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Rheumatology
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Pain Medicine

Fibromyalgia

High EvidenceUpdated: 2025-12-23

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Red Flags

  • Polymyalgia rheumatica (proximal stiffness, raised ESR, age greater than 50)
  • Inflammatory arthritis (joint swelling, morning stiffness greater than 1 hour)
  • Hypothyroidism (fatigue, weight gain, constipation)
  • Vitamin D deficiency (diffuse aches, weakness)
  • Malignancy (weight loss, night sweats, new bone pain)
  • Neurological signs (weakness, sensory loss, reflex change)
Overview

Fibromyalgia

1. Clinical Overview

Summary

Fibromyalgia is a chronic widespread pain disorder characterised by generalised musculoskeletal pain, fatigue, non-restorative sleep, and cognitive dysfunction ("fibro fog"). It is considered a central sensitisation syndrome, where the central nervous system amplifies pain signals. Fibromyalgia affects approximately 2-4% of the population, predominantly women (9:1 ratio), and often coexists with other functional syndromes including irritable bowel syndrome, chronic fatigue syndrome, and migraine. Diagnosis is clinical, based on the ACR 2016 criteria, after exclusion of other conditions. Management is multimodal: patient education, graded aerobic exercise, and pharmacotherapy (duloxetine, pregabalin, or amitriptyline). Opioids are NOT recommended as they worsen outcomes. Cognitive behavioural therapy can improve coping and function.

Key Facts

  • Definition: Chronic widespread pain with central sensitisation; not an inflammatory or degenerative disease
  • Prevalence: 2-4% of the population; 80-90% female
  • Peak age: 30-50 years
  • Core symptoms: Chronic widespread pain, fatigue, non-restorative sleep, cognitive dysfunction
  • Diagnostic criteria: ACR 2016 (Widespread Pain Index + Symptom Severity Scale)
  • Key pharmacotherapy: Duloxetine, pregabalin, amitriptyline (low dose)
  • NOT recommended: Opioids, NSAIDs (ineffective)

Clinical Pearls

Fibromyalgia is REAL Pain: The pain is not "in the patient's head" — neuroimaging shows altered central pain processing. Validating the patient's experience is essential for therapeutic relationship.

The Big Three Comorbidities: IBS, migraine, and depression are the three most common comorbidities. If you diagnose one, screen for the others.

Opioids Make It Worse: Counter-intuitively, opioids do not help and may worsen outcomes by promoting opioid-induced hyperalgesia and dependence. They are NOT recommended by any international guideline.

Why This Matters Clinically

Fibromyalgia is common, debilitating, and frequently misunderstood. Patients often feel disbelieved and have typically consulted multiple specialists before diagnosis. A clear explanation, validation, and evidence-based management plan can be transformative. Conversely, inappropriate investigations, diagnostic uncertainty, and opioid prescribing worsen outcomes.


2. Epidemiology

Incidence & Prevalence

  • Prevalence: 2-4% of the population (varies by diagnostic criteria used)
  • Sex ratio: Female:Male 9:1 (though this may be narrowing with newer criteria)
  • Peak onset: 30-50 years
  • Trend: Increasing recognition; prevalence stable

Demographics

FactorDetails
AgeOnset typically 30-50 years; can occur at any age including adolescence
Sex80-90% female
EthnicityAll ethnic groups
SocioeconomicAll socioeconomic groups; higher reported disability in lower SES

Risk Factors

Non-Modifiable:

  • Female sex
  • Family history of fibromyalgia (genetic component)
  • History of physical or emotional trauma

Modifiable:

Risk FactorAssociation
Poor sleepStrong bidirectional relationship
Physical deconditioningWorsens symptoms
Psychological distressAnxiety, depression exacerbate
ObesityAssociated with worse outcomes
History of chronic regional painMay generalise to fibromyalgia

3. Pathophysiology

Mechanism

Step 1: Genetic and Environmental Predisposition

  • Genetic factors affect pain processing (e.g., serotonin transporter gene polymorphisms)
  • Environmental triggers: physical trauma, infection, psychological stress
  • These factors may initiate chronic pain pathway dysfunction

Step 2: Central Sensitisation

  • Central nervous system amplifies pain signals
  • Reduced descending pain inhibition from brainstem
  • Increased excitatory neurotransmitters (glutamate, substance P)
  • Decreased inhibitory neurotransmitters (serotonin, noradrenaline, GABA)

Step 3: Altered Brain Activity

  • Functional MRI shows increased activity in pain-processing regions
  • Reduced grey matter volume in areas involved in pain modulation
  • Increased connectivity between pain matrix regions

