Background/Objectives: Immediate-type hypersensitivity reactions (HSRs) to proton pump inhibitors (PPIs) represent a clinically relevant adverse drug reaction and pose diagnostic and management challenges, including variable cross-reactivity (CR). Drug provocation testing (DPT) is the diagnostic gold standard, but real-life use after testing remains uncertain. This study aimed to describe clinical features, diagnostic outcomes, CR profiles, and real-life PPI use in patients with immediate-type PPI hypersensitivity. Methods: Single-center ambispective study of 40 patients evaluated for immediate-type PPI HSRs (2014–2023). Index reactions, culprit PPI, and skin test/DPT results were recorded retrospectively. Patients tolerating an alternative PPI on DPT were followed prospectively; real-life tolerance and use were assessed by structured telephone interview. Results: Among 40 patients (87.5% female; mean age 48 years), lansoprazole was the most frequent culprit (50%); anaphylaxis occurred in 65%. Skin tests were positive in 25% (n = 9), and a shorter interval from reaction to testing was associated with positivity (p = 0.025). CR was detected in 25% (n = 10), most often between lansoprazole and pantoprazole. All 29 patients undergoing DPT tolerated at least one alternative PPI. In real-life follow-up (n = 27), 11 (40.7%) restarted PPIs without recurrence; 1 (3.7%) developed a mild cutaneous reaction despite negative testing. Fifteen (55.6%) did not restart therapy; 4 (14.8%) cited drug-related anxiety or physician-advised avoidance. Conclusions: In immediate-type PPI hypersensitivity, skin test sensitivity appears time-dependent, supporting early evaluation. DPT identifies safe alternatives, yet behavioral and clinician-related barriers limit real-life implementation; addressing these barriers is essential to optimize PPI allergy management.

Background/Objectives: Quinolones are among the most frequently implicated antibiotics in immediate hypersensitivity reactions, yet diagnostic evaluation remains challenging and the real-world behaviour of patients after de-labeling has received little attention. We examined the diagnostic work-up, outcomes, and post-de-labeling drug-use behaviour of patients with suspected quinolone hypersensitivity. Methods: This single-centre ambispective study included 29 patients evaluated between January 2020 and April 2024. Clinical, demographic, skin test, and drug provocation test (DPT) data were extracted retrospectively. Patients in whom allergy had been excluded or a safe alternative identified were contacted by structured telephone interview between May and June 2025. Results: Anaphylaxis was the most common index reaction (42.9%), and ciprofloxacin was the most frequently implicated agent (57.1% of drug instances). Skin tests were positive in 84.2% of cases, but the positive predictive value in the DPT-tested subset was only 20.0%. Of the 12 reached patients, 11 had quinolone allergy excluded; among these, only 4 (36.4%) had reused the de-labeled quinolone, while 7 (63.6%) had avoided it, including 4 who declined it when clinically indicated. Conclusions: Quinolone skin tests show limited specificity, and successful de-labeling does not guarantee real-world drug use. Patient anxiety and counselling are central to effective management.

Background and Objectives: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a rare autosomal dominant disorder caused by mutations in the SERPING1 gene and is characterized by considerable clinical variability among affected individuals. Although genotype–phenotype correlations have been reported, data from populations with high consanguinity rates remain limited. Therefore, this study aimed to construct pedigrees of HAE-C1INH families harboring SERPING1 mutations and to investigate whether mutation type is associated with phenotypic characteristics, particularly age at disease onset and C1 inhibitor functional activity. Materials and Methods: Eleven HAE-C1INH probands and their families were followed up at the Allergy and Immunology Department of Internal Medicine, Ege University Faculty of Medicine. Of the 295 family members identified through pedigree construction, 109 had symptoms compatible with HAE-C1INH, and 53 of these symptomatic individuals had both a confirmed SERPING1 genetic result and an available C1-INH functional measurement. Pedigrees were created using the Progeny Pedigree Drawing Software (Progeny Genetics LLC, Delray Beach, FL, USA). Demographic data, disease characteristics, C1-INH function levels, and SERPING1 mutation types were obtained from patient files. Results: A total of 295 individuals (151 males and 144 females) from 11 HAE-C1INH families were identified through pedigree construction. The analytical cohort comprised 53 symptomatic individuals, of whom 7 (13.2%) were homozygous for the variant. Among heterozygous patients (n = 46), 27 (58.7%) had missense mutations, 7 (15.2%) had nonsense mutations, 7 (15.2%) had large deletions, and 5 (10.9%) had frameshift deletion mutations. Patients carrying missense mutations had significantly higher median C1-INH functional activity (28.5%) than those with other mutation types (14.1%) (p = 0.026), and the median age of disease onset was significantly later in the missense group (20 years) than in the non-missense group (8 years) (p < 0.001). Annual HAE attack frequency was also lower in the missense group (median, 12 vs. 48 attacks per year; p = 0.009). Conclusions: Exploratory individual-level analyses showed higher residual C1-INH functional activity and later symptom onset among individuals carrying missense SERPING1 variants than among those carrying pooled non-missense loss-of-function variants. However, familial clustering and the small number of independent families limit the strength and generalizability of these findings.

