[Registry of Members of the Association of Patients with Hereditary Angioedema of Perú]. / Registro de miembros de la Asociación de Pacientes con Angioedema Hereditario de Perú.

OBJECTIVE: To report the registry of the HAE Peruvian patient's association. METHODS: We used the questionnaire of the Latin American HAE committee. Consent was requested from the patient's association to report the data. RESULTS: We report data of 63 patients, 51 Female, 12 Male, range age between 6 to 74 years. Nine under 18 years old, 5/9 between 6 to 13 years. Forty-five HAE C1-INH type I, 12 HAE-FXII, 5 HAE UNK, 1 AAE. Symptoms onset average age in 56/62 HAE patients was 16.8. In a group of 50/62 adult HAE patients, the average diagnostic delay approximately was 19.3 years. Laboratory tests: we can perform C4 complement C1-inhibitor antigenic and functional tests. Treatments: The patients have access to tranexamic acid (TA) and attenuated androgens. We do not have registered specific long-term prophylaxis treatments. We used moderate/high doses of TA, in most patients up to 6 gr i.v./in 24 hours, we start with the treatment immediately the HAE acute crisis is beginning, it helps to the HAE attacks are less symptomatic, resolves in a few days and decrease the frequency. CONCLUSIONS: We present 63 members of the Association of Patients with Hereditary Angioedema of Perú. We have improved blood tests for HAE diagnosis. Moderate and high doses of Tranexamic Acid are used for prophylaxis and acute crisis respectively, with acceptable response. No deaths have been reported due to HAE crisis in the patient's association.

OBJETIVO: Reportar el registro de pacientes de la Asociación de Pacientes con Angioedema Hereditario de Perú, AEH. MÉTODOS: Se utilizó el cuestionario del Comité de AEH, de la Sociedad Latinoamericana de Alergia, Asma e Inmunología (SLAAI). Se solicitó el consentimiento a la Asociación de Pacientes para reportar los datos. RESULTADOS: Se reportan datos de 63 pacientes, 51 mujeres y 12 hombres, en un rango de edad entre 6 y 74 años. Nueve menores de 18 años, 5/9, entre 6 y 13 años. 45 con AEH-C1-INH tipo I, 12 AEH-FXII, 5 AEH-D, 1 AEA. La edad promedio de inicio de síntomas en 56/62 pacientes fue de 16,8. En 50/62 pacientes adultos con AEH, el promedio de tiempo de espera en el diagnóstico fue de 19,3 años. Laboratorio: Se puede desarrollar C4 complemento, C1-Inhibidor antigénico y funcional. Tratamientos: Se cuenta con acceso al ácido tranexámico (AT) y andrógenos atenuados. No se cuenta con tratamientos específicos para profilaxis de largo plazo. Se utilizaron dosis moderadas/altas de (AT), hasta 6 g por I V/ en 24 horas, inmediatamente, al inicio de las crisis de AEH, ayuda a que los ataques no sean tan intensos y tengan menor duración y frecuencia. CONCLUSIONES: Se presentan 63 miembros de la Asociación de Pacientes con Angioedema Hereditario de Perú. Se han mejorado los exámenes sanguíneos para el diagnóstico del AEH. Se utilizaron dosis moderadas/altas de ácido tranexámico con aceptable respuesta en los pacientes. No se han presentado decesos por crisis de AEH en los miembros de la Asociación.

The Disease Burden of Hereditary Angioedema: Insights from a Survey in French-Canadians from Quebec.

Background: Limited data are available on the clinical profile and disease burden of hereditary angioedema (HAE) in Canadians. Objective: This study aimed to assess HAE disease characteristics and the burden of disease in Canadians with HAE types I, II, and normal levels of C1 inhibitor (nC1-INH). Materials and Methods: A 46-item patient survey evaluating clinical characteristics and burden of disease was developed and disseminated by the HAE patient organization Angio-oédeme héréditaire du Québec in Quebec, Canada, from May 2019 to February 2020. The survey received Research Review Board ethics approval. Results: In the 35 respondents, HAE type I was the most common (46%), followed by nC1-INH (43%). Female participants were significantly younger at first symptom presentation than males (p=0.04). Prior to diagnosis, 69% of participants underwent unnecessary treatments and procedures, with a 10-year delay between first symptoms and diagnosis. Before starting the current treatment, 42% of participants experienced weekly HAE attacks. Most participants identified experiencing attacks in the abdomen (89%), followed by the larynx (66%), feet (66%), hands (63%), and face (63%). Most attacks were severe or moderate, yet almost half of patients waited >1 hr before getting medical attention at their last emergency department (ED) visit. HAE was associated with decreased health-related quality of life, leading to significant functional impairment in personal and professional life. As compared to HAE type I/II, patients with HAE nC1-INH were treated more often with tranexamic acid for long-term prophylaxis, and their condition was less controlled, resulting in more attacks and ED visits. Conclusion: HAE manifests in this patient population as frequent moderate-to-severe attacks and a high disease burden; the HAE subtype may differentially affect care requirements. There is an urgent need for increased awareness and education on HAE among treating physicians.

