If not angioedema, what is it? Diagnostic approach to facial edema.

Facial edema is a relatively frequent clinical presentation encountered in patients seen in allergology and dermatology clinics. The differential diagnosis is broad, and sometimes the definitive diagnosis can be a challenge for the clinician. Facial angioedema itself encompasses different etiopathologies (histaminergic, bradykinergic, etc.) that must be distinguished from other causes of facial edema, such as allergic contact dermatitis, granulomatous conditions, inflammatory causes, infections, neoplasms or paraneoplastic syndromes, autoimmune diseases, among other entities hereby referred as miscellanea. A proper diagnostic approach is essential to order the appropriate tests, as well as to prescribe a targeted treatment. This review focuses on entities that present with facial edema and summarize their characteristic clinical features.

[What are the main symptoms of urticaria and how are they systematically recorded?] / Was sind Leitsymptome bei Urtikaria, und wie werden sie systematisch erfasst?

Wheals or angioedema or both are the main symptoms of urticaria. The small number of the symptoms usually makes diagnosis easy. What is not trivial, however, is the comprehensive systematic recording and assessment of these symptoms and, above all, their sequelae, which affect many areas of the patient's life. Disease activity, quality of life and disease control can and should be measured before and during treatment in order to optimally adapt therapeutic measures. The instruments developed for this purpose have become easier and more convenient to use in recent years thanks to user-friendly platforms such as mobile health apps.

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 Patient Charter for Chronic Urticaria.

Chronic urticaria (CU) is the recurring development of wheals (aka "hives" or "welts"), angioedema, or both for more than 6 weeks. Wheals and angioedema occur with no definite triggers in chronic spontaneous urticaria, and in response to known and definite physical triggers in chronic inducible urticaria. Approximately 1.4% of individuals globally will have CU during their lifetime. The itching and physical discomfort associated with CU have a profound impact on daily activities, sexual function, work or school performance, and sleep, causing significant impairment in a patient's physical and mental quality of life. CU also places a financial burden on patients and healthcare systems. Patients should feel empowered to self-advocate to receive the best care. The voice of the patient in navigating the journey of CU diagnosis and management may improve patient-provider communication, thereby improving diagnosis and outcomes. A collaboration of patients, providers, advocacy organizations, and pharmaceutical representatives have created a patient charter to define the realistic and achievable principles of care that patients with CU should expect to receive. Principle (1): I deserve an accurate and timely diagnosis of my CU; Principle (2): I deserve access to specialty care for my CU; Principle (3): I deserve access to innovative treatments that reduce the burden of CU on my daily life; Principle (4): I deserve to be free of unnecessary treatment-related side-effects during the management of my CU; and Principle (5): I expect a holistic treatment approach to address all the components of my life impacted by CU. The stated principles may serve as a guide for healthcare providers who care for patients with CU and translate into better patient-physician communication. In addition, we urge policymakers and authors of CU treatment guidelines to consider these principles in their decision-making to ensure the goals of the patient are achievable.

Clinical Evaluation of Pediatric Patients with Hereditary Angioedema.

Hereditary angioedema is a rare, potentially life-threatening disease. There is a lack of data describing the clinical course of hereditary angioedema (HAE) in children. We aimed to evaluate the clinical characteristics of pediatric patients with hereditary angioedema: The age of disease onset, age at diagnosis, the frequency of angioedema attacks, the total number of attacks before diagnosis, the regions where angioedema attacks were observed, accompanying abdominal pain, and serum levels of C4 and C1 esterase inhibitor were obtained and recorded. In addition, the results of SERPING1 (C1INH) gene sequence analysis of the patients in this group were also collected from medical records and recorded. While none of the patients reported a skin rash as a symptom of attack, there was formication observed in the region of angioedema in 46.9% (n = 15) of the patients and pruritus in 6.2% (n = 2) of the patients. At disease onset, the complaints of the patients regarding location of edema were on the hands of 32.3% (n = 10), on the feet of 9.7% (n = 3), on the faces of 25.7% (n = 8), and abdominal attacks in 32.3% of the patients (n = 10). Four different variants, one of which was novel, were detected in the SERPING1 gene in eight different families. The results of this study suggest that hereditary angioedema is diagnosed only when the patient requests examination following recurrent angioedema. Severe laryngeal edema attacks in patients without a diagnosis of HAE are fatal at a higher rate than attacks in patients with a diagnosis. Thus, awareness of the symptoms of HAE is necessary, and correct diagnosis is essential to proper treatment.