Background and Objectives: Systemic mastocytosis (SM) is a clonal mast cell disorder characterized by abnormal mast cell accumulation and activation in multiple organs, leading to mediator-related symptoms, including anaphylaxis. Drug hypersensitivity reactions (DHRs) are a major clinical challenge in SM, but their frequency and characteristics remain undefined. This study aimed to evaluate the frequency of drug allergy, identify high-risk drug groups, investigate reaction characteristics, and examine the relationship between drug reactions, baseline serum tryptase levels, and SM subtypes in patients with SM. Materials and Methods: We retrospectively analyzed 34 patients diagnosed with SM between 2009 and 2024 at Ege University Faculty of Medicine. Clinical features, SM subtypes, baseline serum tryptase levels, and DHR characteristics were recorded. Reactions to antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, anesthetics, radiocontrast media (RCM), and COVID-19 vaccines were graded using the Ring and Messmer anaphylaxis classification. Results: Among 34 patients, the mean age was 48.6 ± 13.3 years, 53% were male, and 10 (29.4%) had DHRs. The most common culprit drugs were NSAIDs (17.6%) and β-lactam antibiotics (14.7%). Anaphylaxis was the predominant reaction, frequently associated with hypotension. In 5 patients (14.7%), drug-induced anaphylaxis was the initial and only manifestation of SM. No hypersensitivity reactions occurred to quinolones, general anesthetics, or COVID-19 vaccines. Median baseline tryptase was 50.25 µg/L (min–max: 8.59–200.00) overall, and 41.85 µg/L (min–max: 19.00–200.00) among those with DHRs. Conclusions: Patients with SM are at increased risk of severe DHRs, particularly to NSAIDs and beta-lactam antibiotics. In some patients, drug allergy may be the first and only manifestation of SM. Measurement of baseline serum tryptase is essential in patients with drug-induced anaphylaxis. A comprehensive allergy assessment, including tolerance testing and individualized counseling, is crucial to ensure safe pharmacological management.

Purpose: Reduced serum IgM is increasingly encountered in adults evaluated for inborn errors of immunity (IEI), yet its clinical relevance and diagnostic utility remain uncertain. While some patients meet criteria for selective IgM deficiency (SIgMD), others remain unclassified, reflecting significant diagnostic heterogeneity. This study aimed to characterize adult IEI patients with low serum IgM and to assess the prognostic value of IgM levels for clinical outcomes. Methods: Among 378 adult IEI patients followed at a tertiary immunology center, 43 individuals (11.4%) with low serum IgM were included. Clinical, immunological, genetic, and treatment data were analyzed, and associations between IgM levels and clinical outcomes were assessed using regression and ROC analyses. Results: The median age was 58 years, and most patients were referred following incidental detection of hypogammaglobulinemia. Recurrent infections and allergic diseases were the most common manifestations and generally preceded IEI diagnosis. While most clinical features occurred before diagnosis, hepatobiliary disease, lymphoproliferation, osteoporosis, and malignancies showed variable timing. Median IgM memory B-cell and naïve CD8⁺ T-cell percentages were below the reference range, with reductions observed in 52.9% and 53.8% of patients, respectively, and elevated IgE levels in 35.7%. Pathogenic or likely pathogenic variants were identified in a subset of patients, often without clear genotype–phenotype correlation. Serum IgM levels demonstrated limited predictive value for clinical outcomes. Conclusion: Low serum IgM in adults reflects a heterogeneous immunodysregulatory state rather than a uniform immunodeficiency. Serum IgM levels alone provide limited discriminatory and prognostic value, underscoring the need for integrated clinical and immunological assessment in diagnosis and management.

Background/Objectives: We examined how allergy findings related to candidate-agent identification, subsequent real-world imaging and clinical outcomes. Methods: This single-centre retrospective cohort included 29 adults evaluated between January 2019 and May 2025 for contrast media hypersensitivity. Imaging and outcomes between allergy evaluation and a structured telephone interview in July 2026 were assessed retrospectively and verified in national electronic health records, without prospective follow-up. Primary outcomes were skin test positivity and new hypersensitivity reactions during subsequent contrast administration. Results: The culprit contrast agent was not documented by name in 18 patients (62.1%); median evaluation delay was 60 months. Skin tests were positive in 1/20 patients (5.0%); skin-test-negative candidate agents were identified in 19/20 (95.0%). New reactions occurred in 3/14 contrast recipients (21.4%), all with immediate Brown Grade III index reactions to iohexol. Subsequent reactions included one cardiac arrest after iohexol and two Grade II reactions after iodixanol. Of seven patients imaged without contrast, four had candidate agents but reported continuing patient and physician concerns. No Holm-adjusted comparison was significant. Conclusions: Skin testing identified a candidate agent in most tested patients, but candidate identification did not establish clinical tolerance or independent protection. A shared, individualised imaging plan should communicate agent selection, premedication decisions, test limitations and precautions to patients and radiologists while preserving access to necessary imaging.