Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Gastroenterology
Low Fecal Elastase: Potentially Related to Transient Small Bowel Damage Resulting from Enteric Pathogens
Salvatore, Silvia*; Finazzi, Sergio†; Barassi, Alessandra†; Verzelletti, Mascia*; Tosi, Anna*; Melzi d'Eril, Gian Vico‡; Nespoli, Luigi*
*Clinica Pediatrica Universitaria, Università dell'Insubria, Varese, Italy; †Laboratorio di Analisi Chimico-Cliniche, Ospedale di Circolo, Varese, Italy; ‡Dipartimento di Scienze Biologiche Sperimentali e Cliniche, Uiversità dell'Insubria, Varese, Italy
Address correspondence to Silvia Salvatore, Cliinica Pediatrica, Ospedale F. Del Ponte, Via F. Del Ponte 19, 21100 Varese, Italy (e-mail: email@example.com).
Fecal elastase is considered to be a highly sensitive and specific non-invasive exocrine pancreatic function test. However, enteropathy may theoretically cause decreased exocrine pancreatic enzyme secretion through alteration of enteric hormone release.
Objective: The aim of this study was to evaluate the possible influence of transient small bowel damage on pancreatic elastase secretion.
Methods: We studied 166 children (aged 4 months to 14 years, mean 2 years); 114 of these children had acute enteritis and 52 children were control subjects (with gastro-intestinal symptoms or extra-intestinal diseases). Feces were collected from each patient 3 days after the onset of diarrhea and then tested for fecal elastase, bacterial pathogens, Rotavirus, and Adenovirus. Liquid fecal samples were not considered eligible for elastase measurement. Pancreatic elastase was measured using an ELISA method (Sche.Bo.Tech, Germany). We classified the results, expressed in μg/g stool, as: severe pancreatic insufficiency (<100 μg/g), moderate pancreatic insufficiency (100 to 200 μg/g), and normal (>200 μg/g).
Results: In the acute enteritis group we found severe levels in 14 (12%) children, moderate levels in 18 children (16%), and normal levels in 82 children (72%). In contrast, 52 of 52 (100%) control subjects demonstrated normal results. Statistical analysis (Wilcoxon rank test) demonstrated a significant difference between the enteritis and control groups (P < 0.01). Serial measurement of fecal elastase performed in 10 patients with enteritis showed a progressive increase of levels in 6 patients and an early decline with subsequent increases in the other 4 patients.
Conclusions: Transient exocrine pancreatic insufficiency may be present in transient small bowel disease, caused by both bacterial and viral infections, possibly related to reduced enteric CCK secretion.
Fecal elastase (FE) is considered to be a highly sensitive and specific exocrine pancreatic function test. It is more sensitive than chymotrypsin for severe, moderate, and mild pancreatic insufficiency (1,2). Pancreatic elastase is not degraded during intestinal transit and thereby FE reflects exocrine pancreatic function (1,2). Several reports show its utility in cystic fibrosis with pancreatic involvement (3–7) and chronic pancreatitis in adults (8,9). In celiac disease its level seems inversely related to the degree of enteropathy with restoration of normal value when healing of mucosal damage occurs (10). In our study we evaluated the influence of transient small bowel damage, caused by infection, on FE.
MATERIALS AND METHODS
We sampled 166 patients (range 4 months–14 years, mean age 2 years) admitted to our hospital; 114 of these patients were admitted for acute enteritis and there were 52 control subjects (e.g., respiratory disease, functional abdominal pain, failure to thrive, and Toddler's diarrhea). Feces were collected from each patient at least 48 hours after the onset of diarrhea and tested for fecal elastase, bacterial pathogens, Rotavirus, and Adenovirus. In the last 10 consecutive patients recruited, serial measurements of FE were performed on the 3rd, 7th, 10th, and 15th day of diarrhea. As dilution of FE (stool water content >85%) occurs in diarrhea and causes false low results (11,12), liquid fecal samples were discarded from the study. All stool specimens were frozen at −20°C before analysis. FE was measured using the ELISA method according to the manufacturer's instructions (ScheBo.Tech, Germany). This measurement involved employing two binding monoclonal antibodies (IC 10A and II D 5F) to two distinct epitopes of FE. One hundred milligrams of stool were diluted 1:500 in sample wash buffer and the FE concentration (μg/g wet weight of stools) was measured photometrically. The manufacturers provide the following clinical ranges: severe pancreatic insufficiency (<100 μg/g), moderate pancreatic insufficiency (≥100≤200 μg/g), and normal (>200 μg/g). We decided to avoid any invasive and expensive pancreatic diagnostic procedures in our patients because of the self-limiting nature of the diseases.
