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Dosage de l’élastase fécale d’origine pancréatique chez les nourrissons

Annales de Biologie Clinique. Volume 66, Numéro 5, 549-52, Septembre-Octobre 2008, article original

DOI : 10.1684/abc.2008.0262

Résumé

Summary

Auteur(s) : NA Benahmed, D Manene, L Barbot, N Kapel , Laboratoire de coprologie fonctionnelle, APHP, Groupe hospitalier Pitié-Salpêtrière, Paris.

Résumé : Objectifs et méthodes : le dosage de l’élastase fécale est maintenant de pratique courante chez les nourrissons se présentant avec un diagnostic néonatal de mucoviscidose ou chez ceux présentant un retard de croissance staturo-pondérale précoce, ceci afin de détecter le plus précocement possible une insuffisance pancréatique exocrine. Cependant, il n’existe que peu de données dans la littérature concernant l’interprétation d’une mesure isolée de ce marqueur dans cette population. Dans cette étude rétrospective, nous analysons l’évolution de la concentration fécale de l’élastase dosée chez 236 nourrissons durant les 2 premières années de vie. Résultats : la concentration fécale de l’élastase était supérieure à 200 μg/g (seuil normal) dans un premier échantillon obtenu chez 122 patients (51,7 % des patients inclus) et inférieure à 200 μg/g chez les 114 patients restants. Une évolution pathologique après un premier dosage normal a été observée chez 18 nourrissons (14,8 %), conduisant à poser un diagnostic d’insuffisance pancréatique exocrine à la fin du suivi. A l’inverse, une normalisation de l’élastase a été retrouvée chez 52 nourrissons (45,6 %) ayant eu un premier dosage anormal. Conclusion : cette étude montre qu’il faut rester prudent dans l’interprétation de ce marqueur chez les nourrissons. Un diagnostic précoce de l’insuffisance pancréatique est en effet fondamental chez les nourrissons afin de proposer le plus rapidement possible une prise en charge thérapeutique par enzymothérapie substitutive. Une seule mesure de l’élastase ne permet pas toujours d’exclure ou de poser définitivement le diagnostic d’insuffisance pancréatique dans cette population et un prélèvement de contrôle dosé à distance peut être nécessaire.

Mots-clés : élastase pancréatique, selles, nourrissons, insuffisance pancréatique

Illustrations

ARTICLE

Auteur(s) : NA Benahmed, D Manene, L Barbot, N Kapel

Laboratoire de coprologie fonctionnelle, APHP, Groupe hospitalier Pitié-Salpêtrière, Paris

Article reçu le 10 Juin 2008, accepté le 29 Juin 2008

Direct function test performed after stimulation with secretin and cholecystokin, and collection of pancreatic secretions for H⁺, bicarbonate and enzyme analysis is the most accurate method for the evaluation of exocrine pancreatic function, and is therefore still considered by many investigators as the gold standard for pancreatic investigation [1]. However, this method is time-consuming, expensive and cannot be used in infants due to its invasive character. The measurement of pancreatic proteases in feces is thus generally preferred in the pediatric routine because of its low invasiveness [2]. For several years, determination of fecal chymotrypsin has been used as an accepted indirect test for exocrine pancreatic function [3]. More recently, numerous studies have shown the better sensitivity of pancreatic elastase-1 (E1) determination for the evaluation of pancreatic function [4]. Fecal E1 determination is thus of routine use in infant population presenting with a neonatal diagnosis of cystic fibrosis or in infants with poor weight gain and growth in order to precociously detect pancreatic insufficiency (PI). In neonate population, low levels of fecal elastase can be observed during the first weeks of life due to pancreatic maturation deficit, especially in preterms. However, previous data have shown that E1 levels currently normalize within one month [5, 6]. There are few data regarding the value of one spot measure of elastase to assess pancreatic status in this population. The aim of this retrospective study was to analyze the follow-up of fecal elastase measurement during the first 2 years of life in a non selected population of infants.

