Evaluation of Arthritis

AIMS

Types of arthritis


Symptoms of arthritis


Signs of arthritis


Treatment of arthritis
 Types of Arthritis

Rheumatoid arthritis (RA)

Osteoarthritis (OA)


Sero-negative arthritis
 Ankylosing spondylitis
 Psoriatic arthritis
 Reactive arthritis
 Enteropathic arthritis


Crystal arthropathies
 ABCDs of arthritis
stands for :
 A: ALIGNMENT
 B: BONY MINERALIZATION
 C: CARTILAGE SPACE
 D: DISTRIBUTION
 S: SOFT TISSUE
Normal joint
structure
NORMAL SUBCHONDRAL BONE DESTRUCTION
Osteoarthritis : Definition
 A chronic joint disorder in which there is progressive
softening and disintegration of articular cartilage
accompanied by new growth of cartilage and bone at the joint
margins (osteophytes) and capsular fibrosis
 OA: classification

Primary or idiopathic


Secondary
 Infection
 Dysplasia
 Perthes
 SCFE
 Trauma
 AVN
 Etiology


Genetic


Metabolic


Hormonal


Mechanical


Ageing
 Mechanism 1

Disparity between:-

stress applied to articular cartilage

and
strength of articular cartilage
 Mechanism 2

Increased stress (F/A)


Increased load eg BW or activity
Decreased area eg varus knee or dysplastic hip
 Mechanism 3

Weak cartilage

age

stiff eg ochronosis

soft eg inflammation

abnormal bony support eg AVN
Osteoarthritis

 Jointspace narrowing
 Osteophytosis
 Subchondral cysts
 Subchondral sclerosis
OA
HIP (OA)
 Femoral neck buttressing
 Tilt deformity ( flattening of head surface with osteophyte at
anteroinferior aspect)
 Superior >medial migration
 Secondary OA due to previous trauma or inflammatory
arthritis
KNEE(OA)

 Erect weight-bearing AP film

 Unicompartmental
 Sharpening of tibial prominence
 Loose bodies
 Varus deformity
 Patellar tooth sign – irregular anterior patellar surface
OA Affecting Foot
 OA SPINE
 Vacuum Phenomenon
 Accumulation of Nitrogen
 Degenarative etiology
 Better seen in Extension
 Excludes infective etiology
 In peripheral joints
physiological
Osteoarthritis

SPGR

T1W
Osteoarthritis

SPGR

T2 FATSAT
 Symptoms

pain

swelling

stiffness

deformity

instability

loss of function
 Treatment

Analgesia

Oral viscosupplements

Intrarticular steroids

Intrarticular viscosupplements

Altered activity

Walking aids

Physiotherapy

arthroscopy

osteotomy

arthrodesis

excision arthroplasty

replacement arthroplasty
TKR
RHEUMATOID ARTHRITIS
 Bilateral symmetry
 Periarticular soft
tissue swelling
 Uniform joint space loss
 Marginal erosions
 Juxta-articular osteoporosis
 Joint deformity
Rheumatoid arthritis
Pathogenesis
Disability in Early RA

 Inflammation
◦ Swollen
◦ Stiff
◦ Sore
◦ Warm
 Fatigue
 Potentially
Reversible
RA
RA-Deformity
 Boutonniere deformity :
flexion deformity at PIP jt & hyperextension at DIP

 Swan neck deformity :

combination of flexion at
DIP and extension at PIP
 RA

B/L KNEE ANKYLOSIS

RA
RA
RA-foot deformity
RA (cervical spine)

 Atlantodental interspace > 3.0mm

 Odontoid erosions
 Subluxation
 Pseudo basilar invagination
 Reduced disc space
 Apophyseal joint: erosion, sclerosis,
ankylosis
 Sharpened pencil spinous process
ADI > 3.0mm
RA (SHOULDER)

