Successful treatment of a facial attack of angioedema with icatibant in a patient with idiopathic angioedema.

Angioedema (AE) is related to the activation of the contact phase system—kallikrein and generation of bradykinin. Different types of AE are recognized: hereditary or acquired deficit of the C1 inhibitor, drug-related, or idiopathic. Treatment of idiopathic nonhistaminergic AE (IAE) is difficult because corticosteroids, antihistamine drugs, and adrenalin are inefficacious. We describe a patient with an IAE and an acute attack of facial AE that was successfully treated with the bradykinin receptor antagonist icatibant. This case report strengthens the relevance of bradykinin formation in IAE and underlines the effectiveness of icatibant as a therapeutic option in acute IAE. Angioedema (AE) is characterized by recurrent attacks of nonpruritic swelling of subcutaneous and submucosal tissues not associated to urticaria. The pathogenesis of AE is linked to an activation of the contact phase system—kallikrein, which leads to the ultimate generation of bradykinin as the main vasopermeabilizing substance [1]. Different clinical forms of AE are recognized: paradigmatic is hereditary AE (HAE), due to a congenic defect of the complement C1 inhibitor (C1 inh) with an autosomal transmission. In type I HAE, antigenic and functional levels of C1 inh are less than 50% of normal values. Less commonly, there is a dysfunctional C1 inh protein with normal antigenic levels but reduced activity on C1 esterase (HAE type II). Angioedema with a typical appearance of recurrent attacks of dermis and mucosae may occur late in life as an acquired condition, with reduced antigenic and functional C1 inh. Acquired AE is associated to malignancies or lymphoproliferative disorders, monoclonal gammopathies, or other conditions [2]. Angioedema may also represent adverse effects of drugs such as angiotensin-converting enzyme inhibitors, estrogens, or nonsteroidal anti-inflammatory drug. In this latter case, levels of C1 inh are generally not altered or only minimally affected. Finally, in some patients, the occurrence of AE attacks with a clinical onset after the third to fourth decade of life is not associated to C1 inh alteration and absence of other clinical accompanying conditions or drugs (idiopathic AE [IAE]). Bradykinin seems also to play a relevant pathogenic role in IAE. For treatment of AE, corticosteroids, epinephrine, and antihistamine drugs are ineffective, whereas concentrate of plasma-derived C1 inh has long been proved efficacious. Recently, a specific bradykinin B2 receptor antagonist, icatibant, has been introduced for the treatment of HAE attacks [3]. Perhaps, although plasma-derived C1 inh concentrate is very effective in those conditions characterized by reduced or dysfunctional C1 inh such as HAE and acquired AE, it is completely inefficacious in those conditions with normal levels of C1 inh, such as angiotensin-converting enzyme inhibitor–related AE or IAE. Although some beneficial effects have been reported with tranexamic acid in preventing attacks of IAE, at the moment, there is not specific therapy for this disabling condition. We report a case of the successful treatment of a facial AE attack in a patient with IAE. The patient, a 50-year-old white man, complained of the recent appearance of recurrent attacks of AE, involving mainly the facial region. The attacks started about 1 year before, without any precipitating condition and with an increasing frequency reaching 2 to 3 attacks per month. Angioedema attacks were nonpruritic, not associated to urticaria, lasted about 36 hours, and resolved spontaneously. Antihistamine drugs and corticosteroids were almost completely ineffective. The patient was also prescribed a prophylactic dose of levocetirizin (5 mg twice a day) for about a month without any beneficial effect on frequency and severity of AE attacks. Physical examination did not show any relevant sign. Laboratory investigation showed normal levels of C1 inh, C3 and C4, inflammatory markers, autoimmunity, and immunoglobulins (Table). The skin prick test for common inhalants and foods gave negative response while specific immunoglobulin E for foods was in the reference range.