Patients and methods

This retrospective study included all fecal elastase assays performed from February 2000 until February 2008 in infants of less than 2 years. For each of them, 1 to 14 stool samples were successively analyzed. Pancreatic E1 concentration was determined using a “sandwich” type enzyme immunoassay (Schebo-Biotech, Guiessen, Germany) which combines the use of two monoclonal antibodies binding to 2 distinct epitopes specific to human pancreatic E1. Results were expressed as μg/g of stool. Using this assay, the limit of detection was 15 μg/g of stool and 200 μg/g of stool was considered as the lower normal limit. Results are given as median (range). Data were analyzed using the Statview (Abacus^® Concepts, Berkeley, CA) statistical software package and statistical comparisons were performed using the Fisher’s exact test.

Results

This study processed 2655 samples issued from 2245 patients; 157 samples were excluded from analysis due to their meconial origin (n = 8) or because insufficient information concerning the sampling date (n = 149). Only one spot measure was performed in 1940 patients. E1 concentration was below the detection limit in 224 patients; between 15 and 100 μg/g in 90 patients, between 100 and 200 μg/g in 89 patients and over 200 μg/g (normal cut-off) in 1537 patients (no PI).

A follow-up with 2 to 14 samples per patient (median: 2) was performed in 236 infants (110 females, 126 males) aged between 5 to 674 days at the day of enrolment (first sample), thus allowing the measurement of E1 in 562 samples. E1 was over 200 μg/g in a first sample obtained at day 195 (7-674) in 122 patients (51.7% of patients) and below 200 μg/g in the first sample obtained at day 73 (5-606) in 114 patients. There was no significant difference in the age of infants at the time of first sampling in those 2 groups.

Fecal E1 levels remained over the normal limit in the successive samples (2 to 4 samples analysed per patient, median: 2) in 104/122 infants (= 85.2% of patients presenting with a first normal measurement) whereas an alteration was observed in 18 infants (14.8% of these patients) at day 207 (15-569). E1 levels were below 25, 100 and 200 μg/g in 5, 6 and 7 infants respectively, leading to the diagnosis of PI. There was no significant difference in the age of those infants at the time of PI diagnosis.

In 114 patients, the first measurement of E1 was below 200 μg/g. In those patients, fecal E1 was undetectable in 44 samples at day 45 (7-515); between 15 and 100 μg/g in 33 samples obtained at day 90 (9-488) and between 100 and 200 μg/g in 37 samples obtained at day 85 (5-606). There was no significant difference in the infant’s age at the time of this first sampling in those 3 groups of patients. In this population, 62/114 (54.4%) had a confirmed PI with E1 concentrations below 200 μg/g at the end of follow-up. This abnormal pancreatic functionality was observed in 38/44 infants (86.4%) with a first E1 level below 15 μg/g. In this population, E1 was undetectable in 36 infants and below 25 μg/g in the remaining 2 infants at the end of the follow-up. In contrast, only 16/33 infants with a first E1 concentration below 100 μg/g (48.5%) and 8/37 infants with a first E1 concentration below 200 μg/g (21.6%) remained with PI during the follow-up.

In the remaining population, a normalization of fecal E1 was observed i.e. 52/114 infants (45.6%). Only 6/44 infants with a first undetectable E1 level had a normal level at the end of the follow-up (median: J437, range: 73-577) whereas 17/33 infants with first concentration between 15 and 100 μg/g (51.5%) and 29/37 with first concentration between 100 and 200 μg/g (78.4%) had a normal E1 concentration at the end of the follow-up which occurred at J117 (9-488) and J101 (25-581) in those two groups, respectively.

