title: Autoantibodies and lymphoproliferative diseases in acquired C1-inhibitor deficiencies.
abstract: Angioedema due to acquired C1-inhibitor (C1-INH) deficiency (also referred to as "acquired angioedema") is a rare, life-threatening disease with poorly defined etiology, therapy, and prognosis. To define the profile of acquired C1-INH deficiency and to facilitate the clinical approach to these patients, we report on 23 patients with acquired C1-INH deficiency followed for up to 24 years (median, 8 yr), and review the literature. We measured C1-INH activity with chromogenic assay and detected autoantibodies to C1-INH by enzyme-linked immunosorbent assay (ELISA). Median age at onset of angioedema was 57 years (range, 39-75 yr). All patients had C1-INH function and C4 antigen below 50% of normal. C1q was reduced in 17 patients. Autoantibodies to C1-INH were present in 17 patients. Long-term prophylaxis of attacks with danazol was effective in 2 of 6 patients, and with tranexamic acid, in 12 of 13 patients. Therapy with C1-INH plasma concentrate was necessary in 12 patients: 9 had rapid positive response and 3 became progressively resistant. Associated diseases at the last follow-up were non-Hodgkin lymphomas (3 patients), chronic lymphocytic leukemia (1 patient), breast cancer (1 patient), monoclonal gammopathies of uncertain significance (13 patients). In 4 patients no pathologic condition could be demonstrated. Compared with the general population, patients with acquired C1-INH deficiency present higher risk for B-cell malignancies, but not for progression of monoclonal gammopathies of uncertain significance to malignancy. Antifibrinolytic agents are more effective than attenuated androgens in long-term prophylaxis. Patients with acquired C1-INH deficiency may be resistant to replacement therapy with C1-INH plasma concentrate.
authors.affiliation: Department of Internal Medicine, University of Milan, IRCCS Ospedale Maggiore, Milan, Italy. marco.cicardi@unimi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Cicardi
authors.forename: Lorenza C
authors.initials: LC
authors.lastname: Zingale
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pappalardo
authors.forename: Anna
authors.initials: A
authors.lastname: Folcioni
authors.forename: Angelo
authors.initials: A
authors.lastname: Agostoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000799:Angioedema / Q000209:etiology* / Q000517:prevention & control; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology*; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D015922:Complement C1q / Q000172:deficiency; D003181:Complement C4 / Q000172:deficiency; D003613:Danazol / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015151:Immunoblotting; D008232:Lymphoproliferative Disorders / Q000150:complications* / Q000276:immunology*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications* / Q000378:metabolism*; D008875:Middle Aged; D015843:Serpins / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use
chemical_list: D000933:Antifibrinolytic Agents; D001323:Autoantibodies; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003181:Complement C4; D004965:Estrogen Antagonists; C469952:SERPING1 protein, human; D015843:Serpins; D015922:Complement C1q; D003613:Danazol