Introduction
Hereditary angioedema (HAE) is a rare disease characterized by recurrent, unpredictable swelling episodes (angioedema, AE) most commonly caused by bradykinin release. The burden of HAE is substantial; therefore, several special factors should be considered, particularly when managing pediatric patients (PedPs). The most prevalent form of HAE (estimated prevalence is 1:50,000 [1]) is associated with inborn deficiency, or dysfunction of C1 inhibitor (C1INH) (HAE‐C1INH).
Since the publication of the first international pediatric HAE‐C1INH consensus in 2017 [2], significant advancements have been made in the diagnosis and management of PedPs with HAE‐C1INH (ped‐HAE‐C1INH). There is a current unmet need for updated, evidence‐based practice parameters to guide clinical care.
New emerging HAE types with normal C1INH (HAE‐nC1INH) have been described in the last 25 years, with a much lower prevalence than HAE‐C1INH, but their true prevalence is unknown. In these HAE types, the first clinical symptoms usually occur in adulthood, the pathophysiology remains poorly understood, there are no approved treatments, and no clinical trials have been conducted [3]. Therefore, the authors agreed that HAE‐nC1INH would not be included within the scope of this guideline; however, the available literature is summarized in Data S1: Section 1.
Throughout this guideline, HAE refers to all types of HAE, including HAE‐nC1INH, while HAE‐C1INH is used when a statement is only true for this endotype.
Scope and Purpose
The objective of this guideline is to provide evidence‐based recommendations for the management of ped‐HAE‐C1INH. This includes diagnosis, treatment of HAE attacks, short‐term (STP) and long‐term prophylaxis (LTP), and recommendations for self‐administration, individualized therapy, quality of life (QoL), and comprehensive care. It is anticipated that this guideline will provide practicing physicians (especially pediatricians) with valuable information about the management of HAE and promote knowledge transfer to non‐specialist clinicians.
Intended Audience
The intended target users of this pediatric guideline are healthcare providers caring for patients with AE. Since HAE is often managed by multidisciplinary teams, the providers who may use this guideline are: pediatricians, allergists, immunologists, internists, dermatologists, otolaryngologists, surgeons, dentists, emergency department physicians, nurses, pharmacists, policy makers, hospital administrators, genetic counselors, and payers. This guideline is intended for a global audience, and its recommendations were synthesized with the aim of supporting equitable care and outcomes across diverse populations and healthcare settings with variable resources.
Methods
Steering Committee, International Taskforce, and the HAWK Group
The Steering Committee (StCom) was composed of the authors of the previous international consensus on the management of ped‐HAE‐C1INH2, all experienced HAE specialists, and expanded by three additional experts. They defined the scope and purpose of the guideline and selected the members of the International Taskforce (ITF). The Hereditary Angioedema Working Group (HAWK Group) consisted of the representatives of Hereditary Angioedema International (HAEi) and healthcare professionals who attended the Pediatric HAE Guideline Meeting (P‐GM), held during the 14th C1 Inhibitor Deficiency and Angioedema Workshop on May 30, 2025, in Budapest, Hungary, https://2025.haenetworkshop.hu (Data S1: Section 2).
Identifying the Evidence
Literature search was performed with a focus on articles published from January 1, 2016, to January 14, 2025. PubMed and OVID‐Medline databases were searched (Data S1: Section 3). Later, newly published articles were monitored, and relevant information was incorporated into the guideline.
Summarizing and Evaluating the Evidence
The level of evidence was decided based on the quality of articles supporting the recommendation (Table 1 [4]), and the strength of recommendation based on the GRADE recommendations (Table 2 [5]).
Recommendation Development and Approval
Experts from the StCom and ITF reviewed the published evidence and developed recommendations based on the aforementioned criteria (Tables 1 and 2) through multiple rounds of deliberation. The recommendations were presented with the proposed level of evidence and strength of recommendation to the attendees of the P‐GM. Attendees then voted anonymously via electronic voting.
80% consensus was acceptable (Figure S1).
Results
Nomenclature, Definitions
Classification and nomenclature of HAE in PedPs do not differ from that of adults [6, 7]. Information on specific age groups within the HAE pediatric population differs from country to country; PedPs are underrepresented in HAE registries (Data S1: Section 5 and Table S1). Only a handful of PedPs have been included in the recently established International Chronic Angioedema Registry (CARE) [8].
Although the pediatric population is biologically heterogeneous [9], pediatric sections of the international HAE guidelines and pediatric consensus documents [2, 4, 10] address ped‐HAE‐C1INH under 18 years of age and do not specify age groups (Data S1: Section 6).
Consistent with the International Council for Harmonization guidelines, we are proposing four pediatric age groups as suggested by the FDA, with slight modifications [11]: Age category I. Neonates: birth through younger than one monthAge category II. Infants: one month to younger than two yearsAge category III.
Children: 2 years to younger than 12 yearsAge category IV. Adolescents: 12 years to younger than 18 years
RECOMMENDATION 1
We recommend that future clinical studies consider the dynamic development milestones of pediatric patients with hereditary angioedema and stratify them accordingly.91% agreementLevel of evidence: consensus
RECOMMENDATION 2
We recommend that national and international hereditary angioedema repositories report pediatric patient census periodically.92% agreementLevel of evidence: consensus
Pathophysiology of HAE‐C1INH
HAE‐C1INH is caused by C1INH deficiency resulting from pathogenic variants in the SERPING1 gene [12]. To date, more than 800 variants have been described that are considered pathogenic/likely pathogenic [13]. They result in impaired synthesis of C1INH (HAE‐C1INH‐Type1) or synthesis of dysfunctional C1INH (HAE‐C1INH‐Type2) [14].
C1INH is a protein responsible for inhibiting numerous proteases, mainly in the complement (C1r, C1s, mannose‐associated serine protease 1 and 2), contact (plasma kallikrein (PKa), factor XIIa), fibrinolysis pathway (plasminogen‐plasmin), and intrinsic coagulation (factor XIa) systems [15]. Reciprocal activation of factor XII and plasma prekallikrein results in active PKa, which cleaves high molecular weight kininogen (HK), releasing bradykinin (BK) [16]. This cascade is not sufficiently inhibited in C1INH deficiency.
As a result, BK is produced in excess, binds to its bradykinin B2 receptor (BDKRB2), which is constitutively present on vascular endothelial cells and is considered to be responsible for mediating endothelial hyperpermeability and angioedema in HAE‐C1INH [17]. Activation by BK triggers intracellular signaling mechanisms that ultimately lead to the opening of cadherin endothelial junctions, increased vascular permeability, and AE formation [12] (Figure 1).
