Giuliano Bertazzoni 1 Chiara Boccardo 2 Valentina Di Biagio 2 Enrico Baldini 3 Lorena Cipollone 2 1 Department of Internal Medicine and Medical Specialties, “Sapienza” University of Rome, Italy 2 UOC Emergency Medicine, Department of Emergency, “Policlinico Umberto I”, Rome, Italy 3 Postgraduate School in Emergency Medicine, “Sapienza” University of Rome, Italy Corresponding author: Giuliano Bertazzoni Department of Internal Medicine and Medical Specialties, “Sapienza” University of Rome Viale del Policlinico 155 00161 Rome, Italy E-mail: giuliano.bertazzoni@uniroma1.it Abstract Introduction: drug-induced angioedema is a trans- ient swelling of the subcutaneous layer of the skin or submucosal layer of the respiratory or gastroin- testinal tracts. These drugs decrease the activity of the enzyme responsible for the degradation of bradykinin, which is then overproduced causing vasodilation and increased permeability. The aim of this piece of research is to identify descriptions of new drugs that can induce angioedema, in light of the latest scientific discoveries. Materials and methods: a bibliographic research was conducted using keyword “angioedema drug- induced ” limited to human race, identifying 267 articles in the last 5 years (2012-2016). Exclusion criterias were applied and the data obtained was organized in a database. The overall sample is composed of 5.387 patients who have had angioe- dema and are reported in 12 articles; in 4.732 ca- ses angioedema is due to one (or more) drugs. Results: the average age of patients with angioe- dema is 65 +/- 11 years, with a slight predominan- ce of the female gender. Some of these patients were already hospitalized, generally in Critical Ca- re Units such as the Stroke Unit; some others were directly hospitalized from the Emergency Room. Discussion: evidence has shown bradykinin pla- ying a crucial role in the pathogenesis of most forms of non-allergic angioedema, while histamine acts as the major biological mediator in allergic angioedema, with urticaria, rash and flushing, and bronchocostriction. This review highlights the need of training for both emergency physicians in Emergency Departments, and nurses in Triage sta- tions on the diagnosis of this disease that, whilst rare, may be induced by several drugs, whose number is growing. KEY WORDS: angioedema, drug, emergency. Introduction Drug-induced angioedema is a transient swelling of the subcutaneous layer of the skin or submucosal la- yer of the respiratory or gastrointestinal tracts; can be non-responsive to antihistamines, cortisone and epi- nephrine (1-6). These drugs decrease the activity of the enzyme responsible for the degradation of brady- kinin, which is then overproduced causing vasodila- tion and increased permeability. Acquired angioedema is characterized by absence of family history, late on- set of symptoms, and failure to respond to antihistami- nes, cortisone and epinephrine (7, 8). The clinical presentation is similar to that of hereditary angioedema. Clinical manifestations usually occur wi- thin the second decade of life in the case of hereditary angioedema, and after the fourth decade in the case of acquired angioedema. Angioedema consists of re- curring, self-limiting swellings without any associated urticaria or itch. Swellings usually last 2-4 days. ACE-I is the first group of drugs to be discovered as a cause of angioedema, however several new drugs ha- ve been recently reported. Most of the articles in the literature identify drug-induced angioedema as a re- sult of treatments with angiotensin receptor blockers (ARB), and direct renin inhibitors, all antihypertensive drugs also used to treat heart failure (9). Other drugs such as inhibitors dipeptidyl peptidase IV (oral agents) and diclofenac (NSAID), have now been reported in studies conducted between 2008 and 2010 (6, 10). A literature review for the years 2010-2011 re- veals more than 250 cases of drug-induced angioede- ma (11-13), and other studies have described cases of angioedema in patients taking antidiabetic oral (inhibi- tors of DPP-4) or thrombolytic therapy with tissue pla- sminogen activator (14-16). To sum up, on the basis of clinical diagnosis, studies have identified new drugs that may be involved in the genesis of angioedema; it is still missing the objective support of the laboratory. Prevention & Research 2016; 5(4):101-108 101 Review article Drug-induced angioedema: an update on new cases and new drugs @ CIC Edizioni Internazionali