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Angioedema, hereditary, 8(HAE8)

MedGen UID:
1780930
•Concept ID:
C5543528
•
Disease or Syndrome
Synonyms: ANGIOEDEMA, HEREDITARY, 8; HAE8
 
Gene (location): HS3ST6 (16p13.3)
 
Monarch Initiative: MONDO:0030298
OMIM®: 619367

Definition

Hereditary angioedema-8 (HAE8) is an autosomal dominant disorder characterized clinically by recurrent and self-limited episodes of localized edema in various organs, including the face, tongue, larynx, and extremities. In rare cases, swelling of the tongue or larynx can lead to airway obstruction. Abdominal attacks may also occur, resulting in abdominal pain, vomiting, and diarrhea. The disorder results from enhanced vascular permeability (summary by Bork et al., 2021). For a discussion of genetic heterogeneity of HAE, see 106100. [from OMIM]

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
•Concept ID:
C0000737
•
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
See: Feature record | Search on this feature
Diarrhea
MedGen UID:
8360
•Concept ID:
C0011991
•
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
See: Feature record | Search on this feature
Episodic vomiting
MedGen UID:
333228
•Concept ID:
C1838993
•
Finding
Paroxysmal, recurrent episodes of vomiting.
See: Feature record | Search on this feature
Laryngeal edema
MedGen UID:
6017
•Concept ID:
C0023052
•
Pathologic Function
An abnormal accumulation of fluid and swelling in the tissues of the larynx.
See: Feature record | Search on this feature
Edema of the dorsum of hands
MedGen UID:
752076
•Concept ID:
C2732374
•
Finding
An abnormal accumulation of fluid beneath the skin on the back of the hands.
See: Feature record | Search on this feature
Swollen lip
MedGen UID:
116100
•Concept ID:
C0240211
•
Sign or Symptom
Enlargement of the lip typically due to fluid buildup or inflammation.
See: Feature record | Search on this feature
Facial edema
MedGen UID:
154241
•Concept ID:
C0542571
•
Pathologic Function
Swelling due to an excessive accumulation of fluid in facial tissues.
See: Feature record | Search on this feature
Angioedema
MedGen UID:
1543
•Concept ID:
C0002994
•
Pathologic Function
Rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues of the skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue during a period of minutes to several hours. The swelling can also occur elsewhere, typically in the hands. Angioedema is similar to urticaria, but the swelling is subcutaneous rather than on the epidermis.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Cold Urticaria Syndromes: Diagnosis and Management.
Diaz VL, Gribbons KB, Yazdi-Nejad K, Kuemmerle-Deschner J, Wanderer AA, Broderick L, Hoffman HM
J Allergy Clin Immunol Pract 2023 Aug;11(8):2275-2285. Epub 2023 Jun 7 doi: 10.1016/j.jaip.2023.05.040. PMID: 37290539
Hereditary Angioedema: A Review of the Current and Evolving Treatment Landscape.
Betschel SD, Banerji A, Busse PJ, Cohn DM, Magerl M
J Allergy Clin Immunol Pract 2023 Aug;11(8):2315-2325. Epub 2023 Apr 26 doi: 10.1016/j.jaip.2023.04.017. PMID: 37116793
Current medical management of hereditary angioedema: Follow-up survey of US physicians.
Riedl MA, Banerji A, Gower R
Ann Allergy Asthma Immunol 2021 Mar;126(3):264-272. Epub 2020 Oct 26 doi: 10.1016/j.anai.2020.10.009. PMID: 33122123

