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Update in Rheumatology. Wilmer L. Sibbitt, Jr., M.D. 1 1 Departments of Internal Medicine, Rheumatology and Neurology University of New Mexico Health Sciences Center , Albuquerque, NM, USA. Educational Objectives: 1. To be aware of advances in diagnosis of rheumatic diseases

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update in rheumatology

Update in Rheumatology

Wilmer L. Sibbitt, Jr., M.D. 1

1Departments of Internal Medicine, Rheumatology and Neurology

University of New Mexico Health Sciences Center , Albuquerque, NM, USA

slide2

Educational Objectives:

1. To be aware of advances in diagnosis of rheumatic diseases

2. To understand the application of new antirheumatic therapies

slide3

Disclosure

  • Wilmer L. Sibbitt, Jr., MD is:
  • an employee of the University of New Mexico Health Sciences Center
  • funded in part by research grants from the National Institutes of Health and Ferring Pharmaceuticals, Inc
  • an expert consultant for

- Becton Dickinson, Inc.,

- AVANCA Medical Devices, Inc.,

- Meditech Dupross, Inc.,

- Ferring Pharmaceuticals, Inc.

- Avasca Medical, Inc.

- IMS Expert Services, Inc.,

  • Co-founder of AVANCA Medical Devices, Inc, (acquired by Global Medical Solutions, Inc) and Avasca Medical, Inc. (IP acquired by Abbott Interventional)
slide5

Major Rheumatic Diseases

  • Osteoarthritis
  • Rheumatoid Arthritis
  • Systemic Lupus erythematosus
  • Systemic Sclerosis
  • Spondyloarthropathies
  • Poly-Dermatomyositis
  • Crystal - Induced Arthritis
  • Septic Arthritis
  • Vasculitis
slide7

Reasons to Perform Arthrocentesis

  • Noninflammatory - a non-inflammatory effusion can only be confirmed by arthrocentesis.
  • Crystal-induced arthritis - can only be diagnosed definitely by arthrocentesis.
  • Hemorrhagic Effusion - can only be excluded by arthrocentesis.
  • Infectious - Infectious arthritis and the causative organism can only be diagnosed definitely with arthrocentesis.
  • Painful Effusion - A painful effusion is most easily decompressed with arthrocentesis.
  • Injection therapy - The effusion should be decompressed and infection excluded prior to intraarticular injection therapy.
slide8

Update on Arthrocentesis and Intraarticular Therapy

  • Anesthesia - Patients prefer local anesthesia.
  • One needle two syringe technique - permits anesthesia, dilation of joint space, arthrocentesis, and IA injection with one needle stick.
  • Use of antineedlestick safety devices - required by Joint Commission; reduces risk to provider
  • Use of safety aspiration syringes - reduces pain and complications and improves IA outcome for patients.
  • Use of sonographic image guidance - reduces pain and complications and improves IA outcome for patients.
  • Frequency of intraarticular corticosteroid injections - IA injections can be up q 3 months.
  • Intraarticular Hyaluronate - New IA HA preparations, now 1 injection preparations.
slide9

Arthrocentesis - Anesthesia Options

  • Pre-procedure local anesthesia with lidocaine.
  • Pre-procedure local anesthesia with topical ethyl chloride or other coolants.
  • General anesthesia - most common in children.
  • No pre-procedure local anesthesia.
  • Marcaine (bipuvicaine) is not a good immediate agent for local anesthesia and in continuous intraarticular anesthesia in orthopaedics has been associated with cartilage injury.
  • New Data: >90% patients prefer local anesthesia with lidocaine for IA procedures

Park KS et al:Should local anesthesia be used for arthrocentesis and joint injections? Rheumatol Int. 2009 Apr;29(6):721-3.

slide10

Anesthesia and Arthrocentesis: Pain Scores

8.9± 0.9

96%

4.8± 1.2

4%

Arthrocentesis without

Anesthesia Pain Score

Arthrocentesis with

Anesthesia Pain Score

96% of Patients

Prefer Anesthesia

From: Park K et al 2007, J Rheumatol. 2006;33:771-8

slide11

One Needle Two Syringe Technique

  • Technique developed by interventional radiologists
  • One needle (21 or 22 gauge for arthrocentesis, 22 or 25 gauge for dry joint or small joints, 0.5 inch for small joints, 1-1.5 inch for intermediate joints, 1.5 to 2.0 inch for large joints, 6-9 mm spinal needle for hip)
  • 1-3 ml syringe for small joints, 3-10 ml for larger joints, 5-20 ml for effusions.
  • Chlorhexidine antisepsis.
  • Place 1 to 5 mls 1% lidocaine into syringe.
  • Be certain needle can be removed with finger tips
  • Advance needle while alternatively aspirating and injecting.
  • In dry joint, dilate joint space with lidocaine
  • After dilating joint space or obtaining synovial fluid, rotate syringe off of needle, place treatment syringe on, aspirate, and then inject.

Sibbitt WL Jr et al J Rheumatol. 2009 Sep;36(9):1892-902

slide12

Select an Appropriate Size Syringe

  • 1 ml - IP, MCP
  • 3 ml - IP, MCP, Wrist, Ankle
  • 5 ml - Wrist, Ankle, Shoulder, Knee
  • 10 ml - Knee
  • 20 ml - Knee, especially large effusions.

1 ml

3 ml

5 ml

10 ml

20 ml

slide13

Mark Anatomy with Pen and Choose Approach

Patella

Lateral

Suprapatellar

Bursa

Anteriolateral

Inferiopatellar

Approach

Patellar

Tendon

Tibial

Plateau

slide15

22 g 1.5 inch Needle - Repetitively Aspirate and Inject Lidocaine, Adjust Needle Position As Necessary

Aspiration

Injection

slide16

Joint Space Encountered when Synovial Fluid is Returned or Needle Touches Joint Cartilage

Synovial Fluid Returned

After Touching Cartilage, Easy Injection of Lidocaine without Resistance

slide17

After Lidocaine Injection, Syringe Exchange is Performed

Needle in Intraarticular Position, Fluid in Hub

1)Twist RPD off of Needle 2) or Rotate Needle off of RPD

slide18

Attach IA Therapy Syringe and Inject

Inject IA Therapy

1)Twist Syringe on Needle2) or Rotate Needle on Syringe

slide19

Anti-Needlestick Devices

  • Needlestick Safety and Prevention Act, OSHA, and JCHAO mandate healthcare worker safety (HCW) and antineedlestick devices
  • 10-30 needlesticks/100,000 needles
  • High risk HCV, HBV, HIV, chronic disability
  • Safety devices reduce NS by 70%

Adams D et al J Hosp Infect 2006:64:50-5.

  • Safety devices can be used effectively for IA procedures and reduce needlesticks

Moorjani GR et al Arthritis Rheum. 2008 Jun 24;58(7):1907-1914.

slide20

Anti-Needlestick Devices

  • Retractable syringes: Procedur-SF, Integra, BakSnap, SafePro, InviroSnap, VanishPoint (VP) - Disadvantage premature activation, restriction of needle length to 1.5 in, splatter, and with VP fixed needle.
  • Shielded Needles: Eclipse, SafetyGlide, SureGuard, Magellan - Disadvantage restriction of needle length to 1.5 in, bulky
  • Shielded Syringes: Safety-Lok, Monoject Safety, DAS syringe - Disadvantage restriction of needle length to 1.5 in, bulky, somewhat awkward

Moorjani GR et al Arthritis Rheum. 2008 Jun 24;58(7):1907-1914.

slide21

Anti-Needlestick Devices

  • Combination with patient safety devices: RPD syringe with Shielded needle

Moorjani GR et al Arthritis Rheum. 2008 Jun 24;58(7):1907-1914.

