Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Allergy, Asthma & Clinical Immunology
Published in: Allergy, Asthma & Clinical Immunology 1/2010

Open Access 01-12-2010 | Review

Pediatric hereditary angioedema due to C1-inhibitor deficiency

Author: Henriette Farkas

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2010

Login to get access

Abstract

Hereditary angioedema (HAE) resulting from the deficiency of the C1 inhibitor (C1-INH) is a rare, life-threatening disorder. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. In approximately 50 per cent of cases, clinical manifestations may appear during childhood. The complex management of HAE in pediatric patients is in many respects different from the management of adults. Establishing the diagnosis early, preferably before the onset of clinical symptoms, is essential in cases with a positive family history. Complement studies usually afford accurate diagnosis, whereas molecular genetics tests may prove helpful in uncertain cases. Appropriate therapy, supported by counselling, suitable modification of lifestyle, and avoidance of triggering factors (which primarily include mechanical trauma, mental stress and airway infections in children) may spare the patient unnecessary surgery and may prevent mortality. Prompt control of edematous attacks, short-term prophylaxis and intermittent therapy are recommended as the primary means for the management of pediatric cases. Medicinal products currently used for the treatment of children with hereditary angioedema include antifibrinolytics, attenuated androgens, and C1-INH replacement therapy. Current guidelines favour antifibrinolytics for long-term prophylaxis because of their favorable safety profile but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1-INH replacement therapy is also an effective and safe agent for children. Regular monitoring and follow-up of patients are necessary.
Literature
1.
Agostoni A, Aygoren-Pursun E, Binkley KE, Blanch A, Bork K, Bouillet L, Bucher C, Castaldo AJ, Cicardi M, Davis AE: Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004, 114: S51-131. 10.1016/j.jaci.2004.06.047.CrossRefPubMed
2.
Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M: C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009, 15: 69-78. 10.1016/j.molmed.2008.12.001.CrossRefPubMed
3.
Barakat J: Hereditary angioedema in chlidren. Angioedema. 2010, 1: 15-19.
4.
Gompels MM, Lock RJ, Abinun M, Bethune CA, Davies G, Grattan C, Fay AC, Longhurst HJ, Morrison L, Price A: C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005, 139: 379-394. 10.1111/j.1365-2249.2005.02726.x.PubMedCentralCrossRefPubMed
5.
Bowen T, Cicardi M, Bork K, Zuraw B, Frank M, Ritchie B, Farkas H, Varga L, Zingale LC, Binkley K: Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Ann Allergy Asthma Immunol. 2008, 100: S30-40. 10.1016/S1081-1206(10)60584-4.CrossRefPubMed
6.
Cicardi M, Zingale L, Zanichelli A, Deliliers DL: Established and new treatments for hereditary angioedema: An update. Mol Immunol. 2007, 44: 3858-3861. 10.1016/j.molimm.2007.06.004.CrossRefPubMed
7.
Frank MM, Jiang H: New therapies for hereditary angioedema: disease outlook changes dramatically. J Allergy Clin Immunol. 2008, 121: 272-280. 10.1016/j.jaci.2007.11.019.CrossRefPubMed
8.
Pappalardo E, Caccia S, Suffritti C, Tordai A, Zingale LC, Cicardi M: Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates. Mol Immunol. 2008, 45: 3536-3544. 10.1016/j.molimm.2008.05.007.CrossRefPubMed
9.
Kalmar L, Bors A, Farkas H, Vas S, Fandl B, Varga L, Fust G, Tordai A: Mutation screening of the C1 inhibitor gene among Hungarian patients with hereditary angioedema. Hum Mutat. 2003, 22: 498-10.1002/humu.9202.CrossRefPubMed
10.
