Fibromyalgia a n evolving concept

1. Fibromyalgia an evolving concept Robert M. Bennett, MD, FACP, FRCP, MACR Professor of Medicine and Nursing • Oregon Health & Science University

2. 3O years ago: West J Med 134: 405‑413, May 1981 “Fibrositis is a misnomer for a very common form of non-articular rheumatism. The name implies an inflammatory process in fibro-connective tissue which has never been verified”.

3. Fibromyalgia is the third commonest cause of chronic pain 100 59.1 Prevalence (%) 50 27.0 5.0 3.0 1.3 0 Low back pain Osteoarthritis Fibromyalgia Gout Rheumatoid arthritis 1Rooks DS. CurrOpinRheumatol. 2007;19:111-117. 2Lawson K. NeuropsychiatrDis Treat. 2008;4:1059-1071. 3Bennett RM, et al. BMC MusculoskeletDisord. 2007;8:27.4Lawrence RC, et al. Arthritis Rheum. 2008;58:26-35. 5Helmick CG, et al. Arthritis Rheum. 2008;58:15-25.

4. 30 years ago the cause of fibromyalgia was a puzzle Thought to be mainly a disease of muscles

5. The First Reference to “Fibrositis” Postulated an inflammation of fibrous tissue between muscle bundles (hence “fibrositis) Published in the British Medical Journal in 1904

6. 1904 - Histologic proof of Gower’s hypothesis? Stockman R. Edinburgh Medical Journal, 1904, 15:107-116 Supported Gowers’ hypothesis regarding inflammation of fibrous tissue

7. 1915 - The first textbook on fibrositis All unexplained symptoms were attributed to “fibrositis” (i.e. a wastebasket diagnosis) Llewellyn and Jones of Bath

8. Understanding FM 1900 – 1930s A disorder of painful muscles Nerve impulses Peripheral tissues

9. 1904 - Histologic proof of Gower’s hypothesis? Stockman R. Edinburgh Medical Journal, 1904, 15:107-116 Stockman’s muscle histology could never be duplicated

10. “Psychogenic Rheumatism” FM was considered to be a result of psychoneurosis Boland, Annals of the Rheumatic Diseases 1947;6:195-203

11. “It’s all in your head” “Unexplained symptoms” are often still viewed as psychogenic in origin: SomatizationHypochondriasisMasked depression etc.

12. First “Scientific” Study in FM Moldofsky et al. Psychosomatic Med. 37:341-351, 1975

13. Electroencephalogram (EEG) sleep stages Deep sleep Delta (1- 3cps) Awake/alert Alpha (8-12 cps)

14. Abnormal EEG in sleeping FM patients Fibromyalgia Alpha + delta EEG waves Sleep disruption in healthy subjects caused pain and fatigue

15. 1981 - First study comparing fibromyalgia patients to healthy individuals Yunus et al. Seminars Arthritis and Rheumatism 1981, 11:151-171

16. FM patients often have: Irritable bowel Irritable bladder Chronic fatigue Restless legs Dizziness “Fibro-fog” Cold intolerance Multiple sensitivities

17. 1990 - The ACR Classification Criteria Arthritis Rheum. 1990;33:160-172 American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia: Report of the Multicenter Criteria Committee F Wolfe, HA Smythe, MB Yunus, RM Bennett, C Bombardier, DL Goldenberg, P Tugwell, SM Campbell, M Abeles, and P Clark In addition to defining FM, the name was changed from “fibrositis” to “fibromyalgia”

18. ACR defined fibromyalgia + Widespread pain ≥ 11 of 18 tender points

19. 1600 1200 800 400 0 Publication of the ACR criteria led to an explosion of research in fibromyalgia National Library of Medicine references on fibromyalgiain 5-Year Increments 2005-09 1980-84 1985-89 1990-94 1995-99 2000-05

20. What has been found? Sensory impulses are amplified at level of spinal cord and brain in fibromyalgia patients “Central sensitization”

21. Evidence for central sensitization in FM • Hyperalgesia / allodynia • Elevated CSF levels of neurotransmitters • Temporal summation (“wind-up”) • Enhanced somatosensory potentials • Increased activity on fMRI and SPECT scans • Impaired DNIC • Response to centrally acting drugs

22. 1988 - First “nervous system” study in FM Found that the CSF of FM patients had elevated levels of substance P This finding focused attention on the nervous system, and away from muscle Lumbar puncture Vaeroy et al. Pain 32:21-26, 1988

23. Abnormal sensory processing in FM • Hyperalgesia / allodynia • Elevated CSF levels of neurotransmitters • Temporal summation • Enhanced somatosensory potentials • Increased activity on fMRI scans • Impaired DNIC • Response to centrally acting drugs

24. Functional Brain Imaging SPECT MRS PET f MRI

25. SPECT scan in FM patients at rest Increased brain activity in areas that are involved in pain processing Guedj E, European Journal of Nuclear and Molecular Imaging , 2007, 34:130-4.

