Lorena Maggioni

Angioedema without urticaria: a large clinical survey

Background: Angioedema without major urticarial flares (hives) is poorly understood. Its causes are diverse, and little is known about its pathogenic mechanisms. We report on our 11 years of experience with this condition and propose a classification of patients affected by angioedema unaccompanied by urticaria. Methods: From 1993 through 2003 at our outpatient clinic, 929 consecutive patients were examined for recurrent angioedema unaccompanied by urticaria. A detailed history was taken to identify known causes of angioedema, with special attention to external allergenic agents. Each patient underwent a complete physical examination, routine laboratory tests (blood cell count, protein electrophoresis, erythrosedimentation rate, examination of stool for ova and parasites, pharyngeal and urine cultures, sinus and dental radiography, and measurements of antitissue autoantibodies and rheumatoid factor in plasma), and complement parameters (C1 inhibitor, C4 and C1q). Further testing was done when pertinent, based on clinical findings. When all results were negative, response to H1-antihistamine was considered. Results: Angioedema could not be classified in 153 patients who were lost to follow-up (16.4%). Among the 776 cases with adequate data, these types of angioedema were identified: 124 (16%) related to external agents such as a drug, insect bite or foodstuff; 85 (11%) related to treatment with angiotensin-converting enzyme inhibitor; 55 (7%) associated with an autoimmune disease or infection; and 197 (25%) caused by C1 inhibitor deficiency. In the other 315 cases (41%), the etiology was undiscovered: 254 cases (33% of the study sample) were idiopathic histaminergic; 40 (5%) were idiopathic nonhistaminergic; and 21 (3%) had other causes of peripheral or generalyzed edema. Interpretation: Our data indicated that angioedema without urticaria could be classified according to specific clinical and pathogenic characteristics, and we have suggested a work-up for patients experiencing this condition.

High‐molecular‐weight kininogen cleavage correlates with disease states in the bradykinin‐mediated angioedema due to hereditary C1‐inhibitor deficiency

The inherited deficiency of C1‐inhibitor (C1‐INH), which can be quantitative (type I) or qualitative (type II), is characterized by recurrent attacks of oedema, and it is known as hereditary angioedema due to C1‐INH deficiency (HAE‐C1‐INH). The frequency of symptoms varies widely among patients and in the same patient during life.

Complement and contact system activation in acute congestive heart failure patients

Recent experimental data indicate a pathogenic role of complement activation in congestive heart failure (CHF). The aim of this study was to evaluate contact and complement systems activation in patients hospitalized for an acute episode of CHF. Forty‐two of 80 consecutive patients admitted at our hospital with confirmed diagnosis of acute CHF were enrolled. They underwent blood sampling within 24 h from admission (T0) and at clinical stability (T1). Patients were stratified for ejection fraction (EF) based on echocardiographic test. We measured plasma levels of C3, C4, sC5b‐9 and cleaved high molecular weight kininogen (contact activation marker). At T1, C3 levels increased significantly compared to T0 (97 ± 2 versus 104 ± 3% of total pooled plasma, P < 0·01). Classifying patients according to EF, only patients with preserved EF presented a significant increase of C3 from T0 to T1 (99 ± 3 versus 108 ± 4%, P = 0·03). When the sample was stratified according to clinical outcome, C3 (98 ± 3 versus 104 ± 4%, P = 0·03) and sC5b‐9 levels (204 ± 10 versus 230 ± 11 ng/ml, P = 0·03) were increased in patients who had positive outcome after hospitalization. CHF patients with preserved EF and positive outcome after hospitalization showed higher levels of sC5b‐9 in the T1 period compared with T0 (211 ± 14 versus 243 ± 14 ng/ml, P = 0·04). Our results suggest that the complement system reacts differently if CHF occurs with preserved or reduced EF. This finding is interesting if we consider the difference in epidemiology, pathogenesis and possible therapeutic approaches of these two clinical entities.