Füst G, Széplaki G, Csuka D, Varga L, Farkas H: Increase in the yearly attack frequency in HAE patient treated with Danazol for 6 years. 6th C1-inhibitor Deficiency Workshop. Budapest, Hungary. 2009
11.
Nielsen EW, Johansen HT, Holt J, Mollnes TE: C1 inhibitor and diagnosis of hereditary angioedema in newborns. Pediatr Res. 1994, 35: 184-187. 10.1203/00006450-199402000-00012.CrossRefPubMed
12.
Nurnberger W, Stannigel H, Muntel V, Michelmann I, Wahn V, Gobel U: [In-vivo activation of the 4th component of the complement system (C4) in premature and term infants with generalized bacterial infections]. Klin Padiatr. 1990, 202: 141-146. 10.1055/s-2007-1025507.CrossRefPubMed
13.
Hogasen AK, Overlie I, Hansen TW, Abrahamsen TG, Finne PH, Hogasen K: The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency. J Perinat Med. 2000, 28: 39-48. 10.1515/JPM.2000.006.CrossRefPubMed
14.
Frank MM, Gelfand JA, Atkinson JP: Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. 1976, 84: 580-593.CrossRefPubMed
15.
Bygum A: Hereditary angio-oedema in Denmark: a nationwide survey. Br J Dermatol. 2009, 161: 1153-1158. 10.1111/j.1365-2133.2009.09366.x.CrossRefPubMed
16.
Bork K, Meng G, Staubach P, Hardt J: Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006, 119: 267-274. 10.1016/j.amjmed.2005.09.064.CrossRefPubMed
17.
Martinez-Saguer I, Rusicke E, Aygören-Pürsün E, Kreuz W: Clinical surveillance program of pediatric hereditary angioedema (HAE) patients undergoing home treatment. AAAAAI 2009. Washington, DC, United States. 2009
18.
El-Hachem C, Amiour M, Guillot M, Laurent J: [Hereditary angioneurotic edema: a case report in a 3-year-old child]. Arch Pediatr. 2005, 12: 1232-1236. 10.1016/j.arcped.2005.03.052.CrossRefPubMed
19.
O'Bier A, Muniz AE, Foster RL: Hereditary angioedema presenting as epiglottitis. Pediatr Emerg Care. 2005, 21: 27-30. 10.1097/01.pec.0000150985.81109.0d.CrossRefPubMed
20.
Krishnamurthy A, Naguwa SM, Gershwin ME: Pediatric angioedema. Clin Rev Allergy Immunol. 2008, 34: 250-259. 10.1007/s12016-007-8037-y.CrossRefPubMed
21.
Shah UK, Jacobs IN: Pediatric angioedema: ten years' experience. Arch Otolaryngol Head Neck Surg. 1999, 125: 791-795.CrossRefPubMed
22.
Doherty G: Acute and chronic airway obstruction in children. Anaesthesia & Intensive Care Medicine. 2009, 10: 191-195. 10.1016/j.mpaic.2009.02.005.CrossRef
23.
Bork K, Hardt J, Schicketanz KH, Ressel N: Clinical studies of sudden upper airway obstruction in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. Arch Intern Med. 2003, 163: 1229-1235. 10.1001/archinte.163.10.1229.CrossRefPubMed
24.
Janardhanan D, Nair S, Subramanian TS: Recurrent abdominal pain due to hereditary angioedema. Indian J Pediatr. 2007, 74: 83-84. 10.1007/s12098-007-0034-x.CrossRefPubMed
25.
Lindecken KD, Adolph M, Paterakis S: [Pedicle torsion, hemorrhagic ovarian infarct. A rare cause of pediatric acute abdomen]. Zentralbl Chir. 1991, 116: 679-682.PubMed
26.
Foix-L'Helias L, Weiss L, Mollet-Boudjemline A, Fallik D, Trioche-Eberschweiler P, Labrune P: Recurring acute abdominal pains in an adolescent as the presenting manifestations of hereditary angioneurotic oedema. Acta Paediatr. 2005, 94: 1158-1161. 10.1080/08035250410026338.CrossRefPubMed
27.
Sanchez A, Ecochard A, Maestracci M, Rodiere M: [Hereditary angioedema causing colocolic intussusception]. Arch Pediatr. 2008, 15: 271-274. 10.1016/j.arcped.2007.12.004.CrossRefPubMed
28.
Pritzker HA, Levin TL, Weinberg G: Recurrent colocolic intussusception in a child with hereditary angioneurotic edema: reduction by air enema. J Pediatr Surg. 2004, 39: 1144-1146. 10.1016/j.jpedsurg.2004.03.075.CrossRefPubMed
29.
Farkas H, Harmat G, Fekete B, Karadi I, Visy B, Varga L: Acute abdominal attack of hereditary angioneurotic oedema associated with ultrasound abnormalities suggestive of acute hepatitis. Acta Paediatr. 2002, 91: 971-974. 10.1080/080352502760148720.CrossRefPubMed
