Pharmacogenetic markers of development of angioneurotic edema as a secondary side effect to enalapril in patients with essential arterial hypertension.

BACKGROUND: Angioneurotic edema is the most dangerous complication in angiotensin-converting enzyme inhibitors (ACEIs) therapy. Based on the current data, the clinical and genetic predictors of angioedema development are still understudied, which demonstrates the relevance of this study. OBJECTIVE: To reveal the pharmacogenetic predictors of the angioedema as a secondary side effect to enalapril in patients with essential arterial hypertension. METHODS: The study enrolled 111 subjects randomized into two groups: study group, patients with the angioedema as a secondary side effect to enalapril; and control group, patients without adverse drug reaction. All patients underwent pharmacogenetic testing. RESULTS: An association between the development of the angioneurotic edema and the genotypes AA rs2306283 of gene SLCO1B1, TT rs4459610 of gene ACE, and CC rs1799722 of gene BDKRB2 in patients was revealed. CONCLUSION: The findings justify further investigations of the revealed genetic predictors of angioedema with larger-size patient populations.

Airway Involvement and Intervention in Non-ACE-Inhibitor-Induced Angioedema.

OBJECTIVES: Characterize the presentation of patients with non-angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema and determine risk factors associated with patient disposition and possible need for airway intervention. METHODS: The medical records of adult patients in the Emergency Department (ED) and diagnosed with non-ACEI-induced angioedema over 4.5 years were included. Demographics, vital signs, etiology, timeline, presenting symptoms, physical exam including flexible laryngoscopy, medical management, and disposition were examined. Statistical analyses were conducted using SPSS V 23.0 software calculating and comparing means, standard deviations, medians, and correlation of categorical and ordinate variables. RESULTS: A total of 181 patients with non-ACEI-induced angioedema were evaluated with flexible laryngoscopy by otolaryngology. Notably, 11 patients (6.1%) required airway intervention and were successfully intubated. Statistically significant factors (p ≤ 0.05) associated with airway intervention included the diastolic blood pressure (DBP) and mean arterial pressure (MAP) (p = 0.006 and 0.01 respectively), symptoms of dysphonia (p = 0.018), the presence of oropharyngeal, supraglottic, and hypopharyngeal edema (p ≤ 0.001 for each site), and the number of edematous anatomic subsites documented on physical exam (p < 0.001). Other patient demographics, prior history of angioedema, heart rate, systolic blood pressure, symptom onset, number of symptoms at presentation, and medication administered in the ED did not correlate with airway intervention. CONCLUSION: Dysphonia, DBP, MAP, anatomic location of edema and edema in multiple sites are associated with airway intervention and a higher level of care in non-ACEI-induced angioedema and can be useful in risk assessment in patient management. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2282-2287, 2024.

Angioedema after rt-PA infusion led to airway emergency: a case report of rescue treatment with fresh frozen plasma

Abstract The authors report the case of a 71-year-old woman presented to the Emergency Department with acute ischemic stroke. She was treated with rt-PA and interventional endovascular revascularization and developed rapidly progressing angioedema that led to emergency intubation. The standard treatment was not very effective and the swelling improved after infusion of fresh frozen plasma. Angioedema after rt-PA infusion could be a life-threatening emergency that requires quick airway management by skilled professionals. As this condition is triggered by several factors, such as unregulated histamine and bradykinin production, the traditional treatment recommended by the guidelines may not be sufficient and the use of FFP can be considered as a safe and valuable aid.

The effect of continuing versus withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers on mortality and major adverse cardiovascular events in hypertensive patients undergoing elective non-cardiac surgery: study protocol for a multi-centric open-label randomised controlled trial.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) are commonly prescribed to patients with hypertension. These drugs are cardioprotective in addition to their blood pressure-lowering effects. However, it is debatable whether hypertensive patients who present for non-cardiac surgery should continue or discontinue these drugs preoperatively. Continuing the drugs entails the risk of perioperative refractory hypotension and/or angioneurotic oedema, while discontinuing the drugs entails the risk of rebound hypertension and myocardial ischaemia. The aim of this study is to evaluate the effect of continuation vs withholding of ACEIs/ARBs on mortality and other major outcomes in hypertensive patients undergoing elective non-cardiac surgery. METHODS: The continuing vs withholding of ACEIs/ARBs in patients undergoing non-cardiac surgery is a prospective, multi-centric, open-label randomised controlled trial. Two thousand one hundred hypertensive patients receiving ACEIs/ARBs and planned for elective non-cardiac surgery will be enrolled. They will be randomised to either continue the ACEIs/ARBs including on the day of surgery (group A) or to withhold it 24-36 h before surgery (group B). The primary endpoint will be the difference in the composite outcome of all-cause in-hospital/30-day mortality and major adverse cardiovascular and non-cardiovascular events. Secondary endpoints will be to evaluate the differences in perioperative hypotension, angioneurotic oedema, myocardial injury, ICU and hospital stay. The impact of the continuation vs withholding of the ACEIs/ARBs on the incidence of case cancellation will also be studied. DISCUSSION: The results of this trial should provide sufficient evidence on whether to continue or withhold ACEIs/ARBs before major non-cardiac surgery. TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2021/01/030199. Registered on 4 January 2021.

