U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Angioedema, hereditary, 6(HAE6)

MedGen UID:
1785484
Concept ID:
C5543516
Disease or Syndrome
Synonyms: ANGIOEDEMA, HEREDITARY, 6; HAE6
 
Gene (location): KNG1 (3q27.3)
 
Monarch Initiative: MONDO:0023660
OMIM®: 619363

Definition

Hereditary angioedema-6 (HAE6) is an autosomal dominant disorder characterized by onset of episodic subcutaneous and submucosal swelling in adulthood. The face, mouth, and tongue are often affected; some patients have distal limb or abdominal edema. Levels of complement component inhibitor (C1INH; 606860) are normal (summary by Bork et al., 2019). For a discussion of genetic heterogeneity of HAE, see 106100. [from OMIM]

Clinical features

From HPO
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.
Swollen lip
MedGen UID:
116100
Concept ID:
C0240211
Sign or Symptom
Enlargement of the lip typically due to fluid buildup or inflammation.
Facial edema
MedGen UID:
154241
Concept ID:
C0542571
Pathologic Function
Swelling due to an excessive accumulation of fluid in facial tissues.
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.

Professional guidelines

PubMed

Kesh S, Bernstein JA
Ann Allergy Asthma Immunol 2022 Dec;129(6):692-702. Epub 2022 Aug 19 doi: 10.1016/j.anai.2022.08.003. PMID: 35988876
Maurer M, Aygören-Pürsün E, Banerji A, Bernstein JA, Balle Boysen H, Busse PJ, Bygum A, Caballero T, Castaldo AJ, Christiansen SC, Craig T, Farkas H, Grumach AS, Hide M, Katelaris CH, Li HH, Longhurst H, Lumry WR, Magerl M, Martinez-Saguer I, Riedl MA, Zhi Y, Zuraw B
J Allergy Clin Immunol 2021 Dec;148(6):1526-1532. Epub 2021 May 25 doi: 10.1016/j.jaci.2021.05.016. PMID: 34048855
Perego F, Wu MA, Valerieva A, Caccia S, Suffritti C, Zanichelli A, Bergamaschini L, Cicardi M
Expert Opin Biol Ther 2019 Jun;19(6):517-526. Epub 2019 Mar 26 doi: 10.1080/14712598.2019.1595581. PMID: 30912460

Recent clinical studies

Etiology

Craig TJ, Reshef A, Li HH, Jacobs JS, Bernstein JA, Farkas H, Yang WH, Stroes ESG, Ohsawa I, Tachdjian R, Manning ME, Lumry WR, Saguer IM, Aygören-Pürsün E, Ritchie B, Sussman GL, Anderson J, Kawahata K, Suzuki Y, Staubach P, Treudler R, Feuersenger H, Glassman F, Jacobs I, Magerl M
Lancet 2023 Apr 1;401(10382):1079-1090. Epub 2023 Feb 28 doi: 10.1016/S0140-6736(23)00350-1. PMID: 36868261
Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K
Cochrane Database Syst Rev 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2. PMID: 36326435Free PMC Article
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
Pancholy N, Craig T
Curr Opin Pediatr 2019 Dec;31(6):863-868. doi: 10.1097/MOP.0000000000000832. PMID: 31693598
Banerji A, Riedl MA, Bernstein JA, Cicardi M, Longhurst HJ, Zuraw BL, Busse PJ, Anderson J, Magerl M, Martinez-Saguer I, Davis-Lorton M, Zanichelli A, Li HH, Craig T, Jacobs J, Johnston DT, Shapiro R, Yang WH, Lumry WR, Manning ME, Schwartz LB, Shennak M, Soteres D, Zaragoza-Urdaz RH, Gierer S, Smith AM, Tachdjian R, Wedner HJ, Hebert J, Rehman SM, Staubach P, Schranz J, Baptista J, Nothaft W, Maurer M; HELP Investigators
JAMA 2018 Nov 27;320(20):2108-2121. doi: 10.1001/jama.2018.16773. PMID: 30480729Free PMC Article