Transmission patterns of C1-INH deficiency hereditary angioedema favors a wild-type male offspring: Our experience at Chandigarh, India.

BACKGROUND: Deficiency of C1-inhibitor (C1-INH) protein, caused by pathogenic variants in the Serpin family G member 1 (SERPING1) gene, is the commonest pathophysiological abnormality (in ∼95 % cases) in patients with hereditary angioedema (HAE). C1-INH protein provides negative control over kallikrein-kinin system (KKS). Although the inheritance of the HAE-C1-INH is autosomal dominant, female predominance has often been observed in patients with HAE. OBJECTIVE: To analyze the risk of transmission of SERPING1 gene variant from father or mother to their offspring. METHODS: Pedigree charts of 42 families with a confirmed diagnosis of HAE-C1-INH and a pathogenic variant in the SERPING1 gene were analysed. Patients with HAE who had had at least one child were included for analyses to assess the risk of transmission from the father or mother to their offspring. RESULTS: Overall, 49 % (189/385) of all offspring inherited the genetic defect. In the subgroup analyses, 54.8 % (90/164) female offspring and 44.8 % (99/221; p < 0.02) male offspring inherited the genetic defect. Inheritance of the genetic defect was significantly lower in male offspring. Fathers with SERPING1 gene variant had a statistically significant skewed transmission of the wild type to the male offspring as compared to the variant (57.8 % wild type vs. 42.1 % variant; p < 0.02), whereas no statistically significant difference was found when a father transmitted the variant to a female offspring. Mothers with SERPING1 gene variant had no statistically significant difference in variant transmission to male or female offsprings. CONCLUSION: Results of the study suggest that the transmission pattern of SERPING1 gene variant favours the transmission of wild-type alleles in males, especially when the father is the carrier; hence, overall, fewer males and more female offspring inherited the variant. This could be because of a selection of wild-type male sperms during spermatogenesis, as the KLK system has been reported to play a crucial role in the regulation of spermatogenesis. Although, a similar pattern was observed in the maternal transmission of the SERPING1 gene variant; the difference was not statistically significant, likely because of a small sample size.

COVID-19 infection and vaccination in patients with hereditary angioedema: a multicentric study.

Summary: Background. Due to similarities between the pathophysiological mechanisms of hereditary angioedema (HAE) and COVID-19, it has been hypothesized that SARS-CoV-2 infection may trigger HAE attacks or, alternatively, that HAE patients may experience different of COVID-19 disease severity. Furthermore, the potential for COVID-19 vaccination to trigger angioedema attacks in patients with HAE is still not completely defined. The objective is to characterize the exacerbations and clinical manifestations associated with COVID-19 infection and describe the adverse effects of COVID-19 vaccination in patients with HAE.Methods. Retrospective observational, descriptive, non-interventional, multicenter study conducted in four Allergy Units and Departments in Central Portugal between March 2020 and July 2022. HAE patient data were obtained from electronic medical records. Results. The study included 34 patients (67.6% female): 26 with HAE type 1, 5 with HAE type 2, and 3 with HAE with normal C1 inhibitor. Most patients with HAE type 1 and 2 were receiving long-term prophylaxis. Among the 32 patients who received COVID-19 vaccination, 86 doses, were administered with one angioedema attack (1.2%) associated with vaccination. A small increase in the average number of attacks was observed in the year following COVID vaccination (7.1 versus 6.2 in the previous year, p = 0.029), however, this difference is unlikely to be clinically significant, as the context of the COVID-19 pandemic likely introduced numerous confounders. During the study period, 16 HAE patients had COVID-19, all presenting with mild disease. Four out of 16 patients (25%) reported angioedema attacks during COVID-19, and 43.8% during the convalescence period (3 months after infection). Conclusions. Patients with HAE can safely receive COVID-19 vaccination. The severity of COVID-19 infection does not appear to be increased in HAE patients.

