Assessment of clinical phenotypic characteristics of patients with angioedema without wheals in a turkish population.

Background: Angioedema (AE) is defined as localized, self-limited swelling of subcutaneous tissues and mucosa. Objective: The aim of this study was to compare the phenotypic characteristics of patients with AE without wheals. Methods: This prospective study included adult patients with recurrent AE without wheals. Demographic and laboratory data of the patients were recorded in the patient file when they presented to the outpatient clinic between August 2018 and August 2020. The patients were contacted by phone to evaluate whether their AE had gone into remission between October 2023 and January 2024. The phenotypic characteristics of AE subtypes were compared. Results: The study included a total of 143 patients. The average age, age of onset of AE, rates of diabetes mellitus, hypertension and coronary artery disease were higher in the patients with angiotensin-converting enzyme inhibitor (ACEI) use related acquired AE (AAE) (AAE-ACEI). The rates of allergic rhinitis, drug allergy, atopy, and aeroallergen sensitivity, and the median total immunoglobulin E level were higher in patients with idiopathic histaminergic AAE (AAE-IH). The rate of face and/or perioral AE attacks was higher in the patients with AAE-ACEI, AAE-IH, and idiopathic non-histaminergic AAE. The rate of AE attacks in limbs, abdominal, genital and other parts of the body was higher in patients with hereditary AE (HAE). The baseline AE activity score was lower in the patients with AAE-IH and higher in the patients with HAE. In long-term follow-up, the remission rate of AE attacks was significant higher in patients with AAE-ACEI and AAE-IH. Conclusion: The phenotypic characteristic features of Turkish patients with AE without wheals may vary, depending on the underlying AE pathogenesis. C1 inhibitor level and function, complement C4 and C1q, and genetic tests contributed to the diagnosis; other laboratory tests did not contribute to the diagnosis.

Chronic Inducible Urticaria.

Chronic inducible urticaria (CIndU) is characterized by the appearance of hives (urticaria) and/or angioedema in response to specific triggers or stimuli. For accurate diagnosis, anamnesis-driven specific, and if available, standardized trigger testings, as well as patient reported outcomes, should be applied. The currently recommended treatment algorithm is the same as for chronic spontaneous urticaria but is largely off-label for CIndU. New, and possibly more disease-specific, treatment options are needed for CIndU patients, who are often severely impacted by their disease. Several clinical trials are currently ongoing.

Classification, Diagnosis, and Pathology of Angioedema Without Hives.

A clear disease classification schema coupled with an understanding of the specific mechanisms involved in the different types of angioedema without hives informs the diagnostic assessment. The recommended approach involves several key steps. Foremost is the recognizing of the clinical clues which allow for the differentiation of mast cell-mediated disorders from bradykinin-mediated angioedema. Enhanced vascular permeability related to bradykinin is of critical importance to identify given the implications for disease morbidity and risk of mortality. The ability to efficiently categorize and diagnose all forms of angioedema results in improved patient outcomes.

Contact System Activation and Bradykinin Generation in Angioedema: Laboratory Assessment and Biomarker Utilization.

The role of contact system activation has been clearly established in the pathogenesis of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH). C1 inhibitor (C1INH)-protease complexes, levels of functional C1INH, plasma kallikrein activation, and cleavage of high-molecular-weight kininogen have each been associated with disease activity. More recently, HAE with normal levels of C1INH (HAE-nl-C1INH) has been recognized. Six genetic mutations have been identified which are linked to HAE-nl-C1INH phenotypes. The majority of individuals with HAE-nl-C1INH fall into the unknown category. There is substantial evidence that bradykinin generation underlies the recurrent attacks of swelling in some of these cohorts.

Update on Urticaria and Angioedema.

Urticaria and angioedema are caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically, and anaphylaxis must be ruled out if urticaria or angioedema is present. A limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers when and if triggers are identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses.

Mast cell degranulation and bradykinin-induced angioedema - searching for the missing link.

Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is one such clinical entity. In this paper, we explore the existing evidence that mast cells (MCs) degranulation may contribute to the activation of the kallikrein-kinin system cascade, followed by bradykinin formation and angioedema. We present the multidirectional effects of MC-derived heparin and other polyanions on the major components of the kinin-kallikrein system, particularly on the factor XII activation. Although, bradykinin- and histamine-mediated symptoms are distinct clinical phenomena, they share some common features, such as some similar triggers and a predilection to occur at sites where mast cells reside, namely the skin and mucous membranes. In addition, recent observations indicate a high incidence of hypersensitivity reactions associated with MC degranulation in the HAE-C1-INH patient population. However, not all of these can be explained by IgE-dependent mechanisms. Mast cell-related G protein-coupled receptor-X2 (MRGPRX2), which has recently attracted scientific interest, may be involved in the activation of MCs through a different pathway. Therefore, we reviewed MRGPRX2 ligands that HAE-C1-INH patients may be exposed to in their daily lives and that may affect MCs degranulation. We also discussed the known inter- and intra-individual variability in the course of HAE-C1-INH in relation to factors responsible for possible variability in the strength of the response to MRGPRX2 receptor stimulation. The above issues raise several questions for future research. It is not known to what extent a prophylactic or therapeutic intervention targeting the pathways of one mechanism (mast cell degranulation) may affect the other (bradykinin production), or whether the number of mast cells at a specific body site and their reactivity to triggers such as pressure, allergens or MRGPRX2 agonists may influence the occurrence of HAE-C1-INH attacks at that site.

Effects of Two Different Cold Application Methods After Rhinoplasty: A Randomized Clinical Trial.

The aim of this prospective, randomized controlled clinical trial was to evaluate the effects of two methods of cold application on eye ecchymosis, periorbital edema, pain around the eyes and face, and patient comfort in postoperative rhinoplasty patients. Patients were randomly divided and evaluated in two groups: an ice in disposable latex gloves (IDLG) group and a cooling gel eye mask (CGEM) group. We used the CONSORT checklist to report the study. There were no significant differences between the groups in terms of age, gender, preoperative blood pressure, respiration, fever status, oxygen saturation, or postoperative vital signs. Patients in the IDLG group had significantly higher scores for pain around the eyes, facial pain, and periorbital edema on the first postoperative day, and significantly higher facial edema scores during the first postoperative hour (p ≤ .05). Patients in the CGEM group reported that they slept more comfortably (p ≤ .05). The results of our study showed that CGEMs reduce pain, periorbital edema, and facial edema after rhinoplasty.

[Facial swelling due to angioedema: often mast cell mediated, but not always]. / Gelaatszwellingen door angio-oedeem.

Most cases of angioedema are mast cell mediated. We present three patients with angioedema, who were admitted to our emergency room or outpatient clinic. One of them did have mast cell mediated angioedema, despite insufficient response to initial antihistamine treatment. The other patients had more rare cases of angioedema, i.e. hereditary angioedema with C1-inhibitor deficiency and angiotensin converting enzyme inhibitor associated angioedema. We discuss similarities and differences in symptoms, diagnosis and treatment between these causes of angioedema. We recommend keeping the differential diagnosis of angioedema in mind when a patient with angioedema is presented, including rarer pathophysiological explanations.

Acute angioedema in Cape Town emergency centres and a suggested algorithm to simplify and improve management.

