Management Of Angioedema Research Articles

Closing Gaps in Hereditary Angioedema Management: Addressing Delays in On-Demand Treatment

Closing Gaps in Hereditary Angioedema Management: Addressing Delays in On-Demand Treatment

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

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. 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). 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. A total of 142acute 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. 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.

A Comprehensive Management Approach in Pediatric and Adolescent Patients With Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare autosomal-dominant disorder; most cases are characterized by low plasma levels of C1 esterase inhibitor (C1-INH). Clinical manifestations of HAE due to C1-INH deficiency include unpredictable, acute, recurrent episodes of nonpruritic swelling that can affect the face, trunk, limbs, and the respiratory, gastrointestinal, and genitourinary tracts. Attacks can be disfiguring, disabling, painful, and even life-threatening if laryngeal swelling occurs. Symptoms of HAE generally manifest in childhood. Effective medications are available and approved to treat HAE in children. However, evidence informing use of these medications in pediatric clinical practice is limited. Hereditary angioedema management plans are critical to optimize outcomes and should address on-demand treatment for acute attacks and plans to prevent potentially fatal laryngeal attacks. The plan should also comprise a holistic approach to address nonclinical aspects of HAE, including quality of life (QoL) and psychological issues. This article provides an overview of HAE management principles that health care providers can apply to treat pediatric patients to improve their QoL.

Long-term prophylaxis in hereditary angioedema management: Current practices in France and unmet needs.

Background: Hereditary angioedema (HAE) is characterized by unpredictable and potentially life-threatening attacks of cutaneous and submucosal swelling. Over the past decade, new agents, based on a better understanding of the underlying biologic mechanisms of HAE, have changed the face of long-term prophylaxis (LTP). Objective: The objective was to describe current practices and unmet needs with regard to LTP for HAE in expert centers in France. Methods: The study was conducted in France in 2020. Based on their experience with patients with HAE who had visited their center at least once in the past 3 years, physicians from 25 centers who are expert in the management of HAE were requested to fill in a questionnaire that encapsulated their active patient list, criteria for prescribing LTP, and medications used. They were asked about potential unmet needs with currently available therapies. They were asked to express their expectations with regard to the future of HAE management. Results: Analysis was restricted to 20 centers that had an active patient file and agreed to participate. There were 714 patients with C1 inhibitor (C1-INH) deficiency, of whom 423 (59.2%) were treated with LTP. Altered quality of life triggered the decision to start LTP, as did the frequency and severity of attacks. Ongoing LTP included androgens (28.4%), progestins (25.8%), lanadelumab (25.3%), tranexamic acid (14.2%), intravenous C1-INHs (5.6%), and recombinant C1-INH (0.7%). Twenty-nine percent of the patents with LTP were considered to still have unmet needs. Physicians' concerns varied among therapies: poor tolerability for androgens and progestins, a lack of efficacy for tranexamic acid and progestins, dosage form, and high costs for C1-INHs and lanadelumab. Physicians' expectations encompassed more-efficacious and better-tolerated medications, easier treatment administration for the sake of improved quality of life of patients, and less-expensive therapies. Conclusion: Despite the recent enrichment of the therapeutic armamentarium for LTP, physicians still expressed unmet needs with currently available therapies.