Uncovering the true burden of hereditary angioedema due to C1-inhibitor deficiency: A focus on the Asia-Pacific region.

Hereditary angioedema (HAE) due to C1-inhibitor deficiency or dysfunction is a rare genetic disorder that causes recurrent episodes of swelling in various parts of the body. Treatment goals of HAE aim to "normalize" life for all patients; however, lack of diagnostic facilities and limited access to effective treatment options in developing nations cause delays in diagnosis and place a significant burden on patients. In this review, we aim to highlight the burden of disease caused by C1-inhibitor HAE across the Asia-Pacific region, considering its epidemiology, morbidity and mortality, and socioeconomic and psychological impact. We also review the availability of guideline-recommended diagnostic facilities and treatments, and how patients are currently managed. Data were collected from published literature and HAE experts in the region, who provided information regarding diagnosis and management in their countries. Current practice was reviewed against international guidelines, as well as local guidelines/consensus used in Australia, Japan, and China. Suggestions are provided for improving the time to diagnosis in the region, increasing access to guideline-recommended treatments, and providing support to reduce the burden on patients and caregivers. There is an urgent need to improve HAE services and provide access to life-saving treatment in developing countries, and efforts should be made to increase awareness of guideline recommendations in high-income economies that do not currently provide long-term prophylactic treatments.

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

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

Universal Access to On-Demand Treatment of Patients with Hereditary Angioedema, the Chilean Experience.

Background: In Chile, patients with hereditary angioedema (HAE) type I and type II are protected under Ley Ricarte Soto (LRS), which guarantees access to on demand plasma-derived C1-INH (pdC1-INH) since 2018. We aimed to analyze the first 3 years of LRS. Methods: Review of the LRS database between 2018 and 2021. Results: During the study period, 154 patients were covered by LRS, with an estimated prevalence of HAE in Chile at 0.8:100,000 inhabitants. A delay in diagnosis of 22 years was noted, 50 patients received epinephrine during an attack before the diagnosis of HAE. Mean number of attacks per year was 8, with 50% of adults and 42% of children experiencing more than 1 attack per month. Conclusion: Disease awareness must improve to reduce the diagnostic delay of HAE. Long-term prophylactic medications should be included in LRS to treat patients with high attack rates and control the costs of frequent on-demand treatment with pdC1-INH.

Hereditary Angioedema patient experiences of medication use and emergency care.

BACKGROUND: Hereditary angioedema (HAE) is a rare inherited illness characterised by recurrent swellings. Four percent of HAE attacks are life threatening throat swellings requiring urgent medical intervention. The aim of this study was to gain an in depth understanding of patient experiences of use of treatment and emergency care. METHODS: 65 participants completed an online survey including open ended questions about their experiences and/or completed an in-depth interview. Interview participants were asked to share and talk about up to five images that they felt best represented their life experiences with HAE. Data were analysed using reflexive thematic analysis. RESULTS: Treatment experiences highlighted the life changing nature of new treatments and benefits for quality of life, but also illustrated common barriers to treatment administration. Emergency care experiences illustrated how throat attacks and fear of their future occurrence could be traumatic. DISCUSSION: Findings indicate that HAE patients need psychological support to process fears and negative experiences. In addition, psychological barriers to treatment administration must be addressed to ensure treatment is used effectively. Education for emergency practitioners is also needed to improve emergency treatment and reduce the psychological burden of delayed emergency care.

[Health related to quality life of patients with hereditary angioedema in Argentina. A multicenter study]. / Calidad de vida relacionada con la salud en pacientes con angioedema hereditario de Argentina. Estudio multicéntrico.

