Arthritis of joints

Arthritis: inflammation of synovial joints is called arthritis.

Types of arthritis:

A. Non-Inflammatory arthritis
I. Osteoarthritis
II. Post-traumatic arthritis
III. Coagulopathic arthritis

B. Inflammatory arthritis:
I. Immune-mediated
• Seropositive arthritis- Rheumatoid arthritis
• Seronegative arthritis- Ankylosing spondylosis, Reactive arthritis, enteropathic
arthritis, Psoriatic arthritis
II. Infective arthritis
III. Crystal associated arthritis
• Gout (Sodium Urate)
• Pseudogout (Hydroxyapatite-Calcium-pyrophosphate)

Difference between inflammatory and non-inflammatory arthritis:

Inflammatory arthritis Non-Inflammatory arthritis
1. Worsening of pain Typically, in the morning Typically, in the evening or
after hard works
2. Swelling of joint Usually, present, soft tissue Usually, present, bony
3. Redness and warmth Sometimes Rarely
4. Morning stiffness >1 hour <30 minutes
5. Fever, drenching night Present Absent
sweats, unintentional
weight loss
6. Systemic features Sometimes Absent
7. CRP & ESR raises Frequent Uncommon
8. Synovial fluid WBC WBC>2000/mm3 WBC<2000/mm3
9. Example Rheumatoid arthritis Osteoarthritis
 Bones:
Definition: bone is a specialized connective tissues composed of intercellular calcified material,
the bone matrix and bone cells.
o Hydroxyapatite responsible for hardening of
Functions: bone.
o mechanical support, o Osteopontin or osteocalcin is produced by
o force transmission, osteoblasts and contributes to the regulation of
o internal organ protection, bone formation, mineralization, and calcium
o mineral homeostasis, homeostasis. Serum
o Hematopoiesis. o Osteopontin levels are used as a specific marker
of osteoblast activity.
Composition of bone:
o Matrix (extracellular component of bone)
• Osteoid -35% (Demineralized bone matrix)
▪ Type-I collagen
▪ Proteins
1. Glycosaminoglycans
2. Osteopontin or osteocalcin
• Minerals-65% (Mainly hydroxyapatite-[Ca10(PO4)6(OH)2])
▪ Calcium
▪ Phosphorus Bone matrix-----
o Bone cells o Woven bone-produced rapidly, haphazard
• Osteoblast arrangement of collagen, less structural integrity,
• Osteocytes always abnormal in adults,
• Osteoclasts o Lamellar bone-produce slowly, parallel arrangement
of collagen, more structural integrity.

Joints:
Definitions: Joints occur where two or more discrete bones meet each other in the body. These
joints can be fixed or can allow movement between the bones.

Types of joints:
There are three main types:
o Fibrous joints: join bone or cartilage by fibrous tissue and allow very little movement,
such as in the sutures of the skull.
o Cartilaginous joint:
• Primary cartilaginous joints- between bone and hyaline cartilage. Example-
xiphisternal joint.
 • Secondary cartilaginous joints- two bone ends are covered in a thin layer of
hyaline cartilage and these two ends are joined by interposed fibrous cartilage.
Example-symphysis pubis, vertebrae.

o Synovial joints: allows wide ROM and contains synovial cavity filled with synovial fluid
and enclosed by synovial membrane.
Types of synovial joint:
Synovial membrane:
The synovial membrane (also known as the synovial stratum, synovium or stratum synoviale): is
a specialized connective tissue that lines the inner surface of capsules of synovial joints and
tendon sheath.

