dr. Indarwati Setyaningsih,Sp.

S(K)
Consultant Neurologist
Department of Neurology
RSUP Dr.Sardjito
 Introduction..
 Causes include various self-limited illness
and disabling and life-threatening.
 Is it Arthritis or Arthralgia?
 Musculoskeletal emergencies (infection,
sepsis, compartment syndrome…).
 History.. Age
 <30= SLE, Ankylosis spodylitis, Reactive
Arthritis.
 30-50= RA, Systemic sclerosis, Gout.
 >50= OA, Pseudogout, Polymyalgia
Rheumatica
 Any Age group= Psoriatic arthritis,
Enteropathic arthritis
 History.. Sex
 >Female:
 SLE, RA, OA, Systemic sclerosis, Ankylosis
spodylitis, Polymyalgia Rheumatica.
 Male=Female:
 Psoriatic arthritis, Enteropathic arthritis
Pseudogout.
 >Male:
 Gout, Reactive Arthritis.
 History.. Sites
 Site:
 Symmetrical= RA, SLE, Systemic sclerosis
 Asymmetrical=OA
 Large joints=OA
 DIP (Distal Interphalangeal) Joint= OA, Psoriatic
arthritis
 MCP (Metacarpophalangeal), PIP( Proximal
Interphalangeal) = RA, SLE
 1st MTP (Metatarsophalangeal)= Gout, OA
 Spine= OA, Ankylosis spodylitis, Psoriatic arthritis,
Reactive arthritis
 History.. Sites
 Pain character:
 Aggravated by motion= Mechanical
 Relieved by motion= Inflammatory.
 Duration:
 <6 wks= viral arthritis, systemic rheumatic diseases
 >6 wks=systemic rheumatic diseases
 Associated Signs:
 Morning stiffness: >1hr= RA, Inflammatory
>30 min= OA
 History.. Sites
 Associated Simptoms:
 Multi-system involvement= Systemic
rheumatic diseases.
 Past Medical history:
 Trauma, fracture, surgical procedures…
 Medication list:
 Drug induced lupus.
 Diuretics.
 Physical Examination
 Joint:
 Soft tissue swelling, warm, effusion…=
Inflammation.
 Inflammation signs extended= septic arthritis,
crystal induced arthritis, fracture.
 Passive motion (N), active(↓↓)= bursitis, tendinitis,
muscle injury.
 Passive motion (↓↓), active(↓↓)= Synovitis
 Physical Examination
 General Examination:
 parotid enlargement, oral ulceration, heart
murmurs, pericardial or pleural friction rubs,
crackle…= systemic disease.
 Fever= infection, reactive arthritis, RA, SLE, Crystal
induced arthritis…
 Subcutaneous nodules= RA, RHD, Gout (tophi)
 Skin manifestations= psoriasis, RA, SLE…
 Eye disease (keratoconjunctivitis sicca, uveitis.
Conjunctivitis, episcleritis…)
 Laboratory Studies..
 Basic: Complete Blood Count, Urinalysis,Renal
Function test , Liver Function Test
 Acute phase reactant: ESR, CRP.
 Antibody tests:
 ANA= SLE
 Anti-dsDNA= SLE
 Anti-native DNA,= SLE
 RF= RA
 Anti-CCP antibody=RA
 Laboratory Studies..
 Uric acid concentration= Gout
 Synovial fluid analysis= infection, crystal
induced arthritis, inflammatory..
 Hepatitis B and C
 Parvovirus serology
 Rheumatoid Factor..
 Rheumatoid Arthritis
 Connective tissue diseases
 Viral infection
 Leishmaniasis
 Leprosy
 Tuberculosis
 Sarcoidosis
 Liver diseases
 Subacute bacterial endocarditis
Imaging Studies..
 X-ray:
 RA
 Chronic Gout
 OA
 Ankylosing spondylosis.
 MRI:
 Ankylosing spondylosis.
Normal Joint..
 Osteoarthritis
 Articular cartilage failure induced by a complex
interplay of genetic, metabolic, biochemical, and
biomechanical factors
 With secondary components of inflammation
 Initiating mechanism is damage to normal
articular cartilage by physical forces (macrotrauma
or repeated microtrauma)
 Not necessarily normal consequence of aging
 Risk Factors
 Age
 Female versus male sex
 Obesity
 Lack of osteoporosis
 Occupation
 Sports activities
 Previous injury
 Muscle weakness
 Proprioceptive deficits
 Genetic elements
 Clinical Features
 Age of Onset > 40 years
 Commonly Affected Joints
 Cervical and lumbar spine
 First carpometacarpal joint
 Proximal interphalangeal joint
 Distal interphalangeal joint
 Hip
 Knee
 Subtalar joint
 First metarsophalangeal joint
 Clinical Diagnosis
 Symptoms
 Pain
 Stiffness
 Gelling