For statistical analysis, because none of the data showed a gaussian distribution, a comparison of paired differences was performed with the Wilcoxon rank test. Differences with P values <0.01 were considered significant.
In the acute enteritis group (114 patients) we found severe FE levels in 14 patients (12%)(5 Rotavirus, 1 Adenovirus, 3 Salmonella, and 5 with non-identified pathogens), moderate levels in 18 patients (16%)(9 Rotavirus, 3 Salmonella, and 6 with non-identified pathogens), and normal levels in 82 patients (72%)(38 Rotavirus, 3 Adenovirus, 11 Salmonella, and 30 with non-identified pathogens) (Table 1;Fig. 1). Rotavirus was found in 52 (46%) patients with enteritis, Adenovirus in 4 patients (3.5%), Salmonella in 17 patients (15%) and no pathogens were identified in 41 patients (36%). Overall, the FE levels were compatible with severe or moderate pancreatic insufficiency in 32 (28%) of patients with acute enteritis. In contrast, 52 of 52 (100%) control subjects had normal results. In the 10 patients with infectious diarrhea who received follow-up evaluation, FE showed two different patterns. In 6 patients (2 Rotavirus, 3 Salmonella, 1 non-identified pathogens), FE showed a progressive increase with pathologic levels in 3 patients after 3 days and 2 patients after 7 days, with normalization of all patients in 10 days and a further increase by 15 days from the onset of diarrhea (Fig. 2a). In the other 4 patients (3 Rotavirus, 1 non-identified pathogens), we noticed normal levels at the first determination, but then decreased levels in the subsequent 2 follow-up samples. Pathologic FE levels and a concomitant increased number of stools were seen in 3 patients (2 Rotavirus and 1 non-identified pathogen) at 10 days from onset of diarrhea. This was followed by a subsequent increased FE levels with normalization of FE, by 15 days in 2 patients (Fig 2b). Neither the diet nor the severity of dehydration were significantly correlated with the values of FE. Serum amylase tested in patients with enteritis did not correlate with FE.
Statistical analysis showed a significant difference between the enteritis and control groups (P < 0.01)(Fig. 3).
In our study we showed that FE may be severe or moderately abnormal in 28% of patients with infectious enteritis. Rotavirus and Salmonella were the most common identified pathogens (20/32, 62.5%) associated with pathologic FE levels. As all liquid fecal samples were discarded and normal results were found in patients with Toddler's diarrhea, we considered the possibility of false positive FE caused by dilution effect very unlikely. Serial measurements of FE showed pathologic levels 3 days after the onset of diarrhea in 3 children, after 1 week, in 2 of the 3, after 10 days in 3 different patients and after 2 weeks in 2 of the latter 3. Interestingly, the suspected enteropathy responsible for the decreased pancreatic secretion may take more than 15 days to recover as supported by pathologic level of follow-up FE determination in 2 patients with severe infectious enteritis caused by Rotavirus. Our finding of low FE in 27% of Rotavirus and 35% of Salmonella enteritis may reflect the presence of transient enteropathy in these patients. Although we did not perform biopsies in our patients because of the self-limiting disorders, our results are consistent with previous reports of subtotal villous atrophy in either Rotavirus or bacterial enteritis (EPEC, Salmonella) demonstrated in up to 50% of patients with protracted diarrhea (13,14).
Preliminary results of our study (15) had suggested the hypothesis that decreased release of CCK by the damaged intestinal mucosa, even due to a transient infectious event, could be responsible for low FE results. This speculation has been recently supported, in 6 patients with enteropathy and FE pathologic levels, by restoration of normal pancreatic enzyme levels after secretin-CCK test (16). These findings provided evidence of the secondary origin of pancreatic insufficiency in patients with enteropathy (due to a reduction of pancreatic stimulation by the inflamed intestine) with normal pancreatic secretory capacity and response to appropriate humoral stimuli. In the same study, a highly significant correlation between duodenal morphology and inflammation and levels of FE has been shown in different enteropathies (16).