 Soft tissue swelling

 Rotator cuff rupture
 Head erosions
 Tapered distal clavicle due

to erosions
 Irregular coracoid process
RA (ELBOW)


Enlarged Olecranon bursa
 Fat pad sign
 Supinator notch sign: erosion at

proximal ulna
RA-ELBOW
 RA (KNEE)

 Uniform bicompartmental joint space loss

 Patellofemoral joint also involved
 Soft tissue swelling
 Baker’s cyst
 Subchondral cysts
Rheumatoid Arthritis

T1W

T1GR
E
Rheumatoid Arthritis
◦ Rheumatoid arthritis is a synovial disease
-Osteoarthritis is a disease of the cartilage.
-Volar subluxation never in osteoarthritis

Normal joint
Degenerative v/s Inflammatory

Unicompartmental Bicompartmental
Disability in RA
 Most of the disability in RA is a result of the INITIAL burden of
disease
 People get disabled because of:
◦ Inadequate control
◦ Lack of response
◦ Compliance
 GOAL: control the disease early on!
 Medical management
NSAIDS
Steroids
Oral
Intra-articular
DMARDS
Synthetic
Methotrexate
Hydroxychloroquine
Leflunomide
Sulfasalazine
 Biologics
 Monoclonal Antibodies to TNF
◦ Infliximab
◦ Adalimumab
 Soluble Receptor Decoy for TNF
◦ Etanercept
 Receptor Antagonist to IL-1
◦ Anakinra
 Monoclonal Antibody to CD-20
◦ Rituximab
NSAIDs

 Cyclo-oxygenase inhibitors

 Do not slow the progression of the disease

 Provide partial relief of pain and stiffness

 DMARDs
Disease Modifying Anti-Rheumatic Drugs

 Reduce swelling & inflammation

 Improve pain
 Improve function
 Have been shown to reduce radiographic progression
(erosions)
Methotrexate (MTX)
 Dihydrofolate reductase inhibitor

 ↓ thymidine & purine nucleotide synthesis

 “Gold standard” for DMARD therapy

 7.5 – 30 mg weekly

 Absorption variable
 Elimination mainly renal
MTX adverse effects
 Hepatotoxicity
 Bone marrow suppression
 Dyspepsia, oral ulcers
 Pneumonitis
 Teratogenicity

 Folic acid reduces GI & BM effects

 Monitoring
◦ FBC, ALT, Creatinine
Sulphasalazine
 Sulphapyridine + 5-aminosalicylic acid

 Remove toxic free radicals

 Remission in 3-6 month

 Elimination hepatic

 Dyspepsia, rashes, BM suppression

 Chloroquine, Hydroxychloroquine
 Mechanism unknown
◦ Interference with antigen processing ?
◦ Anti- inflammatory and immunomodulatory

• For mild disease

Chloroquine cont
Side effects

 Irreversible Retinal toxicity, corneal deposits

 Ophthalmologic evaluation every 6 months

Leflunomide

 Competitive inhibitor of dihydroorotate

dehydrogenase (rate-limiting enzyme in de
novo synthesis of pyrimidines)

 Reduce lymphocyte proliferation

Leflunomide
 Oral cont
 T ½ - 4 – 28 days due to EHC
 Elimination hepatic

 Action in one month

 Avoid pregnancy for 2 years
Side effects of leflunomide
 Hepatotoxicity

 BM suppression

 Diarrhoea

 rashes
Combination therapy (using 2 to
3) DMARDs at a time works
better than using a single
DMARD
Common DMARD
Combinations

 Triple Therapy
◦ Methotrexate, Sulfasalazine, Hydroxychloroquine

 Double Therapy
◦ Methotrexate & Leflunomide
◦ Methotrexate & Sulfasalazine
◦ Methotrexate & Hydroxychloroquine
BIOLOGIC THERAPY
• Complex protein molecules

• Created using molecular biology methods

• Produced in prokaryotic or eukaryotic cell cultures

Tumour Necrosis Factor (TNF)

 TNF is a potent inflammatory cytokine

 TNF is produced mainly by macrophages

and monocytes

 TNF is a major contributor to the

inflammatory and destructive changes that
occur in RA

 Blockade of TNF results in a reduction in a

number of other pro-inflammatory
cytokines (IL-1, IL-6, & IL-8)
Strategies Monoclonal Antibody (Infliximab &
for Reducing Adalimumab)
Effects of
TNF
Trans-Membrane
Bound TNF

Macrophage

Soluble TNF
Side Effects
 Infection
◦ Common (Bacterial)
◦ Opportunistic (Tb)
 Demyelinating Disorders
 Malignancy
 Worsening CHF
Glucocorticoids
 Potent anti-inflammatory drugs
 Serious adverse effects with long-term use
 To control the diaseas
 Indications
◦ As a bridge to effective DMARD therapy

◦ Systemic complications (e.g. vasculitis)

What is Juvenile Idiopathic Arthritis?

 Most common childhood chronic disease

causing disability.

 About 7/100,00 newly diagnosed children with

JIA per year.

 Prevalence about 1/1,000 children = 1,000

children in BC with JIA.

 7 subtypes.

 Disease begins at any time during childhood or

adolescence.
Characteristics of JIA

 To be considered JIA, onset must occur before 16 years of

age.
 JIA is heterogeneous: the presentation of the disease and
its natural history vary among individuals and over time.
 The disease is typically classified into categories based on
the symptoms displayed and their severity.
 Systemic arthritis
 Oligoarthritis
 Rheumatoid-factor positive (RF+) polyarthritis
 Rheumatoid-factor negative (RF-) polyarthritis
 Enthesitis-related arthritis
 Psoriatic arthritis
 Undifferentiated

G.ahrq.gov/dmardsjia.cfm.
Juvenile Idiopathic Arthritis

 Child under 16 years old

 At least one joint with objective signs of arthritis:

› Swelling, or two of the following: pain with movement,

warmth of the joint, restricted movement, or tenderness

 Duration of more than 6 weeks

 Other causes have been excluded (ex. Infections, Lupus and

other connective tissue diseases, malignancies)
Common Diagnostic Myths About Arthritis in
Childhood……

 All kids with JIA have fevers.

 All kids with JIA have rashes.

 A child with joint pain (but no arthritis) must have JIA.

 All arthritis is painful.

 If a child has a positive rheumatoid factor, they must have

arthritis.

 If x-rays are normal, there is no arthritis.

 Pathogenesis

 Heterogeneous group of diseases characterized by

chronic inflammatory processes involving the synovial
membrane, cartilage, and bone

 The classification of JIA subgroups based on clinical and

laboratory characteristics including the number of affected
joints and the presence of autoimmune markers

 Th1 cell-mediated disorder, driven by a population of T

cells producing inflammatory cytokines and chemokines
 Clinical features of JRA:
 Joint pain, stiffness, and
swelling: These are the most
common symptoms of JRA,
but many children do not
recognize, or do not report,
pain. Stiffness and swelling
are likely to be more severe
in the morning.
 Loss of joint function: Pain,
swelling, and stiffness may
impair joint function and
reduce range of motion.
Some children are able to
compensate in other ways
and display little, if any,
disability. Severe limitations
in motion lead to weakness
and decreased physical
function and sometimes to
invalidization.
Clinical features of JRA:

 Limp: A limp may

indicate a
particularly severe
case of JRA, although
it also may be due to
other problems that
have nothing to do
with arthritis, such
as an injury. In JRA, a
limp often signals
knee involvement.
 Clinical features of JRA:
 Eye irritation, pain, and
redness: These
symptoms are signs of
eye inflammation. The
eyes may be sensitive
to light. In many cases,
however, eye
inflammation has no
symptoms. If the
inflammation is very
severe and not
reversed, it can
cause loss of vision.
The most common
types of eye
inflammation in JRA are
uveitis and iritis. The
names refer to the part
of the eye that is
 Recurrent fevers:
Fever is high and
comes and goes with
no apparent cause.
Fever may “spike” (go
high) as often as
several times in one
day.

