FIBROMYALGIA INGRAM F ANDERSON. Consultant Rheumatologist

Transcription

1 FIBROMYALGIA INGRAM F ANDERSON Consultant Rheumatologist

2 Fibromyalgia is a riddle wrapped in a mystery inside an enigma

3 Fibromyalgia not a new Disease. 1904: Gowers coined the term fibrositis to describe a chronic musculoskeletal pain condition : Moldofsky et al. described an abnormality in deep, or non- REM, sleep in fibrositis patients suggesting central nervous system (CNS) involvement : Smythe and Moldofsky were among the first to propose diagnostic criteria for fibrositis : Multicenter criteria committee of the American College of Rheumatology (ACR) adopted the term fibromyalgia due to lack of inflammatory changes in muscles of patients 4 Established the ACR criteria for fibromyalgia 2010: New diagnostic criteria developed recently 5,6

4 The Prevalence of Fibromyalgia Prevalence estimated to be 2.0% in the general US population 1,2 3.4% of women 0.5% of men Occurs in 2% to 6% of patients in primary care settings and in 10% to 20% of patients presenting to rheumatologists 3 1. Wolfe et al. Arthritis Rheum 1995;38(1): Chakrabarty and Zoorob. Am Fam Physician 2007;76(2): Lindell et al. Scand J Prim Health Care 2000;18(3):

5 Risk Factors for Fibromyalgia: Familial Influences Fibromyalgia is strongly familial (the odds ratio is 8.5 for first-degree relatives) 1 Genetic factors may be involved in the etiology of fibromyalgia and in pain sensitivity 1,2 Fibromyalgia coaggregates with major mood disorder in families 1 Mood disorders and fibromyalgia may share some inherited factors 1. Arnold et al. Arthritis Rheum 2004;50(3): Light et al. Pain Res Treat 2012;2012:

6 FIBROMYALGIA A DIFFERENT TYPE OF PAIN SENSITIVITY Fibromyalgia is the prototype for a fundamentally different type of pain syndrome in which pain is Not due to tissue damage or inflammation (inflammatory pain) Not due to damage to or a lesion of the nervous system (neuropathic pain) Frequently accompanied by other symptoms (eg, fatigue, sleep disturbance, depression, and anxiety) Fibromyalgia is likely due to abnormal pain processing by the nervous system

7 Symptoms of fibromyalgia P M S psychological problems irritable bladder fatigue migraines cognitive dysfunction widespread pain tender points sleep disturbances headaches paresthesias orthostatic hypotension fluid retention irritable bowel Raynaud's syndrome

8 Evaluation of Fibromyalgia: Characteristic Clinical Features Widespread body aches, pains, and tenderness Fatigue Cognitive impairment Sleep disturbance Morning stiffness Prior depressive and anxiety symptoms Impaired social, sexual and occupational functioning Catastrophizing (ifa)

9 Evaluation of Fibromyalgia: Comorbid Medical Disorders Disorder Prevalence Rates (%) Chronic fatigue syndrome Irritable bowel syndrome Temporomandibular disorder 75 Tension and migraine headache Multiple chemical sensitivities Interstitial cystitis Chronic pelvic pain 18 Aaron and Buchwald. Best Pract Res Clin Rheumatol 2003;17(4):

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11 Sjogren Paraneoplastic; Infective /Post-Inf: multiple enthesopathy; myeloma; Lyme,Chikungunya,Brucella

12 American College of Rheumatology (ACR) 1990 Criteria for Fibromyalgia Wolfe et al. Arthritis Rheum 1990;33(2): Considered widespread when present in all of the following: Left side of the body Right side of the body Above the waist Below the waist Axial skeleton (cervical spine, anterior chest, thoracic spine, or low back) Must be present for at least three months Pain in 11 of 18 tender point sites on digital palpation Digital palpation should be performed with an approximate force of 4 kg For a tender point to be considered positive, the subject must state that the palpation was painful

13 The 18 Tender Point Sites Occiput suboccipital muscle insertions Trapezius midpoint of the upper border Supraspinatus above the scapula spine near the medial border Gluteal upper outer quadrants of buttocks Greater trochanter Low cervical anterior aspects of the intertransverse spaces at C5 - C7 Second rib second costochondrial junctions Lateral epicondyle 2 cm distal to the epicondyles Knee medial fat pad proximal to the joint line

