Coeliac disease 

• the lining of the small bowel is damaged due to a protein gluten. 
• Gluten is found in grains such as wheat, barley, triticale and rye. 
• Proteins very similar to gluten are found in oats and may also cause coeliac disease.

• Can develop at any age
  • Affects both adults and children Any age, median age of diagnosis is 40 years
  • Older patients over age 60 years represent 20% of cases
  • May present as Failure to Thrive in infants
• Positive family history strong predictive value
• Prevalence: 1 per 120-300
• More common in white patients and rare in Asian patients – Coeliac disease should not be excluded on the basis of a patient’s ethnicity or appearance
• Some patients have minimal or no obvious symptoms, or only extra‑intestinal issues
• One-third of patients with coeliac disease are overweight or obese at diagnosis
• More common in women (75% of adult cases)
• Family History increases risk
  • Monozygotic twins: 75% concordance rate
  • First degree relatives: 10% have Celiac Disease
  • Second degree relatives: 3-6% have Celiac Disease

Pathophysiology

• Small Bowel exposure to Antigens in cereal grains (rye, wheat, barley)
• Immunologic disorder of Small Bowel
  • Abnormal T Cell and IgA and IgG Antibody response
  • Enhanced immunogenic response to gliadin (Alcohol-soluble portion of gluten) at lamina propria
  • Results in intense local inflammation at villous resulting in villous atrophy
  • Significantly decreases absorptive surface
• Related to HLA Class II DQA1*0501 and DQB1*0201 (HLA-DQ2 and HLA-DQ8)
  • Associated with other Autoimmune Conditions
    • Chromosomal abnormality
      • Turner’s Syndrome (6%)
      • Down Syndrome (8%)
      • Williams Syndrome (8%)
    • Autoimmune Conditions
      • Type I Diabetes Mellitus (2-8% comorbidity)
      • Autoimmune Thyroid disease (3%)
      • Dermatitis Herpetiformis
      • Sjogren’s Syndrome
      • Primary biliary Cirrhosis
      • Addison’s Disease
      • Systemic Lupus Erythematosus
      • Selective IgA Deficiency (2-8%)
      • Alopecia Areata
      • Autoimmune Hepatitis
      • Sarcoidosis
      • Vitiligo
      • Psoriasis

Presentation

1. Fatigue/Lethargy
2. Diarrhoea/ Loose bowel motions
3. Weight Loss
4. Thinned hair
5. Borderline ↓ BMI/ weight loss
6. Mild anemia 
7. Oligomenorrhoea
8. Abdo pain, bloating
9. Less typical – lethargy, headaches, osteoporosis, iron deficiency, transaminase elevation, infertility, other autoimmune disease, dermatitis herpetiformis

Diagnosis/ Investigations

When to test for coeliac disease

• Offer serological testing for coeliac disease 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

• Consider serological testing for coeliac disease in people with any of the following:
  • 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 syndrome
  • Turner syndrome

1. Coeliac serology
   1. Total immunoglobulin A (IgA)
   2. transglutaminase (tTG-IgA) antibody – has lower sensitivity in children under three years of age
   3. anti-deamidated gliadin peptide (DGP-IgG) antibody

Option 1: 

tTG-IgA   +  DGP-IgG

Medicare Benefits Schedule (MBS) item number 71164

double antibody test ($39.90) is the preferred one-step approach.

      Or

Option 2: 

tTG-IgA  +  Total IgA level 

If the IgA level is low 🡪 preform DGP-IgG

MBS item number 71163, single antibody test ($24.75).

• both test tTG-IgA and DPG-IgG have >85% sensitivity and >90% specificity
• false negative rate of 10–15% – Not valid if on gluten free diet or taking immune suppressants
• Positive coeliac disease serology in isolation is insufficient for the diagnosis of coeliac disease.
• The higher the titre of serology, the greater the positive predictive value for coeliac disease.
• In patients with risk factors for coeliac disease, negative coeliac disease serology has lower negative predictive value, so further work-up should be considered.15
• Patients with persistently positive coeliac disease serology but normal small intestinal histology may have ‘potential’ (or ‘latent’) coeliac disease, and follow-up is recommended.

Confirmation

1) Gastroscopy with small bowel biopsies

• Gold standard for diagnosing celiac disease.
• Important to perform while the patient is on a gluten-containing diet to avoid false negatives
• causes patchy involvement of the proximal small intestine,
• multiple biopsies are recommended (eg two from the first and four from the second part of the duodenum)
• microscopic findings
  1. Raised intra-epithelial lymphocytes
  2. crypt hyperplasia
  3. villous atrophy

False positive: Other causes to consider

• Giardia
• common variable immunodeficiency
• Crohn’s disease
• tropical sprue
• autoimmune enteropathy
• cow’s milk protein intolerance 
• medications (eg olmesartan).

False negative:  Gluten Free Diet (GFD) or immunosuppression can obscure changes of villous atrophy.

     If unable to follow gluten containing diet prior to gastroscopy: HLA DQ2/8 genotyping

2) Human leukocyte antigen DQ2/8 genotyping

• The absence of HLA susceptibility means that coeliac disease is unlikely and further investigations can focus on other diagnoses (likelihood of coeliac disease <1%).
• The presence of HLA susceptibility genes is not diagnostic of coeliac disease, so NEED Gluten challenge for definitive diagnosis
• HLA typing is expensive (Medicare Benefits Schedule item number 71151; $118.85), so it is important to use it prudently 
• HLA typing is a ‘once only’ test as a person’s genotype does not change.
• HLA typing results are not adversely affected by a GFD 
• HLA DQ2/8 Used in specific situations
  • When coeliac disease serology and/or small bowel examination is inconclusive or equivocal
  • When there has been failure to improve on a gluten-free diet
  • When a person has commenced a gluten-free diet prior to assessment by serology or small bowel examination 
  • unwilling or unable to undertake a gluten challenge prior to investigation
  • In patients clinically assessed to be at higher risk of coeliac disease in order to exclude those where further testing for coeliac disease is not required
  • Joint BSPGHAN and Celiac UK guidelines (2013) suggest that positive serological tests with positive HLA typing and typical symptoms can confirm diagnosis without a biopsy.