Hereditary Angioedema Management: From Dealing to Leading

A two-part digital symposium series entitled ‘Hereditary Angioedema (HAE) Management: From Dealing to Leading,’ took place during the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress, held in Prague, Czechia, in July 2022. The first symposium, ‘The Journey Towards Disease Control in HAE’, held on 1st July 2022, was chaired by Markus Magerl, Department of Dermatology and Allergy, Charite Universitätsmedizin, Berlin, Germany. Speakers Grzegorz Porębski, Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Kraków, Poland, and Mauro Cancian, Department of Systems Medicine, University of Padova, Italy, discussed how the advent of new disease-specific HAE treatments have contributed to the evolution of the HAE management guidelines, and the resulting impact on the lives of patients with HAE. The latest international management guidelines from the World Allergy Organization (WAO)/EAACI newly define the goals of treatment in HAE as achieving total control of the disease and normalising patients’ lives, stressing that this can currently only be achieved by long-term prophylactic (LTP) treatment. The second symposium, ‘Making the Goals of HAE Management Achievable with Subcutaneous C1-Inhibitor’, held on 2­nd July 2022, was chaired by Pavlína Králíčková, Department of Clinical Immunology and Allergology, University Hospital Hradec Králové, Czechia, who also provided a brief overview of the development of the subcutaneous formulation of C1-inhibitor for LTP. Emel Aygören-Pürsün, Angioedema Clinic and Center for Hereditary Angioedema, University Hospital Frankfurt, Goethe University, Germany, and Teresa Caballero, Allergy Department, Hospital Universitario La Paz, Madrid, Spain, then used case studies to highlight the necessity of assessing and monitoring a patient’s disease activity, the associated quality of life, and disease control to allow for possible adaptations to the treatment plan. Both speakers also highlighted how the use of subcutaneous C1-inhibitor for LTP can contribute towards the achievement of the goals of HAE treatment, namely achieving total disease control and normalising patients’ lives.

Guidelines for management of hereditary angioedema: What is new? What is missing?

Background: Hereditary angioedema is an autosomal dominant disease that presents with recurrent episodic swelling of the submucosal and/or subcutaneous tissues of the cutaneous, gastrointestinal, and respiratory systems. Evaluation and treatment guidelines have been published nationally and internationally to aid the treating provider. Methods: A review of the most cited and most recent updated guidelines was undertaken to review key points and to explore real-world feasibility of incorporating them into clinical practice. The International World Allergy Organization/European Academy of Allergy and Clinical Immunology (WAO/EAACI) Guideline for the Management of Angioedema - The 2017 Revision and Update, and the consensus reports from the Hereditary Angioedema International Working Group, the Joint Task Force on Practice Parameters focused practice parameter update, and the most recently updated US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema were reviewed and summarized. Results: Key points that have been consistent throughout the guidelines include recommendations for evaluation and classification of hereditary angioedema as well as evidence-based guidelines for treatment. Further attention is required on the evaluation and continuous assessment of the burden of illness and quality of life (QoL). Conclusion: The guidelines for management of hereditary angioedema provide a framework for the clinician. However, the physician-patient dialog with regard to the patient disease experience, which includes attack frequency, severity, and Qol, must be continually assessed.

Global perceptions of the current and future impacts of COVID-19 on hereditary angioedema management.

Background: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected health-care provision across the globe. Management of chronic ailments has become challenging because of the strained health-care resources and social distancing measures that prevent on-site clinical visits and treatments. Hereditary angioedema (HAE) is a debilitating, chronic disease characterized by unpredictable swelling attacks in various parts of the body. Controlling HAE symptoms often requires long-term prophylactic medication use and regular medical care; however, limited scientific information has been published about HAE medical care during the COVID-19 pandemic. Objective: To gather patient and health-care professional (HCP) perspectives on the global impact that COVID-19 has had, and the future impact it will have on HAE medical care and to identify differences in perceptions across economic and geographic boundaries. Methods: We conducted two independent but similar online global surveys to capture patient and HCP perspectives on the impact that COVID-19 has had, and the future impact it will have on HAE medical care. Results: Both patients and HCPs globally reported that the pandemic has limited the availability of HAE medical care, and they expect the restrictions to continue far beyond the pandemic. In addition, the results of our study suggested that telehealth use has increased across the globe but has been more successfully implemented in high-income countries. Conclusion: Patients and HCPs expect that HAE-related care will be negatively impacted by the pandemic for many years. Disparities in medical care and technologic infrastructure may exacerbate these challenges in non-high-income countries. Supportive tools and global infrastructure should be established to provide aid to non-high-income countries throughout the pandemic and several years after.

Hereditary Angioedema Management: Individualization

Hereditary angioedema (HAE) is a chronic, incurable disease characterized by recurrent, unpredictable episodes of swelling in various parts of the body. The presentation of HAE is highly variable, and multiple treatment options are available for disease control and prophylaxis. HAE management plans should therefore be individualized to reduce mortality and morbidity in a way that prioritizes quality of life based on each patient’s lifestyle, preferences, and goals. This report discusses the key considerations in HAE management and patient-centered care, including the use of shared decision making and the vital roles performed by nurse practitioners and other health care providers.

Red meat causing delayed anaphylactic airway edema: a case report

<p class="abstract">The goals of emergency management of angioedema include prevention of spontaneous eruption, maintaining and securing the airway and to stop the progression of the disease. Laryngeal edema is one of the life-threatening complications of angioedema that can be managed by endotracheal intubation or emergency tracheostomy or cricothyrotomy. Recently, delayed onset food induced anaphylactic reactions are being recognised widely due to better clinical knowledge and technology that can substantiate the diagnosis. The classical finding of anaphylaxis to only proteins have been disproved and delayed onset food allergy (i.e.) 3-6 hours after ingestion of food has been attributed to specific carbohydrate moieties in glycolipids and glycoproteins such as Galactose-α-1,3-galactose found in red meat (beef, pork and lamb). Even though it is seen rarely in the Indian population, it should be a part of the diagnostic algorithm in order to prevent fatal complications. Hereby reporting 39 years old male with undiagnosed red meat allergy presented with features of foreign body sensation throat and laryngeal oedema and managed conservatively with steroids and nebulisation.</p>

A follow-up survey of patients with acquired angioedema due to C1-inhibitor deficiency.

Acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a rare form of bradykinin-mediated angioedema. It is diagnosed by complement testing; its treatment consists of the management of angioedema (AE) attacks and of underlying disease. Evaluate the results of the clinical follow-up of patients with C1-INH-AAE. Between 1999 and 2020, 3938 patients with angioedema were evaluated, and 17 diagnosed with acquired C1-INH deficiency were followed-up. Mean age of the 17 patients was 61years at diagnosis. In 33%, ACE inhibitors provoked AE attacks. Autoantibodies against C1-INH were detected in 10 patients at diagnosis and in a further patient during follow-up. The AE attacks involved the skin in 70.6%, the upper airways in 41.2% and the tongue/lip in 52.9% of patients. Twelve of the 17 patients had an underlying condition, mainly (n=11) lymphoproliferative disease. In 10 patients diagnosed with a haematological disorder, AAE symptoms preceded the onset of the latter. One patient has not experienced an AE attack since diagnosis. Twelve patients were treated for angioedema attacks, and 32% of the attacks required acute treatment. PdC1-INH was used to relieve AE attacks, and rituximab for the treatment of underlying disease (in six patients). Six patients had multiple AE attacks before any treatment. The symptom-free period increased in five patients after the on-demand administration of pdC1-INH concentrate and following treatment of the underlying disease in two patients. Early diagnosis of C1-INH-AAE and underlying disease is indispensable to reduce disease burden by introducing appropriate, individualized treatment and regular follow-up.

