fibromyalgia syndrome (fibromyositis, fibrositis)

Introduction

• common, non-articular musculoskeletal disorder
• disorder of stage 4 sleep
• a diagnosis of exclusion
• pain in the muscles, ligaments & tendons
• pain is poorly localized.

* also see chronic fatigue syndrome/myalgic encephalomyelitis

Etiology

• unknown
• associated disorders:
  • tension headache
  • irritable bowel syndrome
  • chronic fatigue syndrome
  • dysmenorrhea
  • anxiety disorders
  • may occur in patients with inflammatory disorders
    • rheumatoid arthritis
    • systemic lupus erthematosus
    • Sjogren's syndrome
  • hypophosphatasia

Epidemiology

• 4-11% of population; 2% of U.S. population >= 18 years
• more common in women (3.4%) than men (0.5%)
• typically presents in middle-age women, but onset of pain often occurs earlier in life

Pathology

• allodynia
• hyperalgesia
• central sensitization with disinhibition of pain signals
  • dysregulation of dopaminergic neurotransmission
  • increased NMDA receptor sensitivity
  • hypothalamic-pituitary dysfunction
  • glial activation, neuroinflammation

Genetics

• implicated genes may be involved in serotonin & catecholamine metabolism
  • COMT, ADRB2, HTR2A, SLC6A3, DRD4 exon 3 repeats, GCH1, TAAR1, CNR1, RGS4, GRIA4
  • HLA polymorphisms
  • unknown micro RNA effects

Clinical manifestations

• widespread, chronic pain
• pain radiating diffusely from the axial skeleton
• muscle & joint pain & tenderness all over (> 3 months)
  • no evidence of synovitis
• headache
• jaw dysfunction
• morning stiffness
• muscle stiffness
• muscle cramps/twitches
• subjective sensations of swelling
• fatigue
• non-restorative sleep (awakening unrefreshed)
• exercise intolerance, dyspnea due to deconditioning
• weight gain
• paresthesias & numbness
• shooting pains
• multiple chemical sensitivity
• postural hypotension with dizziness
• difficulty urinating
• blurred vision
• anxiety, depression, cognitive difficulties 'fibro fog'
• dysphagia, swallowing difficulties
• rectal pain
• irritable bowel syndrome
• various skin complaints
• symptomatic distress across multiple symptoms
• myofascial trigger points (11 of 18) bilaterally
  • occiput: posterior cervical trigger: at the insertion of the suboccipital muscle
  • trapezius ridge: midpoint, upper border
  • supraspinatus/levator scapula trigger (paravertebral), above medial scapular spine
  • cervical: anterior aspect of intertransverse space C5-C7
  • second costochondral junction
  • lateral epicondyle: 2 cm distal to the epicondyle
  • upper gluteal area: outer quadrant of buttock in the anterior fold of the gluteus maximus
  • greater trochanter: posterior to trochanteric prominence
  • anserine bursa (medial aspect of knee)
• RED FLAGS that suggest another diagnosis
  • fever
  • anemia
  • weight loss
  • synovitis

Diagnostic criteria

• widespread pain* present for >= 3 months
• no other diagnosis to explain symptoms

* Widespread pain index & symptom severity scale

Laboratory

• no diagnostic laboratory tests (avoid excessive testing)
• initial laboratory testing
  • complete blood count (CBC) is generally normal
  • thyroid function tests are normal
  • serum chemistries generally within normal limits
    • serum electrolytes, serum Ca+2, serum phosphate, serum creatinine, serum alkaline phosphatase*, serum creatine kinase*
  • ESR or serum C-reactive protein (serum CRP) generally normal
  • urinalysis normal
• other testing not routinely indicated (do not order)
  • CD4/CD8 ratio may be increased
  • serum growth hormone may be diminished
  • rheumatoid factor (RF) & anti-CCP Ab are negative
  • antinuclear antibody (ANA) is negative
  • low erythrocyte ATP
  • low serum serotonin
  • high CSF substance P
  • increased CSF nerve growth factor

* questionable

* 9,3% of patients with fibromylagia found to have consistently low serum alkaline phosphatase levels consistent with hypophosphatasia

Diagnostic procedures

• sleep encephalogram may reveal alpha/delta pattern

Complications

• increased risk of suicide (hazzard ratio 1.5)

Differential diagnosis

• depression
• metabolic imbalance
• hypothyroidism
• polymyalgia rheumatica
• polymyositis/dermatomyositis
• hepatitis C infection
• sleep apnea
• restless legs syndrome

