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Angioedema, hereditary, 5(HAE5)

MedGen UID:
1780904
Concept ID:
C5543508
Disease or Syndrome
Synonyms: ANGIOEDEMA, HEREDITARY, 5; HAE5
 
Gene (location): ANGPT1 (8q23.1)
 
Monarch Initiative: MONDO:0030293
OMIM®: 619361

Definition

Hereditary angioedema-5 (HAE5) is an autosomal dominant disorder characterized by localized and self-limiting edema of the subcutaneous or submucosal tissue due to an episodic increase in vascular permeability. Affected individuals have onset of episodic swelling of the face, lips, hands, and abdomen in the second decade of life. Treatment with tranexamic acid may be effective in reducing the severity and frequency of the attacks (summary by Bafunno et al., 2018). For a discussion of genetic heterogeneity of hereditary angioedema, 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.
Nail bed hemorrhage
MedGen UID:
830602
Concept ID:
C0877087
Sign or Symptom
Small areas of bleeding (hemorrhage) under the fingernail or toenail.
Nailfold capillary tortuosity
MedGen UID:
863168
Concept ID:
C4014731
Finding
An increased number of turns of the blood vessels of the nailfold with a charactereistic winded or twisted appearance of the blood vessels.

Professional guidelines

PubMed

Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygören-Pürsün E, Banerji A, Bara NA, Boccon-Gibod I, Bork K, Bouillet L, Boysen HB, Brodszki N, Busse PJ, Bygum A, Caballero T, Cancian M, Castaldo A, Cohn DM, Csuka D, Farkas H, Gompels M, Gower R, Grumach AS, Guidos-Fogelbach G, Hide M, Kang HR, Kaplan AP, Katelaris C, Kiani-Alikhan S, Lei WT, Lockey R, Longhurst H, Lumry WR, MacGinnitie A, Malbran A, Martinez Saguer I, Matta JJ, Nast A, Nguyen D, Nieto-Martinez SA, Pawankar R, Peter J, Porebski G, Prior N, Reshef A, Riedl M, Ritchie B, Rafique Sheikh F, Smith WB, Spaeth PJ, Stobiecki M, Toubi E, Varga LA, Weller K, Zanichelli A, Zhi Y, Zuraw B, Craig T
Allergy 2022 Jul;77(7):1961-1990. Epub 2022 Feb 3 doi: 10.1111/all.15214. PMID: 35006617
Brodszki N, Frazer-Abel A, Grumach AS, Kirschfink M, Litzman J, Perez E, Seppänen MRJ, Sullivan KE, Jolles S
J Clin Immunol 2020 May;40(4):576-591. Epub 2020 Feb 17 doi: 10.1007/s10875-020-00754-1. PMID: 32064578Free PMC Article
Charlesworth EN
Allergy Asthma Proc 2002 Sep-Oct;23(5):337-9. PMID: 12476544

Recent clinical studies

Etiology

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
Longhurst HJ, Lindsay K, Petersen RS, Fijen LM, Gurugama P, Maag D, Butler JS, Shah MY, Golden A, Xu Y, Boiselle C, Vogel JD, Abdelhady AM, Maitland ML, McKee MD, Seitzer J, Han BW, Soukamneuth S, Leonard J, Sepp-Lorenzino L, Clark ED, Lebwohl D, Cohn DM
N Engl J Med 2024 Feb 1;390(5):432-441. doi: 10.1056/NEJMoa2309149. PMID: 38294975
Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygören-Pürsün E, Banerji A, Bara NA, Boccon-Gibod I, Bork K, Bouillet L, Boysen HB, Brodszki N, Busse PJ, Bygum A, Caballero T, Cancian M, Castaldo A, Cohn DM, Csuka D, Farkas H, Gompels M, Gower R, Grumach AS, Guidos-Fogelbach G, Hide M, Kang HR, Kaplan AP, Katelaris C, Kiani-Alikhan S, Lei WT, Lockey R, Longhurst H, Lumry WR, MacGinnitie A, Malbran A, Martinez Saguer I, Matta JJ, Nast A, Nguyen D, Nieto-Martinez SA, Pawankar R, Peter J, Porebski G, Prior N, Reshef A, Riedl M, Ritchie B, Rafique Sheikh F, Smith WB, Spaeth PJ, Stobiecki M, Toubi E, Varga LA, Weller K, Zanichelli A, Zhi Y, Zuraw B, Craig T
Allergy 2022 Jul;77(7):1961-1990. Epub 2022 Feb 3 doi: 10.1111/all.15214. PMID: 35006617
Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X
Cochrane Database Syst Rev 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4. PMID: 33141449Free PMC Article
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

Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygören-Pürsün E, Banerji A, Bara NA, Boccon-Gibod I, Bork K, Bouillet L, Boysen HB, Brodszki N, Busse PJ, Bygum A, Caballero T, Cancian M, Castaldo A, Cohn DM, Csuka D, Farkas H, Gompels M, Gower R, Grumach AS, Guidos-Fogelbach G, Hide M, Kang HR, Kaplan AP, Katelaris C, Kiani-Alikhan S, Lei WT, Lockey R, Longhurst H, Lumry WR, MacGinnitie A, Malbran A, Martinez Saguer I, Matta JJ, Nast A, Nguyen D, Nieto-Martinez SA, Pawankar R, Peter J, Porebski G, Prior N, Reshef A, Riedl M, Ritchie B, Rafique Sheikh F, Smith WB, Spaeth PJ, Stobiecki M, Toubi E, Varga LA, Weller K, Zanichelli A, Zhi Y, Zuraw B, Craig T
Allergy 2022 Jul;77(7):1961-1990. Epub 2022 Feb 3 doi: 10.1111/all.15214. PMID: 35006617
Brodszki N, Frazer-Abel A, Grumach AS, Kirschfink M, Litzman J, Perez E, Seppänen MRJ, Sullivan KE, Jolles S
J Clin Immunol 2020 May;40(4):576-591. Epub 2020 Feb 17 doi: 10.1007/s10875-020-00754-1. PMID: 32064578Free PMC Article
Patel G, Pongracic JA
Allergy Asthma Proc 2019 Nov 1;40(6):441-445. doi: 10.2500/aap.2019.40.4267. PMID: 31690390
Bellanti JA, Settipane RA
Allergy Asthma Proc 2018 Sep 1;39(5):329-331. doi: 10.2500/aap.2018.39.4169. PMID: 30153885Free PMC Article
Axelrod S, Davis-Lorton M
Mt Sinai J Med 2011 Sep-Oct;78(5):784-802. doi: 10.1002/msj.20288. PMID: 21913206

Therapy

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
Longhurst HJ, Lindsay K, Petersen RS, Fijen LM, Gurugama P, Maag D, Butler JS, Shah MY, Golden A, Xu Y, Boiselle C, Vogel JD, Abdelhady AM, Maitland ML, McKee MD, Seitzer J, Han BW, Soukamneuth S, Leonard J, Sepp-Lorenzino L, Clark ED, Lebwohl D, Cohn DM
N Engl J Med 2024 Feb 1;390(5):432-441. doi: 10.1056/NEJMoa2309149. PMID: 38294975
Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Aygören-Pürsün E, Banerji A, Bara NA, Boccon-Gibod I, Bork K, Bouillet L, Boysen HB, Brodszki N, Busse PJ, Bygum A, Caballero T, Cancian M, Castaldo A, Cohn DM, Csuka D, Farkas H, Gompels M, Gower R, Grumach AS, Guidos-Fogelbach G, Hide M, Kang HR, Kaplan AP, Katelaris C, Kiani-Alikhan S, Lei WT, Lockey R, Longhurst H, Lumry WR, MacGinnitie A, Malbran A, Martinez Saguer I, Matta JJ, Nast A, Nguyen D, Nieto-Martinez SA, Pawankar R, Peter J, Porebski G, Prior N, Reshef A, Riedl M, Ritchie B, Rafique Sheikh F, Smith WB, Spaeth PJ, Stobiecki M, Toubi E, Varga LA, Weller K, Zanichelli A, Zhi Y, Zuraw B, Craig T
Allergy 2022 Jul;77(7):1961-1990. Epub 2022 Feb 3 doi: 10.1111/all.15214. PMID: 35006617
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
Obtułowicz K
Pol Arch Med Wewn 2016;126(1-2):76-85. doi: 10.20452/pamw.3273. PMID: 26842379

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
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
Sugi MD, Menias CO, Lubner MG, Bhalla S, Mellnick VM, Kwon MH, Katz DS
Radiographics 2018 Sep-Oct;38(5):1352-1369. doi: 10.1148/rg.2018170148. PMID: 30207931
Spickett G
J R Coll Physicians Edinb 2014;44(1):50-4. doi: 10.4997/JRCPE.2014.112. PMID: 24995449

Clinical prediction guides

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
Longhurst HJ, Lindsay K, Petersen RS, Fijen LM, Gurugama P, Maag D, Butler JS, Shah MY, Golden A, Xu Y, Boiselle C, Vogel JD, Abdelhady AM, Maitland ML, McKee MD, Seitzer J, Han BW, Soukamneuth S, Leonard J, Sepp-Lorenzino L, Clark ED, Lebwohl D, Cohn DM
N Engl J Med 2024 Feb 1;390(5):432-441. doi: 10.1056/NEJMoa2309149. PMID: 38294975
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
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
Deeks ED
Drugs 2010;70(1):73-81. doi: 10.2165/11204500-000000000-00000. PMID: 20030426

Recent systematic reviews

Rayner DG, Liu M, Chu AWL, Chu X, Guyatt GH, Oykhman P, Cao DJ, Moellman J, Ben-Shoshan M, Baker DR, Waserman S, Lang D, Sheikh J, Mathur SK, Beck LA, Khan DA, Oliver ET, Asiniwasis RN, Cole EF, Wheeler KE, Runyon L, Chan J, Trayes KP, Eftekhari S, Gardner DD, Winders T, Saini SS, Bernstein JA, Chu DK
J Allergy Clin Immunol 2024 Oct;154(4):996-1007. Epub 2024 Jun 7 doi: 10.1016/j.jaci.2024.05.026. PMID: 38852861
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
Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X
Cochrane Database Syst Rev 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4. PMID: 33141449Free PMC Article
Lawlor CM, Ananth A, Barton BM, Flowers TC, McCoul ED
Otolaryngol Head Neck Surg 2018 Feb;158(2):232-239. Epub 2017 Nov 7 doi: 10.1177/0194599817737974. PMID: 29112487
Riha HM, Summers BB, Rivera JV, Van Berkel MA
J Emerg Med 2017 Nov;53(5):662-679. Epub 2017 Sep 20 doi: 10.1016/j.jemermed.2017.05.037. PMID: 28939396

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