• Gluten free diet induced symptom resolution, normalised serology, mucosal healing
• If been on a gluten free diet – consider doing a challenge and doing ensodpy after 6 weeks (onset of symptoms not sufficient, may jsut be FODMAP effect)

Gluten-sensitive or wheat‑sensitive patients

• Many Australians adopt a GFD(gluten free diet) without assessment for coeliac disease. 
• This poses a diagnostic dilemma as coeliac disease serology and intestinal histology can become falsely negative if the patient has been on a GFD for more than a few months. 
• Many Australians remove gluten from their diet because they feel it helps improve gastrointestinal or other symptoms.
• For these people, a definitive diagnosis is desirable as:
  • a formal diagnosis of coeliac disease will ensure strict treatment and follow-up of a serious medical illness
  • many people who self-report ‘gluten sensitivity’ are not actually sensitive to gluten. These patients, instead of excluding gluten, may benefit more from excluding other symptom-inducing wheat components, such as fermentable carbohydrates (FODMAPs)

• There are two diagnostic approaches –
  • option 1 : HLA-DQ2/8 genotyping
  • Option 2: Gluten challenge, then testing
    • Approximately 3–6 g of gluten consumed daily for two weeks will cause intestinal changes of coeliac disease in 50–70% of affected adults, with the development of positive serology after four weeks in 10–55%.
    • To optimise the diagnostic yield, patients should be encouraged to return to consuming 3–6 g or more of gluten each day for, ideally, six or more weeks. 
    • This daily amount of gluten can be found in two to four slices of wheat bread, two to four Weet-Bix or 0.5–1 cup of cooked pasta.

Paediatric population

• The tTG assay has lower sensitivity in children under three years of age. 
• Ensure DGP-IgG testing is performed alongside tTG-IgA to overcome this issue.
• Children with coeliac disease may present with more ‘classical’ complaints than adults
• high-titre tTG is strongly predictive of coeliac disease in children, suggest small intestinal biopsies can be avoided if children meet the following criteria
  • Characteristic symptoms
  • TTG X 10 ULN
  • Positive endomysial antibody
  • Positive HLA susceptibility

Screening

• Worthwhile screening first degree relative for HLA DQ2/8 – if negative no further required
  • (risk in first degree relative is 1/10)
• If asymptomatic gene – could consider screening 2-3 years during childhood

Management

1. Education
2. Gluten free diet + dietician referral
3. Refer to coeliac support group
4. Explain that family members will need to be screened with coeliac Ab testing

Ongoing review/ follow up

1. Symptom control
2. Check response to a gluten-free diet:
   • check antibody concentrations
   • Ab should start to fall by 3–6 months but can remain elevated (even despite adequate dietary adherence)
3. check adherence
   • persistently elevated antibodies or ongoing gastrointestinal symptoms should prompt referral to a dietitian for assessment of adherence and reinforcement of advice
4. Repeat blood tests (q6-12 months):

• Coeliac Ab (tTG, DGP, total IgA)
  • frequently used as a surrogate marker of intestinal healing
  • titres generally normalise on a GFD in 12 months
  • persistently positive titres suggest ongoing gluten exposure
• TSH & T4
• F/u on any micronutrient deficiencies
• Look for evidence of malabsorption – FBC, E/LFT, TFT, IS, Ca, Phos, Fasting/random glucose, zinc, Mg

5. Repeat gastroscopy at 18-24months to review for healing & repeat biopsy
6. BMD  every 2 yrs
7. Encourage membership with Coeliac society

Complications

• Increased Risk of Malignancies:
  • Lymphomas: Higher risk, especially Non-Hodgkin lymphoma.
  • Small Bowel Adenocarcinomas: Increased risk over time.
• Reproductive Issues:
  • Pregnant Women: Higher risk of miscarriage and congenital birth defects.
  • Infertility
• Growth and Development:
  • Children: Short stature and failure to thrive.
• Nutrient Malabsorption:
  • Osteopenia: Due to calcium deficiency.
  • Bleeding Diathesis: Due to vitamin K deficiency.
  • Anemia: Due to iron, folate, or vitamin B12 deficiency.
  • Lack of Exercise Endurance: Due to overall poor nutrition.
  • Seizures: Due to nutrient deficiencies.

Screen and treat nutrient deficiencies and other complications:

1. Iron
2. B12
3. vitamin D
4. calcium and folate
5. bone mineral density
6. screen for other associated conditions if clinically relevant
   1. type 1 diabetes
   2. autoimmune thyroid disease
   3. liver function
7. review immunisation status
   1. particularly consider pneumococcal vaccination as infection with this organism is higher in patients with coeliac disease, probably secondary to functional hyposplenism
8. screen first-degree relatives

Pearls and Other Issues

• Untreated Celiac Disease: Leads to chronic ill health and complications.
• Common Issues: Secondary lactose intolerance, increased risk of osteoporosis, epilepsy, infections, bowel cancer, and jejunal lymphoma.
• Calcium Deficiency: Affects dentition.
• Autoimmune Screening: Recommend screening for type 1 diabetes and thyroid function problems due to common genetic background.