Recent clinical studies

Etiology

Efficacy and Safety of Donidalorsen for Hereditary Angioedema.
Riedl MA, Tachdjian R, Lumry WR, Craig T, Karakaya G, Gelincik A, Stobiecki M, Jacobs JS, Gokmen NM, Reshef A, Gompels MM, Manning ME, Bordone L, Newman KB, Treadwell S, Wang S, Yarlas A, Cohn DM; OASIS-HAE Team
N Engl J Med 2024 Jul 4;391(1):21-31. Epub 2024 May 31 doi: 10.1056/NEJMoa2402478. PMID: 38819395
Once-Daily Oral Berotralstat for Long-Term Prophylaxis of Hereditary Angioedema: The Open-Label Extension of the APeX-2 Randomized Trial.
Kiani-Alikhan S, Gower R, Craig T, Wedner HJ, Kinaciyan T, Aygören-Pürsün E, Banerji A, Bernstein JA, Anderson J, Collis P, Johnston DT, Desai B, Tomita D, Gagnon R, Tachdjian R, Soteres DF, Farkas H, Caballero T, McNeil D, Jacobs J, Lumry WR; APeX-2 investigators
J Allergy Clin Immunol Pract 2024 Mar;12(3):733-743.e10. Epub 2023 Dec 18 doi: 10.1016/j.jaip.2023.12.019. PMID: 38122865
Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.
Maurer M, Ensina LF, Gimenez-Arnau AM, Sussman G, Hide M, Saini S, Grattan C, Fomina D, Rigopoulos D, Berard F, Canonica GW, Rockmann H, Irani C, Szepietowski JC, Leflein J, Bernstein JA, Peter JG, Kulthanan K, Godse K, Ardusso L, Ukhanova O, Staubach P, Sinclair R, Gogate S, Thomsen SF, Tanus T, Ye YM, Burciu A, Barve A, Modi D, Scosyrev E, Hua E, Letzelter K, Varanasi V, Patekar M, Severin T; PEARL-1 and PEARL-2 trial investigators
Lancet 2024 Jan 13;403(10422):147-159. Epub 2023 Nov 23 doi: 10.1016/S0140-6736(23)01684-7. PMID: 38008109
Lanadelumab in Patients 2 to Less Than 12 Years Old With Hereditary Angioedema: Results From the Phase 3 SPRING Study.
Maurer M, Lumry WR, Li HH, Aygören-Pürsün E, Busse PJ, Jacobs J, Nurse C, Ahmed MA, Watt M, Yu M; SPRING Investigators
J Allergy Clin Immunol Pract 2024 Jan;12(1):201-211.e6. Epub 2023 Sep 18 doi: 10.1016/j.jaip.2023.09.009. PMID: 37730089
Inhibition of Prekallikrein for Hereditary Angioedema.
Fijen LM, Riedl MA, Bordone L, Bernstein JA, Raasch J, Tachdjian R, Craig T, Lumry WR, Manning ME, Alexander VJ, Newman KB, Revenko A, Baker BF, Nanavati C, MacLeod AR, Schneider E, Cohn DM
N Engl J Med 2022 Mar 17;386(11):1026-1033. doi: 10.1056/NEJMoa2109329. PMID: 35294812

Diagnosis

Epidemiology, economic, and humanistic burden of hereditary angioedema: a systematic review.
Guan X, Sheng Y, Liu S, He M, Chen T, Zhi Y
Orphanet J Rare Dis 2024 Jul 8;19(1):256. doi: 10.1186/s13023-024-03265-z. PMID: 38978028Free PMC Article
Systemic inflammation biomarkers during angioedema attacks in hereditary angioedema.
Gil-Serrano J, Labrador-Horrillo M, Galvan-Blasco P, Sala-Cunill A, Bigas P, Pereira-González J, Luengo O, Cardona V, Guilarte M
Front Immunol 2024;15:1400526. Epub 2024 Jun 17 doi: 10.3389/fimmu.2024.1400526. PMID: 38953032Free PMC Article
Cold Urticaria Syndromes: Diagnosis and Management.
Diaz VL, Gribbons KB, Yazdi-Nejad K, Kuemmerle-Deschner J, Wanderer AA, Broderick L, Hoffman HM
J Allergy Clin Immunol Pract 2023 Aug;11(8):2275-2285. Epub 2023 Jun 7 doi: 10.1016/j.jaip.2023.05.040. PMID: 37290539
Hereditary Angioedema: A Review of the Current and Evolving Treatment Landscape.
Betschel SD, Banerji A, Busse PJ, Cohn DM, Magerl M
J Allergy Clin Immunol Pract 2023 Aug;11(8):2315-2325. Epub 2023 Apr 26 doi: 10.1016/j.jaip.2023.04.017. PMID: 37116793
Factor XII Contact Activation.
Naudin C, Burillo E, Blankenberg S, Butler L, Renné T
Semin Thromb Hemost 2017 Nov;43(8):814-826. Epub 2017 Mar 27 doi: 10.1055/s-0036-1598003. PMID: 28346966

