Coeliac Disease:

Symptoms, Diagnosis, Treatment and Management

Dr Matthew Kurien Senior Clinical Lecturer and Honorary Consultant Gastroenterologist, University of Sheffield

Benign Diseases

• Review the CD Basics

• Hot topics

– Diagnosis

• Detection/ Serology/ Paeds vs Adults

– Treatment

• Gluten Free Diet/ Adherence/ Prescriptions

– Follow-up

• Problems/ Non-responders/ Refractory CD

• Other Gluten related disorders

Talk Outline

“Some people talk in their sleep. Lecturers talk while other people sleep” - Albert Camus (Nobel Prize for Literature 1957)

4

University of Bologna, c. 1350, Laurentius de Voltolina

Quiz

1. Name these famous people?

2. What do they have

in common?

Gluten Attack!

Damaged Villi Normal Villi

Marsh

Crite

ria

0 Normal

1 Raised Intra epithelial Lymphocytes

(IEL)

2 Raised IEL + Crypt Hyperplasia

3a Partial Villous Atrophy

(PVA)

3b Subtotal villous atrophy

(SVA)

3c Total villous atrophy

TVA)

What is the estimated Prevalence of

Adult Coeliac Disease in the UK?

1:100,000

1:1,000

1:10,000

1:100

Coeliac Disease

The historical prevalence of coeliac disease was 1 in 8000

Coeliac Disease affects ~ 1% of the adult population

• The commonest age for presentation is between the 4th to 6th Decade

• For every paediatric case diagnosed there are 9 adult cases

• Coeliac disease affects 1% of the adult population!

• For every adult case diagnosed there are 3-4 cases still not recognised

• People with undiagnosed adult

coeliac disease generally have a normal BMI and may even be overweight

Coeliac Disease can affect many organs and the gut is just the entrance point

Symptoms of Coeliac Disease

Diarrhoea

Classical Symptoms

Weight Loss Failure to thrive

CD - Symptoms Beyond Diarrhoea, Weight Loss and Anaemia

Diagnosis of Coeliac Disease

Diagnosis - Tip of the Iceberg

• 1 in every 4 CD patients detected

• Delays – Norstrom et al. BMC Gastro 2011 • Symptoms to Diagnosis – 9.7 years • 1st Doctor to Diagnosis – 5.8 years

5%

Coeliac serology

Schyum et al. UEG Journal 1(5) 319-325

EMA- endomysial Ab; tTG- tissue transglutaminase Ab; DGP - deamidated gliadin peptide

Next steps

• Explain that serology is not diagnostic

• Refer to a GI specialist for biopsy

• Maintain normal diet

NICE Guideline (2015) NG20

• Symptomatic – Diminished QoL

– Increased presentations to healthcare professionals

– Increased medical interventions (abdominal surgery/ endoscopy)

– Adverse pregnancy outcomes

– Increased lymphoma

– Mortality?

• Asymptomatic – Uncertainty if reduces risk of complication

– Improves QOL??

Consequences of Undiagnosed CD

Ludvigsson et al. UEG Journal 3(2) 106-120

Surgery and CD

Population Screening for CD

Ludvigsson et al. UEG Journal 2015 3(2): 106-120

Case-finding for CD

• Case-finding is a strategy for targeting resources at individuals or groups who are suspected to be at risk for a particular disease.

• Offer serological testing to:

– People with any of the following: • persistent unexplained abdominal or gastrointestinal symptoms

• faltering growth

• prolonged fatigue

• unexpected weight loss

• severe or persistent mouth ulcers

• unexplained iron, vitamin B12 or folate deficiency

• type 1 diabetes, at diagnosis

• autoimmune thyroid disease, at diagnosis

• irritable bowel syndrome (in adults)

– first-degree relatives of people with coeliac disease

Case-finding

NICE Guideline (2015) NG20

• Consider serological testing – metabolic bone disorder (reduced bone mineral density or

osteomalacia)

– unexplained neurological symptoms (particularly peripheral neuropathy or ataxia)

– unexplained subfertility or recurrent miscarriage

– persistently raised liver enzymes with unknown cause

– dental enamel defects

– Down's syndrome

– Turner syndrome

Case-finding

NICE Guideline (2015) NG20

J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):136-60.

To Biopsy or Not Biopsy?

Treatment for CD

Adult adherence to a Gluten-Free Diet

See, Kaukinen, Makharia, Gibson, Murray. Nat. Rev. Gastroenterol. Hepatol. 12, 580–591

CDAT/ Biagi

Assessing Adherence

Adherence

Dietitian Assessment Symptom response Coeliac Serology

Histology

Gluten Peptides

What factors influence Adherence?

• Cognitive, emotional and socio-cultural influences

• Membership of an advocacy group – eg. Coeliac UK

• Regular dietetic follow-up

• Prescriptions for Gluten Free foods • Hall NJ et al. Intentional and inadvertent non-adherence in adult coeliac disease. A cross-sectional survey. Appetite

2013;68:56-62.

