Disclosures

• None vs Ortho: How Do You Tell?

Andrew J. Gross, MD Rheumatology Clinic Chief Associate Clinical Professor University of California, San Francisco

Objectives Clinical Case #1

• Recognize the key features of polymyalgia • A 66 year old man comes to see you rheumatica complaining of pain. The pain came on suddenly about 3 weeks ago, • Recognize inflammatory back pain initially affecting his right shoulder and • Know the of subacute then the left. The pain radiates down monoarticular arthritis into the upper arms and somewhat across his upper back and is • Know the hallmarks of . exacerbated by shoulder abduction. • Distinguish rheumatoid arthritis from • He also complains of new onset lower osteoarthritis by hand joint involvement back and hip discomfort.

1 All of the following symptoms tipped you off Clinical Case #1 - Question to the diagnosis of PMR EXCEPT:

You diagnose him with (PMR). All of the following symptoms tipped you off to the 67% diagnosis of PMR EXCEPT: a. Morning stiffness lasting >45 minutes a. AM stiffness >45 min b. Hand numbness b. Hand numbness c. Pain & stiffness affects the lower back and pelvic c. lower back stiffness girdle 19% d. Pain & stiffness improves with activity d. Better w/ activity 9% 3% 2% e. ESR >40 mm/hr e. ESR >40 mm/hr

i n s s h r m e e s s 5 b n f n t i v i t y m / m u m s t i f 0 n c k w / a c a > 4 n d b SR H a r E w e B e t t e r o A M stiffness >4 l Dasgupta B, et al, Ann Rheum Dis 2012, EULAR/ACR Classification Criteria

Clinical Case #1 - Question Some Tips about PMR

You diagnose him with Polymyalgia Rheumatica (PMR). • Typical distribution of All of the following symptoms tipped you off to the PMR symptoms… diagnosis of PMR EXCEPT: • Subdeltoid & a. Morning stiffness lasting >45 minutes biceps are b. Hand numbness common in one or both c. Pain & stiffness affects the lower back and pelvic girdle • Patients may develop d. Pain & stiffness improves with activity adhesive capsulitis e. ESR >40 mm/hr

Dasgupta B, et al, Ann Rheum Dis 2012, EULAR/ACR Classification Criteria Salvarani, C, et al, Nat Rev Rheumatol, 2012, PMID 22825731

2 Some more Tips about PMR Some more Tips about PMR

• PMR is uncommon in patients < 60 years old • PMR is uncommon in patients < 60 years old 97 cases of PMR identified during a 10 year study from • ESR is helpful - but it is <40 mm/hr in 10-20% of patients Olmstead County, Minnesota – CRP can be helpful when ESR is <40 0-49 years 1 in a million 50-59 years 1 in 5,000 • 15% will have (new onset head pain) 60-69 years 1 in 2,000 – New onset head pain 70-79 years 1 in 900 – Scalp tenderness – Jaw claudication when chewing – Sudden vision loss or diplopia

Chuang TY, et al, Ann Intern Med 1983, PMID 6982645 Dasgupta B, et al, Ann Rheum Dis 2012, EULAR/ACR Classification Criteria

Things patients with PMR often tell me When To Refer PMR to a rheumatologist

• “I feel like I am 100 years old!” • Rheumatologists are generally pleased to see cases • “I need to crawl out of bed in of PMR the morning” • Partial response to treatment with – • “I feel okay as long as I keep should have fully response to 15-20 mg/d. moving, but I stiffen up as • Difficulty tapering prednisone soon as I sit down – like the • Symptoms of tin man” • “That prednisone is a miracle”

3 Clinical Case #2 Clinical Case #2

• A 26 year old man comes to see you • The shoulder exam is notable for complaining of shoulder pain. The pain limitation in shoulder ROM (abduction, came on about 3 weeks ago, initially internal & external rotation) without affecting his right shoulder and then weakness in the rotator cuff muscles. the left. The pain does not radiate. There is some tenderness over the Range of motion of motion of both glenohumeral joint. No effusion. shoulders is limited. • Cervical spine flexion & rotation as • He also notices pain and stiffness in well as lumbar spine flexion are his and lower back. This is somewhat limited. Straight leg raise is worse recently, but has been present unremarkable. on an off for the past couple of years. • Hip rotation is also somewhat limited. • He complains of a hour of morning • The remainder of the joint exam is stiffness in his shoulders and low unremarkable. back.

