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Fibromyalgia

Chapter 385 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders

KEY CLINICAL POINTS

  • Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain, tenderness, and associated neuropsychological symptoms (fatigue, sleep disturbance, cognitive dysfunction).
  • Prevalence is ~2% globally, with ~4% in women and <1% in men; higher in patients with rheumatic diseases (up to 30% comorbid FM).
  • Diagnosis requires widespread pain (WPI ≥ 7) and symptom severity score (SSS ≥ 5) or WPI 4–6 with SSS ≥ 9, along with 3-month duration of symptoms.
  • Non-pharmacologic treatments (exercise, CBT, physical therapy) and pharmacologic agents (duloxetine, pregabalin, SNRIs) are first-line; opioids are contraindicated.
  • Central nervous system dysregulation, genetic predisposition, and psychosocial factors are key pathophysiological mechanisms.

1. DEFINITION & OVERVIEW

Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread musculoskeletal pain, tenderness, and associated neuropsychological symptoms. It is defined by chronic widespread pain and tenderness, with associated fatigue, sleep disturbances, and cognitive dysfunction. FM is considered a chronic overlapping pain syndrome due to its association with other pain conditions.

2016 Diagnostic Criteria for Fibromyalgia

Widespread Pain Index (WPI) Symptom Severity Score (SSS) Diagnostic Criteria
WPI ‡7 and SSS ‡5 Generalized pain in ‡4/5 regions Fulfills all criteria
WPI 4–6 and SSS ‡9 Pain present for ‡3 months Fulfills all criteria

1.1 Central Nervous System Involvement

FM is associated with central sensitization, altered pain processing, and dysregulation of the central nervous system. These mechanisms contribute to heightened pain sensitivity, fatigue, and sleep disturbances.

1.2 Associated Symptoms

Patients often report fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. These symptoms may have a greater impact on quality of life than pain itself.

2. EPIDEMIOLOGY

Worldwide prevalence is ~2%, with ~4% in women and <1% in men. Higher prevalence in patients with rheumatic diseases (e.g., RA, SLE). Risk factors include sleep disturbances, physical inactivity, and obesity. Cultural factors influence help-seeking behavior, but prevalence remains consistent across regions.

2.1 Gender Disparity

FM is 8–3 times more common in women than men. In clinical settings, the ratio is ~8:1, but population studies suggest closer to 3:1.

2.2 Comorbid Conditions

FM frequently coexists with chronic musculoskeletal, infectious, metabolic, and psychiatric conditions. Up to 30% of patients with rheumatoid arthritis or SLE have comorbid FM.

3. ETIOLOGY & PATHOPHYSIOLOGY

FM is associated with central nervous system dysregulation, genetic predisposition, and psychosocial factors. Altered sensory processing, genetic variants in pain and stress pathways, and central sensitization contribute to pathogenesis. No definitive etiology is established, but central pain-processing abnormalities are central to the syndrome.

3.1 Genetic Factors

Genes involved in pain, stress response, and serotonin/monoamine metabolism are implicated. Shared pathways with mood disorders suggest comorbidity with depression and anxiety.

3.2 Central Sensitization

Altered sensory afferent processing and impaired descending inhibitory control lead to hyperalgesia and allodynia. Functional MRI shows activation of pain-processing brain regions.

4. CLINICAL FEATURES

Widespread pain ( ≥ 18/20 body regions), fatigue, sleep disturbances, cognitive dysfunction, and mood disorders are core features. Pain is poorly localized, severe, and persistent, with functional impairment as a key outcome.

4.1 Pain Characteristics

Pain is widespread (above/below waist, axial skeleton), poorly localized, and resistant to usual treatments. Tenderness is present at 18 specific sites.

4.2 Neuropsychological Symptoms

Fatigue, sleep disturbances, and cognitive dysfunction are common. These symptoms often have a greater impact on quality of life than pain itself.

5. DIFFERENTIAL DIAGNOSIS

FM must be differentiated from inflammatory arthritis, connective tissue diseases, infectious conditions, degenerative joint disease, and psychiatric disorders. Table 385-1 lists key differential diagnoses.

