Malabsorptive disorders and coeliac disease

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Chapter 11 MALABSORPTIVE DISORDERS AND COELIAC DISEASE

KEY POINTS

• Malabsorption may present with weight loss, bloating, diarrhoea and specific vitamin and nutrient deficiencies.
• Identification of the underlying cause and replacement of any nutrient deficiencies are the cornerstones of management.
• Coeliac disease, bacterial overgrowth, food-cobalamin malabsorption, pancreatic insufficiency and malabsorption after gastric surgery are commonly seen in clinical practice.
• Coeliac disease affects 1% of the population and is often undiagnosed as many patients are asymptomatic.
• IgA antibodies to tissue transglutaminase and endomysium have a high sensitivity and specificity for coeliac disease. The diagnosis is confirmed by endoscopic small intestine biopsy.
• Serological testing for coeliac disease is appropriate in cases of weight loss, iron or folate deficiency, osteoporosis, irritable bowel syndrome and in at-risk groups including first-degree relatives of diagnosed cases, type 1 diabetes, autoimmune thyroid disease and Down syndrome.
• A lifelong gluten-free diet is the only effective treatment and ameliorates the malabsorptive and neoplastic risks of coeliac disease.

INTRODUCTION

The body obtains nutrients from food by the absorption of food components that have been broken down by digestion. Malabsorption is the failure of the processes of digestion and absorption, and may present with weight loss, bloating, diarrhoea and a myriad of specific vitamin and nutrient deficiencies. Identification of the underlying cause and replacement of vitamin and nutrient deficiencies are the cornerstones of management (see Figure 11.1). An aetiologic classification of malabsorption is listed in Table 11.1 with the types commonly seen in clinical practice summarised in Table 11.2.

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FIGURE 11.1 Management of malabsorption.

TABLE 11.1 Classification of malabsorption

Pancreatic insufficiency

Chronic pancreatitis
Cystic fibrosis
Pancreatic carcinoma

Mucosal disease

Coeliac disease
Crohn’s disease
Tropical sprue
Short bowel syndrome
Post radiotherapy
IgA deficiency and common variable immunodeficiency
Amyloidosis
Bile salt deficiency

Bacterial overgrowth
Biliary obstruction
Chronic cholestatic liver disease
Other

Post gastric surgery
Intestinal lymphangiectasia

TABLE 11.2 Common types of malabsorption in clinical practice

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PANCREATIC INSUFFICIENCY

Pancreatic disease resulting in pancreatic lipase activity to less than 10% of normal will cause steatorrhoea and weight loss as a result of fat malabsorption. Common causes of pancreatic insufficiency include cystic fibrosis, chronic pancreatitis, pancreatic resection and, occasionally, pancreatic carcinoma.

Steatorrhoea is characterised by offensive pale floating stools that are difficult to flush and although often most marked in pancreatic disease, steatorrhoea can also be a feature of biliary or diffuse intestinal mucosal disease.

Testing for pancreatic insufficiency

The measurement of stool fat in a 72 hour stool collection while consuming 80–100 g of fat per day is the best validated test for pancreatic insufficiency. Excretion of more than 7 g of fat per day suggests steatorrhoea. Of note, severe diarrhoea of any cause can result in up to 14 g of stool fat daily, while a low-fat diet can result in less than 7 g of fat per day in patients with fat malabsorption.

Treatment

Treatment is with pancreatic enzyme supplements. At least 30,000 units of pancreatic lipase are given with each meal with some experts suggesting 90,000 units. The addition of a proton pump inhibitor reduces enzyme denaturation by gastric acidity.

BILE SALT DEFICIENCY

A deficiency of the detergent-like activity of bile salts in the absorption of fat is commonly found in bacterial overgrowth, Crohn’s disease of the terminal ileum, surgical resection of the terminal ileum, bile salt transporter defects at the terminal ileum, chronic biliary obstruction and chronic cholestatic liver disease such as primary biliary cirrhosis and primary sclerosing cholangitis.

Bacterial overgrowth

In health, the bacteria that are cultured from the small intestinal lumen are transiently present in counts of less than 104 per mL of jejunal content. Stasis of luminal contents due to impaired motility or structural abnormalities can result in bacterial overgrowth. Excess bacteria can produce malabsorption by deconjugating bile salts, rendering them inadequate for micelle formation and fat digestion. Bacterial-induced B12 deficiency may also occur.

Aetiology

Diabetes, scleroderma and chronic intestinal pseudo-obstruction impair small bowel motility while surgery, Crohn’s disease, radiation, non-steroidal antiinflammatory drug (NSAID)-related strictures and multiple small intestine diverticula cause structural changes that promote stasis.

