Acquired C1 inhibitor deficiency: Management and prognosis
- Marco Cicardi, MD
Marco Cicardi, MD
- Professor of Medicine
- Università degli Studi di Milano, Italy
Acquired angioedema due to deficiency of C1 esterase inhibitor, also called acquired angioedema and abbreviated C1INH-AAE, is a rare syndrome of recurrent episodes of angioedema, without urticaria, which is associated with B cell lymphoproliferative disorders in some patients . Angioedema typically affects the skin or mucosal tissues of the upper respiratory and gastrointestinal tracts. The swelling is self-limited, although laryngeal involvement may cause fatal asphyxiation. Clinically, this disorder is very similar to hereditary angioedema, although acquired angioedema develops in older patients and is frequently associated with underlying disease, whereas the hereditary disorder presents in younger patients who are otherwise healthy .
This topic review will discuss the management and prognosis of C1INH-AAE. The clinical manifestations, epidemiology, pathogenesis, and diagnosis of this disorder are reviewed elsewhere. (See "Acquired C1 inhibitor deficiency: Clinical manifestations, epidemiology, pathogenesis, and diagnosis".)
Hereditary angioedema, which is caused by mutations in the gene for C1INH, is discussed separately. (See "Hereditary angioedema: Pathogenesis and diagnosis" and "Hereditary angioedema: Epidemiology, clinical manifestations, exacerbating factors, and prognosis" and "Hereditary angioedema: Treatment of acute attacks" and "Hereditary angioedema: General care and long-term prophylaxis".)
OVERVIEW OF MANAGEMENT
The management of a patient with acquired angioedema involves several components :
●Educating the patient about the potential triggers and early recognition of angioedema attacks and ensuring that the patient understands that there is a real risk of fatal asphyxiation with attacks involving the upper airway. (See 'Patient education about laryngeal edema' below and 'Avoidance of exacerbating factors' below.)
- Pappalardo E, Cicardi M, Duponchel C, et al. Frequent de novo mutations and exon deletions in the C1inhibitor gene of patients with angioedema. J Allergy Clin Immunol 2000; 106:1147.
- Cicardi M, Aberer W, Banerji A, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy 2014; 69:602.
- Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol 2013; 131:1491.
- Zuraw BL, Banerji A, Bernstein JA, et al. US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract 2013; 1:458.
- Cicardi M, Bork K, Caballero T, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy 2012; 67:147.
- Cicardi M, Zingale LC, Pappalardo E, et al. Autoantibodies and lymphoproliferative diseases in acquired C1-inhibitor deficiencies. Medicine (Baltimore) 2003; 82:274.
- Cicardi M, Bergamaschini L, Cugno M, et al. Pathogenetic and clinical aspects of C1 inhibitor deficiency. Immunobiology 1998; 199:366.
- Zanichelli A, Badini M, Nataloni I, et al. Treatment of acquired angioedema with icatibant: a case report. Intern Emerg Med 2011; 6:279.
- Zanichelli A, Bova M, Coerezza A, et al. Icatibant treatment for acquired C1-inhibitor deficiency: a real-world observational study. Allergy 2012; 67:1074.
- Cicardi M, unpublished data.
- Patel NS, Fung SM, Zanichelli A, et al. Ecallantide for treatment of acute attacks of acquired C1 esterase inhibitor deficiency. Allergy Asthma Proc 2013; 34:72.
- Schneider L, Lumry W, Vegh A, et al. Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor. J Allergy Clin Immunol 2007; 120:416.
- Agostoni A, Aygören-Pürsün E, Binkley KE, et al. 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.
- Markovic SN, Inwards DJ, Frigas EA, Phyliky RP. Acquired C1 esterase inhibitor deficiency. Ann Intern Med 2000; 132:144.
- Bork K, Fischer B, Dewald G. Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy. Am J Med 2003; 114:294.
- Rousset-Jablonski C, Thalabard JC, Gompel A. Tamoxifen contraindicated in women with hereditary angioedema? Ann Oncol 2009; 20:1281.
- Ricketti AJ, Cleri DJ, Ramos-Bonner LS, Vernaleo JR. Hereditary angioedema presenting in late middle age after angiotensin-converting enzyme inhibitor treatment. Ann Allergy Asthma Immunol 2007; 98:397.
