Fibromyalgia or Arthritis

Transcription

1 Fibromyalgia or Arthritis

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3 Evaluation of Fibromyalgia Practical diagnosis and treatment

4 Fibromyalgia Widespread Chronic Pain >3 months Pain above and below the waist, on both sides of the body and axial skeleton. 11 of 18 tender points on digital exam. 4Kg. Pressure. painful not just tender. 2 nd diagnosis not excluded. Major sleep disturbance in > 75% of patients.

5 Aching, burning, or even tingling muscles. 10 times more common in females. Pain aggravated by exertion and stress. Fatigue present in 90%. Tiredness vs. fatigue. 30% of patients have major depression or anxiety disorders. Irritable bowel syndrome common. Bladder symptoms common. Overlaps Myofascial Pain Syndrome. Normal ESR unless a concurrent syndrome.

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7 Fibromyalgia is a Pain modulation Disorder. FM does not exclude any systemic or arthritic disease. Arthritis of various types is common in FM. Normal blood tests and X-rays are not uncommon in several arthritic disorders. Ie. Osteoarthritis, Spondyloarthropathies, -Psoriatic arthritis, early rheumatoid arthritis, Hepatitis C.

8 Absence of swelling of joints. Absence of Significant loss of Range of motion of spine or other joints. Absence of inflammation in blood work ie: CRP, ESR. Pain in the muscles or in between joints. Burning or paraesthesia type of pain-so-called pain equivalents.

9 Clinical Features of Fibromyalgia

10 Pain Intensity Augmented Pain Processing in Fibromyalgia Fibromyalgia Subjective Pain Control Stimulus Pressure Control SI Stimulus Intensity (kg/cm 2 ) SII SI = contralateral primary somatosensory cortex SII = secondary somatosensory cortex Gracely RH, et al. Arthritis Rheum. 2002;46:

11 Central Sensitization Neuroplasticity contributes, the CNS is not hardwired. Wind-Up phenomenon is dependent on activation of the NMDA receptors. One cause of central Sensitization. Manifested by allodynia(reduction in pain threshold) and hyperalgesia(persistant pain).

12 Fibromyalgia: A Disorder of Enhanced Pain Sensitivity Fibromyalgia is the prototype for a fundamentally different type of pain syndrome in which pain is: 1,2 Not due to tissue damage or inflammation (inflammatory pain) Not due to damage to or a lesion of the peripheral nervous system (neuropathic pain) Frequently accompanied by other symptoms (e.g., fatigue, sleep disturbance, depression, and anxiety) Fibromyalgia pain is likely due to an abnormal responsiveness or functioning of the central nervous system 3 Serotonin (5-HT) and Norepinephrine (NE) in CSF 4 1. Woolf CJ. Ann Intern Med. 2004;140: Gracely RH, et al. Arthritis Rheum. 2002; 46: Staud R, et al. Nat. Clin. Pract. 2006; 2: Russell IJ et al. Cerebrospinal fluid biogenic amine in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum 1992; 35 (5):

13 Pain Modulation: Serotonin and Norepinephrine Pain is associated with increased excitation and decreased inhibition of ascending pain pathways 1,2 Descending pathways modulate ascending signals 1,2 Norepinephrine (NE) and serotonin (5-HT) are key neurotransmitters in descending inhibitory pain pathways 1,2 Increasing the availability of NE and 5-HT may promote pain inhibition centrally 1 Anterior Cingulate Cortex Thalamus Hypothalamus Periacqueductal Grey (PAG) Dorsolateral Pontine Tegmentum Rostroventral Medulla Pain Transmission Neuron Dorsal horn Amygdala 1. Fields HL, et al. Annu Rev Neurosci. 1991;14: Fields H, Nat Rev Neuro. 2004; 5: Descending Modulation PAG indirectly controls pain transmission in the dorsal horn 2

14 Elevated Substance P Levels

15 Chronic Sleep Disturbance Abnormal sleep EEGs.Nearly all FM patients describe non-restorative sleep.the earliest (1975) objective abnormality found in FM was a disruption of deep sleep (stages 3 and 4) by a fast "waking" rhythm (alpha-delta sleep) on EEG recording.many sleep studies have since replicated this finding.the abnormality is not specific for FM and does not occur in all patients

16 6. Unrefreshed sleep 7. Post-exertional malaise lasting >24hrs.

17 Alpha-intrusion into Delta sleep Less common in chronic insomniacs,who get more Beta EEG in light sleep. Post-accident patients with pain and fatigue. Nocturnal Myoclonus patients. Acute Rheumatoid Arthritis Patients. Post- Flu patients (post-infection). Therefore sensitive, not specific. Indication of nonrefreshed sleep. % alpha freq.-increase in pain and fatigue. % delta freq. overnight decrease in pain.

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19 Patients Perspective on the Impact of FMS Fibromyalgia had a substantial negative impact on social and occupational function. Patients reported: Disrupted relationships with family and friends, Social isolation, Reduced activities of daily living and leisure activities, Avoidance of physical activity, Loss of career or inability to advance in careers or education 1. Arnold, L., Crofford, L., Mease, P., Burgess, S., Palmer, S., Abetz, L., Martin, S. (2008). Patient perspectives on the impact of fibromyalgia. Patient Education and Counseling 73:

20 Stepwise Treatment for Fibromyalgia Identify location, severity of symptoms and effect on function. Evaluate for co-morbid psychiatric and medical conditions. Evaluated psychological stressors and physical barriers to function. Provide education regarding Fibromyalgia. Encourage exercise according to fitness level. Provide appropriate pharmaceutical Rx. Provide cognitive therapy for those with serious coping problems.