Prescriptions

Helping patients adhere

• Prescriptions been available since 1960

• Not Junk Food – staple foods approved by the Advisory

Committee on Borderline Substances

• Allowances determined by age and sex – Eg. male 19-59 years = 18 units, female 19

- 74 years = 14 units

Bread / rolls

Breakfast cereals

Crackers and crispbreads

Flour / flour-type mixes

Oats

Pasta

Pizza bases

Fact or Fiction?

– No budget supermarkets had GF foods

– Large supermarkets and online- median 22 items

– GF food 3-4 x more expensive than non GF foods

GF Prescriptions

• Cost – 25.7 million (0.3% of prescribing budget)

• 40% of CCGs is England- restricting or removing these prescriptions for CD and DH patients

Follow – up care for CD

CD: The Patient Journey

Primary Secondary

Non Responsive Coeliac Disease (NRCD)

• Definition

– persistent symptoms, signs or laboratory abnormalities typical of CD despite 6–12 months of dietary gluten avoidance

– 7-30% of all CD patients

NRCD

Review original diagnosis: Biopsy, HLA, serology, FHx

Dietary review

Repeat gastroscopy with biopsy and aspirate Colonoscopy and biopsy Faecal elastase Stool culture Bloods inc inflammatory markers, thyroid function

Exclude other causes: SBBO PEL

Fructose intolerance Lactose intolerance

Consider RCD?

No coeliac disease

Gluten contamination

Microscopic colitis Exocrine pancreatic insufficiency

Giardiasis Hyperthyroidism

Figure 1. Diagnostic algorithm for NRCD. FHx= Family History NRCD= Non-responsive coeliac disease; PLE= Protein losing enteropathy; SBBO=small bowel bacterial overgrowth; RCD= Refractory coeliac disease. BSG guidelines adopted from Mooney et al.

JGLD 2012

NRCD Algorithm

Refractory Coeliac Disease

• Definition

– Persistent or recurrent malabsorptive symptoms and signs with villous atrophy, despite a strict gluten free diet for more than 12 months.

– The Oslo definitions for coeliac disease and related terms. Ludvigsson et al. Gut. 2013 Jan; 62(1): 43–52.

Grey Cases

NRCD

Refractory Coeliac Disease

Adherence?

Refractory coeliac disease

• Rare cause of NRCD unknown true incidence ? 1.5%

• Diagnosis of exclusion

• Persistent changes of CD despite strict adherence to GFD

• Pre‐malignant condition

• Type 1 – polyclonal expansion of IELs and villous atrophy

• Type 2 – includes ulcerative jejunitis,

– clonal expansion of abberant IELs (CD8+ TCR γδ cells)

• Enteropathy Associated T‐cell Lymphoma (EATL)

Management

• Nutrition, nutrition, nutrition

• Gluten free diet

• Enteral vs PN

• Micronutrients

• Monitor for Re‐feeding Syndrome

Prognosis

• Type1 – 90‐100% 5 year survival

• Type2 – 50% 5 year survival

• Ulcerative jejunitis – Dismal

• EATL – 20‐30% 2 year survival

– 50 times more common in someone with coeliac disease, the annual incidence is low (0.5‐1 per million people)

• Not necessarily a linear progression

Other Gluten related disorders

Allergy

Cianferoni A. Wheat allergy: Diagnosis and Management. journal of Asthma and Allergy 2016:9 13–25

Prevalence: 0.2-1%

Hype?! Health?!

Non Coeliac Gluten (Wheat) Sensitivity

NCGS Prevalence: All self reported

Country Year N % Prevalence

2012 5896 5.9% Secondary care referrals

2012 916 4% NZ children report gluten avoidance

2013 7798 0.6% National Health and Nutrition Examination

Survey

2013 1002 2.9% 13% report symptoms related to gluten population survey but only 3.7% on GFD

2014 910 41.2% Athletes!

2014 1184 9.4% Adult General Population

2015 14701 0.8% National Health and Nutrition Examination

Survey

Gluten-free diets gaining in popularity: Health or hype: USA today 2008

• Reuter’s online • GFD $1.31 billion in US 2011

• $ 1.68 billion in 2015

Not just Gluten!!!

The GFD may not be a good thing

Innate Immune

Response?

DEFINE YOUR PATIENT

Mooney PM & Sanders DS Neurogastroenterol Motil 2013

Non

Coeliac

Gluten

Sensitivity

IBS

overlap

Allergy

IgE

Non-IgE

Adaptive Immune

Response

Coeliac

Disease

EMA/TTG

Villous

Atrophy

on Biopsy

FOD

MAP’s

IBS

• Review the CD Basics

• Hot topics

– Diagnosis

• Detection/ Serology/ Bulb biopsies/ Paeds vs Adults

– Treatment

• Gluten Free Diet/ Adherence/ Prescriptions

– Follow-up

• Problems/ Non-responders/ Refractory CD

• Other Gluten related disorders

Summary

Email: matthew.kurien@sth.nhs.uk

Twitter: @shefgastro. @mattkurien Keep up to date with the latest gastroenterology news in Sheffield through our Twitter feed

Thank you