Reactive Arthritis and Osteoarthritis

Question 1

What is reactive arthritis and when does it often occur?

Answer 1

A sterile inflammation in joints following infection especially urogenital (e.g. chlamydia trachomatis) and GI infections (e.g. salmonella, shigella, calmpylobacter infections)

NB it is not due to ongoing infection so antimicrobials do not work.

Question 2

Name 3 important extra-articular manifestations of reactive arthritis.

Answer 2

• Enthesopathy
• Skin inflammation
• Eye inflammation

Question 3

What can reactive arthritis be a first manifestation of?

Answer 3

HIV

Hep C infection

Question 4

Who is most likely to get reactive arthritis?

Answer 4

Young adults with a genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. salmonella infection)

Question 5

How long does it take for symptoms of reactive arthritis to manifest?

Answer 5

Can occur 1-4 weeks after infection and the infection may be mild.

Question 6

Describe the musculoskeletal symptos of reactive arthritis.

Answer 6

Arthritis - symmetrical, oligoarthritis (<5 joints), lower limbs typically affected

Enthesitis - heel pain (Achilles), swollen fingers (dactylitis), p_ainful feet_ (metatarsalgia due to plantal fasciitis)

Spondylitis - sacroiliitis (inflammation of sacro-illiac joints), spondylitis (inflammation of spine)

Question 7

Describe the extra-articular features of reactive arthritis.

Answer 7

Question 8

What are the differences between rheumatoid and reactive arthritis?

Answer 8

Question 9

How is diagnosis of reactive arthritis established? Name important investigations.

Answer 9

Clinical diagnosis, investigations for other causes of arthritis (e.g. septic arthritis) and investigations including:

Microbiology - cultures of microbes from blood, throat, urine, stool, urethra and cervix. Serology for HIV and Hep C etc.

Immunology - check for rheumatoid factor and HLA-B27

Synovial fluid examination (involves pus aspiration) -especially if only single joint affected.

Question 10

What are the differences in synovial fluid culture results in reactive and septic arthritis? Would you give antibiotics or joint lavage?

Answer 10

Septic arthritis positive

Reactive arthritis negative

So you would give antibiotic therapy for septic arthritis but not for reactive.

Joint lavage would also be done in septic arthritis (because build up of metalloproteinases can destroy cartilage)

Question 11

How is reactive arthritis treated?

Answer 11

No antibiotics.

• articular - NSAIDs
• intra-articular - corticosteroid therapy
• extra-articular - typically self-limiting, hence symptomatic therapy e.g. topical steroids & keratolytic agents in keratoderma
• Refractory disease - oral glucocorticoids, steroid-sparing agents e.g. sulphasalazine

Question 12

What is osteoarthritis?

Answer 12

Chronic slowly progressive disorder due to failure of articular cartilage that typically affecting joints of the hand (especially those involved in pinch grip), spine and weight-bearing joints (hips and knees)

Question 13

What does osteoarthritis typically affect?

Answer 13

Joints of the hand

• Distal interphalangeal joints (DIP)
• Proximal interphalangeal joints (PIP)
• First carpometacarpal joint (CMC)

Spine

Weight-bearing joints of lower limbs

• esp. knees and hips
• First metatarsophalangeal joint (MTP)

Question 14

What are the signs and symptoms of osteoarthritis?

Answer 14

• Joint pain - worse with activity, better with rest
• Joint crepitus - creaking, cracking grinding sound on moving affected joint
• Joint instability
• Joint enlargement - e.g. Heberden’s nodes
• Joint stiffness after immobility (‘gelling’)
• Limitation of motion

Question 15

What are the radiographic features of osteoarthritis?

Answer 15

• Joint space narrowing
• Subchondral bony sclerosis
• Osteophytes
• Subchondral cysts

Question 16

What is the name for osteophytes at….

a) the DIP joints?
b) the PIP joints?

Answer 16

Signs of osteoarthritis = Heberden’s joints, Bouchard’s nodes

Question 17

What are the radiographic differences between rheumatoid arthritis and osteoarthritis?

