PERKULIAHAN REUMATOLOGI

IPD UNILA 2011

Disampaikan oleh
Dr FERMIZET RUDY SpPD-FINASIM

dr FERMIZET RUDY SpPD-FINASIM

 POKOK BAHASAN

1. PENDEKATAN DIAGNOSIS PENYAKIT

SENDI
2. OSTEOARTRITIS (PROSES
DEGENERATIF)
3. REUMATOID ARTRTITIS (PROSES
AUTOIMUN)
4. GOUT (PROSES METABOLISME)
dr FERMIZET RUDY SpPD-FINASIM
 POKOK BAHASAN

1. PENDEKATAN DIAGNOSIS
PENYAKIT SENDI

– KELUHAN
– PEMERIKSAAN
– LEBORATORIUM
– IMAGING

dr FERMIZET RUDY SpPD-FINASIM

 DIAGNOSIS & EVALUASI
• Pemeriksaan pasien (Anamnesis & PF)
• Arthrocentesis & Pemeriksaan cairan sendi
– A. Pemeriksaan
• 1. Pemeriksaan umum
• 2. pemeriksaan mikroskopik
• 3. Kultur
– B. Interpretasi

dr FERMIZET RUDY SpPD-FINASIM

Pemeriksaan pasien

 Arthritis ?
 Ada atau tidak kelainan ekstra artikular?
 Setiap kelainan sendi perlu diajukan tiga
pertanyaan :
 1. Adakah proses peradangan ?
 2. Berapa banyak sendi yang terkena ?
 3. Sendi mana yang mengelami kelainan ?

dr FERMIZET RUDY SpPD-FINASIM

Pemeriksaan pasien (lanjutan)

 Peradangan sendi ditandai adanya :

 Kemerahan , rasa panas, bengkak, dan
sendi kaku pagi hari paling tidak selama 30
menit
 Gout artritis umumnya mengenai satu
sendi (monoarticular)
 Reumatoid arthritis umumnya mengenai
banyak sendi (polyarticular)

dr FERMIZET RUDY SpPD-FINASIM

Pemeriksaan pasien (lanjutan)

 Osteoarthritis dan psoriatic arthritis lebih

sering mengenai distal interphalangeal
(DIP)
 Manifestasi Extra-articular seperti
demam, rash, nodule atau neuropathy

dr FERMIZET RUDY SpPD-FINASIM

 Penting dikonsultasikan

Dermatologist (AP, SLE, vasculitis, etc.)

Ophthalmologist (AS, RA - chloroquin, Behcet)
ENT (reactive arthritis, RA)
Dentist (Sjögren’s, RA)
Neurologist (neuropathies, CNS involvement)
Psychiatrist (chr. pain, fibromyalgia, SLE)
Urologist (reactive arthritis - Reiter, STD)
Gynecologist (reactive arthritis, STD)

dr FERMIZET RUDY SpPD-FINASIM

PEMERIKSAAN LABORATORIUM
RUTIN

dr FERMIZET RUDY SpPD-FINASIM

Pemeriksaan Laboratorium 1.
General, immunological

1. Acute phase reactants

• ESR, CRP
2. Hematology
• RBC, leukocytes, platelets, Hgb, Htc
• blood smear
3. Immunology
• rheumatoid factor (Latex, Rose-Waaler)
• ANF (immunofluorescence: Hep-2 cells)
• DNA, ENA, RNP, Sm, SS-A, SS-B autoantibodies
• complement (CH50, C3, C4)
• immunocomplexes
• cryoglobulin
• other

dr FERMIZET RUDY SpPD-FINASIM

Pemeriksaan Laboratorium 2.
Cairan Synovial
1. General assessment
• color (yellow)
• clarity, opacity (clear-opalescens)
• viscosity (inflammation: decreased)
2. Cell count
3. Crystal analysis (polarized light)
• urate: yellow
• Ca-pyrophosphate: blue
4. Microbiology (smear, culture)
5. Biochemistry
• glucose (infection, tb: low)
• protein, complement, RF ??

dr FERMIZET RUDY SpPD-FINASIM

 Histology
(Nilai Diagnostik)

Rheumatoid arthritis (?)

