Background: Biologic agents are widely used in clinical practice, but hypersensitivity reactions (HSRs) may limit their use. Rapid drug desensitization (RDD) allows patients to safely continue essential therapy by inducing temporary tolerance, but evidence on newer biologics such as daratumumab, brentuximab vedotin, and pertuzumab remains scarce. Methods: We retrospectively reviewed 11 patients who underwent RDD for biologic-induced HSRs between 2020 and 2024 at a tertiary allergy center. Each protocol was jointly designed by an experienced allergist and clinical pharmacist and carried out in the intensive care unit under close nurse and physician supervision. Demographic, clinical, and laboratory data, reaction grades, skin test results, premedication regimens, and breakthrough reactions (BTRs) were analyzed. Results: A total of 43 RDD cycles were performed for rituximab (n = 18), brentuximab vedotin (n = 13), daratumumab (n = 9), and pertuzumab (n = 3). Six patients underwent skin testing, two with positive results. Four patients (36%) experienced only mild cutaneous BTRs during their first RDD cycle, and no severe events occurred. The overall BTR rate per cycle was 9.3%. Extending premedication to more than 24 hours before desensitization reduced BTR frequency from 17% to 4%. Conclusion: RDD proved to be a safe and effective approach for managing HSRs to both common and less frequently used biologic agents. All patients completed treatment without discontinuation. Extended premedication period, multidisciplinary planning, and intensive care unit-based monitoring appear to enhance procedural safety and support the broader implementation of RDD in clinical allergy practice. Plain Language Summary: Biologic drugs are important treatments for many immune, blood, and cancer-related diseases. However, some patients develop allergic or hypersensitivity reactions that prevent them from continuing these medicines. RDD is a medical procedure that allows patients to safely receive a medication that previously caused a reaction. It works by gradually introducing small doses of the drug until the body temporarily tolerates it. In this study, we reviewed the experiences of 11 adult patients who had allergic reactions to biologic agents such as rituximab, brentuximab vedotin, daratumumab, and pertuzumab. A total of 43 desensitization cycles were performed under close medical and nursing supervision in an intensive care unit. The desensitization plans were designed together by allergists and clinical pharmacists. The results showed that the procedure was safe and effective. Mild reactions occurred in a few cases, but no serious problems were seen. When premedication (such as steroids and antihistamines) was started more than 24 hours before the procedure, allergic symptoms were less frequent. This highlights the importance of careful planning and teamwork in making desensitization safer for patients.

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.

Background/Objectives: Systemic mastocytosis (SM) is a rare clonal mast cell disorder associated with mediator-related symptoms and a broad range of neurocognitive and sleep-related complaints. Fatigue, insomnia, and brain fog are frequently reported in clinical practice, but objective polysomnographic data in this patient population remain limited. As overweight and obesity are established contributors to sleep-disordered breathing, polysomnography (PSG) findings in patients with SM should be interpreted with caution when a control group is not available. This study aimed to characterize sleep architecture, sleep continuity, and sleep-disordered breathing in adult patients with SM who underwent PSG. Methods: This single-center observational study included nine adult patients diagnosed with SM from the Ege University Mastocytosis Database between January 2023 and January 2024. No control group was included. All patients underwent overnight laboratory PSG after discontinuation of antihistamine therapy for at least seven days. Demographic characteristics, SM subtype, baseline serum tryptase levels, Epworth Sleepiness Scale (ESS) scores, and brain fog-like cognitive complaints were recorded. PSG parameters included total sleep time, sleep efficiency, sleep onset latency, wake after sleep onset, rapid eye movement (REM) latency, sleep stage distribution, arousal burden, apnea–hypopnea index (AHI), oxygenation parameters, and periodic limb movements. Results: The study included four women and five men, with a median age of 50 years. Eight patients had a body mass index (BMI) ≥ 25 kg/m², indicating that the cohort was predominantly overweight or obese. The most common SM subtype was indolent SM. The median baseline serum tryptase level was 55.9 ng/mL, and the median ESS score was 9. Only two patients had excessive daytime sleepiness according to ESS > 10, whereas six patients reported brain fog-like complaints. Median sleep efficiency was 91.4%, total sleep time was 344 min, sleep onset latency was 9 min, and wake after sleep onset was 11 min. Median REM latency was 128.5 min. Sleep stage distribution showed median N1, N2, N3, and REM sleep proportions of 3%, 54%, 26%, and 16.7%, respectively. One patient had no observed REM sleep, and two patients had no measurable N3 sleep. The median number of arousals was 55. The median AHI was 8.2 events/hour. Although eight of nine patients met PSG criteria for obstructive sleep apnea (OSA), including five with mild and three with severe disease, this finding should be interpreted in the context of the high prevalence of overweight/obesity in the cohort. All patients with BMI ≥ 25 kg/m² had OSA, whereas the only normal-weight patient did not. Conclusions: In this single- center observational study, PSG demonstrated frequent sleep-disordered breathing, REM-related changes, and variable arousal burden in patients with SM; however, these findings cannot be separated from the predominance of overweight/obesity and the absence of a control group. Brain fog-like complaints were common, although excessive daytime sleepiness was present in only a minority of patients. Because most patients were overweight or obese and no control group was included, these findings cannot be attributed directly to SM. However, the results suggest that objective sleep assessment may be useful in selected patients with SM, particularly when fatigue, non-restorative sleep, or cognitive complaints are present. Larger controlled studies with BMI-matched groups are needed to clarify the relationship between SM, mast cell mediator activity, and sleep abnormalities.

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.