OBJECTIVE: To describe health relaed quality of life in a cohort of stable adult outpatients with hereditary an-gioedema (HAE) with validated tools. METHODS: An observational, cross-sectional, and descriptive study was performed, carried out in patients with hereditary angioedema, coming from the City of Buenos Aires and its provinces: Corrientes, Chubut, Entre Ríos and Santa Fe. The HAE-QoL and SF-12v2 health questionnaires were applied to assess the related quality of life. with health. RESULTS: 100 patients were included; median age: 41.5 years (range: 18-77); 65% were female, and 79% had type 1 HAE. Asymptomatic, mild, moderate and severe cases accounted for 6, 29, 38, and 27% of participants, respectively. Seventeen percent of patients were receiving long-term prophylaxis. Icatibant was the most fre-quent treatment for acute episodes. All health domains SF-12v2 scores were lower than expected in general population, excepting "vitality" and "physical functioning". Total and all specific domains HAE-QoL scores were reduced. Differences between women and men and in every age-defined group were demonstrated for sev-eral specific domains. CONCLUSIONS: Health relaed to quality life was notably reduced in Argentinean patients with HAE, when imple-menting the HAE.QoL, and SF-12v2 questionnaries. The need for multidisciplinary strategies approaching this complex disease is highlighted.

OBJECTIVO: Describir la calidad de vida relacionada con la saluden pacientes adultos, ambulatorios y estables con angioedema hereditario, mediante cuestionarios validados. MÉTODOS: Estudio descriptivo, transversal y observacional, llevado a cabo en pacientes con angioedema here-ditario, procedentes de la Ciudad de Buenos Aires y sus provincias: Corrientes, Chubut, Entre Ríos y Santa Fe. Se aplicaron los cuestionarios HAE-QoL y SF-12v2 para evaluar la calidad de vida relacionada con la salud. RESULTADOS: Se incluyeron 100 pacientes, con mediana de edad de 41.5 años (rango: 18-77), principalmente de género femenino (65%). La forma más frecuente de angioedema hereditario fue el tipo 1 (79%). Los casos asintomáticos, leves, moderados y severos representaron el 6, 29, 38 y 27%, respectivamente. El 17% recibía profilaxis a largo plazo. Icatibant fue el tratamiento más prescrito para los episodios agudos de angioedema. Todos los puntajes de los dominios de salud del SF-12v2 fueron menores de lo esperado, excepto "vitalidad" y "funcionamiento físico". Se observó disminución en los puntajes totales y en todos los dominios del HAE-QoL. Se reconocieron diferencias entre las mujeres y los hombres, y para grupo etario en los puntajes de los dominios específicos. CONCLUSIONES: La calidad de vida relacionada con la salud disminuyó considerablemente en pacientes argentinos con angioedema hereditario al aplicar los cuestionarios HAE-QoL y SF-12v2. Es importante desarrollar estra-tegias multidisciplinarias para abordar esta enfermedad compleja.

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.

Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare and life-threatening condition characterized by recurrent localized edema. We conducted a systematic screening of SERPING1 defects in a cohort of 207 Czech patients from 85 families with C1-INH-HAE. Our workflow involved a combined strategy of sequencing extended to UTR and deep intronic regions, advanced in silico prediction tools, and mRNA-based functional assays. This approach allowed us to detect a causal variant in all families except one and to identify a total of 56 different variants, including 5 novel variants that are likely to be causal. We further investigated the functional impact of two splicing variants, namely c.550 + 3A > C and c.686-7C > G using minigene assays and RT-PCR mRNA analysis. Notably, our cohort showed a considerably higher proportion of detected splicing variants compared to other central European populations and the LOVD database. Moreover, our findings revealed a significant association between HAE type 1 missense variants and a delayed HAE onset when compared to null variants. We also observed a significant correlation between the presence of the SERPING1 variant c.-21 T > C in the trans position to causal variants and the frequency of attacks per year, disease onset, as well as Clinical severity score. Overall, our study provides new insights into the genetic landscape of C1-INH-HAE in the Czech population, including the identification of novel variants and a better understanding of genotype-phenotype correlations. Our findings also highlight the importance of comprehensive screening strategies and functional analyses in improving the C1-INH-HAE diagnosis and management.

A National Survey of Hereditary Angioedema and Acquired C1 Inhibitor Deficiency in the United Kingdom.

BACKGROUND: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care. OBJECTIVE: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients. METHODS: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data. RESULTS: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home. CONCLUSIONS: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients.

Acquired Angioedema in Selected Neoplastic Diseases.

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

The Disease Burden and Societal Costs of Hereditary Angioedema.

