Management of Coeliac Disease

Learning objectives

By the end of this chapter, participants will be able to:

• Recall the role of each healthcare professional (HCP) in the management of coeliac disease (CD)
• Recognise what foods should be avoided in a gluten-free diet (GFD)
• Identify conditions associated with CD

Gluten-free diet (GFD)

• Currently, the only available treatment of CD with proven efficacy is a lifelong and strict GFD.¹
• A GFD can help with symptom relief and reducing the risk of complications. However, it is uncertain whether the approach is beneficial in asymptomatic patients.²
• The first step is to educate patients about which foods contain gluten and encourage patients to eat naturally occurring gluten-free food with alternative sources of starch (e.g. rice, corn, potatoes).² Infographic patient information can help provide guidance on which foods contain gluten (e.g. Figure 1).

Figure 1: Information on foods containing gluten

• Removal of gluten (<20 mg gluten intake per day) from the diet will result in symptomatic, serological and histological remission in most patients with CD.³
  • With strict dietary adherence, the titre of CD-specific antibodies normalises.¹
  • Strict dietary adherence should improve mucosal healing and remission of most gastrointestinal symptoms.² However, only 57–76% of patients achieve full mucosal healing thanks to the diet.² Ongoing medical evaluation by a gastroenterologist is needed.²
  • Gastrointestinal symptoms are expected to improve within a few weeks on a GFD, while problematic histologic and serological responses, such as vitamin deficiencies, are resolved within 1–2 years.⁴
• Following a GFD can be challenging for patients due to increased cost, negative social impact and potential nutritional deficiencies.⁵
• If the GFD is not established by an HCP, there is an increased risk of weight gain, hyperlipidaemia, hyperglycaemia, and coronary heart disease.⁵
• Post-menopausal women with CD following a GFD may require nutrient supplementation (usually calcium, vitamin D and alkaline phosphatase).²

Additional management options

• Patients should be encouraged to join CD support groups, where applicable and available.²
• Adolescents with CD should undergo a structured transition to adult care: this should be a collaborative effort (between the patient, their family or caregiver, their doctor and dietician) and involve patient education on GFD, as well as familiarisation with healthcare access and available psychological support.^5,6
• Patients with severe CD may not respond to a GFD and may require hospital admission, repletion of fluids and electrolytes, intravenous nutrition, iron, vitamins, and occasionally, steroids.³
• Currently, the only available treatment of CD with proven efficacy is a lifelong and strict GFD.¹ Novel treatment approaches may involve immunotherapy and TG2 inhibitors. These approaches are undergoing further study to better understand the benefits for specific subgroups of CD patients.²
• A summary of novel treatment options at the forefront of research is provided below:

Multidisciplinary HCP team for management of CD

• Current approaches to CD diagnosis and treatment do not always meet the required best-practice standards for many reasons including inadequate HCP training, delay in diagnosis, and potential for financial burden to patients (due to the increased cost of a GFD).⁹

Figure 2: Flowchart of management of CD by HCPs

• Gastroenterologists are well placed to diagnose and manage CD: their specialist knowledge supports a timely diagnosis of CD, particularly in patients with very mild symptoms who are often challenging for general physicians to recognise.⁹
• Primary care physicians are well placed to request initial screening tests for CD (serology tests) and may provide long-term follow-up for patients with CD.²
• Newly diagnosed patients should be referred to a dietitian to discuss dietary management. The dietician plays an essential role in CD management, providing patient education on gluten avoidance and sufficient nutrient intake (including vitamins, fibre and calcium) during a GFD.^2,10
• Patients who do not respond to a GFD should return to a dietitian for investigation of the causes. If there is no evidence of continuing gluten intake, referral to a gastroenterologist with experience in the evaluation of non-responsive CD is recommended. Although gluten exposure is the most common cause of non-responsive CD, it is important to exclude other conditions that could explain the symptoms, such as irritable bowel syndrome, other food intolerances, microscopic colitis or small intestinal bacterial overgrowth.^1,10
• Once CD has been stabilised, annual follow-up by a doctor should include checking on intact absorption in the small intestine (full blood count, ferritin, serum folate, vitamin B₁₂, calcium, alkaline phosphatase), associated autoimmune conditions (TSH, thyroid hormones, serum glucose), liver function (aspartate aminotransferase / alanine aminotransferase) and dietary adherence (anti-TG2 or EMA tests).²
• Nurses should also be considered as part of a quality healthcare framework. They are often accessible and well placed to support CD management by providing practical advice on symptom management and treatment adherence, as well as referral to the dietitian and/or gastroenterologist as needed. Nurses may also arrange blood tests and monitor the prescription of gluten-free foods and anthropometry (weight and body mass index).¹¹
• Pharmacists can also support CD patients by liaising with the medical team involved and addressing patients’ prescription needs, as well as providing general advice and support.¹²