Angioedema postoperatorio de inicio tardío, desencadenado por un inhibidor de la enzima convertidora de angiotensina: previsión de vía aérea de emergencia / Late-onset postoperative angioedema triggered by angiotensin-converting enzyme inhibitor: an emergent airway forethought

El angioedema es una situación potencialmente mortal, debido al riesgo de compromiso de la vía aérea que da lugar a un deterioro de la función respiratoria, hipoxia y, por último, paro cardiopulmonar. Puede ser provocado o desencadenado por agentes farmacéuticos, factores emocionales o fisiológicos, traumatismo de la vía aérea superior, o estrés quirúrgico.Un varón de 46 años de edad, a quien se había prescrito previamente perindopril, desarrolló angioedema de lengua 4h después de recibir el alta de la UCPA (unidad de cuidados postanestésicos). Se convocó a un equipo multidisciplinar, que destacó una estrategia de manejo de la vía aérea en caso de empeoramiento. Dicha estrategia consistió en intubación con fibroscopio por parte del anestesiólogo, o bien traqueostomía quirúrgica practicada por el equipo de cirugía, realizándose ambas técnicas con el paciente despierto y ventilación espontánea.El objetivo de este informe de caso es alertar de que el angioedema es una situación potencialmente mortal. Para un manejo óptimo, es importante preparar de antemano una estrategia detallada de manejo de la vía aérea, a implementar por parte de un equipo multidisciplinar. (AU)

Angioedema is a potentially life-threatening condition due to the risk of airway compromise leading to deterioration of respiratory function, hypoxia, and ultimately, cardiopulmonary arrest. It can be either unprovoked or triggered by pharmaceutical agents, emotional or physiologic factors, upper airway trauma, or surgical stress.A 46-year-old man previously prescribed perindopril developed angioedema of the tongue 4h after being discharged from the Post Anesthesia Care Unit (PACU). A multidisciplinary team was called and they outlined an airway management strategy to use in the event of worsening. The strategy consisted of either fiberoptic intubation by an anesthesiologist or surgical tracheostomy performed by the surgical team, both performed with the patient awake and in spontaneous ventilation.The aim of this case report is to raise awareness that angioedema is a potentially life-threatening condition. For optimal management, it is important to prepare in advance a detailed airway management strategy to be implemented by a multidisciplinary team. (AU)

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.

[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.

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)

The US Hereditary Angioedema Association Scientific Registry: hereditary angioedema demographics, disease severity, and comorbidities.

BACKGROUND: Hereditary angioedema (HAE) and idiopathic nonhistaminergic angioedema (INHA) are ultra-rare diseases whose natural histories and comorbidities are incompletely understood. OBJECTIVE: To develop a national patient-centric registry to address these deficiencies in our knowledge and improve our ability to assess the real-world impact of therapeutic interventions. METHODS: Data from members of the US HAE Association were collected into an online registry between 2009 and April 7, 2021. Cohorts were categorized by reported physician diagnosis. Patient reported data were collected using a series of questionnaires. Demographic, natural history, and family history outcomes of the HAE due to C1 inhibitor deficiency (HAE-C1INH) participants were compared with those of the combined HAE with normal C1 inhibitor (HAE-nl-C1INH) plus INHA group. The prevalence of comorbid conditions in the HAE-C1INH group was compared with the general US population. RESULTS: A total of 485 HAE-C1INH, 26 HAE-nl-C1INH, and 70 INHA participants were included in the analysis. Delay to diagnosis was shorter in HAE-C1INH (5 vs 11 years), but both had decreasing delays over time. Differences in attack frequency and location were found between the groups. Morbidity surrogates including emergency department visits, hospitalizations, unnecessary abdominal surgeries, and intubations were strikingly high as was mortality with 36.9% of HAE-C1INH and 15.4% of HAE-nl-C1INH participants reporting family members who died from a HAE attack. Females with HAE-C1INH had a significant increase in the prevalence of depression, sleep disorders, kidney disease, anemia, and hepatitis. Cardiovascular comorbidities were significantly reduced in the HAE-C1INH group. CONCLUSION: The US HAEA Scientific Registry provides a mechanism to enhance our knowledge of HAE and INHA.