The synovial membrane is variable but often has two layers:

o The outer layer, or subintima, can be of almost any type of connective tissue – fibrous
(dense collagenous type), adipose (fatty; e.g. in intra-articular fat pads) or areolar (loose
collagenous type).
o The inner layer (in contact with synovial fluid), or intima, consists of a sheet of cells
thinner than a piece of paper.
Synovial cells:
Synovial Prominent
Resemble Function
cell organelle
Type A Macrophage Mitochondria Phagocytosis
Endoplasmic Secrete hyaluronic acid, and proteins complex
Type B Fibroblast
reticulum (mucin) of synovial fluid
The synovium: is smooth except near the osseous insertion, where it is thrown into numerous
villous folds. The synovial lining lacks a basement membrane, which allows for efficient
exchange of nutrients, waste, and gases between blood and synovial fluid.
Synovial fluid: is a hyaluronic acid–rich plasma filtrate that acts as a viscous lubricant and
provides nutrition for the articular hyaline cartilage.
Non-
Normal Inflammatory Septic Bleeding
inflammatory
Volume
<3.5 >3.5 >3.5 >3.5 >3.5
(ml)
Viscosity High High Low Mixed Low
Clarity Clear Clear Cloudy Opaque Mixed
Color Colorless/straw Straw/yellow Yellow Mixed Red

WBC/mm3 <200 <2,000 5,000-75,000 >50,000 Similar to blood level

Polys (%) <25 <25 50-70 >70 Similar to blood level

Gram
None None None Positive None
stain
Glucose (mg/dl) concentration in synovial fluid is nearly equal to serum.
Hyaline cartilage:
o It is a unique connective tissue ideally suited to serve as an elastic shock absorber and
wear-resistant surface.
o Composition: water (70%), type II collagen (10%), proteoglycans (8%), and
chondrocytes.
o The collagen fibers enable resistance to tensile stresses and transmit vertical loads; water
and proteoglycans limit compression and friction.
o Hyaline cartilage lacks blood vessels, lymphatics, and nerves.

Chondrocytes:
o Synthesize and enzymatically digest matrix,
o Chondrocytes secrete degradative enzymes in inactive forms and enrich the matrix with
enzyme inhibitors.
o Diseases that destroy articular cartilage do so by activating the degradative enzymes and
decreasing the production of their inhibitors, leading to matrix breakdown.
o Cytokines such as IL-1 and TNF are released by chondrocytes, synoviocytes, fibroblasts,
and inflammatory cells and trigger degradative processes.
 Osteoarthritis:
Introduction:
Osteoarthritis is a non-inflammatory, chronic, degenerative conditions of joints, characterized by
degeneration of articular cartilage and formation of new bone, i.e. osteophytes.

Incidence
o hip OA (symptomatic)
▪ 88 per 100,000 per year
o knee OA (symptomatic)
▪ 240 per 100,000 per year
Risk factors
o modifiable
▪ articular trauma
▪ muscle weakness
▪ heavy physical stress at work
▪ high impact sporting activities
o non-modifiable
▪ gender
▪ females >males
▪ increased age
▪ genetics
▪ developmental or acquired deformities
▪ hip dysplasia
▪ slipped capital femoral epiphysis
▪ Legg-Calvé-Perthes disease

Typed of osteoarthritis:
A. According to cause:
a. Primary
b. Secondary
1. Trauma
2. Pre-existing bone diseases-RA, Spondyloarthropathy, Gout, septic arthritis, Paget
disease, osteonecrosis.
3. Drugs- corticosteroids, anti-cancer drugs.
4. Chronic generalized diseases- DM, COPD, malignancy,
5. Bleeding disorders- hemophilia,
6. Hemoglobinopathies- sickle cell disease
7. Metabolic disease- hemochromatosis, chondrocalcinosis, acromegaly
8. Neuropathies
B. According to joint damage: symptomatic and asymptomatic.
C. According to pattern of joint involvement: localized and generalized OA),
D. According to the type of bone reaction: hypertrophic and atrophic OA
E. According to the disease process: progressive and inactive OA
F. According to nature: ‘sporadic’ or ‘common-or-garden OA’ and ‘atypical forms of OA’