BACKGROUND: According to the current treatment guidelines, the goals of treatment of patients with hereditary angioedema (HAE) are to achieve total control of the disease and to normalize patients' lives. OBJECTIVE: This study aims to establish the entire burden of HAE comprising disease control, treatment satisfaction, reductions in quality of life, and societal costs. METHODS: Adult patients with HAE under treatment at the Dutch national center of reference completed a cross-sectional survey in 2021. The survey consisted of different questionnaires: angioedema-specific questionnaires (4-week Angioedema Activity Score and Angioedema Control Test), quality of life questionnaires (Angioedema Quality of Life [AE-QoL] questionnaire and EQ-5D-5L), the Treatment Satisfaction Questionnaire for Medication (TSQM), and societal costs questionnaires (iMTA Medical Consumption Questionnaire and iMTA Productivity Cost Questionnaire). RESULTS: The response rate was 78% (69 of 88). The entire sample had a mean Angioedema Activity Score of 16.61, and 36% of participants had poorly controlled disease as expressed by the Angioedema Control Test. The mean quality of life in the entire sample was 30.99 as expressed by the AE-QoL and 0.873 as expressed by the EQ-5D-5L utility value. Utilities dropped by 0.320 points during an angioedema attack. TSQM scores ranged from 66.67 to 75.00 across its 4 domains. On average, total costs per year incurred €22,764, predominantly existing of HAE-medication costs. Total costs showed substantial variation between patients. CONCLUSIONS: This study describes the entire burden of HAE among Dutch patients comprising disease control, quality of life, treatment satisfaction, and societal costs. These results can inform cost-effectiveness analyses that can aid reimbursement decisions for HAE treatments.

Living With Hereditary Angioedema in Australia: Findings From a National Observational Study Using Short Message Service to Monitor the Burden of Disease.

BACKGROUND: To understand the impact and burden of disease experienced by patients with hereditary angioedema (HAE). OBJECTIVE: To determine whether the use of short message service (SMS) to communicate with patients with HAE facilitates the collection of attack rate, medication use, and quality of life measurements. METHODS: Patients aged 12 years and older with doctor-confirmed HAE C1-inhibitor deficiency types I and II were invited to participate. We devised a novel method for monitoring attacks by using questions weekly via SMS to gain a more accurate picture of the burden of HAE in Australian patients in real time. RESULTS: A total of 2,648 weekly SMS messages were sent to 47 participants; 1,892 responses were received (71%). Participants reported 463 attacks across all treatment groups. Sixty percent of attacks were treated. Icatibant and C1-inhibitor concentrate were administered IV for 210 and 67 attacks, respectively. Of the 463 recorded attacks, 23 necessitated presentation to the hospital (5%), predominantly for facial and/or throat swelling. Several participants reported attacks (n = 186), which they chose not to treat. Most of those attacks were rated mildly severe. Twenty-one participants reported lost days owing to HAE attacks (44.7%). Fifty-eight attacks (17%) resulted in time away from work or school, equating to a total of 85.5 days lost. CONCLUSIONS: This study was a first of its kind, real-world, prospective, observational study of Australian patients living with HAE. Despite the availability of effective on-demand therapies, HAE remains burdensome. Wider access to safe and effective prophylactic therapies is needed for patients living with HAE.

Hereditary Angioedema With Normal C1 Inhibitor: US Survey of Prevalence and Provider Practice Patterns.

BACKGROUND: Hereditary angioedema (HAE) with normal C1-INH (HAE-nl-C1INH) is phenotypically similar to HAE resulting from C1-INH deficiency (HAE-C1INH). Confirmatory diagnostic tests for HAE-nl-C1INH are limited and few clinical study data exist regarding management of the condition. Therefore, survey studies may provide initial estimates of prevalence, diagnosis, and management patterns of this condition. OBJECTIVE: To estimate the prevalence and describe current management patterns for HAE-nl-C1INH in the United States (US). METHODS: We conducted an Internet-based survey of US physicians to estimate the prevalence of the HAE-nl-C1INH population in the United States. Potential participating physicians were identified from the US Hereditary Angioedema Association database and IQVIA Xponent prescription database. Eligible physicians were invited to complete an online survey between June and September 2021. RESULTS: A total of 113 physicians provided data for the estimation of HAE-nl-C1INH prevalence and 81 physicians treating HAE-nl-C1INH patients provided data about treatment patterns. In bias-corrected analysis, we estimated 1,230 to 1,331 HAE-nl-C1INH patients within the United States between May 2019 and April 2020. Mean time to diagnosis for HAE-nl-C1INH was approximately 6 years (range, 2.4-13.5 years). Response to medication was commonly used to inform diagnosis (antihistamine response or nonresponse used by 73% of physician respondents, corticosteroids by 57%, or HAE-specific medications by 74%), and Factor XII genetic testing was used by 43%. CONCLUSIONS: These survey data provide estimates of HAE-nl-C1INH prevalence in the United States as well as current diagnosis and management strategies. Results may be useful for developing studies to assess treatment efficacy and safety, and potentially improve the diagnosis for and management of this patient population.