Diagnosis of HAE‐C1INH
Clinical Symptoms
The characteristic symptoms of HAE‐C1INH in PedPs (similarly to adults) include recurrent swelling of the subcutaneous and/or submucosal tissues. Although the genetic variant is present from conception, clinical symptoms are extremely uncommon (but have been reported) in utero and during infancy [18]. The usual age of onset of attacks varies from 4.4 to 18 years with a mean age of first attack at the age of 10, with no difference between boys and girls [19, 20, 21, 22].
Early onset of symptoms may predict a more severe subsequent course of disease [20, 21, 23, 24]. The frequency and severity of the symptoms show intra‐ and inter‐individual variability. Symptoms often worsen during puberty most likely due to hormonal changes [22, 25, 26].
Subcutaneous AE (of the extremities, face, trunk, and genitals) without wheals or itching is the most common and often the earliest symptom in PedPs. It may last 1 to 5 days before resolving spontaneously [27]. Erythema marginatum, a map‐like rash, is reported as a prodromal symptom in 42%–58% of PedPs [23].
Facial AE may extend to the upper airway mucosa [19, 20, 28].
AE of the submucosal tissue of the intestinal wall can cause abdominal tenderness, colicky abdominal pain, nausea with vomiting, diarrhea, and hypovolemia. Cases of intestinal obstruction (ileus) and intussusception have also been described [19, 20, 23, 28]. As abdominal pain is frequent in the general pediatric population, abdominal attacks may be an unrecognized symptom of HAE‐C1INH [29, 30, 31].
Symptoms of upper airway angioedema (UAAE) include lump sensation, dysphagia, hoarseness, aphonia, tachypnea, dyspnea, and stridor [32]. In general, UAAE first occurs after the age of 11 and is life‐threatening, often causing death from asphyxiation if left untreated. Compared to adults, death by asphyxiation is less common in ped‐HAE‐C1INHs [33], however, upper airway obstruction may develop quickly in children due to smaller airway diameters, necessitating immediate medical attention [34, 35, 36, 37, 38].
Laboratory Testing
Complement Testing
The diagnosis of HAE‐C1INH is easily established by the biochemical evaluation of quantitative (antigenic) and/or functional (activity) C1INH. HAE‐C1INH‐Type1 and HAE‐C1INH‐Type2 can be differentiated based on these measurements [4, 39]. C4 levels are low in HAE‐C1INH due to the activation of the classical pathway of the complement system.
Consequently, C4 levels are used as a screening test in resource‐limited settings. Specific biochemical analysis of quantitative and functional C1INH and C4 is mandatory for a definitive diagnosis (Table 3).
The accurate performance of plasma complement tests requires careful sample collection, freezing, and storage [40, 41]. Recently, dry blood spot (DBS) sampling was introduced for complement testing, making sample handling easier [42, 43].
Early identification of ped‐HAE‐C1INH is essential; however, some aspects must be considered regarding the levels of complement system proteins in the first year of life [2]. Complement levels in the umbilical cord blood of full‐term neonates can be lower than maternal levels due to the immaturity of the complement system [44, 45, 46, 47, 48, 49].
Both antigenic and functional C1INH levels in newborns correspond to approximately 60% to 70% of adult values [50, 51, 52]. Premature babies have lower quantitative and functional C1INH than full‐term newborns [51, 53]. C1INH reaches adult levels in most cases at 6 months to 1 year of age.
Therefore, complement tests performed before this period should be repeated after one year of age [54, 55].
The use of C4 levels for screening could also lead to misdiagnosis if performed early in life, and cases of congenital C4 deficiency may obscure proper diagnosis [46, 56] (Figure 2).
Genetic Testing
Genetic testing is not required to confirm the diagnosis of HAE‐C1INH, unless preimplantation diagnosis or prenatal testing is considered, or in cases where biochemical tests are uncertain, as is the case in neonates and early infancy. Genetic analysis can be of significant assistance in instances where biochemical analyses are not feasible locally. Genetic testing can be performed on blood from the umbilical cord, peripheral blood, or buccal swab [2, 45, 57].
However, in case of a buccal swab, a proper sampling method should be used to ensure the sufficient quality and quantity of the acquired DNA.
Genetic diagnosis may be helpful in cases where the disease‐causing gene variant in the family is known. However, the gene variant responsible for C1INH deficiency (SERPING1) is only identified in 90% to 92% of patients with HAE‐C1INH [58, 59]. Thus, in cases where the disease‐causing gene variant in the family is not known, a negative genetic test does not totally exclude the diagnosis of HAE‐C1INH.
Pathogenic and non‐pathogenic SERPING1 mutations have been recorded in genetic repositories [60] (Figure 2).
Genetic analysis allows the identification of a pathogenic gene variant in the embryo during the gestational period [61]. The decision whether to perform prenatal diagnosis should be made by the parents after receiving appropriate counseling and careful evaluation of the benefits and risks.
Family History/Family Screening, Newborn Screening
Early identification of HAE in PedPs through family and newborn screening can improve access to life‐saving treatments, reduce the burden of disease, and minimize parental anxiety [45, 62, 63]. Inheritance of HAE is autosomal dominant, meaning that screening first‐degree relatives carries a high yield. Family history of HAE‐C1INH can be absent in 25% of cases (de‐novo pathogenic variants).
Recent studies highlight that the implementation of family screening programs exhibits considerable global variability, influenced by factors such as healthcare infrastructure, cultural attitudes, and health literacy [62, 64, 65].
Establishing family‐based outreach screening programs and culturally sensitive education could improve acceptance of family screening and detection rates [40, 66]. The increasing availability and improved affordability of genetic testing will also ensure more equitable access to family and newborn screening strategies [67]. When the family genetic variant is known, genetic testing can be a convenient and accurate method of neonatal testing (Figure 2A).
Differential Diagnosis of HAE‐C1INH
Angioedema attacks in patients with HAE‐C1INH can mimic several conditions, potentially leading to delayed and misdiagnosis [68]. Since the clinical manifestation of HAE‐nC1INH is almost the same as that of HAE‐C1INH, this disorder is one of the most important differential diagnostic options [3].
Clinicians evaluating attacks of AE in patients suspected of having HAE‐C1INH without a family history of HAE should consider a wider differential of medical conditions depending on clinical presentations, such as upper airway obstruction, abdominal pain syndromes, and subcutaneous swelling, pain, or rash [69].