 Physical examination
 Crepitus
 Bony enlargement
 Decreased range of motion
 Malalignment
 Tenderness to palpation

 The more features, the more likely the diagnosis

 Radiographic Features

Joint space narrowing

Subchondral sclerosis
Marginal osteophytes
Subchondral cyst
 Joint Space Narrowing
OA typically asymmetrical

Paget’s disease
 Subchondral Sclerosis
 Increased bone density or thickening in the
subchondral layer
 Osteophytes
 Bone spurs
 Subchondral Cysts
 Fluid-filled sacs in subchondral bone
 OA of the Knee: Classic
Criteria
1. Greater than 50 years of age
2. Morning stiffness for less than 30 minutes
3. Crepitus on active motion of the knee
4. Bony tenderness
5. Bony enlargement
6. No palpable warmth

 3 of 6 criteria give sensitivity of 95% and

specificity of 69%
 OA of the Knee: Addition of X-
rays

 ACR Criteria of:

1. knee pain
2. radiographic evidence of osteophytes
3. one of three additional findings:
 age greater than 50 years of age
 morning stiffness of less than 30 minutes
 crepitus

 Sensitivity and specificity for OA of 91 and 86%

Hand Osteoarthritis
 Diagnosis by hand pain
 Plus at least three of the following four features:
1. Hard tissue enlargement of 2 or more of 10 selected
joints.
 The 10 selected joints are the second and third distal
interphalangeal (DIP) joints, the second and third proximal
interphalangeal (PIP) joints, and the first carpometacarpal
(CMC) of both hands
2. Hard enlargement of two or more DIP (Distal
Interphalangeal) joints
3. Fewer than three swollen metacarpophalangeal (MCP)
joints
4. Deformity of at least 1 of the 10 selected joints

