CMAJ • October 24, 2006; 175 (9). doi:10.1503/cmaj.060535.
© 2006 CMA Media Inc. or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
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Research

Angioedema without urticaria: a large clinical survey

Lorenza C. Zingale, Laura Beltrami, Andrea Zanichelli, Lorena Maggioni, Emanuela Pappalardo, Benedetta Cicardi and Marco Cicardi

From the Department of Internal Medicine, San Giuseppe Hospital, University of Milan, Milan, Italy

Correspondence to: Dr. Lorenza Zingale, Università degli Studi di Milano, Dipartimento di Medicina Interna, Ospedale San Giuseppe, Via San Vittore 12, 20123 Milano, Italy; fax 39 02 85994165; lorenza.zingale{at}unimi.it

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.




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