Table 385-1: Common Conditions in the Differential Diagnosis of Fibromyalgia

Category Conditions
Inflammatory Polymyalgia rheumatica, RA, Spondyloarthritides, SLE, Sjögren’s syndrome
Infectious Hepatitis C, HIV, Lyme disease, Parvovirus B19, EBV
Noninflammatory Degenerative joint/spine disease, Myofascial pain, Bursitis, Tendinitis
Endocrine Hypo- or hyperthyroidism, Hyperparathyroidism
Neurologic Multiple sclerosis, Neuropathic pain
Psychiatric Major depressive disorder
Drugs Statins, Aromatase inhibitors

5.1 Inflammatory Conditions

Conditions like rheumatoid arthritis, lupus, and polymyalgia rheumatica must be excluded via history, physical exam, and labs.

5.2 Psychiatric Comorbidities

Depression and anxiety are common but not diagnostic. Screening for major depressive disorder is essential.

6. INVESTIGATIONS & DIAGNOSIS

Routine labs (CBC, ESR, CRP, TSH) and imaging (spine/joint radiographs) are normal in FM. Diagnostic criteria focus on patient-reported symptoms and physical findings rather than lab tests.

Table 385-2: Laboratory and Radiographic Testing in Patients with Fibromyalgia Symptoms

Test Purpose
ESR/CRP Rule out inflammation
CBC Check for anemia or infection
TSH Evaluate thyroid dysfunction
ANA/anti-CCP Screen for autoimmune diseases
Creatine phosphokinase Rule out muscle disease
Viral/bacterial serologies Exclude infectious causes
Spine/joint radiographs Diagnose inflammatory arthritis

6.1 Laboratory Tests

Normal results in FM without comorbidities. Tests are used to exclude other conditions (e.g., anemia, thyroid dysfunction).

6.2 Imaging

Radiographs are used sparingly for inflammatory arthritis. MRI is reserved for suspected spinal or neurological involvement.

7. MANAGEMENT & TREATMENT

Management focuses on improving function and quality of life. Non-pharmacologic strategies (exercise, CBT, physical therapy) and pharmacologic agents (SNRIs, gabapentin) are first-line. Opioids are contraindicated.

Table 385-3: Drugs with Demonstrated Efficacy in Fibromyalgia

Drug Class Examples
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Duloxetine, Milnacipran
Alpha-2-Delta Ligands Pregabalin, Gabapentin
Tricyclic Antidepressants Amitriptyline
Sedating Antidepressants Cyclobenzaprine
TENS Transcutaneous Electrical Nerve Stimulation

7.1 Non-Pharmacologic Approaches

Physical activity (aerobic exercise, strength training), cognitive-behavioral therapy, and physical therapies (acupuncture, TENS) are recommended. Patient education and goal-setting are critical.

7.2 Pharmacologic Therapy

First-line drugs include SNRIs (duloxetine, milnacipran), alpha-2-delta ligands (pregabalin, gabapentin), and tricyclic antidepressants (amitriptyline). Opioids are avoided due to lack of efficacy and risk of misuse.

8. PROGNOSIS & COMPLICATIONS

FM is a chronic, fluctuating condition with significant impact on quality of life. Complications include depression, sleep disorders, and functional impairment. Early intervention improves outcomes.

8.1 Functional Impact

FM leads to reduced physical, mental, and social functioning. Pain and fatigue are often exacerbated by activity.

9. SPECIAL CONSIDERATIONS

FM requires a multidisciplinary approach. Psychosocial factors, comorbid conditions, and patient education are critical. Treatment should focus on improving function rather than eliminating pain.

9.1 Psychosocial Factors

Stress, trauma, and interpersonal violence are associated with FM. PTSD should be screened for and treated if present.

9.2 Pregnancy and Pediatrics

FM is common in women of reproductive age. Treatment during pregnancy should avoid teratogenic agents. Pediatric FM is rare but possible.

10. KEY POINTS & CLINICAL PEARLS

FM is a chronic pain syndrome with widespread musculoskeletal pain and associated neuropsychological symptoms. Diagnosis is based on patient-reported symptoms and physical findings. Management focuses on improving function and quality of life through non-pharmacologic and pharmacologic strategies. Opioids are contraindicated. Early intervention and patient education are critical for optimal outcomes.