 Rash: A light rash may

come and go without
explanation.
 Myalgia (muscle
aches): This is similar
to that achy feeling
that comes with the
flu. It usually affects
muscles throughout
the whole body, not
just one part.
Clinical features of JRA:
 Lymph node swelling. Swollen lymph nodes are
noticed most often in the neck and under the
jaw, above the clavicle, in the armpits, or in the
inguinal region.
 Weight loss. This is common in children with
JRA. It may be due to the child’s simply not
feeling like eating.
 Growth problems:
Children with JRA often
grow more slowly than
average. Growth may be
unusually fast or slow in
an affected joint, causing
one arm or leg to be
longer than the other.
General growth
abnormalities may be
related to having a
chronic inflammatory
condition such as JRA or
to the treatment,
especially glucocorticoids
Laboratory tests in JRA

 ANA (antinuclear antibody)

 RF (Rheumatoid factor )
 CRP (C-reactive protein)
 ESR (erythrocyte sedimentation rate)
 CCP (Cyclic Citrullinated Peptide

Antibody) test
 Treatment
 The goals: eliminate active disease, normalize joint function,
preserve normal growth, prevent long-term joint damage,
and prevent patient disability
 The American College of Rheumatology Pediatric 30 criteria
(ACR Pedi 30) defines improvement as involving at least 3 of
6 core set variables, with no more than 1 of the remaining
variables worsening by > 30%.
 The 6 core set includes
◦ Physician global assessment

◦ active joint count

◦ number of joints with limited range of motion

◦ Inflammatory markers

◦ patient or parent assessments

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Medications Doses Side effects

(mg/kg)
Aspirin 50-120 Stomack pain, vomiting,
gastrointestinal
bleedings, headache,
Ibuprofen 10-30 blood in the urine, fluid
retention, thinning and
Tolmentin 10-15 scarring of the skin
(especially with
naproxen), stomach
Naproxen 5-20 ulcer (aspirin).
Slow-acting anti-rheumatic drugs (SAARDs)

Medications Doses Side effects

(mg/kg)
Hydroxychlo- 5-7 Upset stomach, skin
roquine rash and a eye
(Plaquenil) damage. A child who
takes this drug should
Sulfasalazine have his/her eyes
(Azulfadine) examined at least
every six months by
an ophthalmologist
Gold compaunds

Medications Doses(weekly, Side effects

depending from
body weight )
Auranofin, 20 kg – 10 mg Skin rash,
Ridaura, 30 kg – 20 mg mouth sores,
Myochrysine 40 kg – 30 mg kidney
Solganol problems, a low
50 kg – 40 mg
blood count or
> 50 kg – 50 mg anemia
Immune System Medications (Cytostatics)

Medications Doses Side effects

Methotrexate Typically 7.5 to Loss of appetite,

(Rbeumatrex) 25 mg a week nausea or
vomiting, skin
Azathioprine rash, unusual
(Imuran) bleeding or
Cyclophospha bruising,
mide tiredness or
(Cytoxan) weakness,
sterility.
Other medications

 Biologic Agents, which blocks the protein TNF

Etanercept (Enbrel)
Infliximab (Remicade)
 Glucocorticoid Drugs (Dexamethasone,
Methylprednisolone, Cortef, Prednisolone and Prednisone)
 Analgesics (acetaminophen [Tylenol, Panadol], tramadol

[Ultram])
Very important parts of treatment for
juvenile arthritis:
 Therapeutic exercises
 Sports and Recreational Activities
 Splints
Very important parts of treatment for juvenile
arthritis:
 Morning Stiffness Relief
 Diet
 Eye Care
 Dental Care
 Surgery
GOUT
.
OBJECTIVES
 Identify diagnostic criteria for gout

 Identify 3 treatment goals for gout

 Name the agents used to treat the acute flares of gout and
the chronic disease of gout
Why Worry About Gout ?

