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fibromyalgia syndrome (fibromyositis, fibrositis)

- 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: a) tension headache b) irritable bowel syndrome c) chronic fatigue syndrome [32] d) dysmenorrhea e) anxiety disorders f) may occur in patients with inflammatory disorders [14] - rheumatoid arthritis - systemic lupus erthematosus - Sjogren's syndrome g) hypophosphatasia [48] Epidemiology: 1) 4-11% of population; 2% of U.S. population >= 18 years [32] 2) more common in women (3.4%) than men (0.5%) [32] 3) 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 [40] Genetics: - implicated genes may be involved in serotonin & catecholamine metabolism - COMT, ADRB2, HTR2A, SLC6A3, DRD4 exon 3 repeats, GCH1, TAAR1, CNR1, RGS4, GRIA4 [32] - HLA polymorphisms - unknown micro RNA effects [32] Clinical manifestations: - widespread, chronic pain [14] - pain radiating diffusely from the axial skeleton [32] - muscle & joint pain & tenderness all over (> 3 months) - no evidence of synovitis - headache - jaw dysfunction [32] - 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 [32] - postural hypotension with dizziness - difficulty urinating - blurred vision - anxiety, depression, cognitive difficulties 'fibro fog' - dysphagia, swallowing difficulties - rectal pain - irritable bowel syndrome [47] - various skin complaints - symptomatic distress across multiple symptoms [14] - myofascial trigger points (11 of 18) bilaterally a) occiput: posterior cervical trigger: at the insertion of the suboccipital muscle b) trapezius ridge: midpoint, upper border c) supraspinatus/levator scapula trigger (paravertebral), above medial scapular spine d) cervical: anterior aspect of intertransverse space C5-C7 e) second costochondral junction f) lateral epicondyle: 2 cm distal to the epicondyle g) upper gluteal area: outer quadrant of buttock in the anterior fold of the gluteus maximus h) greater trochanter: posterior to trochanteric prominence i) anserine bursa (medial aspect of knee) - RED FLAGS that suggest another diagnosis a) fever b) anemia c) weight loss d) synovitis Diagnostic criteria: - widespread pain* present for >= 3 months - no other diagnosis to explain symptoms [32] * Widespread pain index & symptom severity scale [32] Laboratory: 1) no diagnostic laboratory tests (avoid excessive testing) 2) initial laboratory testing [14] - 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 3) other testing not routinely indicated (do not order) [14] a) CD4/CD8 ratio may be increased b) serum growth hormone may be diminished c) rheumatoid factor (RF) & anti-CCP Ab are negative d) antinuclear antibody (ANA) is negative e) low erythrocyte ATP [32] f) low serum serotonin g) high CSF substance P h) increased CSF nerve growth factor [32] * questionable [14] * 9,3% of patients with fibromylagia found to have consistently low serum alkaline phosphatase levels consistent with hypophosphatasia [48] Special laboratory: - sleep encephalogram may reveal alpha/delta pattern Differential diagnosis: 1) depression 2) metabolic imbalance 3) hypothyroidism 4) polymyalgia rheumatica 5) polymyositis/dermatomyositis 6) hepatitis C infection 7) sleep apnea 8) restless legs syndrome [14] Complications: - increased risk of suicide (hazzard ratio 1.5) Management: 1) regular low-impact aerobic exercise is 1st line treatment [14,49] a) aerobic fitness b) focus on adequate stretching of involved muscles c) Tai chi may be of benefit - may be as good if not better than aerobic exercise [35] d) yoga may be of benefit d) first line even if patient is too