The pathophysiological mechanisms of panniculitis in ZZ-AAT deficiency subjects have yet to be determined. As some hypotheses suggest an inflammatory process mediated by neutrophils invading the subcutaneous fat layer, others speculate that accumulation of polymers play a key role. Though, the most logical mechanism seems to be the unopposed anti-inflammatory proteolytic damage by neutrophil-serine proteinases (NE and PR3) in the context of deficient serum levels of AAT. The histological features of panniculitis, especially neutrophil invasion, could explain the rapid clinical resolution of inflammation with AAT augmentation therapy. Numerous cases have reported a successful resolution of the skin after initiation of AAT augmentation therapy. However, various concentrations of AAT augmentation therapy have been postulated as starting dose, and there is no consensus about the maintenance dosage in order to prevent the recurrence of panniculitis. Furthermore, an acute inflammatory event like panniculitis may lead to progression or initiation of liver cirrhosis.