Answer 17

Question 18

What does joint space narrowing indicate?

Answer 18

Loss of articular cartilage - occurs in osteoarthrits(primary abnormality) and rheumatoid arthritis (secondary to synovitis damage)

Question 19

Describe the articular cartilage in osteoarthritis. Why does it develop?

Answer 19

Defective and irreversible

Develops due to…

• Excessive loading on joints
• Abnormal joint components

Question 20

List some risk factors that contribute to the development of osteoarthritis.

Answer 20

Question 21

What do the weight bearing properties of articular cartilage depend on ?

Answer 21

Collagen scaffold

High aggrecan content

Question 22

Describe the composition of healthy articular cartilage.

Answer 22

• Avascular and aneural
• Collagen - >90% is type II
• Chondrocytes
• Proteoglycan monomers* (aggrecan) - MW~ 2-3million kDa, 100 chondroitin sulphate chains, 60 keratan sulphate chains.
• Monomers arranged into supramolecular aggregates consisting of central hyaluronic acid filament and non-covalently linked aggrecan
• 80% of net weight is water because negatively charged chemical groups of GAGs attract water.

Question 23

What are proteoglycans and where are they found?

Answer 23

Proteoglycans - glycoproteins containing one or more sulphated glycosaminoglycan (GAG) chains

• Found in articular cartilage.
• Aggrecan is the major proteoglycan in articular cartilage.

Question 24

What are GAGs? Name some common GAGs.

Answer 24

GAG - glycosaminoglycan (chains)

GAGs are repeating polymers of disaccharides and include:

• Chondroitin sulphate (disaccharides are: glucuronic acid and N-acetyl galactosamine)
• Heparan sulphate
• Keratan sulphate (disaccharides are: galactose and N-acetyl lucosamine)
• Dermatan sulphate
• Heparin

Question 25

What is the only non-sulphated GAG? What is its role?

Answer 25

Hyaluronic acid is the only non-sulphated GAG and is major component of synovial fluid where it has an important role in maintaining synovial fluid viscosity Hyaluronic acid (**disaccharides are: glucuronic acid and N-acetyl glucosamine)**

Question 26

Give some examples of proteoglycans of these groups: 1. Intra-cellular 2. Cell-surface associated 3. Secreted into ECM

Answer 26

Intra-cellular * Serglycin Cell surface associated * Betaglycan * Syndecan Secreted into ECM * Aggrecan * Decorin * Fibromodulin * Lumican * Biglycan

Question 27

Describe the cartilage changes in osteoarthritis.

Answer 27

reduced proteoglycan reduced collagen chondrocyte changes e.g. apoptosis

Question 28

Describe the bone changes in osteoarthritis.

Answer 28

**Changes in denuded sub-articular bone** * Proliferation of superficial osteoblasts --\> production of sclerotic bone e.g. subchondral sclerosis * Focal stress on sclerotic bone --\> focal superficial necrosis **New bone formation at the joint margins (termed osteophytes)** * Sometimes you can detect osteophytes ‘at the bedside’ * Osteophytes at the distal inter-phalangeal joints =‘Heberden’s nodes’ * Osteophytes at the proximal inter-phalangeal joints =‘Bouchard’s nodes’

Question 29

How would you manage osteoarthritis?

Answer 29

* Education * Physical therapy – physiotherapy, hydrotherapy * Occupational therapy * Weight loss where appropriate * Exercise * Analgesia (no disease modifying osteoarthrtis drugs (DMOAD) available) * Paracetamol * Non-steroidal anti-inflammatory agents * Intra-articular corticosteroid injection * Joint replacement

Question 30

Which therapuetic approaches to osteoarthritis are commonly used but not approved in UK?

Answer 30

Glucosamine and chondroitin sulphate - dietary supplements Intra-articular injections of hyaluronic acid - to increase lubrication (viscosupplementation), but this has only been used in knee joint and is still experimental. Aim to increase viscosity in synovial fluid.