Fibromyalgia

Only 3 medications are FDA approved for Fibromyalgia:

1) Duloxetine (Cymbalta) 2) Milnacipran (Savella) 3) Pregabalin (Lyrica) *Opioids and NSAIDS not effective for FM pain*

Things that have a role in FM but we don't know to what extent they are causative:

1) HPA axis dysregulation 2) Genetic Predisposition 3) Environmental Insult 4) Allostatic load

Although no diagnostic laboratory tests currently exist for fibromyalgia, appropriate initial studies include workup to rule out

1) Hypothyroidism (thyroid-stimulating hormone [TSH]) 2) Inflammatory myopathies (creatine phosphokinase [CPK]) 3) Polymyalgia Rheumatica (erythrocyte sedimentation rate [ESR]) 4) Lupus (antinuclear antibody [ANA]) 5) Chronic infections, Anemia (complete blood count [CBC] with differential). 6) Sleep studies and joint fluid analysis may be helpful

Tender Points

1) Occiput - suboccipital muscle insertions 2) Trapezius - midpoint of upper border 3) Supraspinatus - above medial border of scapular spine 4) Low cervical - anterior aspects of inter-transverse spaces at C5-C7 5) 2nd rib - Costochondral junction 6) Lateral Epicondyle 7) Gluteal - upper outer quadrants of buttocks 8) Greater Trochate 9) Knee - medial fat pad proximal to joint line

Meds for Fibromyalgia treat the

1) Sleep 2) Anxiety/Depression 3) Pain

Differential Diagnosis - Endocrine Hyperparathyroidism, Cushing's syndrome

Blood work may show electrolyte abnormalities (hypercalcemia); exam may show typical Cushingoid features, provocative testing.

Hyperparathyroidism, Cushing's syndrome

Blood work may show electrolyte abnormalities (hypercalcemia); exam may show typical Cushingoid features, provocative testing.

Hypothyroidism

Both can have profound fatigue, muscle weakness, generalized malaise. TFTs routine part of w/u.

Differential Diagnosis - Endocrine Hypothyroidism

Both can have profound fatigue, muscle weakness, generalized malaise. Thyroid Function Tests routine part of w/u.

Peripheral neuropathies, entrapment syndromes, neurologic disorders (Carpal tunnel syndrome, MS, myasthenia gravis)

Both may have paresthesias, cognitive dysfunction more FM, depress. Myofascial pain syndromes are localized and characterized by presence of trigger points, usually axial.

Sleep aids

1) TCA: amitriptyline, nortriptyline, doxepin, cyclobenzaprine/flexeril 2) Trazodone (serotonin modulator) 3) For restless leg: Pramipexole (Dopamine agonist), BZDs 4) Herbal remedies - valerian root, wild lettuce, Jamaican dogwood, passionflower, hops, L-theanine, Magnesium, melatonin, 5-HTP (hydroxytryptophan) 5) Cyclobenzaprine, Amitryptyline, Gabapentin, Pregabalin 6) Not recommended: Zolpidem, Benzodiazepines

Meds for anxiety/depression

1) mixed reuptake inhibitors - Venlafaxine - Duloxetine (Cymbalta) - Tramadol - Milnacipran (Savella) These have analgesic and antidepressant/anxiolytic activity 2) SSRIs: Fluoxetine, Paroxetine, Sertraline

Osteoarthritis

- worsens with use but is limited to joints and is unlikely to cause broad pain distribution

Initial Management of FM

Lifestyle stuff is always first Non-pharm fist, then pharm to help with sleep, mood, depression, pain Multimodal Tx approach includes lifestyle, complementary therapy, cognitive beavioral stuff BEFORE MEDICATIONS

Which of the following should not be included in the initial management of this patient? a) Cognitive therapy b) Instruction on normalizing sleep patterns c) Amitriptyline 25 mg/day d) A graded exercise program e) Patient education about fibromyalgia

*Amitriptyline 25 mg/day* As mentioned previously, initial management of fibromyalgia should focus on NONpharmacologic therapy, including: - patient education - sleep management - cognitive therapy - graded education program. Analgesics and anti-inflammatory drugs (eg, naproxen) are generally ineffective. Concomitant depression should be treated, but such treatment alone will not improve fibromyalgia. If initial nonpharmacologic management does not improve the patient's symptoms, a medication that is effective against fibromyalgia should be added.

