Fibromyalgia: Friend or Foe

Educational Objectives

The goal of this program is to improve the management of fibromyalgia (FM). After hearing and assimilating this program, the clinician will be better able to:

1. Diagnose FM in patients through use of the American College of Rheumatology criteria.

2. Recognize the clinical manifestations of FM.

3. Consider a multidiscliplinary approach in the management of FM.

Summary

Fibromyalgia (FM): syndrome (not disease) characterized by chronic musculoskeletal aches, pains, and stiffness; pain on digital palpation, but articular pathology absent

American College of Rheumatology (ACR) criteria (1990): FM — history of chronic widespread pain (CWP) for ≥3 mo in all 4 quadrants of body and in ≥11 of 18 tender point (TP) sites on digital palpation when 4 kg pressure applied; myofascial pain syndrome (MPS) — involves 1 to 3 quadrants; includes regional pain syndromes; if untreated, sometimes progresses to FM; more common in men; much better prognosis than FM; digital TP sites — 10 in upper back and neck; 4 in buttocks; 4 in lateral epicondyles and anserine bursa of knees

Revised ACR criteria (2010): FM diagnosed if CWP present based on widespread pain index (includes number of painful body regions; symptom severity scale includes fatigue, waking unrefreshed, cognitive symptoms, and symptoms that last ≥3 mo); no examination of TPs; 1990 and 2010 criteria both valid

Epidemiology: FM affects 2% to 5% of adult population (CWP diagnosed in 10%-20%) in United States; majority 35 to 60 yr of age; 90% women; FM most common subset of CWP

Triggers of FM and related conditions: include infectious diseases, physical trauma, psychologic stress, peripheral pain syndromes, hormonal abnormalities, drugs, vaccinations, and catastrophic events (eg, war)

Signs and symptoms: widespread pain with TPs (100%); generalized weakness reported but muscle strength normal; unrefreshing sleep; fatigue (in majority but not all patients); morning stiffness; tension headaches; painful periods; irritable colon or functional bowel disease; subjective report of numbness, swelling, and/or tingling; lace-like red skin mottling; reports of fever, swollen glands, and/or dry eyes; varying degrees of cognitive dysfunction; significant psychopathology; nocturnal myoclonus or restless legs syndrome (RLS); pelvic pain and urethal syndromes; vulvodynia or vaginismus; complex regional pain syndrome (reflex sympathetic dystrophy [RSD])

Diagnostic work-up: confirm history of CWP for ≥3 mo; perform physical examination, take careful patient history, and order selected laboratory testing; rule out other types of CWP; evaluate comorbidities

Conditions associated with FM: include chronic fatigue syndrome (CFS; ≈50% of patients with CFS also have FM and vice versa) and RSD (100% of patients with RSD have FM, but only 5% of those with FM have RSD); FM vs CFS — patients with CFS usually have distinct starting point of infectious or viral process and more reports of fevers and swollen glands; joint and muscle aches more common in FM

Etiopathogenesis of FM: multifactorial syndrome characterized by abnormal sensory processing of pain signals; nociceptive or noxious stimuli produce hyperalgesia or increased sensitivity; nonnociceptive stimuli produce allodynia or painful response to nonpainful stimulus; repeated insults lead to “wind up” phenomenon, resulting in central sensitization and pain amplification through sensory afferent ascending pain pathways; lumbar puncture shows elevated levels of cerebrospinal fluid (CSF) substance P and nerve growth factor, relative deficiency of serotonin, and activation of N-methyl-d-aspartate (NMDA) receptors

Pain classifications: acute pain — normal in FM; chronic pain — psychogenic (not part of FM); regional (MPS); central (FM); sources of chronic pain — neuropathic (not part of FM); nociceptive (hyperalgesia with neuroplasticity can lead to causalgia and hyperpathia); allodynia (becomes nociceptive with chronic stimulation)

Clinical manifestations: hormonal — blunted cortisol response to stress; decreased nocturnal growth hormone secretion; activation of proinflammatory cytokines (eg, interleukin 6) caused by impaired cortisol response; muscle and nerve — increased DNA fragmentation in mitochondria; nuclear magnetic resonance spectroscopy shows increased phosphodiester peaks indicating damage to sarcolemmal membranes; much evidence in literature for small-fiber neuropathy; dysautonomia — fight-or-flight response blunted due to chronic stimulation; vasomotor instability; hypervigilance to, eg, noise, light, touch, heartbeats; diminished 24-hr heart rate variability; sustained unopposed stimuli can lead to RSD; sleep — 85% of patients with FM have sleep abnormality resulting in α-wave intrusion into δ-wave sleep or upper airway resistance patterns; leads to decreased production of melotonin and growth hormone while sleeping; RLS — seen in 10% to 15% of patients with FM; cytokines — levels normal and cannot be measured in serum; however, studies in vitro show cytokine dysregulation; glial cells in spinal cord shown to influence cytokine production (opiates stimulate cytokine production by glial cells, leading to hyperalgesia; therefore, narcotics contraindicated in management of FM); pain processing augmented

Comorbidities: ≈45% of patients have posttraumatic stress disorder; ≈45% of young women have some type of severe psychosocial distress; 10% have bipolar disorder

Differential diagnosis: numerous pseudo-FM syndromes; rule out autoimmune disease, cancer, substance abuse, malnutrition, bipolar disorder, early stages of multiple sclerosis or myasthenia gravis, low thyroid or high parathyroid levels, vitamin D deficiency, and infection

Treatment: patient education most important component; adherence to therapy also important; multidisciplinary approach recommended; individualize treatment goals; successful outcome involves optimal function (patient not necessarily free from pain); prescribe rules for sleep hygiene to ensure patient wakes refreshed; advise using lazy Susans to prevent unnecessary reaching; patient should carry weight equally; if at computer terminal, use good chair, have glare-proof screen at eye level, and keyboard in position to prevent carpal tunnel syndrome

Local remedies: trigger and TP injections; nerve blocks; topical agents containing aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs; eg, diclofenac), or capsaicin; topical anesthetics; onabotulinumtoxinA (Botox); heat; dry needling; acupuncture

Systemic remedies: tricyclic antidepressants relax muscles and promote sleep; selective serotonin reuptake inhibitors (SSRIs) not effective for pain but anxiolytic; serotonin-norepinephrine reuptake inhibitors also available; dopaminergic agent for RLS; occasional use of bendzodiazepines for muscle relaxation (option as long as patient does not develop tolerance); anticonvulsants (eg, gabapentin) for burning and tingling; nonnarcotic analgesics (eg, tramadol) and NSAIDs for analgesia; tizanidine decreases CSF substance P levels

Approved drugs for treatment of FM: duloxetine (Cymbalta), milnacipran, and pregabalin (Lyrica) approved by Food and Drug Administration; duloxetine may be better for fatigue or certain arthritic pain; pregabalin may be better for depressed mood

Adverse event profiles: SSRIs associated with withdrawal symptoms; pregabalin causes significant weight gain in 20% to 30% of patients

Clinical practice: common to combine low doses of drugs from each class; central pain states treated with multifactorial approach

Nonpharmacologic therapies: strong evidence — patient education; aerobic exercise; treatments that target sympathetic nervous system; cognitive behavioral therapy; weak evidence — physical therapies; TP injections controversial

Pharmacologic therapies: no evidence of efficacy — opioids; steroids; NSAIDs (no evidence of efficacy for FM, but help with arthritis and other conditions); guaifenesin; benzodiazepines (but speaker believes drugs helpful)

Prognosis: 50% of all patients with FM never diagnosed or treated, and generally do well; most of those diagnosed early and educated about FM show improvement 2 yr later; majority of patients with FM seen by primary care physician better 2 yr later, but not majority of those seen by rheumatologist (those with persistent symptoms for >2 yr do not do as well)

Disability: 90% of patients with FM work full time, but ≤30% change jobs or job descriptions to accommodate symptoms; 10% of those unable to work have low educational attainment, psychiatric disorder, and/or medical cormorbidities; patient education, ergonomic assistance, and positive attitude about what patient can do associated with less disability

New treatments: integrated interventions that address sympathetic nervous system (approaches that influence pulse, blood pressure, and vasomotor control helpful [eg, biofeedback, hypnosis, relaxation techniques]); categories for new drug development — sensory afferent ascending pathway; descending pathway (not very effective); cerebral metabolism; muscle metabolism

Readings

Giacomelli C et al: Fibromyalgia: a critical digest of the recent literature. Clin Exp Rheumatol 2013 Nov-Dec;31(6 Suppl 79):S153-7; Haliloglu S et al: Fibromyalgia in patients with other rheumatic diseases: prevalence and relationship with disease activity. Rheumatol Int 2014 Mar 4; Häuser W et al: Review of pharmacological therapies in fibromyalgia syndrome. Arthritis Res Ther 2014 Jan 17;16(1):201; Hawkins RA: Fibromyalgia: a clinical update. J Am Osteopath Assoc 2013 Sep;113(9):680-9; Kuhn A, Landmann A: The classification and diagnosis of cutaneous lupus erythematosus. J Autoimmun 2014 Feb-Mar;48-49:14-9; Lami MJ et al: Systematic review of psychological treatment in fibromyalgia. Curr Pain Headache Rep 2013 Jul;17(7):345; Lee J et al: Chronic widespread pain, including fibromyalgia: a pathway for care developed by the British Pain Society. Br J Anaesth 2014 Jan;112(1):16-24; Lunn MP et al: Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev 2014 Jan 3;1:CD007115. doi:10.1002/14651858.CD007115.pub3; Martín J et al: Evaluation of the interdisciplinary PSYMEPHY treatment on patients with fibromyalgia: a randomized control trial. Pain Med 2014 Feb 27. doi:10.1111/pme.12375; Michalski JP, Kodner C: Systemic lupus erythematosus: safe and effective management in primary care. Prim Care 2010 Dec;37(4):767-78, vii; Navarra SV et al: Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 2011 Feb 26;377(9767):721-31; Navarra SV et al: Studies of Filipino patients with systemic lupus erythematosus: autoantibody profile of first-degree relatives. Lupus 2011 Apr;20(5):537-43; Peng X et al: Long-term evaluation of opioid treatment in fibromyalgia. Clin J Pain 2014 Jan 28; Satoh M et al: Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum 2012 Jul;64(7):2319-27; Skaer TL: Fibromyalgia: disease synopsis, medication cost effectiveness and economic burden. Pharmacoeconomics 2014 Feb 7; Stephenson JL, Shipman AR: The Systemic Lupus International Collaborating Clinics criteria have replaced the American College of Rheumatology guidelines for the diagnosis of systemic lupus erythematosus. Clin Exp Dermatol 2014 Apr;39(3):431-2; Wallace DJ: Is there a role for cytokine based therapies in fibromyalgia. Curr Pharm Des 2006;12(1):17-22; Wichainun R et al: Sensitivity and specificity of ANA and anti-dsDNA in the diagnosis of systemic lupus erythematosus: a comparison using control sera obtained from healthy individuals and patients with multiple medical problems. Asian Pac J Allergy Immunol 2013 Dec;31(4):292-8; Wolfe F et al: Mortality in fibromyalgia: a study of 8,186 patients over thirty-five years. Arthritis Care Res (Hoboken) 2011 Jan;63(1):94-101; Wolfe F 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.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Wallace was recorded at the James R. Klinenberg, MD, Symposium on Rheumatic Diseases: Hot Topics in Rheumatology, held on February 22, 2014, in Pasadena, CA, and presented by Cedars-Sinai Department of Medicine. For information about upcoming CME activities presented by Cedars-Sinai Medical Center, please visit www.csme.edu/cme. The Audio-Digest Foundation thanks Dr. Wallace  and the Cedars-Sinai Medical Center for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

IM612101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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