FPIAP appears to be influenced not only by clinical characteristics but also by management strategies. Delayed reintroduction and multi-food elimination were associated with later tolerance, while observation-first management was associated with earlier tolerance acquisition. These findings suggest that commonly used strategies such as prolonged elimination or delayed reintroduction may warrant reconsideration in selected infants and support a more individualized and less restrictive approach to management. Full article

Kounis syndrome (KS) describes the occurrence of acute coronary syndromes precipitated by allergic, hypersensitivity, or anaphylactic reactions and represents a unique intersection between immunologic activation and cardiovascular disease. The epidemiology of KS is likely underestimated due to diagnostic overlap with other cardiac and allergic conditions and limited awareness across medical specialties. This narrative review focuses on the distinctive features of KS in special populations, emphasizing how patients’ age, comorbidities, immune status, and vascular substrate modify presentation, diagnosis, and outcomes. In elderly patients, polypharmacy, increased plaque vulnerability, and endothelial dysfunction favor Type II and III KS. Pediatric cases, although rare, are predominantly Type I and strongly associated with food allergies, insect stings, vaccines, and antibiotics, with under-recognition driven by diagnostic bias and ethical concerns surrounding invasive testing. Patients with coronary stents, cardiac devices, chronic kidney disease, and those receiving dialysis exhibit heightened susceptibility due to chronic inflammation, foreign-body hypersensitivity, and prothrombotic states. Pregnancy and the peripartum period represent a unique immuno-hemodynamic milieu in which Th2 immune shift, increased coronary vasoreactivity, and obstetric triggers can compromise both maternal and fetal perfusion. Additional risk modulation is observed in atopic individuals, asthmatics, patients with autoimmune, inflammatory, oncologic, psychiatric, and neurodevelopmental conditions, as well as in COVID-19 and post-infectious states. We propose a host-modified framework for KS that complements traditional classification by integrating immune phenotype and vascular substrate, enabling improved risk stratification and personalized preventive strategies. Full article

Allergic anisakiasis (AA), caused by the ingestion of fish contaminated with Anisakis larvae, has emerged as a growing global health concern due to the increasing consumption of raw or undercooked seafood. Anisakis simplex is identified as the primary etiologic species, responsible for gastrointestinal symptoms, IgE-mediated (Type I) or cell-mediated (Type IV) manifestations, and gastro-allergic anisakiasis (GAA), a unique clinical overlap between parasitic infection and acute IgE-mediated food allergy. In this review, we analyzed the epidemiology of Anisakis simplex allergy, the main diagnostic methods to confirm a diagnosis of food allergy, its clinical manifestations, and how these differ in different countries around the world. This multidisciplinary synthesis provides, for the first time, an integrated understanding of Anisakis-induced disease mechanisms across human, animal, and cellular levels. The persistence of allergenic proteins despite standard food processing underscores the need for improved diagnostic tools, public health surveillance, and preventive strategies—particularly in populations with high seafood consumption or occupational exposure. A comprehensive approach combining clinical, molecular, and immunological perspectives is essential to address the expanding global burden of allergic anisakiasis. Full article

Introduction: Food allergies and intolerances represent a growing pediatric health concern. While stress-related outcomes have received increasing attention, fatigue symptoms in children with food hypersensitivity remain insufficiently characterized. The aim of the study was to evaluate perceived stress and fatigue in children with food hypersensitivity. Material and Methods: We conducted an observational cross-sectional study including 339 children aged 1–18 years with specialist-confirmed food allergy, food intolerance, or mixed pathology. Data were collected through structured parent-reported interviews incorporating the Perceived Stress Questionnaire (PSQ) and the Fatigue Assessment Scale (FAS). Results: Children with food allergy had significantly higher perceived stress and fatigue scores compared to those with food intolerance (p < 0.05), with the highest levels observed in the mixed pathology group. Both perceived stress and fatigue scores increased with age, with adolescents showing the highest values. A moderate positive correlation was identified between stress and fatigue (r = 0.49, p < 0.0001). In multivariable analyses, higher stress and fatigue scores were significantly associated with age and diagnostic category, including mixed pathology, after adjustment for sex and anthropometric indicators. Higher scores were also associated with the presence of multiple clinical symptoms, such as sleep disturbances and concentration difficulties. Conclusions: Food hypersensitivity in children is associated with a significant psychological burden characterized by elevated perceived stress and fatigue, particularly in adolescents and in those with more complex diagnostic profiles. These findings highlight the importance of multidisciplinary management strategies integrating accurate diagnosis, nutritional counseling, and psychosocial support in order to address the broader impact of pediatric food hypersensitivity. Full article

