19th July 2023

Diseases of the Small Bowel

This section focuses on diseases that predominantly affect the small bowel – the duodenum, jejunum and/or the ileum. As the small bowel is the main site of absorption of nutrients and minerals for the body, disease within this part of the bowel often results in malabsorption and secondary malnutrition. Please refer to the topic “Infection and Inflammation” for detail on inflammatory bowel disease.

Coeliac Disease

Coeliac disease is a chronic autoimmune systemic condition characterised by intolerance to gliadin in gluten and prolamins in wheat, barley and rye. Exposure to these allergens causes a pro-inflammatory response resulting in villous atrophy in the proximal small bowel mucosa, reducing its ability to perform its absorption functions. It can present in childhood following introduction of gluten into the diet or adulthood – this is now the most common timing of presentation, with the average age of diagnosis in the UK around 40 years old. Typical symptoms include abdominal pain, bloating, diarrhoea, weight loss, failure to thrive, fatigue, arthralgia and pallor. Clues within the presentation to suggest possible coeliac disease include anaemia (secondary to iron +/or B12 +/or folate deficiency), dermatitis herpetiformis (blistering skin rash on extensor sites), aphthous ulcers, buttock wasting or faltering growth. Patients will typically have raised IgA tissue transglutaminase antibodies (anti-tTGA) and IgA endomysial antibodies (anti-EMA IgA). These should be checked alongside total IgA levels, as those with IgA deficiency may get false negative results. The gold standard for diagnosis is endoscopy with small intestine biopsies – this requires continued gluten-containing diet for at least 6 weeks prior to endoscopy. Eliminating gluten from the diet is the mainstay of treatment. Those diagnosed with dermatitis herpetiformis should be offered dapsone. Complications include mineral deficiencies – namely calcium, B12, folate, iron, vitamin D, osteoporosis, hyposplenism and small bowel lymphoma.

Small Intestine Bacterial Overgrowth (SIBO)

SIBO is excessive colonisation of the small bowel with bacteria – usually coliforms, which produce gas from fermenting carbohydrates. This causes GI symptoms – most commonly abdominal bloating and pain, flatulence and diarrhoea. Risk factors include previous bowel resection or gastric bypass, connective tissue disorders (systemic sclerosis, Ehlers-Danlos, rheumatoid arthritis) and medications (narcotics and PPIs). The excessive bacteria impair the small bowel’s absorptive function, causing vitamin and nutrient deficiencies, including vitamin B12, vitamin D and iron. Folate levels, however, tend to be elevated due to its synthesis by the bacteria. The gold standard diagnostic test used to be a culture of duodenal aspirates; however, its invasive nature and expense has resulted in the most up-to-date guidelines recommending hydrogen breath testing with either glucose or lactulose as the first line investigation. SIBO can be treated with a course of broad-spectrum antibiotics – most commonly rifaximin 550mg three times daily for 14 days.

Bile Acid Malabsorption (BAM)

BAM is a chronic condition caused by failed reabsorption of bile in the terminal ileum and subsequent accumulation in the colon, where it stimulates water and electrolyte secretion. It can be idiopathic or occur secondary to ileal dysfunction (resection or Crohn’s disease), coeliac disease, pancreatic insufficiency, bacterial overgrowth or following cholecystectomy. BAM presents with chronic non-bloody greasy pungent diarrhoea. It can be diagnosed using the selenium homocholic acid taurine (SeHCAT) test, however, this is no longer recommended by NICE. Other tests that aid diagnosis include a trial of treatment – 48-hour total stool bile acid levels or fasting C4 levels. The mainstay of treatment is implementing a low-fat diet and oral bile acid binders – most commonly cholestyramine.

Neuroendocrine Neoplasms (NENs) of the GI Tract 

GI NENS, previously called neuroendocrine tumours (NETs), are rare slow growing tumours of enterochromaffin cells. Most occur sporadically, however, some occur as part of a genetic syndrome, including MEN1 (10% of all GI NENs), Von Hippel Lindau, Neurofibromatosis-1 and Tuberous Sclerosis. GI NENs are most commonly found in the small bowel, rectum, pancreas, stomach and appendix. Most are non-functional and asymptomatic, leading to delays in diagnosis. Functional NENs (approximately 40%) release large amounts of vasopressor peptides into the circulation causing symptoms. Carcinoid syndrome, affecting <10% of NEN patients, predominantly occurs when the tumour metastasises to the liver and releases hormones including serotonin. This leads to the classic symptoms of Carcinoid syndrome – diarrhoea, flushing, wheeze and abdominal pain. Fibrosis of the right-sided heart valves and right-sided heart failure (carcinoid heart syndrome) can also occur. Other functional NENs that secrete specific hormones are shown in table 1.

Table 1: Functional Neuroendocrine Neoplasms of the GI Tract

Functional NENs can be investigated using a 24-hour urine 5-HIAA test, where levels will be raised. The validity of this test can be affected by foods and drugs that contain or trigger the release of serotonin, causing false positives. Diagnosis is made by CT/MRI abdominal imaging or on histology from biopsies taken during endoscopy. Management is complex and requires regional MDT discussion but typically:

• Localised and resectable tumours – endoscopic or surgical resection
• Functional tumours –monthly somatostatin analogue subcutaneous injections (usually octreotide or lanreotide)
• Metastatic tumours – somatostatin analogues, radionuclide therapy (MIBG), chemotherapy, and embolisation of hepatic metastases

Peutz-Jeghers Syndrome (PJS)

PJS is a rare condition characterised by multiple hamartomatous polyps throughout the GI tract, most commonly affecting the jejunum. It is caused by a mutation in the STK11 gene, 50% occurring de novo and 50% inherited in an autosomal dominant fashion. Around 50% of patients will present in their 1st or 2nd decade of life with bowel obstruction. Other symptoms include GI bleeding (overt or presenting as iron deficiency anaemia), abdominal pain and distension. A hallmark sign is pigmented macules on the buccal mucosa, perioral areas, lips, fingers and toes. Diagnosis is confirmed with genetic testing. Polyps can be resected under endoscopic guidance. Patients have a 93% lifetime risk of malignancy – intestinal most commonly (39% colorectal cancer, 19% small bowel cancer) but also extra-intestinal (breast, pancreatic and ovarian/testicular cancer).

Whipple’s Disease

Whipple’s disease is a rare disease caused by infection with Tropheryma whipplei – a gram positive actinobacteria. It most commonly affects middle-aged men. Early symptoms include abdominal pain, joint pain, weight loss, diarrhoea, lymphadenopathy, steatorrhoea and skin hyperpigmentation. The disease later spreads and affects the central nervous system (CNS) and heart. CNS symptoms include synchronised abnormal ocular and masticatory movements, abnormal facial movements, memory or consciousness impairment, seizures and ataxia. Cardiac manifestations include endocarditis or myocarditis. Diagnosis is made based on jejunal biopsies taken at upper GI endoscopy (PAS-positive granules in the villi) or by PCR of CSF or lymph nodes (positive for T.Whipplei DNA). Initial treatment of Whipple’s disease is 2 weeks of IV ceftriaxone or benzylpenicillin. This is followed by a 1-year maintenance treatment of oral co-trimoxazole. If there is CNS involvement, oral doxycycline and hydroxychloroquine are added.