Diagnosis

Breath tests for carbohydrate and bile acid malabsorption have poor sensitivity and specificity and the gold standard of quantitative jejunal culture is not routinely available. In practice, a clinical diagnosis is usually made when there is a response to antibiotic therapy in the context of one of the predisposing conditions noted earlier.

Treatment

Options include nutritional supplementation, correction of structural abnormalities or antibiotic therapy on an intermittent, cyclic or regular basis with tetracycline, doxycycline, metronidazole, cephalexin or amoxycillin with clavulanic acid.

MUCOSAL DISEASE

Diseases that damage the mucosa of the small intestine will directly impair absorption. Examples include coeliac disease, Crohn’s disease, tropical sprue, short bowel syndrome, post radiotherapy, IgA deficiency and amyloidosis. Coeliac disease is the most common cause of malabsorption due to mucosal disease.

Coeliac disease

In patients with coeliac disease, wheat proteins known as gluten and their equivalents in rye and barley trigger an immune response in the mucosa of the small intestine. These proline-rich proteins resist digestion and are deamidated by an enzyme known as tissue transglutaminase in the intestinal mucosa. Antigen presenting cells with specific HLA heterodimers on their surface (HLA-DQ2 in 95% and HLA-DQ8 in 5% of cases) present the antigen to CD4+ T cells resulting in an immune response that leads to mucosal damage characterised by intraepithelial lymphocytosis, villous atrophy and crypt hyperplasia. This mucosal damage or enteropathy is most marked in the proximal small intestine and impairs absorption.

Prevalence

In Caucasian populations, around 1% of individuals have coeliac disease. The prevalence is higher in certain at-risk groups including individuals with Down syndrome, type 1 diabetes, IgA deficiency, autoimmune thyroid disease and in first-degree relatives of patients with coeliac disease who have a 5% risk.

Clinical presentation

The classical presentation with weight loss, abdominal distension, lethargy and steatorrhoea is uncommon. In fact, 30% of patients are overweight at diagnosis. Many patients have no symptoms at all, termed silent coeliac disease.

Coeliac disease should be considered as a possible underlying cause in cases presenting with irritable bowel syndrome (up to 5% are affected), osteopenia or osteoporosis, infertility, iron or folate deficiency, recurrent oral aphthous ulcers and unexplained weight loss.

Diagnosis

A flow diagram summarising the diagnosis and management of coeliac disease is shown in Figure 11.1.

Testing for coeliac disease is only reliable in individuals consuming a gluten-containing diet.

In studies comparing controls with coeliac cases known to have villous atrophy on small intestine biopsy, antibodies to endomysium (IgA-EMA) and tissue transglutaminase (IgA-tTG) have been shown to have a 90%–100% sensitivity and specificity and are the recommended tests for serological screening. The IgA antigliadin antibody has approximately an 80%–90% sensitivity and specificity. The sensitivity of all of these assays is lower in cases with lesser degrees of histologic abnormality (e.g. intraepithelial lymphocytosis or crypt hyperplasia only). In IgA-deficient individuals serologic testing with IgG antibodies to the same antigens is known to have a much lower sensitivity for coeliac disease (around 30%).

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FIGURE 11.2 Diagnosis and management of coeliac disease.

*IgA deficient individuals will have negative results. **If strong clinical suspicion remains, check HLA haplotype.

IBS = irritable bowel syndrome; IgA-EMA = endomysium antibody; IgA-tTG = tissue transglutaminase antibody.

A small intestine biopsy on a gluten-containing diet is essential to confirm a diagnosis of coeliac disease. An increased number of lymphocytes in the small intestine epithelium (intraepithelial lymphocytosis) is the earliest abnormality on routine histology, but only a minority of patients (10%) with this finding will have coeliac disease, as assessed by positive serology. Crypt hyperplasia and partial or complete villous atrophy are typical findings that are diagnostic in the presence of positive serology.

The HLA-DQ2 and DQ8 alleles that predispose to coeliac disease are present in 30% of Caucasians, and their absence effectively excludes the diagnosis of coeliac disease in cases of doubt.

Management

Management focuses on the replacement of any nutritional deficiencies and commencement of a gluten-free diet with support and monitoring.

Assessment of nutritional deficiencies

Iron, folate and vitamin D deficiencies are common at diagnosis and replaced with oral supplements. Around 12% will have associated B12 deficiency related to food-cobalamin malabsorption requiring parenteral replacement.

Instituting a gluten-free diet

Newly diagnosed patients must consult with a dietician for expert advice regarding a gluten-free diet and the interpretation of food labels. Joining a local support group (e.g. their state Coeliac Society in Australia) is strongly recommended for educational meetings and local contacts.

Consider associated diseases

Autoimmune thyroid disease and primary biliary cirrhosis are more common in individuals with coeliac disease.

Assessment for osteoporosis

Significant remineralisation occurs in the first 12 months on a gluten-free diet so bone density is usually assessed 12 months after diagnosis in patients at risk.