 Prevalence increasing
 May be signal for unrecognized
comorbidities : ( Not to point of
searching)

Obesity (Duh!)
Metabolic syndrome
DM
HTN
CV disease
Renal disease
“Disease of Kings”

Rich foods have a higher

concentration of protein. This could
cause major problems for a person
afflicted with gout.

 ORGAN MEATS
 WILD GAME
 SEAFOOD
 LENTILS
 PEAS
 ASPARAGUS
 YEAST
 BEER
URATE, HYPERURICEMIA & GOUT

 Urate: end product of purine metabolism

 Hyperuricemia: serum urate > urate solubility (> 6.8

mg/dl)

 Gout: deposition of monosodium urate crystals in tissues

HYPERURICEMIA & GOUT

 Hyperuricemia caused by
Overproduction
Underexcretion

 No Gout w/o crystal deposition

 THE GOUT CASCADE
 Urate
 Oevrproduction Underexcretion

 Hyperuricemia

 ________________________________________

 Silent Gout Renal Associated

 Tissue manifestations CV events &
 Deposition mortality
What is Gouty Arthritis

 Purines are not properly

processed in our body
 Excreted through

kidneys and urine

 Hyperuricemia- build-

up of uric acid in body

and joint fluid
GOUT: A Chronic Disease of 4 stages

 Asymptomatic hyperuricemia

 Acute Flares of crystallization

 Intervals between flares

 Advanced Gout & Complications

ACUTE GOUTY FLARES
 Abrupt onset of severe joint inflammation, often nocturnal;
Warmth, swelling, erythema, & pain;
Possibly fever
 Untreated? Resolves in 3-10 days
 90% 1st attacks are monoarticular
 50% are podagra
SITES OF ACUTE FLARES

 90% of gout patients

eventually have
podagra : 1st MTP joint
GOUT
GOUT
Sites

 Can occur in other

joints, bursa & tendons
INTERVALS SANS FLARES
 Asymptomatic

 If untreated, may advance

 Intervals may shorten

 Crystals in asx joints
 Body urate stores increase
Gout
ADVANCED GOUT
 Chronic Arthritis

 X-ray Changes

 Tophi Develop

 Acute Flares continue

ADVANCED GOUT

 Chronic Arthritis
 Polyarticular acute flares

with upper extremities

more involved
TOPHI

 Solid urate deposits in

tissues
TOPHI

 Irregular & destructive

TOPHI RISK FACTORS

 Long duration of hyperuricemia

 Higher serum urate

 Long periods of active, untreated gout

RADIOLOGIC SIGNS
X-RAYS
DIAGNOSING GOUT

 Hx & P.E.

 Synovial fluid analysis

 Not Serum Urate

SERUM URATE LEVELS
 Not reliable

 May be normal with flares

 May be high with joint Sx from other causes

GOUT RISK FACTORS

 Male
 Postmenopausal female
 Older
 Hypertension
 Pharmaceuticals:

Diuretics, ASA,
cyclosporine
GOUT RISK FACTORS
 Transplant
 Alcohol intake
Highest with beer
Not increased with wine
 High BMI (obesity)
 Diet high in meat & seafood
SYNOVIAL FLUID ANALYSIS (Polarized Light
Microscopy)
 The Gold standard

 Crystals intracellular during attacks

 Needle & rod shapes

 Strong negative birefringence

SYNOVIAL FLUID
Differential Diagnosis
 Acute Gout: septic arthritis, pseudogout, Reactive arthritis,
acute rheumatic fever and other crystalline arthropathies.
 Chronic tophaceus gout: Rheumatoid Arthritis, Pseudogout,
seronegative spondyloarthropathies and erosive
osteoarthritis.
Gout vs. CPPD