exhausted to exercise [47] - exercise rehabilitation [47] 2) cognitive behavioral therapy more effective than exercise a) assessment of psychosocial stress & stressors b) may be delivered over the telephone c) exercise in combination improves outcomes [19] 3) alternative/complementary therapy may provide temporary relief a) physical therapy - ischemic compression may be applied for 3 minutes to extinguish trigger point pain b) transcutaneous electrical nerve stimulation (TENS) may improve movement-evoked pain & other clinical outcomes [42] c) acupuncture [8,47] d) biofeedback e) hypnotherapy f) stress management & relaxation therapy g) mindfulness [47] h) group therapy may be beneficial 4) life style changes a) obtain enough sleep b) ergonomic work changes c) healthy diet - adequate intake of water-soluble vitamins d) morning bright-light may improve function & diminish pain sensitivity, possibly by altering sleep patterns [33] e) green eyeglasses may reduce anxiety & opiate use in patients with fibromyalgia [45] 5) pharmacologic therapy of modest benefit [14] a) does not usually respond to NSAIDs or glucocorticoids (avoid) [14] b) opiate analgesics should be avoided [3,6] - tramadol is exception [6,14] c) pregabalin (Lyrica) [6,10,11] (FDA-approved 06/2007) may improve pain [34] & sleep [11] - benefit of pregabalin is similar to minalcipran & duloxetine [34] - dizziness common; discontinue pregabalin for dizziness d) serotonin & norepinephrine reuptake inhibitors (SNRI) - milnacipran (Savella), FDA-approved, benefits modest & adverse effects common [18] - duloxetine (Cymbalta) FDA approved 2009 [12,14,21] - agent of choice with comorbid anxiety & depression [14] - number needed to treat to benefit 1 person = 7 - 1 in 6 patients with 30% improvement of pain [12] - discontinuation from adverse effects 15-27% - SNRI: venlafaxine (Effexor), duloxetine moderate-certain evidence [46] - agents of choice for pregabalin failure [14] e) 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 [4] - combination or low-dose amitriptyline + fluoxetin better than either alone [6] - TCAs provide the most pain benefit & reduce fatigue & sleep disturbances f) low-dose selective serotonin reuptake inhibitor (SSRI) - fluoxetine (Prozac) [5] - sertraline (Zoloft) - paroxetine (Paxil) - none are FDA-approved g) atypical antidepressants - trazodone (Desyrel) - bupropion (Wellbutrin) h) other analgesics - gabapentin (Neurontin) [4,6,9] - minimal evidence supports a clinically meaningful benefit [41] - may be helpful for sleep disturbance [47] - capsaicin [6] - cyclobenzaprine (Flexeril) 5-30 mg PO QHS - may inhibit CNS pain fibers [4] - Cannabis (marijuana) [50] - subjective improvement in pain (82%) - improvement in sleep (77%), - improvement in stress, anxiety, & mood (69%) [50] i) other mood therapies - alprazolam for anxiety [3] - SAMe may help with depression [6] j) clonazepam (Klonopin) for poor sleep due to restless legs k) Xyrem [6] may help with pain, fatigue, sleep l) guaifenesin 600 mg BID-TID - use Humibid m) pramipexole (Mirapex) 4.5 mg QD [7] n) 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 6) natural/herbal products are promising [4] a) SAMe (S-adenosylmethionine) b) capsaicin 7) patient education a) identify life stressors b) disorder is not degenerative, crippling or deformative c) treatment is available d) Arthritis Foundation [6] Comparative biology: - infusion of IgG from fibromyalgia patients into mice caused fibromyalgia-like symptoms in the mice [44] - 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 [43] - annual cost ~$6000/patient [32]