Subcutaneous AE of the extremities, trunk, and face might mimic allergic or immunoregulatory diseases, such as systemic lupus erythematosus, juvenile dermatomyositis, orofacial granulomatosis (Melkersson‐Rosenthal Syndrome), hypocomplementemic urticarial vasculitis syndrome, capillary‐leak syndrome (Clarkson's disease), cellulitis, ethmoiditis, and contact dermatitis, or post‐traumatic swelling [68]. Genital AE may be misdiagnosed as orchitis or testicular torsion [23]. Erythema marginatum is often misdiagnosed as urticaria [70, 71].
As unexplained abdominal pain is very common in infants and children, a number of causes should be considered, such as colic, constipation, viral gastroenteritis, acute appendicitis, intussusception, and volvulus, among other less common conditions [69]. In contrast, children presenting with a history of recurrent relentless episodes of colicky abdominal pain should be screened for HAE‐C1INH, regardless of family history of this disease [72]. During abdominal AE attacks, intestinal‐wall edema and free peritoneal fluid (ascites) should be looked for by abdominal ultrasound, CT scan, or MRI in the emergency department [29, 30, 73, 74, 75, 76, 77, 78, 79, 80].
Complete blood count and blood chemistry are often not helpful because neutrophilia and a mild increase in CRP and D‐dimer may occur secondary to an HAE attack [81, 82, 83, 84, 85]. Clinical response to HAE‐specific acute medications helps to confirm abdominal HAE attack in cases of high suspicion of HAE.
The differential diagnosis of UAAE in pediatrics includes allergic food reactions, croup, pseudocroup, foreign body aspiration, and acute epiglottitis [23].
Progression of symptoms and treatment response can help narrow the differential diagnosis. In clinical practice, differentiation of mast cell‐mediated AE (AE‐MC) and BK‐mediated AE is the primary focus, as there is limited data regarding other types of AE in the pediatric population. AE‐MC, such as in the case of anaphylaxis, with or without urticaria (hives), is associated with a rapid onset and progression (within minutes to a few hours), good response to antihistamines, glucocorticoids, or epinephrine, and resolution within 12 to 24 h from the onset.
Wheezing, hypotension, and nausea/vomiting may be associated and exposure to a known trigger (i.e., allergen) can support this diagnosis [86]. In contrast, HAE attacks tend to peak at 12 to 24 h from onset and may persist up to several days; they do not respond to epinephrine, H1‐antihistamines, or glucocorticoids—all of which are clues to help clinicians differentiate between BK‐ and MC‐mediated AE [86, 87].
RECOMMENDATION 3
We suggest clinicians evaluating a pediatric patient presenting with recurrent peripheral edema and/or upper airway edema and/or recurrent abdominal pain of unknown origin to consider hereditary angioedema and to perform laboratory testing for the diagnosis of hereditary angioedema regardless of family history of angioedema.96% agreementLevel of evidence: consensus
RECOMMENDATION 4
We recommend that all first‐degree relatives of hereditary angioedema patients be considered to be at risk of this disease and should be tested as early as possible.96% agreementLevel of evidence: high
RECOMMENDATION 5
We recommend performing biochemical analysis of C4 level, C1 inhibitor antigenic and functional levels in pediatric patients who are suspected to have hereditary angioedema. Two congruent results are required for the confirmation or exclusion of the diagnosis of hereditary angioedema with C1 inhibitor deficiency.89% agreementLevel of evidence: high
RECOMMENDATION 6
We recommend that pediatric patients who are first‐degree relatives of patients with hereditary angioedema with normal C1 inhibitor, are screened for the pathogenic variant known in the family.83% agreementLevel of evidence: consensus
RECOMMENDATION 7
We recommend that pediatric patients who have symptoms characteristic of hereditary angioedema without a family history of hereditary angioedema and with normal C4, C1 inhibitor antigenic and functional levels, are assessed for the known pathogenic variants.85% agreementLevel of evidence: consensus
RECOMMENDATION 8
We recommend screening newborns with a positive family history of hereditary angioedema with complement testing (C4 level, C1 inhibitor antigenic and functional levels) and/or genetic tests if the pathogenic variant is known in the family. Complement tests should be repeated after one year of age.81% agreementLevel of evidence: moderate
Management of HAE
Comprehensive Care Centers, Transition Process From Pediatric to Adult Care
Comprehensive care centers (CCCs) are an important resource in the management of HAE, as the multi‐faceted nature of the disease requires the availability of specialized resources in terms of diagnostics and therapy, as well as coordinated care by various specialists throughout the patient's lifetime [88, 89, 90]. Where a CCC cannot provide its own pediatric care by an expert, close cooperation with the associated pediatric department is essential. To ensure the quality of care provided by a CCC on a sustained basis, regular auditing by an external institution should be considered.
In the majority of ped‐HAE‐C1INHs, other family members are also affected. This allows centers in which pediatric and adult patients are treated under one roof to implement a family‐centered approach. The transition from pediatric to adult services must be prepared early (at approximately 12–15 years of age) and in a structured manner [89, 91] (Data S1: Section 7).
RECOMMENDATION 9
We recommend the follow‐up of pediatric patients with hereditary angioedema to be done by experienced clinicians at a specialized comprehensive care center.94% agreementLevel of evidence: consensus
RECOMMENDATION 10
We recommend ensuring the transition of hereditary angioedema patients from pediatric to adult care for continuous patient care by starting discussions with patients, caregivers, and their future physicians at an early stage88% agreementLevel of evidence: consensus
Education, Counseling
HAE imposes a pervasive burden upon affected PedPs and their family [92, 93, 94]. Fortunately, the available options for acute and prophylactic treatments provide an optimistic prospect for PedPs to enjoy a future free of disease‐related restrictions.
HAE‐specific education is essential for PedPs, family members, and caregivers [23, 44, 95, 96] (Data S1: Section 8). Patient organizations serve as resources for management insights, care guidelines, and support networks. Written information detailing the nature of HAE, potential triggers, identification of early attack signs and symptoms, treatments, action plans, and acute and prophylactic therapy should be available to PedPs and all responsible caretakers.
Medication self‐administration techniques, storage, refill processes, emergency and expert physician contacts must be clearly delineated. Emergency Cards and multilingual action plans are recommended. The action plan contains what medication to use, how and when to use it in case of an HAE attack, and when further medical care is necessary.
The overarching goal of childhood management is to coordinate a therapeutic plan designed to enable PedPs' full engagement in social, academic, or physical activities of their choice [97, 98].