Which of the following conditions is the most likely Clinical Case #2 cause of this man’s shoulder, neck and lower back pain:

Which of the following conditions is the most likely cause of this man’s shoulder, neck and 82% lower back pain: a. AS a. b. PMR b. Polymyalgia Rheumatica c. RA c. Rheumatoid Arthritis d. SLE d. Systemic Erythematosus e. CPPD e. Calcium Pyrophosphate Dihydrate Disease 10% (CPPD) 4% 1% 1%

R A D AS R LE P M S P P C

4 Clinical Case #2 Typical distribution of involved joints in Which of the following conditions are a likely rheumatoid arthritis cause of this 26 y.o. man’s shoulder, neck and (and lupus) lower back pain: a. Ankylosing Spondylitis b. Polymyalgia Rheumatica (age >50) c. Rheumatoid Arthritis d. Systemic Lupus Erythematosus e. Calcium Pyrophosphate Dihydrate Disease (CPPD) (usually older people, typically spares lumbar spine)

www.studyblue.com

Rheumatoid Psoriatic Ankylosing Osteoarthritis Ankylosing Spondylitis Arthritis Arthritis Spondylitis

https://dundeemedstudentnotes.wordpress.com/2014/06/16/polyarthritis/

5 Ankylosing Spondylitis - sacroiliitis AS – “bamboo spine”

Ankylosing Spondylitis Clinical Case #2

All of the following symptoms are associated with DIAGNOSIS inflammation of the spine (spondylitis) EXCEPT: Non-radiographic stage Radiographic stage a. Pain & stiffness improve with exercise. b. Onset of back pain was insidious Back pain Back pain Back pain c. Back pain & stiffness gets worse at night Sacroiliitis on Radiographic Syndesmophytes MRI sacroiliitis d. Burning pain in the thighs with standing e. Symptoms began before age 40

Time (years)

Rudwaliet M, et al. Arthritis Rheum . 2005;52(4):1000-1008.

6 All of the following symptoms are associated with inflammation of the spine (spondylitis) EXCEPT: Clinical Case #2

All of the following symptoms are associated with inflammation of the spine (spondylitis) EXCEPT: 62% a. Improves w/ exercise a. Pain & stiffness improve with exercise. b. Insidious onset b. Onset of back pain was insidious c. Pain worse at night c. Back pain & stiffness gets worse at night d. Burning pain in thighs d. Burning pain in the thighs with standing e. Symptoms <40 y.o. 14% 14% e. Symptoms began before age 40 7% 4%

t t s . s e o n 0 y . o s t h i g h 4 e x e r c i s e u < o n s w / d i r s e a t n i g h m s s i o I n y m p t p r o v e S m P a i n w o I Burning pain i

Inflammatory Back Pain: NHANES 2009-2010 Hallmark Features

Feature Odds Ratios Insidious onset 12.7 • 19.2% of US Adults age 20-69 years old reported chronic axial pain Pain at night (with improvement upon getting up) 20.4 • In patients with chronic axial pain, 28% to 35.5% Age at onset <40 years 9.9 had Inflammatory Back Pain Improvement with exercise 23.1 • US prevalence of IBP: 5% to 6% No improvement with rest 7.7

Sensitivity 79.6% & Specificity 72.4% Positive LR = 79.6/(100-72.4) = 2.9 ~ Probability = 14% • Self-reported prevalence of ankylosing spondylitis = 0.55 LR=likelihood ratio Sieper J, et al, Ann Rheum Dis 2009, PMID 19147614 Reveille JD, et al. Arthritis Care & Res . 2012;64(6):905-910.Weisman MH, et al . Ann Rheum Dis. Rudwaleit M, et al. Ann Rheum Dis . 2009; 68(6):777-83. Ozgocmen S, et al. J Rheumatol . 2010;37(9):1978. 2013;72(3):369-373.

7 When to refer a patient with back pain to a rheumatologist AS: Treatment

• Inflammatory Back Pain • HLA-B27+ (present in 85-95% of patients with AS) • Elevated CRP Axial disease only • Sacroiliitis on imaging (x-rays or MR) • Family history of Ankylosing Spondylitis TNF NSAID NSAIDs sulfasalazine inhibitors

Physical Therapy

Poddubnyy D, van Tubergen A, Landewé R, et al. Ann Rheum Dis 2015;74:1483–1487 Braun J, et al.,, Ann Rheum Dis 2011; 70: 896-904; van der Heijde D, et al, Ann Rheum Dis 2011; 70:905-08

