What is the differential diagnosis and potential treatment for a 46-year-old woman with chronic, worsening abdominal pain, normal Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), lipase, urinalysis, Computed Tomography (CT) abdomen/pelvis, and right upper quadrant ultrasound?

Differential Diagnosis and Management for Chronic Abdominal Pain with Negative Workup

In a 46-year-old woman with 10 weeks of worsening, diffuse abdominal pain and repeatedly normal imaging and laboratory studies, the most likely diagnoses are functional gastrointestinal disorders (particularly irritable bowel syndrome), cannabinoid hyperemesis syndrome given daily marijuana use, or less commonly, conditions requiring advanced imaging such as pelvic venous disorders or mesenteric panniculitis.

Key Differential Diagnoses

High Probability Diagnoses

• Irritable Bowel Syndrome (IBS): The presentation of chronic abdominal pain (>12 weeks), diffuse location, and normal extensive workup strongly suggests a functional gastrointestinal disorder 1. The Rome IV criteria include abdominal pain associated with altered bowel habits, though she denies bowel changes, which doesn't exclude the diagnosis 1.

• Cannabinoid Hyperemesis Syndrome: Daily marijuana use is a critical red flag. This syndrome causes chronic abdominal pain, nausea, and frequent ED visits with negative workup 1. The pattern of repeated ED presentations with normal studies is characteristic.

• Visceral Hypersensitivity: Severe abdominal pain and bloating without structural abnormality suggests altered central nervous system processing of visceral pain 1. This is common in functional disorders and explains the discordance between symptom severity and normal testing 1.

Moderate Probability Diagnoses

• Pelvic Venous Disorders (Pelvic Congestion Syndrome): Though typically postmenopausal, this can occur in reproductive-age women and causes chronic pelvic/lower abdominal pain 1. Standard CT may miss this diagnosis as it requires specific venous-phase imaging or MRI with dynamic sequences 1.

• Mesenteric Panniculitis: This inflammatory condition of mesenteric fat can cause chronic abdominal pain and may be subtle on standard CT imaging 2. It presents with diffuse pain and normal laboratory values.

• Chronic Pelvic Inflammatory Disease or Adhesive Disease: Though she denies vaginal discharge, chronic PID can present with persistent pain and normal acute-phase testing 1.

Lower Probability but Important to Exclude

• Occult Malignancy: At age 46, ovarian or other pelvic malignancy must be considered, especially with worsening pain 1. However, two normal CT scans make this less likely.

• Small Intestinal Bacterial Overgrowth (SIBO): Can cause chronic abdominal pain and bloating, though typically associated with more prominent bloating and bowel habit changes 1.

Recommended Diagnostic Approach

Immediate Next Steps

1. Detailed Clinical Reassessment

• Marijuana use pattern: Specifically ask about hot shower relief of symptoms (pathognomonic for cannabinoid hyperemesis) 1
• Pain characteristics: Relationship to menstrual cycle (suggests gynecologic etiology) 1
• Bowel pattern details: Even subtle changes in frequency, consistency, or sensation of incomplete evacuation 1
• Psychological comorbidities: Anxiety, depression, somatization, and sleep disturbance are highly associated with functional disorders 1

2. Additional Laboratory Testing

• Tissue transglutaminase IgA with total IgA: To exclude celiac disease, which commonly presents with chronic abdominal pain 1
• CA-125: If pelvic pathology suspected, though sensitivity is limited 1
• Fecal calprotectin: If any concern for inflammatory bowel disease 1

Advanced Imaging (If Initial Reassessment Suggests Structural Pathology)

3. MRI Pelvis with Contrast

• This is the problem-solving examination of choice for chronic pelvic pain with nondiagnostic CT 1
• Can identify pelvic venous disorders with time-resolved post-contrast sequences showing ovarian vein reflux 1
• Superior for detecting endometriosis, adhesive disease, and subtle pelvic masses 1
• Order if: Pain has pelvic/lower abdominal predominance, cyclical component, or if pelvic venous disorder suspected 1

4. Consider Pelvic Ultrasound with Doppler

• Transvaginal ultrasound is first-line for gynecologic causes 1
• Doppler can identify engorged periuterine/periovarian veins (≥8mm), low-velocity flow, and altered flow with Valsalva suggesting pelvic congestion 1
• This should have been done already but appears to have been omitted 1

Functional Testing (If Structural Pathology Excluded)

5. Breath Testing for SIBO/Carbohydrate Intolerance

• Hydrogen-methane breath testing with glucose or lactulose if bloating is prominent or dietary triggers suspected 1
• Consider empiric low-FODMAP diet trial before testing 1

Treatment Recommendations

If Functional Disorder Diagnosed (Most Likely)

Pharmacologic Management:

• Dicyclomine 10-20mg four times daily: Antispasmodic for IBS-related pain, works via anticholinergic and direct smooth muscle effects 3
• Central neuromodulators: Low-dose tricyclic antidepressants (amitriptyline 10-25mg nightly) or SSRIs for visceral hypersensitivity 1
• Avoid chronic opioids: High risk of dependence without addressing underlying pathophysiology 1

Non-Pharmacologic Management:

• Mandatory marijuana cessation: If cannabinoid hyperemesis suspected, this is curative 1
• Dietary modification: Low-FODMAP diet trial for 4-6 weeks 1
• Brain-gut behavioral therapies: Cognitive behavioral therapy, gut-directed hypnotherapy, or mindfulness-based stress reduction 1
• Diaphragmatic breathing exercises: For abdominophrenic dyssynergia if bloating/distention prominent 1

If Pelvic Venous Disorder Confirmed

• Hormonal suppression: Estrogen overstimulation contributes; consider progestins or GnRH agonists 1
• Interventional radiology referral: For possible ovarian vein embolization 1

Critical Clinical Pitfalls

Common Errors to Avoid:

1. Ordering more CT scans: Two normal contrast-enhanced CT abdomen/pelvis studies are sufficient. Additional CT adds radiation without diagnostic yield 1, 4. If structural pathology is still suspected, MRI is the next step 1.

2. Missing cannabinoid hyperemesis syndrome: Daily marijuana use with chronic abdominal pain, nausea, and frequent ED visits is the classic presentation 1. Specifically ask about hot shower use for symptom relief.

3. Failing to perform pelvic ultrasound: This is the recommended first-line imaging for reproductive-age women with pelvic pain and appears to have been omitted 1.

4. Dismissing functional disorders: Normal testing does not mean "nothing is wrong." Functional GI disorders cause real suffering and respond to specific treatments 1.

5. Inadequate pain management: While avoiding opioids, ensure appropriate use of antispasmodics, neuromodulators, and behavioral interventions 1, 3.

6. Not addressing psychological comorbidities: Anxiety, depression, and somatization are integral to functional disorders, not separate issues 1.

Addressing Patient Frustration

Therapeutic relationship is critical:

• Validate that her pain is real and acknowledge the frustration of negative testing 1
• Explain that functional disorders are diagnosable conditions with effective treatments, not "diagnoses of exclusion" 1
• Set realistic expectations: improvement rather than complete cure is the goal 1
• Emphasize the importance of keeping this appointment rather than returning to the ED, as continuity of care is essential for functional disorders 1