Inflammatory Arthritis Flashcards
What is rheumatoid arthritis?
Inflammatory autoimmune disorder characterized by joint pain, swelling, and synovial destruction
What is the aetiology of rheumatoid arthritis?
- Chronic inflammatory autoimmune disorder of unknown etiology
- Hypotheses suggest the aetiology is multifactorial, with the following factors playing a role:
- Genetic predisposition - seems to be associated with specific HLA types e.g. HLA DRB1 gene
- Environmental triggers - infection and smoking increase anti-CCP
- Hormonal factors - higher incidence in females (3:1)
- Prevalence peaks 35-50 years of age
What is the pathophysiology of rheumatoid arthritis?
- Initially, non-specific inflammation affects the synovial tissue, which is later amplified by activation of T cells
- Triggers e.g. smoking, infection or trauma have been implicated
- With time it may lead to inflammatory joint effusion and synovial hypertrophy as well as progressive destruction and deterioration of cartilage and bone
- Inflammatory pannus (inflammatory granulation tissue) forms which produces proteinases that destroy the cartilage extracellular matrix
- Tendon rupture and soft tissue damage can occur leading to joint instability and subluxation
- Chronic phase - fibrosis, deformity
Explain the pathophysiology of the generation of auto-antibodies in rheumatoid arthritis?
- Susceptibility genes lead to the conversion of arginine (A) into citrulline (C) → protein will unfold due to loss of positive charge
- The unfolded protein acts as an antigen - autoimmune response mediated by auto-reactive CD4+ T cells
- Involvement of pro-inflammatory CD4+ Th1 and Th17 effector cells and macrophages
- Driven by a type IV hypersensitivity mechanism, but secondary type III hypersensitivity responses also occur as anti-citrullinated peptide antibodies (can be generated in the lungs from smoking) can form immune complexes with the citrullinated proteins produced in an inflamed synovium → neutrophil infiltration and activation
Explain the pathophysiology of rheumatoid factor?
- IgM or IgA antibody that binds to Fc region of IgG
- Found in ~80% of patients with RA (15% are negative for RF)
- Patients with high titres of RF are more at risk of extra-articular disease
Explain the pathophysiology of anti-CCP.
- Can be present for several years prior to articular symptoms
- More likely to be associated with erosive damage
- Associated with current/previous smoking history
- Correlates with disease activity and levels remain positive despite treatment
- Low sensitivity - absence does not exclude disease
What are the articular manifestations of rheumatoid arthritis?
- Polyarthralgia
- Symmetrical pain and swelling of affected joints
- Rapid onset
- Most commonly in the small joints of the hands and feet (PIPs/MCPs and MTPs)
- Larger joints e.g. knees, shoulders, elbows and atlantoaxial joint can also be affected as the disease progresses
- Early morning stiffness > 30 mins that usually improves with activity
- Reduction in grip strength
- Joint deformities (‘rheumatoid hand’)
- Swan neck deformity: PIP hyperextension and DIP flexion
- Boutonniere deformity: PIP flexion and DIP hyperextension
- Atlanto-axial subluxation
What are the extra-articular manifestations of rheumatoid arthritis?
- Systemic inflammation can cause extra-articular co-morbidities
- Constitutional symptoms: low-grade fever, myalgia, malaise, fatigue, weight loss, night sweats
- Lungs: interstitial fibrosis, pneumoconiosis (Caplan syndrome), rheumatoid lung nodules, pleuritis, pleural effusions
- Heart: pericarditis, myocarditis, increased risk of CVD
- Skin: pyoderma gangrenosum, Raynaud’s phenomenon, rheumatoid skin nodules
- Eye: keratoconjunctivitis
- Other MSK: osteopenia/osteoporosis, Sjogren syndrome
What is the typical presentation of rheumatoid arthritis?
- Swelling of affected joints
- Synovial proliferation and reactive joint effusion cause soft tissue swelling - symmetrical synovitis (doughy swelling)
- Positive compression tests of MCP and MTP joints
- Bouchard’s nodes - bony swellings of proximal IPJ (also see in OA)
- 25% of patients develop rheumatoid nodules, most commonly on extensor surfaces or sites of frequent mechanical irritation
- Necrotising granulomas with a palisade of macrophages surrounding a central area of collagen necrosis
- Synovial herniation - cysts e.g. Baker’s cyst
What are the investigations and their findings of rheumatoid arthritis?