Approximately 1–2% of infants have cow’s milk protein allergy (CMPA). From a clinical perspective, diagnosing CMPA using the oral food challenge (OFC) is high risk, necessitating safer alternatives. One possible alternative is component-resolved diagnostics (CRD). This narrative review examines specific IgE (sIgE) thresholds for cow’s milk protein in predicting outcomes of OFCs in European children. Eligible studies focusing on CRD in European pediatric populations were identified through PubMed and Scopus databases. Our findings highlight the crucial role of Bos d 8 (casein) in the diagnostic process. Among the analyzed milk components, Bos d 8 appeared to be a promising marker for predicting positive OFC outcomes in several cohorts. However, due to significant population heterogeneity, conflicting findings exist, with some studies indicating that no single molecular component is consistently superior to whole cow’s milk specific IgE. While other molecules, such as Bos d 6 and lactoferrin, showed limited diagnostic utility, specific IgE to Bos d 8 demonstrated the highest clinical value. Although the double-blind, placebo-controlled food challenge (DBPCFC) remains the gold standard for CMPA diagnosis, the use of Bos d 8 in CRD is a key step toward risk stratification and may help reduce the need for high-risk OFCs in selected patients. Full article

Introduction: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in early infancy and poses important clinical and economic challenges for affected children, their families, and healthcare systems. In Latin America, variability in diagnostic and therapeutic approaches remains substantial. Objective: We aim to systematically review the available evidence on CMPA, with emphasis on clinical characteristics, diagnosis, management, and economic impact, and to provide a complementary cost analysis of specialized formulas in the Colombian context. Methods: A systematic review was conducted according to PRISMA guidelines to synthesize current evidence on CMPA in pediatric populations. Studies published between 2010 and 2023 were screened using predefined eligibility criteria, and 46 studies were included in the qualitative synthesis. A complementary cost analysis was also performed to estimate the six-month costs associated with specialized infant formulas in Colombia, based on average age-specific formula consumption and standardized 2025 market prices. Results: The reviewed evidence confirms that CMPA is a heterogeneous condition with variable clinical manifestations and persistent diagnostic challenges, particularly in non-IgE-mediated presentations. Elimination of cow’s milk protein followed by oral food challenge remains the reference diagnostic approach. Breastfeeding with maternal dairy exclusion is consistently recommended as the preferred first-line strategy, whereas extensively hydrolyzed and amino-acid-based formulas are used when breastfeeding is not feasible or is insufficient. Estimated six-month costs ranged from COP 4,337,640 to COP 14,480,700 (approximately USD 1100–3600), depending on formula type. Conclusions: CMPA requires early recognition, careful clinical evaluation, individualized nutritional management, and improved access to effective and affordable treatment strategies. Full article

Background: Central compartment atopic disease (CCAD) is a recently developed terminology used to describe a specific phenotype of chronic rhinosinusitis (CRS). The aim of this study is to provide a thorough analysis of the clinical and radiological characteristics by assessing the prevalence of symptoms, asthma, allergy, aeroallergen sensitization and radiological sinus involvement. Methods: The authors searched for articles on PubMed, Cochrane, and Embase databases. A review of the articles was carried out following PRISMA guidelines; all articles were assessed for quality according to NICE criteria. Afterwards, the meta-analysis was performed with STATA 18SE software. Studies were also assessed for heterogeneity and risk of publication bias. Mean Lund-Mackay (LMK) score of patients with and without CCAD was compared. Results: A total of 16 studies were included, including 1254 patients with CRS; 537 of these were diagnosed with CCAD. The most prevalent symptoms were obstruction at 78% and congestion at 70%, followed by rhinorrhea at 66%, hyposmia at 54%, and facial pain at 24%. Dust mite at 71% was the most prevalent sensitization. Overall, the prevalence of asthma in patients with CCAD was 26%, prevalence of allergy was 67%. The mean difference in LMK scores was −3.38 in CCAD. Conclusions: Patients frequently present with nasal obstruction and congestion; the most common allergen sensitization is to dust mites. Findings on allergy and asthma prevalence support the “Unified Airway Disease” concept and emphasize the importance of a multidisciplinary approach to managing this phenotype. CCAD patients usually do not develop very high LMK scores; high scores may rule out this diagnosis. PROSPERO registration number: CRD420261361696. Full article