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.

Facial Angioedema after the first dose of Covishield (adenovirus-vectored severe acute respiratory syndrome coronavirus 2 vaccine): follow-up after the second and third booster doses.

Mass vaccination campaigns are essential to control the ongoing novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic. The Covishield vaccine consists of the replication-deficient simian adenovirus vector ChAdOx1, which contains the full-length structural spike protein of SARS-CoV-2. Occasionally, it can lead to cutaneous reactions that contribute to fear of vaccination, hesitancy, and incomplete vaccination schedules. We report a case of facial angioedema following the first dose of Covishield in a 63-year-old woman with no previous history of allergies or hypersensitivity to drugs or vaccines. No rebound of angioedema was recorded after the second homologous and third heterologous doses.

DRESS syndrome induced by imatinib.

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a severe, potentially life-threatening drug-induced hypersensitivity reaction characterized by cutaneous eruptions, fever, diffuse lymphadenopathy, along with eosinophilia and elevated liver enzymes. The severity and potential organ damage associated with DRESS mandates withdrawing the offending drug and provide a suitable replacement. We report a 55-year-old man who developed prolonged fever, generalized maculopapular rash and facial edema after 3 weeks of starting imatinib for chronic myeloid leukemia (CML). A diagnosis of DRESS was confirmed by eosinophilia and skin biopsy findings, along with a consistent RegiSCAR score. Imatinib was stopped and he was initiated on low-dose steroids, which led to complete resolution of rash and eosinophilia. A rechallenge with imatinib was positive, and he was switched to dasatinib for further therapy, following which he attained an optimal molecular response. DRESS following imatinib has only been reported in eight patients so far. In this report we summarize the current evidence for managing DRESS and its impact on the treatment of CML.

[Medicaments and oral healthcare. Medicaments potentially inducing angioedema and/or urticaria]. / Serie: Medicamenten en mondzorg. Medicamenten die angio-oedeem en/of urticaria kunnen induceren.

Angioedema stems from increased vasodilation and vascular permeability, resulting in extravasation of fluid. Hereditary and acquired types of angioedema can be distinguished, with 3 and 4 subtypes, respectively. Groups of medicaments potentially inducing angioedema are, among others: ACE inhibitors, angiotensin II receptor blockers, dipeptidyl peptidase-4 inhibitors, thrombocyte aggregation inhibitors and immunosuppressive agents. Urticaria is characterised by red, slightly raised swellings, usually associated with a strong itching sensation and can be subdivided in an acute and a chronic type. Mast cells in the uppermost layer of the skin or the mucous membranes release a lot of histamine, increasing the dilation and permeability of blood capillaries, resulting in extravasation of fluid. Medicaments potentially inducing urticaria are, among others, the following groups: analgesics, anaesthetics, antibiotics, antidepressants, antihistamines, antihypertensives, antifungals, corticosteroids, H2 blockers, cancer medicaments, muscle relaxants, thrombocyte aggregation inhibitors and vaccines. Medical history and being alert when administering and prescribing anaesthetics, analgesics and antibiotics are very important in the prevention or treatment of angioedema and/or urticaria.

[Facial angioedema following pharmacotherapy with an ACE inhibitor]. / Angio-oedeem in het aangezicht na medicatie met een ACE-remmer.

A 56-year-old women suddenly had a swelling on her right cheek and on the right side of her upper lip, for which she decided to first visit her family physician and subsequently her family dentist. During the past two years, she was treated for an ovarian carcinoma by an oncologist. Recently, she was using the antihypertensive ACE inhibitor enalapril, prescribed by her family physician. Consultation between her family dentist, family physician and oncologist led to the diagnosis angioedema as an adverse effect of enalapril. The family physician replaced enalapril by the angiotensin II receptor blocker losartan. Subsequently, the swelling disappeared within two days. This angioedema type occurs most frequently in the head and neck area. Oropharyngeal, tongue and laryngeal oedema are very dangerous because they may cause airway obstruction. Today, a live-threatening or fatal condition is mostly prevented as a result of better vigilance of dentists and physicians. Nevertheless, such a condition will still occur occasionally.