slide22

100%

Conventional Syringe

Control Safety Syringe

Percent

Signi-

ficant

Pain

(VAPS≥5)

50%

0%

Baseline

Pain

(p>0.55)

Anesthesia

Pain

(p<0.001)

Pain at

6 months

(p=0.46)

Procedure

Pain

(p<0.001)

Pain at

2 weeks

(p<0.002)

Patient Safety Devices - RPD Syringe

Michael AA et al. Device effect on local injection therapy of osteoarthritis: A randomized controlled trial. Arthritis Rheum 2008.

slide23

US-Image Guidance

Portable US Unit with Multiple Imaging and Doppler Capabilities

slide24

Ultrasound-Directed Procedures

US - IA Injection

with Assistant

US - IA Injection

with One-hand

slide25

Summary: Safety Devices for IA

  • -safety devices mandated by Needlestick Safety and Prevention Act, OSHA, and JCHAO
  • - safety devices cost more than conventional needles and syringes($0.50 to $2.00 US)
  • - safety devices reduce needlesticks to HCW and injuries to patient
  • - reduce complications including hemorrhage
  • - improve arthrocentesis yield
  • - reduce needle trauma and is less painful.
  • - significantly improves responder rate and reduces non-responder rateof IA injections

Sibbitt WL Jr et al J Rheumatol. 2009 Sep;36(9):1892-902

slide26

Ultrasound Guidance for IA Injections

Sibbitt WL Jr et al J Rheumatol. 2009 Sep;36(9):1892-902

slide27

Ultrasound Guidance for IA Injections

Sibbitt WL Jr et al J Rheumatol. 2009 Sep;36(9):1892-902

slide28

Summary: US- Guidance for IA

  • US image guidance is increasingly used in rheumatology
  • - is more time-consuming and more costly
  • - cost-effectiveness is uncertain
  • - improves arthrocentesis success and yield
  • - permits more accurate placement.
  • - is less painful.
  • - significantly improves responder rate and reduces non-responder rate of IA injections

Sibbitt WL Jr et al J Rheumatol. 2009 Sep;36(9):1892-902

slide30

Updated Therapy for Osteoarthritis

  • Glucosamine or Glucosamine/Chondroitin supplements
  • Reduce injury to joint (weight loss, treat gout, etc).
  • Acetaminophen and analgesics
  • Conventional or COX-2 Inhibitor NSAIDS
  • IA injections with corticosteroids
  • IA injections with hyaluronic acid
  • Reconstructive surgery

American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the Medical Management of Osteoarthrits of the Hip and Knee, Arthritis & Rheumatism. 2000:43;1905-1915

slide31

Hyaluronate for Intraarticular Injections

  • First isolated by Palmer and Meyer from bovine eyes in 1934
  • Marketed for human use in the early 1980s using HA derived from rooster comb
  • Polysaccharide chain made of repeating Polysaccharide chain made of repeating disaccharide units of N-acetylglucosamine and glucuronic acid
  • Synthesized naturally by Type B synoviocytes
slide32

IA INJECTION OF HYALURONIC ACID

  • Usually Grade 1-3 OA
  • Failed local measures, acetaminophen, NSAIDS, and 1-2 corticosteroid injections, especially with ultrasound
  • Advantageous to avoid or delay total joint arthroplasty
  • No infection
  • Exclusion of confounding arthritides
  • No hypersensitivity to HA
  • Can afford cost $300 to $450 for HA
slide33

HYALURONIC ACID PREPARATIONS

  • Euflexxa(1% sodium hyaluronate) 3-injection series (one week apart), Bioengineered
  • Orthovisc(1% sodium hyaluronate) 3-injection series (one week apart), Bioengineered
  • Hyalgan(1%sodium hyaluronate) 3-5-injection series (one week apart),
  • Supartz(1% sodium hyaluronate) 3-5-injection series (one week apart),
  • Synvisc(HylanG-F 20) 3-injection series (one week apart), - Synvisc-One, 1 injection
slide35

