Fulminant hepatic failure in the setting of progressive ANCA-associated vasculitis associated with a rare alpha-1 antitrypsin phenotype, ’PiEE'

Abstract

Abnormalities in alpha-1 antitrypsin (AAT) proteins are risk factors for human disease. While the most common is AAT deficiency, a genetic disorder associated with chronic obstructive pulmonary disease, additional disorders associated with AAT abnormalities are increasingly recognised. We describe a middle-aged woman who presented with fulminant hepatic and multiorgan failure. Evaluation revealed the patient to have a rare AAT phenotype PiEE. Her clinical presentation was consistent with antineutrophilic cytoplasmic antibody-associated vasculitis, and her history suggested features of panniculitis. This is the first description of this rare homozygous AAT phenotype and possible disease associations with the ’E' protein. Given that abnormal AAT are under-recognised, and that new mutations and phenotypes continue to be identified, we will need to expand on our knowledge base and report clinical manifestations associated with these abnormal phenotypes.

Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features

“…Of note, how patients with BTC and A1ATD respond to approved therapies and whether they exhibit a specific mutational profile remain largely unexplored [ 15 ]. As A1ATD might affect hepatocyte homoeostasis, liver function and its regenerative response, such knowledge might be valuable when managing patients with hepatotoxic medications or intended curative surgery involving extended resections [ 16 , 17 , 18 , 19 , 20 ]. Finally, an increased peripheral level of AAT was reported to be associated with metastasis and poor prognosis in various cancers, including hepatocellular carcinoma, and thus might have a potential interest in pre-operative settings in BTC [ 21 , 22 , 23 ].…”

Panniculitis As the First Clinical Manifestation of Myeloperoxidase–Positive Perinuclear Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: Comment on the Article by Micheletti et al

“…Panniculitis is associated with systemic lupus erythematosus, sarcoidosis, lymphoma, histiocytosis, and infectious diseases, but typically not with AAV. In the literature, we found 8 cases of an association of AAV with panniculitis between 1994 and 2020 (2–9). We believe that panniculitis should be included in the cutaneous manifestations of AAV.…”