Different Patterns of Response in Hypersensitivity Reactions to Arylpropionic Acid Derivatives.

BACKGROUND: Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce. OBJECTIVE: To characterize in detail patients reporting DHRs to APs. METHODS: We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches. RESULTS: Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P = .005 and P = .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P = .0002 and P = .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required. CONCLUSIONS: Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs.

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.

Concomitant medication in patients with bradykinin-mediated angioedema - there's more than ACE inhibitors.

Bradykinin-mediated angioedema is a rare, non-allergic, potentially life-threatening disease. ACE inhibitor-induced angioedema and hereditary angioedema (HAE) are the two most common presentations. Therapeutic options, pathophysiology and diagnosis continue to be investigated, with considerable progress in HAE over the last few decades. For all patients with bradykinin-mediated angioedema, there are several medications that should be avoided or administered with caution. Some of the triggering medications are well known, while others are suspected or of unknown significance. A common denominator is that there is no approved therapy for bradykinin-mediated angioedema as a drug side effect. Some medications, such as tissue plasminogen activator, have a higher incidence of angioedema with potential airway compromise than ACE inhibitors, although this fact is widely underappreciated. In this review, we aim to summarize what is currently known and recommended about concomitant medication in HAE patients and the interaction of other bradykinin-influencing drugs.

Unusual cause of unilateral facial oedema: intramuscular dirofilariasis.

INTRODUCTION: Unilateral facial oedema may occur due to inflammatory, infective, or cystic pathology; patients often seek medical help at an early stage. CASE REPORT: We report one such case caused mimicking a parotid abscess, caused by dirofilariasis. CONCLUSION: Dirofilariasis is an emerging zoonosis and should be considered a differential diagnosis of atypical facial swelling. It is equally important for clinicians, radiologists, and pathologists to be familiar with the diagnostic characteristics to avoid misdiagnosis.

Genetic Variants Leading to Urticaria and Angioedema and Associated Biomarkers.

Advances in next generation sequencing technologies, as well as their expanded accessibility and clinical use over the past 2 decades, have led to an exponential increase in the number of identified single gene disorders. Among these are primary atopic disorders-inborn errors of immunity resulting in severe allergic phenotypes as a primary presenting feature. Two cardinal aspects of type I immediate hypersensitivity allergic reactions are hives and angioedema. Mast cells (MCs) are frequent primary drivers of these symptoms, but other cells have also been implicated. Even where MC degranulation is believed to be the cause, mediator-induced symptoms may greatly vary among individuals. Angioedema-particularly in the absence of hives-may also be caused by hereditary angioedema conditions resulting from aberrant regulation of contact system activation and excessive bradykinin generation or impairment of vascular integrity. In these patients, swelling can affect unpredictable locations and fail to respond to MC-directed therapies. Genetic variants have helped delineate key pathways in the etiology of urticaria and nonatopic angioedema and led to the development of targeted therapies. Herein, we describe the currently known inherited and acquired genetic causes for these conditions, highlight specific features in their clinical presentations, and discuss the benefits and limitations of biomarkers that can help distinguish them.