AATD is usually diagnosed following pulmonary or hepatic manifestations; however, rarer presentations may alert clinicians to its presence. Of these, panniculitis and anti-neutrophilic cytoplasmic autoantibody (ANCA)-positive vasculitis are the most commonly reported. Panniculitis is a histopathological finding from skin biopsies attributable to many causes. However, lobular fat necrosis with dense neutrophil infiltration on biopsy may represent AAT-related disease, a subtype associated with significant morbidity and frequent relapses. Treatment with doxycycline, dapsone and AAT replacement therapy have all shown reliable effect, with the latter particularly effective in refractory disease. A significant body of work has been performed examining the role of AATD variants in ANCA vasculitis. The association between antibodies against both myeloperoxidase and proteinase (PR)3 (both neutrophil derived) and AATD has been shown to be significant, with clear evidence of over-representation of the AATD variants in ANCA vasculitis cohorts. While in vitro mechanistic evidence exists demonstrating a role for AAT replacement in anti-PR3 positive disease, there is little evidence for its use in vivo. In addition to these two conditions, AATD has also been associated with other systemic illness but the associations are as yet not fully proven.