26. Important new concept: the body has a mechanism for modulating pain Brain This inhibitory pain system is dysfunctional in FM patients Descending inhibition Peripheral tissues Spinal cord

27. This pain dampening system originates in a brain area called the “periaqueductal gray” Activation of the PAG stimulates the pain inhibitory system PAG Spinal cord

28. Understanding FM 1995 - 2009 A disorder of sensory amplification Peripheral tissues

29. 2009 - What are “tender points” Found that FM tender points had the typical features of myofascial trigger points

30. What are myofascial trigger points? There are several hundred myofascial trigger point locations in the body

31. Understanding FM 2009 - present FM now thought to be a disorder of both peripheral pain generators and central sensitization This latest understanding of FM is crucial for planning effective treatment strategies Peripheral tissues

32. What causes fibromyalgia? • Environmental insults • Infections • Trauma • Prolonged stress • PTSD • Disordered sleep • Alpha-delta sleep • Sleep apnea • Hereditary influences • Genes (COMT, serotonin receptor) • Epigenetics (changes in gene expression) Not just one gene but many

33. 30 years ago the cause of fibromyalgia was a puzzle Thought to be mainly a disease of muscles

34. Central Pain generators sensitization Genes Environment 30 years later - some of the puzzle is now in place

35. Next speaker please

36. Fibromyalgia Information Foundation Spring Conference 2010 Welcome and orientation - Sharon Clark, PhD Fibromyalgia: An Evolving Concept - Robert M Bennett, MD Diagnosis and Mis-diagnosis - Atul Deodhar, MD Guided Stretch Break - Janice Holt Hoffman How Can I Help Myself? - Kim Dupree Jones, PhD How Can Medications Help Me? - Robert M Bennett, MD Roundtable: Questions and Answers - Drs Bennett, Deodhar and Jones, moderated by Dr Sharon Clark

37. Diagnosis and Misdiagnosis Atul Deodhar MD, FACR, MRCPAssociate Professor of MedicineMedical Director, Rheumatology ClinicsOregon Health & Science University

38. Why do you need a specialist? To make the correct diagnosis To ‘rule out’ other causes of generalized pain To ‘rule in’ common problems that go hand-in-hand with fibromyalgia (sleep apnea, restless legs, irritable bowel, depression etc) Fibromyalgia can co-exist with other rheumatic conditions and they shouldn’t be missed either To develop a comprehensive treatment plan

39. How do I make the diagnosis of FM? History & Physical Examination is usually enough to make the diagnosis of fibromyalgia Blood tests & other investigations rule out other causes of generalized pain which may have different and effective treatments It is not “since they could not find anything else on blood tests, they told me I have FM”

40. How do I make the diagnosis of FM? • FM patients usually have • Generalized Pain • Tenderness all over • Fatigue • Sleep disturbance • Depression/anxiety • Cognitive dysfunction • Irritable Bowel Syndrome • FM patients usually do not have • Weight loss • Joint swelling as seen in rheumatoid arthritis • Major organ (kidney, heart, lungs, brain) dysfunction • Abnormal lab tests

41. FM Symptoms Source: National Fibromyalgia Association Survey

42. Do I have ‘Lupus’? Do I have ‘MS’? Autoimmune disease affecting multiple organs in a specific fashion – generalized tenderness but nothing else on examination is not lupus! Over-diagnosed with positive anti-nuclear antibody (ANA) test Autoimmune disease that presents with specific neurological deficits – true weakness, sensation loss, visual loss etc. Generalized tenderness but normal neurological examination is not MS!

43. “My MRI scan showed Arthritis” MRI scans are extremely sensitive and show all sorts of ‘abnormalities’ which may or may not have any clinical relevance Everyone in this room has ‘spurs’, bulging discs, degenerative discs, and “arthritis” in the spine but not everyone has chronic back pain There is no direct correlation between what you find on the MRI scan and the ‘generalized pain and tenderness’ as seen in FM

44. Take Home Message After the age of 30, completely normal MRI scan of the spine is as rare as hen’s teeth There is poor correlation between ‘arthritis’ changes as seen on the MRI scan and patient’s symptoms

45. Other common causes of generalized pain Chronic hepatitis C Hypothyroidism, Hyperparathyroidism Metastatic cancer, Multiple myeloma Vitamin D Deficiency Polymyalgia rheumatica OA, RA, Sjögren’s syndrome, SLE

46. ACR Classification Criteria for FM • Widespread body pain • Pain on both left and right sides of the body • Pain above and below the waist • Axial pain present • Pain persisting ≥3 months • ≥11 of 18 tender points (painful to 4 kg pressure)

47. New ACR ‘Diagnostic Criteria’ for Fibromyalgia Widespread Pain Index • Shoulder girdle, L & RUpper arm L & R Lower arm L & R Hip buttock/trochanter L R Upper leg L & R Lower leg L & R Jaw L & RChest Abdomen Upper back Lower back Neck Symptom Severity Scale (0-3) • Cognitive symptomsWaking Un-refreshedFatigue Does Pt have somatic symptoms? • No symptomsFew symptomsModerate numberGreat deal of symptoms 0 to 9 0 to 3 0 to 19 Wolfe F. et al. Arthritis care & Research 2010;62(5):600–610

48. New ACR ‘Diagnostic Criteria’ for Fibromyalgia Patient can be Diagnosed as FM if they have: • Widespread pain index (WPI) 7 & symptom severity (SS) scale score 5 or WPI 3–6 and SS scale score 9 • Symptoms have been present at a similar level for at least 3 months • The patient does not have a disorder that would otherwise explain the pain Wolfe F. et al. Arthritis care & Research 2010;62(5):600–610

49. Take Home Message Your doctor doesn’t have to ‘rule out’ other diseases to diagnose fibromyalgia Fibromyalgia can co-exist with other diseases such as lupus, rheumatoid arthritis etc. Be Aware: Once the diagnosis is made, there is a risk of blaming all symptoms on fibromyalgia

50. What else do I look for every time I see a patient with Fibromyalgia? • Sleep disturbance: • Sleep Apnea Syndrome • Restless Leg Syndrome • Depression/Anxiety/Stress • Functional status, de-conditioning • Irritable Bowel Syndrome • I also look for signs & symptoms that do not fit