Monitoring compliance

Titres of IgA antigliadin and tTG antibodies usually fall to normal levels after 6 and 12 months of compliance with a gluten-free diet respectively. A small intestine biopsy after 6–12 months on a gluten-free diet can be useful to document histologic improvement and dietary compliance. Long-term follow-up is required.

Screen first-degree relatives serologically, as 5% will have coeliac disease.

MALABSORPTION AFTER GASTRIC SURGERY

Partial or total gastrectomy is commonly associated with malabsorption of fat, iron, vitamin B12 and vitamin D. Gastric atrophy with loss of acidity, rapid transit, impaired pancreatic stimulation and asynchronous pancreatic and biliary secretions contribute. Monitoring after surgery facilitates early replacement of any deficiencies.

LACTASE DEFICIENCY

A genetically determined deficiency of the brush border enzyme lactase commonly develops in adulthood, affecting 80%–100% of African and Asian individuals and 25% of Caucasians. Lactose (milk sugar) that is not digested and absorbed is metabolised by colonic bacteria resulting in diarrhoea, abdominal cramps and bloating after meals. A small intestine biopsy for measurement of disaccharidase activity or a lactose-hydrogen breath test can confirm the diagnosis. Reducing dietary lactose ameliorates the symptoms.

FOOD-COBALAMIN MALABSORPTION

Vitamin B12 deficiency commonly presents with fatigue or macrocytic anaemia. When severe and prolonged, neurological manifestations such as sensory neuropathy or spastic ataxia may occur. Levels of plasma homocysteine and methylmalonic acid are elevated by B12 deficiency and can be useful to confirm the diagnosis where serum B12 levels are only borderline low without clinical features of deficiency.

The most common cause of B12 deficiency is food-cobalamin malabsorption, where vitamin B12 (also known as cobalamin) cannot be liberated from food or intestinal transport proteins (70% of cases). Age-related gastric atrophy, metformin use, acid suppression with proton pump inhibitors, gastrectomy and alcohol abuse can contribute to food-cobalamin malabsorption. Less common causes of B12 deficiency include a dietary deficiency of B12 in strict vegetarians (5% of cases) and pernicious anaemia (20% of cases). Testing for antibodies to intrinsic factor and parietal cells will identify pernicious anaemia, which causes an autoimmune gastritis of the gastric body and fundus with impaired acid and intrinsic factor secretion. Antibodies to intrinsic factor have 50% sensitivity and 90% specificity for the diagnosis of pernicious anaemia, respectively, while antiparietal cell antibodies have a 90% sensitivity and 50% specificity. Currently B12 deficiency is treated by parenteral vitamin B12 replacement but there is increasing evidence that oral replacement may be satisfactory in many cases provided large doses of 0.5–1 mg are taken daily.

SUMMARY

Malabsorption occurs when there is failure of the processes of digestion and absorption. The cardinal clinical features include weight loss, bloating, diarrhoea and a myriad of specific vitamin and nutrient deficiencies. Identification of the underlying cause and replacement of vitamin and nutrient deficiencies are the cornerstones of management.

The causes of malabsorption are: mucosal disease (coeliac disease, Crohn’s disease, short bowel syndrome, post-radiation therapy, IgA deficiency, amyloidosis and tropical sprue); pancreatic insufficiency, bile salt deficiency and bacterial overgrowth. The common types of malabsorption seen in clinical practice are coeliac disease, lactase deficiency, food-cobalamin malabsorption, pancreatic insufficiency and malabsorption after gastric surgery.

In patients with coeliac disease, wheat proteins known as gluten and their equivalents in rye and barley trigger an immune response in the mucosa of the small intestine. The enteropathy is most marked in the proximal small intestine and impairs absorption. The classical presentation is weight loss, abdominal distension, lethargy and steatorrhoea. However, this presentation has become uncommon and most patients are asymptomatic. Diagnostic tests for coeliac disease detect antibodies to endomysium and tissue transglutaminase. A small intestine biopsy on a gluten-containing diet is essential to confirm a diagnosis of coeliac disease. Management focuses on the replacement of any nutritional deficiencies and the commencement of a gluten-free diet with support and monitoring.

FURTHER READING

Andres E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251-259.

Dewar DH, Ciclitira PJ. Clinical features and diagnosis of celiac disease. Gastroenterology. 2005;128(4 Supplement 1):S19-S24.

DiMagno EP. Gastric acid suppression and treatment of severe exocrine pancreatic insufficiency. Best Pract Res Clin Gastroenterol. 2001;15(3):477-486.

Riley SA, Marsh MN. Maldigestion and malabsorption. In Feldman M, Freidman LS, Brandt LJ, editors: Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management, 8th edn., Philadelphia: WB Saunders, 2006.

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