A 76-year-old white woman presents with a 3-month history of diffuse pain involving both the upper half and the lower half of the body. She has a past history of trigeminal neuralgia, recurrent neck pain, and headaches. Her pain is mostly over soft tissue; it worsens throughout the day and is more severe after activity. On examination, the patient has no joint swelling or crepitus, but there is tenderness over multiple joints and bursae. No rash is visible. Neurologic examination yields normal results. Radiographs of the hands are normal; radiographs of the cervical spine show bone spurs. MRI of the skull and brain shows normal findings, and MRI of the cervical spine shows bone spurs without spinal-cord compression. On laboratory evaluation, the patient has an ESR of 32 mm/hr and a low-titer positive test result for rheumatoid factor (RF). Which of the following is the most likely diagnosis? New-onset rheumatoid arthritis Polymyalgia rheumatica Cervical spinal stenosis Fibromyalgia Osteoarthritis

*Fibromyalgia* ESR < 50, pain worse in morning == PMR unlikely No supportive physical findings == OA unlikely No joint swelling + new onset == RA unlikely No spinal cord/nerve root compression = Cervical Spine Stenosis unlikely The finding of diffuse pain and tenderness that persists throughout the day without joint swelling is consistent with fibromyalgia. Given that the ESR is < 50 mm/hr and the pain is typically worse in the morning, polymyalgia rheumatica is unlikely. Bone spurs in the cervical spine are frequently asymptomatic and are unlikely to be causing her symptoms in the absence of any evidence of spinal-cord or nerve-root compression. Osteoarthritis is also an unlikely cause in the absence of supportive findings on physical examination. New-onset rheumatoid arthritis should present with joint swelling in addition to pain. Whereas a low-titer positive RF test result is often found in patients with new-onset rheumatoid arthritis, it is also found in about 15% of elderly patients WITHOUT rheumatoid arthritis.

- 56 yo white woman - pain all over - pain began 1 year ago in neck and shoulders - spread to hips, pelvic area, and exremities - affects muscles, bones, and joints - poor sleep and memory - worsen with activity - hx of migraine and chronic GI pain - ESR 32 mm/hour - RF and ANA negative

*Fibromyalgia* - Diffuse pain involving both the shoulder girdle and the pelvic girdle that worsens with activity and is not limited to muscles or joints is typical of fibromyalgia, as are disordered sleep, poor memory, and a history of other pain syndromes (eg, migraine headaches and functional bowel disorder). - Diffuse small-fiber neuropathy can cause generalized pain but is not associated with the other features described, and it often gives rise to findings on neurologic examination. - The pain of osteoarthritis worsens with use but is limited to joints and is unlikely to cause the broad pain distribution seen in this patient. - In polymyositis, weakness is the most prominent symptom, and pain, if present, is limited to muscles. - In polymyalgia rheumatica, stiffness and pain improve with activity, and the ESR is usually higher than 50 mm/hr.