Injection of Hyaluronate (Hyaluronan)

One-Needle Two Syringe Technique

slide38

Updated Therapy for RA

  • 1st-Low dose corticosteroids - short/long term
  • 1st -Methotrexate - long term
  • 2nd - Leflunomide - long term
  • 2nd - Anti-TNF Agents (anti-Tumor Necrosis Factor) - best overall therapy
  • 3rd - Kineret ® (anakinra) - IL-1 receptor
  • 3rd - Orencia ® (abatacept)- anti-T cell agent
  • 3rd - Rituxan® (Rituximab) – anti-B cell therapy
  • 1st-3rd - Corticosteroid joint injections
  • 4th - Reconstructive surgery

Reference: American College of Rheumatology 2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis Arthritis & Rheumatism. Vol. 59, No. 6, June 15, 2008, pp 762-784

methotrexate
Methotrexate
  • Obtain PPD, Chest X-ray, renal and hepatic tests, and exclude HCV before starting
  • Good long-term efficacy and tolerability
  • Slows radiographic measured erosions
  • Hi-risk in elderly and renal impaired patients
  • Chemical monitoring indicated
  • Hepatic biopsy rarely indicated
  • Be aware of pulmonary toxicity in first 4 months of therapy
anti tnf drugs
Anti-TNF Drugs
  • Enbrel® - entanerocept - SC - 50 mg/wk
  • Humira® - adalimumab - SC - 40 mg/q 2wks
  • Remicade® -infliximab - IV - 3-10mg/kg/4-8 wks
  • Cimzia® - certolizumab - SC - 400 mg/4 wks
  • Simponi® - golimumab - SC - 50-100 mg/4 weeks
anti tnf drugs41
Anti-TNF Drugs

TNF-MTX

TNF

Percent Responding

MTX

Placebo

Months

slide42

Orencia ® (abatacept) anti-T cell agent

  • Fully human soluble immunoglobulin fusion protein
  • Selective Co-stimulation Modulator
  • Interferes with CD80/86-CD28 interaction.
  • 30 min IV infusions at 0, 2, and then q 4 weeks.
  • < 60 kg 500 mg, 60-100 kg 750 mg and weighing >100 kg 1000 mg.
  • 50.4 % response (ACR) rate at 6 months (19.5% placebo)
  • Infections, headache, flu-like symptoms, infusion reactions, nausea.
slide44

Rituxan® (Rituximab)anti-B cell agent

  • depletes CD20+ B-cells
  • methylprednisolone 100 mg IV, then
  • two-1000 mg IV infusions at 0 and 2 weeks.
  • 51 % response rate at 6 months (14% placebo)
  • Infections, flu-like symptoms, infusion reactions, severe mucocutaneous reactions.
slide45

Warning with Biologic Anti-Rheumatic agents!

  • Active infection - TB, HCV, HCB should be excluded.
  • Biologic agents should not be given with any active infection.
  • If PPD +, must receive prophylactic therapy
  • Patients should receive non-live vaccines
  • Vaccinate for pneumococcus and influenza.
  • Infections should be promptly treated and agent withheld at least temporarily
  • Herpes Zoster (shingles) should be recognized and treated promptly.
  • Be aware of increased incidence of lymphoma.
slide48

Diagnostic Tests for Gout

  • Serum uric acid x several times
  • Athrocentesis for crystal examination
  • Exclusion of RA, SLE, infection, CPPD, Reiter’s syndrome
  • Hand and foot radiographs
  • CBC, Cr, uric acid, Ca, Electrolytes Hepatic enzymes, UA
  • 24 hr urine for creatinine and uric acid
slide50

