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

Open Access 01-12-2010 | Review

Acquired angioedema

Authors: Marco Cicardi, Andrea Zanichelli

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

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Abstract

Acquired angioedema (AAE) is characterized by acquired deficiency of C1 inhibitor (C1-INH), hyperactivation of the classical pathway of human complement and angioedema symptoms mediated by bradykinin released by inappropriate activation of the contact-kinin system. Angioedema recurs at unpredictable intervals, lasts from two to five days and presents with edema of the skin (face, limbs, genitals), severe abdominal pain with edema of the gastrointestinal mucosa, life-threateing edema of the upper respiratory tract and edema of the oral mucosa and of the tongue. AAE recurs in association with various conditions and particularly with different forms of lymphoproliferative disorders. Neutralizing autoantibodies to C1-INH are present in the majority of patients. The therapeutic approach to a patient with AAE should first be aimed to avoid fatalities due to angioedema and then to avoid the disability caused be angioedema recurrences. Acute attacks can be treated with plasma-derived C1-INH, but some patients become non-responsive and in these patients the kallikrein inhibitor ecallantide and the bradykinin receptor antagonist icatibant can be effective. Angioedema prophylaxis is performed using antifibrinolytic agents and attenuated androgens with antifibrinolytic agents providing somewhat better results. Treatment of the associated disease can resolve AAE in some patients.
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Literature
1.
Caldwell JR, Ruddy S, Schur PH, Austen KF: Acquired C1 inhibitor deficiency in lymphosarcoma. Clin Immunol Immunopathol. 1972, 1: 39-52. 10.1016/0090-1229(72)90006-2.CrossRef
2.
Zingale LC, Castelli R, Zanichelli A, Cicardi M: Acquired deficiency of the inhibitor of the first complement component: presentation, diagnosis, course, and conventional management. Immunol Allergy Clin North Am. 2006, 26: 669-90. 10.1016/j.iac.2006.08.002.CrossRefPubMed
3.
Bygum A: Hereditary angio-oedema in Denmark: a nationwide survey. Br J Dermatol. 2009, 161: 1153-8. 10.1111/j.1365-2133.2009.09366.x.CrossRefPubMed
4.
Zuraw BL: Clinical practice. Hereditary angioedema. N Engl J Med. 2008, 359: 1027-36. 10.1056/NEJMcp0803977.CrossRefPubMed
5.
Agostoni A, Aygören-Pürsün E, Binkley KE, Blanch A, Bork K, Bouillet L, Bucher C, Castaldo AJ, Cicardi M, Davis AE, De Carolis C, Drouet C, Duponchel C, Farkas H, Fáy K, Fekete B, Fischer B, Fontana L, Füst G, Giacomelli R, Gröner A, Hack CE, Harmat G, Jakenfelds J, Juers M, Kalmár L, Kaposi PN, Karádi I, Kitzinger A, Kollár T: 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
6.
Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A: Plasma bradykinin in angio-oedema. Lancet. 1998, 351: 1693-7. 10.1016/S0140-6736(97)09137-X.CrossRefPubMed
7.
Davis AE: C1 inhibitor and hereditary angioneurotic edema. Annu Rev Immunol. 1988, 6: 595-628. 10.1146/annurev.iy.06.040188.003115.CrossRefPubMed
8.
Zingale LC, Zanichelli A, Deliliers DL, Rondonotti E, De Franchis R, Cicardi M: Successful resolution of bowel obstruction in a patient with hereditary angioedema. Eur J Gastroenterol Hepatol. 2008, 20: 583-7. 10.1097/MEG.0b013e3282f1c995.CrossRefPubMed
9.
Bouillet-Claveyrolas L, Ponard D, Drouet C, Massot C: Clinical and biological distinctions between type I and type II acquired angioedema. Am J Med. 2003, 115: 420-1. 10.1016/S0002-9343(03)00396-6.CrossRefPubMed
10.
Eck SL, Morse JH, Janssen DA, Emerson SG, Markovitz DM: Angioedema presenting as chronic gastrointestinal symptoms. Am J Gastroenterol. 1993, 88: 436-9.PubMed
11.
Schreiber AD, Zweiman B, Atkins P, Goldwein F, Pietra G, Atkinson B, Abdou NI: Acquired angioedema with lymphoproliferative disorder: association of C1 inhibitor deficiency with cellular abnormality. Blood. 1976, 48: 567-80.PubMed
12.
Hauptmann G, Lang JM, North ML, Oberling F, Mayer G, Lachmann P: Acquired c1-inhibitor deficiencies in lymphoproliferative diseases with serum immunoglobulin abnormalities. A study of three cases. Blut. 1976, 32: 195-206. 10.1007/BF00995913.CrossRefPubMed
