Professor of Pediatrics-Gastroenterology, Chair Department of Pediatrics, Aristotle University, Thessaloniki, Greece, AHEPA University Hospital, Thessaloniki, Greece
Received December 13, 2002; accepted December 18, 2002.
Address correspondence to Sanda Nousia-Arvanitakis, AHEPA University Hospital,
Stylponos Kyriakides 1, 54006, Thessaloniki, Greece (e-mail: email@example.com).
This editorial accompanies an article. Please see Low Fecal Elastase: Potentially Related to Transient Small Bowel Damage Resulting from Enteric Pathogens. S. Salvatore, S. Finazzi, A. Barassi, M. Verzelletti, A. Tosi, G. Vico Melzi d'Eril, L. Nespoli. J Ped Gastroenterol Nutr 2003;36:392–396.
Invasive diagnostic approaches to the evaluation of impaired exocrine pancreatic function, such as the secretin-pancreozymin test or the Lundh test are time-consuming, unpopular with children, and expensive. Numerous indirect or tubeless pancreatic function tests have been applied as alternatives. Human pancreatic elastase, which is an enzyme highly specific for the pancreas, was first detected in pancreatic secretions and feces by Sziegoleit (1,2). Fecal elastase-1 concentration is correlated to duodenal elastase output because the enzyme is not degraded during intestinal passage (3). It is the test of choice among indirect tests in assessing exocrine pancreatic function in children (4–7). It has been shown to be more sensitive than fecal chymotrypsin (8) or breath tests (9). Human pancreatic elastase activity in the stool is thought to reflect exocrine pancreatic function because of the excellent stability of this enzyme in the intestinal lumen. Determination of fecal elastase activity is a non-invasive, simple, relatively inexpensive, reproducible, highly specific, and sensitive test of exocrine pancreatic function.
An important disadvantage of the fecal elastase test is its inability to differentiate between primary exocrine pancreatic insufficiency and exocrine pancreatic dysfunction associated with intestinal villous damage. Abnormal fecal elastase concentrations have been found in patients with small bowel damage (10). Decreased fecal elastase-1 concentration was first described in celiac disease (11,12) and later in other causes of villous atrophy such as cow milk protein enteropathy (13). It is most interesting that low fecal elastase-1 values have even been demonstrated in transient intestinal damage resulting from enteric pathogens, mainly Rotavirus and Salmonella, as reported by Salvatore et al. in this issue (14). The dilution factor, which may produce false-low elastase values, was excluded because stool samples were collected on the third day from the onset of diarrhea and liquid stools were discarded. The authors conclude that their finding of low fecal elastase in acute enteritis may reflect the presence of transient enteropathy resulting in reduced pancreatic secretion. Although biopsies were not performed in this study, subtotal villous atrophy has been previously demonstrated in Rotavirus and Salmonella enteric infection (15).
Whatever the mechanism, exocrine pancreatic dysfunction, which is associated with intestinal damage, appears to be a reversible phenomenon. Fecal elastase-1 concentrations become normal after restoration of the jejunal mucosal morphology. This may take 3 to 6 months on gluten-free diet in celiac disease (12). Even transient intestinal damage, which is thought to be responsible for the decrease of elastase in acute enteritis, may require as long as 15 days to recover as supported by the duration of the gradual increase of fecal elastase-1 concentration to reach normal levels (14).
Direct study of the interaction between the enterocytes and the acinar cells may elucidate the cause of pancreatic enzyme disturbance in intestinal atrophy. Alternatively, the investigation of the reversibility of the phenomenon may offer indirect information. Abnormal exocrine pancreatic function in the presence of mucosal damage, even transient during an episode of enteritis, may be attributed to the absence of hormonal signals from the gut rather than acinar cell defect (12). Mucosal damage may lead to reduced secretin and cholecystokinin secretion resulting in abnormal secretion of pancreatic enzymes that occurs because the pancreas does not receive the appropriate hormonal signal.
In earlier studies, various degrees of exocrine pancreatic dysfunction have been documented in association with villous atrophy using direct or indirect methods other than the fecal elastase test (16). The same mechanism has been postulated in those studies, which have documented failure of secretin and cholecystokinin release in untreated patients with celiac disease (17,18). Jejunal mucosal integrity is necessary for the normal secretion of enteric hormones by the respective cells located in the small intestinal mucosa.
Although fecal elastase concentration is considered to be an excellent non-invasive test of exocrine pancreatic function with sensitivity and specificity exceeding 90% for moderate and severe exocrine pancreatic insufficiency (19,20), the method has poor sensitivity in the differentiation between primary exocrine pancreatic insufficiency and primary intestinal damage. Consequently, low fecal elastase-1 concentration may indicate an underlying enteropathy causing disturbances of exocrine pancreatic secretion rather than pancreatic acinar cell dysfunction. It may either reflect exocrine pancreatic insufficiency or functional derangement of pancreatic secretion influenced by the abnormal intestinal mucosal morphology. The fecal elastase-1 test, therefore, is a useful test in assessing exocrine pancreatic function in known cases of cystic fibrosis or chronic pancreatitis. In the diagnostic approach to patients having evidence of malabsorption, however, this diagnostic tool should be combined with other tests such as sweat chlorides, serum antigliadin antibodies, endomysium antibodies, tissue transglutaminase, and jejunal mucosa biopsy, when indicated, to examine the intestinal mucosa integrity, before a final diagnosis is reached.
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