Clinical Case #3 Clinical Case #3

• 45 year old man comes to see you with left knee To identify the cause of the knee swelling, what is the swelling for the past 7 days. He has no other best next test to obtain: complaints. A. Aspirate Knee Fluid for cell count and crystal search • ROS is unremarkable. No fevers or rashes B. MRI of knee • Physical Exam: unremarkable except for swelling C. X-ray of knee and warmth of the left knee with limited ROM. D. CBC with Differential E. Rheumatoid factor & CCP antibody

8 To identify the cause of the knee swelling, what Differential Diagnosis of is the best next test to obtain Sub-Acute Monoarticular Arthritis

Non-Inflammatory Inflammatory 59% • Cartilage or ACL tear • Infectious A. Aspirate Knee Fluid • Flare of osteoarthritis – Lyme Disease B. MRI of knee • Mimics of joint swelling – Gonococcus C. X-ray of knee – • Crystal D. CBC w/ diff 24% – Body habitus (adipose – CPPD – Gout E. RF & CCP tissue) and tendinitis 9% • Autoimmune 6% 3% – Spondyloarthritis Aspirate the Knee! – Palindromic

e f i d e f l u d i C C P – Other systemic disease F k n / e f e o F & n I R K R B C w M C t e X-ray of knee i r a A s p

Synovial Fluid Analysis Synovial Fluid Analysis Cell Count & Crystal Search Cell Count & Crystal Search

Non- Inflammatory Infectious • Green top tube preferred Inflammatory e.g. e.g. Type (lavender top tub will work) e.g. rheumatoid crystal or • 1-10 cc osteoarthritis arthritis septic

• CPT: 89051; 89060 Clear Turbid Turbid Appear- Viscous yellow yellow (do not freeze) ance • Refrigerated amber less viscous less viscous • Okay for up to 2 days

<2000 2000 - 50,000 >50,000 Quest Diagnostics WBC cells/mm 3 cells/mm 3 cells/mm 3 • Test Code 4707 PMNs LabCorp Cell Mononuclear and/or PMNs Type • Test Code 005231 lymphocytes

Zuber TJ, Am Fam Phys 2002 Zuber TJ, Am Fam Phys 2002 www.aafp.org/afp/2002/1015/p1497.html www.aafp.org/afp/2002/1015/p1497.html

9 Synovial Fluid Analysis Cell Count & Crystal Search Tips on subacute septic arthritis

Erythema Chronicum Migrans

Zuber TJ, Am Fam Phys 2002 www.aafp.org/afp/2002/1015/p1497.html

Tips on subacute septic arthritis Tips on subacute septic arthritis

Lyme Disease Lyme Disease Gonococcus • Unlikely unless traveled to • Unlikely unless traveled to • Sexually transmitted disease Lyme endemic region Lyme endemic region • Classically initially presents • Initial phase with erythema • Initial phase with erythema with tenosynovitis of the migrans rash & sometimes migrans rash & sometimes wrist eventually settling in to fever and diffuse arthralgia fever and diffuse arthralgia become a septic joint. • If untreated, later can • If untreated, later can • Can involve multiple joints develop monoarticular develop monoarticular • Often with scattered pustular arthritis, usually of the knee arthritis, usually of the knee skin rash (easy to miss) • Lyme ELISA & WB will be • Lyme ELISA & WB will be • DNA testing from urine and strongly positive strongly positive throat swab. • No role for testing joint fluid www.findarthritistreatment.com/eight-causes-of-migrating-arthritis/ • No role for testing joint fluid • No role for culture from blood or joint fluid.

10 Forms of Spondyloarthritis Tips on spondyloarthritis

Reactive arthritis • Sterile oligoarticular arthritis, • Occurs in 15% of patients usually of lower extremities with psoriasis • Develops 10-14 days • More common in people with following an infectious psoriasis affecting the scalp process, usually dysentery or diffuse severe disease or chlamydia urethritis • Sometimes associated with – Conjunctivitis or – Urethritis (independent of Chlamydia) • More than 50% of cases will resolve in <6 months.

Psoriasis Clinical Case #5

D

AB

11 A Case 5: A 50 year old healthy active Case 5: A 50 year old healthy active woman with woman with severe exacerbation of exacerbation of chronic right shoulder pain. chronic right shoulder pain. Which image is most likely associated with her Which image is most likely A.disorder? A associated with her disorder? A B. B 30% 30% CD C. C 22% 18% B D. d CD B

A B C D

T2 MRI

A Case 5: A 50 year old healthy active A A. Rheumatoid arthritis (late disease) woman with exacerbation of chronic B. Milwaukee Shoulder Syndrome (apatite- right shoulder pain. associated destructive arthritis) Which image is most likely C. associated with her disorder? D.

