What is the diagnostic workup and treatment for a patient presenting with pasty stools, potentially indicating malabsorption or pancreatic insufficiency, with a history of conditions such as celiac disease, cystic fibrosis, or gastrointestinal infections?

Workup of Pasty Stool

Begin with comprehensive blood testing and fecal elastase-1 measurement, followed by celiac serology and stool inflammatory markers, as pasty stools most commonly indicate either pancreatic exocrine insufficiency or small bowel malabsorption. 1, 2

Initial Blood Work

Obtain the following essential tests to screen for malabsorption and identify underlying causes:

• Complete blood count (CBC) to detect anemia from iron, folate, or B12 malabsorption, which indicates small bowel pathology 1, 3, 2
• ESR and CRP have high specificity for organic disease; elevated values mandate aggressive investigation 1, 2
• Comprehensive metabolic panel including albumin (low levels indicate protein malabsorption or protein-losing enteropathy), liver function tests, and electrolytes 1, 3, 2
• Iron studies, vitamin B12, and folate to identify specific malabsorption patterns 1, 2
• Thyroid function tests to exclude hyperthyroidism as a cause 1, 2
• Calcium levels to detect metabolic disturbances 2

Celiac Disease Screening

Test IgA tissue transglutaminase (IgA-tTG) with quantitative IgA level simultaneously, as this combination has >90% sensitivity and specificity for celiac disease 1, 2. This is critical because:

• Celiac disease presents with malabsorption and pale/pasty stools 3
• IgA deficiency occurs in 2.6% of celiac patients, causing false-negative IgA-tTG results 2
• If IgA-deficient, use IgG-based tests (IgG tissue transglutaminase or IgG deamided gliadin peptides) 2

Fecal Elastase-1 Testing

Measure fecal elastase-1 to assess for pancreatic exocrine insufficiency (PEI), the most common cause of severe steatorrhea and pasty stools 1:

• Levels <500 μg/g suggest PEI, though this can also occur with untreated celiac disease, small intestinal bacterial overgrowth (SIBO), or watery stool samples 1
• Levels <200 μg/g are more specific for true pancreatic insufficiency 1
• Note that fecal elastase-1 can be falsely low in villous atrophy from any cause (celiac disease, giardiasis, other enteropathies) and normalizes after mucosal recovery 4

Important caveat: The specificity of fecal elastase-1 is low when villous atrophy is present, regardless of underlying disease 4. If elastase is low, you must determine whether this represents primary pancreatic disease or secondary reduction from mucosal disease.

Stool Studies

Obtain the following stool tests:

• Stool culture and Giardia antigen/PCR to exclude infectious causes, particularly Giardia which has >95% sensitivity/specificity and remains common even without travel history 2
• Fecal calprotectin (threshold 50 mg/g) or lactoferrin to screen for inflammatory bowel disease, with pooled sensitivity 0.81 and specificity 0.87 2
• Consider qualitative fecal fat or spot fat testing if steatorrhea is suspected and patient doesn't respond to initial treatments 1

Endoscopic Evaluation

Proceed to upper endoscopy with distal duodenal biopsies if:

• Celiac serology is negative but small bowel malabsorption is still suspected clinically 1
• Fecal elastase is low and you need to differentiate primary pancreatic disease from mucosal disease 4
• Patient has alarm features (weight loss, anemia, hypoalbuminemia) 1, 5

Perform colonoscopy with ileoscopy if:

• Patient is >45 years old (cancer screening indication regardless of symptoms) 5
• Inflammatory markers or fecal calprotectin are elevated 1
• Symptoms suggest inflammatory bowel disease 1

Colonoscopy with biopsies from ascending and transverse colon is essential to exclude microscopic colitis, as rectosigmoid biopsies alone have 34-43% false-negative rate 1.

Consider Small Intestinal Bacterial Overgrowth (SIBO)

Test for SIBO if patient has risk factors (prior abdominal surgery, diabetes, systemic sclerosis, immunosuppression) 1:

• Hydrogen-methane breath testing is preferred where available 1
• Empiric treatment with rifaximin 550 mg twice daily for 1-2 weeks is effective in 60-80% of proven SIBO cases 1
• SIBO can cause low fecal elastase and intolerance to pancreatic enzyme replacement therapy 1

Diagnostic Algorithm Summary

1. Start with blood work (CBC, inflammatory markers, albumin, iron studies, thyroid function) and celiac serology with IgA level 1, 2
2. Measure fecal elastase-1 to assess pancreatic function 1
3. Obtain stool studies (culture, Giardia, calprotectin) 2
4. If fecal elastase <200 μg/g and no mucosal disease suspected: Consider trial of pancreatic enzyme replacement therapy (PERT) at 50,000 units lipase with meals, 25,000 with snacks 1
5. If celiac serology negative but malabsorption suspected: Proceed to upper endoscopy with distal duodenal biopsies 1
6. If inflammatory markers elevated or age >45: Proceed to colonoscopy with ileoscopy and biopsies from multiple sites 1
7. If SIBO suspected: Consider breath testing or empiric antibiotic trial 1

Common Pitfalls to Avoid

• Do not skip quantitative IgA testing when ordering celiac serology, as IgA deficiency causes false negatives 2
• Do not interpret low fecal elastase as definitive pancreatic insufficiency without excluding mucosal disease, as villous atrophy from any cause lowers elastase 4
• Do not rely on rectosigmoid biopsies alone for microscopic colitis; sample ascending and transverse colon 1
• Do not skip Giardia testing even without travel history 2
• Do not increase PERT doses beyond 10,000 units lipase/kg/day without investigating other causes (SIBO, mucosal disease, non-adherence) 6, 7