In a patient with Hashimoto's thyroiditis presenting with bloody diarrhea, an elevated C‑reactive protein and a normal erythrocyte sedimentation rate, what is the differential diagnosis?

Differential Diagnosis for Bloody Diarrhea in a Patient with Hashimoto's Thyroiditis, Elevated CRP, and Normal ESR

The most likely diagnoses to consider are inflammatory bowel disease (particularly Crohn's disease or ulcerative colitis), infectious colitis, and ischemic colitis, with IBD being the primary concern given the elevated CRP and bloody diarrhea pattern.

Primary Diagnostic Considerations

Inflammatory Bowel Disease (IBD)

• IBD is the leading diagnosis to pursue, as bloody diarrhea with elevated inflammatory markers is a hallmark presentation 1
• CRP has 73% sensitivity and 78% specificity for discriminating organic disease in patients with chronic diarrhea 2
• Notably, up to 28% of children with Crohn's disease and 42% with ulcerative colitis can have normal ESR at diagnosis, making the normal ESR in this case consistent with IBD 3
• Order fecal calprotectin immediately as the American Gastroenterological Association recommends it as the most sensitive screening test for IBD, with 81% sensitivity and 87% specificity at a threshold of 50 μg/g 1
• Fecal calprotectin has a negative likelihood ratio of 0.06, making it excellent for ruling out IBD if negative 1

Infectious Colitis

• Bacterial pathogens causing invasive diarrhea (Salmonella, Shigella, Campylobacter, enteroinvasive E. coli, C. difficile) commonly present with bloody diarrhea and elevated CRP 4
• Obtain stool cultures, ova and parasites, and C. difficile testing as first-line diagnostic tests 4
• An elevated WBC count with neutrophil predominance supports invasive bacterial infection 4

Ischemic Colitis

• Consider in patients with vascular risk factors, particularly if abdominal pain is out of proportion to examination findings 4
• Elevated lactate levels ≥2.0 mmol/L suggest intestinal ischemia and warrant urgent evaluation 4
• This diagnosis becomes more likely in older patients or those with cardiovascular disease 4

Understanding the CRP-ESR Discordance

Why CRP is Elevated While ESR is Normal

• CRP rises within 12-24 hours of inflammation onset and peaks at 48 hours, making it ideal for detecting acute inflammatory processes 2
• ESR has a much longer half-life and may remain normal early in acute disease or can be falsely normal due to various factors 5
• CRP/ESR disagreements occur in 20-33% of patients and can result from: (1) slight fluctuations around normal limits, (2) different time courses of elevation, or (3) CRP rising and falling faster than ESR 6
• The elevated CRP with normal ESR pattern suggests an acute inflammatory process rather than chronic inflammation 5

Hashimoto's Thyroiditis Connection

• Hashimoto's thyroiditis itself can cause low-grade systemic inflammation with elevated acute-phase reactants, though this typically does not cause bloody diarrhea 7
• Patients with Hashimoto's have been shown to have higher mean ESR, fibrinogen, and serum amyloid A compared to controls, suggesting systemic inflammation 7
• However, CRP levels in Hashimoto's thyroiditis patients do not typically reach levels seen in acute inflammatory conditions like IBD 8
• The bloody diarrhea is almost certainly unrelated to the Hashimoto's diagnosis and represents a separate acute gastrointestinal pathology 8

Additional Differential Diagnoses to Consider

Less Common but Important Causes

• Diverticulitis with colonic bleeding: Can present with bloody diarrhea and elevated CRP, particularly in older patients 2
• Colorectal malignancy: Can cause bloody diarrhea, though typically presents with more chronic symptoms 2
• Radiation colitis: Only relevant if patient has history of pelvic radiation 2
• Drug-induced colitis: NSAIDs, immunotherapy agents, and other medications can cause colitis 2

Recommended Diagnostic Algorithm

Immediate Laboratory Testing

• Fecal calprotectin (most important screening test for IBD) 1
• Stool studies: Culture, ova and parasites, C. difficile toxin 4
• Complete blood count with differential to assess for leukocytosis, anemia, and thrombocytosis 2
• Comprehensive metabolic panel including creatinine, liver function tests 2
• Serum lactate if ischemic colitis is suspected 4

Imaging and Endoscopy

• CT abdomen/pelvis with IV contrast if severe symptoms, fever, or concern for complications 4
• Colonoscopy with biopsies is the gold standard for diagnosing IBD and should be pursued if fecal calprotectin is elevated or infectious workup is negative 1
• Withhold antibiotics for at least 2 weeks prior to endoscopy when clinically feasible to maximize culture yield 2

Critical Clinical Pitfalls

• Do not rely on ESR alone to rule out IBD, as normal ESR occurs in up to 28-42% of IBD patients at diagnosis 3
• Do not assume the elevated CRP is related to Hashimoto's thyroiditis, as CRP is typically not elevated in thyroid disease except subacute thyroiditis 8
• Do not delay colonoscopy if fecal calprotectin is elevated, as this significantly increases the likelihood of IBD requiring treatment 1
• Recent NSAID use can suppress CRP, so obtain a detailed medication history 2
• In immunocompromised patients, CRP may be falsely low despite significant infection 2