Hymenoptera venom allergy is a cause of anaphylaxis, which significantly affects patients’ daily lives due to the constant fear of accidental stings. Venom immunotherapy (VIT) is the only treatment capable of preventing severe systemic reactions (SSRs). Limited long-term real-life data are available, integrating both clinical and immunological outcomes. A five-year prospective observational study was conducted on 35 patients with a history of SSR who underwent VIT at a tertiary allergy center in Southern Italy; two of them had a diagnosis of systemic mastocytosis. Most patients were sensitized to Vespula, but others to Apis, Polistes dominula and Vespa crabro, reflecting the exposure pattern characteristic of Mediterranean regions. Clinical outcomes following accidental re-stings and serological trends, including total IgE, venom-specific IgE, and baseline serum tryptase, were assessed at treatment initiation and after five years of maintenance therapy. During the entire follow-up, all patients tolerated VIT. No SSRs occurred after accidental stings in 17/35 patients, confirming clinical protection achieved with VIT. Vespula serum-specific IgE presented a highly significant decrease; total IgE, tryptase and specific IgE for Apis, Polistes dominula and Vespa crabro showed a statistically significant decrease. Our findings reinforce the role of VIT as a well-tolerated, effective and disease-modifying treatment in a real-world setting. Full article

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory syndrome of the sinonasal mucosa that is imperfectly captured by phenotypes with or without nasal polyps. Since allergic rhinitis (AR) and atopy often occur alongside CRS, the term “allergic CRS” is commonly used. However, it is uncertain whether this term indicates a specific allergen-related, IgE-mediated endotype or merely represents a clinical overlap. We synthesize epidemiologic data, mucosal immunobiology, epithelial barrier dysfunction, and host–microbe interactions that can generate IgE-rich type 2 inflammation in CRS. We propose an operational entity test (objective CRS; clinically relevant allergy; evidence of IgE relevance in target tissue; exposure–response patterns; and differential response to allergy-directed interventions) to guide hypothesis testing rather than diagnosis. Using this framework, allergic fungal rhinosinusitis and central compartment atopic disease emerge as the clearest clinical prototypes where allergen contact patterns and IgE relevance plausibly contribute to disease expression. In contrast, microbial superantigens and other non-allergen stimuli can drive local IgE amplification, limiting the specificity of systemic sensitization as a causal marker. We discuss therapeutic implications, including biologics targeting type 2 pathways and epithelial alarmin blockade, and outline research priorities for endotype-resolved cohorts and mechanism-informed trials to test whether allergic CRS should evolve from a heuristic descriptor into a validated endotype. Full article

Hypersensitivity reactions to iodinated contrast media (ICM) are traditionally categorized as immediate or delayed reactions, involving IgE-mediated pathways, non–IgE-dependent mast cell or complement activation, or T cell–mediated immune mechanisms. However, we observed that some individuals develop systemic inflammatory responses that do not fit these established categories. We describe here a case series of three patients who developed cytokine release syndrome (CRS)-like reactions following iodinated contrast administration, which were initially difficult to distinguish from sepsis and were only recognized after recurrent episodes. Clinical presentation, laboratory findings, cytokine profiles, allergy investigations, and treatment outcomes were reviewed. All patients developed fever, rigors, and hypotension within 5 to 70 h after exposure, accompanied by leukocytosis and markedly elevated inflammatory markers despite negative microbiological investigations. Serum tryptase levels remained within the normal range with no significant rise, while cytokine analyses demonstrated elevations of pro-inflammatory interleukin-6 and other cytokines in patients 1 and 3 where samples were available. Standard corticosteroid premedication did not prevent recurrence, and one patient developed systemic symptoms following intradermal testing. All patients improved with high-dose systemic corticosteroids and supportive care. These findings suggest that ICM may induce a cytokine-mediated inflammatory phenotype distinct from classical hypersensitivity reactions, highlighting the importance of early clinical recognition to guide diagnosis and management. Full article