Related

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

Specific

fibromyalgia in the elderly

General

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

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 519-20
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 787-89
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, 1955-57
  4. Prescriber's Letter 7(12):67 2000
  5. Journal Watch 22(8):63, 2002 Arnold LM et al A randomized, placebo-controlled, double-blind, flexible- dose study of fluoxetine in the treatment of women with fibromyalgia. Am J Med 112:191, 2002 PMID: 11893345
  6. Prescriber's Letter 12(1):3 2005 Fibromyalgia Update Detail-Document#: 210103 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 12(9): 2005 Special Report on Drugs and Natural Products for Fibromyalgia Detail-Document#: 211008 (subscription needed) http://www.prescribersletter.com
  8. Martin DP et al, Improvement in fibromyalgia symptoms with acupuncture: Results of a randomized controlled trial. Mayo Clin Proc 2006; 81:749 PMID: 16770975
  9. Arnold LM, Goldenberg DL, Stanford SB, Lalonde JK, Sandhu HS, Keck PE Jr, Welge JA, Bishop F, Stanford KE, Hess EV, Hudson JI. Gabapentin in the treatment of fibromyalgia: A randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum. 2007 Mar 28;56(4):1336-1344 [Epub ahead of print] PMID: 17393438
  10. Prescriber's Letter 14(8): 2007 Lyrica for Fibromyalgia Detail-Document#: 230805 (subscription needed) http://www.prescribersletter.com
  11. Mease PJ et al, A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. J Rheumatol 2008, 35:502 PMID: 18278830
  12. Prescriber's Letter 15(7): 2008 Detail-Document#: 240712 (subscription needed) http://www.prescribersletter.com
  13. Hauser W et al Treatment of fibromyalgia syndrome with antidepressants: A meta-analysis. JAMA 2009 Jan 14; 301:198. PMID: 19141768
  14. Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  15. Goldenberg DL Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Curr Opin Rheumatol 1993, 5(2):199-208 PMID: 8452771
  16. Veterans Administration Memorandum Dec 24, 2009 Recent VHA Findings regarding chronic pain conditions and suicide risk
  17. Wang C et al. A randomized trial of tai chi for fibromyalgia. N Engl J Med 2010 Aug 19; 363:743. PMID: 20818876 - Yeh GY et al. Prescribing tai chi for fibromyalgia - Are we there yet? N Engl J Med 2010 Aug 19; 363:783. PMID: 20818882
  18. Arnold LM et al. Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: Results of a randomized, double-blind, placebo- controlled trial. Arthritis Rheum 2010 Sep; 62:2745. PMID: 20496365 http://dx.doi.org/10.1002/art.27559
  19. McBeth J et al. Cognitive behavior therapy, exercise, or both for treating chronic widespread pain. Arch Intern Med 2011 Nov 14 PMID: 22082706 Arch Intern Med. Published online November 14, 2011
  20. Bradley LA. Pathophysiology of fibromyalgia. Am J Med. 2009 Dec;122(12 Suppl):S22-30. PMID: 19962493
  21. Russell IJ, Mease PJ, Smith TR et al Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo- controlled, fixed-dose trial. Pain. 2008 Jun;136(3):432-44 PMID: 18395345
  22. Arnold LM. Advances in the management of fibromyalgia. CNS Spectr. 2009 Oct;14(10 Suppl 8):12-6; discussion 17-8. PMID: 20128144
  23. Buskila D. Developments in the scientific and clinical understanding of fibromyalgia. Arthritis Res Ther. 2009;11(5):242 PMID: 19835639
  24. Williams DA. The role of non-pharmacologic approaches in the management of fibromyalgia. CNS Spectr. 2009 Dec;14(12 Suppl 16):10-2; discussion 12-4. PMID: 20568689
  25. Wolfe F. Fibromyalgia wars. J Rheumatol. 2009 Apr;36(4):671-8 PMID: 19342721
  26. Wolfe F, Clauw DJ, Fitzcharles MA et al The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10 PMID: 20461783
  27. Agency for Healthcare Research and Quality (AHRQ) Research Review - Final - Jan. 26, 2015 Treatments for Fibromyalgia in Adult Subgroups. http://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2040
  28. Fitzcharles MA, Ste-Marie PA, Pereira JX et al Fibromyalgia: evolving concepts over the past 2 decades. CMAJ. 2013 Sep 17;185(13):E645-51 PMID: 23649418
  29. Atzeni F, Cazzola M, Benucci M et al Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol. 2011 Apr;25(2):165-71 PMID: 22094193
  30. Choy E, Marshall D, Gabriel ZL et al A systematic review and mixed treatment comparison of the efficacy of pharmacological treatments for fibromyalgia. Semin Arthritis Rheum. 2011 Dec;41(3):335-45.e6 PMID: 21868065
  31. McBeth J, Mulvey MR. Fibromyalgia: mechanisms and potential impact of the ACR 2010 classification criteria. Nat Rev Rheumatol. 2012 Jan 24;8(2):108-16 PMID: 22270077
