• Information
  1. Characteristics
  2. Symptoms
  3. American College of Rheumatology Criteria for Fibromyalgia
  4. Differential Diagnosis
  5. Pathogenesis
  6. Treatment

A. Characteristics

1. Also called fibrositis, fibromyositis, myofasciitis (may be slightly distinct syndromes)
2. Prevalence is ~2% overall (~3.4% of women and ~0.5% of men)
3. Usually occurs in young and middle aged women
4. Symptoms are usually intermittent, waxing and waning
5. Pain in muscles, fascia, connective tissue is prominent feature
6. Repeated tissue analyses has failed to show histological inflammation or other abnormality
7. Various biochemical abnormalities have been described inconsistenly
8. Thus, etiology of fibromyalgia remains obscure
9. May be a variant of chronic fatigue syndrome (CFS)
10. May be classified as functional somatic syndrome

B. Symptoms

1. Musculoskeletal
   1. Diffuse pain, usually "pins and needles" in muscles, tendon insertions
   2. Tender points on examination
   3. Swelling in or near joints, without fluid accumulation within joint
2. Neurological
   1. Difficulty concentrating
   2. Normal memory
   3. Anxiety or depression
   4. Diffuse paresthesias
   5. Sleep Disorder
   6. Headache
   7. Cerebrospinal Fluid (CSF) and Electromyogram (EMG) Normal
3. Common Psychiatric Associations [2]
   1. Depression
   2. Anxiety and Somatization
   3. Posttraumatic stress

C. American College of Rheumatology Criteria for Fibromyalgia [3]

1. History of widespread pain >3 months duration (axial skeleton and four body quadrants)
2. Pain in at least 11 of 18 paired tender points on examation
3. The paired tender points are:
   1. Occiput: suboccipital muscle insertions
   2. Cervical: anterior aspects of intertransverse spaces C5-7
   3. Trapezius: midpoint of upper border
   4. Supraspinatus: origins above scapular spine near medial border
   5. Second rib: second costochondral junctions
   6. Lateral epicondyle: 2cm distal to epicondyles
   7. Gluteal: upper outer quadrants of buttocks
   8. Greater Trochanter: posterior to trochanteric prominences
   9. Knees: medial fat pad proximal to joint line

D. Differential Diagnosis

1. Must rule out multisystem inflammatory disorders, including lyme disease
2. ESR and CRP usually normal
3. Muscle related enzymes (CK, aldolase, LDH) always normal
4. Full rheumatologic evaluation usually indicated, with ANA, RF, ESR
5. No specific laboratory abnormalities have been identified

E. Pathogenesis [4]

1. No histologic abnormalities have been identified
2. Pathogenesis is unclear but abnormal pain sensation processing implicated
3. Abnormalities in Pain Sensation
   1. Fibromyalgia patients clearly experience pain differently than unaffected persons
   2. Abnormal central nervous system (CNS) processing of pain believed to be causative
   3. High cerebrospinal fluid (CSF) substance P
   4. Upregulation of spinal synapse N-methyl-D-aspartate (NMDA) receptors
   5. CNS leads to pain sensitization causing amplication of normally innocuous sensations
   6. NMDA receptor appears to be the most important
   7. Reduced levels of CSF norepinephrine
4. Serotonin Regulation
   1. Low serum serotonin foudn in small studies but not confirmed in larger studies
   2. Low serum tryptophan, the precursor of serotonin
5. Insulin Like Growth Factor 1 (IGF-1)
   1. IGF-1 is the major mediator of effects of growth hormone
   2. Reduced serum levels in ~33% of patients with fibromyalgia
   3. Symptoms of growth hormone deficiency present in many fibromyalgia patients
   4. These symptoms include low energy, reduced exercise capacity, cold intolerance
   5. Muscle weakness and redcued lean body mass are also found in fibromyalgia
   6. Growth hormone therapy increased serum IGF-1 and improved symptoms in patients [4]
6. Low tissue magnesium
7. Abnormal hypothalamic-pituitary-adrenal axis, but not specific to fibromyalgia