Tuberculosis
Sarcoidosis
Gout
Hemochromatosis
Multicentric reticulohistiocytosis (RHS)
Pigmented villonodular synovitis

dr FERMIZET RUDY SpPD-FINASIM

 Nilai dignostik
berdasarkan kelainan sendi
Characteristic Status Representative Disease
Inflammation Present ► RA, SLE, Gout
Absent ► OA
Number Monoarticular ► Gout, Ttauma, Septic arthritis, OA
of involved joints
Oligoarticular ► PA, IBD
Polyarticular ► RA, SLE
Site of joint DIP ► OA, PA,
involvement MCP, wrists ► RA, SLE
MTP(1) ► Gout , OA

PA = Psoriatic Arhtritis, IBD = Inflammation Bowel Disease

dr FERMIZET RUDY SpPD-FINASIM

 Nilai dignostik
berdasarkan kelainan sendi
Characteristic Status Representative Disease
Inflammation Present ► RA, SLE, Gout
Absent ► OA
Number Monoarticular ► Gout, Ttauma, Septic arthritis, OA
of involved joints
Oligoarticular ► PA, IBD
Polyarticular ► RA, SLE
Site of joint DIP ► OA, PA,
involvement MCP, wrists ► RA, SLE
MTP(1) ► Gout , OA

PA = Psoriatic Arhtritis, IBD = Inflammation Bowel Disease

dr FERMIZET RUDY SpPD-FINASIM

 Nilai dignostik
berdasarkan kelainan sendi
Characteristic Status Representative Disease
Inflammation Present ► RA, SLE, Gout
Absent ► OA
Number Monoarticular ► Gout, Ttauma, Septic arthritis, OA
of involved joints
Oligoarticular ► PA, IBD
Polyarticular ► RA, SLE
Site of joint DIP ► OA, PA,
involvement MCP, wrists ► RA, SLE
MTP(1) ► Gout , OA

PA = Psoriatic Arhtritis, IBD = Inflammation Bowel Disease

dr FERMIZET RUDY SpPD-FINASIM

 Nilai dignostik
berdasarkan kelainan sendi
Characteristic Status Representative Disease
Inflammation Present ► RA, SLE, Gout
Absent ► OA
Number Monoarticular ► Gout, Ttauma, Septic arthritis, OA
of involved joints
Oligoarticular ► PA, IBD
Polyarticular ► RA, SLE
Site of joint DIP ► OA, PA,
involvement MCP, wrists ► RA, SLE
MTP(1) ► Gout , OA

PA = Psoriatic Arhtritis, IBD = Inflammation Bowel Disease

dr FERMIZET RUDY SpPD-FINASIM

 Arthrocentesis & Pemeriksaan
cairan sendi

• Pemeriksaan cairan sendi memberikan

keterangan yang spesifik tentang keadaan
penyakit sendi
• Kontraindikation :
– Adanya infeksi ditempai yang sakit
– Adanya kelainan darah
– Pasien tidak kooperatif

dr FERMIZET RUDY SpPD-FINASIM

 A. Tipe pemeriksaan
• 1. Pemeriksaan makroskopik
– Cairan opaque  pemeriksaan pewarnaan
Gram
– Bila cairan hemoragis  kelainan darah,
trauma
• 2. Pemeriksaan Mikroscopik
– Monosodium urate  gout
– Calsium ppyrophosphate  pseudogout
• 3. Kultur
– Untuk gonococcus, tubercle bacilli atau fungi

dr FERMIZET RUDY SpPD-FINASIM

 Pemeriksaan cairan sendi
Measure (Normal) Group 1(Non Group 2 Group 3
inflammatory) (Inflammatory) (Purulent)
Volume (ml)(knee) < 3,5 Often > 3,5 Often > 3,5 Often > 3,5

Clarity Transparent Transparent Translucent to Opaque

opaque
Color Clear yellow Yellow to Yellow to green
opalescent
WBC (per mcL) < 200 200-300 3000-50.000 > 50.000

PMN < 25% <25% 50% or more 75% or more

Culture Negative Negative Negative Usually positive

Glucose (mg/dL) ± serum ± serum > 25, < serum <25, << serum

dr FERMIZET RUDY SpPD-FINASIM

 Pemeriksaan cairan sendi
Measure Normal Group 1(Non Group 2 Group 3
inflammatory) (Inflammatory) (Purulent)
Volume (ml)(knee) < 3,5 Often > 3,5 Often > 3,5 Often > 3,5

Clarity Transparent Transparent Translucent to Opaque

opaque
Color Clear yellow Yellow to Yellow to green
opalescent
WBC (per mcL) < 200 200-300 3000-50.000 > 50.000

PMN < 25% <25% 50% or more 75% or more

Culture Negative Negative Negative Usually positive

Glucose (mg/dL) ± serum ± serum > 25, < serum <25, << serum

dr FERMIZET RUDY SpPD-FINASIM

 Pemeriksaan cairan sendi
Measure Normal Non Group 2 Group 3
inflammatory (Inflammatory) (Purulent)
Volume (ml)(knee) < 3,5 Often > 3,5 Often > 3,5 Often > 3,5

Clarity Transparent Transparent Translucent to Opaque

opaque
Color Clear yellow Yellow to Yellow to green
opalescent
WBC (per mcL) < 200 200-300 3000-50.000 > 50.000

PMN < 25% <25% 50% or more 75% or more

Culture Negative Negative Negative Usually positive

Glucose (mg/dL) ± serum ± serum > 25, < serum <25, << serum

dr FERMIZET RUDY SpPD-FINASIM

 Pemeriksaan cairan sendi
Measure Normal Non Inflammatory Group 3
inflammatory (Purulent)
Volume (ml)(knee) < 3,5 Often > 3,5 Often > 3,5 Often > 3,5

Clarity Transparent Transparent Translucent to Opaque

opaque
Color Clear yellow Yellow to Yellow to green
opalescent
WBC (per mcL) < 200 200-300 3000-50.000 > 50.000

PMN < 25% <25% 50% or more 75% or more

Culture Negative Negative Negative Usually positive

Glucose (mg/dL) ± serum ± serum > 25, < serum <25, << serum

dr FERMIZET RUDY SpPD-FINASIM

 Pemeriksaan cairan sendi

Measure Normal Non Inflammatory Purulent

inflammatory
Volume (ml)(knee) < 3,5 Often > 3,5 Often > 3,5 Often > 3,5

Clarity Transparent Transparent Translucent to Opaque

opaque
Color Clear yellow Yellow to Yellow to green
opalescent
WBC (per mcL) < 200 200-300 3000-50.000 > 50.000

PMN < 25% <25% 50% or more 75% or more

Culture Negative Negative Negative Usually positive

Glucose (mg/dL) ± serum ± serum > 25, < serum <25, << serum

dr FERMIZET RUDY SpPD-FINASIM

 B. Interpretasi

• Analisis cairan sendi adalah diagnostik pada :

– 1. Kasus infeksius
– 2. Adanya microcristalline arthritis
• Adanya glukosa dan protein dalam cairan
sendi tidak begitu bermakna

dr FERMIZET RUDY SpPD-FINASIM

 Diagnosis Banding
berdasarkan cairan sendi

Noninflammatory Inflammatory (Purulent) Hemorrahgic

Degeneratif joint ds RA Pyogenic Hemophillia or other

Trauma Gout/ pseudogout bacterial hemorrhagic
Osteochondroitis Reiter’s syndrome infection diathesis
Osteochondromatosis Rheumatic fever Trauma
Neuropathic arthropathy SLE Neuropathic
arthropathy
Hypertrophic Scleroderma
osteoarthropathy Hemangioma and
Tuberculosis other benign
Mycotic infection neoplasma

dr FERMIZET RUDY SpPD-FINASIM

 Diagnosis Banding
berdasarkan cairan sendi
Group 1 Inflammatory Group 3
(Noninflammatory) (Purulent) Hemorrahgic