LARGE RETROSPECTIVE STUDY ANALYZING ROLE OF STEROIDS USE IN INTUBATED PATIENTS WITH ANGIOEDEMA

SESSION TITLE: Allergy and Airway Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Glucocorticoids are routinely given as treatment for angioedema yet the benefit is unclear and there is insufficient evidence of its role in angioedema management. In this study, we compared patients who did or did not receive corticosteroids for different angioedema subgroups. METHODS: We performed a cohort retrospective analysis of a total of 3290 angioedema patients (1241 intubated) across 185 US hospitals from period 01/2016-01/2020. Diagnosis codes were used to identify angioedema cases and time of intubation was calculated from mechanical ventilation procedure codes. Descriptive analyses of patient’s characteristics i.e. age, sex, frequencies of types of angioedema, duration of intubation, steroids administration, ICU hours, and the total length of stay were conducted. RESULTS: A total n=3,290 angioedema patients, n=205 in allergic angioedema, n=1,955 in unspecified angioedema, and n=1,151 in ACE Inhibitor angioedema were included in the study. ICU hours: Steroids did not affect ICU hours in any subgroup however, age was found to be a significant factor (P=0.001). Assuming all other variables remain constant, we found that for every additional year, a patient with any angioedema would be in the ICU for 0.51 hours longer. Total length of stay: steroids did not have a significant effect on the total length of stay in any subgroup. Length of intubation: steroids were not found to have a significant effect on the length of intubation in any subgroup. Steroids, Age, and sex relationship with the type of angioedema: there were no statistical differences in the rates of steroid use among three subgroups. A total of 61% of allergic angioedema, 63% unspecified angioedema, 63% ACE inhibitors induced angioedema and all combined 62.61% of patients received steroids. There is an association between intubation time and angioedema type (P=0.02). In the ACE Inhibitor subgroup, 58% of patients were not intubated, 9% were intubated for <24 hours, 25% were intubated for 24-96 hours, and 5% were intubated for >96 consecutive hours. In the allergic subgroup, 68% of patients were not intubated, 10% were intubated for <24 hours, 19% were intubated for 24-96 hours, and 3% were intubated for >96 consecutive hours. In the unspecified subgroup, 64% of patients were not intubated, 9.16% were intubated for <24 hours, 22% were intubated for 24-96 hours, and 5% were intubated for >96 consecutive hours. CONCLUSIONS: Steroids administration has no effect on ICU hours, length of intubation, and the total length of stay across all subgroups of angioedema. CLINICAL IMPLICATIONS: To our knowledge, this is the largest observational study conducted on intubated angioedema patients. It shows that steroids were given in 2/3 of intubated angioedema patients without any meaningful outcomes. Steroids use can potentially complicate the clinical picture and expose vulnerable patient populations to side effects. DISCLOSURES: No relevant relationships by Napatkamon Ayutyanont, source=Web Response No relevant relationships by Asma Jamil, source=Web Response No relevant relationships by Scott Kubomoto, source=Web Response No relevant relationships by Chandra Patel, source=Web Response No relevant relationships by Abu Tahir Taha, source=Web Response No relevant relationships by Sarah Wilson, source=Web Response

Breakthroughs in hereditary angioedema management: a systematic review of approved drugs and those under research.

Hereditary angioedema (HAE) is a rare genetic disorder, characterized by recurrent and unexpected potentially life-threatening mucosal swelling. The impairment underlying HAE could be a defect in C1-inhibitor activity, or in its serum concentration. Patients affected by HAE should be treated with on-demand or prophylactic drugs. Lifelong C1-inhibitor supplementation is sometimes required. In this review, we review the currently approved drugs for HAE due to C1-inhibitor defect and to describe those under research. In particular, we focused on the mechanisms of action, routes of administration, and efficacy of these therapies. A systematic review of the literature was performed using the PubMed database for original articles and clinical trials of HAE treatments from 2005 to 2019. The approved HAE treatments can minimize the risk of death, but they are not effective in complete healing from the disease. The new gene therapies seem to provide promising opportunities for the treatment of hereditary angioedema. However, there are still many unmet needs, including efficacy, route, and timing of administration.

Solutions for management of angiotensin-converting enzyme–induced angioedema in a high risk population: a single center retrospective observational study