 Sensitivity and Specificity for hand OA of 94 and 87%

Hip Osteoarthritis Diagnosis
 Use history, physical, laboratory, and radiographic
features (ACR)
 Hip Pain, plus at least two of the following three
features:
1. ESR of less than 20 mm/h
2. Radiographic osteophytes
3. Joint space narrowing on radiography
 Sensitivity of 89 percent and a specificity of 91 percent
 Typical OA work-up
 History
 Physical Examination
 Consider following (especially if OA of knees or
hips)
 Erythrocyte sedimentation rate (ESR)
 Rheumatoid factor titers
 Evaluation of synovial fluid
 Radiographic study of affected joints
 Goals of Treatment
 Control pain and swelling
 Minimize disability
 Improve the quality of life
 Prevent progression
 Education
 Chronic Condition and Management
 Non-pharmacologic
Treatment
 Weight Loss
 Ten-pound weight loss over 10 years decreased the
odds for developing knee OA by 50%
 Even a modest amount of weight loss may be
beneficial
 Rest
 Short period of time, typically 12-24 hours
 Prolonged rest can lead to muscle atrophy and
decreased joint mobility
 Non-pharmacological
Treatment
 Physical Therapy
 “Manual therapy" may be more beneficial than
exercise programs that focus on muscle
strengthening, endurance training, and improved
coordination
 May be more beneficial in those with mild OA
 Ultrasound therapy may have some benefit based
on 2009 Cochrane Review
Non-pharmacologic Treatment
 Knee Braces/Shoe Inserts
 Cochrane reports a “sliver of benefit”
 73% taping for 3 weeks reported
improvement (elastic knee sleeve)
 Acupuncture
 Cochrane January 2010
 Very small improvements in pain and
physical function after 8 weeks and 26
weeks
 Non-pharmacological
Treatment
 Exercise – focus on low load
exercise
 Tai Chi
 Yoga
 Swimming
 Biking
 Walking
NSAIDs
 Tend to avoid for long-term use
 Rash and hypersensitivity reactions
 Abdominal pain and gastrointestinal bleeding
 Impairment of renal, hepatic, and bone marrow function, and
platelet aggregation
 Central nervous system dysfunction in the elderly
 Low dose ibuprofen (less than 1600 mg/day) may have less
serious GI toxicity
 Nonacetylated salicylates (salsalate, choline magnesium
trisalicylate), sulindac, and nabumetone appear to have less
renal toxicity
 Indomethacin should be avoided for long-term use in
patients with hip OA
 associated with accelerated joint destruction
 Acetaminophen
 Cochrane 2009 Review
 NSAIDs are superior to acetaminophen for
improving knee and hip pain in people with OA
 Treatment effect was modest
 Median trial duration was only six weeks
 In OA subjects with moderate-to-severe levels of
pain
 NSAIDs > Acetaminophen > Placebo
 NNT for Acetaminophen 4 to 16
 1000mg three to four times daily
Topical NSAIDs
 A 2004 meta-analysis included 13 trials involving almost
2000 patients
 Randomly assigned to topical NSAID, oral NSAID, or
placebo
 Significant short term (one to two weeks) efficacy for pain
relief and functional improvement when topical NSAIDs
were compared to placebo
 Effect was not apparent at three to four weeks
 Topical NSAIDs were generally inferior to oral NSAIDs
 However topical route was safer than oral use
 Topical Diflofenac (1% gel or patch)
COX-2 Inhibitors
 COX-2 inhibitors appear to be as effective NSAIDs
 Associated with less GI toxicity
 However increased risk of CV events
 Use of low dose ASA may negate the GI sparing
effects of COX-2 inhibitors
 Those who are receiving low dose aspirin and a
COX-2 selective agent may benefit from antiulcer
prophylaxis
Capsaicin
 Capsaicin Ointment 0.025% (qid) & 0.075% (bid)
 Principle ingredient of chili peppers (substance P)
 Love It!
 Tolerability: Medium
 50% experience burning which wanes
 50% decrease in pain, 25% with placebo
 Apply 2-4 times per day
Glucosamine
 Glucosamine Sulfate 1500mg po daily
 Supplement, typically not covered
 Cochrane 2009
 Rotta preparation glucosamine was superior to placebo
in the treatment of pain and functional impairment
 Non-Rotta preparation failed to show benefit
 Majority of trials that have evaluated the
effectiveness of glucosamine sulfate demonstrated
significant clinical benefits
 Glucosamine hydrochloride trials are scarce and
much less convincing
 Bottom-Line, most likely beneficial if Rotta brand
and Sulfate formulation, not HCL example : Bon
Vit
 Injections
 Corticosteroid
 Safety: High for short-term use, data on
frequency and degree of use is limited.
 Study of pt’s receiving 8 injections over 2
year period showed no ill effects in
comparison with pt’s receiving placebo.
 Hyaluronic Injections of
Knees
 Safety: High
 Tolerability: Medium. Small number pts get
flare up of symptoms.
 Efficacy: Low. Recent Meta-analyses and
reviews small clinical effect. 75% were
satisfied with treatment. Lasts 3-4 months.
 Narcotics for Refractory
Pain
 Vicodin/Oxycodone
 Safety: Medium
 Tolerability: Medium
 Constipation, somnolence, mental status changes
 Use of opiates indicated in those who are not
candidates for surgery and who continue to
have moderate to severe pain despite being on
NSAIDs or selective cyclooxygenase (COX)-2
inhibitors
Joint Replacement
 Surgical candidate?
 Often greater improvement in pain rather than
function
 Recovery can be strenuous and lengthy
 Infection rate 1%
 Low mortality 0.6% to 0.7%
 Complications include thrombo-embolic events 5%
Rheumatoid Arthritis
 Is a lifelong progressive disease that produces
significant morbidity, and premature mortality in
some

 50% have to stop work after 10y

Figure 2. RA of the hands in different stages of disease
 Epidemiology
 May present at any age

 Commonly, late child bearing age in females, and

6th-8th decade in males

 Affects 1% of population
 Pathology
 Symmetrical deforming polyarthropathy,
affecting the synovial membrane of peripheral
joints

 Has a genetic component.

 Presentation
 May have a fulminant onset, but commonly
insidious over weeks to months
 Classically small joints initially – Proximal
Interphalangeal, Metacarpophalangeal,
Metatarsophalangeal
 Pain, swelling, stiffness – especially early
morning
Rheumatoid Nodule
Stage I:
Acute: synovial thickening; confined to joint capsule
Stage II:
Persistent inflammation  pain, joint damage
Stage III:
Inflammation and damage limiting joint
function
Stage IV:
Permanent joint damage and deformity  disability
 Bloods
 Anaemia of chronic disease
 ESR^ + CRP ^ - acute phase reactants
 CRP is more specific than ESR
 Not always ^ in small joint dx
 RhF - positive in 50%