CD CD

B B

T2 MRI roentgenrayreader.blogspot. T2 MRI com

12 Clinical Case #6 Clinical Case #6

49 year old woman with multiple Which of the following studies will be most complaints. Most of her complaints useful in establishing this patient’s diagnosis? focus on pain at various locations. These problems have been present for A. Antinuclear antibody assay 6 months. Pain is particularly intense B. Rheumatoid factor assay over the neck, shoulders, low back, hips, knees, hands and feet. Pain is C. Anti-cyclic citrullinated peptide antibody severe in the AM and worsens over the D. HLA-B27 course of the day. Activity seems to E. No additional studies make the pain worse. She sleeps poorly. She has abdominal pains, occasional loose stool, and she has as well. She has pruritic skin rashes that are transient.

Which of the following studies will be most useful Clinical Case #6 in establishing this patient’s diagnosis? Which of the following studies will be most 56% useful in establishing this patient’s diagnosis? A. ANA A. Antinuclear antibody assay B. RF B. Rheumatoid factor assay C. CCP C. Anti-cyclic citrullinated peptide antibody D. HLA-B27 D. HLA-B27 17% E. None 14% E. No additional studies 6% 6%

F P 7 e A R C 2 n C B o AN N HLA-

13 Clinical Case #6 Inflammatory vs. Non-inflammatory

49 year old woman with multiple complaints. Most of her complaints • What is your worst time of day? focus on pain at various locations. • Duration of AM stiffness? These problems have been present for 6 months. Pain is particularly intense • Does the pain/stiffness improve/worsen with over the neck, shoulders, low back, activity? hips, knees, hands and feet. Pain is severe in the AM and worsens over the course of the day. Activity seems to make the pain worse. She sleeps ANA – Lupus poorly. She has abdominal pains, RF & CCP – RA occasional loose stool, and she has HLA-B27 – AS headaches as well. She has pruritic skin rashes that are transient.

What are the hallmarks of fibromyalgia? What are the hallmarks of (Choose 3) fibromyalgia? (choose 3) a) Widespread pain a) Widespread pain b) Joint Pain b) Joint Pain c) Non-restful sleep c) Non-restful sleep d) Depression d) Depression e) e) Fatigue f) Obesity f) Obesity

n n y i a i o n i t a P s i s t d p n r e s a i p F a t i g u e O b e r e J o s p D e e i d W N on-restful sleep

14 Diagnosis of Fibromyalgia Diagnosis of Fibromyalgia

• Fatigue Widespread Widespread • Poor Sleep Pain Pain • Cognitive (>3 months) (>3 months) Problems • Other Sx

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

ACR classification criteria – Wolfe F, et al, Arthritis Rheum 1990 ACR classification criteria – Wolfe F, et al, Arthritis Rheum 1990 ACR diagnostic criteria – Wolfe F, et al, Arthritis Rheum 2010 ACR diagnostic criteria – Wolfe F, et al, Arthritis Rheum 2010

Tender Point Exam

ACR fibromyalgia classification criteria: pain at 11 of 18 points Fibromyalgia is present when: WPI score ≥7 WPI 3-6 or SS score ≥5 SS score ≥9

Clauw D, 2014, JAMA, PMID 24737367 Wolfe F et al, J Rheumatol 2011, PMID 24737367

15 /Migraine Diagnosis of Fibromyalgia Chronic eye TMJ disorder irritation/dryness

Irritable bowel Atypical chest syndrome pain • Fatigue Widespread • Poor Sleep Polyuria/frequency Fibromyalgia Dypsnea Pain • Cognitive (“interstitial cystitis”) (>3 months) Problems Dermatitis/ • Other Sx Dyspareunia/ pruritis vulvodynia Multiple other Muscle Cramps sensitivities disease

Chronic fatigue Paresthesia

ACR classification criteria – Wolfe F, et al, Arthritis Rheum 1990 modified from Aaron LA, et al. Arch Int Med. 2000;160:221-227. ACR diagnostic criteria – Wolfe F, et al, Arthritis Rheum 2010

Work-up Tip offs that suggest your patient may have fibromyalgia: • Laboratory Tests • X-rays of affected • Multiple different pain complains – ESR, CRP areas to investigate – Eg. Back pain, knee pain, neck pain – CBC w/ diff joint damage • Activity has consequences – Comprehensive – Eg. If I do ___, I will be in bed for 2 days Metabolic Panel (inc. • No position relieves pain symptoms LFTs, Calcium) • Biopsy tissues that appear affected (ie. • The person has odd complaints – – Fasting Glucose skin rashes) “my body feels like it has tinnitus” – Hepatitis B & C • You walk into the room and the lights – TSH, free T4 are turned down (). – Vitamin D 25-OH • EMG for persistent • “Pan-positive review of systems” – CPK (if appropriate) neurologic • You feel exhausted after the – ANA (rarely) symptoms interview