14 Proposed ACR 2010 Preliminary Diagnostic Criteria for Fibromyalgia Patient satisfies the following 3 criteria: Widespread pain index (WPI) 7 and symptom severity (SS) scale score 5 or WPI between 3-6 and SS scale score 9 Symptoms present at a similar level 3 months Does not have a disorder that may explain the pain Ascertainment of symptoms WPI is the number of areas of the body (19 prespecified areas) in which the patient had pain over the last week (score 0-19) SS scale score: fatigue, waking unrefreshed, cognitive symptoms Clinician indicates the level of severity in each of the 3 categories Scored on a scale of 0 = no problem, 1 = slight or mild, 2 = moderate, 3 = severe The sum of severity of somatic symptoms in general (0 = no symptoms, 1 = few symptoms, 2 = a moderate number of symptoms, 3 = a great deal of symptoms) Final score between 0 and 12

15 SF-36 health survey measures Physical Mental

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17 Increased muscle pain in FM vs controls

18 The Possible Role of Central Sensitization in Fibromyalgia Central sensitization amplifies nociceptive impulses 1,2 Amplification is a result of the plasticity of neuronal synapses following past pain experiences Increased sensitivity to pain may be manifested by changes in response to evoked pain 1,2 Allodynia: experience of pain from normally non-noxious stimuli (eg, light touch) Hyperalgesia: exaggerated or amplified response to painful stimuli 1. Woolf. Ann Intern Med 2004;140(6): Lee et al. Arthritis Res Ther 2011;13(2):211.

19 The Neuromatrix Concept of Pain

20 A LINK BETWEEN STRESS AND FMS? Disturbances in the stress-response systems in fibromyalgia Hypothalamic-pituitary-adrenal (HPA) axis Some studies show or suggest a mild-moderate alteration in the dynamic function of the HPA axis in patients with fibromyalgia 1-3 Autonomic nervous system dysfunction 4 Impaired sympathetic response to stressors Altered heart rate variability Some patients with severe fibromyalgia may have a dorsal root ganglia sodium channelopathy 5 1. Clauw and Chrousos. Neuroimmunomodulation 1997;4(3): Mease. J Rheumatol Suppl 2005;75: Lyon et al. Pain Med 2011;12(8): Petzke and Clauw. Curr Rheumatol Rep 2000;2(2): Vargas-Alarcon et al. BMC Musculoskelet Disord 2012;13(1):23.

21 A Pathological Link Between Stress and FMS? (Cont.) Stress and proinflammatory cytokines Some stressors may induce the production of proinflammatory cytokines 1 Proinflammatory cytokines can induce physiologic, behavioral, and hormonal changes (sickness symptoms) that include exaggerated pain responses (hyperalgesia) 2 Some cytokines induce neuroendocrine and central monoaminergic changes similar to those thought to be associated with depression and pain enhancement 3 1. Maier. Brain Behav Immun 2003;17(2): Watkins and Maier. Annu Rev Psychol 2000;51: Anisman and Merali. Ann Med 2003;35(1):2-11.

22 Louis Pasteur's theory of germs is ridiculous fiction." -- Pierre Pachet, Professor of Physiology at Toulouse 1872

23 Neurotransmitters in FMS Substance P Elevated in cerebrospinal fluid of fibromyalgia patients compared with controls 1-3 May play a role in hyperalgesia along with pronociceptive excitatory amino acids (glutamate) acting at the non-nmda receptor 4 Serotonin (5-HT) and norepinephrine (NE) Evidence of dysfunction in both 5-HT and NE in fibromyalgia 5,6 5-HT and NE mediate endogenous pain pathways via the descending inhibitory pain pathways in the brain and spinal cord 7 Glutamate and GABA 8 The decreased expression of glutamic acid decarboxylase, a rate-limiting enzyme in the conversion of glutamate to GABA, may result in an imbalance of excitatory and inhibitory neurotransmission pain pathways 1. Russell et al. Arthritis Rheum 1994;37(11): Vaerøy et al. Pain 1988;32(1): Lyon et al. Pain Med 2011;12(8): Watkins et al. Brain Res 1994;664(1-2): Russell et al. J Rheumatol 1992;19(1): Russell et al. Arthritis Rheum 1992;35(5): Fields et al. Annu Rev Neurosci 1991;14: Fitzgerald and Carter. Med Hypotheses 2011;77(3):

