Epidemiology
- Most common in females 20–50 years old.
Etiology
- Associated Conditions:
- Major depressive disorder (MDD) and generalized anxiety disorder (GAD).
- Irritable bowel syndrome (IBS).
- Chronic fatigue syndrome / Myalgic encephalomyelitis.
- Interstitial cystitis / painful bladder syndrome.
- Tension and migraine headaches.
- Somatic symptom disorder.
- Triggers: Physical/emotional trauma, psychological stress, severe viral infections.
Pathophysiology
Central pain processing dysfunction (central sensitization / neuroendocrine dysregulation; abnormal pain amplification).
Clinical features
- Chronic Widespread Pain:
- Present for ≥ 3 months.
- Involves both sides of the body, above and below the waist, and axial skeleton.
- Characterized by hyperalgesia (exaggerated pain response) and allodynia (pain from non-painful stimuli). c
- Systemic Symptoms:
- Fatigue & non-restorative sleep (“waking unrefreshed”). c
- Cognitive disturbance (“fibro fog”: impaired memory, poor concentration).
- Paresthesias, mood disturbances, and morning stiffness.
- Physical Exam (PE):
- Point tenderness at multiple soft tissue sites (e.g., trapezius, lateral epicondyle, medial knee).
- Normal joint examination (no synovitis, joint effusion, erythema, warmth, or structural deformities).
- Normal objective neurological exam (normal muscle strength, deep tendon reflexes, and sensation).
Diagnostics
- Initial/Screening: Clinical diagnosis based on ACR Criteria (Widespread Pain Index [WPI] ≥ 7 + Symptom Severity [SS] score ≥ 5 OR WPI 3–6 + SS ≥ 9; symptoms persisting for ≥ 3 months without another explanatory disorder).
- Key Labs (to exclude secondary causes):
- CBC, BMP: Normal.
- Inflammatory markers: ESR and CRP are normal (crucial negative finding). c2
- TSH: Normal (rules out hypothyroidism).
- Creatine Kinase (CK): Normal (rules out inflammatory/statin-induced myopathy).
- Confirmatory/Gold Standard: None (clinical diagnosis of exclusion).
- Autoantibodies: ANA, RF, anti-CCP are not routinely indicated unless specific signs of connective tissue disease are present (reduces false positives).
- Imaging/Biopsy: Not indicated; radiographically and histologically normal.
Differential Diagnostics
| Feature | Fibromyalgia (FM) | Polymyositis (PM) | Polymyalgia Rheumatica (PMR) |
|---|---|---|---|
| Demographics | F, 20–55 yo | F > M, > 40 yo | Age > 50 yo (peak 70s) |
| Core Symptom | Widespread chronic pain, fatigue, insomnia | Painless proximal muscle weakness | Proximal morning stiffness/pain (shoulders, hip girdle) |
| Strength | Normal | Decreased (proximal) | Normal (pain-limited ROM) |
| CK / Aldolase | Normal | Markedly elevated (↑↑) | Normal |
| ESR / CRP | Normal | Normal or mild ↑ | Markedly elevated (↑↑, ESR > 50) |
| Diagnostic Test | Clinical | Muscle biopsy (CD8+ endomysial) | Clinical + rapid steroid response |
| 1st-Line Tx | Exercise, Duloxetine, TCAs, Pregabalin | High-dose prednisone (± MTX/AZA) | Low-dose prednisone (10–20 mg) |
| Key Association | IBS, tension headaches, depression | Interstitial lung disease, malignancy | Giant Cell Arteritis (GCA) |
- Polymyalgia Rheumatica (PMR): c
- Diff by age > 50 yo, morning stiffness localized to shoulder/hip girdle, markedly elevated ESR/CRP (> 40–50 mm/hr), and dramatic response to low-dose systemic corticosteroids.
- Hypothyroidism:
- Diff by elevated TSH, weight gain, delayed DTR relaxation phase, cold intolerance, and possible mild ↑ CK.
- Polymyositis / Dermatomyositis: c
- Diff by objective proximal muscle weakness (difficulty climbing stairs, combing hair), elevated CK/aldolase, abnormal EMG, and positive muscle biopsy.
- Rheumatoid Arthritis (RA):
- Diff by symmetric peripheral inflammatory arthritis (MCP, PIP, MTP), joint swelling/synovitis, elevated ESR/CRP, and (+) RF / anti-CCP antibodies.
- Systemic Lupus Erythematosus (SLE):
- Diff by systemic features (malar rash, photosensitivity, oral ulcers, serositis, nephritis, cytopenias), (+) ANA, and (+) anti-dsDNA/anti-Smith.
Treatment
- First-line (Non-Pharmacologic - Preferred):
- Regular low-impact aerobic exercise (walking, swimming).
- CBT and sleep hygiene education.
- Second-line (Pharmacotherapy):
- SNRIs: Duloxetine, Milnacipran (preferred if comorbid depression/neuropathic pain).
- TCAs: Amitriptyline (improves sleep and central pain).
- Gabapentinoids: Pregabalin (preferred if prominent sleep disruption).
- Refractory:
- Combination pharmacotherapy (e.g., SNRI + Pregabalin); pain rehabilitation.
- Ineffective / Contraindicated (High-Yield USMLE Trap):
- Avoid Opioids, Systemic Steroids, and NSAIDs (ineffective for central pain; high risk of adverse effects).