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Fecal Tumor Necrosis Factor- and Calprotectin as Differential Diagnostic Markers for Severe Diarrhea of Small Infants

Kapel, N*; Roman, C†; Caldari, D†; Sieprath, F†; Canioni, D‡; Khalfoun, Y‡; Goulet, O†; Ruemmele, F M†

Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Gastroenterology

Objective: The etiology of early-onset diarrhea of neonates and small infants that persists despite bowel rest is heterogeneous. Two different categories of disorders presenting with diarrhea in the first weeks of life can be distinguished: constitutive intestinal epithelial disorders (microvillus atrophy [MVA] or epithelial dysplasia [ED]) and immune-inflammatory disorders, (autoimmune enteropathy [AIE] or inflammatory colitis [IC]). We aimed to evaluate in a prospective manner the use of fecal inflammatory markers in the differential diagnosis of severe persistent diarrhea.

Material and Patients: Twenty-five patients (17 males) were enrolled in this study (median age 8 months). Fourteen children had a constitutive enterocyte disorder (group 1: MVA = 8, ED = 6), and 11 patients had an immuno-inflammatory disease (group 2: AIE = 5, IC = 6). Stool samples were collected at the time of diagnosis and stored at −80° until tumor necrosis factor (TNF)-α and calprotectin were measured by enzyme-linked immunoadsorbent assay.

Results: No significant differences in age at onset of diarrhea or in stool volumes were observed between both groups. In group 1, fecal TNF-α was undetectable/normal in 14 of 14 children, whereas group 2 showed dramatically elevated TNF-α levels (mean 3,104, range 237-18,078 pg/g) in 8 of 11 patients. Similarly, calprotectin levels were undetectable/normal in 14 of 14 patients in group 1 and highly raised in 11 of 11 patients in group 2 (median 1,145, range 375-3,095 μg/g), P < 0.01. Under therapy, these inflammatory parameters normalized.

Conclusions: Determination of fecal inflammatory markers is a simple method helping to distinguish constitutive from immuno-inflammatory etiologies of severe persistent diarrhea. These data also suggest that constitutive enterocyte disorders are not accompanied by an inflammatory mucosal reaction.

Author Information

*Laboratory of Functional Coprology, Pitié-Salpétrière Hospital, Paris France; †Pediatric Gastroenterology Unit, Department of Pediatrics, Necker-Enfants Malades Hospital, University René Descartes, Paris, France; and ‡Department of Pathology, Necker-Enfants Malades Hospital, University René Descartes, Paris, France

Received June 6, 2005; accepted July 8, 2005.

Address correspondence and reprint requests to Dr. F. M. Ruemmele, Pediatric Gastroenterology Unit, Hôpital Necker-Enfants Malades, INSERM EMI0212, Necker Faculty of Medicine, University René Descartes, Paris V, 149 Rue de Sèvres, F-75743 Paris, Cedex 15, France. (e-mail:

© 2005 Lippincott Williams & Wilkins, Inc.