Pathogenesis:
The lesions of OA stem from degeneration of the articular cartilage and disordered repair.
Genetic factors, environmental factor and mechanical stress→ predispose to chondrocyte injury
that causes matrix alteration→Chondrocytes proliferate and synthesize proteoglycans, but
degradation exceeds synthesis→ leads to changes in proteoglycan Composition→ Chondrocytes
secrete matrix metalloproteases (MMPs) that degrade the type-II collagen network→Cytokines
IL-1, IL-6, IL-8, PG E2, NO, TNF from chondrocytes and synovial cells, and TGF-β from
synovial cells→ TGF-B induces the production of MMPs→low-level inflammation contributes
to disease progression→ matrix water content increases, proteoglycan concentration decreases,
and horizontally arranged collagen type II fibers in the superficial zone are cleaved→result
in fissures and clefts that create a granular and soft articular surface→chondrocytes die, full-
thickness portions of cartilage are sloughed into the joint, forming loose bodies→Exposed
subchondral bone becomes the new articular surface→Advanced disease is characterized by
chondrocyte loss and severe matrix degradation→ Although chondrocytes may proliferate and
attempt to repair damaged matrix, continued degradation exceeds repair in early OA→ Late OA
is evidenced by loss of both matrix and chondrocytes with subchondral bone damage.

Sites:
o Typically, only one or a few joints are involved, except in the uncommon generalized
variant. The joints commonly involved include the hips, knees, lower lumbar and
cervical vertebrae, proximal and distal interphalangeal joints of the fingers, first
carpometacarpal joints, and first tarsometatarsal joints.
o Heberden nodes, prominent osteophytes at the distal interphalangeal joints, are common
in women.
o Wrists, elbows, and shoulders are usually spared.

Histologic findings of OA:

o the characteristic fibrillation of articular cartilage.
o Eburnated articular surface (Exposed subchondral bone becomes the new articular
surface, which is burnished by friction with the opposing surface, giving it the
appearance of polished ivory) exposing subchondral bone
o subchondral cysts
o residual damaged articular cartilage
o Mushroom-shaped bony outgrowths (osteophytes) develop at the margins of the articular
surface and are capped by fibrocartilage and hyaline cartilage that gradually ossify.
 o Symptoms and signs of osteoarthritis
o Pain
• Insidious onset over months or years
• Variable or intermittent nature over time (‘good days, bad days’)
• Mainly related to movement and weight-bearing, relieved by rest
• Only brief (< 15 mins) morning stiffness and brief (< 5 mins) ‘gelling’ after rest
• Usually only one or a few joints painful
o Other symptoms:
• Joint stiffness (particularly short-lasting
stiffness after a period of inactivity)
• Fatigue
• Sleep disturbance
• Depression
• Reduced functional ability and activities
o Clinical signs
• Restricted movement due to capsular thickening or blocking by osteophyte
• Palpable, sometimes audible, coarse crepitus due to rough articular surfaces
• Bony swelling around joint margins
• Deformity, usually without instability
• Joint-line or periarticular tenderness
• Mild or absent synovitis
• Weakness and wasting of muscles acting on the joint

Classifications:
The Outerbridge classification: according to the changes to the articular surface of all synovial
joints, particularly by arthroscopy----
Grade Findings
1 Softening and swelling of the cartilage
2 Fragmentation and fissuring of the cartilage in an area less than ½ inch in diameter
3 Fragmentation and fissuring of the cartilage in an area more than ½ inch in diameter
4 Exposure of underlying bone.

