β1-Antitrypsin deficiency and chronic pancreatitis

Abstract

Alpha 1-antitrypsin deficiency is a genetic disorder commonly associated with pulmonary and hepatic injury. Low serum levels of this glycoprotein result in an imbalance between circulating protease and protease inhibitors, which is thought to play a role in the development of emphysema. In recent studies, a protease-to-protease inhibitor imbalance in patients with alpha 1-antitrypsin deficiency was thought to be a mechanism contributing to the development of chronic pancreatitis. The heterozygous phenotype and low levels of this glycoprotein have been reported to occur more frequently in patients with chronic pancreatitis than in healthy controls. We report a patient with Pi-SS phenotype alpha 1-antitrypsin deficiency and chronic pancreatitis complicated by recurrent pancreatic pseudocysts and chronic abdominal pain. Our case supports the association between chronic pancreatitis and alpha 1-antitrypsin deficiency. Furthermore, this case provides support for the use of pancreatic stent drainage in the management of intractable abdominal pain in patients with chronic pancreatitis and a dominant stricture.

A Review of α1-Antitrypsin Deficiency

“…Although other disease associations have been suggested, they are less well established (99), including glomerulonephritis (100); celiac disease (101); lung, colorectal, and bladder cancers (102); intracranial and intraabdominal aneurysms (103); fibromuscular dysplasia (104); and pancreatitis (105).…”

1-Antitrypsin deficiency * 3: Clinical manifestations and natural history

“…An association between AAT deficiency and pancreatitis has been the subject of some case reports and case-control studies, [41][42][43] but other studies have found no difference in AAT phenotype in patients with pancreatitis compared with controls. 44 Witt et al recently found no difference in allele frequency between a group of patients with chronic pancreatitis and control subjects.…”

Role of proteases and antiprotease in the etiology of chronic pancreatitis

“…Thus, the low serum activity of this glycoprotein results in an imbalance between circulating proteases as aggressive enzymes are thought to play a role in the development of chronic pancreatitis. [18] Studies by Haber et al ., (1991), have also shown that mortality of experimental pancreatitis is increased with reduced concentrations of circulating α-1AT. [19] The decrease in the antiprotease may result in the activation of proteases that release into the blood stream leading to membrane damage.…”

“…Some findings indicated increased prevalence of PiS and PiZ in chronic alcoholic patients, while others indicated no difference. [182223] Serum α-1AT concentrations were greater in patients with pancreatitis who were sampled shortly after an acute attack of pancreatitis compared to pancreatitis patients sampled at other times, or to alcoholic controls. [19] Increased α-1AT concentration was found in pancreatic juice of patients with chronic pancreatitis by Miszczuk-Jamska et al .…”