Alpha-1-Antitrypsin Deficiency: Epidemiological Studies and Other AATD Associated Diseases

Abstract Alpha-1-antitrypsin deficiency (AATD) is a relatively common but under-recognized condition that predisposes to lung disease (e.g., emphysema, chronic bronchitis, and bronchiectasis), liver disease (e.g., chronic hepatitis, cirrhosis, and hepatocellular carcinoma), and skin disease (i.e., panniculitis). AATD has also been associated with vasculitis [especially anticytoplasmic antibody-positive vasculitides like granulomatosis with polyangiitis (GPA), previously called Wegener’s granulomatosis]. This chapter will first discuss the overall prevalence of AATD and the evidence that AATD is under-recognized. The clinical manifestations of individuals with AATD will then be reviewed, with the discussion of each organ system involvement addressing the epidemiology; clinical features, including signs and symptoms and associated laboratory features; natural history; and prognosis. Where appropriate, the specific clinical manifestations associated with particular genotypes are discussed. The most common clinical sequelae—lung and liver disease—are discussed first, followed by a discussion of panniculitis, vasculitis, and a brief discussion of other clinical conditions for which associations with AATD have been speculated but not confirmed.