Hyperuricemia Syndromes

  • Stage 1 -Asymptomatic hyperuricemia (uric acid < 7.0 mg/dl)
  • Stage 2 - Acute gouty arthritis (acute gout)
  • Late Stage 2 - Intercritical gout (frequently occuring acute gout)
  • Stage 3 - Tophaceous or chronic gout
  • Uric acid nephrolithiasis
  • Acute uric acid nephropathy
  • Chronic sodium urate nephropathy or interstitial nephritis
therapy for gout
Therapy for Gout
  • Acute: NSAIDS, Prednisone, IA Corticosteroids
  • Prophylaxis: Colchicine .5-.6 mg qd-bid
  • Chronic: Allopurinol 100-900 mg qd to keep uric acid below 6 mg/dl,
  • Febuxostat 40 to 80mg qd
  • Urocosuric agents less preferable.
  • Do not use high dose colchicine - toxic!
  • Do not use IV colchicine - may be fatal!
  • Avoid NSAIDs with renal insufficiency
updated therapy for acute gout
Updated Therapy for Acute Gout

1) High Dose Oral NSAIDS (if no history of PUD, hemorrhagic diathesis, anticoagulants, ASA sensitivity or renal insufficiency)

2) NO High Dose Oral Colchicine (toxic)

3) NO Intravenous Colchine (toxic and sometime fatal)

4) Short term high dose oral corticosteroids

5) Intraarticular injected corticosteroids

5) Continue Allopurinol, Febuxostat or uricosuric agents through attack.

updated therapy for chronic or tophaceous gout
Updated Therapy for Chronic or Tophaceous Gout

1) Life-long treatment for tophaceous or frequent gout, erosions on radiographs, extreme hyeruricemia (uric acid > 8.6 mg/dl), nephrolithiasis, or osteoarthritis in affected joints.

2) If normal renal function, start prophylactic colchicine 0.6 mg bid, and allopurinol at 100-300 mg qd, increase up to 600 to 900 mg qd based on uric acid

3) For renal impairment (Cr >2 mg/dl or GFR< 50ml/min), start cochicine at 0.6 mg qd and allopurinol 100 mg qd, but increase allopurinol based on serum acid level not GFR; if nephrologists do not permit allopurinol then febuxostat 40 mg per day.

4) No high dose or IV colchicine; discontinue after 6 months,

5) Avoid or limit daily NSAIDS unless no contraindications

6) Do not stop allopurinol, febuxostat, or uricosuric agents during acute gouty attack.

7) Goal is to radically reduce serum uric acid (4.0-5.9 mg/dl)

Reference: Quality of care indicators for gout management. Arthritis Rheum 2004;50:937-43

slide55

CH3

OH

O

H3C

N

N

N

CH3

NC

NH

N

S

CO2H

Febuxostat - Uloric®

Allopurinol

Febuxostat

  • A nonpurine, selective inhibitor of xanthine oxidase
  • FDA approved for treatment of gout
  • Current data support
    • Potent inhibition with significant urate reduction
    • Ability to administer in renal insufficiency1 and mild or moderate hepatic insufficiency with no dosage adjustments2
    • Safe, effective and well tolerated in limited data of allopurinol intolerant patients3

1. Swan et al. Arthritis Rheum. 2003;48(9):S529.

2. Khosravan et al. Arthritis Rheum. 2004;50(9):S806.

3. Becker et al. Arthritis Rheum. 2004;50(9):S803.

slide56

Febuxostat - Uloric®

  • Elimination both hepatic and renal.
  • Can use in subjects hypersensitive to allopurinol.
  • Dosing: Febuxostat 40mg to 80 mg by mouth per day
  • For renal insufficiency start 40 mg po qd
  • Laboratory testing: 2-4 weeks Uric acid, CBC, hepatic enzymes, Cr
  • Most common side effects: nausea (1.3%), arthralgias (1.1%), gout flare, rash (1.6%)
  • Do not use with or adjust dosage with drugs metabolized by xanthine oxidase - theophylline, mercaptopurine, and azathioprine