Critical angioedema induced by a renin angiotensin system blocker in the contemporary era of increasing heart failure: A case report and commentary.

Bradykinin-mediated angioedema, a nonallergic reaction most commonly caused by renin angiotensin system (RAS) blockers, has the potential to lead to a critical condition. RAS blockers are important for treating heart failure and are widely used in clinical settings. We present the case of an 85-year-old man who was administered enalapril after percutaneous coronary intervention for an acute myocardial infarction and developed severe angioedema requiring a tracheostomy. He had multiple risks for angioedema including advanced age, smoking history, renal dysfunction, and longstanding use of an angiotensin receptor blocker. The prompt diagnosis of drug-induced angioedema is critical and depends on physicians' recognition of risk factors and knowledge of pathophysiology. In the present era of increasingly prevalent heart failure, it is imperative that the possibility of angioedema receives attention, especially given the continuing reliance on RAS blockers and the advent of angiotensin receptor neprilysin inhibitors, a new type of heart failure drug.

A case of successful acyclovir desensitization in a bone marrow transplant patient.

INTRODUCTION: The incidence of acyclovir-induced hypersensitivity is rare. To our knowledge, there are four published case reports of oral acyclovir desensitization in adults. Evidence-based guidelines prompt the use of acyclovir for herpes simplex virus (HSV) prophylaxis and treatment. Literature on the cross-reactivity of structurally similar antiviral agents is conflicting, presenting a clinical challenge when choosing an alternative agent. This is a case of successful acyclovir desensitization in an allogeneic stem cell transplant patient. CASE REPORT: A 69-year-old female patient, diagnosed with myelodysplastic/myeloproliferative neoplasm, presented to the hospital for donor mismatch allogeneic bone marrow transplant. The patient reported acyclovir-induced angioedema while receiving treatment for non-complicated herpes zoster (shingles) infection.Management & Outcome: After the acyclovir oral desensitization was conducted in an ICU setting with 1:1 patient-nurse ratio, the patient was successfully started on acyclovir therapy, 800mg by mouth twice daily for HSV prophylaxis with no further complications. Discussion: Oral acyclovir desensitization can provide an option for HSV therapy in patients reporting severe allergy.

Infusion-related angioedema associated with infliximab-abda: Case report.

PURPOSE: A case of infusion-related angioedema associated with the use of an infliximab biosimilar (infliximab-abda) is reported in order to bring awareness that this adverse effect is still highly possible in biosimilars, similar to the reference infliximab biologic. SUMMARY: A 37-year-old white male with a past medical history significant for ileocolonic fistulizing Crohn's disease, depression, and gastroesophageal reflux disease (GERD) presented to an emergency department with shortness of breath, urticaria, and tongue swelling that had developed shortly after initiation of an infusion of infliximab-abda. The patient had no documented allergies at the time of presentation. The patient was taking oral budesonide 9 mg daily and oral azathioprine 50 mg daily for treatment of Crohn's disease. Other medications included oral omeprazole 40 mg every morning for GERD and oral sertraline 100 mg daily for depression. The patient's tongue swelling worsened, and he was intubated for airway protection. The patient received supportive care treatment for angioedema with intravenous (IV) dexamethasone 8 mg every 8 hours, IV diphenhydramine 50 mg every 8 hours, and IV famotidine 20 mg every 12 hours. He was extubated approximately 43 hours later and observed overnight in a medical intensive care unit. He was transferred to a general medicine unit the next day for further care. The total hospital length of stay was 4 days. CONCLUSION: A 37-year-old man developed infusion-related angioedema with use of infliximab-abda. Discontinuation of the biosimilar product along with supportive care brought about resolution of angioedema. There are no prior published reports of infusion-related angioedema reactions secondary to infliximab-abda use.

[Update on perioperative hypersensitivity reactions: joint document from the Brazilian Society of Anesthesiology (SBA) and Brazilian Association of Allergy and Immunology (ASBAI) - Part II: etiology and diagnosis]. / Atualização sobre reações de hipersensibilidade perioperatória: documento conjunto da Sociedade Brasileira de Anestesiologia (SBA) e Associação Brasileira de Alergia e Imunologia (ASBAI) ­ Parte II: etiologia e diagnóstico.

This second joint document, written by experts from the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Society of Anesthesiology (SBA) concerned with perioperative anaphylaxis, aims to review the pathophysiological reaction mechanisms, triggering agents (in adults and children), and the approach for diagnosis during and after an episode of anaphylaxis. As anaphylaxis assessment is extensive, the identification of medications, antiseptics and other substances used at each setting, the comprehensive data documentation, and the use of standardized nomenclature are key points for obtaining more consistent epidemiological information on perioperative anaphylaxis.

