What is the appropriate workup and treatment for a patient presenting with symptoms of fibromyalgia, including widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive difficulties?

Workup for Fibromyalgia

Diagnostic Approach

Fibromyalgia is a clinical diagnosis based on characteristic symptoms—not a diagnosis of exclusion—and requires minimal laboratory testing only to rule out specific alternative diagnoses. 1

Clinical Criteria for Diagnosis

The diagnosis requires the following features present for at least 3 months 2:

• Chronic widespread pain affecting all four body quadrants (above and below waist, left and right sides) 2
• Associated symptoms including fatigue, non-restorative sleep, cognitive dysfunction ("fibro fog"), and mood disturbances 2, 3
• Pain that is disproportionate to any identifiable tissue damage or inflammation 1

Essential Laboratory Testing

Obtain only the following tests to exclude mimicking conditions 4:

• Complete blood count (CBC)
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
• Thyroid-stimulating hormone (TSH)
• Creatine kinase (CK)
• Rheumatoid factor and anti-CCP antibodies (if inflammatory arthritis suspected)

Normal laboratory results support the fibromyalgia diagnosis 1, 4. Avoid extensive testing that provides limited additional benefit 2.

Key Differential Diagnoses to Exclude

Rule out the following conditions through history, physical examination, and targeted testing 5, 4:

• Inflammatory arthropathies (rheumatoid arthritis, spondyloarthropathies) - look for joint swelling, morning stiffness >1 hour, elevated inflammatory markers
• Hypothyroidism - check TSH
• Polymyalgia rheumatica - typically age >50, elevated ESR/CRP
• Myopathies - check CK, assess for proximal muscle weakness
• Systemic lupus erythematosus - check ANA if clinical features suggest

Physical Examination Findings

While the 1990 ACR tender point examination (11 of 18 points) was historically used, clinicians should recognize its limitations and not rely solely on tender points for diagnosis 4. The examination should focus on:

• Absence of joint swelling or synovitis
• Normal muscle strength
• Diffuse tenderness to palpation across multiple body regions
• Absence of neurological deficits

Screening Tool

Use the Fibromyalgia Rapid Screening Tool for patients presenting with diffuse chronic pain 3. This validated instrument helps identify patients who warrant full diagnostic evaluation.

Treatment Algorithm

Step 1: Patient Education and Non-Pharmacological Foundation

Begin immediately with patient education explaining fibromyalgia as a central nervous system pain processing disorder, not tissue damage 6, 1. This reassures patients and reduces unnecessary healthcare utilization 2.

Initiate aerobic and strengthening exercise as the primary intervention (Level Ia, Grade A evidence) 6. Start with low-intensity activities (walking, swimming, cycling) for 10-15 minutes 2-3 times weekly, gradually increasing duration and intensity based on tolerance 6. This has the strongest evidence of any intervention for improving pain, function, and quality of life 6.

Step 2: Add Complementary Non-Pharmacological Therapies (4-6 weeks if insufficient response)

Consider adding the following evidence-based therapies 2, 6:

• Cognitive behavioral therapy (CBT) - particularly beneficial for patients with mood disorders or maladaptive coping strategies 2
• Heated pool therapy/hydrotherapy with or without exercise 6
• Yoga, tai chi, or mindfulness-based stress reduction 2
• Manual acupuncture 2

Step 3: Pharmacological Management (if non-pharmacological approaches insufficient)

Select ONE first-line medication based on predominant symptoms 6:

For Pain with Sleep Disturbance:

Amitriptyline 10 mg at bedtime, increase by 10 mg weekly to target 25-50 mg nightly (Level Ia, Grade A) 6. This provides pain reduction and improved sleep 6. Caution: Avoid in adults ≥65 years due to anticholinergic effects 6.

For Pain with Depression/Anxiety:

Duloxetine 30 mg daily for 1 week, then increase to 60 mg daily (Level Ia, Grade A) 6, 7. Do not exceed 60 mg/day as higher doses provide no additional benefit but increase adverse events 6.

Alternative: Milnacipran 12.5 mg daily, titrate over 1 week to 100-200 mg/day in divided doses (Level Ia, Grade A) 6.

For Pain as Primary Symptom:

Pregabalin 75 mg twice daily, increase after 3-7 days to 150 mg twice daily (300 mg/day total), maximum 225 mg twice daily (450 mg/day) if needed (Level Ia, Grade A) 6, 7. Do not exceed 450 mg/day as 600 mg provides no additional benefit but increases adverse events 6, 7. Adjust dose for creatinine clearance <60 mL/min 6, 7.

Step 4: Reassess and Adjust (4-8 weeks after initiating pharmacotherapy)

Evaluate using pain scores, functional status, and patient global impression of change 6.

If partial response: Consider adding a medication from a different class (e.g., add duloxetine to pregabalin) 6.

If inadequate response: Switch to an alternative first-line medication from a different class 6.

If still inadequate: Consider tramadol 50-100 mg up to four times daily (Level Ib, Grade A), though use with caution given opioid-related risks 6, 3.

Critical Medications to AVOID

Never prescribe the following for fibromyalgia 2, 6:

• Strong opioids - no demonstrated benefit with significant harm (Level Ia, Grade A) 2, 6
• Corticosteroids - no efficacy demonstrated (Level Ia, Grade A) 2, 6
• NSAIDs as monotherapy - no evidence of benefit over placebo for chronic fibromyalgia pain 2, 3

Common Pitfalls to Avoid

• Do not treat fibromyalgia as a diagnosis of exclusion requiring extensive testing 1. Make it a positive clinical diagnosis based on characteristic features.
• Do not rely solely on pharmacological therapy without implementing exercise and behavioral approaches 6. Medications alone are insufficient.
• Do not escalate duloxetine beyond 60 mg/day or pregabalin beyond 450 mg/day - no additional benefit but increased adverse events 6, 7.
• Do not expect large treatment effects - most interventions show small to moderate benefits, requiring realistic patient expectations 6.
• Do not overlook psychiatric comorbidities - depression and anxiety are common and require concurrent management 4, 8.

Monitoring and Follow-up

Reassess every 4-8 weeks initially to evaluate treatment efficacy using standardized measures (visual analog scale for pain, Fibromyalgia Impact Questionnaire for function, Patient Global Impression of Change) 6. Adjust the treatment plan based on response, tolerability, and patient goals 2.