10/15/2018 R. Krishna Chaganti, MD, MS Associate Clinical - - PDF document

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• R. Krishna Chaganti, MD, MS

Associate Clinical Professor UCSF Division of Rheumatology Appleton, CW OA&C, 2017

Disease of the Whole Joint

 Cartilage  Bone  Meniscus  Soft Tissue

Structures

Felson, NEJM, 2006  Complicated by heterogeneity of populations and OA

disease

 Monozygotic twin studies (Spector et al., Rheumatology, 2009)  SNP analysis  IL1R antagonist gene variants

• Higher risk of knee OA progression by SNP analysis (X. Wu et al.,

OA&C, 2013)  GWAS analyses  Hand OA: ALDH1A2 gene variants (Styrkasdottir, 2014)

• UK population, (Zeggini et al., Lancet 2012)

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 Residents of 4 districts of Beijing > 60 years old,

randomly recruited from general public

• Lower prevalence of radiographic hip OA in subjects

living in Beijing with age-matched controls (SOF, NHANEs).

• Higher prevalence of knee OA in older Chinese

women than in Framingham cohort (genetics, physical activity?)

• Lower prevalence of hand OA (CMC, MCP and PIP,

DIP) compared to Caucasians (Framingham study)

• Higher incidence in thumb IP and 2nd and 3rd PIP (OR

1.4-1.5)  Osteophytes  JSN  Subchondral

sclerosis

 Subchondral cysts  Joint deformity  Standing knee  Sunrise views  Pattern of OA  OA in unusual joints

• Elbow, Glenohumeral joint, MCPs

 Joint Structural Defects

• Congenital or Acquired

 Hereditary Connective Tissue Defects

• Some with defined gene mutations

 Metabolic Diseases

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• Legg-Calve-Perthes,

congenital hip dislocation, SCFE

• Femoroacetabular

impingement

• Hypermobility syndrome
• Leg-length discrepancy
• Thoracic scoliosis
• Knee DJD
• Trauma
• Distant
• Surgical (Menisectomy)
• Secondary to

inflammatory disease (RA)  Avascular necrosis  Neuropathic

(Charcot’s joint)

 Syrinx (glenohumeral)  Metabolic:

• CPPD, Ochronosis,

Hemochromatosis, Wilson’s, Gaucher’s  56 year old woman with hand pain  Noticed “bumps” on her fingers for several

years

 Increased pain and swelling over DIP

joints over past year

 Improved with ibuprofen

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(Banks, SE, Clin Rheumatology; 2010)

 What is her diagnosis?  A) Osteoarthritis  B) Psoriatic Arthritis  C) Erosive Osteoarthritis

(Banks, SE, Clin Rheumatology; 2010)

DIP, PIP involvement, central erosive changes Erosive OA Psoriatic Arthritis Central Erosions Yes Sometimes “Fluffy” Periosteal Bone formation No Yes Synovitis Usually Yes Heberden’s Nodes Yes (not specific) No Periarticular erosions No Yes AM stiffness, nighttime waking Sometimes Yes Ankylosis Yes Yes PIP involvement Yes Yes

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 T DIP CMC PIP

• Increases with age, especially postmenopausal women
• Women > Men
• Heberden’s and Bouchard’s nodesgenetic predisposition

RECOMMEND

• Topical capsaicin
• Topical NSAIDs
• Oral NSAIDs
• Tramadol
• >75 years old

Topical NSAIDs more than oral DON’T RECOMMEND

 Intraarticular therapies  Opioid Analgesics

 Conditional

• Splints

!

• ACR and OARSI guideline recommendations
• Mainstay: Combination of pharmacologic

and non-pharmacologic therapy

• Exercise
• Weight Loss
• Walking
• Tai Chi
• Accupuncture

Hochberg MC, et al., Arthritis Care Res 2012

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 Corrective Devices

• Shift the weight-bearing

axis towards the center of the affected varus knee towards Neutral alignment

• Directly Unload Medial

Knee

• Unloader Braces
• Lateral Wedges
• Canes (Contralateral side)
• Flexible Shoes

Hochberg MC, et al. Arthritis Care Res 2012, PMID 22563589 www.rheumatology.org

Recommendations are similar for hip osteoarthritis except no role for topical agents in hip OA Use Acetaminophen first Duloxetine is a last option

!

 Boswellia  Turmeric  Cat’s claw  Avocado-soybean unsaponifiables (ASU)  No known diet that halts OA  Resources:

• Osher Centers for Integrative Medicine
• NIH National Center for Complementary and Integrative Health
• Memorial Sloan Kettering herbal references:

https://www.mskcc.org/cancer-care/diagnosis- treatment/symptom-management/integrative-medicine/herbs

‐May be of benefit ‐Risk is unclear

Most studies indicate no significant benefit in:

 Pain  Function  Joint Structure

GAIT Study (Clegg DO et al., NEJM, 2006)

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Cochrane Meta- analysis

 Less pain at 1-4

weeks

 Effect decreases

• ver time

 No effect after 6

mo.

 Adverse effects do

not seem to be a problem Self reported pain assessed by Knee Injury and

Henricken M, et al. JAMA Intern Med 2015, PMID 25822572

Peter J, et al. Cochrane Database Syst Rev

• 2015. PMID 26490760
• Significant cartilage thickness change in IA Triamcinolone

group v. Saline Clinical significance?

