The real-world safety of sacubitril / valsartan among older adults (≥75): A pharmacovigilance study from the FDA data.

BACKGROUND: Heart failure is a major cause of morbidity and mortality among older adults. Sacubitril-Valsartan (Sac/Val) has been shown to improve patients' outcomes; however, its safety profile among older adults has not been adequately examined. We therefore aimed to examine its safety profile among this population. METHODS: We conducted a retrospective pharmacovigilance study utilizing the FDA's database of safety reports (FAERS). We employed disproportionality analysis comparing Sac/Val to angiotensin receptor blockers (ARBs). We aim to evaluate the reporting of pre-defined adverse events associated with Sac/Val (hypotension, acute kidney injury (AKI), hyperkalemia and angioedema) in two age groups: adults (< 75 years) and older adults (≥ 75). For each subgroup, we calculated reporting odds ratio (ROR) and compared them by calculating P for interaction. RESULTS: The FAERS database encompassed 18,432 unique reports of Sac/Val. Of them, 12,630 (68.5%) subjects were adults (< 75 years), and 5802 (31.5%) were older adults (≥ 75 years), with a median age (IQR) of 68 (59-77). When compared to ARBs, Sac/Val was associated with higher reporting of hypotension, lower reporting of acute kidney injury (AKI) and hyperkalemia, and similar reporting of angioedema. Notably, we did not observe a significant interaction between the age subgroups and the risk estimates (AKI: Pinteraction = 0.72, hyperkalemia: Pinteraction = 0.94, hypotension: Pinteraction = 0.31, and angioedema: Pinteraction = 0.61). CONCLUSIONS: In this postmarking study, none of the prespecified adverse events was reported more frequently in older adults. These findings provide reassurance for safety use of Sac/Val in older adults.

A comparative analysis of chronic inducible urticaria in 423 patients: Clinical and laboratory features and comorbid conditions.

BACKGROUND: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU) which require specific physical or non-physical triggers to occur. They may be isolated or may coexist with chronic spontaneous urticaria (CSU). Despite their frequent appearance in dermatology clinics, there is scarce information on the distinguishing features among the most common subtypes of CIndU as well as isolated CIndU versus CSU plus CIndU. OBJECTIVES: To compare clinical and laboratory characteristics, and comorbid conditions among the most common CIndU types and isolated CIndU versus CSU plus CIndU. METHODS: We retrospectively analysed CIndU patients and compared patients' demographic, clinical and laboratory characteristics across isolated CIndU, CSU plus CIndU, symptomatic dermographism (SD), cold urticaria (ColdU) and cholinergic urticaria (ChoU). RESULTS: A total of 423 patients (~70% isolated CIndU, ~30% CSU plus CIndU, ~5% mixed CIndU subtypes) were included in the study. The most frequent CIndU subtypes were SD (68.6%; 290/423), ColdU (11.4%; 48/423) and ChoU (10.9%; 46/423). Isolated CIndU patients were younger than CSU plus CIndU (33.74 ± 12.72 vs. 37.06 ± 11.84, p = 0.010). Angioedema, emergency referrals, need for systemic steroids, comorbid systemic disorders were more frequent and baseline urticaria control test scores were lower in CSU plus CIndU patients (vs. CIndU, p < 0.001, p = 0.008, p < 0.001, p = 0.031, p = 0.036, respectively). Among CIndU subtypes, ChoU patients were younger (24.9 ± 12.2 vs. 34.47 ± 12.12 vs. 31.38 ± 14.95; p < 0.001) and had male predominance (p < 0.001) while SD patients had no angioedema (p < 0.001) and had higher frequency of increased total IgE levels (p = 0.006). CONCLUSIONS: Isolated CIndU and CSU plus CIndU seems to be different endotypes of CU where CSU plus CIndU presents a more severe and refractory course. There are distinctive features of each CIndU subtype. These suggest involvement of different pathomechanistic pathways in these subtypes that need to be clarified in future studies.

The analysis of the effect of the COVID-19 pandemic on patients with hereditary angioedema type I and type II.