F. Treatment [1,5]

1. Combination drug therapy and other therapy modalities strongly recommended
   1. Cardiovascular excercise is clearly beneficial; effect not maintained when exercise stopped
   2. Cognitive behavioral therapy (CBT) improvement sustained for months
   3. Combination of exercise and CBT with drug therapy is probably most effective
2. Pregabalin (Lyrica®) [5,10]
   1. FDA approved for reduction of pain in patients with fibromyalgia
   2. Pregabalin previously approved for neuropathic pain and as adjunctive anti-seizure
   3. Pregabalin 150-300mg po bid reduced pain in ~50% on pregabalin versus 30% placebo
   4. Side effects: dizziness (38%), somnolence (20%), headache, weight gain, dry mouth
   5. Schedule 5 substance
3. Tricyclic Antidepressants (TCAs)
   1. Best studied and most effective of various pharmacologic therapies
   2. Response within 1-4 weeks to amitriptyline (25-100mg po qhs) - overall ~30% response
   3. Begin with 10-25mg po qhs and increase dose to 50-100mg po qhs
   4. This response wanes compared with placebo after 6 months
   5. Main effect appears to be alteration of sleep patterns and pain perception
   6. Other TCAs may be used if amitriptyline (Elavil®) is not tolerated
   7. Combination of amitriptyline and fluoxetine is most effective therapy to date
4. Cyclobenzeprine (Flexeril®)
   1. Used primarily as a muscle relaxent, main effect is anticholinergic
   2. Starting dose is now 5-10mg po qhs, may increase over time
   3. Full dose is 10mg po tid or 10-30mg qhs only
   4. Less effective than amitriptyline with 10-15% of patients responding at 1 month
   5. 5mg dose may be as effective as 10mg with less sedation
5. Seretonin (SSRI) or Mixed (SNRI) Reuptake Inhibitors
   1. May be effective in some patients, particularly with concomittant depression
   2. Fluoxetine (Prozac®) should be given in the morning because it can disrupt sleep
   3. Flexible dose schedule of fluoxetine (10-80mg/d) clearly better than placebo [6]
   4. Paroxetine may be given in the evening (increased anticholinergic activity)
   5. Combination of amitryptyline 25mg qhs and fluoxetine 20mg qam was more effective than either agent alone [7]
   6. Duloxetine, an SNRI, was effective in one randomized controlled trial [5]
   7. Venlefaxine (Effexor®), an SNRI, has shown mixed results in fibromyalgia
6. Tramadol (Ultram®)
   1. Non-opioid pain medication, non-addicting
   2. Generally good results for management of chronic pain
   3. Moderate activity 200-300mg/day divided dose ±acetaminophen
   4. Tachyphylaxis does not appear to develop
   5. Tramadol+acetaminophen 1 tab qd to tid effective for chronic pain in fibromyalgia [8]
7. Ineffective Medications
   1. NSAIDs
   2. Glucocorticoids
   3. Opiates / Opioids
   4. Hypnotic agents (benzodiazepine and non-benzodiazepine)
   5. Melatonin
   6. Calcitonin
8. Physical Therapy Programs
   1. Massages
   2. Regular exercise program
   3. Relaxation may also be helpful (moreso than medication)
   4. Physical activity is absolutely critical to recovery from this condition
9. Miscellaneous Therapies
   1. Acupuncture had no benefit in randomized trial in relieving pain in fibromyalgia [9]
   2. In patients with reduced IGF-1 levels, growth hormone therapy improves symptoms [8]
   3. Biofeedback
   4. Trigger point injections may be helpful in a minority of patients [1]
   5. Ondansetron or tropisetron - 5-HT3 antagonists (anti-emetic agents)
   6. 5-hydroxytryptophan (serotonin)

References

1. Leventhal LJ. 1999. Ann Intern Med. 131(11):850
2. Abeles AM, Pillinger MH, Soltan BM, Abeles M. 2007. Ann Intern Med. 146(10):726
3. Wolfe F, Smythe HA, Ynus MB, et al. 1990. Arthritis Rheum. 33:160
4. Bennett RM, Clark SC, Walczyk J. 1998. Am J Med. 104(3):227
5. Goldenberg DL, Burckhardt C, Crofford L. 2004. JAMA. 292(19):2388
6. Arnold LM, Hess EV, Hudson JI, et al. 2002. Am J Med. 112(3):191
7. Goldenberg DL, Mayskly M, Mossey C, et al. 1996. Arthritis Rheum. 39(11):1852
8. Bennett RM, Kamin M, Karim R, Rosenthal N. 2003. Am J. Med. 114(7):537
9. Assefi NP, Sherman KJ, Jacobsen C, et al. 2005. Ann Intern Med. 143(1):10
10. Pregabalin for Fibromyalgia. 2007. Med Let. 49(1270):77