Coeliac crisis

• Coeliac crisis is a life-threatening syndrome involving acute and severe dramatic metabolic derangements.¹³
• It is mostly reported in children, but it may also appear in adults.¹³
• Coeliac crisis may develop owing to long-standing, untreated CD, and it is expressed as hypovolaemia, severe diarrhoea, acidosis, hypocalcaemia, hypoalbuminaemia and metabolic disturbances that usually require hospitalisation.^1,13
  • There is an acute onset or rapid progression of gastrointestinal symptoms.^13,14
  • Other symptoms include severe dehydration, haemodynamic instability or orthostatic hypotension, neurological and renal dysfunction, electrolyte imbalances and weight loss.^13,14
• Coeliac crisis treatment involves hospital admission for rehydration and restoration of electrolyte balance.¹
  • Initiation of total parenteral nutrition and/or systemic glucocorticoid therapy is required in about 50% of patients with coeliac crisis.¹⁴
• Rarely, CD may present with acute colonic pseudo-obstruction, with severe abdominal pain, extreme bloating and paralysis of intestines.¹⁵
  • Patients presenting with acute abdominal pain may undergo unnecessary explorative surgery, which may be avoided by the rapid or speedy determination of CD-specific autoantibodies from serum testing. CD is newly diagnosed in approx. 3% of patients presenting to secondary care with unselected acute abdominal pain.¹⁶

Complications associated with untreated CD

The complications listed below can be found in patients with untreated CD and may be identified and managed by different members of the multidisciplinary team:

Figure 3: Comorbidities associated with nutrient deficiencies occurring in CD Adapted from: Kreutz JM, et al. 2020.¹⁷

• Osteoporosis/osteopenia: Reduced bone mineral density is commonly reported in CD. Its onset varies significantly among patients.¹ In severe forms, it may lead to fractures before the diagnosis of CD.¹⁸
• Short stature: There may be a delay in physical growth as a result of malnutrition, resulting in short stature, especially when CD remains undiagnosed until adulthood.¹⁹
• Dermatitis herpetiformis: A skin manifestation of CD, potentially recurrent, with a variable onset among patients. It occurs due to a cross-reaction of IgA autoantibodies to gut tissue transglutaminase (TG2) with the highly homologous epidermal transglutaminase (TG3).²⁰ Symptoms are usually treated with dapsone and may be limited when following a GFD.¹ However, dapsone can be reduced or discontinued after an average of two years on a strict GFD.²⁰
• Non-specific skin conditions: CD patients normally complain about dry skin, easy bruising, brittle nails and thinning hair. Dermatological issues usually arise due to zinc deficiency, and repletion of zinc, iron and fat-soluble vitamins deficiencies can accelerate clinical improvement. Alopecia areata and severe hair loss may coexist with skin conditions and usually require referral to a dermatologist for evaluation.¹⁴
• Malignancies: Commonly reported CD-induced malignancies are intestinal and extra-intestinal lymphomas and carcinomas of the upper digestive tract. The risk is significantly reduced with a strict GFD.¹
• Pancreatitis (chronic or idiopathic recurrent acute): Due to the reduced enterokinase production in the atrophic gut mucosa, pancreatic enzymes are not properly activated during active CD, resulting in pancreas hypofunction, which is mostly reversible on a GFD.²¹ CD may also present as recurrent acute pancreatitis or be complicated by chronic pancreatitis. Both are rare, but for patients with treated CD and persistent diarrhoea, pancreatic exocrine insufficiency may be suspected.¹
• Pneumococcal infection: Hyposplenism and increased risk of infections has been associated with CD. Vaccination against pneumococci, Haemophilus influenzae and meningococci is recommended in some clinics.¹
• Fertility-related issues: Undiagnosed or untreated CD is associated with pregnancy issues, such as infertility or spontaneous abortions in women, and poor foetal outcomes or low birth weight infants. Following a strict GFD reduces the risk of such issues.¹⁴
• Micronutrient deficiencies: These may arise due to untreated CD or strict adherence to a GFD that is unbalanced in vitamins or minerals. Iron deficiency and related anaemia, for example, are common complications of untreated CD but will normally improve with a GFD. In addition, vitamin B12 and zinc deficiencies are other reported deficiencies of untreated CD, along with vitamin D deficiency owing to fat malabsorption. Such deficiencies tend to improve with compliance to a GFD and vitamin supplementation (as required).¹⁴