Degeneratif joint ds RA Pyogenic Hemophillia or other

Trauma Gout/ pseudogout bacterial hemorrhagic
Osteochondroitis Reiter’s syndrome infection diathesis
Osteochondromatosis Rheumatic fever Trauma
Neuropathic arthropathy SLE Neuropathic
arthropathy
Hypertrophic Scleroderma
osteoarthropathy Hemangioma and
Tuberculosis other benign
Mycotic infection neoplasma

dr FERMIZET RUDY SpPD-FINASIM

 Diagnosis Banding
berdasarkan cairan sendi
Group 1 Group 2 Purulent
(Noninflammatory) (Inflammatory) Hemorrahgic

Degeneratif joint ds RA Pyogenic Hemophillia or other

Trauma Gout/ pseudogout bacterial hemorrhagic
Osteochondroitis Reiter’s syndrome infection diathesis
Osteochondromatosis Rheumatic fever Trauma
Neuropathic arthropathy SLE Neuropathic
arthropathy
Hypertrophic Scleroderma
osteoarthropathy Hemangioma and
Tuberculosis other benign
Mycotic infection neoplasma

dr FERMIZET RUDY SpPD-FINASIM

 Diagnosis Banding
berdasarkan cairan sendi
Group 1 Group 2 Group 3
(Noninflammatory) (Inflammatory) (Purulent) Hemorrahgic

Degeneratif joint ds RA Pyogenic Hemophillia or other

Trauma Gout/ pseudogout bacterial hemorrhagic
Osteochondroitis Reiter’s syndrome infection diathesis
Osteochondromatosis Rheumatic fever Trauma
Neuropathic arthropathy SLE Neuropathic
arthropathy
Hypertrophic Scleroderma
osteoarthropathy Hemangioma and
Tuberculosis other benign
Mycotic infection neoplasma

dr FERMIZET RUDY SpPD-FINASIM

 Diagnosis Banding
berdasarkan cairan sendi
Noninflammatory Inflammatory Purulent Hemorrahgic

Degeneratif joint ds RA Pyogenic Hemophillia or other

Trauma Gout/ pseudogout bacterial hemorrhagic
Osteochondroitis Reiter’s syndrome infection diathesis
Osteochondromatosis Rheumatic fever Trauma
Neuropathic arthropathy SLE Neuropathic
arthropathy
Hypertrophic Scleroderma
osteoarthropathy Hemangioma and
Tuberculosis other benign
Mycotic infection neoplasma

dr FERMIZET RUDY SpPD-FINASIM

PEMERIKSAAN IMAGING

dr FERMIZET RUDY SpPD-FINASIM

 Pemeriksaan Imaging

Tujuan :

Nilai diagnostik (RA, AS, OA)

Nilai Differential diagnostik (metast.)
Progresi, indikator pengobatan (erosions)

dr FERMIZET RUDY SpPD-FINASIM

 Imaging
1. X-ray (simple, comparative, tomography)
2. Radioisotope scanning
• Tc-99m scan (bone, joint) - SPECT
• infection: Ga-67, labelled leukocyte scan
• In-111, INFLAMON, anti-granulocyte antibody
3. CT (hernia, tumor)
4. MRI (hernia, soft tissue, early erosions)
• indication: cartilage, tendon, meniscus, muscle
5. Ultrasound (cysts, joints, fluid)
6. Invasive techniques
• arthrography, myelography

dr FERMIZET RUDY SpPD-FINASIM

 Sarana Diagnostik Lain

Arthroscopy: diagnostik and terapi

Electromyography (EMG): myositis, myopathy
Electroneurography (ENG): neuropati
Saliva, tear secretion: Sjögren’s syndrome

dr FERMIZET RUDY SpPD-FINASIM

TERAPI

dr FERMIZET RUDY SpPD-FINASIM

 TERAPI REUMATOLOGIS
• Farmakologis
• symptomatic (NSAID, corticosteroids)
• „disease-modifying” (DMARD)
• Fisioterapi
• Bedah Ortopedi
• Psikoterapi, edukasi, sosial terapi
• (Alternative medicine)

dr FERMIZET RUDY SpPD-FINASIM

 NSAID therapy

dr FERMIZET RUDY SpPD-FINASIM

Elsevier items and derived items © 2006 by Elsevier Inc.
 NSAID mechanism of action:

COOH

Arachidonic acid
COX
NSAID

Prostaglandins

Pain, inflammation,
fever, GI defense
dr FERMIZET RUDY SpPD-FINASIM

Cited from: Vane JR Nature New Biol 1971;231:232 235

 Role of cyclooxygenase (COX)

• COX is involved in the transformation

of arachidonic acid and oxygen into
PGH2 (prostanoid precursor)

• COX inhibition results in decreased PG

production

Cited from: Robinson DR J Rheumatol 1997;24(suppl 47):32-39. dr FERMIZET RUDY SpPD-FINASIM

 NSAID effects
1. Anti-inflammatory (COX-2 PG)
• COX inhibition
• inhibition of free radical production
• lysosomal enzyme inhibition
• capillary permeability inhibition
• leukocyte migration inhibition
• phagocytosis inhibition
2. Analgetic (COX-2 PG)
3. Anti-pyretic

dr FERMIZET RUDY SpPD-FINASIM

 Klasifikasi NSAID

1. Salicylates (aspirin)
2. Pyrazolons (amidazophenum)
3. Pyrazolidines (butazons): phenylbutazon, azapropazon
4. Indols: indomethacin, tolmetin, sulindac
5. Phenylacetates: diclofenac, paracetamol,
phenacetin, aceclofenac
6. Antranilic acid: nifluminic acid
7. Propionates: ibuprofen, tiaprofenate, naproxen
8. Oxicams: piroxicam, tenoxicam
9. Non-acidic NSAIDs: proquazon, nabumeton,
COX-2 selective
dr FERMIZET RUDY SpPD-FINASIM
 NSAID in
inflammatory rheumatic diseases

1. Initial (powerful, short-term, more side effects)

• salicylates - maximum 7-10 days
• phenylbutazon: max. 1-2 weeks
• indomethacinum (3x25-50 mg)
• naproxen (2x250-500mg)
• piroxicam (20-40mg)
• diclofenac (3x25-50mg, SR)
2. Prolonged (weaker, less side effects, longer)
• nabumeton (1g)
• azapropazon (3x300mg)
• niflumic acid (3x250mg)
• ibuprofen ( 3x400mg)
• proquazon (3x200mg)
• sulindac, tolmetin (indomethacinum)
3. Selective COX-2 inhibitors: anytime ?

dr FERMIZET RUDY SpPD-FINASIM

 Gastrointestinal risk
• Nabumeton
• Etodolac
• Ibuprofen
• Aspirin
• Diclofenac
• Naproxen Increased risk
• Indomethacin
• Ketoprofen
• Piroxicam
• Flurbiprofen
• Ketorolac
dr FERMIZET RUDY SpPD-FINASIM
 New hypothesis by Vane
COOH

Arachidonic acid

NSAID
COX-1 COX-2
„constitutive” „inducible”

Prostaglandins Prostaglandins

Defense of gatric Mediators of pain, fever

Hemostasis
mucosa and inflammation
Kidneys
Cited: Paulus HE, Bulpitt KJ. In: Klippel JH, szerk. Primer on the Rheumatic Diseases. 11th ed. Atlanta:
Arthritis Foundation, 1997:442-426; Robinson DR J Rheumatol 1997;24(suppl 47):32-39, Vane JR, Botting
dr FERMIZET RUDY SpPD-FINASIM
RM Inflamm Res 1995;44:1-10.
 Terminology

• Specific COX-2 inhibitor

• Selective COX-2 inhibitor
• „More selective” COX-2 inhibitor
• Preferential COX-2 inhibitor
• Coxibs vs others

dr FERMIZET RUDY SpPD-FINASIM

 COX-1/COX-2 IC80 (%)