Step 4: Peripheral and Secondary Changes

  • Small fibre neuropathy may contribute in some patients
  • Muscle deconditioning from reduced activity
  • Sleep disruption further reduces pain threshold
  • Cognitive dysfunction from chronic pain and poor sleep

Classification

SubtypeFeatures
Pure fibromyalgiaWidespread pain without significant mood disorder
Fibromyalgia with depressionProminent mood symptoms
Fibromyalgia with somatic symptomsMultiple overlapping syndromes (IBS, migraine, TMJ)
Secondary fibromyalgiaOccurring alongside another chronic pain condition (e.g., OA, RA)

Associated Conditions

ConditionPrevalence in Fibromyalgia
Irritable bowel syndrome (IBS)30-70%
Chronic fatigue syndrome20-70%
Migraine/tension headache50%
Depression20-40%
Anxiety disorders30-60%
Temporomandibular disorder (TMD)25%
Interstitial cystitis10-20%

4. Clinical Presentation

Symptoms

Core Symptoms:

Other Common Symptoms:

Atypical Presentations:

Signs

General:

Musculoskeletal:

Neurological:

Red Flags

[!CAUTION] Red Flags — Exclude other diagnoses if:

  • Inflammatory markers elevated (ESR, CRP) — consider PMR, inflammatory arthritis
  • Joint swelling — inflammatory arthritis
  • Objective weakness — myopathy, myositis
  • Neurological signs — MS, neuropathy, spinal pathology
  • Weight loss, night sweats — malignancy
  • New onset after age 50 with proximal stiffness — PMR
  • Abnormal reflexes — neurological disease

Chronic widespread pain (present for ≥3 months) — Described as aching, burning, throbbing
Common presentation.
Fatigue — "I wake up tired"; disproportionate to activity
Common presentation.
Non-restorative sleep — "I never feel refreshed"
Common presentation.
Cognitive dysfunction ("fibro fog") — Difficulty concentrating, memory problems
Common presentation.
5. Clinical Examination

Structured Approach

General:

  • Assess general demeanour (often tired, frustrated)
  • Note previous consultations and investigations

Musculoskeletal:

  • Full joint examination: look for synovitis, effusion, deformity (should be absent)
  • Assess range of movement (typically normal)
  • Palpate for tenderness (widespread, not localised to joints)

Neurological:

  • Power, reflexes, sensation — should be normal
  • Look for objective deficit (not present in fibromyalgia)

Classic Tender Points (Historical — Not Required for Diagnosis):

  • 18 specific tender points (9 pairs) used in 1990 ACR criteria
  • Now replaced by Widespread Pain Index in 2016 criteria
  • Still useful for clinical demonstration

Special Tests

TestTechniquePositive FindingClinical Significance
Tender point examApply 4kg pressure to classic sitesTenderness at ≥11/18 pointsSupports fibromyalgia (historical)
Normal inflammatory markersESR, CRPNormalHelps exclude inflammatory conditions
Normal strength testingManual muscle testingNo objective weaknessExcludes myopathy
Normal reflexesDeep tendon reflexesNormalExcludes neurological pathology

6. Investigations

First-Line (Bedside)

  • Clinical diagnosis — Based on history and examination
  • BMI — Obesity common and worsens symptoms

Laboratory Tests

TestExpected FindingPurpose
FBCNormalExclude anaemia
ESRNormalExclude inflammatory disease
CRPNormalExclude inflammatory disease
TFTsNormalExclude hypothyroidism
Vitamin DMay be low (should correct)Associated with diffuse pain
CalciumNormalExclude hypercalcaemia
HbA1c/GlucoseNormalDiabetes screen
ANA, RFNegative (unless coexisting AI disease)Exclude SLE, RA

Key Point: Investigations are used to EXCLUDE other conditions, not to diagnose fibromyalgia.

Imaging

ModalityIndication
X-raysNOT routine; if concern for OA or inflammatory arthritis
MRINOT routine; if neurological signs or specific joint pathology suspected

Diagnostic Criteria

ACR 2016 Criteria for Fibromyalgia:

Widespread Pain Index (WPI): Score 0-19 Count of painful regions in past week from list of 19 areas

Symptom Severity Scale (SSS): Score 0-12 Rate 0-3 each for:

  • Fatigue
  • Waking unrefreshed
  • Cognitive symptoms
  • Plus presence of somatic symptoms (headache, abdominal pain, depression)

Diagnosis if:

  • WPI ≥7 AND SSS ≥5 OR
  • WPI 4-6 AND SSS ≥9
  • Symptoms present for ≥3 months
  • No other disorder that would explain the pain

7. Management

Management Algorithm

Conservative Management (Foundation of Treatment)

Education:

  • Explain fibromyalgia as a real condition with altered pain processing
  • Validate the patient's experience
  • Set realistic expectations (improvement, not cure)
  • Provide written information (arthritis.org, versusarthritis.org)

Exercise (MOST EFFECTIVE Intervention):

  • Graded aerobic exercise: walking, swimming, cycling
  • "Start low, go slow" — avoid boom-bust patterns
  • 20-30 minutes, 2-3 times per week initially
  • Gradual increase in intensity and duration
  • Strength training also beneficial

Sleep Hygiene:

  • Regular sleep-wake schedule
  • Limit caffeine, alcohol, screen time before bed
  • Address obstructive sleep apnoea if present

Medical Management

Drug ClassDrugDoseKey Points
TCAAmitriptyline10-25mg nocteFirst-line; improves sleep and pain
SNRIDuloxetine30-60mg dailyFirst-line; also treats comorbid depression
AnticonvulsantPregabalin75mg BD, up to 300mg BDFirst-line; helps sleep and pain
SNRIMilnacipran50mg BDAlternative; less commonly used
Muscle relaxantCyclobenzaprine10mg nocteShort-term use; improves sleep

Drugs to AVOID:

Drug ClassReason
OpioidsIneffective; worsen outcomes; hyperalgesia
NSAIDsIneffective for central pain
BenzodiazepinesDependence; worsen sleep quality long-term
CorticosteroidsIneffective; significant side effects

Psychological Management

  • CBT: Improves coping, reduces catastrophising
  • ACT (Acceptance and Commitment Therapy): Promotes acceptance and values-based action
  • Mindfulness-based stress reduction: Reduces pain perception
  • Address comorbidities: Treat depression and anxiety if present

Disposition

  • Primary care management: Majority of patients
  • Rheumatology referral: Diagnostic uncertainty, failed initial treatment
  • Pain clinic referral: Refractory cases, complex polypharmacy
  • Psychology/psychiatry: Significant mood disorder, complex psychosocial factors
  • Follow-up: Regular (3-6 monthly) to monitor symptoms, adjust medications

8. Complications

Immediate (Treatment-Related)

ComplicationTreatmentManagement
Medication side effectsAmitriptyline: dry mouth, drowsinessReduce dose, take earlier in evening
Pregabalin: weight gain, oedema-Consider alternative
Duloxetine: nausea-Take with food, titrate slowly

Early (Months)

  • Physical deconditioning: From avoiding activity; worsens symptoms
  • Iatrogenic harm: From inappropriate opioids, polypharmacy, excessive investigations
  • Mood disorders: Depression and anxiety very common

Late (Years)

  • Chronic disability: Significant proportion have long-term functional impairment
  • Opioid dependence: If inappropriately prescribed
  • Social isolation: From reduced activity and misunderstanding of condition
  • Economic impact: Reduced work capacity, healthcare utilisation

9. Prognosis & Outcomes

Natural History

  • Chronic condition: Symptoms persist for years in most patients
  • Fluctuating course: Periods of relative improvement and flares
  • Complete remission: Rare (less than 25%), but significant improvement possible

Outcomes with Treatment

VariableOutcome
Improvement with multimodal therapy25-50% report significant improvement
Full remissionLess than 25%
Work disability25-50% have difficulty maintaining employment
Response to exerciseNNT approximately 3 for clinically significant improvement
MortalityNo increased mortality from fibromyalgia itself

Prognostic Factors

Good Prognosis:

  • Shorter symptom duration at diagnosis
  • Engaged in regular exercise
  • Low catastrophising
  • Good social support
  • Absence of comorbid depression
  • Younger age

Poor Prognosis:

  • Long duration before diagnosis
  • Comorbid depression/anxiety
  • Opioid use
  • High catastrophising
  • Disability claims/litigation
  • Poor sleep

10. Evidence & Guidelines

Key Guidelines

  1. EULAR 2016 — Revised recommendations for fibromyalgia management. Emphasises patient education and exercise first, then pharmacotherapy. EULAR
  2. ACR 2016 Diagnostic Criteria — Updated criteria using WPI and SSS. ACR
  3. NICE CG193 (2021) — Chronic pain: assessment and management. NICE
  4. Canadian Guidelines (2012) — Comprehensive fibromyalgia management guideline. CMAJ

