Helicobacter pylori - Portal Neonatal

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Introduction
Microvillus inclusion disease
and epithelial dysplasia
Olivier Goulet, Nelly Youssef and Frank M Ruemmele
The definition, presentation and outcome of
intractable diarrhea of infancy (IDI) have changed
considerably over the past three decades, owing to
major improvements in nutritional management,
and a better understanding of the pathology of the
small bowel mucosa.
Definition of protracted and
intractable diarrhea of infancy
Originally, the syndrome of IDI was described by
Avery et al in 1968, based on the following
features: diarrhea occurring in a newborn younger
than 3 months of age, lasting more than 2 weeks,
with three or more negative stool cultures for
bacterial pathogens. 1 Most cases were managed in
hospital, using intravenous fluids while the diarrhea
was persistent and intractable, with a high
mortality rate from infection or malnutrition. 2
Recently, the term ‘severe diarrhea requiring
parenteral nutrition’ was proposed. 3,4 Within this
group of pathologies, two major subtypes can be
differentiated. The first group is made up of
patients with ‘protracted diarrhea of infancy’ (PDI),
which subsides despite its initial severity. PDI can
result from a specific immune deficiency, a sensitization
to a common food protein (e.g. cow’s milk
or gluten), or it can be secondary to a severe
infection of the digestive tract (post-enteritis
syndrome). The second group is characterized by
an ‘intractable diarrhea of infancy’, with onset
within the first 2 years of life. In this second group,
diarrhea persists sometimes for years, despite
prolonged bowel resting and various therapeutic
trials. In most cases, such as constitutive enterocyte
disorders 5 or autoimmune enteropathy, 6 the
situation becomes rapidly life threatening, and
these patients depend on long-term parenteral
nutrition (PN). Some of them are candidates for
intestinal transplantation. Table 1.1 shows the
diagnostic heterogeneity of 65 cases with severe
diarrhea requiring PN for more than 1 month, as
recently analyzed by a French multicenter study. 7
The so-called ‘intractable ulcerating enterocolitis’
of early onset is difficult to classify. 8 It is very
important to distinguish between IDI and PDI,
since children with PDI always recover, sometimes
after only several weeks or months of parenteral
and/or enteral nutrition. In contrast, patients with
IDI never recover, and are dependent on life-long
parenteral nutrition or – in the case of autoimmune
enteropathy – life-long massive immunosuppressive
medication.
Current classification
An attempt to classify intractable diarrhea according
to villus atrophy was proposed, on the basis of
immunohistological criteria emphasizing the role
of activated T cells in the intestinal mucosa. 9 A
multicenter survey from the European Society for
Paediatric Gastroenterology, Hepatology and
Nutrition (ESPGHAN) collected different cases of
IDI and villus atrophy with precisely defined light
microscopic characteristics, categorizing several
types of IDI. 10 On histological analysis, two clearly
different groups of IDI can be separated. The first
one is characterized by a mononuclear cell infiltration
of the lamina propria, and is considered to
be associated with activated T cells. Within this
group, two different clinical presentations can be
distinguished. Patients presenting with additional
extradigestive autoimmune symptoms (such as
diabetes, arthritis, thyroiditis, dermatitis and
nephrotic syndrome) tended to have a later onset
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