Acquired Deficiency of the Inhibitor of the First Complement Component: Presentation, Diagnosis, Course, and Conventional Management Lorenza Chiara Zingale, MD a , Roberto Castelli, MD b , Andrea Zanichelli, MD a , Marco Cicardi, MD a, * a Department of Internal Medicine, San Giuseppe HospitaldAFaR (Ospedale San Giuseppe), University of Milan, Via San Vittore 12, 20123 Milano, Italy b Department of Internal Medicine, IRCCS Fondazione Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milano, Italy Acquired first complement component inhibitor deficiency is a rare syn- drome characterized by consumption of the inhibitor of the first comple- ment component (C1-INH) and hyperactivation of the classic complement pathway. The condition is frequently referred in the literature as ‘‘acquired angioedema,’’ but this term could generate confusion with other forms of nonhereditary angioedema characterized by normal C1-INH; hence, the au- thors prefer not to use it and to refer to this condition as angioedema with acquired C1-INH deficiency. Caldwell and colleagues [1] described the first patient in 1972. Since that time, several other cases have been reported, mostly associated with lym- phoproliferative disorders. In 1986, Jackson and colleagues [2] discovered an autoreactive immunoglobulin G against C1-INH in a patient who had angioedema and acquired C1-INH deficiency. This finding demonstrated that an autoimmune mechanism could be the cause of acquired C1-INH de- ficiency. The relationship between lymphoproliferative-related and autoim- mune C1-INH deficiency has been and continues to be a matter of debate, reflecting the uncertainty in defining the etiopathogenesis of this condition (Fig. 1). * Corresponding author. E-mail address: marco.cicardi@unimi.it (M. Cicardi). 0889-8561/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.iac.2006.08.002 immunology.theclinics.com Immunol Allergy Clin N Am 26 (2006) 669–690