Disclosures. Clinical Case I. Learning Objectives. Fibromyalgia: It s Real, It s Manageable 4/5/18. none

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1 Disclosures Fibromyalgia: It s Real, It s Manageable Andrew J. Gross, MD Professor of Clinical Medicine Rheumatology Clinic Chief Associate Chair of Ambulatory Care, Dept of Medicine University of California, San Francisco none Learning Objectives Recognize patients with Fibromyalgia and other Pain Sensitization Syndromes, identify the mechanisms of pain, and explain the importance of making these diagnoses. Describe the basic treatment approach for fibromyalgia. Clinical Case I 49 year old woman comes to you complaining of fatigue. She also notes problems with pain in many areas. She tells you that she wakes up frequently at night either from pain or thinking about stressful problems from her work. She wakes up in the morning with pain in her shoulders, neck and low back with stiffness, feeling very tired. The stiffness improves quickly, but as the day wears on, pain gets worse and she feels exhausted. She has gained 20 lbs in the past 2 years. She feels depressed because of the poor quality of her life. 1

Clinical Case II (more subtle) A 27 year old woman comes to see you with the chief complaint of ankle pain You see she has had multiple visits for same problem, but she has not responded well to any

X-ray and MRI are unremarkable On further review of her record, she has been seen over the past 6 years for many other problems including tinnitus, eye discomfort, right upper quadrant pain, shoulder

2 Clinical Case II (more subtle) A 27 year old woman comes to see you with the chief complaint of ankle pain You see she has had multiple visits for same problem, but she has not responded well to any of the usual treatments. X-ray and MRI are unremarkable On further review of her record, she has been seen over the past 6 years for many other problems including tinnitus, eye discomfort, right upper quadrant pain, shoulder pain, neck pain, and problems with her memory. Workup for each of these problems has been unrevealing. Fibromyalgia Epidemiology Percentage of the population with fibromyalgia women Wolfe F, et al; Arthritis & Rheum; 1995 men Using 2011 ACR diagnostic criteria in 2445 German People: Prevalence of 2.1% Prevalence increased with age 0.8% 40 years of age 2.5% in years 3.0% in 60 years of age Similar prevalence in women and men (2.4% versus 1.8%; P =0.372) Olmsted County prevalence 6.4% (7.5% of women and 4.9% of men) Wolfe F et al; 2013, Arthritis Rheum; PMID Vincent A, et al; 2012, Arthritis Care & Res PMID Fibromyalgia Epidemiology Using 2011 ACR diagnostic criteria Olmsted County prevalence 6.4% Similar prevalence in women & men: 7.5% women, 4.9% men Fibromyalgia: Can it be reliably diagnosed? Is it physical or psychological? Is a diagnosis helpful or harmful? Is there any effective treatment? Vincent A, et al; 2012, Arthritis Care & Res PMID

Fibromyalgia: Can it be reliably diagnosed? Is it physical or psychological? Is a diagnosis helpful or harmful?

(choose 3) a) Widespread pain b) Joint Pain c) Non-restful sleep d) Depression e) Fatigue f) Obesity Diagnosis of Fibromyalgia

www.ehow.com/about_5059501_fibromyalgia-diagnosis-symptoms.

3 Fibromyalgia: Can it be reliably diagnosed? Is it physical or psychological? Is a diagnosis helpful or harmful? Is there any effective treatment? What are the hallmarks of fibromyalgia? (choose 3) a) Widespread pain b) Joint Pain c) Non-restful sleep d) Depression e) Fatigue f) Obesity Diagnosis of Fibromyalgia Diagnosis of Fibromyalgia Widespread Pain (>3 months) Widespread Pain (>3 months) Fatigue Poor Sleep Cognitive Problems Other Sx Characteristic Tender Points ACR classification criteria Wolfe F, et al, Arthritis Rheum 1990 ACR diagnostic criteria Wolfe F, et al, Arthritis Rheum 2010 ACR classification criteria Wolfe F, et al, Arthritis Rheum 1990 ACR diagnostic criteria Wolfe F, et al, Arthritis Rheum

4/5/18 Tender Point Exam Diagnosis of Fibromyalgia Fatigue Widespread Pain Poor Sleep Cognitive Problems Other Sx (>3 months) Characteristic Tender Points ACR criteria: pain at 11 of 18 points ACR

fibromyalgia: A. Multiple different pain complaints Eg. Back pain, knee pain, neck/shoulder pain A score of 13 points is consistent with a diagnosis of fibromyalgia Sensitivity 93.1% Specificity 91.

4 4/5/18 Tender Point Exam Diagnosis of Fibromyalgia Fatigue Widespread Pain Poor Sleep Cognitive Problems Other Sx (>3 months) Characteristic Tender Points ACR criteria: pain at 11 of 18 points ACR classification criteria Wolfe F, et al, Arthritis Rheum 1990 ACR diagnostic criteria Wolfe F, et al, Arthritis Rheum 2010 Which of the following suggests to you that a patient might have fibromyalgia: A. Multiple different pain complaints Eg. Back pain, knee pain, neck/shoulder pain A score of 13 points is consistent with a diagnosis of fibromyalgia Sensitivity 93.1% Specificity 91.7% Ferrari R, Russell AS, 2013, J Rheumatol Clauw D, 2014, JAMA, PMID Wolfe F et al, J Rheumatol 2011, PMID B. Pan-positive review of systems C. The patient has various hypersensitivity complaints (e.g. your exam room lights are making them sick) D. The patient starts the interview with their birth history E. You are exhausted after the interview ALL OF THE ABOVE! 4

5 TMJ disorder Headache/Migraine Chronic eye irritation/dryness Fibromyalgia overlaps with other Somatic Syndromes Irritable bowel syndrome Polyuria/frequency ( interstitial cystitis ) Dyspareunia/ vulvodynia Muscle Cramps Fibromyalgia In a German Study of FMS patients 53.8% had 1 severe somatic symptoms 32.7% had 2 symptoms Chronic fatigue Paresthesia Atypical chest pain Dypsnea Dermatitis/ pruritis Multiple sensitivities Wolfe F, et al, 2013, Arch Int Med 2013 Wolfe F et al; 2013, Arthritis Care & Res; PMID Buchwald D, Garrity D, Arch Int Med 1994 Aaron LA, et al. 2000, Arch Int Med. PMID Dutch Study of 94,516 participants between , Janssens KAM, et al, Psychosomatic Med 2015 Diagnosis of Fibromyalgia Widespread Pain (>3 months) Fatigue Poor Sleep Cognitive Problems Other Sx but how do I make sure my patient does not have something bad Characteristic Tender Points other disease ACR classification criteria Wolfe F, et al, Arthritis Rheum 1990 ACR diagnostic criteria Wolfe F, et al, Arthritis Rheum

6 It is difficult to be sure Work-up Cervical Myelopathy Fabry s Disease Acute Intermittent Porphyria Ovarian Cancer Whipple s Disease Hypothyroidism Pituitary Adenoma Systemic Lupus Erythematosus Pellagra Polyarteritis Nodosa Amyloidosis Mitochondrial Myopathy Laboratory Tests ESR, CRP CBC w/ diff Comprehensive Metabolic Panel (inc. LFTs, Calcium) Fasting Glucose Hepatitis B & C TSH, free T4 Vitamin D 25-OH CPK (if appropriate) ANA (rarely) Work-up Tips to detect underlying disease Laboratory Tests ESR, CRP CBC w/ diff Comprehensive Metabolic Panel (inc. LFTs, Calcium) Fasting Glucose Hepatitis B & C TSH, free T4 Vitamin D 25-OH CPK (if appropriate) X-rays of affected areas to investigate joint damage Biopsy tissues that appear affected (ie. skin rashes) EMG for persistent neurologic symptoms Perform routine laboratory Screening Evaluate objective findings Invite patients to return to see you if they develop new symptoms ANA (rarely) 6

When To Refer Fibromyalgia does not require specialist evaluation for diagnosis or management Referrals to specialists should be made when workup identifies another process such as: Endocrine disease

7 When To Refer Fibromyalgia does not require specialist evaluation for diagnosis or management Referrals to specialists should be made when workup identifies another process such as: Endocrine disease (Thyroid, Adrenal) Rheumatic Disease (PMR, Ankylosing Spondylitis) GI Disease (Malabsorption - Celiac Sprue) Heart Failure Neurologic disease (MS, ALS, Parkinson's) Fibromyalgia: Can it be reliably diagnosed? Is it physical or psychological? Is a diagnosis helpful or harmful? Is there any effective treatment? What is causing pain? a) Abnormal metabolism of muscle fibers causes persistent tissue degeneration/regeneration b) Increased sensitization of central pain signaling c) Small fiber perineural ischemia d) Psychiatric illness What is causing pain? a) Abnormal metabolism of muscle fibers causes persistent tissue degeneration/regeneration b) Increased sensitization of central pain signaling c) Small fiber perineural ischemia d) Psychiatric illness 7

Subjective Evidence Increased sensitivity to heat, cold, and pressure Marques AP, et al, Clin Rheumatol

Baraniuk JN, et al, BMC Musculoskel Disor, 2004 Patients with Fibromyalgia sense pain differently from

8 Brain How Do We Sense Pain? Nociceptive Networks Patients with Fibromyalgia experience pain differently from unaffected individuals Subjective Evidence Increased sensitivity to heat, cold, and pressure Marques AP, et al, Clin Rheumatol 2005 Maquet D, et al, Eur J Pain 2004 Gibson SJ, et al, Pain 1994 Abeles AM, et al, Ann Intern Med 2007 Baraniuk JN, et al, BMC Musculoskel Disor, 2004 Patients with Fibromyalgia sense pain differently from unaffected individuals Brain Central sensitization to pain Objective Evidence Nociceptive flexion reflex Desmeules JA, et al, Arthritis & Rheum 2003 Also see Banic B, et al, Pain

9 Pain Processing Mechanisms CNS neurotransmitters that are known to either inhibit or facilitate sensory/pain transmission are perturbed in patients with Fibromyalgia What causes pain sensitization? Schmidt-Wilcke T and Clauw DJ; Nat Rev Rheumatol, 2011, PMID What Causes Increased Sensitivity to Pain? Genetic Vunerability Arnold LM, et al, Arthritis Rheum, 2013, PMID Physical Trauma/Illness (infections & injuries) Emotional Trauma (violence & stress & loss) Endorphins Cortisol Neurotransmitters Pain Sensitization Fibromyalgia Pathophysiology: Biological Stress 5 10% of individuals exposed to certain types of infections (for example, Lyme disease, Epstein Barr virus, parvovirus or Q fever) develop CWP, and infections in other regions of the body can also trigger chronic regional pain. Similarly, 10 15% of individuals with acute gastrointestinal infections (for example, with Campylobacter spp., Salmonella spp. or Shigella spp.) subsequently develop IBS. Schmidt-Wilcke T and Clauw DJ; Nat Rev Rheumatol, 2011, PMID Crofford LJ; Trauma, Violence, & Abuse, 2007, PMID Schmidt-Wilcke T and Clauw DJ; Nat Rev Rheumatol, 2011, PMID

Fibromyalgia Pathophysiology: Psychological Distress Individuals with high levels of distress but without pain are 2-fold more likely to develop chronic widespread pain Having psychologically

10 Fibromyalgia Pathophysiology: Psychological Distress Individuals with high levels of distress but without pain are 2-fold more likely to develop chronic widespread pain Having psychologically stressful events in early life (death of a parent, prolonged hospitalization, MVA) increase the risk of developing chronic widespread by % in later life Sexual and physical abuse in childhood and adulthood are associated with FMS in adulthood PTSD reported in 15% to 56% of patients with fibromyalgia Fibromyalgia: Can it be reliably diagnosed? Is it physical or psychological? Is a diagnosis helpful or harmful? Is there any effective treatment? Should I tell the patient they have fibromyalgia? Fietta P et al, Acta Biomed 2007 Hauser W, at al, Arthritis Care Res, 2011 Hauser W, et al, 2013, Pain, PMID Schmidt-Wilcke T and Clauw DJ; Nat Rev Rheumatol, 2011, PMID Should I tell the patient they have fibromyalgia? Costs Related to a Diagnose FMS and Failure to Diagnose FMS No: the label of FMS might lead to increased illness behavior, dependence on health care providers, and increased health service costs. Yes: making a definite diagnosis will reduce the number of referrals, use of multiple health care providers, and costs. Annemans et al, Arthritis Rheum 2008; 58:895 10

11 The Importance of Knowing Health care costs are reduced by diagnosing fibromyalgia Fewer PCP visits Fewer tests ordered Fewer referrals made Fewer drugs prescribed Critical to help set expectations How do I tell my patient they have fibromyalgia? Here s what people with fibromyalgia usually tell me. Annemans et al, Arthritis Rheum 2008; 58:895 Fibromyalgia: Can it be reliably diagnosed? Is it physical or psychological? Is a diagnosis helpful or harmful? Is there any effective treatment? Which intervention is likely to lead to a 50% reduction in pain? a. Cymbalta b. Gabapentin c. Cognitive Behavior Therapy d. Exercise & Physical Therapy e. None of the above 11

Which intervention is likely to lead to a 50% reduction in pain? Treatment of Fibromyalgia A multidisciplinary approach a. Cymbalta b. Gabapentin c. Cognitive Behavior Therapy d.

12 Which intervention is likely to lead to a 50% reduction in pain? Treatment of Fibromyalgia A multidisciplinary approach a. Cymbalta b. Gabapentin c. Cognitive Behavior Therapy d. Exercise & Physical Therapy e. None of the above Medication Mind Body Scascighini L, et al, Rheumatology 2008 How can we control pain? How can we control pain? Brain Brain Norepinephrine impedes pain signaling Gabapentin (Neurontin) Pregabalin (Lyrica) Norepinephrine Elavil Cymbalta Savella Effexor 12

Treatment of Fibromyalgia Cochrane Systematic Review 2013 of duloxetine & milnacipran for fibromyalgia Outcome: Pain Reduction of 50% 28% of Rx group achieved 50% pain reduction 19% of placebo

(Elavil) 25-100mg qhs Dual-reuptake inhibitors (SNRIs) milnacipran (Savella) duloxetine (Cymbalta) 30-120 mg/d venlafaxine (Effexor) gabapentin (Neurontin) pregabalin (Lyrica) cyclobenzaprine

Rev 2013 FDA approved for FMS TIP: Go Slow Goldenberg DL et al, JAMA 2004, PMID 15547167 MacFarlane GJ et al, Ann Rheum Dis 2016, PMID 27377815 Treatment of Fibromyalgia A multidisciplinary approach

13 Treatment of Fibromyalgia Cochrane Systematic Review 2013 of duloxetine & milnacipran for fibromyalgia Outcome: Pain Reduction of 50% 28% of Rx group achieved 50% pain reduction 19% of placebo achieved 50% pain reduction NNTB = 11 Little improvement in fatigue No significant change in quality of life Treatment of Fibromyalgia Syndrome Recommended Tricyclic antidepressants amitriptyline (Elavil) mg qhs Dual-reuptake inhibitors (SNRIs) milnacipran (Savella) duloxetine (Cymbalta) mg/d venlafaxine (Effexor) gabapentin (Neurontin) pregabalin (Lyrica) cyclobenzaprine (Flexeril) tramadol mg/d Equivocal NSAIDs Serotonin reuptake inhibitors (SSRIs) Not Recommended Growth Hormone Sodium oxybate Corticosteroids Opioids Häuser W, et al, Cochrane Database Syst Rev 2013 FDA approved for FMS TIP: Go Slow Goldenberg DL et al, JAMA 2004, PMID MacFarlane GJ et al, Ann Rheum Dis 2016, PMID Treatment of Fibromyalgia A multidisciplinary approach I. Medication Body Mind Scascighini L, et al, Rheumatology 2008 Häuser W, et al, Arthritis Care & Res 2008 Aerobic Exercise (Cochrane Review 2002) (Mannerkorpi K, Curr Opin Rheum 2005) Walking, elliptical machine, cycling, aquatic therapy/exercise Tai Chi (Wang C, et al, NEJM 2010, PMID ) Lifestyle physical activity (pedometer) Aquatic Exercise Stretching & Physical Therapy Weight Training (Resistance) 13

II. Eat Healthy III. Get A Good Night Sleep There is no convincing data to indicate that one diet will help to reduce pain or improve energy levels A.

Weight loss in obese patients with Fibromyalgia is associated with improved function (Shapiro JR, et al, J Psychosom Res 2005) and quality of life (Senna MK, et al, Clin Rheumatol 2012) Holton KF,

14 II. Eat Healthy III. Get A Good Night Sleep There is no convincing data to indicate that one diet will help to reduce pain or improve energy levels A. Higher body mass index (BMI) is associated with fibromyalgia (Yunus MB, et al, Scand J Rheumatol 2002) B. Weight loss in obese patients with Fibromyalgia is associated with improved function (Shapiro JR, et al, J Psychosom Res 2005) and quality of life (Senna MK, et al, Clin Rheumatol 2012) Holton KF, Kindler KL and Jones KD, Rheum Dis Clin North Am, 2009, PMID Sleep deprivation (of stage 4 or delta-wave sleep deprivation) is associated with development of widespread pain. Patients with Fibromyalgia commonly have disturbances in their sleep with periodic arousals (alpha wave intrusion) Improvement in restorative sleep through sleep hygiene tips is associated with improvement in pain Moldofsky H, Rheum Dis Clin North Amer, 2009, PMID Orlandi AC, et al, Rev Bras Rheumatol, 2012, PMID TIPS FOR A BETTER NIGHT'S SLEEP DO: Establish and maintain a regular bedtime and wake-up time every day. Find the amount of sleep you need to feel consistently refreshed. Create a comfortable, quiet, clean and dark environment for sleeping. Your bed and the temperature of your bedroom should be comfortable. Establish a regular pattern of relaxing behaviors for minutes before bedtime. Use the bed and bedroom for sleeping and sex only. Exercise on a regular basis (but not too close to bedtime). DON'T: Don't nap during the day or evening. Don't eat heavy meals or drink large amounts of liquid before bedtime. Don't allow worrying, anger or frustration to keep you awake in bed. Don't lie awake in bed for long periods of time. If not asleep within minutes, leave your bedroom and do something relaxing until you feel sleep again. Don't allow your sleep to be disturbed by your phone, pets, family, etc. Don't use alcohol, caffeine, or nicotine. Also please turn off TV, computer and cell phone at least minutes before bed. All of these may worsen sleep. Courtesy of David Claman, MD, UCSF Sleep Disorders Center Treatment of Fibromyalgia A multidisciplinary approach Medication Body Mind Scascighini L, et al, Rheumatology 2008 Häuser W, et al, Arthritis Care & Res

4/5/18 The Vicious Cycle of Chronic Pain What would life

feel? www.amysullivanmft.com/cognitivebehavioraltherapy.

functioning Brain Descending Signals Modulate

) Emotional stress exacerbates pain and impairs

15 4/5/18 The Vicious Cycle of Chronic Pain What would life be like if you could influence the way you think and feel? Emotional stress exacerbates pain and impairs functioning Brain Descending Signals Modulate Sensitivity To Pain Depression Anxiety Catastrophizing ( ) Emotional stress exacerbates pain and impairs functioning Depression Anxiety Catastrophizing Pain Melzack & Wall Gate Control Theory 15

Train The Brain Cognitive Behavioral Therapy Goals: Education about the nature of fibromyalgia Realistic Goal Setting Relaxation Training Identification of dysfunction thought patterns and Techniques

16 Train The Brain Cognitive Behavioral Therapy Goals: Education about the nature of fibromyalgia Realistic Goal Setting Relaxation Training Identification of dysfunction thought patterns and Techniques to counteract negative automatic thoughts Strategize for maintenance Physical Response and management of flares Does CBT Work? Thoughts Feelings Behavior Bennett RM & Nelson D, Nat Clin Pract Rheumatol, 2006, PMID Bennett RM & Nelson D, Nat Clin Pract Rheumatol, 2006, PMID EULAR 2016 Fibromyalgia Recommendations Strong Recommendation For Aerobic & Strengthening Exercise Weak Recommendation Against Biofeedback Hypnotherapy Massage Treatment of Fibromyalgia A multidisciplinary approach Weak Recommendation For Cognitive Behavioral Therapy Mindfulness / mind-body Acupuncture Meditative Movement Hydrotherapy/spa Strong Recommendation Against Chiropractic therapy No Evidence for Efficacy Trigger point injection Medicine Mind Body MacFarlane GJ et al, Ann Rheum Dis 2016, PMID

Referral by Pain Medicine MD or rheumatologist Admission criteria chronic pain that interferes with lives and have interest/motivation Interdisciplinary evaluation: team then meets to decide if

17 Referral by Pain Medicine MD or rheumatologist Admission criteria chronic pain that interferes with lives and have interest/motivation Interdisciplinary evaluation: team then meets to decide if patient will be admitted. Focus of program is on whole body away from medical management (no Rx) 12 week program Classes 3-4 hrs, 2-3 times/week Textbook/Manual Team: Nurse coordinator Psychologist Physical Therapist Nutritionist Pharmacist (works with PCP) Social Worker (case management) Summary Fibromyalgia represents a condition of central sensitization to pain Systemic disease should be excluded in patients with fibromyalgia Fibromyalgia is important to diagnose to limit unnecessary medical utilization Fibromyalgia is manageable with a interdisciplinary approach Non-pharmacologic Pharmacologic Thanks! 17

Headaches, 37, 42 Hypnotherapy, 101t, 106 Hypothalamic-pituitary-adrenal (HPA) axis, 59, 61, 63, 64, 65

Headaches, 37, 42 Hypnotherapy, 101t, 106 Hypothalamic-pituitary-adrenal (HPA) axis, 59, 61, 63, 64, 65 INDEX Note: page numbers in italic typeface indicate figures. Page numbers followed by a t indicate tables. Abbreviations are for terms listed on pages 135-137. Acetaminophen/tramadol in fibromyalgia,