Bloods
- Raised inflammatory markers (CRP, plasma viscosity, ESR)
- Autoantibodies: presence of Rheumatoid factor (60-70% specific) or anti-CCP antibodies (90-99% specific)
Imaging
- X-ray of hands and feet - helps with diagnosis and determination of disease severity
- Early disease: can be normal, may show soft tissue swelling and periarticular osteopenia
- Late disease: erosions, subluxation
- USS - may be useful in detecting synovial inflammation if their is clinical uncertainty (especially in early RA), useful in making treatment changes
- MRI - extremely sensitive but only use if diagnostic doubt
What is the management of rheumatoid arthritis?
Symptomatic relief
- Analgesics, NSAIDs and steroids can be used short term for symptomatic relief
- Rheumatoid nodules don’t always respond to DMARDs - excision if problematic but recurrence is high
DMARDs (first line)
- Conventional disease modifying anti-rheumatic drugs (cDMARDs) e.g. oral methotrexate (first choice), subcutaneous methotrexate, leflunomide, or sulfasalazine
- Aim to start patients on DMARDs within 3 months of symptom onset
Biological disease modifying anti-rheumatic drugs (second line)
- Given if have tried 2 DMARDs and patient still has DAS28 score > 5.1
- Examples include anti-TNF agents and T cell receptor blockers
What are spondyloarthropathies?
family of inflammatory arthritides characterised by involvement of both the spine and joints, principally in genetically predisposed (HLA B27 positive) individuals
What is HLA B27?
- Diseases associated with the HLA B27 subtype can be remembered with the mnemonic PAIR - psoriatic arthritis, ankylosing spondylitis, IBS (+ enteropathic arthritis), reactive arthritis
- Higher prevalence in the northern hemisphere, especially Scandinavian countries
What are the shared rheumatological features of spondyloarthropathies?
- Sacroiliac and spinal involvement
- Inflammatory arthritis - oligoarticular, asymmetric, predominantly lower limb
- Synovitis: inflammation of joint and tendon sheath linings
- Enthesitis: inflammation at sites where ligaments and tendons attach to bones e.g. Achilles tendinitis, plantar fasciitis
- Dactylitis (‘sausage’ digits): inflammation of the entire digit
What are the shared extra-articular features of spondyloarthropathies?
- Ocular inflammation (anterior uveitis, conjunctivitis)
- Mucocutaneous lesions
- Rare aortic incompetence or heart block
- No rheumatoid nodules
What is ankylosing spondylitis?
Chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine
What is the aetiology of ankylosing spondylitis?
- Genetic predisposition - HLA B27 (90%)
- More common in males (~4:1)
- Typical age of onset is 20-40 years
What is the pathophysiology of ankylosing spondylitis?
What are the articular symptoms of ankylosing spondylitis?
- Spinal and neck pain
- Gradual onset of dull pain that progresses slowly
- Morning stiffness > 30 mins that improves with activity
- Peripheral arthritis (knee, shoulders, hips) - rare
- Late AS - loss of lumbar kyphosis with pronounced cervical lordosis (‘question mark’ posture)
What are the signs of ankylosing spondylitis?
-
Schober’s test: used to measure lumbar spine flexion
- Involves measuring 5cm below the posterior superior iliac crests and 10cm above, whilst the patient is upright, then asking them to bend forwards and remeasuring the distance
- In normal situations it should extend beyond 20cm
- Reduced chest expansion
- Occiput-to-wall (normal = 0)
- Inflammatory enthesitis e.g. of the Achilles tendon, iliac crests - painful on palpation
What are the extra-articular features of ankylosing spondylitis?
- Anterior uveitis
- Cardiovascular involvement (aortic valve/root - aortic regurg)
- Pulmonary involvement (upper lobe fibrosis)
- Asymptomatic enteric mucosal inflammation
- Neurological involvement (rarely A-A subluxation)
- Amyloidosis
What is seen in blood tests for ankylosing spondylitis?
- Raised inflammatory markers
- HLA B27
What is seen in imaging in ankylosing spondylitis?
- X-ray
- Bone density (normal early disease, reduced in later disease)
- May show sclerosis and fusion of the sacroiliac joints
- Bony spurs from the vertebral bodies (syndesmophytes) can bridge the intervertebral disc resulting in fusion, producing a ‘bamboo spine’
- Skinny corners
- Common for X-rays to be normal at the time of presentation
- MRI - can detect sacroiliitis (active inflammation) and earlier changes such as bone marrow oedema and enthesitis of the spinal ligaments
What is the ASAS classification for ankylosing spondylitis?
- In patients with ≳ 3 months back pain and age of onset <45 years
- Sacroiliitis on imaging and ≳1 SpA feature OR HLA-B27 positive and ≳ 2 other SpA features (e.g. inflammatory back pain, arthritis, enthesitis, dactylitis, raised CRP)
What is the non-pharmacological management for ankylosing spondylitis?
Physiotherapy, occupational therapy, orthotics, chiropodist
What is the pharmacological management for ankylosing spondylitis?
- NSAIDs - first line
- Symptomatic - corticosteroids/joint injections, topical steroid eyedrops
- DMARDs e.g. methotrexate, sulfasalazine, leflunomide
- Anti-TNF in severe disease unresponsive to NSAIDs and methotrexate
- Consider other biologics if still unresponsive e.g. secukinumab (anti-IL17)
What is the surgical management for ankylosing spondylitis?
Mainly reserved for hip and knee arthritis, kyphoplasty is controversial and carries considerable risk
What is psoriatic arthritis?
Inflammatory arthritis associated with psoriasis, but 10-15% of patients can have PsA without psoriasis
What is the aetiology of psoriatic arthritis?
Occurs in up to 30% of people affected by skin psoriasis
What are the articular symptoms of psoriatic arthritis?
- Usually an asymmetrical oligoarthritis but can affect the hands in a similar pattern to RA
- Predominantly affects joints of hands and feet
- 20% of cases involve sacro-iliac joints
- Some patients have a predilection for arthritis of the DIP joints of the fingers and/or toes
- Spondylitis, actylisis and enthesitis commonly occur
What are the extra-articular symptoms of psoriatic arthritis?
- Eye disease
- Nail involvement (pitting, onycholysis)
What are the clinical subgroups of psoriatic arthritis?
- Confined to DIP joints hands/feet
- Symmetric polyarthritis (similar to RA)
- Spondylitis (spine involvement) +/- peripheral joint involvement
- Asymmetric oligoarthritis with dactylitis
- 5% of patients have a particularly aggressive and destructive form of the condition known as arthritis mutilans - usually occurs in the hands, involves the reabsorption of bone and collapse of soft tissue
What are the investigations for psoriatic arthritis?
- Bloods - ↑ inflammatory markers, negative RF
- X-ray
- Marginal erosions and ‘whiskering’
- Osteolysis
- Enthesitis
What is the non-pharmacological management for psoriatic arthritis?
Physiotherapy, occupational therapy, orthotics, chiropodist
What is the pharmacological management for psoriatic arthritis?
- NSAIDs - first line
- Symptomatic - corticosteroids/joint injections, topical steroid eyedrops
- DMARDs e.g. methotrexate, sulfasalazine, leflunomide
- Anti-TNF in severe disease unresponsive to NSAIDs and methotrexate
- Consider other biologics if still unresponsive e.g. secukinumab (anti-IL17)
What is enteropathic arthritis?
Refers to an inflammatory arthritis involving the peripheral joints and sometimes the spine, occurring in patients with inflammatory bowel disease
What is the aetiology of enteropathic arthritis?
- 10-20% of IBD sufferers will experience spine or joint problems
- 20% of patients with Crohn’s will have sacroiliitis
- Worsening of symptoms during flare-ups of IBD
What is pathophysiology of enteropathic arthritis?
Organisms with high lipopolysaccharides in cell wall trigger immune reaction
What is the presentation of enteropathic arthritis?
- Patients present with arthritis in several joints, especially knees, ankles, elbows, and wrists, sometimes spine, hips, or shoulders
- GI - loose, watery stool with mucous and blood
- Weight loss
- Low grade fever
- Uveitis
- Pyoderma gangrenosum
- Enthesitis - Achilles tendonitis, plantar fasciitis, lateral epicondylitis
- Aphthous ulcers
What are the investigations for enteropathic arthritis?
- Upper and lower GI endoscopy with biopsy showing ulceration/colitis
- Joint aspirate - no organisms or crystals (rules out septic arthritis and crystal arthropathies)
- ↑ inflammatory markers
- X-ray/MRI - sacroiliitis
- USS - synovitis/tendosynovitis
What is the management of enteropathic arthritis?
- Usually involves finding mediation to manage both the underlying condition and the arthritis
- Management of the arthritis similar to other seropositive arthritis (physio, NSAIDs, DMARDs, anti-TNF etc.)
What is reactive arthritis?
Infection induced systemic illness characterised primarily by an inflammatory synovitis from which viable microorganisms cannot be cultured
What is the aetiology of reactive arthritis?
- Most common preceding infections are urogenital (e.g. chlamydia, neisseria) and enterogenic (e.g. salmonella, campylobacter)
- HLA B27 positive
- Young adults (20-40)
- Equal sex distribution
What is the pathophysiology of reactive arthritis?
- Occurs in response to an infection in another part of the body
- Large joints e.g. the knee become inflamed around 1‐3 weeks following the infection
- The infection triggers an autoimmune arthropathy
What is the presentation of reactive arthritis?
- Present 1-4 weeks after infection
- General symptoms - fever, fatigue, malaise
- Asymmetrical monoarthritis or oligoarthritis
- Enthesitis
- Mucocutaneous lesions
- Keratoderma blennorrhagia
- Circinate balanitis
- Painless oral ulcers
- Hyperkeratotic nails
- Ocular lesions (uni or bilateral) - conjuntivitis, iritis
- Visceral manifestations - mild renal disease, carditis
What is Reiter’s syndrome?
triad of urethritis, conjunctivitis/uveitis/iritis and arthritis
What are the investigations of reactive arthritis?
- Bloods - ↑ inflammatory markers, FBC, U+Es, LFTs, HLA B27 (rarely necessary)
- Cultures - blood, urine, stool
- Joint fluid analysis - rule out infection (aspirate should be negative)
- X-ray of affected joints
- Ophthalmology opinion
What is the management of reactive arthritis?
- Treatment is aimed at the underlying infectious cause and symptomatic relief, including IA or IM steroid injections
- Most cases self-limiting - 90% resolve spontaneously within 6 months
- Remaining 10% - chronic progressive erosive disease, requiring DMARDs
What is gout?
Potentially disabling and erosive inflammatory arthritis caused by the deposition of monosodium urate crystals into joints and soft tissues
What are the causes of increased urate production -> causes of hyperuricaemia?
- High dietary purine intake (red meat, seafood, corn syrup)
- Alcohol
- Inherited enzyme defects
- Usually idiopathic - 90% unknown enzyme deficiency
- HGPRT enzyme deficiency impairs purine nucleotide salvage pathway → degraded to urate
- Myeloproliferative/lymphoproliferative disorders
- Psoriasis
- Haemolytic disorders
What are the causes of reduced urate excretion -> causes of hyperuricaemia?
- Chronic renal impairment
- Volume depletion e.g. heart failure
- Hypothyroidism
- Diuretics
- Cytotoxics e.g. cyclosporin
What are the risk factors of gout?
- Age - rare under 20, decreases after age 80
- More common in men than women
- Very rare in women before the menopause (oestrogen is protective)
- Some evidence for a genetic predisposition
What is the pathophysiology of gout?
- Uric acid is the final compound in the breakdown of purines (A+G) in DNA metabolism
- Recurrent gout flares are the result of the acute inflammatory response to deposited MSU crystals
- Chronic gouty arthritis and tophaceous gout is the result of a chronic granulomatous inflammatory response to deposited crystals
- Histology of gouty tophi - amorphous eosinophilic debris and inflammation (giant cells)
What is the presentation of acute gout?
- Although any joint can be affected the first metatarsal phalangeal (MTP) joint is the classic site of disease
- Ankle and knee are the other most commonly affected joints
- Severe pain, hot swollen joint which may mimic a septic arthritis
- Abrupt onset, often overnight
- Settles in about 10 days without treatment, 3 days with treatment
What is the presentation of chronic tophaceous gout?
- Gouty tophi are painless white accumulations of uric acid which can occur in the soft tissues and occasionally erupt through the skin
- Often diuretic associated
- May get acute attacks
- Chronic gout can result in a destructive erosive arthritis
What are the investigations of gout?
Bloods
- Serum uric acid raised
- May be normal during acute attack (~40%)
- Raised inflammatory markers
- Renal function (ACR and GFR) - cause or effect
Aspiration of synovial fluid
- Polarised microscopy - needle shaped, negative birefringent crystals
- Gram stain and culture to rule out septic arthritis in acute gout
X-rays
- Erosion may be visible in long-standing gout
What is the acute management of gout?
- NSAIDs e.g. naproxen
- Colchicine if NSAIDs not suitable e.g. patients with heart failure, chronic kidney disease
- Side effect: diarrhoea
- Steroids (third line) - orally, IM or intra-articular into joint
- Lifestyle modification is usually enough to prevent further flares
What is the prophylactic therapy of gout?
- Prophylaxis should be started 4-6 weeks after acute attack and requires cover with NSAIDs for first 6 months (or colchicine/steroids) as rapid reduction in uric acid level may result in further exacerbation of gout
- Indications include 2+ acute attacks despite lifestyle modification, presences of gouty tophi and heart failure when unable to stop diuretics
- WHO target for serum uric acid is 300-360µmol/L
- Monitor every 4-6 weeks
What are the other treatment options of gout?
- Xanthine oxidase inhibitors - allopurinol (first line), febuxostat (if allopurinol not tolerated/contraindicated)
- Others:
- Uricosuric drugs - sulfinpyrazone, probenecid
- Can worsen renal impairment
- IL-1 inhibitors - canakinumab
- Uricosuric drugs - sulfinpyrazone, probenecid
What is pseudogout?
Deposition of calcium pyrophosphate in the joints and soft tissues leads to inflammation
What is chondrocalcinosis?
calcium pyrophosphate deposition occurs in cartilage and other soft tissues in the absence of acute inflammation
What is the aetiology of pseudogout?
- Most common in the elderly
- Chondrocalcinosis increases with age
- Both pseudogout and chondrocalcinosis come under the umbrella of Calcium Pyrophosphate Deposition disease (CPPD)
- Related to osteoarthritis - calcium deposition can occur in some cases of OA
- Affects fibrocartilage - knees, wrists, ankles
What are risk factors of pseudogout?
- Hyperparathyroidism
- Familial hypocalciuric hypercalcaemia
- Haemochromatosis
- Wilson’s disease
- Hemosiderosis
- Hypophosphatasia
- Hypomagnesemia
- Hypothyroidism
- Gout
- Neuropathic joints
- Amyloidosis
- Trauma
What is the presentation of pseudogout?
- Monoarthritis - swollen, painful, warm joint
- Knee most commonly affected
What are the investigations for pseudogout?
Aspiration of synovial fluid
- Polarised microscopy - calcium pyrophosphate crystals are envelope shaped, mild positively birefringent
Bloods
- Marked rise in inflammatory markers
What is the management of pseudogout?
- Treat acute episodes appropriately - NSAIDs, colchicine, steroids, rehydration
- No prophylactic management
What is hydroxyapatite deposition disease?
Deposition of basic calcium phosphate in the joints and soft tissues leads inflammation; the shoulder is the most frequently involved site (‘Milwaukee shoulder’)
What is the aetiology of hydroxyapatite deposition disease?
Most common in females, 50-60 years
What is the pathophysiology of hydroxyapatite deposition disease?
- Hydroxyapatite crystal deposition in the supraspinatus tendon
- Release of collagenases, serine proteinases and IL-1
- Acute and rapid deterioration
What is the presentation of hydroxyapatite deposition disease?
Acute onset of severe shoulder pain
What are the investigations for hydroxyapatite deposition disease?
X-ray - calcification can be seen just proximal to the greater tuberosity
What is the management of hydroxyapatite deposition disease?
- NSAIDs, subacromial steroid and local anaesthetic injections for pain relief
- Usually self limiting - pain eases as calcification resorbs
- Physiotherapy
- Surgical removal of calcifications may be appropriate for cases refractory to other attempts of conservative treatment
- Last line - partial or total arthroplasty
What is seen on this xray?
Calcification -> Hydroxyapatite deposition disease
