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Fibromyalgia¶

Chapter 385 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders · Part 11 – Rheumatology & Immunology · Chapter 385

Key Clinical Points¶

Worldwide prevalence is ~2%, with ~4% in women and <1% in men.
Diagnosis requires widespread pain (above and below waist, axial) for at least 3 months.
2016 Diagnostic Criteria: WPI ≥ 7 and SSS ≥ 5 OR WPI 4 to 6 and SSS ≥ 9.
Routine laboratory and radiographic tests yield normal results in FM without comorbidities.
Strong opioid analgesics are to be avoided due to lack of efficacy and risk of worsening symptoms/function.
First-line pharmacologic agents include antidepressants (duloxetine, milnacipran) and anticonvulsants (pregabalin, gabapentin).
Physical conditioning with aerobic exercise is the most helpful nonpharmacologic strategy.
FM is associated with comorbidities including IBS, TMJ, chronic fatigue syndrome, and depression.
Genetic factors are linked to pathways controlling pain and stress responses.
Functional impairment is a key measure of management success, not just pain elimination.

1. DEFINITION & OVERVIEW¶

• Definition: Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain and tenderness. • Core Symptoms: Beyond pain, patients commonly report neuropsychological symptoms: fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. • Chronic Overlapping Pain Conditions: FM is part of a group of conditions sharing underlying mechanisms. These include: ◦ Headache ◦ Facial/jaw pain (TMJ) ◦ Regional myofascial pain (neck or back) ◦ Arthritis ◦ Visceral pain (GI tract, bladder, pelvic/perineal region) • Central Nervous System Role: Evidence implicates the CNS as key to maintaining pain and other core symptoms. • Functional Impact: FM is associated with substantial negative consequences for physical and social functioning.

2. EPIDEMIOLOGY¶

• Prevalence: ~2% worldwide; ~4% in women; <1% in men. • Clinical Setting: Diagnosis is much more common in women than in men (ratio of ~8:1). • Population Studies: Ratio of women to men is closer to 3:1. • Risk Factors: ◦ Higher prevalence in patients with rheumatic diseases (up. to 30% in RA or SLE). ◦ Sleep disturbances ◦ Physical inactivity ◦ Overweight or obesity.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

• Central Nervous System (CNS): Key to maintaining pain and core symptoms. • Genetics: ◦ Linked to pathways controlling pain and stress responses. ◦ Shared neurobiologic pathways with mood disorders. ◦ Genes associated with metabolism, transport, and receptors of serotonin and other monoamines are implicated. • Sensory Processing: ◦ Altered sensory afferent pain processing. ◦ Impaired descending noxious inhibitory control → hyperalgesia and allodynia. • Imaging Findings: Functional MRI shows activation of brain regions involved in pain even for innocuous stimuli. • Other Potential Factors: ◦ Possible small fiber neuropathy. ◦ Potential autoimmune etiology for changes in the peripheral nervous system.

4. CLINICAL FEATURES¶

• Pain and Tenderness: ◦ "Pain all over" (above/below waist, both sides, axial skeleton). ◦ Duration: Must be present most of the day on most days for ≥ 3 months. ◦ Sensitivity: Increased evoked pain sensitivity (e.g., pressure from blood pressure cuff or skin roll). ◦ Tender-point examination: Historically required 11/18 sites; modern criteria focus on patient-reported symptoms. • Neuropsychological Symptoms: ◦ Fatigue: Highly prevalent; often worsened by exercise or unaccustomed activity. ◦ Sleep: Difficulty falling/staying asleep, early-morning awakening; patients awake feeling unrefreshed. May involve restless legs syndrome or sleep-disordered breathing. ◦ Cognitive Dysfunction: Problems with attention, concentration, word retrieval, and short-term memory (processing speed is age-appropriate). ◦ Mood Disorders: Anxiety and depression are common; lifetime prevalence of mood disorders ≈ 80%. • Comorbidities: ◦ Common overlaps: Headache, facial/jaw pain, regional myofascial pain, and visceral pain. ◦ Clinical Significance: Shared pathways mean treatment for one condition may help global symptom management.

5. DIFFERENTIAL DIAGNOSIS¶

• Table 385-1: Common Conditions in the Differential Diagnosis of Fibromyalgia ◦ Inflammatory: Polymyalgia rheumatica; Rheumatoid arthritis, spondyloarthritides; SLE, Sjögren’s syndrome. ◦ Infectious: Hepatitis C, HIV, Lyme disease, Parvovirus B19, Epstein-Barr virus. ◦ Noninflammatory: Degenerative joint/spine/disk disease; Myofascial pain syndromes; Bursitis, tendinitis, repetitive strain injuries. ◦ Endocrine: Hypo- or hyperthyroidism, Hyperparathyroidism. ◦ Neurologic: Multiple sclerosis, Neuropathic pain syndromes. ◦ Psychiatric: Major depressive disorder. ◦ Drugs: Statins, Aromatase inhibitors.

