Celiac Disease Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: This is an underdiagnosed cause of chronic gastrointestinal symptoms and unexplained iron deficiency anaemia in our population. While not as common as in Europe, a 2015 local study showed a seroprevalence of 1.25% in young adults, so it is not rare. You will see it.
High-Yield Definition: Celiac disease is a chronic, immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. (Source: World Gastroenterology Organisation Global Guidelines, 2016).
Clinical One-Liner: Basically, it’s an autoimmune reaction to wheat, rye, and barley that damages the small bowel, leading to malabsorption.
II. Etiology & Risk Factors
Etiology: An autoimmune response to gliadin, a protein component of gluten, in individuals with specific genetic markers (HLA-DQ2 and HLA-DQ8).
Risk Factors:
Non-Modifiable:
Genetics: Presence of HLA-DQ2/DQ8 haplotypes.
Family History: Affects ~10% of first-degree relatives. Always ask about this.
Associated Autoimmune Conditions: Type 1 Diabetes Mellitus, Autoimmune Thyroiditis. Screen these patients if they have GI symptoms.
Genetic Syndromes: Down syndrome, Turner syndrome.
III. Quick Pathophysiology
When a susceptible person eats gluten, their immune system mounts an inappropriate T-cell response in the small intestine. This leads to chronic inflammation, which causes the classic pathological finding: villous atrophy. The intestinal villi, which are responsible for nutrient absorption, become blunted and flattened. No villi, no absorption. This directly explains the diarrhea, steatorrhea, weight loss, and nutritional deficiencies you see.
IV. Clinical Assessment
Red Flags & Immediate Actions:
Weight loss >5% with severe diarrhea: Alert senior, secure IV access, send FBC, RP, LFT, Albumin. Correct electrolytes and rehydrate.
Signs of severe malnutrition (e.g., peripheral edema): Check serum albumin urgently.
Acute, severe abdominal pain: Could be ulcerative jejunitis or lymphoma. Urgent review needed.
History:
Common (>50%): Chronic or recurrent diarrhea, bloating, flatulence, unexplained iron-deficiency anaemia (very high yield), fatigue.
Less Common (10-50%): Weight loss, abdominal pain, nausea, constipation (especially in children), recurrent aphthous ulcers.
Rare (<10%): Dermatitis herpetiformis (an intensely itchy, blistering rash), neurological symptoms (ataxia, neuropathy), abnormal LFTs.
Pertinent Negatives: Ask about blood in stool (less common in celiac, points towards IBD), nocturnal diarrhea (can be present but also an IBD red flag), and travel history (to rule out infectious causes).
Physical Examination:
General: Look for pallor (anaemia), muscle wasting, and signs of weight loss. Check for glossitis or angular stomatitis (nutritional deficiency).
Abdomen: May be distended and tympanic. Often non-tender.
Skin: Check extensor surfaces (elbows, knees) and buttocks for the pathognomonic rash of dermatitis herpetiformis.
Neurology: A basic neurological exam looking for peripheral neuropathy is good practice if symptoms are present.
Clinical Pearl: Don't anchor on classic diarrhea and weight loss. In adults, the most common presentation is actually extra-intestinal, especially persistent, unexplained iron-deficiency anaemia. If your IDA patient isn't responding to iron supplements, think celiac.
V. Diagnostic Workflow
Differential Diagnosis:
Irritable Bowel Syndrome (IBS):
Points For: Bloating, abdominal pain, altered bowel habits.
Points Against: Absence of malabsorption markers (weight loss, anaemia, nutrient deficiencies). Serology will be negative.
How to Differentiate: Celiac serology (anti-tTG IgA).
Inflammatory Bowel Disease (Crohn's/Ulcerative Colitis):
Points For: Chronic diarrhea, abdominal pain, weight loss.
Points Against: Hematochezia (bloody stool) is common in IBD, rare in celiac.
How to Differentiate: Fecal calprotectin will be high. Endoscopy with biopsy will show different histology.
Lactose Intolerance:
Points For: Diarrhea, bloating after dairy intake.
Points Against: Symptoms are specifically linked to dairy, not gluten-containing foods like bread or noodles. No autoimmune markers.
How to Differentiate: Clinical history and response to a lactose-free diet. Note: Secondary lactose intolerance can occur due to villous atrophy in celiac disease.
Investigations Plan:
Crucial First Point: The patient MUST be on a gluten-containing diet for the tests to be accurate. Do not advise them to stop eating bread and noodles before you test.
Bedside / Initial (First 15 Mins): Not much to do at the bedside. The diagnosis is not an acute emergency. Focus on assessing for dehydration or severe malnutrition if the patient is unwell.
First-Line Labs & Imaging:
Serology: This is your primary screening tool. Request Tissue Transglutaminase IgA (tTG-IgA) and Total Serum IgA.
Why both? A selective IgA deficiency can cause a false-negative tTG-IgA result. If Total IgA is low, you must then request IgG-based tests (DGP-IgG or tTG-IgG).
Bloods: FBC (for anaemia), Iron studies, Vitamin B12, Folate, Serum Albumin, Calcium, Phosphate, LFTs (to assess for malabsorption).
