Purpose Inborn Errors of Immunity (IEI) often lead to recurrent infections, immune dysregulation, and an increased risk of malignancies. Due to the heterogeneity in IEI presentations, personalized monitoring is essential for early detection of non-infectious complications. This study aims to document the characteristics and prevalence of malignancies in IEI patients. Methods A retrospective review of 355 patients diagnosed with IEI at the Adult Allergy and Immunology Clinic of Ege University was conducted. Data on demographics, clinical presentations, laboratory results, and immunological and genetic profiles of patients with malignancies were analyzed. Results A total of 40 patients with neoplasia (F/M: 18/22; median age: 51.58 years, range: 18–91) were evaluated. The median ages at IEI symptom onset, diagnosis, and neoplasm diagnosis were 16.5, 45, and 39.5 years, respectively. Malignancy was diagnosed in 60% of patients before IEI, with referrals for low immunoglobulin levels and/or severe infections, and for a genetic profile suggestive of immunodeficiency. The prevalence of malignancy in the overall cohort was 10.42% (37/355), while it was significantly higher in the common variable immunodeficiency (CVID) subgroup, reaching 20.44% (28/137). Lymphoma was the most common malignancy at 45.9%, primarily non-Hodgkin lymphoma (NHL) at 40.5%, with diffuse large B-cell lymphoma (DLBCL) as a key subtype; carcinomas were the second most common at 35.1%. Hematologic malignancies were significantly more frequent among patients with CVID (90.5%), whereas non-hematologic malignancies predominated in the non-CVID group (77.8%) (p = 0.024). Lymphoproliferation was more common in hematologic malignancies (85.7%) compared to non-hematologic malignancies (25.0%) (p < 0.001). Genetic variants were identified in 61% of cases, with 37% classified as pathogenic or likely pathogenic, including variants in TNFRSF13B/TACI, CCDC40, PLCG2, ATM, CARD11, CHEK2, CNV, COPB1, HPS5, LYST, MAPK8IP1, NBS1, NF1, NFKBIA, PI4KA, POLE, SPI1, and TAP2. Conclusions Findings confirm that NHL, particularly DLBCL, is the most prevalent malignancy in this cohort. Given the link between malignancies and underlying IEI, immunologic evaluation is recommended, particularly for NHL patients. The observed predominance of hematologic malignancies among CVID patients and the association with lymphoproliferation further emphasize the need for heightened malignancy surveillance and early immunologic workup in this subgroup. Further research on biomarkers for malignancy prediction in IEI is warranted.

Background and Objectives: Hereditary angioedema (HAE) is characterized by unpredictable skin and mucosal angioedema attacks. We aimed to find the frequency of sexual-activity-triggered attacks (STAs) and understand how the sexual life of HAE with C1-inhibitor deficiency (HAE-C1INH) patients is affected. Materials and Methods: Adult HAE-C1INH patients were included in this cross-sectional study, which started in March 2020. Demographic information, marriage properties, gender-specific sexual life characteristics, and the HAE-specific histories of the patients were collected. The Hospital Anxiety and Depression Scale (HADS) and the Turkish version of the New Sexual Satisfaction Scale (NSSS) were applied to all participants. Results: Among 42 symptomatic HAE patients, 33 (78.57%) had genital attacks and 17 (42.5%) had STAs. Ten (58.8%) had genital pain, tenderness, or swelling, and five (29.4%) had isolated abdominal and groin pain. Eight (47.1%) patients with STAs experienced a HAE attack during their first time engaging in sexual intercourse. Anxiety/depression scales, NSSS scores, and distribution of other HAE attack localizations were similar in patients with and without STAs, and no gender differences were observed. Compared to the patients without STAs, the ratio of patients who stated that their sexual lives were negatively affected and that they lost their sexual desire was higher in patients with STAs. Conclusions: Genital or abdominal attacks triggered by sexual activity may be more common than thought. Sexual activity should also be questioned for evaluating attack triggers. There is a possibility of triggering an attack with the first and ongoing sexual intercourse, and patients should be informed to keep their attack treatment medications ready in advance.

