Many patients with suspected or confirmed allergy to penicillin or β-lactam antibiotics are unnecessarily denied all β-lactam antibiotics (BLA) and instead given a less effective antibiotic with more side effects. However, cefazolin, a first-generation cephalosporin, is a safe and effective treatment option for these patients in most cases. Recent studies show that immunological cross-reactions among BLAs are primarily caused by structural similarities in the side chains and not by the common β-lactam ring. Cefazolin has unique R1 and R2 side chains that largely rule out cross-reactivity with other BLAs. In a case series, 21 patients with a history of alleged or confirmed allergy to BLAs were exposed to cefazolin under real-life conditions, and all but 1 patient (who developed an uncomplicated maculopapular rash) showed no reaction. Therefore, the use of cefazolin is acceptable under clinical supervision in cases of a previous uncomplicated delayed-type reaction. However, in cases of reported or documented clinical reactions to BLA that are indicative of a type I allergy (such as urticaria, angioedema, anaphylaxis), prior to (titrated) administration of cefazolin under appropriate monitoring measures, a diagnostic evaluation in accordance with guidelines, including a negative skin test for cefazolin, is advisable. This procedure avoids the use of less suitable reserve antibiotics and ensures effective treatment without incalculable risk for anaphylaxis.

Isolated solar angioedema (ISA) is an exceptionally rare photodermatosis characterized by transient, painless angioedema triggered by ultraviolet (UV) or visible light exposure, typically presenting without urticaria or pruritus, which complicates diagnosis and treatment. To date, fewer than 10 cases of ISA have been documented in the literature, and the most effective management strategies remain unclear. We describe the case of a 31-year-old woman who presented with recurrent, asymptomatic facial edema affecting her left cheek, perioral region, and eyelids after sun exposure. Each episode resolved within 24 hours without residual urticaria or systemic symptoms. The patient denied urticaria, pruritus, tongue swelling, or respiratory difficulties. Initial treatments, including cetirizine, montelukast, and prednisone, provided minimal relief, suggesting a mechanism beyond histamine-mediated pathways. Laboratory workup with normal complement C4 helped exclude hereditary angioedema, and C-reactive protein (CRP) was mildly elevated, consistent with a nonspecific inflammatory process. A diagnosis of ISA was made based on the consistent temporal relationship with sun exposure, the absence of urticaria, and the exclusion of alternative diagnoses. Given the patient's poor response to conventional therapies, dapsone was initiated due to its efficacy in other forms of idiopathic angioedema and chronic inflammatory dermatoses. Dapsone modulates inflammation by inhibiting neutrophil recruitment, suppressing prostaglandin and leukotriene activity, and scavenging reactive oxygen species. Since dapsone does not directly target the bradykinin pathway and primarily modulates inflammatory processes, its observed clinical benefit in this case may suggest involvement of alternative inflammatory pathways. After three months of therapy, the patient reported a notable decrease in the frequency and severity of flare-ups, as well as enhanced tolerance to sun exposure. This case suggests dapsone may represent a potential therapeutic option for ISA refractory to conventional antihistamines or corticosteroids, although further studies are needed. Awareness of this rare entity and the potential benefits of dapsone may help improve outcomes in patients presenting with refractory ISA.

Chronic spontaneous urticaria (CSU) is a mast cell-mediated skin disease characterized by wheals and/or angioedema. Some patients remain symptomatic despite standard-of-care antihistamines or omalizumab. We report a 44-year-old female with refractory CSU with a history of recurrent widespread erythema and wheals with pruritus for over one year. She was failed to achieve adequate disease control with oral antihistamines and 5 doses of omalizumab 300 mg. She was subsequently treated with anti-IL-4Rα antibody stapokibart 300 mg (loading dose 600 mg) for 35 weeks, with an extended-interval dosing regimen (every 2 week for 9 doses, every 3 weeks for 3 doses, and every 6 weeks for 2 doses). Rapid symptom control was observed by week 2 (Urticaria Activity Score [UAS7] of 0 and Urticaria Control Test [UCT] score of 12), with complete disease control achieved by week 22 (UAS7 of 0 and UCT score of 16). No relapse occurred during 3-month follow-up period.

