What is the possible impression and differential diagnoses for a 35-year-old female (F) patient presenting with abdominal pain, diarrhea, and constipation, with lab results showing normal complete blood count (CBC), negative Helicobacter pylori (H. pylori) test, elevated erythrocyte sedimentation rate (ESR), and normal vital signs?

Diagnostic Impression and Differential Diagnoses

Most Likely Impression: Irritable Bowel Syndrome with Mixed Bowel Habits (IBS-M)

This 35-year-old female meets Rome criteria for IBS with a 6-month history of abdominal pain associated with alternating diarrhea and constipation, bloating, and symptom exacerbation with stress and food intake, in the absence of alarm features and with reassuring initial investigations. 1

Clinical Reasoning

Supporting Features for IBS Diagnosis

• Cardinal symptoms present: Abdominal pain (epigastric, radiating to lower abdomen) with clear temporal relationship to altered bowel habit (initially diarrhea, then constipation, now mixed pattern) 1
• Bloating and visible distension: Highly suggestive of IBS when present with cardinal symptoms 1
• Symptom triggers identified: Pain aggravated by food intake and stress, which demonstrates gut-brain axis dysfunction typical of IBS 1
• Extraintestinal symptoms: Palpitations, easy fatigability, and weight loss can represent somatoform features commonly associated with IBS 1
• Demographics: Female sex and age <45 years increase likelihood of IBS 1
• Chronic duration: 6-month symptom duration with fluctuating pattern is characteristic 1

Reassuring Laboratory Findings

• Normal CBC: Excludes anemia that would suggest malignancy or inflammatory bowel disease 1, 2
• Mildly elevated ESR (21) and CRP (1 mg/dL): These are only minimally elevated and do not suggest significant organic disease; ESR can be mildly elevated in functional disorders 1
• Negative H. pylori: Excludes peptic ulcer disease as cause of epigastric pain 1
• Normal TSH (1.5): Excludes hyperthyroidism as cause of weight loss, diarrhea, and palpitations 3
• Normal CEA (2.2): Provides reassurance against colorectal malignancy 3
• Normal FBS (104): Excludes diabetes as cause of altered bowel habits 1

Critical Consideration: Family History of Colon Cancer

Despite meeting IBS criteria, the family history of colon cancer warrants colonoscopy even at age 35, as this represents an alarm feature that modifies the diagnostic approach. 1, 3, 2 The British Society of Gastroenterology guidelines state that patients over 50 years or with family history of colorectal cancer should undergo colonoscopy regardless of symptom pattern 2. The American College of Gastroenterology recommends colonoscopy is mandatory when weight loss is present, as this constitutes an alarm feature requiring exclusion of colorectal cancer 3.

Differential Diagnoses to Consider

1. Functional Dyspepsia with IBS Overlap

• Epigastric pain as predominant feature suggests possible functional dyspepsia (FD) 1
• Up to 50% of patients have overlap between FD and IBS, reporting two different types of abdominal pain (one related and one unrelated to defecation) 1
• The epigastric location of pain and its radiation pattern could represent FD-IBS overlap syndrome 1

2. Celiac Disease

• Must be excluded with tissue transglutaminase IgA antibodies and total IgA level, as celiac disease commonly presents with chronic abdominal symptoms, weight loss, and altered bowel habits 3, 2
• Coeliac serology should be checked in all patients with IBS symptoms per British Society of Gastroenterology guidelines 1, 2
• This is particularly important given the weight loss and easy fatigability 3

3. Microscopic Colitis

• Should be considered given the alternating diarrhea and constipation pattern 1
• Risk factors include female sex and age, though typically presents in patients >50 years 1
• Requires colonoscopy with right and left colon biopsies (not rectal) for diagnosis 3
• Can only be diagnosed histologically, as colonoscopy appears normal 1

4. Bile Acid Diarrhea (BAD)

• Should be considered in the diarrheal phases of this patient's symptoms 1
• Between one-in-three patients with suspected IBS-D have BAD 1
• Consider SeHCAT scanning or serum 7α-hydroxy-4-cholesten-3-one testing if diarrhea persists 1, 2

5. Inflammatory Bowel Disease (Early/Mild)

• Less likely given normal CBC and only minimally elevated inflammatory markers 1
• Fecal calprotectin should be tested to definitively exclude IBD, particularly given the chronic abdominal complaints and family history considerations 3, 2
• British Society of Gastroenterology recommends fecal calprotectin in patients with diarrhea under age 45 1, 2

6. Colorectal Cancer (Lower Probability but Must Exclude)

• Family history of colon cancer is the key concern 3, 2
• Weight loss, though attributed to other symptoms, requires exclusion of malignancy 3
• Normal CEA is reassuring but does not exclude malignancy 3
• Colonoscopy is mandatory despite young age due to family history 3, 2

7. Post-Infectious IBS

• Initial presentation 6 months ago with acute diarrhea could represent post-infectious IBS 1
• 10-20% of IBS patients relate onset to acute gastrointestinal illness 1
• Post-infectious IBS can present with low-grade inflammation and altered neuroendocrine function 4

Recommended Diagnostic Approach

Immediate Additional Testing Required

1. Celiac serology (tissue transglutaminase IgA with total IgA level) - mandatory in all patients with chronic abdominal symptoms 3, 2

2. Fecal calprotectin - to exclude inflammatory bowel disease in patient under 45 with diarrhea 1, 3, 2

3. Colonoscopy with biopsies - indicated due to:

   • Family history of colon cancer 3, 2
   • Weight loss as alarm feature 3
   • Need to exclude microscopic colitis (requires right and left colon biopsies) 3
   • Need to exclude early IBD 1

4. Upper endoscopy - consider if celiac serology is positive or if epigastric symptoms persist, to evaluate for functional dyspepsia and obtain duodenal biopsies 1, 3

Tests NOT Recommended at This Stage

• Repeat colonoscopy if initial is normal: Not indicated in typical IBS without new alarm features 2
• Abdominal ultrasound: Often detects incidental findings unrelated to symptoms 1
• Hydrogen breath testing for SIBO: Not recommended in patients with typical IBS symptoms 2
• Extensive food allergy testing: True food allergy is rare; patient beliefs about food intolerance should not drive unnecessary testing 1

Common Pitfalls to Avoid

1. Do not attribute weight loss to dietary changes alone without excluding gastrointestinal pathology, especially with family history of colon cancer 3

2. Do not delay colonoscopy based on age alone when alarm features (weight loss, family history) are present 3

3. Do not perform celiac testing after patient starts gluten-free diet, as this causes false-negative results 3

4. Do not rely solely on symptom criteria without performing baseline investigations (CBC, CRP/ESR, celiac serology) as recommended by British Society of Gastroenterology 1, 2

5. Do not miss the overlap between functional dyspepsia and IBS - this patient's epigastric pain may represent both conditions 1

6. Do not overlook psychological comorbidities - palpitations and easy fatigability may represent anxiety or somatization that commonly coexist with IBS and require concurrent management 1

Management Considerations After Diagnosis Confirmed

Once organic disease is excluded and IBS diagnosis is confirmed:

• Patient education about gut-brain axis and how diet, stress, and emotional responses impact symptoms 1
• Dietary modifications: Consider low FODMAP diet trial, avoid trigger foods identified by patient 1
• First-line pharmacotherapy: Antispasmodics for pain, soluble fiber for bowel regulation 5, 6
• Address psychological factors: Screen for anxiety, depression, and stress management needs 1
• Set realistic expectations: IBS is chronic with no cure; treatments aim to improve quality of life 1