A ngioedema -a self-limited, localized swelling that involves subcutaneous tissues or mucosa -can involve the face and other areas. Skin colour is usually unchanged, although it may be heralded by erythema marginatum. There is no burning sensation and itchiness is generally absent. Lesions tend to be large and without clear demarcation; most resolve within 2 or 3 days. 1Frequently the result of the release of histamine, angioedema is often associated with urticarial flares (hives; the association is often called urticaria-angioedema syndrome) and responds to antihistamines and corticosteroids.2 Occasionally, angioedema occurs without urticaria, does not respond to drugs against allergies and tends to last 5-7 days -for example, when it is caused by a deficiency in plasma of C1 esterase inhibitor (C1Inh).To investigate and form classifications for different forms of angioedema unaccompanied by urticaria, we analyzed 929 consecutive patients referred to our university hospital over an 11-year period (January 1993 through December 2003). MethodsOur outpatient clinic for angioedema is a tertiary-level centre where patients are referred mostly by specialists. All clinic patients with a history of recurrent angioedema without major urticaria between January 1993 and December 2003 were considered for the study.From each patient, we obtained a clinical history with information about allergies and their relation to potential causative agents (e.g., foods, drugs, chemicals) and carried out a complete physical examination. We obtained sinus and dental radiographs as well as test results for blood cell count, serum protein electrophoresis, erythrocyte sedimentation rate, Creactive protein, hepatic enzymes, renal function, thyroid function and anti-tissue antibodies (antinuclear antibodies and antibodies to extractable nuclear antigens, to doublestranded DNA, to thyroglobulin and to thyroperoxidase). Stool examinations (for ova and parasites) and urinanalyses were carried out, and pharyngeal and urine samples were cultured. Further specific analyses were performed if deemed necessary.If all test results were negative, response to long-term H1-

Even with all the limitations on any observational analysis, this long-term study suggests for the first time that patients with angioedema started while on ACE-I treatment seem to have a condition predisposing to angioedema that is elicited by the treatment with these drugs. Further studies in this field appear advocated due to the potential severity of angioedema attacks.

Angiotensin-converting enzyme inhibitor-related angioedema is a well documented condition, which seems to occur in up to 1% of treated patients. It represents a problem for both the clinician and the patient: for the clinician, the diagnosis may be difficult due to its peculiar clinical characteristics, whereas for the misdiagnosed patient the delay prolongs a potentially dangerous situation. If the drug is not discontinued, the attacks tend to become worse and even life-threatening. There are now evidences that increased levels of bradykinin have an important role in the pathophysiology of attacks and, moreover, there are genetic factors that render certain individuals susceptible to angiotensin-converting enzyme inhibitor-related angioedema. In this review, the authors analyse the pathogenetic mechanism, the clinical presentation, the management and future perspectives of research on this condition.

In this small sample of treatment-naive hypertensive patients, the antihypertensive effect of barnidipine 10 mg once daily was not significantly different from that of amlodipine 5 to 10 mg once daily.