Kellgren and Lawrence scoring system: According to the X-ray changes—

Stage Categories Findings
0 Normal No features of OA
1 Doubtful Minimal osteophyte, doubtful significance
2 Minor Definite osteophyte, no loss of joint space
3 Moderate Some diminution of joint space
4 Severe Advanced joint space loss and sclerosis of bone
Key pathological features of OA:
Pathology Radiographic correlates
1. Focal areas of loss of articular cartilage Joint space narrowing (if loss is extensive)
2. Bone growth at the joint margins Osteophytes
3. Sclerosis of underlying bone Sclerosis of subchondral bone
4. Cyst formation in underlying bone Bone cysts
5. Loss of bone Bone attrition
6. Varying degrees of synovial inflammation Effusions may be apparent
7. Fibrosis and thickening of the capsule Not visible on radiograph

Investigations:
o Serology: Raised ESR and CRP
o Biomarkers:
Bone deoxypyridinoline (DPD),
resorption pyridinoline, (PYD),
markers amino-terminal cross-linking telopeptide of type I collagen (NTX) and
carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I).
Bone osteocalcin (OC),
formations procollagen type I C propeptide (PICP)
markers bone-specific alkaline phosphatase (BALP)
Cartilage C2M (MMP-derived degradation of type II collagen)
turnover COMP (cartilage oligomeric matrix protein)
All these markers are produced by osteoblast and collage type-I.
MMP- matrix metalloproteinase
 o Genetic screening: also, can help in the identification of differentially expressed
members of the chondrocyte, synovial cell or osteoblast transcriptome in various clinical
stages of the disease.

o IMAGING
o Radiographs
▪ recommended views for hip
▪ standing AP pelvis
▪ AP + lateral hip
▪ optional views
▪ false profile view (e.g. hip dysplasia)
• recommended views for knee
o weight-bearing views of affected joint
• optional views
o knee
▪ sunrise view
▪ PA view in 30 degrees of flexion
• Findings for knee
o pattern of arthritic involvement
▪ medial and/or lateral tibiofemoral, and/or patellofemoral

▪ findings for hip

▪ osteoarthritis
▪ joint space narrowing
▪ osteophytes
▪ subchondral sclerosis
▪ subchondral cysts
▪ pelvic obliquity
▪ may be secondary to spinal deformity
▪ may cause leg-length issues
▪ acetabular retroversion
▪ makes appropriate positioning of acetabular component
more difficult intraoperatively

MRI:
o provides useful information for early OA diagnosis
o more sensitive to detect joint effusion/synovitis, cartilage, labral, and bone marrow
lesions
CT
o 3D assessment of acetabular and proximal femoral anatomy
o surgical planning in cases of femoroacetabular impingement (FAI) or acetabular
dysplasia
o assess the amount of bone stock
Ultrasound
o can depict joint effusions and synovitis by increased synovial vascularization
o can detect osteophytes
o it can be used for image-guided injections

Histology
o loss of superficial chondrocytes
o replication and breakdown of the tidemark
o fissuring
o cartilage destruction with eburnation of subchondral bone

TREATMENT
A. Nonoperative
o NSAIDs and/or tramadol
▪ indications
▪ first line treatment for all patients with symptomatic arthritis
▪ technique
▪ NSAID selection should be based on physician preference, patient acceptability
and cost
o walking stick
▪ decreases the joint reaction force on the affected hip when used in the contralateral
upper extremity
o weight loss, activity modification and exercise program/physical therapy
▪ indications
▪ first line treatment for all patients with symptomatic arthritis
▪ BMI > 25
▪ technique
▪ exercise aimed at increasing flexibility and aerobic capacity
o corticosteroid joint injections
▪ indications
▪ can be therapeutic and/or diagnostic of symptomatic hip osteoarthritis
▪ use for short-term pain relief strongly supported in 2013 AAOS CPG

o controversial treatments
▪ acupuncture
▪ viscoelastic joint injections
▪ glucosamine and chondroitin
 B. Operative for HIP OA:
o arthroscopic debridement
▪ indications
▪ controversial
▪ degenerative labral tears
▪ not recommended for Tönnis grade 2 radiographic arthroses
▪ high rate of conversion to arthroplasty
o periacetabular osteotomy +/- femoral osteotomy
▪ indications
▪ symptomatic dysplasia in an adolescent or young adult with concentrically
reduced hip and mild-to-moderate arthritis
▪ outcomes
▪ mixed results
▪ literature suggest this can delay need for arthroplasty
o femoral head resection
▪ indications
▪ pathological hip lesions
▪ painful head subluxation
o hip resurfacing
▪ indications
▪ young active, male, patients with hip osteoarthritis
▪ increasing concern for metal-on-metal adverse events, procedure therefore
decreasing in use
o total hip arthroplasty (THA)
▪ indications
▪ end-stage, symptomatic or severe osteoarthritis arthritis

▪ preferred treatment for older patients (>50) and those with advanced structural
changes
▪ recommendation is to wait at least 3 months after ipsilateral intaarticular hip
injection to decrease risk of prosthetic joint infection

C. Operative treatment for knee OA:

o high-tibial osteotomy
• indications
▪ younger patients with medial unicompartmental OA
• technique
▪ valgus producing proximal tibial osteotomy
• outcomes
▪ AAOS guidelines: limited evidence for
o unicompartmental arthroplasty (knee)
 • indications
▪ isolated unicompartmental disease
• outcomes
▪ TKA have lower revision rates than UKA in the setting of unicompartmental
OA
o total knee arthroplasty
• indications
▪ symptomatic knee osteoarthritis
▪ failed non-operative treatments
• techniques
▪ cruciate retaining vs. cruciate sacrificing implants show no difference in
outcomes
▪ patellar resurfacing
▪ no difference in pain or function with or without patella resurfacing
▪ lower reoperation rates with resurfacing
▪ drains are not recommended
o controversial treatments
• arthroscopic debridement or lavage
▪ AAOS guidelines: strong evidence against
• arthroscopic meniscal debridement
▪ AAOS guidelines: inconclusive evidence

Early-onset OA:
o Unusually, typical symptoms and signs of OA may present before the age of 45.
o In most cases, a single joint is affected and there is a clear history of previous trauma
Causes:
A. Monoarticular
1. Previous trauma,
2. localized instability
B. Pauciarticular or polyarticular
1. Juvenile idiopathic arthritis
2. Metabolic or endocrine disease: Haemochromatosis, Ochronosis, Acromegaly
3. Spondylo-epiphyseal dysplasia
4. Late avascular necrosis
5. Neuropathic joint
6. Kashin–Beck disease
Assessment scoring system:
Shoulder Oxford shoulder score
Hip Hip Dysfunction and Osteoarthritis Outcome Score ‘HOOS’
Oxford hip score
Harris hip score
Knee Oxford knee score
Knee dysfunction and Osteoarthritis Outcome Score ‘KOOS’
Hand Australian–Canadian Hand Osteoarthritis Index ‘AUSCAN’

UK National Institute for Health and Care Excellence (NICE) 2014 guideline:
Step 1 Take a holistic approach and encourage self-management
Step 2 Introduce the ‘core treatments’ appropriate for most people with OA.
Step 3 Introduce specific non-surgical interventions-non pharmacological or pharmacological
Step 4 Consider surgical options.

Special forms of osteoarthritis:

Rapidly destructive osteoarthritis of the hip or Atrophic destructive OA:
o Rapidly destructive osteoarthritis of the hip, also known as rapidly progressive
osteoarthritis of the hip, is a rare chondrolysis of unknown etiology which can progress to
complete destruction of the femoral head. It is a diagnosis of exclusion.
o Epidemiology-common in middle age to elderly females
o The cause is unknown.
o Clinical presentation- Hip pain, rapid period in which the joint damage progresses with
extensive bone loss, such that the whole head of the femur or humerus may ‘disappear’
o Plain radiograph- varies from rapidly progressive chondrolysis (>2 mm/year or >50%
joint space narrowing/year) to complete osteolysis of the femoral head, very little
osteophyte formation;
o synovial fluid- is usually bloody, and contains large numbers of apatite crystals, which
may contribute to the damage
o MRI-joint effusion and synovitis, bone marrow edema of the femoral head, femoral head
flattening (~92%), subchondral fracture, subchondral cysts
o Treatment- total hip arthroplasty.

