TYPE-I HEREDITARY ANGIO-EDEMA - VARIABILITY OF CLINICAL PRESENTATION AND COURSE WITHIN 2 LARGE KINDREDS

Objectives. Hereditary angiooedema (C1-inhibitor deficiency) is a dise ase with protean manifestations which is often misdiagnosed initially. The purpose of this study was to delineate the clinical spectrum and course of this potentially life-threatening disease. Setting. Ten memb ers of two unrelated affected kindreds were repeatedly hospitalized in our service with attacks of angiooedema. Among the 271 members of the two kindreds 69 were identified who reported typical attacks. Design and subjects. Detailed information on the clinical course and laborato ry data (C1-inhibitor concentration and activity, C4 concentration) we re obtained from 59 of the 69 affected subjects. Results. C1-inhibitor concentration and activity were low in all affected patients. The dis ease had become manifest by age 30 years in 98%. Most patients suffere d from attacks of subcutaneous swellings and abdominal pain, and half of the patients have had attacks affecting the airways. The frequency of attacks ranged from less than one to over 26 per year. Forty-two pe r cent had to be hospitalized at least once. Four have died of acute a irway obstruction. Thirty-eight attacks in 10 patients hospitalized in our service were all treated successfully with fresh frozen plasma or with C1-inhibitor concentrate. Trauma, stress, insect stings and food stuff were triggering factors, but the majority of attacks occurred wi thout an identifiable trigger. Oral contraceptives and pregnancy led t o worsening of symptoms. Nonetheless, all 36 pregnancies reported were carried to term. Twenty-five patients were on continuous treatment wi th attenuated androgens or tranexamic acid, but only seven were free o f attacks in the year preceding the survey. Conclusion. Hereditary ang iooedema is an autosomal dominant disease with great variability of cl inical expression and severity, even within a single kindred. It often goes unrecognized over years, and it may lead to death if, in case of impending airway obstruction, specific therapy is not instituted.