Management

• regular low-impact aerobic exercise is 1st line treatment
  • aerobic fitness
  • focus on adequate stretching of involved muscles
  • Tai chi may be of benefit
    • may be as good if not better than aerobic exercise
  • yoga may be of benefit
  • first line even if patient is too exhausted to exercise
    • exercise rehabilitation
• cognitive behavioral therapy more effective than exercise
  • assessment of psychosocial stress & stressors
  • may be delivered over the telephone
  • exercise in combination improves outcomes
• alternative/complementary therapy may provide temporary relief
  • physical therapy
    • ischemic compression may be applied for 3 minutes to extinguish trigger point pain
  • transcutaneous electrical nerve stimulation (TENS) may improve movement-evoked pain & other clinical outcomes
  • acupuncture
  • biofeedback
  • hypnotherapy
  • stress management & relaxation therapy
  • mindfulness
  • group therapy may be beneficial
• life style changes
  • obtain enough sleep
  • ergonomic work changes
  • healthy diet
    • adequate intake of water-soluble vitamins
  • morning bright-light may improve function & diminish pain sensitivity, possibly by altering sleep patterns
  • green eyeglasses may reduce anxiety & opiate use in patients with fibromyalgia
• pharmacologic therapy of modest benefit
  • does not usually respond to NSAIDs or glucocorticoids (avoid)
  • opiate analgesics should be avoided
    • tramadol is exception
  • pregabalin (Lyrica) (FDA-approved 06/2007) may improve pain & sleep
    • benefit of pregabalin is similar to minalcipran & duloxetine
    • dizziness common; discontinue pregabalin for dizziness
  • serotonin & norepinephrine reuptake inhibitors (SNRI)
    • milnacipran (Savella), FDA-approved, benefits modest & adverse effects common
    • duloxetine (Cymbalta) FDA approved 2009
      • agent of choice with comorbid anxiety & depression
      • number needed to treat to benefit 1 person = 7
      • 1 in 6 patients with 30% improvement of pain
      • discontinuation from adverse effects 15-27%
    • SNRI: venlafaxine (Effexor), duloxetine moderate-certain evidence
    • agents of choice for pregabalin failure
  • tricyclic antidepressant (TCA) at bedtime to correct disorder of stage 4 sleep
    • amitriptyline 10-50 mg PO QHS, higher doses may be necessary
    • generally more effective for pain than SSRI
    • combination or low-dose amitriptyline + fluoxetin better than either alone
    • TCAs provide the most pain benefit & reduce fatigue & sleep disturbances
  • low-dose selective serotonin reuptake inhibitor (SSRI)
    • fluoxetine (Prozac)
    • sertraline (Zoloft)
    • paroxetine (Paxil)
    • none are FDA-approved
  • atypical antidepressants
    • trazodone (Desyrel)
    • bupropion (Wellbutrin)
  • other analgesics
    • gabapentin (Neurontin)
      • minimal evidence supports a clinically meaningful benefit
      • may be helpful for sleep disturbance
    • capsaicin
    • cyclobenzaprine (Flexeril) 5-30 mg PO QHS
      • may inhibit CNS pain fibers
    • Cannabis (marijuana)
      • subjective improvement in pain (82%)
      • improvement in sleep (77%),
      • improvement in stress, anxiety, & mood (69%)
  • other mood therapies
    • alprazolam for anxiety
    • SAMe may help with depression
  • clonazepam (Klonopin) for poor sleep due to restless legs
  • Xyrem may help with pain, fatigue, sleep
  • guaifenesin 600 mg BID-TID
    • use Humibid
  • pramipexole (Mirapex) 4.5 mg QD
  • trigger point injections
    • tendonitis, bursitis & costochondritis trigger points may be injected with xylocaine & steroid
    • anesthetic injection of 0.5% procaine should produce pain/warmth in reference pain zone
• natural/herbal products are promising
  • SAMe (S-adenosylmethionine)
  • capsaicin
• patient education
  • identify life stressors
  • disorder is not degenerative, crippling or deformative
  • treatment is available
  • Arthritis Foundation

Comparative biology

• infusion of IgG from fibromyalgia patients into mice caused fibromyalgia-like symptoms in the mice
  • fibromyalgia-like symptoms in the mice were attentuated when IgG infusions were stopped

Notes

• no treatment provides clinically important benefit for pain or quality of life
• annual cost ~$6000/patient

More general terms

• somatoform pain disorder (psychogenic pain, psychalgia)
• central pain syndrome
• sleep disorder

More specific terms

• fibromyalgia in the elderly

Additional terms

• chronic fatigue syndrome; myalgic encephalomyelitis; neurasthenia; systemic exertion intolerance disease (CFS)
• myofascial trigger point

Patient information

fibromylagia syndrome patient information