RECOMMENDATION 11
We recommend regular education about the course of the disease, early recognition of angioedema symptoms, treatment administration training of children/adolescents, and multi‐disciplinary counseling services of pediatric patients with hereditary angioedema and their families.96% agreementLevel of evidence: consensus
RECOMMENDATION 12
We recommend contacting and educating teachers, coaches, physicians, and others who have care or supervision of pediatric patients with hereditary angioedema and providing them with written information about the disease and treatment, especially the acute treatment of hereditary angioedema attacks. Educational material should be developed with the local community, accessible in preferred languages, to ensure effective communication.95% agreementLevel of evidence: consensus
RECOMMENDATION 13
We recommend that all pediatric patients with hereditary angioedema and their caregivers be informed about national patient organizations and HAE International93% agreementLevel of evidence: consensus
Trigger Factors/Primary Prevention
Trigger Factors
A multitude of factors may trigger HAE attacks at any age; however, most attacks occur spontaneously [99, 100, 101]. Mechanical trauma, physical exertion, dental and surgical procedures, weather changes, airway infections, drugs, and occasionally, mental stress and food may provoke HAE attacks [23, 102, 103, 104, 105, 106, 107, 108]. Dental eruption is not a frequent trigger, but could also act as a provoking factor [109].
In adolescent girls, menstruation, ovulation, and estrogen‐containing contraceptives (ECOCs) are additional triggers [25, 110, 111, 112].
Primary Prevention
The aim of primary prevention is to avoid trigger factors to prevent HAE attacks. However, the activities and lifestyle of patients should be kept as normal as possible. Physical activity, which is beneficial to the healthy development of children and adolescents, should be encouraged individually, and unjustified restrictions on activity should be avoided.
However, physical sports should be considered carefully [109, 113]. Dental, surgical procedures, and endoscopy may provoke HAE attacks [114] (see the section on STP). Upper airway infections are common triggers of HAE attacks in ped‐HAE‐C1INH; therefore, their prevention can reduce HAE's impact on patients' lives.
Mandatory and non‐mandatory vaccinations are recommended as they have proven to be both safe and effective [2, 4]. There is no relationship between duration of breastfeeding, timing of cow's milk introduction, age at symptom onset, and localization of the attacks [115].
Angiotensin converting enzyme inhibitors (ACEIs) and ECOCs, which may initiate or aggravate HAE attacks, should be avoided in pediatric HAE patients whenever possible. Although ACEIs are less often needed during childhood, early initiation of ECOCs in girls is increasingly common. Hormonal contraception with progestin‐only pills may be beneficial [23, 25, 55, 101, 102, 105, 116].
RECOMMENDATION 14
We recommend against the use of estrogen‐containing oral contraceptives in adolescent patients with hereditary angioedema.89% agreementLevel of evidence: moderate
RECOMMENDATION 15
We suggest against the use of angiotensin‐converting enzyme inhibitors in pediatric patients with hereditary angioedema.88% agreementLevel of evidence: low
RECOMMENDATION 16
We recommend that all pediatric patients with hereditary angioedema receive regular immunizations according to the national vaccination schedule.96% agreementLevel of evidence: consensus
RECOMMENDATION 17
We suggest that pediatric patients with hereditary angioedema should have no limitation to physical activity including all sports, provided they have rapid access to their acute treatment. If necessary, prophylaxis may be introduced.86% agreementLevel of evidence: moderate
Treatment of HAE‐C1INH
The goal of treatment is to alleviate the burden of disease, restore the patient's quality of life, and prevent HAE attacks. Medications differ in their mode of action, production methods, and mode of administration. They act through supplementation of C1INH, inhibition of the pathways leading to the release of BK, or blockage of the effect of BK on the vascular endothelium (Figure 1).
Acute Treatment
The aim of acute treatment of HAE attacks is to prevent mortality and to minimize morbidity by decreasing the duration and severity of symptoms. Treatment outcomes have been shown to improve with earlier treatment administration as compared to later‐stage treatment [117, 118, 119]. Early treatment is supported by home treatment or self‐injection after appropriate training of patients/caregivers [118, 120] (see the section on home treatment).
Acute treatment should be immediately available under every circumstance, including at home, kindergarten, school, and while traveling. If an abdominal HAE attack does not improve on HAE treatment, further investigation is required urgently to rule out an acute abdomen. UAAEs require emergency admission to a hospital where airway management is available.
Hospital or other point‐of‐care should also be considered in case of other forms of severe attacks. Well‐known secondary effects of HAE attacks, like anxiety, depression, and loss of productivity, will likely be prevented or minimized by the availability and timely administration of acute treatment [121, 122, 123, 124, 125].
An overview of approved drugs for acute treatment is outlined in Table 4 (data on randomized clinical trials are provided in Table S2). Options include replacement of low levels of C1INH with intravenous (IV) plasma‐derived (pdC1INH) or recombinant human (rhC1INH) C1INH concentrate [22, 118, 126, 127, 128, 129, 130, 131], BDKRB2‐blockade with subcutaneously (SC) administered icatibant [132, 133, 134, 135, 136], inhibition of PKa with SC administered ecallantide [137], or with orally used sebetralstat [138, 139]. Only IV pdC1INH is registered for neonates and infants, while children can use icatibant, IV pdC1INH, and rhC1INH.
Adolescents can be treated with these medications and also with sebetralstat. Given the favorable safety profiles and demonstrated efficacy, each of these treatments is considered a first‐line therapeutic option.
RECOMMENDATION 18
We recommend creating an action plan for acute treatment of angioedema attacks in pediatric patients with hereditary angioedema, considering availability of medications and patient/caregiver preferences.96% agreementLevel of evidence: consensus
RECOMMENDATION 19
In neonates and infants with hereditary angioedema due to C1 inhibitor deficiency between birth and 2 years, we recommend the use of intravenous plasma‐derived C1 inhibitor concentrate as first‐line therapy for acute treatment of angioedema attacks.87% agreementLevel of evidence: moderate
RECOMMENDATION 20
In children with hereditary angioedema due to C1 inhibitor deficiency aged between 2 and 12 years, we recommend the use of icatibant, intravenous plasma‐derived C1 inhibitor concentrate, or intravenous recombinant human C1 inhibitor as first‐line therapy for acute treatment of angioedema attacks.97% agreementLevel of evidence: high
RECOMMENDATION 21
In adolescents with hereditary angioedema due to C1 inhibitor deficiency aged 12 years or older, we recommend the use of ecallantide, icatibant, intravenous plasma‐derived C1 inhibitor concentrate, intravenous recombinant human C1 inhibitor, or sebetralstat as first‐line therapy for acute treatment of angioedema attacks.92% agreementLevel of evidence: high
RECOMMENDATION 22
We recommend acute treatment of angioedema attacks in pediatric patients with hereditary angioedema as early as possible.96% agreementLevel of evidence:Neonates: consensusInfants: consensusChildren: moderateAdolescents: moderate
RECOMMENDATION 23
We recommend home treatment of angioedema attacks to ensure early treatment in pediatric patients with hereditary angioedema.89% agreementLevel of evidence:Neonates: consensusInfants: consensusChildren: moderateAdolescents: moderate
RECOMMENDATION 24
We recommend considering treatment of all angioedema attacks in pediatric patients with hereditary angioedema.89% agreementLevel of evidence: consensus
RECOMMENDATION 25
We recommend that upper airway, facial, and neck edema should always be treated. In case of upper airway edema, pediatric patients with hereditary angioedema should also have an emergency referral to a hospital where airway management is available.99% agreementLevel of evidence: consensus
RECOMMENDATION 26
We recommend supplying all pediatric patients with hereditary angioedema with acute treatment for at least two angioedema attacks even if they are on long‐term prophylaxis.95% agreementLevel of evidence: consensus
RECOMMENDATION 27
We recommend ensuring the availability of appropriate medication for acute treatment of angioedema attacks at any time and anywhere92% agreementLevel of evidence: consensus
Short‐Term Prophylaxis (STP)
STP is necessary for all ped‐HAE‐C1INHs, even in those who have never had an HAE attack. STP is essential for preparation before surgery, intubation, interventional medical procedures, endoscopy, and dental work, especially when the procedure approximates the upper airway [4, 98, 140, 141].
The preferred therapy for STP in all ages is IV pdC1INH 1–6 h before the procedure. Pharmacokinetics suggests a rapid effect and confers protection for approximately 3 days. Weight‐based dosing, especially for children, allows the individualization of STP [114, 142, 143, 144] (Table 5).
Due to a lack of controlled studies with LTP medications, experts suggest STP even for patients who are currently on LTP. Acute treatment should always be available during and after the intervention [140].
RECOMMENDATION 28
We recommend that short‐term prophylaxis be considered in pediatric patients with hereditary angioedema due to C1 inhibitor deficiency before medical, dental, and surgical procedures and any angioedema‐inducing event, especially when procedures involve the upper airway.96% agreementLevel of evidence: moderate
RECOMMENDATION 29
We recommend that acute treatment of angioedema attacks is available during medical, dental, and surgical procedures in pediatric patients with hereditary angioedema.99% agreementLevel of evidence: consensus
RECOMMENDATION 30
We suggest that short‐term prophylaxis should be considered even in pediatric patients with hereditary angioedema due to C1 inhibitor deficiency on long‐term prophylaxis.83% agreementLevel of evidence: low
RECOMMENDATION 31
We recommend intravenous plasma‐derived C1 inhibitor as the first‐line treatment for short‐term prophylaxis in pediatric patients with hereditary angioedema due to C1 inhibitor deficiency.93% agreementLevel of evidence:Neonates: consensusInfants: consensusChildren: moderateAdolescents: moderate
Long‐Term Prophylaxis (LTP)
The primary goal of long‐term treatment in HAE‐C1INH is to achieve full disease control and restore patients' lives to normal. Today, this is only possible through LTP—the regular use of medications designed to prevent attacks [4].
LTP is rarely needed in children under 6 years of age. If, however, LTP is required, then subcutaneously administered, prefilled lanadelumab injection (a fully human IgG1 monoclonal antibody inhibiting PKa) is the only approved treatment option for this indication between 2 and 6 years of age [145]. IV pdC1INH concentrate may also be considered for LTP in this population intermittently, although its use is off‐label, as it is approved for patients aged 6 years and older [22].
In children aged between 6 and 12 years, lanadelumab and IV pdC1INH can be used [145, 146].
Wider therapeutic choices for LTP are available for adolescents. These treatments include garadacimab, a fully human IgG4 monoclonal antibody inhibiting factor XIIa, administered subcutaneously with an autoinjector [147], lanadelumab [148], IV or SC pdC1INH concentrate [149, 150], or berotralstat, a selective oral plasma kallikrein inhibitor [151]. The recommended dosages for this population are consistent with those established for adult patients.
Given the favorable safety profiles and demonstrated efficacy, each of these treatments is considered a first‐line therapeutic option. Note: Berotralstat and lanadelumab have a delayed onset of a few weeks until optimal protective effect is achieved, which should be considered when initiating prophylaxis [152, 153] (Table 6, Table S3).
RECOMMENDATION 32
We recommend evaluating frequency and location of angioedema attacks, burden of disease, quality of life, patients' and caregivers' preferences, and availability of medications when considering long‐term prophylaxis.96% agreementLevel of evidence: consensus
RECOMMENDATION 33
In children with hereditary angioedema due to C1 inhibitor deficiency aged between 2 and 6 years, we recommend the use of lanadelumab or plasma‐derived C1 inhibitor as first‐line long‐term prophylaxis.84% agreementLevel of evidence:Lanadelumab: moderatePlasma‐derived C1 inhibitor: consensus
RECOMMENDATION 34
In children with hereditary angioedema due to C1 inhibitor deficiency aged between 6 and 12 years, we recommend the use of lanadelumab or plasma‐derived C1 inhibitor as first‐line long‐term prophylaxis.82% agreementLevel of evidence: moderate
RECOMMENDATION 35
In adolescents with hereditary angioedema due to C1 inhibitor deficiency aged 12 years or older, we recommend the use of any of the following treatments: berotralstat or garadacimab or lanadelumab or plasma‐derived C1 inhibitor, as first‐line long‐term prophylaxis.91% agreementLevel of evidence: high
RECOMMENDATION 36
We recommend evaluating efficacy and safety of the long‐term prophylactic agent in pediatric patients with hereditary angioedema due to C1 inhibitor deficiency at least three and six months after initiation, then at least annually.92% agreementLevel of evidence: consensus
Home‐Treatment
Self‐administration of medications shortens time to treatment, resulting in less severe attacks and faster resolution. It also reduces family disruption and distress associated with emergency hospital visits. PedPs can be involved in self‐administering treatments, potentially taking full responsibility from their early teens, with exact timing depending on individual maturity [118, 154, 155, 156].
Parenteral treatments can be technically challenging [157], therefore, home care nurse support can be invaluable in facilitating self‐administration training for both carer and child. Since almost everyone with HAE will experience attacks at some point, even asymptomatic PedPs should be trained in self‐management when developmentally appropriate.
Self‐management of prophylactic medications is also important and appears safe [92].
Self‐administration confers generic benefits, namely [158]: An increase in understanding of their medication and wider health needsImproved adherence to medication regimens in the longer term.Enhancing independence and autonomous self‐care.Facilitating the transition from pediatric to adult care.
RECOMMENDATION 37
We suggest that children and adolescents with hereditary angioedema should be encouraged to take an active role in their own care, with the aim of self‐administration of medication from early adolescence.97% agreementLevel of evidence: consensus
RECOMMENDATION 38
We suggest that caregivers of pediatric patients with hereditary angioedema should be educated about the administration of medications for hereditary angioedema.99% agreementLevel of evidence: consensus
Monitoring, Quality of Life
At least an annual (or every 3–6 months if the ped‐HAE‐C1INH is on LTP) follow‐up at an HAE CCC is important, together with ongoing communication with the family practitioner or pediatrician. Growth and development should be closely monitored as in other chronic conditions. Between visits, clinical support should be accessible via phone or email.
At follow‐up visits, clinicians should assess attack frequency and location, response to treatment, side effects, disease burden, HR‐QoL, patient and caregiver preferences, medication availability, adverse events, treatment burden, and concomitant diseases to guide the therapy. Patient data can be recorded using paper‐based or electronic patient records (mobile tools) developed in each country, but HAE TrackR, developed by HAEi, is also available in many languages [159]. Presently, AE‐ and HAE‐specific patient‐reported outcome measures are validated only for adults.
Few studies have assessed illness burden in ped‐HAE‐C1INH, reporting slight HR‐QoL impairment using generic pediatric questionnaires (i.e., KIDSCREEN 27, KINDL, PedsQLTM), dermatology tools (i.e., CDLQI), a non‐validated HAE‐specific questionnaire, and/or a visual analogue scale [93, 113, 124, 160, 161, 162, 163].
HR‐QoL is influenced by age at symptom onset (positively correlated with physical well‐being, negatively with self‐esteem) [113], attack frequency [160, 163], and abdominal attack location [162].
RECOMMENDATION 39
We suggest regularly monitoring health‐related quality of life of children and adolescents with hereditary angioedema.81% agreementLevel of evidence: consensus
RECOMMENDATION 40
We recommend monitoring pediatric patients with hereditary angioedema regularly at least once a year, in close collaboration with their primary care providers, even if they are asymptomatic.87% agreementLevel of evidence: consensus
Individualized Therapy
Ped‐HAE‐C1INHs can present with a wide range of disease severity, and they and their families can have different feelings about approaches to HAE therapy. Therefore, an individualized therapeutic strategy is required. Shared decision making is an appropriate process for decisions and outlining a treatment plan [89, 112, 155, 164, 165].
In addition, ped‐HAE‐C1INHs without a family history are likely to need more education about the disease and treatment options. Prior to puberty, disease activity is often lower, so acute therapy alone may be preferable. Other considerations include needle‐phobia, distance from medical care, and participation in activities that can potentially induce attacks [166, 167].
Finally, caregivers and patients vary in their comfort with administering injectable therapies at home [168]. In‐depth education for patients and their family members on the treatment options available and strategies for avoiding triggers should be personalized, proactive, and reviewed regularly, particularly when there are significant changes in the child or adolescent's life [169].
RECOMMENDATION 41
We recommend that clinicians who care for pediatric patients with hereditary angioedema individualize the treatment plans for patients and their family through shared decision making, which takes their preferences and values into account.94% agreementLevel of evidence: consensus
Variation in the Availability of Healthcare Options and Levels of Healthcare Services
Lack of awareness of HAE among healthcare providers, lack of diagnostic facilities, insufficient availability or access to first‐line treatment options, and health insurance coverage are the major challenges in resource‐limited settings in high‐income countries as well as in low‐to‐middle‐income countries (LMICs) [170, 171, 172]. In LMICs, a large proportion of patients remain undiagnosed, and HAE still remains a fatal disease, associated with a poor QoL [124, 173, 174, 175]. In LMICs (with a lack of access to C1INH levels and C1INH function), C4 levels may be used as an initial screening test (sensitivity up to 80%–85%) for suspected patients with HAE [176].
There is also a remarkable disparity in availability and access to treatment options in LMICs for ped‐HAE‐C1INHs, highlighting opportunities to expand equitable care and innovative use of available resources to provide quality care [177, 178]. Here, second‐line treatment options are often used in PedPs (Tables S4–S6).
In emergency situations (AE involving the upper airway, gastrointestinal tract, neck, or face), when none of the first‐line treatment options are available, solvent detergent treated or fresh frozen plasma (SDP/FFP) can be considered for acute treatment of AE attacks. These agents are associated with a risk of anaphylactic reaction and transmission of blood‐borne infections [179, 180] (Table 4).
For STP, when IV pdC1INH is not available, attenuated androgens (AAs) or tranexamic acid (TXA) can be used 5 days before and continued for 2 days post procedure. SDP or FFP can be an alternative option 1–6 h before the procedure [140, 179, 181, 182, 183, 184, 185, 186] (Table 5).
For LTP, AAs or TXA could be considered in the pediatric population. AAs, such as danazol, stanozolol, and oxandrolone, have historically been utilized for LTP but only with caution. Their use is associated with significant adverse effects [187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199] (Table 6).
If targeted therapies are unavailable, and the need for LTP is high, then AAs could be considered only in adolescents with Tanner stage V and higher, with careful surveillance [176]. Although a few older studies suggested a moderate effect of TXA, an oral antifibrinolytic agent, these findings have not been confirmed in larger‐scale analyses. Although TXA is safe, it is less efficacious than AAs, and a large proportion of patients require either a switch to or the addition of AAs.
A few recent studies on ped‐HAE‐C1INH reported the use of AAs, TXA or a combination of these two drugs for LTP [62, 108, 200, 201] (Table 6).
There is an urgent unmet need to increase awareness among healthcare providers, expand access to diagnostic facilities, and improve the availability and access to first‐line treatment options for ped‐HAE‐C1INHs in LMICs. Patient support groups play a crucial role in this endeavor [202].