Confirmatory / Gold Standard:
Upper GI Endoscopy (OGDS) with Duodenal Biopsy: This is the gold standard. You need multiple biopsies (at least 4-6) from the second part of the duodenum (D2) and beyond. The pathologist will look for villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes (Marsh classification).
VI. Staging & Severity Assessment
We use the Marsh Classification for histological grading from the duodenal biopsy. You don't need to memorise it, but you should understand the principle.
Marsh 0: Normal mucosa.
Marsh I: Increased intraepithelial lymphocytes only.
Marsh II: Crypt hyperplasia.
Marsh III (a, b, c): Progressive villous atrophy (from mild to complete). This is the classic finding.
Marsh IV: Hypoplastic mucous membrane (rare).
Impact on Management: A confirmed Marsh III lesion on biopsy in a patient with positive serology confirms the diagnosis. The degree of atrophy often correlates with the severity of malabsorption.
VII. Management Plan
Immediate Stabilisation (The ABCDE Plan): Only for the rare, acutely unwell patient with severe dehydration or electrolyte imbalance. This is standard resuscitation: IV fluids, correct potassium/magnesium, etc.
Definitive Treatment (The Ward Round Plan):
First-Line, Second-Line, and Only-Line: A strict, lifelong gluten-free diet (GFD). There is no medication for this.
Dietitian Referral: This is mandatory. Do not attempt to counsel the patient yourself. A dietitian is essential to educate on:
Obvious Gluten Sources: Wheat (bread, noodles, biscuits), barley (malt), rye.
Hidden Gluten: Soy sauce (kicap), oyster sauce, processed meats, soups, certain medications. This is the difficult part in Malaysia.
Cross-Contamination: Using the same toaster, chopping board, or cooking oil.
Nutritional Supplementation: Prescribe based on deficiencies found in bloods (e.g., Ferrous Fumarate for IDA, Vitamin B12 injections, Calcium/Vitamin D).
Refractory Cases: If a patient does not respond to a strict GFD after 12 months, they are considered "refractory". This is a specialist problem. They need re-evaluation to confirm the diagnosis and adherence, and may need immunosuppressants like steroids.
Long-Term & Discharge Plan:
Follow-up: Clinic review at 6 months, then annually. Monitor symptoms and repeat serology (tTG-IgA should normalise on a strict GFD).
Bone Mineral Density: Consider a DEXA scan, especially for those diagnosed in adulthood, due to risk of osteoporosis from chronic calcium/vitamin D malabsorption.
Vaccinations: Ensure they are up-to-date, particularly with pneumococcal vaccine, as functional hyposplenism can be a complication.
VIII. Complications
Immediate (from acute presentation): Dehydration, electrolyte disturbance.
Management: IV fluid resuscitation and correction.
Short-Term (disease-related): Osteoporosis/Osteopenia, Iron-deficiency anaemia, other nutritional deficiencies.
Management: Aggressive supplementation and ensuring GFD adherence.
Long-Term (if untreated):
Enteropathy-Associated T-cell Lymphoma (EATL): A rare but serious malignancy of the small bowel.
Management: This is a referral to Oncology/Haematology.
Small Bowel Adenocarcinoma:
Management: Surgical resection and oncology referral.
Infertility and Recurrent Miscarriages:
Management: GFD can improve fertility outcomes.
IX. Prognosis
Excellent with strict adherence to a gluten-free diet. Most patients will have complete resolution of symptoms and mucosal healing. Mortality is increased if the diagnosis is delayed or due to complications like malignancy in untreated disease.
Top 3 Prognostic Factors:
Adherence to the gluten-free diet.
Age at diagnosis (older age is associated with less complete mucosal recovery).
Presence of complications like refractory disease or malignancy.
X. How to Present to Your Senior
"Dr, for your review. This is Puan Lim in Bed 10, a 45-year-old lady with a 2-year history of bloating and fatigue, found to have a microcytic anaemia (Hb 9.5) that is refractory to oral iron. Her tTG-IgA has come back strongly positive at >10 times the upper limit of normal. My main differential is celiac disease. I have counseled her on the need for an OGDS for biopsy to confirm. Plan is to refer her to Gastroenterology for the scope. I have also sent off a full panel to check for other nutritional deficiencies."
XI. Summary & Further Reading
Top 3 Takeaways:
Think of celiac disease in any patient with unexplained iron-deficiency anaemia.
The diagnostic pathway is serology first (tTG-IgA + Total IgA), followed by confirmation with duodenal biopsy. The patient must be eating gluten.
Treatment is a strict, lifelong gluten-free diet, and a dietitian referral is non-negotiable.
Key Resources:
International Guideline: World Gastroenterology Organisation (WGO) Global Guidelines - Celiac Disease (https://www.worldgastroenterology.org/guidelines/celiac-disease/celiac-disease-english)
Clinical Overview: UpToDate - "Diagnosis of celiac disease in adults"
Local Data: Ng et al. (2015). Prevalence of Serum Celiac Antibodies in a Multiracial Asian Population... (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370882/)
Now go and clerk your patients.