Due to the similarity between the pathomechanism of SARS-CoV-2 infections and hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), a possibility emerged that C1-INH-HAE may worsen the course of the infection, or that the infection may influence the severity of angioedema (HAE) attacks in C1-INH-HAE patients. Our study aimed to evaluate the effects of the COVID-19 pandemic on the quality of life (QoL) of Hungarian C1-INH-HAE patients, and to survey the acute course of the infection, post COVID symptoms (PCS), vaccination coverage and the side effects of vaccines in this patient population. 93 patients completed our questionnaire between 1st July 2021 and 31st October 2021. In this same period and between March 2019 and March 2020, 63 patients completed the angioedema quality of life questionnaire (AE-QoL). Out of those patients infected with SARS-CoV-2 in the examined period (18/93 patients; 19%), 5% required hospitalization, 28% experienced HAE attacks in the acute phase of the infection, and 44% experienced PCS. A total number of 142 doses of vaccines were administered to the patients. Serious vaccine reactions did not occur in any case, 4 (5%) out of the 73 vaccinated patients experienced HAE attacks. No significant difference (p = 0.59) was found in the median of the AE-QoL total score, or in the number of HAE attacks prior and during the pandemic. Based on our study, HAE patients did not experience more serious SARS-CoV-2 infection, and it did not aggravate the course of HAE either. Changes in the QoL were not significant, and vaccines were safe in HAE patients.

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification.

BACKGROUND: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting. METHODS: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines. RESULTS: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs. CONCLUSIONS: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Patients With Chronic Spontaneous Urticaria Who Have Wheals, Angioedema, or Both, Differ Demographically, Clinically, and in Response to Treatment-Results From CURE.

BACKGROUND: Patients with chronic spontaneous urticaria (CSU) have spontaneous wheals (W), angioedema (AE), or both, for longer than 6 weeks. Clinical differences between patients with standalone W, standalone AE, and W and AE (W+AE) remain incompletely understood. OBJECTIVE: To compare W, AE, and W+AE CSU patients regarding demographics, disease characteristics, comorbidities, disease burden, and treatment response. METHODS: Baseline data from 3,698 CSU patients in the ongoing, prospective, international, multicenter, observational Chronic Urticaria REgistry (CURE) were analyzed (data cut: September 2022). RESULTS: Across all CSU patients, 59%, 36%, and 5% had W+AE, W, and AE, respectively. The W+AE patients, compared with W and AE patients, showed the lowest male-to-female ratio (0.33), higher rates of concomitant psychiatric disease (17% vs 11% vs 6%, respectively), autoimmune disease (13% vs 7% vs 9%, respectively), and nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity (9% vs 5% vs 2%, respectively) and the highest disease impact. The W patients, compared with W+AE and AE patients, showed the lowest rates of concomitant hypertension (15% vs 21% vs 40%, respectively) and obesity (11% vs 16% vs 17%, respectively), the highest rate of concomitant inducible urticaria (24% vs 22% vs 6%, respectively), and shorter W duration. The AE patients, compared with W+AE and W patients, were older at disease onset, showed longer AE duration, and the best response to increased doses of H1-antihistamines (58% vs 24% vs 31%, respectively) and omalizumab (92% vs 67% vs 60%, respectively). CONCLUSIONS: Our findings provide a better understanding of CSU phenotypes and may guide patient care and research efforts that aim to link them to pathogenic drivers.

Mimics of Allergy and Angioedema: Scombroid, Mast Cell Activation Disorders, and Hereditary Alpha Tryptasemia.

Scombroid poisoning, systemic mastocytosis, and hereditary alpha tryptasemia all present with episodes that resemble allergic reactions. Knowledge regarding systemic mastocytosis and hereditary alpha tryptasemia is quickly evolving. Epidemiology, pathophysiology, and strategies to identify and diagnose are discussed. Evidence-based management in the emergency setting and beyond is also explored and summarized. Key differences are described between these events and allergic reactions.

Hospital admissions for urticaria in a pediatric emergency department of a tertiary care hospital.