BACKGROUND: Angioedema is the most common acute allergic presentation to emergency centres (EC), with hospitalisation rates increasing in high-income countries. Angioedema can complicate with life-threatening laryngeal obstruction. There are no local data; therefore, we aimed to characterise acute angioedema cases presenting to ECs and develop a simple management algorithm. OBJECTIVE: To characterise the clinical presentation, management and outcomes of acute angioedema cases presenting to ECs. Based on these findings, we developed a management algorithm for acute angioedema to improve the care of acute angioedema in South Africa (SA). METHODS: We conducted a retrospective folder review of all patients admitted to Groote Schuur Hospital (tertiary) and Mitchells Plain District Hospital (secondary) ECs from 1  June 2018 to 31  June 2020. Using ICD-10 coding, folders of adults ≥18 years with possible angioedema presenting to the ECs were screened. An allergist extracted demographics, medical history, management and outcome data for each angioedema event. RESULTS: A total of 142 acute angioedema episodes were included, with a median (interquartile range) age of 42 (28 - 58) years, and 62% of patients were female. The majority (124/142, 87%) of acute angioedema EC presentations involved swelling above the shoulders, with airway involvement in 20 (14%) patients, with two patients requiring intubation. Nineteen (13%) patients required admission, with five (26%) admitted to high care/intensive care. Drug-induced angioedema was the most common cause, with 64/142 (45%) linked to a known offending drug, 42/64 (65.6%) being angiotensin-converting enzyme inhibitor (ACE-I). Critical information to guide angioedema management, including past personal/family allergy history, and duration of angioedema prior to EC visit, was not recorded in 64.7% and 37.8% of EC records, respectively. Unnecessary treatment with corticosteroids or antihistamines occurred in 19/53 (36%) and 16/53 (30%) cases with bradykinin-mediated angioedema ACE-I angioedema and hereditary angioedema). Overall, only 36/142 (25%) of angioedema patients were connected to allergy care. CONCLUSION: Angioedema is the most common allergy presentation to two ECs in Cape Town, SA. Bradykinin-mediated angioedema secondary to ACE-I therapy is the single most common offender, and was not appropriately managed in more than a third of cases. Based on these findings, we have developed a management algorithm that easily stratifies patients into bradykinin or mast cell-mediated angioedema with a step-by-step management approach that is applicable to the SA context. Ongoing awareness and education on allergy emergencies are required to ensure accurate diagnosis of less common causes of angioedema (particularly bradykinin-mediated angioedema) and linkage to allergy specialist care.

An unusual case of acquired angioedema associated with monoclonal gammopathies of uncertain significance

Acquired angioedema (AAE) is a rare disease due to the C1 esterase inhibitor (C1-INH) deficiency. Clinically, its symptoms are similar to hereditary angioedema (HAE) with hereditary C1-INH deficiency. Both conditions have the potential to cause upper airway obstruction, which can be fatal in clinical practice and thus require intense attention. Here, we’d like to discuss the clinical presentation, diagnosis and follow up of a special case of AAE associated with monoclonal gammopathies of unknown significance (MGUS) with recurrent upper airway obstruction. The patient was regularly followed up after being discharged from our ward. Measurements of C3–C4 levels were carried out by a hematological test. Due to the rarity of such a disease, especially in Chinese people, relevant diagnosis methods are missing in this patient, so the patient was only diagnosed with AAE-C1-INH associated with MGUS clinically. The latest follow up showed that he still underwent recurrent upper airway obstruction; thus, he remained in a tracheostomy state due to a lack of proper medication prophylaxis and died eventually. This unusual case reminds emergency physicians to pay attention to such disease during clinical practice, and relevant diagnosis method should be improved (AU)

Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges.

Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease.

Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema.

Angioedema is a well-recognized and potentially lethal complication of angiotensin-converting enzyme inhibitor (ACEi) therapy. In ACEi-induced angioedema, bradykinin accumulates due to a decrease in its metabolism by ACE, the enzyme that is primarily responsible for this function. The action of bradykinin at bradykinin type 2 receptors leads to increased vascular permeability and the accumulation of fluid in the subcutaneous and submucosal space. Patients with ACEi-induced angioedema are at risk for airway compromise because of the tendency for the face, lips, tongue, and airway structures to be affected. The emergency physician should focus on airway evaluation and management when treating patients with ACEi-induced angioedema.

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.

Nonepisodic Angioedema with Eosinophilia Following Receipt of the BNT162b2 mRNA COVID-19 Vaccine.

Angioedema with eosinophilia (AE) is a rare disease of unknown etiology characterized by episodic (EAE) or nonepisodic AE (NEAE). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA-based vaccines function as immunogens and intrinsic adjuvants and have been shown to be safe in large-scale trials. However, the long-term adverse reactions, especially those related to eosinophilic complications, have not been fully clarified. We herein report a case of self-limited but severe NEAE that developed in a young woman one week after receiving the second BNT162b2 mRNA vaccine. The symptoms that impaired her activities of daily living, such as edema, gradually resolved with supportive care over 10 weeks without corticosteroid treatment.