30.
Farkas H, Harmat G, Kaposi PN, Karadi I, Fekete B, Fust G, Fay K, Vass A, Varga L: Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema. Eur J Gastroenterol Hepatol. 2001, 13: 1225-1230. 10.1097/00042737-200110000-00016.CrossRefPubMed
31.
Cugno M, Zanichelli A, Bellatorre AG, Griffini S, Cicardi M: Plasma biomarkers of acute attacks in patients with angioedema due to C1-inhibitor deficiency. Allergy. 2009, 64: 254-257. 10.1111/j.1398-9995.2008.01859.x.CrossRefPubMed
32.
Altorjai P, Visy B, Kormos Zs, Harmat G, Fekete F, Farkas H: Pericardiac effusion complicating an acute abdominal attack of hereditary angioneurotic edema. Am J Case Rep. 2008, 9: CR233-236.
33.
Farkas H, Harmat G, Fay A, Fekete B, Karadi I, Visy B, Varga L: Erythema marginatum preceding an acute oedematous attack of hereditary angioneurotic oedema. Acta Derm Venereol. 2001, 81: 376-377. 10.1080/00015550152572985.CrossRefPubMed
34.
Hubiche T, Boralevi F, Jouvencel P, Taieb A, Leaute-Labreze C: [Reticular erythema signalling the onset of episodes of hereditary angioedema in a child]. Ann Dermatol Venereol. 2005, 132: 249-251. 10.1016/S0151-9638(05)79255-3.CrossRefPubMed
35.
Farkas H, Fust G, Fekete B, Karadi I, Varga L: Eradication of Helicobacter pylori and improvement of hereditary angioneurotic oedema. Lancet. 2001, 358: 1695-1696. 10.1016/S0140-6736(01)06720-4.CrossRefPubMed
36.
Assadi FK, Wang HE, Lawless S, McKay CP, Hopp L, Fattori D: Angiotensin converting enzyme inhibitor-induced angioedema: a report of two cases. Pediatr Nephrol. 1999, 13: 917-919. 10.1007/s004670050727.CrossRefPubMed
37.
Quintana EC, Attia MW: Angiotensin-converting enzyme inhibitor angioedema in a pediatric patient: a case report and discussion. Pediatr Emerg Care. 2001, 17: 438-440. 10.1097/00006565-200112000-00009.CrossRefPubMed
38.
Farkas H, Varga L, Szeplaki G, Visy B, Harmat G, Bowen T: Management of hereditary angioedema in pediatric patients. Pediatrics. 2007, 120: e713-722. 10.1542/peds.2006-3303.CrossRefPubMed
39.
Szema AM, Paz G, Merriam L, Stellaccio F, Jen J: Modern preoperative and intraoperative management of hereditary angioedema. Allergy Asthma Proc. 2009, 30: 338-342. 10.2500/aap.2009.30.3225.CrossRefPubMed
40.
Craig T, Riedl M, Dykewicz MS, Gower RG, Baker J, Edelman FJ, Hurewitz D, Jacobs J, Kalfus I: When is prophylaxis for hereditary angioedema necessary?. Ann Allergy Asthma Immunol. 2009, 102: 366-372. 10.1016/S1081-1206(10)60506-6.CrossRefPubMed
41.
Gelfand JA, Sherins RJ, Alling DW, Frank MM: Treatment of hereditary angioedema with danazol. Reversal of clinical and biochemical abnormalities. N Engl J Med. 1976, 295: 1444-1448. 10.1056/NEJM197612232952602.CrossRefPubMed
42.
Zuraw BL: Hereditary angiodema: a current state-of-the-art review, IV: short-and long-term treatment of hereditary angioedema: out with the old and in with the new?. Ann Allergy Asthma Immunol. 2008, 100: S13-18. 10.1016/S1081-1206(10)60581-9.CrossRefPubMed
43.
Cicardi M, Zingale L: How do we treat patients with hereditary angioedema. Transfus Apher Sci. 2003, 29: 221-227. 10.1016/S1473-0502(03)00164-2.CrossRefPubMed
44.
Agostoni A, Cicardi M: Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine (Baltimore). 1992, 71: 206-215.CrossRef
45.
Schneider L, Lumry W, Vegh A, Williams AH, Schmalbach T: Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor. J Allergy Clin Immunol. 2007, 120: 416-422. 10.1016/j.jaci.2007.04.028.CrossRefPubMed
46.
Cocchio C, Marzella N: Cinryze, a Human Plasma-Derived C1 Esterase Inhibitor for Prophylaxis Of Hereditary Angioedema. P T. 2009, 34: 293-328.PubMedCentralPubMed
47.
Boyle RJ, Nikpour M, Tang ML: Hereditary angio-oedema in children: a management guideline. Pediatr Allergy Immunol. 2005, 16: 288-294.CrossRefPubMed