Landmark Trials

Crofford et al. (2005) — Pregabalin for fibromyalgia

  • 529 patients randomised to pregabalin vs placebo
  • Key finding: Pregabalin significantly reduced pain and improved function
  • Clinical Impact: Pregabalin approved for fibromyalgia

Arnold et al. (2004) — Duloxetine for fibromyalgia

  • 207 patients randomised
  • Key finding: Duloxetine 60mg significantly improved pain and function
  • Clinical Impact: Duloxetine approved for fibromyalgia

Busch et al. (2007) — Cochrane review of exercise

  • Systematic review of exercise interventions
  • Key finding: Aerobic exercise improves pain, physical function, and well-being
  • Clinical Impact: Established exercise as cornerstone of treatment

Evidence Strength

InterventionLevelKey Evidence
Aerobic exercise1aCochrane review
CBT1aMultiple RCTs
Pregabalin1bCrofford RCT
Duloxetine1bArnold RCT
Amitriptyline1bMultiple RCTs
Opioids NOT recommended1aSystematic reviews; guideline consensus

11. Patient/Layperson Explanation

What is Fibromyalgia?

Fibromyalgia is a condition that causes pain all over your body, along with extreme tiredness, difficulties sleeping, and problems with memory and concentration (often called "fibro fog"). It is not caused by inflammation or damage to your muscles or joints — instead, it is due to the way your brain and nervous system process pain signals. This means the pain is very real, but the problem lies in the "volume control" for pain being turned up too high.

Is it serious?

Fibromyalgia is not life-threatening and does not damage your joints or organs. However, it can significantly affect your quality of life, your ability to work, and your relationships. The good news is that with the right approach, many people can manage their symptoms and lead fulfilling lives.

How is it treated?

  1. Education: Understanding what fibromyalgia is (and isn't) is the first step to managing it.
  2. Exercise: Gentle, regular exercise like walking, swimming, or cycling is the most effective treatment. It may feel hard at first, so start slowly and build up gradually.
  3. Medication: Drugs like amitriptyline (low dose at night), duloxetine, or pregabalin can help reduce pain and improve sleep. Surprisingly, strong painkillers like opioids (morphine, codeine) do NOT help and can make things worse.
  4. Psychological support: Therapies like CBT (cognitive behavioural therapy) can help you manage pain and improve your quality of life.
  5. Sleep: Improving your sleep quality is important. Good sleep habits and sometimes medication can help.

What to expect

  • There is no "cure" for fibromyalgia, but symptoms can be managed
  • Many people see significant improvement with exercise and the right treatment
  • Symptoms may fluctuate — there will be good days and bad days
  • Building a support network and pacing your activities helps

When to seek help

See your doctor if:

  • Your pain is getting significantly worse
  • You develop new symptoms like joint swelling, fever, or weakness
  • You are struggling to cope emotionally
  • Your current treatments are not helping

12. References

Primary Guidelines

  1. Macfarlane GJ, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318-328. PMID: 27377815
  2. Wolfe F, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46(3):319-329. PMID: 27916278

Key Trials

  1. Crofford LJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52(4):1264-1273. PMID: 15818684
  2. Arnold LM, et al. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum. 2004;50(9):2974-2984. PMID: 15457467
  3. Busch AJ, et al. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev. 2007;(4):CD003786. PMID: 17943797

Further Resources

  • Versus Arthritis Fibromyalgia: versusarthritis.org/about-arthritis/conditions/fibromyalgia
  • Fibromyalgia Action UK: fmauk.org
  • NHS Fibromyalgia: nhs.uk/conditions/fibromyalgia


Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Fibromyalgia management should be individualised. Consult a healthcare professional for personal advice.

Last updated: 2025-12-23

At a Glance

EvidenceHigh
Last Updated2025-12-23

Red Flags

  • Polymyalgia rheumatica (proximal stiffness, raised ESR, age greater than 50)
  • Inflammatory arthritis (joint swelling, morning stiffness greater than 1 hour)
  • Hypothyroidism (fatigue, weight gain, constipation)
  • Vitamin D deficiency (diffuse aches, weakness)
  • Malignancy (weight loss, night sweats, new bone pain)
  • Neurological signs (weakness, sensory loss, reflex change)

Clinical Pearls

  • **The Big Three Comorbidities**: IBS, migraine, and depression are the three most common comorbidities. If you diagnose one, screen for the others.
  • **Red Flags — Exclude other diagnoses if:**
  • - Inflammatory markers elevated (ESR, CRP) — consider PMR, inflammatory arthritis
  • - Joint swelling — inflammatory arthritis
  • - Objective weakness — myopathy, myositis

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines