Musculoskeletal · PANCE / PANRE

Fibromyalgia

Centralized pain syndrome with widespread tenderness, fatigue, and sleep and cognitive disturbance; normal labs and imaging.

Also known as: fibromyalgia, fibro, fibromyalgia syndrome, FMS

Overview

Chronic centralized pain disorder characterized by widespread musculoskeletal pain, fatigue, nonrestorative sleep, cognitive dysfunction ('fibro fog'), and somatic symptoms without inflammation or structural tissue damage.

Epidemiology

Affects 2-4% of adults; female-to-male ratio ~3:1 (closer to 2:1 with newer criteria). Peak onset 30-50. Frequently coexists with other functional somatic syndromes (IBS, chronic headache, interstitial cystitis, TMJ disorder) and with mood and anxiety disorders.

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Risk factors

Female sex
Family history (genetic predisposition)
Adverse childhood experiences, prior trauma or PTSD
Depression and anxiety
Other chronic pain conditions (osteoarthritis, RA, lupus — fibromyalgia coexists in 15-30%)
Sleep disorders, including OSA
Physical or emotional triggering event (motor vehicle accident, infection, surgery)

Pathophysiology

Central sensitization with augmented central nervous system pain processing — reduced descending inhibition, elevated substance P and glutamate, and altered functional connectivity in pain-processing regions. Peripheral tissues are histologically normal.

Clinical presentation

Symptoms

Diffuse musculoskeletal pain >3 months in multiple body regions, often migratory
Profound fatigue, especially morning fatigue and after exertion
Nonrestorative sleep, frequent awakenings
Cognitive symptoms — word-finding difficulty, decreased concentration ('fibro fog')
Headache, paresthesias, dizziness
GI symptoms (IBS overlap), bladder symptoms, dysmenorrhea
Mood disturbance — depression and anxiety common

Signs / physical exam

Tenderness to palpation at multiple soft-tissue sites (no longer required for diagnosis but commonly observed)
Joint exam normal — no synovitis, erythema, or effusion
Neurologic exam normal — no objective weakness, sensory loss, or reflex changes
Skin and muscle exam unremarkable

Differential diagnosis

Hypothyroidism — Fatigue, cold intolerance, weight gain; elevated TSH
Polymyalgia rheumatica — Age >50, proximal stiffness, ESR >40 — fibromyalgia has normal markers
Inflammatory arthritis (RA, SpA) — Synovitis, elevated CRP/ESR, joint imaging changes
SLE / connective tissue disease — Positive ANA with organ involvement; fibromyalgia frequently coexists
Inflammatory myopathy — True weakness, elevated CK
Obstructive sleep apnea / restless legs — Nonrestorative sleep — treat to improve fibromyalgia outcomes
Major depressive disorder — Anhedonia, hopelessness; high comorbidity and overlapping treatment
Statin myopathy — Drug exposure, elevated CK
Chronic fatigue syndrome (ME/CFS) — Post-exertional malaise dominates; significant overlap

Diagnostic workup

Diagnostic criteria

2016 ACR criteria: widespread pain index (WPI) and symptom severity scale (SSS) — pain in 4 of 5 body regions for ≥3 months with WPI ≥7 and SSS ≥5 (or WPI 4-6 and SSS ≥9), and no alternative diagnosis.

Labs

Goal is to exclude alternative explanations — not to confirm fibromyalgia
CBC, CMP, TSH, CRP, ESR, CK, vitamin D, vitamin B12
Consider ANA only if specific connective tissue features (avoid as screen — high false-positive rate)
Consider HCV, Lyme, celiac screen only if clinically indicated

Imaging

Generally NOT indicated — incidental findings on MRI commonly mislead
Image only if focal red-flag findings emerge (true weakness, focal joint signs, neurologic deficits)

Diagnostic algorithm

Domain	First-line
Education	Reassurance: real pain, no tissue damage, not progressive
Exercise	Graded aerobic exercise (walking, swimming, cycling)
Sleep	Sleep hygiene; treat OSA / RLS
Psychological	CBT, mindfulness-based stress reduction
Medication — pain/sleep	Amitriptyline 10-50 mg qhs, cyclobenzaprine qhs
Medication — pain/mood	Duloxetine, milnacipran (SNRI)
Medication — pain/sleep alt.	Pregabalin, gabapentin
Avoid	Chronic opioids, repeat imaging without red flags

Fibromyalgia management — non-pharmacologic measures and SNRIs/TCAs/gabapentinoids are the evidence base; opioids are not.

Treatment

First-line

Patient education — emphasize that pain is real, reflects altered central pain processing, and is not destructive or progressive
Aerobic exercise — graded, low-impact (walking, swimming, cycling); cornerstone of treatment
Sleep hygiene and treatment of sleep disorders (OSA, restless legs)
Cognitive behavioral therapy and mindfulness-based stress reduction
Treat coexisting depression and anxiety

Complications

Functional disability, work absence, reduced quality of life
Depression, anxiety, suicidality (elevated risk)
Polypharmacy and adverse drug effects
Missed alternative diagnosis if criteria applied superficially
Healthcare overutilization and unnecessary imaging or procedures

PANCE pearls

Fibromyalgia is a clinical diagnosis based on symptom criteria and exclusion of alternatives — extensive lab and imaging workup is rarely productive.
Aerobic exercise is more effective than any single medication.
Combining a low-dose TCA at night with an SNRI or pregabalin in the day is a common, evidence-based strategy.
Fibromyalgia frequently coexists with inflammatory arthritis — treating the inflammatory disease alone will not relieve central pain.
Opioids are contraindicated as long-term therapy.

References

ACR 2016 — 2016 Revisions to the ACR Diagnostic Criteria for Fibromyalgia (Wolfe et al., Semin Arthritis Rheum 2016)
EULAR 2017 — EULAR Revised Recommendations for the Management of Fibromyalgia (Macfarlane et al., Ann Rheum Dis 2017)

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