What is the best course of action for a patient with chronic fatigue and intermittent abdominal pain, considering potential underlying conditions such as irritable bowel syndrome (IBS) or celiac disease?

Workup for Chronic Fatigue with Intermittent Abdominal Pain

Begin by screening fatigue severity using a 0-10 numeric rating scale and making a positive diagnosis of IBS if Rome criteria are met without alarm features, then systematically evaluate for treatable causes of both symptoms before considering functional disorders. 1, 2

Initial Clinical Assessment

Fatigue Evaluation

• Screen fatigue severity at every encounter using a 0-10 numeric scale; scores ≥4 require comprehensive evaluation 2
• Assess the multidimensional character: physical (activity level, functional capacity), cognitive (concentration, mental clarity), and emotional domains (motivation, mood) 1
• Document timing relative to meals, bowel movements, and sleep patterns 1
• Evaluate impact on work productivity and daily activities, as identical fatigue scores can produce vastly different disability levels 2

Abdominal Pain Characterization

• Determine if pain meets Rome IV criteria for IBS: recurrent abdominal pain at least 1 day per week in the last 3 months, associated with 2 or more of: related to defecation, change in stool frequency, or change in stool form 1
• Assess for alarm features that require urgent investigation: age >50 years with new symptoms, unintentional weight loss, rectal bleeding, nocturnal diarrhea or pain, family history of colorectal cancer or IBD 1
• Document stool pattern using Rome III classification based solely on consistency: IBS-C (hard stools >25% of time, loose <25%), IBS-D (loose >25%, hard <25%), or IBS-M (both >25%) 1

Associated Symptoms That Add Diagnostic Value

• Screen for extraintestinal symptoms: back pain, bladder symptoms (frequency, urgency, incomplete emptying), gynecological symptoms, headaches, and sleep disturbances 1
• Assess for comorbid functional disorders: fibromyalgia (present in 20-50% of IBS patients), chronic pelvic pain, temporomandibular joint disorder 1
• Evaluate psychological factors: depression, anxiety, catastrophizing, history of early-life adversity or trauma, as these predict chronic pain development and treatment response 1

Laboratory and Diagnostic Workup

Essential Initial Testing

• Complete blood count with differential to evaluate for anemia, which is a treatable cause of fatigue 2, 3
• Comprehensive metabolic panel to assess electrolyte disturbances, liver function, and kidney function 2
• Thyroid function tests (TSH, free T4) to exclude hypothyroidism 2
• Celiac serology (tissue transglutaminase IgA with total IgA level) in patients with IBS-D or IBS-M, as 1 in 3-4 patients with suspected IBS-D may have celiac disease 1
• Fecal calprotectin if suspicion for inflammatory bowel disease exists; if ≥250 μg/g, proceed to colonoscopy 1

Additional Testing Based on Clinical Features

• C-reactive protein and erythrocyte sedimentation rate if inflammatory bowel disease is suspected 3
• Creatine kinase if muscle pain is prominent 2
• SeHCAT scan or serum 7α-hydroxy-4-cholesten-3-one for bile acid diarrhea in IBS-D patients with severe symptoms, as 25-33% may have abnormal bile acid retention 1

When Colonoscopy Is NOT Needed

• In patients with typical IBS symptoms, no alarm features, and normal initial laboratory testing, the diagnosis is secure without colonoscopy 1
• Validation studies show patients meeting Rome IV criteria for IBS-C are 21 times more likely to have IBS-C than organic disease, and IBS-M patients are 11 times more likely to have IBS-M 1

Management Algorithm

If Active Inflammation or Organic Disease Is Found

• Treat the underlying condition aggressively, as fatigue during active IBD is directly related to gut inflammation 1, 3
• Reassess fatigue after achieving disease remission, as it persists in 50% of IBD patients despite clinical and endoscopic remission 1

If Anemia Is Present

• Initiate iron supplementation or erythropoietin as clinically indicated, as this is a Category 1 recommendation for fatigue management 2

If Depression or Anxiety Is Identified

• Start antidepressants, as this is a Category 1 recommendation for fatigue management 2
• Consider low-dose tricyclic antidepressants (e.g., amitriptyline 10-25 mg at bedtime), which rank first for abdominal pain relief in IBS and can be managed by gastroenterologists 1
• Refer to mental health professionals for cognitive behavioral therapy, which shows benefit for both chronic pain and persistent fatigue 1, 2

If Sleep Disturbance Is Present

• Implement cognitive behavioral therapy for insomnia, as sleep difficulties contribute to both fatigue and pain 1, 2

Non-Pharmacological Interventions for Functional Symptoms

For Fatigue

• Prescribe tailored physical activity starting at low intensity and gradually increasing based on tolerance 2
• Recommend moderate aerobic exercise 3-5 times weekly, adapted to functional status 2
• Teach energy conservation strategies: distribute energy throughout the day, prioritize important activities, alternate tasks, and plan structured rest periods 1

For Abdominal Pain

• Consider gut-directed hypnotherapy, which has strong evidence from systematic reviews and meta-analyses for pain relief in IBS and can be delivered online or in groups 1
• Offer cognitive behavioral therapy, which helps patients with insight into how thoughts, feelings, and behaviors relate to pain 1
• Consider mindfulness-based stress reduction, which improves specific IBS symptoms (constipation, diarrhea, bloating) and decreases visceral hypersensitivity, especially in women 1

Pharmacological Options for Abdominal Pain

Peripherally Acting Agents

• Antispasmodics rank second for abdominal pain relief in IBS; dicyclomine 40 mg four times daily showed 82% favorable response vs 55% with placebo in controlled trials 1, 4
• Peppermint oil ranks third for pain relief and performs similarly to antispasmodics 1
• For IBS-D: consider alosetron or eluxadoline; rifaximin may also provide benefit 1
• For IBS-C: secretagogues (linaclotide, plecanatide, lubiprostone) are more efficacious than placebo for reducing abdominal pain 1

Centrally Acting Agents

• Tricyclic antidepressants rank first for abdominal pain relief in network meta-analyses and should be baseline therapy for chronic pain 1
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) can be prescribed and managed by gastroenterologists for patients with limited response to tricyclics 1

Ongoing Management

Setting Expectations

• Explain that IBS has no cure, treatments aim to improve quality of life, and therapy will likely be necessary long-term 1
• Discuss that pain perception is real and multifactorial, involving both peripheral factors (visceral hypersensitivity) and central factors (central sensitization, fear of pain) 1
• Emphasize that addressing central maintaining factors is most critical for symptom relief once peripheral causes are treated 1

Monitoring and Follow-Up

• Reassess fatigue levels at every visit using the same 0-10 numeric scale to track response 2
• Avoid repetitive testing once functional diagnosis is established, as this reinforces illness behavior 5
• Refer to multidisciplinary pain team or specialist if symptoms remain uncontrolled despite comprehensive management 1, 2

Common Pitfalls to Avoid

• Do not dismiss fatigue as merely a symptom of depression without comprehensive evaluation, as treatable medical causes (anemia, hypothyroidism) are common 2, 3
• Do not perform colonoscopy in young patients (<50 years) with typical IBS symptoms and no alarm features, as this leads to unnecessary costs without improving outcomes 1
• Do not focus solely on gastrointestinal symptoms while missing important diagnostic clues from extraintestinal manifestations and psychological comorbidities 1
• Do not label pain as "functional" or "all in your head" in a dismissive manner, as this damages the therapeutic relationship; instead, explain the neurobiology of central sensitization 1
• Do not continue escalating diagnostic workup in patients with established functional disorders, as this increases healthcare costs and reinforces maladaptive illness behavior 5