16 Costs Related to a Diagnose FMS Summary and Failure to Diagnose FMS

• Don’t diagnose patients <50 y.o. with PMR • Recognize inflammatory back pain • Aspirate swollen joints • Recognize calcific tendinitis • Recognize symptoms of fibromyalgia

Annemans et al, Arthritis Rheum 2008; 58:895

Thanks! Treatment of Fibromyalgia

A multidisciplinary approach

Medicine Body

Mind

17 Medications to Treat Fibromyalgia Non-Pharmacologic Therapies for Fibromyalgia

Modest – Strong Evidence for No Evidence for Efficacy Moderate Evidence for Efficacy Very Weak Evidence Efficacy in Fibromyalgia • NSAIDs (Yunus MB, at al, J Rheum 1989) (Goldenberg DL, et al, Arthritis Rheum 1986) • Aerobic Exercise (efficacy not • Chiropractic therapy • Tricyclic antidepressants • (Clark S, et al, J Rheumatol 1985) maintained if exercise stops) • Manual & Massage Therapy – amitriptyline (Elavil) 25-50mg qHS • Benzodiazepenes (Quijada-Carrera J, et al, Pain • Cognitive Behavioral Therapy • Electrotherapy • Dual-reuptake inhibitors (SNRIs) 1996) • Ultrasound – milnacipran (Savella) • Opioids (Sorensen J, et al, Scand J Rheumatol 1995) • Patient Education – duloxetine (Cymbalta) • Group Therapy – venlafaxine (Effexor) • Serotonin reuptake inhibitors (SSRIs) – Fluoxetine (Prozac) 20-80mg/d Weak Evidence for Efficacy No Evidence for Efficacy • gabapentin (Neurontin) • Strength training • Trigger point injection • pregabalin (Lyrica) • Acupuncture • cyclobenzaprine (Flexeril) • Hypnotherapy 10-30mg at bedtime • Biofeedback • tramadol 200-300mg/d • Balneotherapy Goldenberg DL, Burckhardt C, Crofford L, JAMA 2004 Goldenberg DL, Burckhardt C, Crofford L, JAMA 2004 Carville SF, et al, EULAR recommendations, Ann Rheum Dis 2008 Carville SF, et al, EULAR recommendations, Ann Rheum Dis 2008

• Hands – Identifying the DIP, PIP, MCP – Pitting of the fingernails – vs. Dactylitis – Identifying deformities • Heberdon’s & Bouchard’s nodes • Finger joint subluxation from OA • Subluxation of MCPs from RA A Rheumatologist’s Approach to the – – stenosing tenosynovitis Musculoskeletal Examination • Wrists – Wrist vs. CMC – DeQuervain’s • Elbow – – Lateral Epicondylitis – Synovitis of the joint • Foot – Locations for gout including 1 st MTP bursa – Achilles – Talonavicular arthritis – Hammer toe deformities

18 Pattern of Joint Involvement Pattern of Joint Involvement

All of the following All of the following conditions commonly involve conditions often involve MCP joints, wrists and knees EXCEPT: the MCP joints and A. Osteoarthritis wrists EXCEPT: B. Rheumatoid Arthritis C. SLE A. Osteoarthritis D. Parvovirus B19 induced arthritis B. Rheumatoid Arthritis 0% 0% 0% 0% C. SLE • SLE typically has extra-articular D. Parvovirus B19 arthritis t i s s r i SLE t h r i t i s r t h r t h r i t i A a manifestations (rashes) i d 1 9 B O s t e o a r a t o m r u s • Viral Arthritis typically resolves in <6 weeks R h e u r v o v i P a 10 although Chikungunya can last longer

Osteoarthritis

• Osteoarthritis of the hands is common and rheumatology consultation is usually not necessary. It can be managed with: – Acetaminophen 1 gm three times a day – NSAIDs if normal kidney function and no risk factors for gastritis – Topical Diclofenac 1% gel – Hand Therapy – Paraffin baths

http://www.mridoc.com/mskatlas/Arthritis/Arthritis_Common_Joints_Involved/ See American College of Rheumatology Guidelines - www.rheumatology.org

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