48.
49.
Church JA: Oxandrolone treatment of childhood hereditary angioedema. Ann Allergy Asthma Immunol. 2004, 92: 377-378. 10.1016/S1081-1206(10)61578-5.CrossRefPubMed
50.
Barakat A, Castaldo AJ: Hereditary angioedema: danazol therapy in a 5-year-old child. Am J Dis Child. 1993, 147: 931-932.PubMed
51.
Tappeiner G, Hintner H, Glatzl J, Wolff K: Hereditary angio-oedema: treatment with danazol. Report of a case. Br J Dermatol. 1979, 100: 207-212. 10.1111/j.1365-2133.1979.tb05562.x.CrossRefPubMed
52.
Farkas H, Harmat G, Gyeney L, Fust G, Varga L: Danazol therapy for hereditary angio-oedema in children. Lancet. 1999, 354: 1031-1032. 10.1016/S0140-6736(05)76637-X.CrossRefPubMed
53.
Banerji A, Sloane DE, Sheffer AL: Hereditary angioedema: a current state-of-the-art review, V: attenuated androgens for the treatment of hereditary angioedema. Ann Allergy Asthma Immunol. 2008, 100: S19-22. 10.1016/S1081-1206(10)60582-0.CrossRefPubMed
54.
Craig TJ: Appraisal of danazol prophylaxis for hereditary angioedema. Allergy Asthma Proc. 2008, 29: 225-231. 10.2500/aap.2008.29.3107.CrossRefPubMed
55.
Farkas H, Harmat G, Fust G, Varga L, Visy B: Clinical management of hereditary angio-oedema in children. Pediatr Allergy Immunol. 2002, 13: 153-161. 10.1034/j.1399-3038.2002.01014.x.CrossRefPubMed
56.
Agostoni A, Marasini B, Cicardi M, Martignoni GC: Intermittent therapy with danazol in hereditary angioedema. Lancet. 1978, 1: 453-10.1016/S0140-6736(78)91254-0.CrossRefPubMed
57.
Bork K, Staubach P, Hardt J: Treatment of skin swellings with C1-inhibitor concentrate in patients with hereditary angio-oedema. Allergy. 2008, 63: 751-757. 10.1111/j.1398-9995.2007.01577.x.CrossRefPubMed
58.
Farkas H, Jakab L, Temesszentandrasi G, Visy B, Harmat G, Fust G, Szeplaki G, Fekete B, Karadi I, Varga L: Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy. J Allergy Clin Immunol. 2007, 120: 941-947. 10.1016/j.jaci.2007.06.026.CrossRefPubMed
59.
Bork K, Barnstedt SE: Treatment of 193 episodes of laryngeal edema with C1 inhibitor concentrate in patients with hereditary angioedema. Arch Intern Med. 2001, 161: 714-718. 10.1001/archinte.161.5.714.CrossRefPubMed
60.
Kreuz W, Martinez-Saguer I, Aygoren-Pursun E, Rusicke E, Heller C, Klingebiel T: C1-inhibitor concentrate for individual replacement therapy in patients with severe hereditary angioedema refractory to danazol prophylaxis. Transfusion. 2009, 49: 1987-1995. 10.1111/j.1537-2995.2009.02230.x.CrossRefPubMed
61.
Levy JH, O'Donnell PS: The therapeutic potential of a kallikrein inhibitor for treating hereditary angioedema. Expert Opin Investig Drugs. 2006, 15: 1077-1090. 10.1517/13543784.15.9.1077.CrossRefPubMed
62.
Bygum A, Andersen KE, Mikkelsen CS: Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits. Eur J Dermatol. 2009, 19: 147-151.PubMed
63.
Farkas H, Varga L: The Hungarian HAE experience. Transfus Apher Sci. 2003, 29: 229-233. 10.1016/j.transci.2003.08.003.CrossRefPubMed
Metadata
Title
Pediatric hereditary angioedema due to C1-inhibitor deficiency
Author
Henriette Farkas
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Allergy, Asthma & Clinical Immunology / Issue 1/2010
Electronic ISSN: 1710-1492
DOI
https://doi.org/10.1186/1710-1492-6-18

Other articles of this Issue 1/2010

Allergy, Asthma & Clinical Immunology 1/2010 Go to the issue

Review

Clinical experience in T cell deficient patients

Editorial

Hereditary Angioedema Consensus 2010

Research

Food allergy management from the perspective of patients or caregivers, and allergists: a qualitative study

Research

Anaphylaxis to hyperallergenic functional foods

Review

Specific immunotherapy by the sublingual route for respiratory allergy

Research

On demand treatment and home therapy of hereditary angioedema in Germany - the Frankfurt experience