Follow-up consultations

• Patient adherence to the treatment plan is improved by having regular follow-ups (annual reviews) in a specialist CD clinic setting.²
• In the first year after establishing the diagnosis, follow-up needs to be frequent to optimise the chance of dietary adherence, provide psychological support and to optimally motivate the patient to adapt to a new situation.¹⁴
• Patients with severe CD should be encouraged to speak with their family and friends regarding the dietary requirements of a GFD in order to increase the available support for their adherence to a GFD.¹⁴
• The clinic should provide gastrointestinal and dietetic expertise. Follow-up visits could be in either secondary or primary care clinics (depending on the availability of expertise). Should any problems arise, specialist intervention in secondary care clinics should be provided.²
• When following up CD, the physician should evaluate key endpoints (such as the absence of any symptoms and mucosal healing) by evaluating serum antibodies and the overall health status of the patient.^2,14
• Bone mineral density should be evaluated after one year on a GFD to assess for osteopenia or osteoporosis.¹
• Serology markers are measured to assess adherence to GFD. All coeliac-specific antibodies are gluten-dependent. Therefore, a decrease from baseline values within months of a strict GFD, would indicate good patient adherence.¹⁴
• A significant decrease or normalisation of markers of malabsorption, such as steatorrhoea, should be expected with adherence to a GFD.¹⁴
• Liver enzyme abnormalities, if present, need to be followed up. If they are persistent then further assessment (immunological, radiological and/or histopathological) is required.¹⁴
• In adults, neither absence of symptoms nor serology is reliable to evaluate small intestinal damage. However, an early biopsy (within the first 6 months on a GFD) is not recommended, and some villous atrophy is present in about 40% of patients on a strict GFD at one year. It may be reasonable to do a follow-up biopsy in adults after 1–2 years of starting a GFD to assess for mucosal healing.^2,14 Mucosal recovery may take up to two years, and can remain incomplete for longer periods.¹⁴
• Follow-up biopsies may be helpful in identifying patients at increased risk of lymphoma, those with an increased risk of complications or those with refractory CD.²
• Once the disease is stable and the patients manage their diet without problems, annual or biennial follow-ups should be initiated. The physician should check the integrity of small intestinal absorption, associated autoimmune conditions (particularly thyroid disorders and diabetes), liver disease and adherence to GFD by measuring coeliac-specific serum antibodies (anti-TG2 or EMA).¹⁴

Assessing patient adherence on GFD

Treatment plan compliance is affected by several factors, such as age at diagnosis, knowledge of disease and psychological factors. There are four steps to assess dietary adherence that are provided below:²

• Clinical assessment of symptoms: Symptoms similar to those of irritable bowel syndrome are more common in patients with CD who do not adhere to a GFD.
• Dietetic review: This is conducted by a dietician or dedicated physician by completing specific questionnaires. There is no standard of quality control for dietetic reviews, but during these the dietician can assess patient adherence and provide education for a balanced and adequate nutrient intake.
• Serum antibodies: It is still unclear whether they indicate mucosal recovery or not, but serology tests (usually IgA anti-TG2 tests) are recommended for evaluating adherence to a GFD, since persistent positivity indicates regular gluten intake.
• Follow-up biopsy: A duodenal biopsy may be useful to assess mucosal recovery and to exclude refractory CD.

Conclusion

• The goal of CD treatment is to relieve symptoms and achieve mucosal healing, while avoiding complications and maintaining a good quality of life with a nutritionally complete GFD.
• To improve treatment outcomes, patients should receive collaborative expert healthcare and advice from a relevant multidisciplinary team.
• Follow-up of CD is needed to evaluate response to treatment, prevention of complications/comorbidities and patient adherence to the GFD.

References

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