- Gelfand JA, Boss GR, Conley CL, et al. Acquired C1 esterase inhibitor deficiency and angioedema: a review. Medicine (Baltimore) 1979; 58:321.
- Farkas H, Gyeney L, Majthényi P, et al. Angioedema due to acquired C1-esterase inhibitor deficiency in a patient with Helicobacter pylori infection. Z Gastroenterol 1999; 37:513.
- Cicardi M, Frangi D, Bergamaschini L, et al. Acquired C1 inhibitor deficiency with angioedema symptoms in a patient infected with Echinococcus granulosus. Complement 1985; 2:133.
- Jung M, Rice L. Unusual autoimmune nonhematologic complications in chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk 2011; 11 Suppl 1:S10.
- 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.
- Széplaki G, Varga L, Szépvölgyi A, et al. Acquired angioedema associated with primary antiphospholipid syndrome in a patient with antithrombin III deficiency. Int Arch Allergy Immunol 2008; 146:164.
- Schreiber AD, Zweiman B, Atkins P, et al. Acquired angioedema with lymphoproliferative disorder: association of C1 inhibitor deficiency with cellular abnormality. Blood 1976; 48:567.
- Levi M, Hack CE, van Oers MH. Rituximab-induced elimination of acquired angioedema due to C1-inhibitor deficiency. Am J Med 2006; 119:e3.
- Hassan A, Amarger S, Tridon A, et al. Acquired angioedema responding to rituximab. Acta Derm Venereol 2011; 91:733.
- Branellec A, Bouillet L, Javaud N, et al. Acquired C1-inhibitor deficiency: 7 patients treated with rituximab. J Clin Immunol 2012; 32:936.
- Lam DH, Levy NB, Nickerson JM, et al. Acquired angioedema and marginal zone lymphoma. J Clin Oncol 2012; 30:e151.
- Sánchez-Cano D, Callejas-Rubio JL, Lara-Jiménez MA, et al. Successful use of rituximab in acquired C1 inhibitor deficiency secondary to Sjogren's syndrome. Lupus 2008; 17:228.
- Ziakas PD, Giannouli S, Psimenou E, et al. Acquired angioedema: a new target for rituximab? Haematologica 2004; 89:ELT13.
- Castelli R, Wu MA, Arquati M, et al. High prevalence of splenic marginal zone lymphoma among patients with acquired C1 inhibtor deficiency. Br J Haematol 2016; 172:902.
- Maruta T, Tateishi M, Fujie Y, et al. [Anesthesia and perioperative management in a patient with acquired angioedema]. Masui 2011; 60:862.
- Farkas H, Kőhalmi KV, Zotter Z, et al. Short-term prophylaxis in a patient with acquired C1-INH deficiency. J Allergy Clin Immunol 2014; 134:478.
- Levi M, Choi G, Picavet C, Hack CE. 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.
- 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.
- Hauptmann G, Mayer S, Lang JM, et al. Treatment of acquired C1-inhibitor deficiency with danazol. Ann Intern Med 1977; 87:577.
- Tengborn L, Blombäck M, Berntorp E. Tranexamic acid--an old drug still going strong and making a revival. Thromb Res 2015; 135:231.
- Cicardi M, Beretta A, Colombo M, et al. Relevance of lymphoproliferative disorders and of anti-C1 inhibitor autoantibodies in acquired angio-oedema. Clin Exp Immunol 1996; 106:475.
- OVERVIEW OF MANAGEMENT
- PREPARATION FOR ACUTE ANGIOEDEMA EPISODES
- Patient education about laryngeal edema
- Written treatment plan
- Airway management in laryngeal edema
- Pharmacologic treatment of acute attacks
- - C1 inhibitor concentrate
- - Recombinant C1 inhibitor
- - Icatibant
- - Plasma
- - Ecallantide
- - Ineffective therapies
- AVOIDANCE OF EXACERBATING FACTORS
- ASSOCIATED DISORDERS
- Monitoring for development
- Management of identified disorders
- Monitoring MGUS
- PROPHYLAXIS TO PREVENT ANGIOEDEMA EPISODES
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS