Osteoarthritis and Reactive Arthritis 1. Describe the pathogenesis, clinical features and management of reactive arthritis
Direct infection of joints – septic arthritis Inflammatory arthritis following infection – reactive arthritis Definition: Sterile inflammatory synovitis following an infection o Important extra-articular manifestations: Enthesopathy Skin inflammation Eye inflammation o Infections associated with reactive arthritis: Urogenital e.g. Chlamydia trachomatis Enterogenic infections e.g. Salmonella, Shigella, Campylobacter NB. Reactive arthritis may be first manifestation of HIV or Hep C. o Young adults – 20-40 years o Genetic predisposition and environmental trigger: HLA-B27 and e.g. Salmonella infection Symptoms follow 1-4 weeks after the infection Initial infection may be mild or inapparent in 10% of cases o
Clinical features of reactive arthritis Musculoskeletal symptoms 1. Arthritis Inflammation and morning joint stiffness Pattern of joints involved: i. Asymmetrical ii. Oligoarthritis (<5 joints) iii. Lower limbs typically affected 2. Enthesitis Inflammation where a ligament, tendon, fascia or capsule insert into bone Examples: i. Heel pain (Achilles tendon, plantar fascia) ii. Swollen fingers (dactylitis) iii. Painful feet (metatarsalgia due to plantar fascilitis) 3. Spondylitis = inflammation of the spine Sacrolitis – sacroiliac joint inflammation
Extra-articular features 1. Ocular Sterile conjunctivitis 2. Genito-urinary Sterile urethritis 3. Mucocutaneous Circinate balanitis (inflammation of the glans penis) Psoriasis-like rash on hands and feet (Keratoderma blennorhagia)
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Reiter’s syndrome: dysentery.
clinical triad of arthritis, conjunctivitis and urethritis following infectious
Compare Reactive arthritis with Rheumatoid arthritis: Feature
Rheumatoid arthritis
Reactive arthritis
Sex ratio Age
Female>Male All ages Polyarticular Symmetrical MCP, PIP, wrists, MTPs No No (cervical spine only) No Subcutaneous nodules Skin vasculitis Yes HLA-DR4
Male>Female 20-40 years Oligoarticular Asymmetrical Large joints Yes Yes Yes Keratoderma Balanitis
Arthritis Enthesitis Spondylitis Urethritis Skin Rheumatoid factor HLA association
No HLA-B27
Diagnosis of Reactive Arthritis • Clinical diagnosis (i.e. bedside) •
Investigations to exclude other causes of arthritis e.g. septic arthritis o Microbiology – Microbial cultures, serology o Immunology – Rheumatoid factor, HLA-B27 o Synovial fluid examination
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Arthrocentesis – the aspiration of fluid from a joint with a puncture needle, and the fluid is then analysed (it will look for the presence of rheumatoid factors, etc.) Stool cultures are required for analysis to determine reactive arthritis associated with enteritis (the causative bacterium or other infectious agent). Gram stain and culture to define causative organism and its antibiotic sensitivities. Radiology is important as some radiographs (such as of the hand) can be important in demonstrating some clinical features of reactive arthritis.
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Treatment Again, the main objectives in treating this condition include reducing inflammation, and maintain functioning of the joints involved. This incorporates… • Articular o NSAIDs o Intra-articular corticosteroid therapy • Extra-articular o Typically self-limiting, hence symptomatic therapy • No role for antibiotics • Refractory disease o Sulphasalazine (corticosteroids) The prognosis for reactive arthritis is very good. 2 out of 3 patients recover within 6 months; however 50% of these patients may experience further episodes of the condition. Unfortunately, 15% of patients develop an erosive disease which requires systemic steroid administration for treatment.
Septic Arthritis Predisposing factors: Impaired host defence o Elderly and young o Chronic illness e.g. diabetes, liver disease o Immunosuppressive medication e.g. corticosteroids
Direct penetration o Invasive procedures e.g. arthroscopy o IVDA o Puncture wounds Joint damage o Prosthetic joints, chronic arthritis e.g. rheumatoid arthritis. • • •
Usually associated with impaired host immunity or direct injury to joint Needs rapid diagnosis to prevent joint destruction Treatment o Antibiotic therapy o Drainage of joint
2. Describe the pathogenesis, clinical features and management of osteoarthritis
Osteoarthritis •
Osteoarthritis (OA) is a misnomer as it is not a disease of bone. Instead, it is a disease of cartilage that is associated with bone in a joint (articular cartilages in the knee are an example). The disease process in cartilage is: • First, there is a breakdown of proteoglycan and collagen in the cartilage. • The cartilage loses much of its water content. • Finally, there is thinning and fibrillation (where the cartilage has a more fibrous as opposed to smooth structure) of the cartilage.
Bony changes (sclerosis and osteophytes) are secondary processes and unrelated (not linked) to being caused by osteoporosis – they occur as the body tries to compensate for the loss of cartilage.
Osteoarthritis is: •
Slowly progressive disorder that typically affects the: o Joints of the hand Distal interphalangeal joints (DIP) Proximal interphalangeal joints (PIP) First carpometacarpal joint (CMC) o Spine o Weight bearing joints of lower limbs Knees and hips First metatarsophalangeal joint (MTP)
• May result in: o o o o o o
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
• Due to: o o o
Defective articular cartilage and damage to underlying bone Develops for 2 reasons: 1. Excessive loading on joints 2. Abnormal joint components Trauma:
o o o
Trauma to the matrix induces the release of growth factors from the matrix which in turn cause release of metalloproteinases (from chondrocytes) which cause rapid joint destruction via collagen and proteoglycan breakdown in the cartilage of the joint. In OA, the proteoglycans (which are a key part of the normal structure) break down and become fragmented, and therefore, the water content of the cartilage diminishes. As a result, the collagen (supporting network) also degenerates. This causes the cartilage to thin, and as a result, the bones are able to get closer together – in some extreme cases, they may touch and rub together – this will cause pain in the joints, and as the osteophytes generate more bone to compensate for the cartilage lost, the condition worsens.
Pathology • • •
Focal areas of damage to articular cartilage New bone formation at the joint margins (osteophytosis) Changes in the subchondral bone (sclerosis)
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Irreversible loss of articular cartilage
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Normal weight-bearing properties of articular cartilage depend on intact collagen scaffold and high aggrecan content Collagen and aggrecan turnover is slow o Half-life aggrecan – 3-4 years o Half-life collagen – decades
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Cartilage changes in osteoarthritis:
Reduced proteoglycan Chondromalacia Increased cartilage hydration Chondromalacia = softening of cartilage because of increased water : proteoglycan ratio in cartilage matrix. Cleavage of aggrecan in osteoarthritis mediated by ADAMTS aggrecanases Aggrecan fragments present in OA joint. Small molecular inhibitors of ADAMTS-4, -5 future therapies for OA? o Reduced collagen o Increased chondrocyte proliferation Intrinsic repair mechanism – matrix synthesis Abnormal mechanical stress leads to chondrocytes producing inflammatory mediators in OA tissue e.g. growth factors and cytokines which may have important roles in the disease o Focal areas of chondrocyte apoptosis Bone changes in OA o Changes in denuded sub-articular bone Proliferation of superficial osteoblasts results in production of sclerotic bone Focal stress on sclerotic bone can result in focal superficial necrosis in underlying bone and bone marrow. o o
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Clinical Features of OA • • • • • • • •
Old population Insidious onset over many years Mechanical pain that worsens with activity Bony enlargement, but no true swelling, warmth, erythema Progressive loss of joint range of motion Short-term stiffness (less than 30 mins) in morning and after rest. Osteophytes at the DIP joints are termed: Heberden’s nodes Osteophytes at the PIP joints are termed Bouchard’s nodes o Osteophytes = abnormal sclerotic subchondral bone and overgrowths at the joint margins, called osteophytes as a result of the bone attempting repair.
Radiographic Changes in OA • • • •
Joint space narrowing Subchondral bony sclerosis Osteophytes Subchondral cysts
A summary of the pathogenesis of OA… • • • • •
Old age and trauma are associated with the breakdown of cartilage collagen and proteoglycans. This in turn leads to a loss of water from the cartilage (the importance of water in cartilage has already been outlined). The cartilage then thins, becomes fibrillated (looks “furry”), and softens (which effectively makes it useless), and there is apparent moistening of the cartilage. Secondary proliferation of osteoblasts causes sclerosis and osteophytes (cysts in the bone). Secondary synovitis is also caused through the mechanism previously mentioned.
Treatment of OA • •
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Reassurance to the patient is very important – they do not have rheumatoid arthritis, and often patients know no better and think that they are suffering from this – of course rheumatoid arthritis is more severe than osteoarthritis. Non-Pharmacological treatment: o Weight loss is important if load-bearing joints (such as the knees) are affected. o Physiotherapy is important, firstly to increase muscle tone (of wasted muscles), and also to regain muscle (especially important in cases of quadriceps muscle wasting). o Hydrotherapy o Occupational therapy o Exercise Treatment of pain: o Analgesics, NSAIDs, and COX-2 inhibitors offer pharmacologic therapy. o Intra-articular steroids are often used to reduce inflammation and swelling. Joint replacement
Finally, probably the most important fact that you should have gained from this lecture is that osteoarthritis is an active metabolic process, and not just due to old age and the “wear and tear” of old joints.