BACKGROUND: Urticaria is a common disorder, estimated to affect 2.1 to 6.7% of children and adolescents, and is a frequent cause of emergency department (ED) admissions. METHODS: The aim of this study was to retrospectively characterize the clinical features of children and adolescents with a diagnosis of urticaria, evaluated in a tertiary care pediatric ED between 2015 and 2019. Statistical analysis was performed using IBM SPSS Statistics®, version 27.0. RESULTS: A total of 2254 episodes of urticaria were counted with 98.1% corresponding to acute urticaria (AU). A suspected trigger factor was identified in 51.6% of the episodes, namely infections (27.8%), drugs (9.9%) and food (7.6%). From these episodes, excluding infections, only 59.2% were referred to an Allergy Consultation for further study, with only 18.8% (drug) and 28.3% (food) confirmed as the AU trigger. Of the 43 episodes of chronic urticaria (CU), 79% were referred to consultation, with 23 being diagnosed with chronic spontaneous urticaria, 8 with inducible urticaria and 3 with both entities. Older age (p < 0.001), personal history of atopy (p = 0.019) and angioedema (p = 0.003) were factors associated with CU, while the presence of other accompanying symptoms (p = 0.007) was associated with AU. Older age (OR = 1.2; p < 0.001) and the presence of angioedema (OR = 2.7; p = 0.007) were identified as independent factors for CU. CONCLUSION: The majority of episodes corresponded to AU. Infections were the main suspected trigger, followed by drugs and food, with an overall confirmation rate ranging from 18 to 30%, highlighting the importance of an allergologic follow-up evaluation.

Documented Adverse Drug Reactions and Discontinuation of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Chronic Kidney Disease.

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation. METHODS: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented ADRs with treatment discontinuation. RESULTS: There were 882,441 (73.0%) individuals in the current user group and 326,794 (27.0%) in the discontinued group. There were 26,434 documented ADRs, with at least one documented ADR in 7,520 (0.9%) current users and 9,569 (2.9%) of the discontinued group. ADR presence was associated with treatment discontinuation, aOR 4.16 (95% CI: 4.03, 4.29). The most common documented ADRs were cough (37.3%), angioedema (14.2%), and allergic reaction (10.4%). ADRs related to angioedema (aOR 3.81, 95% CI: 3.47, 4.17), hyperkalemia (aOR 2.03, 95% CI: 1.84, 2.24), peripheral edema (aOR 1.53, 95% CI: 1.33, 1.77), or acute kidney injury (aOR 1.32, 95% CI: 1.15, 1.51) were associated with treatment discontinuation. CONCLUSION: ADRs leading to drug discontinuation were infrequently documented. ADR types were differentially associated with treatment discontinuation. An understanding of which ADRs lead to treatment discontinuation provides an opportunity to address them at a healthcare system level.

Prevalence of concomitant angioedema in chronic spontaneous urticaria: A systematic review and meta-analysis.

BACKGROUND: Angioedema (AE) is a condition associated with considerable morbidity and mortality that can significantly affect quality of life. AE often occurs in patients with CSU although the true prevalence remains unknown. Therefore, we conducted this systematic review and meta-analysis to summarize the available data. OBJECTIVE: This study is conducted with the aim of retrieving data from all published studies and create the pooled prevalence of AE in CSU patients. METHODS: Narrative reviews of AE and CSU, a systematic review, and a meta-analysis were conducted. The Ovid Medline and Embase databases were systematically searched per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Studies were eligible if they were in English and measured the prevalence of AE in CSU in adults or children. Two reviewers independently extracted data and appraised each study's quality. Estimated prevalence and 95% confidence interval (CI) values were pooled using random-effects meta-analysis. RESULTS: Seventeen studies from 16 countries were included. The pooled prevalence of AE in patients with CSU was 36.5% (95%CI, 30.9-42.5%; I2 = 96%). The pooled estimated prevalence of AE in patients with CSU was 44.0% (95%CI, 34.1-54.5%) in Europe, 44.5% (95%CI, 28.5-61.8%), America, and 29.4% (95%CI, 24.7-34.7%) in Asia. CONCLUSIONS: Our systematic review and meta?analysis showed that AE affects over one-third of CSU patients, although the prevalence from individual study varied considerably, ranging from 5 to 67 percent. Subgroup-analysis found that AE is more prevalent in Europe and America than in Asia.

