What is the initial diagnostic approach for a patient presenting with chronic diarrhea, specifically regarding blood screens and further testing?

Chronic Diarrhoea Blood Screen

For patients presenting with chronic diarrhoea, obtain a comprehensive blood panel including full blood count, ESR, CRP, urea and electrolytes, liver function tests, calcium, vitamin B12, folate, iron studies, and thyroid function tests, along with IgA tissue transglutaminase (IgA-tTG) and a second test to detect celiac disease in IgA deficiency. 1

Essential Blood Tests

Core Screening Panel

• Full blood count to detect anaemia (suggesting malabsorption, inflammatory bowel disease, or coeliac disease) 1
• ESR and CRP have high specificity but low sensitivity for organic disease; abnormal results warrant aggressive investigation 1
• Urea and electrolytes to assess for dehydration and electrolyte disturbances 1
• Liver function tests to screen for hepatobiliary disease 1
• Calcium to detect hypercalcaemia (parathyroid disease) or hypocalcaemia (malabsorption) 1
• Vitamin B12, folate, and iron studies to identify malabsorption patterns 1
• Thyroid function tests to exclude thyrotoxicosis as a cause 1

Celiac Disease Screening (Mandatory)

• IgA tissue transglutaminase (IgA-tTG) is the primary test with >90% sensitivity and specificity when using thresholds of 7-15 AU/mL 1
• Second test for IgA deficiency detection is essential because selective IgA deficiency occurs in 2.6% of celiac patients (versus 0.14-0.2% in general population), causing false-negative IgA-tTG results 1
• Options for IgA-deficient patients include IgG tissue transglutaminase or IgG deaminated gliadin peptides 1
• Alternatively, measure quantitative IgA level alongside IgA-tTG; if normal, confirms accuracy of negative IgA-tTG 1

Additional Stool and Serologic Testing

Stool Studies

• Stool cultures and microscopy should be performed despite low yield in immunocompetent patients from developed countries with chronic symptoms 1
• Giardia antigen test or PCR is strongly recommended with >95% sensitivity and specificity; Giardia is a common treatable cause throughout the United States 1
• Fecal calprotectin (threshold 50 mg/g) or fecal lactoferrin (threshold 4.0-7.25 mg/g) to screen for inflammatory bowel disease, with pooled sensitivity 0.81 and specificity 0.87 for calprotectin 1
• Laxative screen should be performed early in specialist referral practice, including detection of anthraquinones, bisacodyl, and phenolphthalein in urine, and magnesium and phosphate in stool 1

Tests to Avoid or Use Selectively

• ESR and CRP alone should not be used to screen for IBD due to inferior performance compared to fecal markers (CRP sensitivity 0.73, specificity 0.78; ESR performs worse) 1
• Ova and parasites testing (other than Giardia) should be avoided unless travel history to or recent immigration from high-risk areas 1

Interpretation and Clinical Context

High-Specificity Findings

• Abnormal initial screening tests (elevated ESR, anaemia, low albumin) have high specificity for organic disease and mandate thorough investigation 1, 2
• These findings distinguish organic pathology from functional disorders like irritable bowel syndrome 2, 3, 4

Common Pitfalls to Avoid

• Do not overlook IgA deficiency when interpreting negative celiac serology; always include a second test or quantitative IgA level 1
• Do not rely on ESR/CRP alone for IBD screening; use fecal calprotectin or lactoferrin instead 1
• Do not skip Giardia testing even in patients without travel history; it remains a common treatable cause 1
• Repeat laxative screens may be necessary as patients may ingest laxatives intermittently 1

Additional Considerations for Bile Acid Diarrhoea

• Bile acid diarrhoea testing is suggested but tests are not widely available in North America 1
• Empiric trial of bile acid binders (cholestyramine) is reasonable when bile acid diarrhoea is suspected, particularly in patients with terminal ileum resection or post-cholecystectomy 1