Update on perioperative hypersensitivity reactions: joint document from the Brazilian Society of Anesthesiology (SBA) and Brazilian Association of Allergy and Immunology (ASBAI) - Part II: etiology and diagnosis / Atualização sobre reações de hipersensibilidade perioperatória: documento conjunto da Sociedade Brasileira de Anestesiologia (SBA) e Associação Brasileira de Alergia e Imunologia (ASBAI) - Parte II: etiologia e diagnóstico

Abstract This second joint document, written by experts from the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Society of Anesthesiology (SBA) concerned with perioperative anaphylaxis, aims to review the pathophysiological reaction mechanisms, triggering agents (in adults and children), and the approach for diagnosis during and after an episode of anaphylaxis. As anaphylaxis assessment is extensive, the identification of medications, antiseptics and other substances used at each setting, the comprehensive data documentation, and the use of standardized nomenclature are key points for obtaining more consistent epidemiological information on perioperative anaphylaxis.

Resumo Este segundo documento, escrito por especialistas da Associação Brasileira de Alergia e Imunologia (ASBAI) e da Sociedade Brasileira de Anestesiologia (SBA) interessados no tema anafilaxia perioperatória, tem por objetivo revisar os mecanismos fisiopatológicos, agentes desencadeantes (em adultos e crianças), assim como a abordagem diagnóstica durante e após o episódio. Por se tratar de uma avaliação abrangente, a identificação das medicações, antissépticos e outras substâncias usadas em cada região, registros detalhados, e nomenclatura padronizada são pontos fundamentais para a obtenção de dados epidemiológicos mais fidedignos sobre a anafilaxia perioperatória.

67-year-old man • upper extremity pain & edema • recent diagnosis of heart failure • Dx?

► Upper extremity pain ► Upper extremity edema ► Recent diagnosis of heart failure.

Update on perioperative hypersensitivity reactions: joint document of the Brazilian Society of Anesthesiology (SBA) and Brazilian Association of Allergy and Immunology (ASBAI) - Part I: post-crisis guidelines and treatment / Atualização sobre reações de hipersensibilidade perioperatória: documento conjunto da Sociedade Brasileira de Anestesiologia (SBA) e Associação Brasileira de Alergia e Imunologia (ASBAI) - Parte I: tratamento e orientação pós-crise

Abstract Experts from the Brazilian Association of Allergy and Immunology (ASBAI) and the Brazilian Society of Anesthesiology (SBA) interested in the issue of perioperative anaphylaxis, and aiming to strengthen the collaboration between the two societies, combined efforts to study the topic and to prepare a joint document to guide specialists in both areas. The purpose of the present series of two articles was to report the most recent evidence based on the collaborative assessment between both societies. This first article will consider the updated definitions, treatment and guidelines after a perioperative crisis. The following article will discuss the major etiologic agents, how to proceed with the investigation, and the appropriate tests.

Resumo Especialistas da Associação Brasileira de Alergia e Imunologia (ASBAI) e da Sociedade Brasileira de Anestesiologia (SBA) interessados no tema anafilaxia perioperatória reuniram-se com o objetivo de intensificar a colaboração entre as duas sociedades no estudo desse tema e elaborar um documento conjunto que possa guiar os especialistas de ambas as áreas. O objetivo desta série de dois artigos foi mostrar as evidências mais recentes alicerçadas na visão colaborativa entre as sociedades. Este primeiro artigo versará sobre as definições mais atuais, formas de tratamento e as orientações após a crise no perioperatório. No próximo artigo serão discutidos os principais agentes causais e a condução da investigação com testes apropriados.

A case of late-onset larynx angioedema after ranibizumab intravitreal injection: Ranibizumab-related angioedema.

This case report describes an unusual case of late-onset larynx angioedema after ranibizumab intravitreal injection. A 72-year-old female patient presented to our clinic for decreased vision; right eye (RE) fundoscopy and optical coherence tomography (OCT) revealed mild chorioretinal atrophy and choroidal neovascularization with subretinal fluid. A ranibizumab injection was planned in the RE, with standard pretreatment with daily oral administration of betamethasone, cetirizine, and ranitidine because her medical history revealed two adverse drug reactions (ADRs) to contrast media (CM). Despite the premedication, 2 h after injection, the patient referred throat closing sensation and dyspnea that resolved within few hours by betamethasone 4 mg intramuscular injection, without further reoccurrence. In occasion of the second intravitreal injection, video rhinofibrolaryngoscopy revealed subglottic edema that resolved within few hours by betamethasone 4 mg intramuscular injection. This report suggests that, even in cases of intravitreal injection, patients with history of allergy, despite the anti-allergic treatment, should be hospitalized to detect late onset of such a life-threatening complication.