 Similar Acute attacks

 Different crystals under Micro;

Rhomboid, irregular in CPPD
Gout vs CPPD
 RA vs Gout

 Both have polyarticular, symmetric arthritis

 Tophi can be mistaken for RA nodules

RA vs Gout
Therapy
 Diet is usually impractical, ineffective and rarely adhered to in
clinical practice.
 Indications for pharmacological therapy includes: inability to
reverse secondary causes, tophaceus gout, recurrent acute
gout and nephrolithiasis.
 Gout Management Approach
INITIATE • Treat acute flare rapidly with
(acute flare) anti-inflammatory agent

• Initiate urate-lowering therapy to

RESOLVE achieve sUA <6
• Use concomitant anti-
(urate-lowering therapy) inflammatory prophylaxis for up to
6 mo to prevent mobilization flares

• Continue urate lowering

MAINTAIN therapy to control flares and
(treatment to control sUA) avoid crystal deposition
• Prophylaxis use for at least 3-6
months until sUA normalizes 139

139
TREATMENT GOALS

 Rapidly end acute flares

Protect against future flares
Reduce chance of crystal inflammation

 Prevent disease progression

Lower serum urate to deplete total body urate pool
Correct metabolic cause
ENDING ACUTE FLARES
 Control inflammation & pain & resolve the flare
 Not a cure
 Crystals remain in joints
 Don’t try to lower serum urate during a flare
 Choice of med not as critical as alacrity & duration
Acute Flare Med Choices

 NSAIDS

 Colchicine

 Corticosteroids
Colchicine

Colchicine- reduces pain, swelling, and inflammation; pain

subsides within 12 hrs and relief occurs after 48 hrs

Prevent migration of neutrophils to joints

Side effects

 Nausea
 Vomiting
 Diarrhea
 Rahes
MED Considerations
 Colchicine :
Not as effective “late” in flare
Drug interaction : Statins, Macrolides, Cyclosporine
Contraindicated in dialysis pt.s
Cautious use in : renal or liver dysfunction; active infection,
age > 70
2012 ACR Management Guidelines for Acute
Gouty Arthritis

 The choice of pharmacologic agent depends on severity of

the attack
◦ Monotherapy for mild/moderate attack
◦ Combination therapy for severe attack or those refractory
to monotherapy
 Acceptable combination therapy approaches include
◦ Colchicine and NSAIDS
◦ Oral steroids and colchicine
◦ Intra-articular steroids with all other modalities
 Continue current therapy during flare
 Patient education on signs of flare for self treatment

146 D, et al. Arthritis Care Res (Hoboken). 2012 Oct;64(10):1447-61

Kanna
TREATMENT GOALS
 Rapidly end acute flares
Protect against future flares
Reduce chance of crystal inflammation

 Prevent disease progression

Lower serum urate to deplete total body urate pool
Correct metabolic cause
5 Gout Commandments
 Hyperuricemia ≠ Gout
 Goal sUA < 6
 Use prophylaxis for at least 3 months after initiating gout
therapy
 Do not stop gout medication unless patient is showing
evidence of drug toxicity or adverse reaction
 Ask your friendly rheumatologist for help!

148
PROTECTION VS. FUTURE FLARES
 Colchicine : 0.5-1.0 mg/day
 Low-dose NSAIDS

 Both decrease freq & severity of flares

 Prevent flares with start of urate-lowering RX
Best with 6 mos of concommitant RX

 Won’t stop destructive aspects of gout

TREATMENT GOALS
 Rapidly end acute flares
Protect against future flares
Reduce chance of crystal inflammation

 Prevent disease progression

Lower serum urate to deplete total body urate pool
Correct metabolic cause
PREVENT DISEASE PROGRESSION
 Lower urate to < 6 mg/dl : Depletes
Total body urate pool
Deposited crystals

 RX is lifelong & continuous

 MED choices :

Uricosuric agents
Xanthine oxidase inhibitor