  32. Grimm L, Diamond D Fibromyalgia: A Pain-Processing Problem. Medscape. September 22, 2016 http://reference.medscape.com/features/slideshow/fibromyalgia
  33. Brooks M Bright-Light Treatment Shows Promise for Fibromyalgia Medscape - Jun 13, 2017. https://www.medscape.com/viewarticle/881527
  34. Argoff C. Pregabalin is effective in reducing fibromyalgia pain. Evid Based Med. 2017 Apr;22(2):70-71. Epub 2017 Feb 27. PMID: 28242609
  35. Wang C, Schmid CH, Fielding RA, et al Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial. BMJ 2018;360:k851 PMID: 29563100 http://www.bmj.com/content/360/bmj.k851 - Price A The unintended consequences of tai chi for fibromyalgia. The bmj opinion. March 21, 2018 http://blogs.bmj.com/bmj/2018/03/21/amy-price-the-unintended-consequences-of-tai-chi-for-fibromyalgia/ - Wang C Time to rethink exercise for fibromyalgia care. The bmj opinion. March 21, 2018 http://blogs.bmj.com/bmj/2018/03/21/chenchen-wang-time-to-rethink-exercise-for-fibromyalgia-care/
  36. Derry S, Cording M, Wiffen PJ, Law S, Phillips T, Moore RA. Pregabalin for pain in fibromyalgia in adults. Cochrane Database Syst Rev. 2016 Sep 29;9:CD011790. Review. PMID: 27684492
  37. Gilron I, Chaparro LE, Tu D et al Combination of pregabalin with duloxetine for fibromyalgia: a randomized controlled trial. Pain. 2016 Jul;157(7):1532-40. PMID: 26982602
  38. Arthritis Foundation http://www.arthritis.org - National Center for Complementary and Inegrative Health Fibromyalgia: In Depth https://www.nccih.nih.gov/health/fibromyalgia-in-depth
  39. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014 Apr 16;311(15):1547-55. doi: 10.1001/jama.2014.3266. Review. PMID: 24737367
  40. Albrecht DS, Forsberg A, Sandstrom A, et al. Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation. Brain Behav Immun 2019 Jan; 75:72. PMID: 30223011 Free Article https://www.sciencedirect.com/science/article/pii/S0889159118302423
  41. Goodman CW, Brett AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med 2019 Mar 25; PMID: 30907944 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2728959
  42. Harris S Kathleen Sluka, PT, PhD, on Perfect TENS For Fibromyalgia? Electrical stimulation device 'another tool in our arsenal' to control FM pain, reduce fatigue MedPage Today. AMERICAN COLLEGE OF RHEUMATOLOGY Reading Room 03.31.2020 https://www.medpagetoday.com/reading-room/acrr/generalrheumatology/85703 - Dailey DL, Vance CGT, Rakel BA et al Transcutaneous Electrical Nerve Stimulation Reduces Movement-Evoked Pain and Fatigue: A Randomized, Controlled Trial. Arthritis Rheumatol. 2019 Nov 18. PMID: 31738014 https://onlinelibrary.wiley.com/doi/10.1002/art.41170
  43. Mascarenhas RO, Souza MB, Oliveira MX et al Association of Therapies With Reduced Pain and Improved Quality of Life in Patients With Fibromyalgia. A Systematic Review and Meta-analysis. JAMA Intern Med. Published online October 26, 2020 PMID: 33104162 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772354
  44. Goebel A, Krock E, Gentry C et al. Passive transfer of fibromyalgia symptoms from patients to mice. J Clin Invest 2021 Jul 1; 131:e144201. PMID: 34196305 PMCID: PMC8245181 (available on 2021-10-01) https://www.jci.org/articles/view/144201 - Tracey KJ. From human to mouse and back offers hope for patients with fibromyalgia. J Clin Invest 2021 Jul 1; 131:e150382. PMID: 34196306 PMCID: PMC8245165 (available on 2022-07-01) https://www.jci.org/articles/view/150382
  45. Lou N For Chronic Pain Patients, Consider Green-Tinted Glasses? Mixed results with green light therapy for fibromyalgia MedPage Today October 24, 2022 https://www.medpagetoday.com/meetingcoverage/asa/101375
  46. Ferreira GE et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: Overview of systematic reviews. BMJ 2023 Feb 1; 380:e072415. PMID: 36725015 PMCID: PMC9887507 Free PMC article https://www.bmj.com/content/380/bmj-2022-072415 - Stannard C, Wilkinson C. Rethinking use of medicines for chronic pain. BMJ 2023 Feb 1; 380:170. PMID: 36724987 https://www.bmj.com/content/380/bmj.p170
  47. NEJM Knowledge+ Rheumatology
  48. Injean P, Tan J, Lee S, Downey C. Could Some Patients With Fibromyalgia Potentially Have Hypophosphatasia? A Retrospective Single-Center Study. ACR Open Rheumatol. 2023. Sept 3 PMID: 37661663 Free article https://acrjournals.onlinelibrary.wiley.com/doi/full/10.1002/acr2.11591
  49. Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76:318-28. PMID: 27377815
  50. Singla A et al. A cross-sectional survey study of cannabis use for fibromyalgia symptom management. Mayo Clin Proc 2024 Apr; 99:542. PMID: 38569809 https://www.mayoclinicproceedings.org/article/S0025-6196(24)00025-9/abstract