24 The pain brain pain loop peripheral tissues pain generators spinal cord and brain central sensitization

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26 Neuroimaging studies in fibromyalgia Hypoperfusion of thalamus and head of the caudate nucleus (Mountz) SPECT confirmation of Mountz work in thalamus (Kwiatek) fmri of cortical response to pain (Petzke) abnormal subjective pain cortical response consistent with central sensitization

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28 Standardizing physical functioning metrics for norm-based comparisons fibromyalgia congestive heart failure chronic lung disease asthma average adult average well adult Physical Component Summary (PCS) Source: Adapted from Ware and Kosinski, 2001

29 Impact of FMS on FUNCTION and QUALITY of LIFE Fibromyalgia has a high impact on quality of life 1,2 Low quality-of-life scores Decreased mental health and physical and social functioning Increased bodily pain Total annual costs: R48000 versus R20000 for the typical beneficiary 3 Total direct and indirect costs: $CAD7,333 per patient per 6 months % of patients receive disability payment 5 1. Wolfe et al. Arthritis Rheum 1997;40(9): Robinson et al. J Rheumatol 2003;30(6): Penrod et al. J Rheumatol 2004;31(7): Wolfe et al. J Rheumatol 1997;24(6):

30 Mean Baseline Scores for SF-36 Impact of Fibromyalgia on Function and Quality of Life: Health-related Quality of Life Health-related Quality of Life: US norms 1 vs. fibromyalgia patients 2 1. Ware et al. SF-36 Health Survey: Manual & Interpretation Guide. 1993, Arnold et al. Pain 2005;119(1-3):5-15.

31 Stepwise Treatment of Fibromyalgia Confirm diagnosis Identify important symptom domains, their severity, and level of patient function Evaluate for comorbid medical and psychiatric disorders Assess psychosocial stressors, level of fitness, and barriers to treatment May require referral to a specialist for full evaluation Provide education about fibromyalgia Review treatment options Arnold. Arthritis Res Ther 2006;8(4):212.

32 Stepwise Treatment of Fibromyalgia (Cont.) As a first - line approach for patients with moderate to severe pain, trial with evidence - based medications Provide additional treatment for comorbid conditions Adjunctive CBT for patients with prominent psychosocial stressors, and/or difficulty coping, and/or difficulty functioning Encourage exercise according to fitness level This slide contains information on treatment regimens that are off-label in the EU and US Arnold. Arthritis Res Ther 2006;8(4):212.

33 Mechanisms of Pain Modulation and Pharmacological Treatment Descending inhibitory pathways (NE/5-HT, enkephalins) Peripheral sensitization Na + channel modulators Carbamazepine Oxcarbazepine TCAs Topiramate Lamotrigine Lidocaine. Spinal Cord TCAs, SNRIs, SSRIs α-adrenergic blocking agents Opioids Tramadol Cannabinoids Central sensitization Ca 2+ channel modulators Gabapentin Levetiracetam Oxcarbazepine NMDA antagonists Ketamine Dextromethorphan Lamotrigine Pregabalin Methadone Memantine.

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35 Pharmacological Interventions FDA-approved medications Pregabalin (Lyrica) 1 Duloxetine (Cymbalta) 2 Milnacipran (Savella) 3 Treatments with demonstrated efficacy (non-fda Approved) Cyclic medications 4 Cyclobenzaprine Tricyclic antidepressants Alpha-2-delta ligands Gabapentin 5 1. Pregabalin full prescribing information Duloxetine full prescribing information Arnold et al. Psychosomatics 2000;41(2): Arnold et al. Arthritis Rheum 2007;56(4):

36 Adjunctive pain medications* Membrane stabilizers Alpha-2 adrenergic agonists 5-HT3 antagonists NMDA receptor antagonists *None of these agents is currently indicated for the treatment of fibromyalgia by the FDA Leventhal LJ. Ann Intern Med 1999;131:850-8

37 Psychological distress Depression Anxiety PTSD Existential crisis Consider cognitive behavioral therapy

38 Associated syndromes Irritable bowel Irritable bladder Restless legs Postural hypotension

39 Summary: Understanding Fibromyalgia Fibromyalgia is a fundamentally different type of pain syndrome one of enhanced pain sensitivity without evidence of a neurological deficit or peripheral abnormality Dysfunction in the body s pain processing pathways may play a key role Genetic and environmental factors are likely involved in fibromyalgia Patients experience high degrees of medical and psychiatric comorbidity Fibromyalgia detracts from quality of life and exacts societal costs A carefully planned, stepwise treatment is best

40 Private Collection IFA