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Diarrhoea due to small bowel diseases

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Abstract

Small intestinal diseases are a common, though often overlooked cause of diarrhoeal illness. Fully 1% of the Caucasian population are affected by coeliac disease and a substantial portion of children living in poverty in the developing world are affected by environmental enteropathy. These are but two examples of the many diseases that cause mucosal injury to the primary digestive and absorptive organ in our body. While diarrhoea may be a common, though not universally seen symptom of small bowel mucosal disease, the consequent malabsorption can lead to substantial malnutrition and nutrient deficiencies. The small intestine, unlike the colon, has been relatively inaccessible, and systematic evaluation is often necessary to identify and treat small intestinal mucosal diseases that lead to diarrhoea. Immunodeficiency states, including HIV enteropathy, adult autoimmune enteropathy, drug-associated enteropathy, and tropical sprue continue to occur and require specific therapy. All patients with severe diarrhoea or diarrhoea associated with features suggestive of malabsorption may have a disease of the small intestinal mucosa that requires careful evaluation and targeted management.

Introduction

This chapter will cover the clinical features of small intestinal diseases that can result in chronic diarrhoea (Table 1). A major focus will be on coeliac disease and other disorders that can mimic the clinical features, pathologic changes, and occasionally overlap with coeliac disease. We will address small intestinal overgrowth, tropical sprue, Whipple's disease and briefly discuss common variable immunodeficiency and other miscellaneous disorders.

Section snippets

Clinical clues for small bowel origin of diarrhoea

The small intestine is both a secretory and absorptive organ. Disorders of the small intestine can be primarily malabsorptive or secretory in nature but most disorders on the small intestine mucosa result in both excess secretion and failure of absorption. Diarrhoea of small bowel origin is more often non-inflammatory and high output. Improvement of diarrhoea after fasting suggests an osmotic component of the symptoms. Postprandial diarrhoea, bloating, malodorous flatus, and pale stools which

Coeliac disease

The most common inflammatory disorder of the small intestine in the Western world is coeliac disease. This is a chronic inflammation due to an immune reaction to dietary gluten which is present in wheat, barley, and rye.

Non-responsive coeliac disease

Approximately 10–20% of patients with coeliac disease will continue to have frequent symptoms or will have a relapse of symptoms despite an initial response to a gluten-free diet. The most common persistent symptoms are diarrhoea, and the most common explanation is continued contamination of the diet with gluten, either advertent or inadvertent [15]. A systematic approach to these patients is most valuable and will often reveal causes (Fig. 3). A systematic evaluation by an expert dietician is

Refractory coeliac disease

Refractory coeliac disease probably affects no more than 1–2% of patients. It is defined as severe malabsorptive symptoms that have persisted or recurred despite verified strict adherence to a gluten-free diet for at least 6 months in whom other causes of non-response (see above) have been either ruled out or adequately treated and who do not have overt lymphoma [16]. Much of what is known about refractory sprue comes from case series in national and international referral centres. The disorder

Small intestine bacterial overgrowth

Small intestine bacterial overgrowth occurs when symptoms are related to increased numbers of small bowel bacteria – by definition, >105 bacteria/mm3 in small bowel fluid culture [22]. These bacteria are usually but not exclusively anaerobic.

Whipple's disease

Whipple's disease is a rare disorder, primarily affecting the intestine but also affecting extraintestinal locations including the joints, lungs, central nervous system, heart and the eyes [30]. It is a chronic infection by Tropheryma whipplei, a fastidious intracellular organism. The modes of infection, transmissibility and predisposition to infection are poorly understood.

Tropical sprue

While coeliac disease is the most common chronic enteropathy in the developed world, tropical sprue is one of the most common disorders in certain parts of the developing world. The cause has never been identified [36] but is assumed to result from exposure to enteric bacteria.

Adult autoimmune enteropathy

Autoimmune enteropathy was first described in young children, often neonates who have a syndrome characterized by 1) severe diarrhoea with malabsorption, 2) total villous atrophy, and 3) anti-enterocyte antibodies. By definition, this condition does not respond to any form of food exclusion diet, and the patients lack obvious immunodeficiency [40]. The disorder also occurs in adults. It is thought that the immune system targets the components of the enterocyte via activation of the innate and

Conclusion

In summary, coeliac disease and these other disorders with malabsorptive symptoms can overlap or can be confused with each other. In particular, coeliac disease can be associated with small intestine bacterial overgrowth and in the context of IgA deficiency coeliac disease also with giardiasis. Small intestinal bacterial overgrowth itself can be seen in patients with immune deficiencies. Tropical sprue must always be considered in residents in or who travel to tropical sprue areas and travel

Conflict of interest

Grant support: Alba Therapeutics (>$50,000).

Advisory Board: Alvine Pharmaceuticals, Inc. (<$10,000).

Consultant: Ironwood, Inc. (<$10,000), Flamentera (<$10,000).

Actogenix (<$10,000), Bayer Healthcare Pharmaceuticals (<$10,000), Vysera Biomedical (<$10,000), 2G Pharma, Inc. (<$10,000), ImmunosanT, Inc (<$10,000), Shire US Inc (<$10,000).

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