Background: There is an increasing rate of angiotensin-converting enzyme (ACE) inhibitor-induced angioedema in the United States which has not plateaued since this side effect was first described in 1980. There are no studies reporting a plateau, decrease in the incidence or decrease in the rate of rise in high risk populations. High risk populations are defined as African Americans, female sex, and age older than 65. Objectives: The objective of this manuscript is to determine the incidence of angioedema in a high risk, urban population over a 7-year period, and to determine impactful solutions on its management by anesthesiologists. Methods: PubMed was queried with the keywords angioedema, ACE inhibitor-induced angioedema, and anesthesiology angioedema management. Subset keyword searches included angioedema incidence and high risk populations, and emergency room anesthesiology angioedema management. Our medical center’s data repository was queried to identify the number of emergency department visits between January 2007 and December 2013. We then queried the database to determine the number of cases that were diagnosed as angioedema. A subset of patients was identified that included all patients that presented with angioedema, and who had a current ACE inhibitor prescription. The medical records of the admitted patients were reviewed to determine whether angioedema was induced by an ACE inhibitor or another etiology. The annual occurrence rates of angioedema and ACE inhibitor-induced angioedema were then calculated. Analysis of the medical records also determined the extent of anesthesiology involvement. Results: There were a total of 478 cases of ACE inhibitor-induced angioedema during the 7-year period. The incidence of ACE inhibitor-induced angioedema rose from 0.17 in 2007 to 0.53 in 2013. There is no evidence of plateau for this rise and current rate of rise appears to be exponential. African Americans, female sex, and age 65 and younger were associated with a greater incidence of ACE inhibitor-induced angioedema. One hundred thirty-three patients that presented to the emergency department with ACE inhibitor-induced angioedema were admitted, and 22 of these patients required intubation. Anesthesiology was consulted 23 times, and performed 14 (63.6%) of the intubations.

Evaluation and Management of Angioedema in the Emergency Department.

Angioedema is defined by non-dependent, non-pitting edema that affects several different sites and is potentially life-threatening due to laryngeal edema. This narrative review provides emergency physicians with a focused overview of the evaluation and management of angioedema. Two primary forms include histamine-mediated and bradykinin-mediated angioedema. Histamine-mediated forms present similarly to anaphylaxis, while bradykinin-mediated angioedema presents with greater face and oropharyngeal involvement and higher risk of progression. Initial evaluation and management should focus on evaluation of the airway, followed by obtaining relevant historical features, including family history, medications, and prior episodes. Histamine-mediated angioedema should be treated with epinephrine intramuscularly, antihistaminergic medications, and steroids. These medications are not effective for bradykinin-mediated forms. Other medications include C1-INH protein replacement, kallikrein inhibitor, and bradykinin receptor antagonists. Evidence is controversial concerning the efficacy of these medications in an acute episode, and airway management is the most important intervention when indicated. Airway intervention may require fiberoptic or video laryngoscopy, with preparation for cricothyrotomy. Disposition is dependent on patient’s airway and respiratory status, as well as the sites involved.

Orolingual Angioedema After Tissue Plasminogen Activator Administration in Patients Taking Angiotensin-Converting Enzyme Inhibitors

Orolingual angioedema is a rare adverse effect (1%-5%) of tissue plasminogen activator (tPA) that can lead to significant morbidity in patients with acute ischemic stroke. It is thought that increased levels of bradykinin and histamine resulting from tPA administration can result in angioedema. Angiotensin-converting enzyme (ACE) inhibitors can also lead to increased levels of bradykinin and appear to be a risk factor for tPA-associated angioedema. A literature review was conducted to examine previous cases of orolingual angioedema associated with tPA administration in patients also taking ACE inhibitors to better understand the relationship between ACE inhibitors and tPA-induced angioedema. Over a 20-year period, 27 patients who experienced angioedema with tPA while on ACE inhibitor therapy were identified. In this patient population, the onset of angioedema symptoms appeared as soon as 15 min after the tPA bolus and as late as 2 hr after the tPA infusion. Most patients required a combination of supportive medications such as corticosteroids (81.5%), antihistamines (74%), and epinephrine (18.5%) for the management of angioedema. Severe presentations of orolingual angioedema resulted in intubation for airway protection (26%). Symptom resolution ranged from shortly after the administration of supportive medications to 72 hr after symptom onset. Orolingual angioedema after tPA administration has the potential to cause significant morbidity, indicating patients should be monitored closely for a few hours after administration for the development of airway compromise. ACE inhibitors should not be the preferred antihypertensive agents for patients who require blood pressure lowering prior to tPA administration.