FE is considered to be an excellent non-invasive marker of exocrine pancreatic function. The sensitivity and specificity of FE is greater than 90% for moderate and severe exocrine pancreatic insufficiency, clearly superior to fecal chymotrypsin (1–3,6,8,9,12,17). It is also simple, relatively cheap, stable (5), with very low intra-individual variation (1,2,18). A significant correlation exists between FE and stimulated duodenal volume, and the bicarbonate, amylase, lipase, and trypsin concentration of duodenal aspirates (1,2,6,9). In normal conditions, both neural (entero-pancreatic, cholinergic, vago-vagal reflexes) and hormonal (cholecystokinin) pathways mediate the pancreatic enzyme response to intestinal stimulants. CCK seems to be the major mediator of the response to high loads of amino acids and fatty acids (19). Immuno-histochemistry identified approximately 1650 CCK cells per cross-section in the duodenum of humans (20) and jejunal mucosal integrity is necessary for the normal secretion of enteric hormones by the respective cells located in the small bowel mucosa (10). The close link between the small bowel mucosa and the exocrine function of the pancreas is highlighted in celiac disease. In 10 of 30 celiacs (33%) FE was subnormal at diagnosis. After 2 months of gluten-free diet, FE deficiency persisted in only 2 patients, possibly related to a more severe enteropathy (21), and independent of nutritional status (22). Recently, FE was found to be inversely related to the degree of intestinal damage in celiac disease, emphasizing the role of gluten-related mucosal damage on abnormal secretion of pancreatic enzymes, related possibly to reduced hormonal signaling (10). In celiacs pancreatic impairment has been associated with CCK abnormalities (23–25) and is clearly a reversible phenomenon as it recovers with gluten-free diet (26,27) and restoration of the mucosa (10).
In recent years, a few patients with different malabsorption diseases (celiac disease, Giardiasis, cow-milk sensitive enteropathy, Crohn disease, and small bowel syndromes) showed low FE at diagnosis and normalization of FE with restoration of small bowel integrity. This data further supports the close relationship between decreased FE and enteropathy regardless of the underlying diseases (4,16,17,28–30).
In conclusion, low FE and transient exocrine pancreatic insufficiency may be present in infectious enteropathy, possibly related to reduced enteric CCK secretion. As the specificity of FE in differentiation between “primary” exocrine pancreatic insufficiency and intestinal malabsorption seems rather poor (30), persisting pathologic FE could reflect morphologic and functional derangements of the small bowel mucosa and could indicate further investigation to exclude underlying enteropathy. As dilution effect (stool water content >85%) may account for false positive FE results (11,12), liquid fecal samples should not be used for FE determination. If only watery stools are available, lyophilization of the feces should be performed (11).
1. Stein J, Jung M, Sziegoleit A, et al. Immunoreactive elastase I: clinical evaluation of a new noninvasive test of pancreatic function. Clin Chem 1996; 42:222–226.
2. Loser C, Mollgaard A, Folsch UR. Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test. Gut 1996; 39:580–86.
3. Soldan W, Henker J, Sprossig C. Sensitivity and specificity of quantitative determination of pancreatic elastase 1 in feces of children. J Pediatr Gastroenterol Nutr 1997; 24:53–5.
4. Gullo L, Graziano L, Babbini S, et al. Faecal elastase 1 in children with cystic fibrosis. Eur J Pediatr 1997; 156:770–72.
5. Wallis C, Leung T, Cubitt D, et al. Stool elastase as a diagnostic test for pancreatic function in children with cystic fibrosis. Lancet 1997; 350:1001.
6. Walkowiak J, Cichy WK, Herzig K-H. Comparison of fecal elastase-1 determination with the secretin-cholecystokinin test in patients with cystic fibrosis. Scand J Gastroenterol 1999; 34:202–07.
7. Cade A, Walters MP, Mc Ginley N, et al. Evaluation of fecal pancreatic elastase-1 as a measure of pancreatic esocrine function in children with cystic fibrosis. Pediatr Pulmonol 200; 29:172–6.
8. Gullo L, Ventrucci M, Tomassetti P, et al. Fecal elastase 1 determination in chronic pancreatitis. Dig Dis Sciences 1999; 44:210–3.
9. Katschinski M, Schirra J, Bross A, et al. Duodenal secretion and fecal excretion of pancreatic elastase-1 in healthy humans and patients with chronic pancreatitis. Pancreas 1997; 15:191–200.
10. Nousia-Arvanitakis S, Karagiozoglou-Lamboudes T, Aggouridaki C, et al. Influence of jejunal morphology changes on exocrine pancreatic function in celiac disease. J Ped Gastroenterol Nutr 1999; 29:81–5.