Angioedema is a pathophysiologic process characterized by increased vascular endothelial hyperpermeability, leading to fluid accumulation and tissue swelling. This process is reversible in most cases; therefore, it is clinically exhibited by exacerbations and remissions. Patients experience paroxysmal, unpredictable, and slowly progressing episodes of swelling of the face, extremities, genitals, tongue, and larynx, and severe abdominal pains. Attacks affecting the oropharyngeal and upper airways impose a considerable life-threatening risk. Intestinal wall edema can cause bowel obstruction, mimicking "acute abdomen" and leading to unnecessary surgical interventions. As a chronic and recurrent disease with an undulating course, angioedema significantly affects the patient's quality of life and coping competence, presenting a considerable burden on health-providing systems. Understanding the pivotal role of C1 Inhibitor in the early 1960s and following research contributed to a better understanding of disease mechanisms. It led to unprecedented advancements in developing treatments for both attacks and prophylaxis. In parallel, international clinical guidelines and a new nomenclature have been established, assisting the diagnosis and treatment. Recently, the scope of angioedema has been expanded to include genetic variants and drug-induced angioedema. Treating angioedema associated with C1INH deficiency differs from treating allergic edema, such as in anaphylaxis and urticaria; therefore, a comprehensive evaluation, including laboratory studies, family history, and genotyping, is required. In such cases, focusing the treatment on bradykinin-dependent mechanisms is indicated for preventing attacks and reducing disease burden. This review aims to update the reader's scope of the various expressions of angioedema syndromes. It encompasses the pathophysiologic mechanisms, clinical algorithms for diagnosis, and an updated appraisal of the recommended pharmacologic treatment options for treating attacks and preventing their recurrence.

Background and Objectives: Symptomatic dermographism (SD) is the most common type of physical urticaria; however, data on its clinical characteristics and factors associated with disease severity remain limited. This study aimed to evaluate clinical features, triggering factors, associated conditions, and factors associated with disease severity in patients with SD. Materials and Methods: This cross-sectional study included 174 patients followed at a tertiary dermatology center. Data were collected using a structured questionnaire. Disease severity was categorized as severe versus non-severe using a non-validated, patient-reported classification. Factors associated with severe disease were analyzed using univariate and multivariable logistic regression models. Results: The median age was 33.0 years (IQR 27.0-40.2), and 57.4% of patients were female. Severe disease was present in 36.8% of cases. In multivariable analysis, male sex was independently associated with lower odds of severe disease (adjusted OR 0.40, 95% CI 0.20-0.82; p = 0.01). Angioedema and psychological stress were associated with disease severity in univariate analyses but not after adjustment. Persistent symptoms were more frequently reported among patients with severe disease. Conclusions: Male sex was associated with lower disease severity in this cohort. However, given the cross-sectional design and the use of a non-validated severity assessment, these findings should be interpreted as exploratory and hypothesis-generating, and do not support clinical risk stratification or causal inference.

Bupropion, a norepinephrinedopamine reuptake inhibitor, is widely prescribed for major depressive disorder and smoking cessation due to its favourable side-effect profile. Although hypersensitivity reactions are uncommon, delayed-onset urticaria has been reported. We present a case of early-onset urticaria occurring within days of bupropion initiation, highlighting the temporal sequence of angioedema followed by urticaria, nocturnal symptom exacerbation and associated clinical decision-making challenges. The patient developed angioedema on day 4 of treatment, followed by urticaria beginning on day 5. Antihistamine therapy was initiated, but urticarial symptoms persisted. Bupropion was subsequently discontinued, leading to complete resolution of symptoms within 7 days. The Naranjo adverse drug reaction probability score of 7 indicated a probable association. This case highlights the need for clinical awareness of early-onset cutaneous hypersensitivity reactions associated with bupropion, even though they are not commonly described in the literature.