Trends in Treatments With Disease-Specific and Interfering Drugs in Patients With Hereditary Angioedema in Sweden.

BACKGROUND: Hereditary angioedema (HAE) is caused by low levels of or defects in C1 inhibitor. Although disease activity may be modified by prophylaxis, emergency treatment, treatment for comorbidities, and oral contraceptives, the extent of their use is unclear. OBJECTIVE: To investigate trends in the use of disease-specific and interfering drugs in patients with HAE compared with the general population in Sweden. METHODS: In a nationwide, longitudinal study, 239 patients with HAE and 2 383 controls were compared with the Prescribed Drug Register (2005-2019). These data reflect rates of dispensed prescriptions from pharmacies in Sweden. RESULTS: Attenuated androgens were used by approximately 10% of patients with HAE. The number of individuals treated with prophylactic plasma-derived C1 inhibitor increased during this period to reach almost 25% in men and 35% in women in 2019. Tranexamic acid was prescribed to 5% to 15% of patients, primarily children and young adults. Rates of prescriptions for icatibant, an emergency medication, showed a steady increase since its introduction in 2010, in particular among middle-aged women, suggesting poorly controlled disease. The use of diuretics, calcium channel blockers, and gestagens was more common in patients with HAE than in controls, whereas angiotensin-converting enzyme inhibitors were rarely collected. CONCLUSIONS: Despite concerns regarding side effects, approximately 10% of patients with HAE received attenuated androgens for long-term prophylaxis. The common use of emergency medication also suggests poorly controlled disease in many patients, highlighting the need for increased focus on prophylactic treatment.

Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE. OBJECTIVE: To investigate the estimated minimal prevalence, needs, and potential interventions for the diagnosis and management of HAE in the AP. METHODS: A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Patient profiles and the presence of diagnostic facilities or tests, regional and national HAE guidelines, and patient support groups were reported and compared. RESULTS: Completed questionnaires were received from 14 representatives of 12 member countries and territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02/100,000 population, with significant heterogeneity across different centers. Only one-half and one-third had registered on-demand and prophylactic medications, respectively. Few had patient support groups (58%) or regional guidelines (33%), and their existence was associated with the availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age at HAE diagnosis (P = .017). CONCLUSIONS: Hereditary angioedema in the AP differs from that in Western countries. Hereditary angioedema-specific medications were registered in only a minority of countries and territories, but those with patient support groups or regional guidelines were more likely to have better access. Asia Pacific-specific consensus and guidelines are lacking and urgently needed.

Phenotypic and Genotypic Characterization of Hereditary Angioedema in Saudi Arabia.

Hereditary angioedema (HAE) is a potentially life-threatening autosomal dominant disorder affecting roughly 1:50,000 individuals. It is commonly characterized by swelling of the larynx, gastrointestinal tract, extremities, and skin. There is growing genetic heterogeneity associated with this disease but more than 95% of mutations are found in SERPING1, the gene which encodes complement 1 inhibitor (C1-INH). HAE cohorts from several populations have been published but no large scale study has been reported from the Arab world to date. Here we document the clinical and genetic findings of HAE patients from a single Saudi institution, which is a major referral center at the national level. A total of 51 patients across 17 unrelated families were recruited including two large multi-generational families, of which one contained an in-frame exonic deletion that was resolved through MLPA. Two cases were negative for all the genes we tested (including F12, PLG, ANGPT1, MYOF, KNG1, and HS3ST6). The predominant HAE subtype in our cohort was type I, at 76%. We were able to uncover a mutation in 49 patients (96%). No type III (normal C1-INH) patients were encountered in the clinic, suggesting that this subtype does not play a major role in HAE pathogenesis in Saudi Arabia. Additionally, the existence of four patients with consistently normal complement 4 (C4) levels alongside abnormal C1-INH profiles highlights the utility of dual screening for both proteins in suspected patients.