6. INVESTIGATIONS & DIAGNOSIS¶

Initial Assessment: Evaluate for common entities in the differential diagnosis (Table 385-1).
Routine Laboratory Testing (Table 385-2): ◦ Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) ◦ Complete blood count (CBC) ◦ Thyroid-stimulating hormone (TSH)
Guided by History and Physical Examination (Table 385-2): ◦ Complete metabolic panel ◦ Antinuclear antibody (ANA), Anti-SSA, and anti-SSB ◦ Rheumatoid factor and anti-CCP ◦ Creatine phosphokinase (CPK) ◦ Viral (e.g., hepatitis C, HIV) and bacterial (e.g., Lyme) serologies ◦ Spine and joint radiographs
Application of 2016 ACR Criteria (Figure 2): ◦ Step 1: Calculate Widespread Pain Index (WPI) and Symptom Severity Scale (SSS). ◦ Step 2: Determine eligibility → (WPI ≥ 7 and SSS ≥ 5) OR (WPI 4 to 6 and SSS ≥ 9). ◦ Step 3: Confirm duration → Symptoms must be present in a stable level for ≥ 3 months.

7. MANAGEMENT & TREATMENT¶

Nonpharmacologic Treatment: ◦ Physical Conditioning: Aerobic exercise is the most helpful strategy; reduces tenderness and enhances self-efficacy. ◦ Progression Strategy: Start at low levels → slow but consistent advancement; supervised or water-based programs for inactive patients. ◦ Cognitive-Behavioral Therapy: Improve sleep hygiene and reduce "illness behaviors.
Pharmacologic Approach: ◦ Strategy: Use single agents to treat multiple symptom domains (e.g., pain + sleep). ◦ Pain & Sleep focus: Cyclobenzaprine, sedating antidepressants (amitriptyline), or alpha-2-delta ligands (gabapentin, pregabalin). ◦ Pain, Fatigue, Anxiety, & Depression focus: Duloxetine or milnacipran. ◦ Inflammatory Management: Use glucocorticoids or NSAIDs only for identified inflammatory triggers; these are not effective for FM-specific symptoms.
Contraindications & Warnings: ◦ Strong Opioids: Avoid due to lack of efficacy and risk of worsening symptoms/function. ◦ Tramadol: Generally discouraged due to opioid-related adverse effects.

8. PROGNOSIS & COMPLICATIONS¶

• Management Goals: Focus on improved function and quality of life rather than total elimination of pain. • Clinical Monitoring: Routine testing is discouraged unless the symptom complex changes; MRI of spine is discouraged unless inflammatory or neurologic features are present.

9. KEY PEARLS & CLINICAL TRAPS¶

• Diagnostic Rule: FM is a clinical diagnosis based on widespread pain and neuropsychological symptoms; routine labs/imaging are typically normal. • Treatment Priority: Physical conditioning (aerobic exercise) is the cornerstone of nonpharmacologic management. • Medication Selection: Choose agents that target multiple domains (e.g., gabapentin for pain/sleep, duloxetine for pain/anxiety). • Opioid Warning: Strong opioids are ineffective and potentially harmful in FM patients.

Reference Tables¶

TABLE 385-1 Common Conditions in the Differential Diagnosis of Fibromyalgia Inflammatory Polymyalgia rheumatica…¶

Harrison's 22e, p.2965

Inflammatory
Polymyalgia rheumatica
Inflammatory arthritis: rheumatoid arthritis, spondyloarthritides
Connective tissue diseases: systemic lupus erythematosus, Sjögren’s syndrome
Infectious
Hepatitis C
HIV infection
Lyme disease
Parvovirus B19 infection
Epstein-Barr virus infection
Noninflammatory
Degenerative joint/spine/disk disease
Myofascial pain syndromes
Bursitis, tendinitis, repetitive strain injuries
Endocrine
Hypo- or hyperthyroidism
Hyperparathyroidism
Neurologic Diseases
Multiple sclerosis
Neuropathic pain syndromes
Psychiatric Disease
Major depressive disorder
Drugs
Statins
Aromatase inhibitors

TABLE 385-2 Laboratory and Radiographic Testing in Patients with Fibromyalgia Symptoms Routine Erythrocyte…¶

Harrison's 22e, p.2965

Routine
Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
Complete blood count (CBC)
Thyroid-stimulating hormone (TSH)
Guided by History and Physical Examination
Complete metabolic panel
Antinuclear antibody (ANA)
Anti-SSA (anti–Sjögren’s syndrome A) and anti-SSB
Rheumatoid factor and anti–cyclic citrullinated peptide (anti-CCP)
Creatine phosphokinase (CPK)
Viral (e.g., hepatitis C, HIV) and bacterial (e.g., Lyme) serologies
Spine and joint radiographs