RECOMMENDATION 42
We suggest, when none of the first‐line treatment options are available, using fresh frozen or solvent detergent plasma for acute treatment of angioedema attacks involving the upper airway, gastrointestinal tract, neck, or face in pediatric patients with hereditary angioedema due to C1 inhibitor deficiency.86% agreementLevel of evidence: low
RECOMMENDATION 43
We suggest, when none of the first‐line treatment options are available, to consider using attenuated androgens, antifibrinolytics, fresh frozen or solvent detergent plasma for short‐term prophylaxis in pediatric patients with hereditary angioedema due to C1 inhibitor deficiency.81% agreementLevel of evidence: consensus
RECOMMENDATION 44
We suggest, when none of the first‐line treatment options are available, to consider the use of antifibrinolytics for long‐term prophylaxis in children and adolescents with hereditary angioedema due to C1 inhibitor deficiency.83% agreementLevel of evidence: consensus
RECOMMENDATION 45
We suggest, when none of the first‐line treatment options are available, the use of attenuated androgens for long‐term prophylaxis in adolescents with hereditary angioedema due to C1 inhibitor deficiency with Tanner stage V, administering the lowest effective dose.81% agreementLevel of evidence: low
RECOMMENDATION 46
We recommend the monitoring of blood pressure, weight, height, lipid profile, liver function, and fasting blood sugar and performing liver ultrasonography in all adolescents with hereditary angioedema due to C1 inhibitor deficiency receiving long‐term prophylaxis with attenuated androgens. Follow‐up should be conducted three and six months after the introduction of treatment, then every six months.82% agreementLevel of evidence: consensus
Registries and Biobanks
A key tool for optimizing the management of HAE is the use of disease registries [203]. Several national registries for HAE are active today (Data S1: Section 12). Additionally, the Angioedema Center of Reference and Excellence (ACARE) [204] Network promoted an international registry, CARE [8].
Ideally, disease registries should be associated with biobanks, defined as any systematic, collaboration‐ready repository of biological specimens intended for clinical research, with a specific focus on rare diseases.
RECOMMENDATION 47
We suggest establishing and maintaining registries with biobanking capabilities for hereditary angioedema, which include pediatric patients, allow patients and clinicians to enter high‐quality data, and ensure data protection.82% agreementLevel of evidence: consensus
Emerging Therapies
Several trials are either recently completed or being conducted in pediatric HAE patients. These studies and their details are outlined in Table 7.
Currently, two trials are evaluating acute therapies. KONFIDENT‐KID is evaluating an oral PKa inhibitor (sebetralstat) in subjects aged 2–11 years [207] and RAPIDe‐3 is evaluating an oral BDKRB2 antagonist (deucrictibant) in adolescent and adult patients [208].
Two phase 3 LTP trials have been recently published. APEX‐P evaluated an oral PKa inhibitor (berotralstat) in subjects aged 2–11 years [205] and OASIS‐HAE evaluated a SC prekallikrein mRNA silencing therapy (donidalorsen) in adults and adolescents [206].
There are two ongoing phase 3 LTP trials in adolescents and adults. CHAPTER‐3 is evaluating an oral BDKRB2 antagonist (deucrictibant) [209] and ALPHA‐ORBIT is evaluating an SC extended half‐life monoclonal antibody inhibitor of PKa (navenibart) [210].
Although one study (OASIS‐HAE) was published before the P‐GM, it does not provide sufficient data to make a specific recommendation [206]. In the meantime, the FDA approved donidalorsen (Dawnzera) for LTP in adolescent and adult patients [211]. Additionally, APEX‐P, an interim analysis on berotralstat in children, was published after the P‐GM [205], and as such, no specific recommendation could be made at this time for this drug in children.
Conclusions and Future Perspectives
Ped‐HAE‐C1INHs deserve special attention in the diagnosis and management of their disease. Early diagnosis, family screening, education and counseling of patients and their caregivers, selection of appropriate individualized therapy, development of a therapeutic strategic plan with shared decision making, centralized care, and regular follow‐up of patients are essential to reach the goal of ensuring that these young patients can lead normal lives similar to their peers. Future goals include spreading knowledge about the disease, ensuring correct diagnosis, and ensuring that targeted therapies are available to all PedPs, conducting clinical trials of new therapies in children, developing HAE centers, and collecting and publishing as much real‐world data as possible.
Author Contributions
H.F., I.M.‐S., K.B., A.E.G., A.S.G., H.R.H., A.L., A.Z., M.M., S.B., T.Cr. conceptualized the manuscript. Literature review and material preparation was performed as follows: “Introduction” H.F. “Scope and purpose, Intended audience, Steering Committee, International Taskforce, and the HAWK Group” S.B., S.C., “Identifying the evidence and Summarizing and evaluating the evidence” H.R.H., “Recommendation development and approval” S.B., S.C., “Nomenclature, definitions” A.R., “Pathophysiology of HAE‐C1INH” G.P., B.Z., “Clinical symptoms” K.B., I.M.‐S., A.Z., “Complement testing” A.S.G., “Genetic testing” A.E.G., “Family history/family screening, newborn screening” J.P., “Differential diagnosis” J.A.B., “Comprehensive care centers, transition process from pediatric to adult care” M.M., “Education, counseling” S.C., C.I., “Trigger factors/primary prevention” I.B.‐G., “Acute treatment” C.H.K., E.A.‐P., “Short‐term prophylaxis” T.Cr., “Long‐term prophylaxis” D.M.C., F.C., A.L., “Home‐treatment” H.J.L., “Monitoring, quality of life” T.C., “Individualized therapy” A.M., “International variation in availability of healthcare options and levels of healthcare, services” A.J., D.V.N., “Registries and biobanks” M.C., “Emerging therapies” S.B., M.C., “Conclusions and future perspectives” H.F.
The first draft of the complete manuscript was compiled by H.F. and H.R.H., who oversaw revisions. All authors reviewed and/or contributed critical revisions during the manuscript development. All authors approved the manuscript.
Funding
The authors have nothing to report. The Pediatric HAE Guideline Meeting was held during the 14th C1 Inhibitor Deficiency and Angioedema Workshop on 30 May, 2025, Budapest, Hungary. The Workshop was supported by unrestricted sponsorship grants from the following companies: CSL Behring, KalVista Pharmaceuticals, Takeda, BioCryst, Pharming, Pharvaris, Otsuka, Astria Therapeutics, Intellia Therapeutics.
Limited support for conference participation was made available to attendees on the Steering Committee and the International Task Force from the budget of the Workshop.
Conflicts of Interest
H. Farkas has received research grants from CSL Behring and Pharvaris; speaker fees from Biocryst, CSL Behring, Pharming, Pharvaris, and Takeda; travel grants from Astria, Biocryst, CSL Behring, Intellia, Ionis, KalVista, ONO Pharmaceutical, Pharming, Pharvaris, and Takeda; and served as an advisor/consultant for Astria, Biocryst, CSL Behring, Intellia, Ionis, KalVista, ONO Pharmaceutical, Pharming, Pharvaris, and Takeda. I.
Martinez‐Saguer has received honoraria, research funding, and travel grants from BioCryst, CSL Behring, Pharming, Octapharma, KalVista, and Takeda/Shire, and/or has served as a consultant and/or participated in advisory boards for these companies. K. Bork has received research grants and/or lecture fees from CSL Behring and Takeda for unrelated projects.