21 Management Create a Therapeutic alliance. Avoid enabling behavior (codependency). Discourage passivity and endless passive types of treatment (physio,acupucture, acupressure. Diagnose and treat all physical disorders. Treat sleep disturbance. Treat depression.

22 Management-cont. Treat local areas- bursitis, tendonitis, joints local steroid injections, spray and stretch. put out the fires Correct biomechanics-i.e. orthotics, supports, arch supports, leg lengths. NSAIDS usually helpful. Tricyclics helpful. Anticonvulsants- Neurontin, Valproic acid,tegretal, Lyrica.

23 Other Treatment Tricyclics- Amitriptyline 10 mg.-200mg. - Trazodone 25mg.- 300mg. Hypnotics- BZD. adverse effects. Imovane SSRI s- helpful with pain and depression. Exercise Therapy Improvement in Function. Cognitive Therapy-.

24 Enhancing Patient Outcomes Group Education and Social Support Lifestyle Changes CBT Targeted for Function, Coping, Sleep Good Nutrition Low to Moderate physical activity Stress Reduction Consistent Routine Lesley M Arnold, Women's Health Research Program, University of Cincinnati College of Medicine, Piedmont Avenue, Cincinnati, Ohio 45219, USA

25 Duloxetine in the Treatment of Fibromyalgia CYMBALTA (duloxetine hydrochloride) is indicated for the symptomatic relief of major depressive disorder (MDD), for the management of neuropathic pain associated with diabetic peripheral neuropathy (DPN), for the symptomatic relief of anxiety causing clinically significant distress in patients with generalized anxiety disorder (GAD), and for the management of pain associated with fibromyalgia (FM).

26 Reduction in FIQ Least-squares Mean Change from Baseline to Endpoint FIQ Total Score at 3 Months Study 1 1 Study 2 2 Study 3 3 Proof of Concept Phase III Phase III Pivotal Pivotal Arnold LM, et al. Arthritis Rheum 2004;50: Russell IJ, et al., Pain 2008;136(3): Arnold LM, et al. Pain 2005;119: Duloxetine 60 mg Duloxetine 120 mg or 60/120 mg The FIQ is an assessment and evaluation instrument developed to measure fibromyalgia syndrome (FMS) patient status, progress and outcomes The FIQ -12 consists of ten Placebo items: Physicial Impairment * ** * 2. Feel good 3. Work -20 *** *** missed 4. Do work * P.05, ** P.01, *** P.001 vs. placebo 5. Pain 6. Fatigue 7. Rested 8. Stiffness 9. Anxiety The data used for study 1 are change from baseline to week 12, the protocol-defined primary efficacy measure. Data 10. for studies Depression 2 and 3 are LOCF endpoint scores during 3-month active treatment phase.

27 Reduction in Pain Least-squares Mean Change Study 2: 3-Month Phase III Pivotal Study BPI Average Pain Severity: Time Course of Efficacy Weeks *** *** *** *** *** *** * *** * *** *** *** *** *** Endpoint LOCF *** *** * P.05, *** P.001 vs. placebo Placebo (N=118) Duloxetine 60 mg/d (N=116) Duloxetine 120 mg/d (N=114) Arnold LM, et al. Pain 2005; 119:5-15.

28 BPI Average Pain Mean Change Reduction FIQ Total Mean Change Duloxetine: Therapy-by-Subgroup, Patients With and Without MDD BPI Average Pain Reduction FIQ Total Reduction 0 No Current MDD n=371 Current MDD No Current MDD Current MDD n=156 n=365 n= Δ = 1 * Δ = 1.4 * Δ = 6.6 * Δ = Duloxetine Placebo Therapy by subgroup P value = Therapy by subgroup P value = * p<0.001 vs. placebo; + p < vs. placebo. MDD = Major Depressive Disorder, FIQ = Fibromyalgia Impact Questionnaire. Arnold L.M. et al. J Women s Health, 2007; 16(8): Data on File Eli Lilly.

29 Eular - Annals of Rheumatic Disease Recommendations Level 1 evidence for benefit for exercise therapy. Also good evidence for benefit of Tai Chi, meditation, accupuncture and congitive therapy. No benefit from SSRI s or MAO inhibitors. Weak evidence for benefit from pharmacologic therapy. Narcotics contraindicated.

30 Lyrica- approved in FM. 14 week blinded Placebo- controlled monotherapy. Doses from 300mg. To 600 mg./day. Significant improvement in pain scores, fibromyagia impact scores (FIQ), sleep measures, and pt. impression of change. One other study showed improvement in sleep. Has a greater effect on sleep directly and a lesser effect through reduction of pain.

31 Other Notes: British study on Cost- effectiveness of Lyrica. Cytokine changes seen in Fibromyalgia associated with cervical trauma. Positive Effects of SSRI s on inflammatory arthritis in rats.

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