NOT YOUR AVERAGE CASE OF ANGIOEDEMA

Introduction Allergists are commonly consulted for management of angioedema in hospitalized patients. It is also an opportunity for the allergist to assess for and recognize other causes of life-threatening swelling. Case Description A 26-year old man with a complex PMH of ESRD on dialysis, HTN, and multiple gunshot wounds(GSW) who was admitted after sustaining GSW to his back and leg. Allergy/Immunology was consulted for five days of refractory “angioedema” despite treatment with steroids and antihistamines. The patient and medical team reported symptom onset after the patient had a first lifetime seizure and was started on levetiracetam. He reported waking up with swelling of his whole face, neck, tongue and throat along with shortness of breath. He was treated with methylprednisolone and diphenhydramine with some improvement. The levetiracetam and most of his other medications were discontinued, but his swelling continued to wax and wane. He was also treated with epinephrine once with reported improvement in swelling. The allergy team recommended evaluation for underlying SVC syndrome upon consultation which was suggested by findings on CT scan and confirmed by venogram which were performed after several days delay. However, the patient expired from complications of his large blood clot two days later. Discussion This case points towards the important fact that sometimes a red herring like starting a new medication can cause a delay in making the correct diagnosis when it comes to new-onset swelling. Recognition of life-threatening angioedema masqueraders may mean the difference between life and death.

The Icatibant Outcome Survey: experience of hereditary angioedema management from six European countries.

BackgroundHereditary angioedema (HAE) due to C1‐inhibitor deficiency (C1‐INH‐HAE) is a rare, potentially fatal, bradykinin‐mediated disease. Icatibant is a bradykinin B2 receptor antagonist originally approved in 2008 in the European Union and 2011 in the United States as an acute therapy option for HAE attacks in adults.ObjectiveTo compare demographics, disease characteristics and treatment outcomes of icatibant‐treated HAE attacks in patients with C1‐INH‐HAE enrolled in the Icatibant Outcome Survey across six European countries: Austria, France, Germany, Italy, Spain and the UK.MethodsThe Icatibant Outcome Survey [IOS; Shire, Zug, Switzerland (NCT01034969)] is an international observational study monitoring the safety and effectiveness of icatibant. Descriptive, retrospective analyses compared IOS country data derived during July 2009–April 2015.ResultsOverall, 481 patients with C1‐INH‐HAE provided demographic data. A significant difference across countries in age at onset (P = 0.003) and baseline attack frequency (P < 0.001) was found although no significant differences were found with respect to gender (majority female; P = 0.109), age at diagnosis (P = 0.182) or delay in diagnosis (P = 0.059). Icatibant was used to treat 1893 attacks in 325 patients with majority self‐administration in all countries. Overall, significant differences (all P < 0.001) were found across countries in time to treatment [median 1.8 h; median range: 0.0 (Germany–Austria) to 4.4 (France) h], time to resolution [median 6.5 h; median range: 3 (Germany–Austria) to 12 (France) h] and attack duration [median 10.5 h; median range: 3.1 (Germany–Austria) to 18.5 (France) h].ConclusionThese data form the first European cross‐country comparison of disease characteristics and icatibant use in patients with C1‐INH‐HAE who are enrolled in IOS. International variation in icatibant practice and treatment outcomes across the six European countries assessed highlight the need to further investigate the range of country‐specific parameters driving regional variations in icatibant use.

Diagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor Deficiency

Acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a rare disease with no prevalence data or approved therapies. To report data on patients with C1-INH-AAE followed at Angioedema Center, Milan (from 1976 to 2015). Diagnostic criteria included history of recurrent angioedema without wheals; decreased C1-INH antigen levels and/or functional activity of C1-INH and C4 antigen less than 50% of normal; late symptom onset (>40 years); no family history of angioedema and C1-INH deficiency. In total, 77 patients (58% females; median age, 70 years) were diagnosed with C1-INH-AAE and 675 patients with hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) (1 patient with C1-INH-AAE/8.8 patients with C1-INH-HAE). Median age at diagnosis was 64 years. Median time between symptom onset and diagnosis was 2 years. Sixteen patients (21%) died since diagnosis, including 1 because of laryngeal edema. Angioedema of the face was most common (N= 63 [82%]), followed by abdomen (N= 51 [66%]), peripheries (N= 50 [65%]), and oral mucosa and/or glottis (N= 42 [55%]). Forty-eight of 71 patients (68%) had autoantibodies to C1-INH. In total, 56 patients (70%) used on-demand treatment for angioedema including intravenous pdC1-INH 2000 U (Berinert, CSL Behring, Marburg, Germany) (N= 49) and/or subcutaneous icatibant 30 mg (Firazyr, Shire; Milano, Italy) (N= 27). Eventually, 8 of 49 patients receiving pdC1-INH became nonresponsive; all had autoantibodies. Thirty-four patients received long-term prophylaxis with tranexamic acid (effective in 29) and 20 with androgens (effectivein 8). The incidence of C1-INH-AAE was 1 for every8.8 patients with C1-INH-HAE. Thirty percent of the deaths were related to the disease. Treatments approved for C1-INH-HAE are effective in C1-INH-AAE, although with minimal differences.

Emergency Department Airway Management of Severe Angioedema: A Video Review of 45 Intubations

Angioedema is an uncommon but important cause of airway obstruction. Emergency airway management of angioedema is difficult. We seek to describe the course and outcomes of emergency airway management for severe angioedema in our institution. We performed a retrospective, observational study of all intubations for angioedema performed in an urban academic emergency department (ED) between November 2007 and June 2015. We performed a structured review of video recordings of each intubation. We identified the methods of airway management, the success of each method, and the outcomes and complications of the effort. We identified 52 patients with angioedema who were intubated in the ED; 7 were excluded because of missing videos, leaving 45 patients in the analysis. Median time from arrival to the ED to the first intubation attempt was 33 minutes (interquartile range 17 to 79 minutes). Nasotracheal intubation was the most common first method (33/45; 73%), followed by video laryngoscopy (7/45; 16%). Two patients required attempts at more invasive airway procedures (retrograde intubation and cricothyrotomy). The intubating laryngeal mask airway was used as a rescue method 5 times after failure of multiple methods, with successful oxygenation, ventilation, and intubation through the laryngeal mask airway in all 5 patients. All patients were successfully intubated. In this series of ED patients who were intubated because of angioedema, emergency physicians used a range of methods to successfully manage the airway. These observations provide key lessons for the emergency airway management of these critical patients.

Emergency Department Management of Hereditary Angioedema Attacks: Patient Perspectives

Emergency department (ED) management of hereditary angioedema (HAE) has been hindered by misdiagnosis and limited treatment options. Food and Drug Administration approval of 4 on-demand HAE therapies starting in 2009 and the publication of ED guidelines for angioedema management in 2014 should facilitate improvement of HAE management in the ED. The objective of this study was to identify patient-reported areas for improvement in ED management of HAE attacks. Patients with self-reported HAE with C1 inhibitor deficiency who attended the 2015 HAE Association Patient Summit were asked to complete an anonymous 30-question survey. Questions addressed patient characteristics and HAE management in the ED. Patients indicated that understanding of HAE in the ED needed improvement (99%, 104 of 105 patients). Recognition of HAE as a diagnosis (48%, 50 of 105 patients), appreciation of HAE as a serious disease (45%, 47 of 105 patients), and medication management (59%, 62 of 105 patients) were identified as areas needing improvement. Among 39 patients who required ED care within the last year, 6 did not receive any HAE-targeted therapy, and treatment with corticosteroids (n= 3), epinephrine (n= 2), and antihistamines (n= 7) was reported. Among 68 patients whose treatment plan was to receive home on-demand therapy, 26 required ED care because of an inability to receive on-demand therapy at home as outlined in their treatment plan. Having a treatment plan was associated with a greater likelihood of receiving HAE therapy in the ED (99% vs 74%, P= .002). HAE management in the ED can be improved with a focus on recognition of HAE attacks and administration of effective HAE therapies.