A.E. Germenis has received honoraria and travel support from CSL Behring and Swixx BioPharma, and he is President of the Hellenic Society of Angioedema. A.S.
Grumach has received speaker/consultancy fees from Catalyst, CSL Behring, KalVista Pharmaceuticals, Multicare Pharma, Pharvaris, Pint Pharma, AstraZeneca, and Takeda; a scholarship from the Brazilian Council of Research (CNPq); and a grant of researcher initiative from Takeda. H.R. Horváth has received travel grants from CSL Behring and Takeda.
A. Zanichelli has received honoraria, meeting/travel support, and/or served on advisory boards for Astria, BioCryst, CSL Behring, KalVista, Otsuka, Pharvaris, and Takeda. M.
Magerl has received speaker/advisor fees and/or research funding from Argo, Astria, Biocyrst, CSL Behring, Intellia, Ionis/Otsuka, KalVista, Medscape, Octapharma, Pharvaris, Takeda/Shire. S. Betschel has received consulting fees and speaker honoraria not related to this study from Astria, Biocryst, KalVista, CSL Behring, and Takeda; and grants or contracts from Astria, Ionis, Biocryst, KalVista, CSL Behring, Pharvaris, and Takeda.
E. Aygören‐Pürsün has received speaker/consultancy fees personally or to the institution and/or grants from Astria, Biocryst, CSL Behring, Intellia, Otsuka, Pharming, Pharvaris, and Takeda. J.A.
Bernstein has served as an investigator and consultant for ADARx, Ajou University, Allergy therapeutics, Amgen, Apogee, Areteia, ARS, Astra Zeneca, Astria, Biocyrst, Blueprint Medicine, Celldex, Cogent, CSL Behring, Eli Lilly, Escient, Evommune, Fresenius Kabi, Genentech, GSK Incyte, Intellia, Ionis, Japan Tobacco Company, Jasper, KalVista, Kenvue, Kymeria, Kyowa Kirin, Medscape, Merck, Novartis, Opella, Pharming, Pharvaris, Proctor and Gamble, Regeneron, Sanofi, Takeda/Shire, Telios, Teledoc, TEVA, Yuhan, WebMD news; as a consultant for Enanta, Pfizer, RAPT; and as a speaker for Pharming, KalVista, CSL Pharming. I. Boccon‐Gibod is or recently was a speaker, advisor, and engaged in research and educational projects for, and/or received research and consultancy grants from, BioCryst, CSL Behring, KalVista Pharmaceuticals, Novartis, Pharming, Pharvaris, Otsuka, and Takeda.
T. Caballero has received grant research support and/or speaker/consultancy fees from AEDAF, Astria, BioCryst, CSL Behring, Ionis, KalVista, Novartis, Otsuka, Pharvaris, and Takeda. She has also received funding to attend conferences/educational events from BioCryst, CSL Behring, Novartis, and Takeda.
T. Caballero is/has been a clinical trial/registry investigator for Biocryst, Biomarin, CSL Behring, Ionis, KalVista, Novartis, Pharvaris, and Takeda. She is a researcher on the IdiPAZ program for promoting research activities.
M. Cancian has received grant research support and/or speaker/consultancy fees from BioCryst, CSL Behring, KalVista, Novartis, Otsuka, Pharming, Pharvaris, Sanofi, SOBI, and Takeda. S.
Christiansen served as a consultant for BioCryst, CSL, and KalVista and is a member of the Medical Advisory Board US HAEA. D.M. Cohn has received consulting and/or speaking fees from Astria, BioCryst, CSL Behring, Intellia Therapeutics, Ionis Pharmaceuticals, KalVista Pharmaceuticals, Otsuka, Pharvaris, and Takeda, paid to the institution, and research support from KalVista Pharmaceuticals and Pharvaris.
F. Contreras has received speaker/consultancy fees from CSL Behring, Opella, Pint Pharma, Sanofi, and Takeda. S.
Craig has received consultant fees as a health equity informatics advisor to Imagine Pediatrics Inc. for unrelated projects. C. Isaic took part in patient organization activities or served as an advisor for Amberplasma, Astria, Amgen, CSL Behring, HAE International, KalVista, Pears Health Cyber, Pharming, Pharvaris, Swixx BioPharma, Sdružení pro Plazmaferézu, and Takeda.
She also plays a patient representative leadership or membership/advisory role in the HAE Junior patient organization, the ERN RITA patient advisory group, is a member of 2 working groups of the Patient Council of the Czech Healthcare Minister, and is a patient representative in the Critical Medicine Alliance, EU‐X‐CT initiative, EDiHTA, and SYPOVO projects. C.H. Katelaris has received honorarium and travel grant from CSL Behring for presentations; honoraria for presentations for Sanofi, Novartis, and Astrazeneca; and fees for advisory boards from Novartis, CSL Behring, Pharvaris, Intellia, KalVista, and Sanofi.
H.J. Longhurst has engaged in research or educational initiatives with, served as advisor or speaker to, or benefitted from travel/educational support from the following: Astria, CSL Behring, Intellia, KalVista, Pharvaris, and Takeda. A.
MacGinnitie has received consulting and research funding from Pharvaris. J. Peter received speakers' fees, honoraria, or travel support from CSL Behring, KalVista, Pharming, and Takeda, and educational research grants from Astria, Pharvaris, and Takeda.
He also serves as an advisory board member of Astria, Intellia, and Pharvaris. G. Porebski has received speaker fees, and/or consultancy fees, and/or travel support from CSL Behring, Swixx BioPharma, and Takeda.
A. Reshef has received speaker/advisor fees and/or research funding from CSL Behring, Ionis, Pharming, Pharvaris, BioCryst, Teva, Takeda, and Astria. BL.
Zuraw has received consultancy fees from BioCryst, CSL Behring, and Takeda, and fees for serving on the DSMB for BioMarin and CSL Behring. T. Craig's conflicts are research conflicts with ADARx, BioMarin, KalVista, Pharvaris, GSK, CSL Behring, Takeda, Ionis, Intellia, Astria, Pfizer, Regeneron, Sanofi, and Imbrex; speaking conflicts for Takeda, CSL Behring, KalVista, Ionis, and Grifols; consultant conflicts for BioMarin, Intellia, CSL Behring, Takeda, BioMarin, Ionis, Astria, KalVista, CSL Behring, and Biocryst.
He also has Center designations from the International Hereditary Angioedema Association and Alpha. A. Luczay, A.
Jindal, D. Van Nguyen, A.J. Castaldo and H.
Balle Boysen delacre no conflicts of interest.
Supporting information