Update in Rheumatology

1
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

2
Educational Objectives 1. To be aware of
advances in diagnosis of rheumatic diseases 2.
To understand the application of new
antirheumatic therapies
3

• 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)

4
Joint Swelling What is the Cause?
5
Major Rheumatic Diseases

• Osteoarthritis
• Rheumatoid Arthritis
• Systemic Lupus erythematosus
• Systemic Sclerosis
• Spondyloarthropathies

• Poly-Dermatomyositis
• Crystal - Induced Arthritis
• Septic Arthritis
• Vasculitis

6
Joint Swelling - Synovial EffusionArthrocentesis
and Injection therapy
7
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.

8
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.

9
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 gt90 patients prefer local anesthesia
  with lidocaine for IA procedures
• Park KS et alShould local anesthesia be used for
  arthrocentesis and joint injections? Rheumatol
  Int. 2009 Apr29(6)721-3.

10
Anesthesia and Arthrocentesis Pain Scores
96
8.9 0.9
4.8 1.2
4
96 of Patients Prefer Anesthesia
Arthrocentesis without Anesthesia Pain Score
Arthrocentesis with Anesthesia Pain Score
From Park K et al 2007, J Rheumatol.
200633771-8
11
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
  Sep36(9)1892-902

12
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
13
Mark Anatomy with Pen and Choose Approach
Patella
Lateral Suprapatellar Bursa
Anteriolateral Inferiopatellar Approach
Patellar Tendon
Tibial Plateau
14
Antisepsis with Chlorhexidine
15
22 g 1.5 inch Needle - Repetitively Aspirate and
Inject Lidocaine, Adjust Needle Position As
Necessary
Aspiration
Injection
16
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
17
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
18
Attach IA Therapy Syringe and Inject
Inject IA Therapy
1)Twist Syringe on Needle2) or Rotate Needle
on Syringe
19
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 20066450-5.
• Safety devices can be used effectively for IA
  procedures and reduce needlesticks
• Moorjani GR et al Arthritis Rheum. 2008 Jun
  2458(7)1907-1914.

20
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
  2458(7)1907-1914.

21
Anti-Needlestick Devices

• Combination with patient safety devices RPD
  syringe with Shielded needle
• Moorjani GR et al Arthritis Rheum. 2008 Jun
  2458(7)1907-1914.

22
Patient Safety Devices - RPD Syringe
Michael AA et al. Device effect on local
injection therapy of osteoarthritis A
randomized controlled trial. Arthritis Rheum
2008.
23
US-Image Guidance Portable US Unit with
Multiple Imaging and Doppler Capabilities
24
Ultrasound-Directed Procedures
US - IA Injection with Assistant
US - IA Injection with One-hand
25
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 rate of IA injections
• Sibbitt WL Jr et al J Rheumatol. 2009
  Sep36(9)1892-902

26
Ultrasound Guidance for IA Injections
Sibbitt WL Jr et al J Rheumatol. 2009
Sep36(9)1892-902
27
Ultrasound Guidance for IA Injections
Sibbitt WL Jr et al J Rheumatol. 2009
Sep36(9)1892-902
28
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
  Sep36(9)1892-902

29
Osteoarthritis A Progressive Disease
30
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.
2000431905-1915
31
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

32
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

33
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(1sodium 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

34
Effect of IA Hyaluronate (Hyaluronan)
Hyaluronan
35
Injection of Hyaluronate (Hyaluronan)
One-Needle Two Syringe Technique
36
(No Transcript)
37
(No Transcript)
38
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
39
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

40
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

41
Anti-TNF Drugs
TNF-MTX
TNF
Percent Responding
MTX
Placebo
Months
42
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.
• lt 60 kg 500 mg, 60-100 kg 750 mg and weighing
  gt100 kg 1000 mg.
• 50.4 response (ACR) rate at 6 months (19.5
  placebo)
• Infections, headache, flu-like symptoms, infusion
  reactions, nausea.

43
Orencia (abatacept) anti-T cell agent
44
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.

45
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.

46
Chronic or Tophaceous Gout
47
Acute Gout
48
Diagnostic Tests for Gout

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

49
(No Transcript)
50
Hyperuricemia Syndromes

• Stage 1 -Asymptomatic hyperuricemia (uric acid lt
  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

51
Annual Gout Prevalence Among All Enrollees by Age
Group 1990-1999
J Rheumatol Aug 2004
52
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

53
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.

54
Updated Therapy for Chronic or Tophaceous Gout

• 1) Life-long treatment for tophaceous or frequent
  gout, erosions on radiographs, extreme
  hyeruricemia (uric acid gt 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 gt2 mg/dl or GFRlt
  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 200450937-43

55
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.
200348(9)S529. 2. Khosravan et al. Arthritis
Rheum. 200450(9)S806. 3. Becker et al.
Arthritis Rheum. 200450(9)S803.
56
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