The 2025 World Allergy Organization (WAO) Guidelines for the Classification, Diagnosis, and Treatment of Hereditary Angioedema (HAE) with Consideration of Worldwide Disparities provide a comprehensive, evidence-informed, and globally applicable framework for the care of this rare and potentially life-threatening disorder. HAE is a genetic disease characterized by recurrent episodes of subcutaneous and submucosal swelling, most commonly mediated by bradykinin, and is associated with substantial morbidity, impaired quality of life, and a lifelong risk of fatal laryngeal edema. The Guidelines were developed by an international panel of 40 experts from 22 countries, with representation from all world regions, reflecting the commitment of WAO to geographic diversity, inclusiveness, and global relevance. The development process for these guidelines followed a structured and transparent methodology that integrated systematic literature review, appraisal of real-world evidence, and application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework adapted for rare diseases, complemented by a formal Delphi consensus process. This approach was specifically designed to address the limitations of conventional evidence hierarchies in rare disorders, while ensuring clinical applicability across heterogeneous healthcare systems and resource settings. A central element of the guidelines is an updated classification of HAE based on underlying pathophysiology and disease endotypes. The traditional distinction between HAE types 1 and 2 is unified under the term HAE with C1 inhibitor deficiency (HAE-C1-INH), reflecting shared biological mechanisms and management principles. The guidelines also recognize an expanding spectrum of HAE with normal C1 inhibitor (HAE-nC1-INH), including forms associated with pathogenic variants in F12, PLG, ANGPT1, KNG1, MYOF, HS3ST6, CPN1, and DAB2IP, as well as cases with currently unidentified genetic causes. The diagnostic strategy emphasizes early clinical recognition based on characteristic features, including recurrent angioedema without urticaria, abdominal or laryngeal involvement, early symptom onset, and family history. A simplified diagnostic algorithm is proposed, prioritizing the C1 inhibitor functional assay as the preferred initial test when performed in a reliable specialized laboratory. Alternative diagnostic pathways are outlined for settings with limited access to specialized testing, including pragmatic combinations of biochemical assays and selective use of genetic testing, particularly relevant for HAE-nC1-INH and family screening. Management recommendations address on-demand treatment of acute attacks, short-term prophylaxis, and individualized long-term prophylaxis. Universal access to on-demand therapy is emphasized for all patients with confirmed HAE, including those who are asymptomatic, given the unpredictable nature of attacks and lifelong risk. Long-term prophylaxis is addressed within a treat-to-target framework aimed at achieving complete disease control and sustained improvement in health-related quality of life, with regular reassessment and shared decision-making. Empowering patients and caregivers through structured education, access to appropriate medications, and integration with specialized referral centers is associated with earlier treatment, reduced healthcare utilization, and improved equity of care and reduced avoidable morbidity and mortality worldwide. The 2025 WAO Guidelines for Hereditary Angioedema establish an evidence-informed, patient-centered, and forward-looking framework for the classification, diagnosis, and management of HAE. By integrating advances in pathophysiology, diagnostics, and therapeutics with global expert consensus and real-world considerations, the guidelines aim to support consistent, equitable, and high-quality care for patients with HAE across regions and healthcare systems.

Chronic urticaria is a mast cell-mediated condition characterized by the recurrent occurrence of urticaria and/or angioedema. The current definitions and classification stratify urticaria according to time course and etiology: Acute spontaneous urticaria: Spontaneous occurrence of wheals and/or angioedema for a total duration of fewer than six weeks. Chronic spontaneous urticaria (CSU): Spontaneous occurrence of wheals and/or angioedema for a total duration of six weeks or more. This is synonymous with "chronic urticaria" and "chronic idiopathic urticaria.". Chronic inducible urticaria (CIndU): Occurrence of wheals for a total duration of six weeks or more, which is inducible by physical factors (e.g., touch, pressure extremes). This is synonymous with "physical urticaria."[1].

Introduction Second-generation H1-antihistamines are the first-line therapy for chronic spontaneous urticaria (CSU); however, many patients remain symptomatic despite standard treatment. This study aims to identify the clinical and laboratory characteristics associated with high treatment requirements in patients with CSU. Methods This retrospective cohort study analyzed 6,033 adults with CSU who visited a tertiary hospital in Korea between 2002 and 2020. High-treatment-requirement CSU (HTR-CSU) was defined as requiring treatment with ≥4 H1-antihistamines simultaneously or at least one use of omalizumab. Results Of 6,033 patients, 34.5% were classified as HTR-CSU. Compared with non-HTR patients, HTR-CSU patients had a higher rate of long-term follow-up (≥60 months: 7.9% vs. 3.2%, P < 0.001) and more cholinergic urticaria (2.8% vs. 2.0%, P = 0.045), while angioedema was more common in non-HTR-CSU cases (17.8% vs. 13.0%, P < 0.001). The use of sedative H1-antihistamines, leukotriene receptor antagonists, corticosteroids, H2 blockers, and omalizumab was significantly higher in the HTR-CSU group. Laboratory findings showed elevated white blood cell counts (6.6 vs. 6.4 ×10[3]/μL), neutrophil count (3.8 vs. 3.6 ×10[3]/μL), total IgE (155.0 vs. 135.0 IU/mL), C3 (114.3 vs. 111.0 mg/dL), C4 (29.6 vs. 26.9 mg/dL), and D-dimer levels (0.40 vs. 0.34 μg/mL), along with reduced IgG levels (all P < 0.05). Conclusion HTR-CSU is associated with longer disease duration, heavier medication burden, and distinctive laboratory profiles characterized by elevated neutrophil, complement, D-dimer, and IgE levels, as well as decreased IgG levels, suggesting potential differences in immunological mechanisms compared to non-HTR-CSU.