Acquired Angioedema in Selected Neoplastic Diseases.

Background and Objectives. Acquired angioedema is a relatively common revelation accompanying some diseases such as autoimmune or cancer. The study aimed to assess the incidence of one subtype of angioedema-C1-INH-AAE (acquired angioedema with C1 inhibitor deficiency). Material and methods. The study was retrospective and based on 1 312 patients with a final diagnosis of breast cancer, colorectal cancer, or lung cancer: 723 women and 589 men with a mean age of 58.2 ± 13.5 years. The cancer diagnosis according to the ICD (International Classification of Diseases)-10 code, medical history including TNM (Tumour, Node, Metastasis) staging, histopathology, and assessment of the occurrence of C1-INH-AAE angioedema were analysed. Results. C1-INH-AAE occurred more often in patients with cancer than in the control group, as follows: 327 (29%) vs. 53 (6%) for p < 0.05. C1-INH-AAEs were observed most often in the group of patients diagnosed with breast cancer compared to colorectal and lung groups: 197 (37%) vs. 108 (26%) vs. 22 (16%) (p < 0.05). A higher incidence of C1-INH-AAE was observed in the early stages of breast cancer. However, there was no relationship between the occurrence of C1-INH-AAE and the BRCA1 (Breast Cancer gene 1)/BRCA2 (Breast Cancer gene 2) mutation or histopathological types of breast cancer. Conclusion. Angioedema type C1-INH-AAE occurs more often in patients with selected neoplastic diseases, especially in the early stages of breast cancer.

Pediatric chronic urticaria: Clinical and laboratory characteristics and factors linked to remission.

BACKGROUND: Chronic urticaria (CU) is defined as the occurrence of wheals/angioedema for ≥6 consecutive weeks. Until now, guidelines and publications addressing CU have focused mainly on adults. As a result, evidence and guidance in the pediatric population are scarce. METHODS: This study aims to describe clinical and laboratory findings in pediatric CU and to determine factors associated with remission. RESULTS: 185 patients, 54% female, median age at onset of 8.8 years. Angioedema was present in almost half. The most common type of CU was chronic spontaneous urticaria (CSU) in 74%. At least one atopic comorbidity was found in almost a third (35%). In addition, 8% had an autoimmune disorder (exclusively in CSU) and 9% had a psychiatric condition. Basopenia was found in 67% and was more frequently associated with CSU. The basophil activation test (BAT) was positive in 40%. With regard to remission, being of male sex, angioedema absence, the absence of physical triggers, and eosinophil counts >0.51 × 109 /L were associated with shorter CU duration. CONCLUSION: Atopy is a common condition in pediatric CU. CSU is the most common type. Autoimmune comorbidities and basopenia were significantly more common in CSU. In addition, ours is one of the few studies, assessing BAT utility in the pediatric population, being positive in a relevant percentage (40%). BAT positivity was more frequent in CSU. Our results suggest that the absence of angioedema and physical triggers, male sex, and eosinophil counts >0.51 × 109 /L appear to be associated with a better prognosis in terms of remission.

Differences between adult and pediatric chronic spontaneous urticaria from a cohort of 751 patients: Clinical features, associated conditions and indicators of treatment response.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common disease both in the pediatric and in the adult population. However, there are differences between the two patient populations with respect to etiological factors, comorbidities, and treatment responses. Our aim was to determine differences between pediatric and adult CSU in terms of clinical characteristics, laboratory parameters, comorbidities, response to treatment, and indicators of response. METHODS: A retrospective analysis of CSU patients was performed. Data regarding differences between pediatric and adult CSU patients were analyzed. Indicators of treatment response were determined separately in both pediatric and adult patients. RESULTS: Of 751 CSU patients (162 pediatrics and 589 adults), female dominancy (48.8% vs. 69.6%) and rate of angioedema (19.1% vs. 59.8%) were lower, and disease duration (5 months vs. 12 months) was shorter in pediatric patients. Anti-TPO positivity (24.7% vs. 9%), elevated CRP (46.5% vs. 11.1%), eosinopenia (38.5% vs. 18.1%), and skin prick test positivity (39.3% vs. 28.8%) were significantly more frequent in adult patients. Response to antihistamines was higher in the pediatric group, and only 7% used omalizumab versus 20.8% in the adults. The comparisons were also performed between <12-year and ≥12-year patients and yielded similar results. CONCLUSION: Pediatric CSU shows distinct characteristics such as lower incidence of angioedema and antithyroid antibodies, and it responds better to antihistamines. These suggest that CSU becomes more severe and refractory in adolescents and adults. Adolescent CSU shows features similar to adult CSU rather than pediatric CSU.