 Include LFT’s (Liver Function Test) pre-DMARD

use
 Radiology
 Xray hands (include wrists) and feet
 Loss of joint space
 Soft tissue swelling
 Erosions – partic look 5th Metacarpal &
Metatarsal & ulnar styloid, & scaphoid/trapezium
 Peri-articular osteoporosis
 Joint destruction
 Diagnosis
 Distribution of joint involvement
 Morning stiffness
 Active synovitis. Inflammation (swelling,
warmth, or both) on examination
 Symptoms for > 6 weeks
 RhF (Rheumatoid Factor), ESR, CRP
 Diagnosis (American College of
Rheumatology)
 Morning stiffness*
 Arthritis of 3 joint areas*
 Arthritis of hands*
 Symmetric arthritis*
 Sero positive
 Radiological changes
 * for greater than 6 weeks
 Treatment
 To relieve pain & inflammation

 Prevent joint destruction

 Preserve / improve function

 Early diagnosis is essential
 Aim to treat with DMARD’s at 3 months
 Once RA damage is done radiologically, it is largely
irreversible. This usually occurs within first 2 years of
the disease
 The goal is to put the disease into remission
NSAID’s
 Symptom relief
 Minimal role in altering disease process
Glucocorticoids
 Symptom relief
 Some slowing of radiological progression
 Prednisolone > 10mg/d is rarely indicated
 Avoid using without a DMARD
 Use to bridge effective DMARD therapy
 Minimise duration and dose
 Always consider osteoporosis prophylaxis
Methotrexate
 Oral 7.5mg - increased by 2.5mg every 6 weeks to max
25mg. ONCE WEEKLY (allows liver to recover)
 Is an anti-metabolite, cytotoxic drug, which inhibits DNA
synthesis & cellular replication
 Lower dose in elderly & renal impairment as its renally
excreted
 Folic acid (3d after methotrexate) thought to decrease
toxicity
 Avoid cotrimoxazole, trimethoprim, live vaccines
 Can be given subcutaneously if oral absorption poor
Methotrexate cont…..
 Side Effect’s: oral ulcers, nausea,
hepatotoxicity, bone marrow suppression,
pneumonitis
 All respond to dose reduction except
pneumonitis
 Pre-Treatment : Full Blood Count,RFT, LFT,
Chest X-Ray, Patient education
Methotrexate
 Withhold and deal with rheumatologist if;
 WBC < 4
 Neuts <2
 Plts< 150
 > x2 elevation of AST, ALT
 Unexplained low albumin
 Rash or oral ulcers
 dyspnoea
 Deterioration in renal function – decease dose
 Abnormal bruising or sore throat – stop and check Full
blood count
Sulfasalazine / Salazopyrine
 500mg/day – increased by 500mg weekly to 2-3g/d
 Pre-treatment: Full Blood Count (FBC), LFT,RFT
 Stop and deal with rheumatologist as indicated
before
 Headaches, dizziness, nausea –> decrease dose
Hydroxychloroquine
 Least toxic
 Is an anti-malarial
 Yearly optician review – retinal toxicity
 200-400mg/d
 Often used in combo with other DMARD’s
 Check Renal function and electrolytes prior to
starting
 Avoid in eye related maculopathy, diabetes or
other significant eye disease
 Consider stopping after 5 years
Leflunomide (Arava)
 100mg for 3 days, then 20mg/d, can decrease to
10mg/d
 2nd line treatment. Is a new drug.
 Should not be used with other DMARD’s
 May inhibit metabolism of warfarin, phenytoin,
tolbutamide
 Long elimination half life – so may react with
other DMARD’s even after stopping it
 Must not procreate within 2y of stopping. Do
serum levels.
Anti-TNF alpha
 Use for highly active RA in adults who have failed at least 2
DMARD’s, including methotrexate
 Etanercept 25mg subcutaneous twice a week
 Infliximab 3-10mg/kg iv every 4-8 weeks
 Adalimumab 40mg subcutaneous alternate weeks
 Rapid onset (days to weeks)
 Disadvantages: cost & unknown long term effects,
infections, demyelinating syndromes
 Should be given with methotrexate
 High risk atypical infections – low threshold for antibiotic
prophylaxis
GOUT ARTHRITIS
 ACR criteria for acute
gout
 The presence of characteristic urate crystals in the joint fluid, or a
tophus proved to contain urate crystals by chemical means or
polarized light microscopy, or the presence of 6 of the following 12
clinical, laboratory, and radiographic phenomena:
 1. More than one attack of acute arthritis
 2. Maximum inflammation developed within 1 day
 3. Monoarthritis attack
 4. Redness observed over joints
 5. First metatarsophalangeal joint painful or swollen
 6. Unilateral first metatarsophalangeal joint attack
 7. Unilateral tarsal joint attack
 8. Tophus (proven or suspected)
 9. Hyperuricemia
 10. Asymmetric swelling within a joint on x ray/exam
 11. Subcortical cysts without erosions on x ray
 12. Monosodium urate monohydrate microcrystals in joint fluid during
attack
 13. Joint fluid culture negative for organisms during attack
 Diagnosis
 Clinical :
 In men , initial attack monoarticular – 1st MTP
(Metatarsophalangeal ) joint(50% of cases)
Other joints involved – instep/knees/wrists/
olecranon bursa. Often begins at night. Usually
abrupt , severely painful.
 Later attacks – polyarticular
 Precipitants – Minor trauma , diuretic Regimen,
Surgery, severe medical illness, hypouricemic Rx.
 Tophi
 Laboratory:- GOLD STANDARD
 SF Analysis – WBC ct – 2000-100 000/ml
Monosodium urate crystals
TOPHUS
Diagnosis
 Radiologic
 X RAY :
 Punched out erosions –
only 45% of pts have them,
takes 6 yrs to develop
 Martel’s sign