13.
Castelli R, Deliliers DL, Zingale LC, Pogliani EM, Cicardi M: Lymphoproliferative disease and acquired C1 inhibitor deficiency. Haematologica. 2007, 92: 716-8. 10.3324/haematol.10769.CrossRefPubMed
14.
Hauptmann G, Petitjean F, Lang JM, Oberling F: Acquired C1 inhibitor deficiency in a case of lymphosarcoma of the spleen. Reversal of complement abnormalities after splenectomy. Clin Exp Immunol. 1979, 37: 523-31.PubMedCentralPubMed
15.
Levi M, Hack CE, van Oers MH: Rituximab-induced elimination of acquired angioedema due to C1-inhibitor deficiency. Am J Med. 2006, 119: e3-5. 10.1016/j.amjmed.2005.09.018.CrossRefPubMed
16.
Jackson J, Sim RB, Whelan A, Feighery C: An IgG autoantibody which inactivates C1-inhibitor. Nature. 1986, 323: 722-4. 10.1038/323722a0.CrossRefPubMed
17.
Alsenz J, Bork K, Loos M: Autoantibody-mediated acquired deficiency of C1 inhibitor. N Engl J Med. 1987, 316: 1360-6. 10.1056/NEJM198705283162202.CrossRefPubMed
18.
Malbran A, Hammer CH, Frank MM, Fries LF: Acquired angioedema: observations on the mechanism of action of autoantibodies directed against C1 esterase inhibitor. J Allergy Clin Immunol. 1988, 81: 1199-204. 10.1016/0091-6749(88)90891-3.CrossRefPubMed
19.
Mandle R, Baron C, Roux E, Sundel R, Gelfand J, Aulak K, Davis AE, Rosen FS, Bing DH: Acquired C1 inhibitor deficiency as a result of an autoantibody to the reactive center region of C1 inhibitor. J Immunol. 1994, 152: 4680-5.PubMed
20.
Alsenz J, Loos M: The acquired C1-INH deficiencies with autoantibodies (AAE type II). Behring Inst Mitt. 1989, 165-72. 84
21.
Cicardi M, Beretta A, Colombo M, Gioffre D, Cugno M, Agostoni A: Relevance of lymphoproliferative disorders and of anti-C1 inhibitor autoantibodies in acquired angio-oedema. Clin Exp Immunol. 1996, 106: 475-80. 10.1046/j.1365-2249.1996.d01-866.x.PubMedCentralCrossRefPubMed
22.
Cugno M, Castelli R, Cicardi M: Angioedema due to acquired C1-inhibitor deficiency: a bridging condition between autoimmunity and lymphoproliferation. Autoimmun Rev. 2008, 8: 156-9. 10.1016/j.autrev.2008.05.003.CrossRefPubMed
23.
Nettis E, Colanardi MC, Loria MP, Vacca A: Acquired C1-inhibitor deficiency in a patient with systemic lupus erythematosus: a case report and review of the literature. Eur J Clin Invest. 2005, 35: 781-4. 10.1111/j.1365-2362.2005.01571.x.CrossRefPubMed
24.
Nagy L, Hannema A, Swaak A: Acquired C1 inhibitor deficiency associated with systemic lupus erythematosus, secondary antiphospholipid syndrome and IgM monoclonal paraproteinaemia. Clin Rheumatol. 1999, 18: 56-8. 10.1007/s100670050054.CrossRefPubMed
25.
Ochonisky S, Intrator L, Wechsler J, Revuz J, Bagot M: Acquired C1 inhibitor deficiency revealing systemic lupus erythematosus. Dermatology. 1993, 186: 261-3. 10.1159/000247366.CrossRefPubMed
26.
Nakamura S, Yoshinari M, Saku Y, Hirakawa K, Miishima C, Murai K, Tokiyama K, Fujishima M: Acquired C1 inhibitor deficiency associated with systemic lupus erythematosus affecting the central nervous system. Ann Rheum Dis. 1991, 50: 713-6. 10.1136/ard.50.10.713.PubMedCentralCrossRefPubMed
27.
Wasserfallen JB, Spaeth P, Guillou L, Pecoud AR: Acquired deficiency in C1-inhibitor associated with signet ring cell gastric adenocarcinoma: a probable connection of antitumor-associated antibodies, hemolytic anemia, and complement turnover. J Allergy Clin Immunol. 1995, 95: 124-31. 10.1016/S0091-6749(95)70160-5.CrossRefPubMed
28.
Cohen SH, Koethe SM, Kozin F, Rodey G, Arkins JA, Fink JN: Acquired angioedema associated with rectal carcinoma and its response to danazol therapy. Acquired angioedema treated with danazol. J Allergy Clin Immunol. 1978, 62: 217-21. 10.1016/0091-6749(78)90210-5.CrossRefPubMed
29.
Varvarovska J, Sykora J, Stozicky F, Chytra I: Acquired angioedema and Helicobacter pylori infection in a child. Eur J Pediatr. 2003, 162: 707-9. 10.1007/s00431-003-1250-7.CrossRefPubMed
30.
Reche M, Caballero T, López-Trascasa M, Arribas JR, López Serrano MC: Angioedema and transient acquired C1 inhibitor functional deficiency in HIV infection: case report. Aids. 2002, 16: 1561-10.1097/00002030-200207260-00016.CrossRefPubMed