Background Hereditary angioedema (HAE) is a rare autosomal dominant inherited disease characterized by recurrent angioedema episodes and classified as HAE with C1-inhibitor (C1INH) deficiency (HAE-C1INH) and HAE with normal C1-inhibitor (HAE-nlC1INH). It may involve the face, larynx, upper airways, trunk, gastrointestinal system, genital area, and extremities. The angioedema attacks are disabling, and laryngeal edema can lead to asphyxiation and death if it is not treated successfully. We aim to investigate the association between the attack localizations and complement parameters of HAE C1INH patients.Methods Patients with HAE-C1INH from Ege University Faculty of Medicine were included. Patients with HAE-nl-C1INH were excluded from the study. Data on the clinical records were obtained retrospectively. Sociodemographic data, age at disease onset, annual attack frequencies, attack localizations, and complement parameters were recorded.Results One-hundred patients were in the study group. Fifty four percent of them were female. The majority of patients were HAE-C1INH type I (87%). The mean age at disease onset was 12.01 ±7.04 years. Plasma C4 levels were normal in eight patients (8.16%). The most frequently involved localizations were extremities (91%), gastrointestinal system (89%), and genital area (85%). Having a facial attack and erythema marginatum were both found to be correlated with the occurrence of laryngeal edema. Laryngeal edema was seen in 83.8% of the patients with erythema marginatum (P=0.010), and 75.9% of the patients with facial attacks (P<0.001).Conclusion The correlation between erythema marginatum and laryngeal edema was not reported in previous studies. Due to the unpredictable and fatal nature of the laryngeal attacks, all HAE patients and physicians should be alert of the occurrence and emergency treatment of laryngeal edema. We recommend that C4 alone should not be used to exclude the diagnosis of HAE-C1INH. The laboratory work-up should also include C1 inhibitor levels and C1INH function analysis.

Objective: The use of biological agents (BAs) has increased dramatically for inflammatory diseases and this increase has led to a rise in hypersensitivity reactions (HSRs). The symptoms and diagnostic tools for HSRs are not standardized. We aimed to analyze the prevalence of HSRs to anti-rheumatic BAs and to evaluate the usefulness of skin tests (STs) as a diagnostic tool. Materials and Methods: Our study was conducted at the Ege University Medical Faculty, Department of Internal Medicine, Division of Allergy and Clinical Immunology and Division of Rheumatology, Izmir, Turkey. Four hundred sixty patients who received BAs between Jan 1st, 2015, and Jan 1st, 2016, were reviewed in this retrospective cross-sectional study. The prevalence of HSRs was retrospectively evaluated. Ten patients with HSRs were evaluated with STs containing commercially available culprit drugs. The data was collected from hospital records. The age, sex, atopic diseases, primary rheumatic diseases, and anti-rheumatic therapies of the patients were recorded. Results: Two hundred fifty patients were treated with rituximab (RTX), 45 with infliximab, 40 with tocilizumab (TOC), 36 with golimumab, 35 with etanercept, 34 with abatacept, 15 with certolizumab, and 5 with adalimumab. Fifty reactions with RTX and two reactions with TOC were infusion-related (IRRs). Ten HSRs were observed. Eight patients had immediate (7 immediate systemic reactions and 1 local injection site reactions), and 2 had late-onset cutaneous reactions. We detected the ratio of IRRs as 11.3%, immediate HSRs as 1.73%, IgE-mediated reactions as 1.08%, and anaphylaxis as 0.86%. STs were positive in 5 of 8 patients with immediate HSRs. Four of them had anaphylaxis, and remarkably, 3 of these had positive STs. None of the ten patients had high levels of specific IgE and only four had atopic diseases. Total IgE levels were not high and specific IgE levels were not positive in the presence of HSR to BAs (p=0.039). Conclusion: Five of the 8 (62.5%) patients with immediate reactions had positive STs, which suggested IgE-mediated reactions. The prevalence of HSRs to BAs was less than the ones mentioned in the literature.

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.