 CT/MRI/Bone scan
 Sensitive , non specific
Treatment

Acute gouty arthritis:
 Anti- inflammatory drugs ( if s.creat < 2mg/dl,)
 Colchicine preferred in patients without confirmed diagnosis of
gout.
 Endpoints – improvement in jt symptoms/ GI symptoms/ 10 doses taken.
 NSAIDs if diagnosis confirmed. Any NSAID can be used .
 Newer agents – Etoricoxcib 120 OD comparable to indomethacin 50 TID.
 In case of renal failure - oral /iv prednisone.
 Avoid adjusting dosage of urate lowering agents.
 Prophylaxis :
 Only indicated if patient is started on urate lowering Rx.
 Colchicine( 1-3 pills a day)/ NSAID( in colchicine intolerant).
 Does not alter crystal deposition and development of tophi.
 Continue till serum urate levels stabilize and no attacks for 3 – 6
mths.
 If long term prophylactic colchicine given, check Complete Blood
Count ,CK (creatinin kinase) every 6 mths.
 Treatment (contd)
 Control of hyperuricemia
 Differing opinions regarding initiation esp. around
1st attack.
 Clear evidence if erosions + on X-ray / chronic
tophaceous gout/ >2 gout attacks per year.
 Goal : s. urate levels < 6 mg%.
 Serial s. uric acid at least once every 6 months
upon initiation.
 Choice of agents :
 Xanthine oxidase inhibitor
 Uricosuric agents.
 Equal efficacy in pts with normal renal function and who
excrete < 800 mg/day of uric acid.
 Treatment (contd)
 Xanthine oxidase inhibitors
 Allopurinol- only prescription drug available.
 Renally excreted, therefore adjust dose if s.creat > 2mg% or CrCl <50
 Usually Drug of Choice in most patients.
 Side effect – GI / rash / sarcoid like reaction/Allopurinol
hypersensitivity syndrome
 Drug interaction – esp. with 6 MP/azathioprine/
warfarin/theophylline.
 Desensitization protocols exist.
 Oxypurinol – possible option
 Uricosuric agents
 Indications – no history renal calculi , pts <60 yrs, U.A excretion <
800 mg/d
 Contraindication : nephrolithiasis, renal insufficiency
 Limit ASA to 81 mg/day
 Probenecid/ Benzbromarone
 Treatment (contd)
 Adjuvant Regimen
 Control obesity , hyperlipidemia ,Hypertension
 Losartan / fenofibrate – weakly uricosuric
 Diet – moderation in purine intake. Makes a
difference of up to 1mg % in s. uric acid
 Treatment (contd)
 Newer agents
 uricase
 Febuxostat
 Asymptomatic hyperuricemia
 Investigate cause
 No recommendations for treatment.
 References
 Osteoarthritis-How to best avoid surgery. Journal of Family Practice.
July 2009
 Osteoarthritis: Diagnosis and Therapeutic Considerations. AAFP. March
1, 2002.
 FPIN’s Clinical Inquiries. Glucosamine and Chondroitin for
Osteoarthritis. April 1, 2006.
 Cochrane Review. July 2009. Therapeutic ultrasound for osteoarthritis of
the knee or hip.
 Cochrane Review. January 2009. Aquatic exercise for the treatment of
knee and hip osteoarthritis.
 Cochrane Review. July 2009. Exercise for osteoarthritis of the knee.
 Cochrane Review. January 2009. Acetaminophen for osteoarthritis.
 Cochrane Review. January 2009. Braces and orthoses for treating
osteoarthritis of the knee.
 Cochrane Review. October 2009. Glucosamine therapy for treating
osteoarthritis.