30th July 2023

Malabsorptive Diseases

Malabsorption (the impaired absorption of nutrients in the GI tract) is a key cause of malnutrition and hence necessitates further attention. Key conditions are highlighted below, and more information can also be found in the Lower GI Pathology, Upper GI Pathology, Pancreatico-biliary Pathology, and Bowel Infection and Inflammation topics.

Malabsorptive diseases can be broadly subcategorised by the primary site of pathology.

Intestinal causes

Coeliac disease

Coeliac disease is an autoimmune condition in which autoantibodies are produced in response to the protein gliadin found in wheat. It is pathologically characterised by chronic inflammation, crypt hyperplasia and villous atrophy of the small bowel, especially the duodenum. The immune response is mediated by T cells, and hence is a type IV hypersensitivity reaction.

It has 2 peaks of presentation – childhood, when gluten is first introduced into the diet, and early middle age, which is the commonest age of onset in the UK.

The typical presentation is of chronic abdominal pain, postprandial bloating, diarrhoea (often steatorrhea due to the malabsorption), weight loss, fatigue, and in children, failure to thrive. It is often associated with anaemia. Extraintestinal manifestations include dermatitis herpetiformis and arthralgia.

Suspected coeliac disease can be screened for by testing tissue transglutaminase antibodies (anti-tTGA) and IgA anti-endomysial antibodies (anti-EMA IgA). Total IgA levels should also be checked, as IgA deficiency can lead to false negatives. The gold standard diagnostic test is endoscopy, with at least 5 biopsy samples required from different (duodenal) sites. It is essential that a patient continues to eat gluten for the 6 weeks preceding this, or false negatives can occur. The mainstay of treatment is complete elimination of gluten from the diet.

Complications include micronutrient deficiencies, and it is also associated with osteoporosis, hyposplenism, and an increased risk of GI lymphoma.

Inflammatory bowel disease (IBD)

Crohn’s disease and ulcerative colitis can both lead to malabsorption, but this is more common in Crohn’s disease. Malabsorption occurs due to the chronic inflammation of the bowel impairing the ability of the GI tract to absorb nutrients. Malabsorption may also be a consequence of bowel resections, which are sometimes required to treat refractory IBD.

More information on the diagnosis, clinical features and management of IBD can be found in the Bowel Infection and Inflammation topic.

Tropical sprue

Tropical sprue is a condition which can be seen in travellers to tropical regions, and presents with acute or chronic diarrhoea, leading to malabsorption. Folic acid and vitamin B12 are particularly common associated deficiencies. The exact aetiology is unknown, but it is thought to have an infectious cause. It causes pathological features similar to coeliac disease, as bowel mucosa over time will exhibit crypt hyperplasia and villous atrophy.

There is no targeted treatment, and management is instead supportive, including fluid and electrolyte correction, treatment of anaemia, and replacement of any deficient micronutrients.

Whipple’s disease

Caused by infection with Tropheryma whipplei, and has a preponderance to middle aged men. Initially presents with abdominal pain, diarrhoea/steatorrhoea, and weight loss, and is associated with arthralgia, lymphadenopathy and hyperpigmentation of the skin. If untreated, it can progress to affect the CNS and heart, with the most serious consequences including seizures, ataxia, endocarditis and myocarditis.

Diagnosis involves upper GI endoscopy, and a key feature is villous granules that are strongly positive for the Periodic acid-Schiff stain.

Treatment involves 2 weeks of IV ceftriaxone or benzylpenicillin, followed by a 1-year maintenance treatment of oral co-trimoxazole. In cases where the CNS or heart is involved, oral doxycycline and hydroxychloroquine are also given.

Chronic diarrhoeal illnesses

Any chronic diarrhoeal illness can lead to malabsorption, as any intake will not be able to be appropriately absorbed, and over time they can cause chronic inflammation in the gut, which impairs absorption.

As well as other primary bowel diseases already discussed, infectious illnesses such as giardiasis can cause chronic diarrhoea. Giardiasis by the protozoan Giardia lamblia, and is frequently seen in travellers and people living in areas with poor sanitation. Generally self-limiting, it can be treated with metronidazole, if required.

Short gut syndrome

This refers to, quite literally, the occurrence of a shorter than normal small bowel, generally due to bowel resection in the treatment of various diseases, or due to congenital abnormalities. Having a reduced amount of bowel impairs the ability of the GI tract to absorb nutrients. Management is supportive, with nutritional supplements generally required, and even parenteral nutrition in severe cases.

Pancreatic causes

The pancreas produces many enzymes essential for digestion and absorption of nutrients, as its exocrine function. Any disease affecting the pancreas can therefore impair this process and lead to malabsorption; this is globally termed as ‘pancreatic insufficiency’. Symptoms include abdominal pain, postprandial bloating, steatorrhoea and weight loss. It is often associated with diabetes, which is due to impairment of the endocrine function of the gland; as whatever disease process is impairing its exocrine function may also impair its endocrine function.

Pancreatitis and pancreatic cancer may cause pancreatic insufficiency due to the chronic inflammation in the organ. It is also associated with cystic fibrosis due to impairment of mucus production and secretion from the pancreas gland. Obstruction and strictures may also impair the secretions of enzymes, and resection will damage the gland’s function, also.

Diagnosis can be made with the faecal elastase test; samples will be deficient, as this enzyme is produced by the pancreas. Other diagnostic investigations include abdominal imaging such as x-ray, CT and MRI, and ERCP and MRCP for more focused imaging of the pancreaticobiliary tree – with these tests predominantly focused on detecting the cause.

Management involves treatment of the underlying cause and the use of pancreatic enzyme replacements. The most commonly available formulation is Creon, which contains amylase, lipase and protease. Enzymes are typically taken alongside meals and snacks, in order to enable digestion and absorption.

Biliary causes 

The biliary tree is a vital part of the body’s absorption system, through the production and reabsorption of bile acids, which are essential for fat absorption. Bile acids are produced in the liver and then stored and released by the gallbladder. Reabsorption occurs in the terminal ileum.

Any disease affecting the biliary tract can lead to bile acid malabsorption (BAM), as well as those affecting the ileum. This includes primary biliary cholangitis, primary sclerosing cholangitis, gallbladder stones, Crohn’s disease, coeliac disease, pancreatic insufficiency, bacterial overgrowth, or following cholecystectomy or bowel resection.

BAM causes a distinct non-bloody pungent diarrhoea (steatorrhoea), which is generally chronic. The diagnostic test used to be the selenium homocholic acid taurine (SeHCAT) test, but NICE recommendations now advise treatment trials, 48-hour total stool bile acid levels, and fasting C4 levels instead.

Treatment involves a low fat diet and bile acid binders, such as cholestyramine.