Therapy

Efficacy and Safety of Donidalorsen for Hereditary Angioedema.
Riedl MA, Tachdjian R, Lumry WR, Craig T, Karakaya G, Gelincik A, Stobiecki M, Jacobs JS, Gokmen NM, Reshef A, Gompels MM, Manning ME, Bordone L, Newman KB, Treadwell S, Wang S, Yarlas A, Cohn DM; OASIS-HAE Team
N Engl J Med 2024 Jul 4;391(1):21-31. Epub 2024 May 31 doi: 10.1056/NEJMoa2402478. PMID: 38819395
Hereditary Angioedema: A Review of the Current and Evolving Treatment Landscape.
Betschel SD, Banerji A, Busse PJ, Cohn DM, Magerl M
J Allergy Clin Immunol Pract 2023 Aug;11(8):2315-2325. Epub 2023 Apr 26 doi: 10.1016/j.jaip.2023.04.017. PMID: 37116793
Inhibition of Prekallikrein for Hereditary Angioedema.
Fijen LM, Riedl MA, Bordone L, Bernstein JA, Raasch J, Tachdjian R, Craig T, Lumry WR, Manning ME, Alexander VJ, Newman KB, Revenko A, Baker BF, Nanavati C, MacLeod AR, Schneider E, Cohn DM
N Engl J Med 2022 Mar 17;386(11):1026-1033. doi: 10.1056/NEJMoa2109329. PMID: 35294812
Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study.
Banerji A, Bernstein JA, Johnston DT, Lumry WR, Magerl M, Maurer M, Martinez-Saguer I, Zanichelli A, Hao J, Inhaber N, Yu M, Riedl MA; HELP OLE Investigators
Allergy 2022 Mar;77(3):979-990. Epub 2021 Aug 13 doi: 10.1111/all.15011. PMID: 34287942Free PMC Article
8. Hereditary angioedema.
Frank MM
J Allergy Clin Immunol 2008 Feb;121(2 Suppl):S398-401; quiz S419. doi: 10.1016/j.jaci.2007.07.057. PMID: 18241690

Prognosis

Clinical Evaluation of Pediatric Patients with Hereditary Angioedema.
Kırmızıtaş Aydoğdu A, Ürel Demir G
Tohoku J Exp Med 2024 Jan 10;262(1):23-27. Epub 2023 Oct 5 doi: 10.1620/tjem.2023.J083. PMID: 37793880
How Does Pregnancy and Type of Delivery Affect the Clinical Course of Hereditary Angioedema?
Eyice Karabacak D, Can A, Demir S, Yegit OO, Colakoglu B, Buyukozturk S, Gelincik AA
Int Arch Allergy Immunol 2023;184(12):1216-1224. Epub 2023 Sep 6 doi: 10.1159/000531074. PMID: 37673053
COVID-19 and hereditary angioedema: Incidence, outcomes, and mechanistic implications.
Veronez CL, Christiansen SC, Smith TD, Riedl MA, Zuraw BL
Allergy Asthma Proc 2021 Nov 1;42(6):506-514. doi: 10.2500/aap.2021.42.210083. PMID: 34871158Free PMC Article
Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women.
Billebeau A, Fain O, Launay D, Boccon-Gibod I, Bouillet L, Gobert D, Plu-Bureau G, Gompel A; French National Reference Center for Hereditary Angioedema (CREAK)
J Clin Immunol 2021 Jan;41(1):163-170. Epub 2020 Oct 31 doi: 10.1007/s10875-020-00902-7. PMID: 33130967
Development of the Hereditary Angioedema Rapid Triage Tool.
Betschel S, Avilla E, Kanani A, Kastner M, Keith P, Binkley K, Lacuesta G, Borici-Mazi R, Badiou J, Rowe A, Yang WH, Waserman S
J Allergy Clin Immunol Pract 2020 Jan;8(1):310-317.e3. Epub 2019 Jun 22 doi: 10.1016/j.jaip.2019.05.056. PMID: 31238160