Diagnosis

Sinnathamby ES, Issa PP, Roberts L, Norwood H, Malone K, Vemulapalli H, Ahmadzadeh S, Cornett EM, Shekoohi S, Kaye AD
Adv Ther 2023 Mar;40(3):814-827. Epub 2023 Jan 7 doi: 10.1007/s12325-022-02401-0. PMID: 36609679Free PMC Article
Kesh S, Bernstein JA
Ann Allergy Asthma Immunol 2022 Dec;129(6):692-702. Epub 2022 Aug 19 doi: 10.1016/j.anai.2022.08.003. PMID: 35988876
Kazandjieva J, Christoff G
Clin Dermatol 2019 Nov-Dec;37(6):636-643. Epub 2019 Aug 1 doi: 10.1016/j.clindermatol.2019.07.035. PMID: 31864442
Guo C, Greenberger PA
Allergy Asthma Proc 2019 Nov 1;40(6):457-461. doi: 10.2500/aap.2019.40.4271. PMID: 31690394
Patel G, Pongracic JA
Allergy Asthma Proc 2019 Nov 1;40(6):441-445. doi: 10.2500/aap.2019.40.4267. PMID: 31690390

Therapy

Craig TJ, Reshef A, Li HH, Jacobs JS, Bernstein JA, Farkas H, Yang WH, Stroes ESG, Ohsawa I, Tachdjian R, Manning ME, Lumry WR, Saguer IM, Aygören-Pürsün E, Ritchie B, Sussman GL, Anderson J, Kawahata K, Suzuki Y, Staubach P, Treudler R, Feuersenger H, Glassman F, Jacobs I, Magerl M
Lancet 2023 Apr 1;401(10382):1079-1090. Epub 2023 Feb 28 doi: 10.1016/S0140-6736(23)00350-1. PMID: 36868261
Kesh S, Bernstein JA
Ann Allergy Asthma Immunol 2022 Dec;129(6):692-702. Epub 2022 Aug 19 doi: 10.1016/j.anai.2022.08.003. PMID: 35988876
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
Guo C, Greenberger PA
Allergy Asthma Proc 2019 Nov 1;40(6):457-461. doi: 10.2500/aap.2019.40.4271. PMID: 31690394
Banerji A, Riedl MA, Bernstein JA, Cicardi M, Longhurst HJ, Zuraw BL, Busse PJ, Anderson J, Magerl M, Martinez-Saguer I, Davis-Lorton M, Zanichelli A, Li HH, Craig T, Jacobs J, Johnston DT, Shapiro R, Yang WH, Lumry WR, Manning ME, Schwartz LB, Shennak M, Soteres D, Zaragoza-Urdaz RH, Gierer S, Smith AM, Tachdjian R, Wedner HJ, Hebert J, Rehman SM, Staubach P, Schranz J, Baptista J, Nothaft W, Maurer M; HELP Investigators
JAMA 2018 Nov 27;320(20):2108-2121. doi: 10.1001/jama.2018.16773. PMID: 30480729Free PMC Article

Prognosis

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
Can Bostan O, Tuncay G, Damadoglu E, Karakaya G, Kalyoncu AF
Allergy Asthma Proc 2021 Sep 1;42(5):403-408. doi: 10.2500/aap.2021.42.210066. PMID: 34474710Free PMC Article
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
Frank MM
Curr Opin Pediatr 2005 Dec;17(6):686-9. doi: 10.1097/01.mop.0000182382.28552.1c. PMID: 16282771
Gigli I
J Invest Dermatol 1973 Jun;60(6):516-21. doi: 10.1111/1523-1747.ep12703581. PMID: 4122980

Clinical prediction guides

Karabiber E, Kendirlinan R, Çerçi P
J Cosmet Dermatol 2022 Dec;21(12):7163-7169. Epub 2022 Oct 25 doi: 10.1111/jocd.15438. PMID: 36207991
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
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
Ocak M, Nain E, Şahiner ÜM, Akin MŞ, Karabiber E, Şekerel BE, Soyer Ö
Pediatr Dermatol 2021 Jan;38(1):143-148. Epub 2020 Dec 4 doi: 10.1111/pde.14467. PMID: 33275322
Deeks ED
Drugs 2010;70(1):73-81. doi: 10.2165/11204500-000000000-00000. PMID: 20030426

Recent systematic reviews

Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K
Cochrane Database Syst Rev 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2. PMID: 36326435Free PMC Article
Bork K, Machnig T, Wulff K, Witzke G, Prusty S, Hardt J
Orphanet J Rare Dis 2020 Oct 15;15(1):289. doi: 10.1186/s13023-020-01570-x. PMID: 33059692Free PMC Article
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
Aygören-Pürsün E, Magerl M, Maetzel A, Maurer M
Orphanet J Rare Dis 2018 May 4;13(1):73. doi: 10.1186/s13023-018-0815-5. PMID: 29728119Free PMC Article
Craig TJ, Schneider LC, MacGinnitie AJ
Pediatr Allergy Immunol 2015 Sep;26(6):537-44. doi: 10.1111/pai.12425. PMID: 26111105

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...