0
20
60
80

40
DFP 100
L-745,337
rofecoxib
NS-398
etodolac
meloxicam

Warner et al. PNAS 1999; 96:7563-7568

nimesulide
celecoxib
tomoxiprol
diclofenac
sulindac sulphide
piroxicam
meclofenamate
assay

diflunisal
niflumic acid
sodium salicylate

dr FERMIZET RUDY SpPD-FINASIM

fenoprofen
zomepirac
indomethacin
tolmetin
naproxen
ibuprofen
ampyrone
ketoprofen
aspirin
COX-1/COX-2 ratios in whole blood

flurbiprofen
suprofen
ketorolac
Corticosteroid therapy

dr FERMIZET RUDY SpPD-FINASIM

 Corticosteroids
 basis: cortisone, cortisol
 80% bound to transcortin, 10% to albumin,
10% bioactive
 95 kD corticosteroid receptor in plasma
 complex transfers to nucleus
 effect: lipocortin stimulation - phospholipase A2
inhib. - prostanoid metabolism inhibition -
proinflammatory cytokine inhib. (IL-1, IL-2, TNF)
- enzyme inhibition
dr FERMIZET RUDY SpPD-FINASIM
 Corticosteroids in practice
Product Half Mineraloco Ekv.
life rt. dóse
Activity
Cortisol Short + 20 mg
Prednisone Short + 5 mg
Methylpredn. Short - 4 mg
Triamcinolone Mediu - 4 mg
m
Dexamethasone Long - 0.75 mg
Betamethasone Long - 0.6 mg
dr FERMIZET RUDY SpPD-FINASIM
 Practical guidelines

 Disease and its severity

 Planned duration of treatment
 Optimal dose
 Optimal product
 Optimal route of administration (PO, IV)
 Associated diseases
 Chances for steroid sparing
 Alternating dosage
dr FERMIZET RUDY SpPD-FINASIM
 Side effects I.
 Gastrointestinal
 ulcer, gastropathy, pancreatitis
 Endocrine
 Cushing’s syndrome
 acne, hirsutismus, virilismus, impotency
 growth retardation
 hyperglycemia, diabetes, hyperlipidemia
 potassium loss, sodium and fluid retention,
edema
 secondary hypadrenia

dr FERMIZET RUDY SpPD-FINASIM

 Side effects 2.
 Cardiovascular
 hypertension
 edema, CHF
 atherosclerosis
 Locomotor
 myopathy
 osteoporosis, fractures
 aseptic bone necrosis (femoral, humerus,
etc.)
dr FERMIZET RUDY SpPD-FINASIM
 Side effects 3.
 Neuropsychiatric
 convulsions
 psychosis
 characteropathies
 Ocular
 posterior cataract
 glaucoma

dr FERMIZET RUDY SpPD-FINASIM

 Side effects 4.
 Skin
 facial erythema
 thin, fragile skin, petechiae, striae
 retardation of wound healing
 Immunological, infectious
 neutrophilia, monocytopenia,
lymphocytopenia
 increased susceptibility to infections

dr FERMIZET RUDY SpPD-FINASIM

 Ulcer - gastropathy

 Only anecdotic reports

 not significant at low doses
 not proven in large, controlled studies
 usually ulcer is due to concomittant NSAID
treatment

dr FERMIZET RUDY SpPD-FINASIM

 Infections
 bacterial: Staphylococci, Gram negative,
tuberculosis, Listeria
 viral, fungal: rare
 few large studies
 tuberculosis was not more common
 importance of other diseases, other
therapies

dr FERMIZET RUDY SpPD-FINASIM

 General guidelines to dosage
 Always choose the optimal dose, product and
duration for the specific disease
 in children, even 7.5 mg prednisone equivalent
may cause growth retardation
 high dose: short term, slowly decrease
 very short „pulse” therapy: faster decrease
 steroid sparing: methotrexate, azathioprine,
cyclophosphamide

dr FERMIZET RUDY SpPD-FINASIM

 Dosages
 Low dose (< 15 mg/d)
 arthritis, inactive SLE, polymyalgia
 High dose (20-60 mg/d)
 active SLE, vasculitis
 Very high dose („pulse”: 250-1000 mg)
 acut nephritic crisis, vasculitic crisis

dr FERMIZET RUDY SpPD-FINASIM

SELESAI

dr FERMIZET RUDY SpPD-FINASIM