Clinical prediction guides

Efficacy and Safety of Donidalorsen for Hereditary Angioedema.
Riedl MA, Tachdjian R, Lumry WR, Craig T, Karakaya G, Gelincik A, Stobiecki M, Jacobs JS, Gokmen NM, Reshef A, Gompels MM, Manning ME, Bordone L, Newman KB, Treadwell S, Wang S, Yarlas A, Cohn DM; OASIS-HAE Team
N Engl J Med 2024 Jul 4;391(1):21-31. Epub 2024 May 31 doi: 10.1056/NEJMoa2402478. PMID: 38819395
A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema.
Petersen RS, Bordone L, Riedl MA, Tachdjian R, Craig TJ, Lumry WR, Manning ME, Bernstein JA, Raasch J, Zuraw BL, Deng Y, Newman KB, Alexander VJ, Lui C, Schneider E, Cohn DM
Allergy 2024 Mar;79(3):724-734. Epub 2023 Nov 27 doi: 10.1111/all.15948. PMID: 38009241
Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.
Maurer M, Ensina LF, Gimenez-Arnau AM, Sussman G, Hide M, Saini S, Grattan C, Fomina D, Rigopoulos D, Berard F, Canonica GW, Rockmann H, Irani C, Szepietowski JC, Leflein J, Bernstein JA, Peter JG, Kulthanan K, Godse K, Ardusso L, Ukhanova O, Staubach P, Sinclair R, Gogate S, Thomsen SF, Tanus T, Ye YM, Burciu A, Barve A, Modi D, Scosyrev E, Hua E, Letzelter K, Varanasi V, Patekar M, Severin T; PEARL-1 and PEARL-2 trial investigators
Lancet 2024 Jan 13;403(10422):147-159. Epub 2023 Nov 23 doi: 10.1016/S0140-6736(23)01684-7. PMID: 38008109
Inhibition of Prekallikrein for Hereditary Angioedema.
Fijen LM, Riedl MA, Bordone L, Bernstein JA, Raasch J, Tachdjian R, Craig T, Lumry WR, Manning ME, Alexander VJ, Newman KB, Revenko A, Baker BF, Nanavati C, MacLeod AR, Schneider E, Cohn DM
N Engl J Med 2022 Mar 17;386(11):1026-1033. doi: 10.1056/NEJMoa2109329. PMID: 35294812
Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study.
Banerji A, Bernstein JA, Johnston DT, Lumry WR, Magerl M, Maurer M, Martinez-Saguer I, Zanichelli A, Hao J, Inhaber N, Yu M, Riedl MA; HELP OLE Investigators
Allergy 2022 Mar;77(3):979-990. Epub 2021 Aug 13 doi: 10.1111/all.15011. PMID: 34287942Free PMC Article

Recent systematic reviews

Epidemiology, economic, and humanistic burden of hereditary angioedema: a systematic review.
Guan X, Sheng Y, Liu S, He M, Chen T, Zhi Y
Orphanet J Rare Dis 2024 Jul 8;19(1):256. doi: 10.1186/s13023-024-03265-z. PMID: 38978028Free PMC Article
Experience with Intravenous Plasma-Derived C1-Inhibitor in Pregnant Women with Hereditary Angioedema: A Systematic Literature Review.
Brooks JP, Radojicic C, Riedl MA, Newcomer SD, Banerji A, Hsu FI
J Allergy Clin Immunol Pract 2020 Jun;8(6):1875-1880.e3. Epub 2020 Apr 3 doi: 10.1016/j.jaip.2020.03.009. PMID: 32251736
Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies.
Storebø OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, Moreira-Maia CR, Magnusson FL, Holmskov M, Gerner T, Skoog M, Rosendal S, Groth C, Gillies D, Buch Rasmussen K, Gauci D, Zwi M, Kirubakaran R, Håkonsen SJ, Aagaard L, Simonsen E, Gluud C
Cochrane Database Syst Rev 2018 May 9;5(5):CD012069. doi: 10.1002/14651858.CD012069.pub2. PMID: 29744873Free PMC Article

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