Discussion

The assessment of pancreatic function within the youngest pediatric population is of fundamental importance to provide precocious enzyme support so the evaluation of non invasive marker is a major challenge in this population. In our study, 236 infants without any information about clinical state, aged 5-674 day-old at the day of inclusion were longitudinally tested for fecal E1 for the detection of PI. In this population, 122 infants had a normal E1 concentration in the first sample. No significant variation of this E1 levels was observed in 85.2% of infants whereas 14.8% of those infants displayed abnormal fecal E1 concentrations at the end of the follow-up allowing the diagnosis of moderate to severe PI. No correlation between age of diagnosis and seriousness of PI was observed. Walkowiak et al. have studied the progression of pancreatic insufficiency during the first year of life in cystic fibrosis infants carrying two severe mutations [7]. In those patients, abnormal E1 (< 100 μg/g) concentrations were found in all infants at 6 months of age. Our retrospective study shows that PI, even severe ones with undetectable fecal E1 concentrations, can be detected as latter as 428 days of life. In contrast to what is currently observed in adult and children populations [8, 9], a special attention thus should be given to the analysis of E1 concentrations in infants as a precocious diagnosis of pancreatic insufficiency (PI) is crucial for the early introduction of a pancreatic enzyme replacement therapy which will prevent further consequence of malabsorption. One spot measure does not totally exclude PI in this population (figure 1).

In our population, 114 infants exhibited low E1 levels in the first sample which further normalized in 45.6% of the population. We and others have reported a physiological pancreatic insufficiency in preterm neonates, normal levels being observed in preterm and full-term neonates at the second week of life [5, 6, 10]. This study shows that maturation of pancreatic function may be delayed and occur all along the two first years of life. It appears to be rarely observed when fecal E1 is undetectable in a first sample but highly probable in infants displaying a moderate PI in a first sample taken before the age of 2 years. Even in infants with E1 concentration below 100 μg/g, normalization of pancreatic function can be observed within 2 years although a cut-off level of 100 μg/g had shown a very high predictive value in ruling out malabsorption in older cystic fibrosis children [11]. Control measurements are thus required for those infants within the two first years of life in order to confirm PI. Moreover, we must keep in mind that low E1 concentrations can be observed in liquid stools and in patients with intestinal villous atrophy.

References

1 Kitagawa M, Naruse S, Ishiguro H, Nakae Y, Kondo T, Hayakawa T. Evaluating exocrine function tests for diagnosing chronic pancreatitis. Pancreas 1997; 15: 402-8.

2 Goldberg DM. Proteases in the evaluation of pancreatic function and pancreatic disease. Clin Chim Acta 2000; 291: 201-21.

3 Brown GA, Sule D, Williams J, Puntis JW, Booth IW, McNeish AS. Faecal chymotrypsin: a reliable index of exocrine pancreatic function. Arch Dis Child 1988; 63: 785-9.

4 Stein J, Jung M, Sziegoleit A, Zeuzem S, Caspary WF, Lembcke B. Immunoreactive elastase I: clinical evaluation of a new noninvasive test of pancreatic function. Clin Chem 1996; 42: 222-6.

5 Campeotto F, Kapel N, Kalach N, et al. Low levels of pancreatic elastase 1 in stools of preterm infants. Arch Dis Child Fetal Neonatal Ed 2002; 86: F198-F199.

6 Nissler K, Von Katte I, Huebner A, Henker J. Pancreatic elastase 1 in feces of preterm and term infants. J Pediatr Gastroenterol Nutr 2001; 33: 28-31.

7 Walkowiak J, Sands D, Nowakowska A, et al. Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. J Pediatr Gastroenterol Nutr 2005; 40: 199-201.

8 Molinari I, Souare K, Lamireau T, et al. Fecal chymotrypsin and elastase-1 determination on one single stool collected at random: diagnostic value for exocrine pancreatic status. Clin Biochem 2004; 37: 758-63.

9 Naruse S, Ishiguro H, Ko SB, et al. Fecal pancreatic elastase: a reproducible marker for severe exocrine pancreatic insufficiency. J Gastroenterol 2006; 41: 901-8.

10 Kori M, Maayan-Metzger A, Shamir R, Sirota L, Dinari G. Faecal elastase 1 levels in premature and full term infants. Arch Dis Child Fetal Neonatal Ed 2003; 88: F106-F108.

11 Beharry S, Ellis L, Corey M, Marcon M, Durie P. How useful is fecal pancreatic elastase 1 as a marker of exocrine pancreatic disease? J Pediatr 2002; 141: 84-90.