What is the likely diagnosis and treatment for a patient with chronic diarrhea for 1 month, elevated fecal calprotectin level, and no white blood cells (WBCs) in the stool?

Chronic Diarrhea with Elevated Fecal Calprotectin: Diagnosis and Management

This patient most likely has inflammatory bowel disease (IBD), specifically Crohn's disease or ulcerative colitis, and requires colonoscopy with biopsies to establish the diagnosis and guide treatment. 1

Interpretation of Fecal Calprotectin Level

A fecal calprotectin of 178 μg/g falls into the clinically significant range that strongly suggests active intestinal inflammation:

• Values >150 μg/g indicate active inflammatory disease in the gastrointestinal tract, with a specificity of 72% and sensitivity of 81% for detecting endoscopically active disease 2
• At this level, the false positive rate is approximately 15-22%, meaning the vast majority of patients with this elevation have genuine intestinal inflammation 2, 1
• The absence of WBCs in stool does not exclude IBD, as fecal calprotectin is a more sensitive marker for intestinal inflammation than fecal leukocytes 3

Differential Diagnosis

The primary diagnostic consideration with this presentation is inflammatory bowel disease (IBD), which includes:

• Crohn's disease - can affect any part of the GI tract with transmural inflammation 2
• Ulcerative colitis - continuous inflammation limited to the colon and rectum 2

Important caveat: While fecal calprotectin >150 μg/g strongly suggests IBD, other conditions can elevate calprotectin and must be excluded 1, 4:

• Infectious gastroenteritis (though typically presents acutely, not chronically) 5, 4
• Colorectal cancer 4
• NSAID use within the past 6 weeks 5, 4
• Microscopic colitis 4

Essential Diagnostic Workup

Immediate Laboratory Testing

Before or concurrent with gastroenterology referral, obtain 2, 4:

• Complete blood count - assess for anemia (suggesting chronic blood loss), thrombocytosis (indicating inflammation), or leukocytosis 2
• C-reactive protein (CRP) - complementary inflammatory marker, though 20% of active Crohn's patients may have normal CRP 4
• Comprehensive metabolic panel - evaluate electrolytes, renal function, liver function, and albumin 2
• Iron studies - assess iron deficiency from chronic blood loss 2
• Vitamin D level - commonly deficient in IBD 2
• Erythrocyte sedimentation rate (ESR) - additional inflammatory marker 2

Stool Studies

Exclude infectious causes 2, 4:

• Stool culture for bacterial pathogens 2
• Clostridioides difficile testing 2
• Ova and parasites examination 2

Endoscopic Evaluation

Colonoscopy with ileoscopy and biopsies is mandatory for definitive diagnosis 1, 4:

• Complete colonoscopy with terminal ileum intubation is preferred over flexible sigmoidoscopy to assess full disease extent 1
• Multiple biopsies must be obtained even from normal-appearing mucosa to establish histologic diagnosis and differentiate Crohn's disease from ulcerative colitis 1
• Endoscopy allows assessment of disease severity, distribution, and complications 2

Additional Imaging

If Crohn's disease is suspected based on symptoms or initial findings, consider cross-sectional imaging 1:

• MR enterography or CT enterography to evaluate small bowel involvement, strictures, fistulas, or abscesses 1

Treatment Approach

Treatment cannot be initiated until endoscopic and histologic diagnosis is established, as management differs significantly between Crohn's disease and ulcerative colitis 2, 1.

Once IBD is Confirmed

For ulcerative colitis with mild to moderate activity 6:

• Mesalamine (5-aminosalicylic acid) is first-line therapy 6
• Induction dosing: 2.4-4.8 g once daily 6
• Maintenance dosing: 2.4 g once daily after achieving remission 6

For Crohn's disease, treatment depends on disease location, severity, and complications and may include:

• Corticosteroids for induction of remission in moderate to severe disease 2
• Immunomodulators (azathioprine, 6-mercaptopurine) 2
• Biologic therapy (anti-TNF agents, anti-integrin antibodies) for moderate to severe disease 2

Critical Clinical Pitfalls

Do not delay endoscopy - empiric treatment without endoscopic confirmation can mask the diagnosis and delay appropriate therapy 1, 4

Do not assume IBS - with a fecal calprotectin of 178 μg/g, the likelihood of IBD is high, and IBS should only be diagnosed after excluding organic pathology 2, 4

Assess for NSAID use - if the patient has used NSAIDs within 6 weeks, this could falsely elevate calprotectin; however, given one month of diarrhea, IBD remains the primary concern 5, 4

Monitor renal function - if mesalamine is eventually prescribed, baseline and periodic renal function monitoring is mandatory 6

Urgent Gastroenterology Referral

This patient requires urgent (not routine) gastroenterology referral given 4:

• Chronic diarrhea lasting one month
• Significantly elevated fecal calprotectin >150 μg/g
• High probability of IBD requiring prompt diagnosis and treatment

The combination of chronic symptoms with calprotectin >150 μg/g warrants expedited endoscopic evaluation within 2-4 weeks 4.