Comparative Risk of Angioedema With Sacubitril-Valsartan vs Renin-Angiotensin-Aldosterone Inhibitors.

BACKGROUND: Data on angioedema risk among sacubitril-valsartan (SV) users in real-world settings are limited. OBJECTIVES: We sought to evaluate the risk of angioedema among SV new users compared with angiotensin-converting enzyme (ACE) inhibitor and angiotensin-receptor-blocker (ARB) new users separately. METHODS: We conducted a propensity score-matched cohort study, comparing SV new users (no use of SV, ACE inhibitor, ARB 6 months before) and SV new users with prior use (within 183 or 14 days) of ACE inhibitor or ARB (ACE inhibitor-SV and ARB-SV users; recent ACE inhibitor-SV and recent ARB-SV users, respectively) vs ACE inhibitor and ARB new users separately. RESULTS: Compared with ACE inhibitor, SV new (HR: 0.18; 95% CI: 0.11-0.29) and ACE inhibitor-SV users (HR: 0.31; 95% CI: 0.23-0.43) showed lower risk of angioedema. On the other hand, there was no difference in angioedema risk when SV new users (HR: 0.59; 95% CI: 0.35-1.01) or ARB-SV users (HR: 0.85; 95% CI: 0.58-1.26) were compared with ARB new users. Compared with SV new users, ACE inhibitor-SV users (HR: 1.62; 95% CI: 0.91-2.89) trended toward higher angioedema risk, which intensified when the ACE inhibitor to SV switch occurred within 14 days (recent ACE inhibitor-SV) (HR: 1.98; 95% CI: 1.11-3.53). Similarly, ARB-SV users (HR: 2.03; 95% CI: 1.16-3.54) experienced an increased risk compared with SV new users, which intensified for the more recent switchers (recent ARB-SV) (HR: 2.45; 95% CI: 1.36-4.43). CONCLUSIONS: We did not observe an increased risk of angioedema among SV new users compared with ACE inhibitor or ARB users. However, there was an increased risk of angioedema among SV users who recently switched from ACE inhibitor or ARB compared with SV new users.

Incidence of urticaria, angioedema, and type I hypersensitivity reactions associated with fibrinolytic agents in Thailand using the database of the health product vigilance center.

BACKGROUND: Besides hemorrhage, allergic reactions have also been observed in several clinical trials of fibrinolytic agents. These reactions might negatively affect patient outcomes, especially life-threatening type I hypersensitivity reactions such as anaphylaxis. However, there are limited data on the incidence of these reactions. OBJECTIVE: The aim of study was to analyze the incidence of urticaria, angioedema, and type I hypersensitivity reactions from fibrinolytic agents for various indications. METHODS: A retrospective analysis of data from the Thai Vigibase database was conducted. All reports of adverse drug reactions from fibrinolytic agents from 1984 to 2017 were identified using the World Health Organization adverse reaction terminology. The proportion of each suspected adverse drug reaction and the cumulative incidence were calculated. RESULTS: A total of 284 reports were identified in the Thai Vigibase database. The overall incidence of urticaria, angioedema, and type I hypersensitivity reactions for the streptokinase group was 52.64/10,000 persons, with individual incidence rates of 9.64/10,000 persons for urticaria, 8.90/10,000 persons for angioedema, and 34.11/10,000 persons for type I hypersensitivity reactions. In the alteplase group, the overall incidence for all suspected reactions was 18.90/10,000 persons, with individual incidence rates of 3.29/10,000 persons for urticaria, 5.75/10,000 persons for angioedema, and 9.86/10,000 persons for type I hypersensitivity reactions. CONCLUSIONS: Type I hypersensitivity reactions were the most common allergic reactions from fibrinolytic agents. It is necessary to take these reactions into consideration when using fibrinolytic therapy.