Background: The clinical intra-anesthetic changes of perioperative hypersensitivity (POH) are not specific and require a thorough differential diagnosis with other mimicking conditions. Biomarkers such as tryptase and histamine provide supportive evidence for POH. From the suggested cutoffs, a common decision threshold has not been validated for use in daily practice. The aim of this systematic review and meta-analysis is to identify biomarkers investigated for POH and to evaluate their diagnostic performance. Methods: This meta-analysis included original diagnostic accuracy studies comparing patients with clinically suspected POH and controls with no signs of intraoperative hypersensitivity reactions, in whom allergy biomarkers were evaluated, aiming to investigate diagnostic performance of the assays. Data was pooled to evaluate sensitivity and specificity. Results: In seven studies on tryptase and three studies on histamine dosing for the diagnosis of POH/POA, different fixed or dynamic thresholds for positivity were proposed. For tryptase, fixed thresholds had 59.8% sensitivity and 95.2% specificity for an optimal cutoff of 12.68 ng/mL, while dynamic thresholds yielded 77.2% sensitivity and 88.5% specificity. For histamine, fixed cutoffs presented 78% sensitivity and 85% specificity, while dynamic thresholds investigated in a single study yielded 78.2% sensitivity and 91.1% specificity. Estimates for histamine are unreliable due to limited data. Conclusions: From published data, tryptase is clearly the most robust biomarker, dynamic thresholds boost sensitivity without major specificity loss and confirm the added diagnostic value of relative changes over fixed absolute cutoffs. Preliminary results suggest that histamine might have optimal diagnostic performance, but estimates are severely limited by small sample sizes. Full article

Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization. Results: 1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols. Conclusions: RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence. Full article

Background: Almond is one of the most widely consumed tree nuts worldwide; however, almond allergy remains poorly characterized. Despite frequent sensitization, the prevalence of clinically relevant almond allergy appears low, contributing to diagnostic uncertainty. This review summarizes current evidence on the epidemiology, clinical manifestations, and diagnostic challenges of almond allergy. Methods: A narrative review was conducted using PubMed, Scopus, and UpToDate databases. Studies reporting almond-specific data on epidemiology, diagnostics, molecular allergens, and oral food challenge (OFC) outcomes were included. Results: Across heterogeneous studies, clinically confirmed almond allergy appears to be uncommon despite high rates of sensitization, particularly among patients with atopic dermatitis and concomitant tree nut allergy. In sensitized individuals, OFC positivity ranges from 4% to 33%, with anaphylaxis and severe reactions reported in 0.5–12.2% of challenged patients. Conventional diagnostic tests, including skin prick testing and almond-specific IgE, demonstrate limited predictive value, with no reliable cut-off levels for predicting clinical reactivity. Consequently, OFC remains essential for definitive diagnosis. Clinical outcomes vary according to age, ethnicity, and almond processing, with lower OFC positivity observed in pediatric cohorts and reduced reactivity to processed almond products. Conclusions: Almond allergy is relatively rare despite frequent sensitization. Improved almond-specific molecular diagnostics may enhance risk stratification and reduce unnecessary dietary avoidance. Full article

Food allergy is an exaggerated immune response, mediated by Immunoglobulin E (IgE) or by cells, to food antigens. Dogs and cats may present with both dermatological and gastrointestinal manifestations, although non-seasonal pruritus is the most common clinical sign. Despite advances in understanding the immunopathogenesis of this condition, the elimination–provocation test remains the gold standard for diagnosis. However, new diagnostic approaches, like molecular allergen macroarrays and lymphocyte proliferation assays, may complement traditional strategies, opening new perspectives for accurate diagnosis. For long-term management, strict avoidance of offending allergens is essential, but emerging therapeutic interventions, including immunotherapy using food components and targeted modulation of the gut–skin axis, are promising for improving clinical outcomes. This review summarizes current knowledge and highlights innovative approaches that can transform the diagnosis and management of food allergy in companion animals. Full article

Small intestinal bacterial overgrowth (SIBO) is an increasingly recognized condition that influences immune responses. It may be linked to atopic disorders such as bronchial asthma (BA), food allergies (FA), chronic spontaneous urticaria (CSU), and mast cell activation syndrome (MCAS). The aim of our study was to perform a structured literature search to assess the possible correlation between SIBO and the presentation of atopic disorders. The prevalence of SIBO was highest in patients with BA (60–100%) and FA (50–87.5%), followed by MCAS (30.9%) and CSU (27.9%). The diagnosis of SIBO was based on lactulose or glucose breath tests. SIBO exacerbated symptoms of atopic diseases, and treating it within BA and MCAS improved the symptoms, in contrast to CSU. The present evidence suggests a possible crosslink between SIBO and atopic manifestations. Bacterial overgrowth appears to trigger the Th2 immune response via the mucosal pathway and low-grade endotoxemia. These result in the increased synthesis of interleukins involved in allergic reactions (IL-4, IL-5, IL-13). Further studies are essential to confirm the clinical significance of this association. The “gut–allergy axis” may offer new therapeutic options and possibly improve quality of life in patients with atopy. Full article