11. Fisher BP, Hoh S, Wehler, M et al. Fecal elastase 1 in diarrhoea: lyophilization of stool samples may correct false low results due to elevated stool water content insufficiency. Digestion 1999; 60:373,A22.
12. Dominguez-Munoz JE, Hieronymus C, Sauerbruck T, et al. Fecal elastase test: evaluation of a new noninvasive pancreatic function test. Am J Gastroenterol 1995; 90:1834–7
13. Fagundes Neto U, de Castro Ferreira V, Patricio FRS, et al. Protracted diarrhea: the importance of the enteropathogenic E. coli
(EPEC) strains and Salmonella
in its genesis. J Pediatr Gastroenterol Nutr 1989; 8:207–11.
14. Walker-Smith J, Murch S. Gastroenteritis and its sequelae. In: Walker-Smith J, Murch S, eds. Diseases of the Small Intestine in Childhood. Oxford: ISIS Medical Media; Fourth Edition 1999:119–94.
15. Salvatore S, Finazzi S, Melzi d'Eril GV, et al. Low fecal elastase: could it be also related to small bowel damage? J Ped Gastroenterol Nutr 2000; 31(S2):S221.
16. Schappi MG, Smith VV, Cubitt D, Milla PJ, Lindley KJ. Faecal elastase 1 concentration is a marker of duodenal enteropathy. Arch Dis Child 2002; 86:50–3.
17. Walkowiak J. Faecal elastase 1: clinical value in the assessment of exocrine pancreatic function in children. Eur J Ped 2000; 159:869–70.
18. Phillips IJ, Rowe DJ, Dewar P, et al. Faecal elastase 1: a marker of exocrine pancreatic insufficiency in cystic fibrosis. Ann Clin Biochem 1999; 36:739–42.
19. Singer MV. Pancreatic secretory response to intestinal stimulants: a review. Scand J Gastroenterol Suppl 1987; 139:1–13.
20. Schlegel W, Raptis S, Grube D, et al. Estimation of cholecystokinin-pancreozymin (CCK) in human plasma and tissue by a specific radioimmunoassay and the immunohistochemical identification of pancreozymin-producing cells in the duodenum of humans. Clin Chim Acta 1977; 80:305–16.
21. Carroccio A, Iacono G, Ippolito S, et al. Usefulness of faecal elastase-1 assay in monitoring pancreatic function in childhood coeliac disease. Ital J Gastroenterol Hepatol 1998; 30:500–4.
22. Carroccio A, Iacono G, Montalto G, et al. Pancreatic insufficiency in celiac disease is not dependent on nutritional status. Dig Dis Sci 1994; 39:2235–41.
23. Hermanz A, Polanco I, Codoceo R, et al. Gastrointestinal peptide in children with celiac disease. J Pediatr Gastroenterol Nutr 1987; 6:341–5.
24. Polak JM, Bloom SR, McCrossan MV, et al. Cholecystokinin abnormalities in celiac disease. Gastroenterology 1978; 74:1079–82.
25. Maton PN, Selden AC, Fitzpatrick ML, et al. Defective gallbladder emptying and cholecystokinin release in coeliac disease: reversal by gluten-free diet. Gastroenterology 1985; 88:191–6.
26. Carroccio A, Iacono G, Montalto G, et al. Exocrine pancreatic function in children with celiac disease before and after a gluten free diet. Gut 1991; 32:796–9.
27. Collins BJ, Bell PM, Boyd S, et al. Endocrine and exocrine pancreatic function in treated celiac disease. Pancreas 1986; 1:143–7.
28. Masoero G, Zaffino C, Laudi C, et al. Fecal pancreatic elastase 1 in the work up of patients with chronic diarrhea. Int J Pancreatol 2000; 28:175–9.
29. Carroccio A, Verghi F, Santini B, et al. Diagnostic accuracy of fecal elastase 1 assay in patients with pancreatic maldigestion or intestinal malabsorption: a collaborative study of the Italian Society of Pediatric Gastroenterology and Hepatology. Dig Dis Sci 2001; 46:1335–42.
30. Walkowiak J, Herzig KH. Fecal elastase-1 is decreased in villous atrophy regardless of the underlying disease. Eur J Clin Invest 2001; 31:425–30.
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Fecal elastase; small bowel; enteritis; pancreatic function test; CCK
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