Meds for pain

1) Antiepileptics: Gabapentin, Pregabalin (Lyrica) - Can also help with sleep 2) Cyclobenzaprine (Flexeril) improves pain and sleep quality *muscle relaxer* 3) Variable efficacy - Tramadol (Ultram) - central acting analgesic - Naltrexone (Revia) - opioid receptor antagonist (low dose) - Guaifenesin - may have action on glial cells, effect on NMDA (excitatory) receptors. - NSAIDS and opioids not very helpful and associated with serious adverse effects

A 56-year-old white woman presents with diffuse muscle pain and progressive weakness of 3 months' duration. Her past history is negative for illnesses except for mild osteoarthritis in her knees, which she has had for several years. Examination reveals diffuse tenderness of proximal muscles in the shoulder girdle and pelvic girdle with muscle weakness that is worse in proximal muscles. Crepitus is palpated over both knees. No rash or joint swelling is observed, and neurologic examination yields normal results. Which of the following is the most likely diagnosis? Rheumatoid arthritis Fibromyalgia Osteoarthritis Polymyositis Polymyalgia rheumatica

*Polymyositis* The finding of progressive proximal-muscle weakness suggests polymyositis. Although the diffuse pain and tenderness are consistent with fibromyalgia, the presence of progressive proximal-muscle weakness militates against that diagnosis. The absence of joint swelling and the presence of tenderness over muscles rather than over joints make both rheumatoid arthritis and osteoarthritis unlikely. Polymyalgia rheumatica is not typically associated with muscle tenderness or progressive muscle weakness.

Ankylosing spondylitis.

- *3:1 male* - *Motion restriction, imaging features* - Pseudofusion of lumbar and ascending vertebrae - Looks like bamboo spine on X ray - Characteristic imaging findings - *Pain tends to be localized to lumbar spine with AS*

Epidemiology of FM

- 2-3% prevalence - Prevalence in primary care practice 5-10% - females of middle age at increased risk - female:male = 9:1 - Found in most countries, ethnic groups, climates - Also seen in men, children, adolescents, elderly - More common in relative of patients with FM Genetics, Environment, Psychology all have a role *PTSD in 45% of FM patients but only in 3% of population-based controls* *History of Trauma*

Besides the pain...

- 96 % Fatigue ~86% Sleep disturbance ~60% Headaches, lightheadedness ~56% Restless legs, leg cramps Cognitive disturbance - "fibro fog" - short term memory, complex thinking, concentration Mood disorder Hand/foot paresthesias - numb, tingling, cold, neuropathic pain Raynaud's phenomenon - Painful hands and feet and nipples, vasospasm, changing colors Sicca syndrome - dry eyes Abdominal bloat

FM Exacerbation Triggers

- Emotional stress - increased exertion/allostatic load - Infections - Parvo 19, Lyme, HIV, Hep C - Other medical illness or pain generators - Hypothyroidism - Trauma (physical ex/surgery, emotional) - Sx worse with cold, humidity

the older Dx criteria for FM

- History of widespread pain has been present for at least 3 months - Pain is considered widespread when all of the following are present: 1) Pain in both sides of the body 2) Pain above and below the waist 3) In addition, axial skeletal pain (cervical spine, anterior chest, thoracic spine or low back pain) must be present. Pain in 11 of 18 tender point sites on digital palpation

Labs/Routine Workup

- Imaging, labs, muscle biopsy normal. Routine workup includes: 1) CBC (r/o anemia) 2) ESR (r/o rheumatologic diseases) 3) Complete Metabolic Panel 4) Thyroid Function Test 5) Other tests only as indicated: Lyme titer, PPD, RPR, HIV, hepatitis, ANA, RF, Complement panel, CPK

Risk Factors for FM

- Middle age - Female gender - Family history of FM - Stress, depression - Rheumatic disease - Sleep disorders.

Inflammatory myositis and metabolic myopathies.

- Muscle weakness, but not giveway or deconditioning. - Less diffuse pain. - Statin history (statins cause myopathy) - Muscle enzyme tests.

RA, Sjogren's, SLE, MCTD

- Musculoskeletal pain, dry eyes, cold hands and fatigue are symptoms in common. - RA in younger people - affects small joints, not large knee joints (which is osteoarthritis due to wear and tear) - Auto-antibodies that cause joint destruction - *Both may have ANA or RF positive, and may be false positive or concurrent conditions* - *PE should be able to r/o arthritis, rash, even without labs* -- Many avoid because of high false positive rate of ANA and RF (5-10% healthy females).

Polymyalgia rheumatica.

- Older onset - More proximal muscle stiffness and pain - ESR elevated - response to glucocorticoids - a/w Temporal Arteritis which is a/w Blindness (can lead to blindness if not given high dose Corticosteroids)

Non - pharmacologic interventions

- Patient education and support - Exercise - Mind/Body practices - Manual therapy - Behavioral Health - Trigger Point Injections w/ Lidocaine - Acupuncture - Topicals (Lidoderm, heat)

Physical Exam findings

- Tenderness to palpation @ TENDER POINTS - Giveaway muscle weakness (due to pain and stiffness). - Somatic dysfunction - Imaging, labs, muscle biopsy, all normal !!

Musculoskeletal symptoms in FM

- Widespread pain - Stiffness - Paresthesia - Hyperalgesia, allodynia - Pain in low back, may radiate to buttocks and legs - Pain and tightness in neck, radiate to shawl distribution - Muscle pain after even mild exertion - Constant pain -- burning, gnawing, aching, stiffness, soreness. Sometimes worse in morning. "It's a Dx that wont kill you but you wish you were dead"

Fibromyalgia

- diffuse pain and tenderness that persists throughout the day without joint swelling - ESR is lower than 50 mm/hr - pain is typically worse in the morning worsens with activity and is not limited to muscles or joints Disordered sleep, poor memory, and a history of other pain syndromes (eg, migraine headaches and functional bowel disorder). Tenderness to palpation Giveaway muscle weakness (due to pain).

What population is at increased risk for FM

- females of middle age (30-50) Female:Male = 9:1

Polymyalgia Rheumatica

- stiffness and pain improve with activity - ESR usually > 50 mm/hr (suggests that the pain has an inflammatory origin) - acute onset of disabling pain and morning/rest stiffness involving both the upper half and the lower half of the body - not typically associated with muscle tenderness or progressive muscle weakness. - Acute onset disabling pain in both upper and lower body (shoulder and hip girdle) - Median age at diagnosis 72 years, rare under age 50 - RISK: association with temporal arteritis and blindness - Response with steroids! - PMR older onset, more proximal muscle stiffness and pain

Multi-modal/multidisciplinary Treatment Approach to Fibromyalgia

1) psychological and behavioral therapy 2) physical therapy 3) pharmacotherapy Nondrug therapy should be the primary treatment, with pharmacotherapy reserved for those who do not respond to nondrug therapy—namely, patient education, a carefully graded exercise program, and psychological and behavioral therapy Psychological and behavioral therapy includes aggressive depression treatment, cognitive-behavioral therapy, operant-behavioral therapy, relaxation training, sleep hygiene, coping skills, and distraction strategies.

IBS and FM

30% of patients with Irritable Bowel Syndrome have FM. 30-70% of those with FM have IBS.

What is the most effective Treatment approach

A multidimensional approach that includes attention to mind/body/spirit with patient education, CBT, appropriate physical activity and pharmacologic therapy to treat sleep disturbance, psychoemotional aspects and pain seems to be most effective. Strongest evidence is for SNRIs, TCAs, antiepileptics and muscle relaxants.

Advantages of the New Criteria for Dx of FM

Advantages: - Patient can do it themselves - more weight to extra-MS symptoms - can monitor symptoms over time

Weather as FM trigger

Although cold weather can be a trigger for FM symptoms, we do NOT see increased prevalence of FM in cold climates Symptoms may be worse in cold, humidity, but distribution among countries relatively consistent

Differential Diagnosis - Infectious

Check for occult infections, abscesses, dental disease, bacteremia/Subacute bacterial endocarditis. FM can accompany or follow infections, and sometimes persists after appropriate treatment (for example, of Lyme, Hep C). Check serologies if suspicion is high.

Infection

Check for occult infections, abscesses, dental disease, bacteremia/Subacute bacterial endocarditis. FM can accompany or follow infections, and sometimes persists after appropriate treatment (for example, of Lyme, Hep C). Check serologies if suspicion is high.

Chronic fatigue syndrome/SEID

Common to both: - Fatigue - abnormal sleep, - musculoskeletal pain, - impaired memory and concentration - psychiatric conditions How it's different - More ongoing subclinical inflammatory process with low-grade fever, sore throat, lymphadenopathy or pain in cervical and axillary nodes, acute onset

Diagnosing Fibromyalgia: Getting the History

Dig for the history - Risk factors, triggers and associated conditions (slides 10, 11, 14) - Birth trauma, ACEs, repetitive strains, emotional stresses, medical illnesses, surgery, trauma. - Fibromyalgia Impact Questionnaire - Focus on functional capacity - Good documentation helps when your patient applies for disability

Pathogenesis

Disordered pain regulation with central sensitization. - Temporal summation of pain - Decreased endogenous pain inhibition - Changes in pain receptors and pain-related neuropeptides

Psychiatric co-morbid conditions

Don't forget the ddx and co-morbid psychiatric conditions (depression, PTSD)

Exercise for FM patients

Exercise has been proved to provide both subjective and objective improvements in pain and overall sense of well-being. Deconditioning is a major contributing factor to pain. Graded aerobic activity with aerobics (shown), aquatherapy, or stationary bicycles can be transitioned to more rigorous endurance and strength training. Heat and massage provide symptomatic relief for many forms of chronic pain, including fibromyalgia. Trigger-point injections, acupuncture, chiropractic manipulations, and myofascial release are not currently considered evidence-based approaches to therapy. All therapeutic approaches should emphasize self-sufficiency in pain control rather than reliance on others for symptomatic relief.

What is Fibromyalgia?

Fibromyalgia is an idiopathic, chronic, nonarticular pain syndrome. Fibromyalgia is a common and chronic disorder of unknown etiology characterized by widespread pain and tenderness, abnormal pain processing, sleep disturbance, fatigue, and, often, psychological distress, as well as other symptoms. Although fibromyalgia is frequently grouped with arthritis-related conditions, there is no apparent inflammation or damage to the joints, muscles, or other tissues.

Summary slides

Fibromyalgia is an idiopathic, chronic, nonarticular pain syndrome. It is characterized by widespread pain (up and down, side to side) for at least 3 months, and the presence of 11 tender points among 18 specific anatomic sites. It is a multisystem disease with symptoms beyond musculoskeletal: sleep disturbance, fatigue, headache, morning stiffness, paresthesias and anxiety. Nearly 2% of the general population in the US suffers from FM, with females of middle age being at increased risk. Comorbid conditions that overlap with and may also be confused with FM include RA, SLE, PMR, myositis, hypothyroidism, hypoparathyroidism, neuropathies, myofascial pain syndromes. A multidimensional approach that includes attention to mind/body/spirit with patient education, CBT, appropriate physical activity and pharmacologic therapy to treat sleep disturbance, psychoemotional aspects and pain seems to be most effective. The holistic Functional Medicine approach is particularly helpful for many functional somatic syndromes where conventional treatments are inadequate.

Genetic predisposition of FM

First degree relatives of patients with FM are 8.5x more likely to have FM than relatives of patients with RA Multiple candidate genes are being investigated

What is the cause of Fibromyalgia?

Idiopathic, chronic pain syndrome.

Associated Conditions these functional somatic syndromes and other conditions may share a similar pathophysiology and often coexist with FM These conditions likely share a similar pathophysiology of disordered pain processing. Overlapping Syndromes.

Irritable bowel syndrome SEID* - chronic fatigue Chronic headaches Complex regional pain syndrome Interstitial cystitis Chronic lumbalgia Orthostatic intolerance/ Neurally mediated hypotension Obstructive Sleep Apnea Multiple chemical sensitivity Gulf War Syndrome PMS, dysmenorrhea TMJ Noncardiac chest pain Myofascial pain syndrome/repetitive strain syndrome Vulvodynia Interstitial Cystitis (feeling of having a UTI but no pathogens in urine)

Chronic fatigue syndrome/SEID

More ongoing subclinical inflammatory process with low-grade fever, sore throat, lymphadenopathy or pain in cervical and axillary nodes, acute onset Both have Fatigue, abnormal sleep, musculoskeletal pain, impaired memory and concentration, psychiatric conditions

Do FM symptoms occur only in MSK system?

NO -- It is a multisystem disease with symptoms beyond musculoskeletal: - sleep disturbance - fatigue - headache - morning stiffness - paresthesias - anxiety

Subacute bacterial endocarditis

No fever, but feel draggy, all over body myalgia Sounds like FM Need to differentiate it

A 76-year-old white woman presents with the acute onset of disabling diffuse pain and stiffness involving both the pelvic girdle and the shoulder girdle. The pain is worst when she arises in the morning, improves as the day progresses, and worsens toward evening. She reports feeling feverish but has not checked her temperature. Her activity has been limited by pain. The patient was previously healthy except for Heberden nodes, for which she takes acetaminophen as needed. She has no joint swelling or rash. There is mild weakness of her shoulder girdle. There is no tenderness. Neurologic examination is normal. The CBC shows only a mild normocytic anemia. The ESR is 52 mm/hr. Which of the following is the most likely diagnosis? Rheumatoid arthritis Osteoarthritis Polymyositis Polymyalgia rheumatica Fibromyalgia

Polymyalgia Rheumatica - Acute onset disabling pain in both upper and lower body (shoulder and hip girdle) - Median age at diagnosis 72 years, rare under age 50 - ESR >50 mm/hr RISK: association with temporal arteritis and blindness Treat with steroids! Polymyalgia rheumatica is characterized by the acute onset of disabling pain and morning/rest stiffness involving both the upper half and the lower half of the body, along with an ESR> 50 mm/hr, which suggests that the pain has an inflammatory origin. In view of the absence of tenderness and small-joint swelling, rheumatoid arthritis is unlikely. The symptoms suggestive of inflammatory pain and the ESR > 50 mm/hr are atypical for both fibromyalgia and osteoarthritis, rendering those diagnoses less likely as well.

Typical patient of FM

Typical patient is a woman between ages 30-50yo

Is weakness more prevalent in myositis or FM?

Weakeness is more prevalent in inflamm myosisits In FM, weakeness is bc of pain. Limitation in ROM is bc they are stiff, not weak Myopathies are actually weak. It's a more distinguishing feature

Rheumatoid Arthritis

tenderness over joints and small-joint swelling joint swelling in addition to pain Whereas a low-titer positive RF test result is often found in patients with new-onset rheumatoid arthritis, it is also found in about 15% of elderly patients without rheumatoid arthritis. Both have Musculoskeletal pain, dry eyes, cold hands and fatigue . Both may have ANA or RF positive, and may be false positive or concurrent conditions. high false positive rate of ANA and RF (5-10% healthy females).

pain medications for FM

these agents have limited efficacy in fibromyalgia and should mainly be reserved for patients with concomitant nociceptive pain generators (eg, osteoarthritis). Opioids should be avoided because they are both ineffective and potentially addicting. Opioids should be avoided because they are both ineffective and potentially addicting. . Steroids are useful only for patients with coexisting inflammatory processes.

What is the UNDERLYING problem in FM?

underlying problem as disordered pain processing in a patient with genetic predisposition and environmental insult.

polymyositis

weakness is the most prominent symptom, and pain, if present, is limited to muscles. progressive proximal-muscle weakness Muscle weakness, not giveway or deconditioning. Less diffuse pain. Statin history? Muscle enzyme tests.

Fibromyalgia is characterized by

widespread pain (up and down, side to side) for at least 3 months, and the presence of tender points at specific anatomic sites. waxing and waning course of exacerbations usually history of Trauma