Textbook of Pediatric Gastroenterology, Hepatology and Nutrition

Before focusing on microvillus inclusion disease and tufting

enteropathy, we briefly review similarly presenting entities.

In 1968 Avery, Villavicencio and Lilly were the first to describe

a severe chronic diarrhea in 20 infants and they named

it “infantile intractable diarrhea”; according to their description

“(it) was prolonged and intractable despite extensive

hospital therapy” [1].

This syndrome was defined on the basis of some clinic

characteristics, namely: (1) diarrhea of more than 2 weeks

duration, (2) age, less than 3 months, (3) three or more stool

cultures negative for bacterial pathogens, (4) necessity of

intravenous rehydration, and (5) prolonged and intractable

diarrhea despite hospital therapy.

The death rate was very high: 9 out of the 20 babies

(45 %) in Avery et al.’s record had died; it was even higher in

Hyman et al.’s (70 %) record [2].

Heterogeneity and lack of specificity are evident in Avery’s

original report: different pathologies were grouped in

it, some of which with a diagnosis were well defined even at

that time. Only autoptic material was available for the first

cases, and only after the introduction of total parenteral nutrition

(TPN) at the beginning of the 1970s [3] it was possible

to study the matter more in depth, thanks to proximal

small-intestinal biopsy [4] and later on to the development of 

endoscopic techniques, which were safe and adequate for the

infant as well. It became consequently possible to discriminate

different causes for the so-called intractable diarrhea of

infancy [5] but its definition superimposes on the definition

of “protracted diarrhea of infancy”: The latter has duration

in common with it, but a failure to gain weight is enough to

define the picture [6].

Many cases of “protracted diarrhea of infancy” are diet

associated, as a consequence of cow milk or lactose intolerance

or malnutrition. Malnutrition causes intestinal atrophy

and consequently a malabsorption syndrome and diarrhea,

which apparently gets better with fasting. These features

have almost disappeared in the developed countries.

The main causes of “intractable diarrhea of infancy,” including

more severe and longer forms, can thus be summed

up (see also Table 1.1):