Application of the U.S. Food and Drug Administration's Sentinel Routine Querying Tools to the Taiwan Sentinel Data Model-formatted National Health Insurance Research Database.

The U.S. Food and Drug Administration's Sentinel System is a leading distributed data network for drug safety surveillance in the world. The National Health Insurance Research Database (NHIRD) in Taiwan was converted into the Taiwan Sentinel Data Model (TSDM) based on the Sentinel Common Data Model (SCDM) version 6.0.2. The goal of this study was to investigate the feasibility of applying the same study designs, analytic choices, and analytic tools as used by the U.S. Sentinel System to examine the same drug-outcome associations in the TSDM-formatted NHIRD. Four known drug-outcome associations previously examined by the U.S. Sentinel System were selected as the use cases: (1) use of angiotensin-converting enzyme inhibitors (ACEIs) and risk of angioedema, (2) use of warfarin and risk of gastrointestinal bleeding, (3) use of oral clindamycin and risk of Clostridioides difficile infection (CDI), and (4) use of glyburide and risk of serious hypoglycemia. We followed the same study designs and analytic choices used by the U.S. Sentinel System and applied the Sentinel Routine Querying Tools to answer the same study questions within the TSDM-formatted NHIRD. The results showed that ACEIs were associated with a non-significant increase in risk of angioedema compared to beta-blockers (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.89-1.64); warfarin was associated with a higher risk of gastrointestinal bleeding compared to statins (HR: 1.72; 1.50-1.98); glyburide was associated with an increased risk of hypoglycemia compared to glipizide (HR: 1.61, 1.30-2.00). We were unable to evaluate the association between oral clindamycin and risk of CDI due to the low event number. Our study demonstrated that it was feasible to directly apply the publicly available Sentinel Routine Querying Tools within the TSDM-formatted NHIRD. However, sources of heterogeneity other than design and analytic differences should be carefully considered when comparing the results between the two systems.

Etiological causes in patients with acute urticaria and angioedema: A cross-sectional study.

BACKGROUND: Acute urticaria and angioedema are emergency dermatological conditions associated with various etiologic factors. OBJECTIVE: To determine the etiological causes in patients with acute urticaria and angioedema, and to investigate whether more than one etiological cause was present, along with the patients' laboratory values. METHODS: The study was conducted in a tertiary hospital with one center. Etiological causes and laboratory parameters in 284 patients diagnosed with acute urticaria and angioedema were retrospectively studied. RESULTS: A total of 284 patients were included in the study. The mean age of the patients was 42.7 ± 15.6 years, where 163 (57.4%) were women and 121 (42.6%) were men. Acute urticaria and angioedema occurred together in 149 (52.5%) patients. At least one precipitating factor among the predisposing risk factors was present in 220 (77.5%) patients, and more than one precipitating factor was found in 51 (18%) patients. Medication use was found in 157 (55.3%) patients and infection in 54 (19%). The development of urticaria after food consumption was noted in nine (3.2%) individuals. A history of infection and medication intake was present in 50 (17.6%) patients. A joint history of food consumption and medication intake was present in only one patient. Elevated C-reactive protein level was found in 178 (62.7%) patients and elevated anti-streptolysin O titer in 41 (14.4%) patients. Vitamin B12 deficiency was found in 116 (40.8%) patients and vitamin D deficiency in 254 (89.4%). CONCLUSION: Acute urticaria and angioedema may occur as a result of multiple etiological factors, in which different triggers may be present simultaneously.

