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.

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.

X-linked immunodeficiency with magnesium defect, Epstein–Barr virus (EBV) infection, and neoplasia (XMEN) disease is a rare inborn error of immunity caused by loss-of-function mutations in MAGT1 , leading to impaired N-linked glycosylation. Although chronic EBV viremia represents a core feature, the determinants of marked clinical heterogeneity remain poorly understood. We present an integrated clinical and immunological analysis of two siblings carrying the same hemizygous MAGT1 frameshift variant who followed strikingly divergent disease trajectories. Despite shared absence of NKG2D expression, one sibling developed progressive neurodegeneration with central nervous system atrophy, whereas the other presented with EBV-positive Hodgkin lymphoma complicated by lymphoma-associated thrombotic microangiopathy and recurrent autoimmune cytopenias, including the first description of lymphoma-associated thrombotic microangiopathy in XMEN disease. Comparative immunophenotyping revealed shared B-cell maturation defects but distinct T-cell differentiation patterns. To contextualize neurological variability, we propose a pragmatic three-category classification encompassing early-onset neurodevelopmental forms, adult-onset neurodegenerative manifestations, and secondary immune-mediated or vascular involvement of the central and peripheral nervous systems. Together, these findings highlight striking intrafamilial heterogeneity in XMEN disease and support a model in which modifier-sensitive factors influence organ-specific disease expression beyond the primary genetic defect, with important implications for prognosis and surveillance.