SYSTEMIC NECROTIZING VASCULITIDES IN SEVERE ALPHA(1)-ANTITRYPSIN DEFICIENCY

We describe the clinical presentation and outcome in a series of eight patients with systemic necrotizing vasculitis and severe alpha(1)-ant itrypsin (AAT) deficiency followed up at three Swedish hospitals durin g. 1968-92. We also review six other cases reported in the literature during the same period. Diagnosis of severe AAT deficiency was based o n the presence of the PiZZ phenotype, or low plasma total trypsin inhi bitory capacity, or a low plasma AAT concentration (10-40% of the norm al mean value) and presence of the PiSZ or PiFZ phenotype. The diagnos is of systemic vasculitis was biopsy-verified in all eight patients. P retreatment laboratory findings, treatment protocol, and outcome were reviewed in each of the 14 patients. Of the eight patients in the Swed ish series, six had systemic vasculitis of the microscopic polyangiiti s form, one had Wegener's granulomatosis, and another had Henoch-Schon lein purpura. In the series as a whole (n=14), median age at diagnosis was 48 years (range 44-84), the median number of affected organs was eight, and all 14 patients had skin involvement, and either venal or j oint involvement (in most cases both); 71% (10/14) had emphysema; 57% (8/14) had hepatic abnormalities (two having cirrhosis, two fibrosis, and one multiple aneurysms in hepatic arteries); one patient who prese nted with acute ulcerative colitis developed manifest vasculitic syndr ome three years later; and 64% (9/14) died, the major cause of death b eing renal failure. This syndrome, characterized by multiple organ inv olvement and fatal outcome, has been underdiagnosed. Physicians should be alert to the presence of the PiZ AAT deficiency gene in patients w ith systemic vasculitis, especially when the course is progressive or when the patient also has emphysema or cirrhosis. Awareness of those f eatures may aid prompt recognition and enable early treatment.