31.
Farkas H, Gyeney L, Majthenyi P, Fust G, Varga L: Angioedema due to acquired C1-esterase inhibitor deficiency in a patient with Helicobacter pylori infection. Z Gastroenterol. 1999, 37: 513-8.PubMed
32.
Minh D, Czink E, Fust G, Hollan SR: Acquired C1-esterase inhibitor deficiency and recurrent herpes infection in a patient with chronic lymphocytic leukemia. Diagn Immunol. 1983, 1: 68-71.PubMed
33.
Cicardi M, Frangi D, Bergamaschini L, Gardinali M, Sacchi G, Agostoni A: Acquired C1 inhibitor deficiency with angioedema symptoms in a patient infected with Echinococcus granulosus. Complement. 1985, 2: 133-9.PubMed
34.
Wagenaar-Bos IG, Drouet C, Aygören-Pursun E, Bork K, Bucher C, Bygum A, Farkas H, Fust G, Gregorek H, Hack CE, Hickey A, Joller-Jemelka HI, Kapusta M, Kreuz W, Longhurst H, Lopez-Trascasa M, Madalinski K, Naskalski J, Nieuwenhuys E, Ponard D, Truedsson L, Varga L, Nielsen EW, Wagner E, Zingale L, Cicardi M, van Ham SM: Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations. J Immunol Methods. 2008, 338: 14-20. 10.1016/j.jim.2008.06.004.CrossRefPubMed
35.
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: 714-8. 10.1001/archinte.161.5.714.CrossRefPubMed
36.
Frank MM, Jiang H: New therapies for hereditary angioedema: disease outlook changes dramatically. J Allergy Clin Immunol. 2008, 121: 272-80. 10.1016/j.jaci.2007.11.019.CrossRefPubMed
37.
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: 1444-8. 10.1056/NEJM197612232952602.CrossRefPubMed
38.
Melamed J, Alper CA, Cicardi M, Rosen FS: The metabolism of C1 inhibitor and C1q in patients with acquired C1- inhibitor deficiency. J Allergy Clin Immunol. 1986, 77: 322-6. 10.1016/S0091-6749(86)80111-7.CrossRefPubMed
39.
Frank MM, Sergent JS, Kane MA, Alling DW: Epsilon aminocaproic acid therapy of hereditary angioneurotic edema. A double-blind study. N Engl J Med. 1972, 286: 808-12. 10.1056/NEJM197204132861503.CrossRefPubMed
40.
Sheffer AL, Austen KF, Rosen FS: Tranexamic acid therapy in hereditary angioneurotic edema. N Engl J Med. 1972, 287: 452-4. 10.1056/NEJM197208312870907.CrossRefPubMed
41.
Donaldson VH, Rosen FS, Bing DH: Role of the second component of complement (C2) and plasmin in kinin release in hereditary angioneurotic edema (H.A.N.E.) plasma. Trans Assoc Am Physicians. 1977, 90: 174-83.PubMed
42.
Cugno M, Hack CE, de Boer JP, Eerenberg AJ, Agostoni A, Cicardi M: Generation of plasmin during acute attacks of hereditary angioedema. J Lab Clin Med. 1993, 121: 38-43.PubMed
43.
Cugno M, Cicardi M, Agostoni A: Activation of the contact system and fibrinolysis in autoimmune acquired angioedema: a rationale for prophylactic use of tranexamic acid. J Allergy Clin Immunol. 1994, 93: 870-6. 10.1016/0091-6749(94)90380-8.CrossRefPubMed
44.
Cugno M, Cicardi M, Coppola R, Agostoni A: Activation of factor XII and cleavage of high molecular weight kininogen during acute attacks in hereditary and acquired C1-inhibitor deficiencies. Immunopharmacology. 1996, 33: 361-4. 10.1016/0162-3109(96)00086-0.CrossRefPubMed
45.
Cugno M, Cicardi M, Bottasso B, Coppola R, Paonessa R, Mannucci PM, Agostoni A: Activation of the coagulation cascade in C1-inhibitor deficiencies. Blood. 1997, 89: 3213-8.PubMed
46.
Levi M, Choi G, Picavet C, Hack C: Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency. J Allergy Clin Immunol. 2006, 117: 904-8. 10.1016/j.jaci.2006.01.002.CrossRefPubMed
47.
Bork K, Witzke G: Long-term prophylaxis with C1-inhibitor (C1 INH) concentrate in patients with recurrent angioedema caused by hereditary and acquired C1-inhibitor deficiency. J Allergy Clin Immunol. 1989, 83: 677-82. 10.1016/0091-6749(89)90082-1.CrossRefPubMed
48.
Martinez-Saguer I, Rusicke E, Aygören-Pürsün E, von Hentig N, Klingebiel T, Kreuz W: Pharmacokinetic analysis of human plasma-derived pasteurized C1-inhibitor concentrate in adults and children with hereditary angioedema: a prospective study. Transfusion. 2010, 50: 354-60. 10.1111/j.1537-2995.2009.02394.x.CrossRefPubMed
Metadata
Title
Acquired angioedema
Authors
Marco Cicardi
Andrea Zanichelli
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/10.1186/1710-1492-6-14

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