MacAlindon et al., JAMA, 2017

Viscosupplementation with hyaluronic acid (HA) - a natural constituent of joint fluid - to restore the viscoelasticity of synovial fluid

• Debatable efficacy based on data
• Chevalier et al., Ann Rheum Dis 2010
• Meta-analyses also conflicting: 76

trials of Intra-articular injections of HA (IA-HA) for knee OA (Campbell et al, OA &C, 2007)

 Slow acting – benefits appreciated

at 5-13 weeks post injection

 Few adverse events reported: acute

reaction of inflammation and synovitis

Bellamy N, et al. Cochrane Database Syst Rev, 2006  PRPP (TGF-beta, PDF-GF,VEGF)  Bone Marrow Matrix  Adipose MSC  Autologous BM Aspirate  Allogeneic MSCs  Umbilical cord derived MSCs  Wide variation in methodology, no large standardized

clinical trial data to support use at this time

 More standardized methodology and outcome

measures needed

 Strong Marketing Drives the Use

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 65 yo Korean man with DM and stage 4 CKD

presents with 2 days of left foot pain and swelling

 Pain is severe and he is unable to ambulate  No antecedent trauma  Labs: WBC 12K, Cr 3.7, BG 200, uric acid

9

 Synovial fluid: WBC 50,000 (90% PMNs),

gram stain negative

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 What treatment do you recommend?

• A. Naproxen 500 mg PO BID
• B. Colchicine 1.2 mg PO, followed by 0.6 mg

every hour x 3

• C. Prednisone 40 mg PO daily
• D. Intra-articular injection of triamcinolone 40

mg into left ankle

• E. I really don’t like any of these options

 What dose of prednisone do you start?  How long do you treat for?  Do you need to taper?  Your patient is treated with 40 mg of

prednisone tapered by 10 mg every 2-3 days with complete relief of his symptoms

 Are there other options for treatment of

acute gout?

36

100 mg SQ daily x 3 days

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 He returns to your office for follow up. His

flare has resolved. His serum uric acid is 10.

 He wants to know what the likelihood of

having another flare is.

37 38

JRheum Mar 2017, 44 (3) 3  What do you do now?

• A. Start allopurinol 300 mg PO daily
• B. Start febuxostat 80 mg PO daily
• C. Start allopurinol 50 mg PO daily
• D. Obtain further lab testing

 Associated with increased risk for allopurinol

hypersensitivity reaction

• Risk is 0.1-0.4% in general population
• OR in one Thai series 348.33 (95% CI 19.15 – 6336.88)

 Allopurinol is contraindicated in patients who are

carriers for this allele

 Most commonly found in patients of Korean, Han

Chinese, or Thai descent (6-12%)

 ACR recommends genetic testing prior to allopurinol

use in Korean patients with stage 3 CKD or worse, and all patients of Han Chinese or Thai descent

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 Increased risk of allopurinol

hypersensitivity reaction

 Starting dose of 50 mg/d in patients with

CKD stage 4 or worse

 Can uptitrate as needed to achieve uric

acid goal

 Allopurinol is not nephrotoxic!  Febuxostat is now generic  Because patient is Korean and has stage 4

CKD, you check for HLAB*5801, which returns negative

 You start allopurinol 50 mg/d and colchicine

0.6 mg QOD

 Labs 2 weeks later: CBC and LFTs are

normal, uric acid 8

 Continue to slowly titrate allopurinol over 3

months to 300 mg/d

 Uric acid is 6.4  What do you do now?

• A. Continue allopurinol 300 mg/d
• B. Increase allopurinol to 400 mg/d
• C. Switch patient to febuxostat 40 mg/d
• D. Stop colchicine

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 Goal uric acid is <= 6 mg/dl  If tophaceous or erosive disease, goal is <=

5 mg/dl

 ACP Gout CPG 2017: “Evidence was

insufficient to conclude whether the benefits

• f escalating urate-lowering therapy to reach

a serum urate target (“treat to target”)

• utweigh the harms associated with repeated

monitoring and medication escalation.”

 Your patient asks you if there any non-

medical therapies he can try to lower his uric acid level.

 What do you recommend?

• A. Taking cherry extract
• B. Decreasing his food intake and increasing

his physical activity to lose weight

• C. Increasing his intake of low-fat dairy

products

• D. Stop drinking sugar-sweetened drinks

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 His dermatologist recommends starting

azathioprine for treatment of bullous

• pemphigus. What is he at increased risk

for?

• A. Cytopenias
• B. Allopurinol hypersensitivity reaction
• C. More frequent gout flares
• D. Renal dysfunction

Allopuri nol/Feb uxostat  If you are unsure about the diagnosis  If you cannot reach the target uric acid

goal with usual therapy

 If you feel uncomfortable with medication

management in the setting of comorbidities

 Acute gout rx: NSAIDs, systemic steroids, intra-

articular steroids, (anakinra)

 Chronic gout rx: start with low-dose allopurinol

(50-100 mg) and titrate slowly, especially in patients with renal insufficiency

 HLAB*5801 testing in Chinese, Thai, and Korean

patients

 Use flare prophylaxis when starting and

increasing allopurinol

 Uric acid goal <6 or <5 if tophi/erosions

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Acute or subacute attacks that mimic gout  Osteoarthritis

• Chondrocalcinosis

 Acute synovitis presentation

• “pseudogout”

 Chronic synovitis presentation

• “pseudoRA”
• 2nd and 3rd MCPs, wrists,

elbows,glenohumeral and ankles

• Low titer RF 10-30% of patients

 Age  Hemochromatosis  Hypomagnesemia  Hypophosphatasia  Hyperparathyroidism  Joint trauma

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 Crown dens

 Verify CPPD—aspiration to rule out infection, verify

presence of intracellular CPPD crystals

 Acute flare:

• NSAIDs (naproxen 500 BID)
• Colchicine 0.6 mg daily
• Glucocorticoids

 Refractory disease:

• Colchicine prophylaxis
• Methotrexate (?)

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 Don Ng  Sarah Goglin