Etiological causes in patients with acute urticaria and angioedema: A cross-sectional study

Background: Acute urticaria and angioedema are emergency dermatological conditions associated with various etiologic factors. Objective: To determine the etiological causes in patients with acute urticaria and angioedema, and to investigate whether more than one etiological cause was present, along with the patients’ laboratory values. Methods: The study was conducted in a tertiary hospital with one center. Etiological causes and laboratory parameters in 284 patients diagnosed with acute urticaria and angioedema were retrospectively studied. Results: A total of 284 patients were included in the study. The mean age of the patients was 42.7 ± 15.6 years, where 163 (57.4%) were women and 121 (42.6%) were men. Acute urticaria and angioedema occurred together in 149 (52.5%) patients. At least one precipitating factor among the predisposing risk factors was present in 220 (77.5%) patients, and more than one precipitating factor was found in 51 (18%) patients. Medication use was found in 157 (55.3%) patients and infection in 54 (19%). The development of urticaria after food consumption was noted in nine (3.2%) individuals. A history of infection and medication intake was present in 50 (17.6%) patients. A joint history of food consumption and medication intake was present in only one patient. Elevated C-reactive protein level was found in 178 (62.7%) patients and elevated anti-streptolysin O titer in 41 (14.4%) patients. Vitamin B12 deficiency was found in 116 (40.8%) patients and vitamin D deficiency in 254 (89.4%). Conclusion: Acute urticaria and angioedema may occur as a result of multiple etiological factors, in which different triggers may be present simultaneously (AU)

A survey on subtypes and clinical characteristics of 1061 patients with urticaria in the primary care institutes in Japan.

The prevalence of urticaria has been reported mostly in Europe and North America. However, precise information regarding its subtypes and clinical characteristics in primary care practice, especially in Asian countries, are scant. Patients with urticaria and/or angioedema who visited nine primary clinics of accredited dermatologists and allergologists in Japan were recruited from October to November 2020. The information of age, sex, disease duration, urticaria control test (UCT), and concomitant urticaria subtypes were collected. A total of 1061 patients participated. The number of patients was high in the 20 to 50 age groups with a peak in the 40s. The most frequent urticaria subtype was chronic spontaneous urticaria (CSU) followed by dermographism, acute spontaneous urticaria (ASU), angioedema, and cholinergic urticaria (CholU) (66.8%, 22.7%, 18.9%, 14.1% and 5.7% in all patients with urticaria). CSU development increased with age from the 20s to 50s, especially in females. Dermographism had a peak in the 40s. ASU had bimodal peaks in childhood and in the 30s. CholU was common in males in the 10-20s. Most angioedema patients were female with an increase in their 30s. Angioedema was solely present in 14 of 1061 participants (1.3%), while 136 (12.8%) had angioedema concomitant with urticaria. UCT showed poorly controlled urticaria with lower scores in patients with concomitant CSU and other subtypes than in those with CSU alone. Urticaria tends to develop in young to middle-aged females. The most common urticaria subtype is CSU, while the number of patients with CholU is high and that of angioedema is low in Japan.

Pharmacovigilance study of the association between dipeptidyl peptidase-4 inhibitors and angioedema using the FDA Adverse Event Reporting System (FAERS).

Dipeptidyl peptidase-4 (DPP-4) plays a minor role in degrading vasoactive peptides that cause angioedema when angiotensin-converting enzyme (ACE) is present and fully functional. This study investigated the association between DPP-4 inhibitors (DPP-4Is) and angioedema, including cases where the concomitant use of ACE inhibitors (ACEIs) was absent. We obtained data from the US Food and Drug Administration Adverse Event Reporting System and performed a disproportionality analysis, using the reporting odds ratio (ROR) and information component (IC) for signal detection in patients aged ≥ 40 years, stratified by age group and sex. No signal was detected for DPP-4Is when the entire dataset was analyzed. However, a signal was detected for the entire female subset group, the three stratified female groups aged ≥ 60 years, and males in their 40 s. After excluding the data of concomitant ACEI users, most ROR and IC values were lower and significant only for females in their 60 s and males aged ≥ 80 years. Regarding individual DPP-4Is signals, those detected for saxagliptin and sitagliptin in some age groups disappeared after excluding the data of ACEI users. Notably, linagliptin was the only DPP-4I where signals were detected in most female groups, regardless of age and without concomitant ACEI use. Our findings suggest that some DPP-4Is were associated with a higher reporting of angioedema as per age and sex, even in the absence of concomitant ACEI use.