Milwaukee shoulder syndrome

o Milwaukee shoulder syndrome (MSS) is a rare destructive, calcium phosphate crystalline
arthropathy. It encompasses an effusion that is noninflammatory with numerous
aggregates of calcium hydroxyapatite crystals in the synovial fluid, associated with
rotator cuff defects.
 o Signs and symptoms may include the following:
• Limited active range of motion, usually unrestricted passive range of movement
• Joint pain
• Joint inflammation and tenderness
• Synovial hemorrhagic effusion/hematoma
• Radiologic positive findings
• Hydroxyapatite crystals in synovial fluid

o Diagnosis is made with arthrocentesis and Alizarin Red staining along with clinical
symptoms.[5] X-rays, arthrography, ultrasonography, CT imaging and MRI imaging are
also helpful in diagnosing this condition

o Treatment may include the prescription of one or more of the following:

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Intra-articular steroids
• Physical therapy
• Partial or complete arthroplasty

Hypertrophic OA
o It is particularly common at the hip and knee, and characterized by massive osteophyte
formation, with relatively little damage to subchondral bone or cartilage.
o It may be associated with----
• Calcium pyrophosphate dihydrate (CPPD) crystal deposition (chondrocalcinosis),
• Diffuse idiopathic skeletal hyperostosis (DISH), (extensive osteophyte formation
and enthesis calcification).

Erosive inflammatory OA of the interphalangeal joints:

o Site- terminal interphalangeal joints of the hand
o Associated with a lot of inflammation and the development of joint erosions
o Risk factors-rheumatoid arthritis.

Kniest Syndrome
o Rare AD genetic disorder due to COL2A1 gene mutation at chromosome 12.
o Defective type-II collagen synthesis
o Clinical features
o Dwarfism, short limb, kyphoscoliosis, early development of OA
o Hearing difficulty, early cataract and respiratory trat infection
Kashin Beck disease
o an extremely rare polyarticular form of OA affecting 1 in 6 million people in the
Northern China and Eastern Siberia.
o Those affected have symptoms of joint pain, polyarticular swelling and deformity from
childhood. Adults have short stature and their
o Radiographs reveal distorted epiphyses and tubular long bones

Mseleni joint disease:

o It is a chondrodysplasia first described in 1970.
o It is geographically confined to a remote area in the Maputaland region in northern
Kwazulu Natal, South Africa.
o This disease affects most joints but primarily those of the hip; it is a progressive
condition beginning with pain and stiffness until the patient's ability to walk becomes
compromised.
o Mseleni joint disease is characterized by two distinct abnormalities, protrusio acetabuli
that mainly affects females and increases in frequency with age, and hip dysplasia that is
more frequent with age.

Chondrocalcinosis or cartilage calcification:

o Calcification of articular hyaline cartilage, or of the fibrocartilage pads within synovial
joints, such as the menisci of the knee joint (‘chondrocalcinosis’),
o Age- after 50 years
o Risk factors- familial, hyperparathyroidism, hypophosphatemia, idiopathic, gout,
pseudogout.
o Usually, asymptomatic
o Site- foot, ankle, wrist, knee.
o The material that is most commonly found in calcified menisci is made of aggregates of
tiny calcium pyrophosphate dihydrate (CPPD) crystals. If these crystals get dislodged
from the menisci, entering the synovial cavity, they can trigger an intense, self-limiting
synovitis, just like gout – hence the name ‘pseudogout’. The knee is to pseudogout what
the first MTPJ is to gout.
o Attacks result in painful, hot swollen joints, and can be relieved by aspiration of the joint
and injection of steroids, if not contraindicated, and the use of non-steroidal anti-
inflammatory drugs.
o A variant of osteoarthritis called ‘pyrophosphate arthropathy’ has been described in
association with widespread chondrocalcinosis