5.7 - Introduction to Rheumatology

LECTURE NOTES

RHEUMATOLOGY

  • Medical speciality dealing with diseases of musculoskeletal system

    • Includes dealing with bones, joints, muscles, tendons and ligaments

    • There is particular emphasis on diagnosis and treatment of autoimmune joint and connective tissue diseases

  • Arthritis is a disease of the joints.

  • Many types of arthritis but there are two major divisions

    • Degenerative joint disease (osteoarthritis)

    • Inflammatory joint disease

    • This is important because the treatment for the different types of arthritis are different

DEGENERATIVE JOINT DISEASE: OSTEOARTHRITIS

  • Pathological changes cartilage loss and bony remodelling

  • Epidemiology

    • More prevalent with age

    • Previous joint trauma (e.g. footballer’s knees)

    • Jobs involving heavy manual labour

    • Gradul onset - slowly progressive disorder

  • Symptoms and Signs

    • Joint pain - worse with activity and better with rest

    • Joint crepitus - creaking, cracking grinding sound on moving affected joint

    • Joint enlargement - e.g. Heberden’s nodes (bony swelling at the DIP joints are termed as Heberden’s joints)

    • Limitation of range of motion

  • Joints affected are usually

    • Joints of the hand

      • Distal interphalangeal joints (DIP)

      • Proximal interphalangeal joints (PIP)

      • First carpometacarpal joint (CMC)

    • Spine

    • Weight bearing joints of lower limbs

      • Especially knees and hips

      • First metatarsophalangeal joints

  • Radiographic features

    • Joint space narrowing

    • Subchondral bony sclerosis

    • Ostephytes and subchondral cytes

INFLAMMATORY JOINT DISEASE

  • Inflammation - physiological response that helps us deal with injury or infection

  • Excessive/inappropriate inflammatory response reactions can damage the host tissues

  • Clinically manifests with: Redness, pain, heat, swelling and loss of function

  • Physiological, cellular and molecular changes:

    • Increased blood flow

    • Migration of leucocutes into tissues

    • Activation and differentiation of leucocytes

    • Cytokine production

    • TNF-alpha

  • Causes of inflammation

    • Infection → septic arthritis and tuberculosis

    • Crystal arthritis → gout and pseudogout

    • Immune mediated → rheumatoid or seronegative arthritis and systemic lupus erythematosus (SLE

    • First two are secondary and immune mediated is primary

    • First is non-sterile and second 2 are sterile

Septic Arthritis

  • Bacterial infection of a a joint (usualy caused by spread of blood)

  • Risk factors → immunosuppressed, pre-existing joint damage, intravenous drug use

  • Septic arthritis is a medical emergency

    • Untreated, the bacteria can rapidly destroy the joint

  • Clinical presentation

    • Acute, red hot painful swollen joint

    • Usually only 1 joint is affected (monoarthritis)

    • Typically fever: patient is often systemically unwell

  • Consider septic arthritis in any patient with an acute painful, red, hot, swelling of a joint especially if there is a fever

  • Diagnosis is done by joint aspiration and send sample for urgent gram stain and culture

  • Common organisms: staph. aureus, streptococci and gonococcus (more rare)

    • Gonococcal septic arthritis is an exception as it is polyarthritis and is less likely to cause joint destructure

  • Treatment is with a surgical wash-out (lavage) and

Crystal Arthritis

  • Two main types - gout and pseudogout

  • Gout

    • Caused by deposition of monosodium urate (MSU) crystals around the joint

      • Tissue depositions of MSU normally cause gouty arthritis or tophi

      • Tophi are aggregated deposits of MSU in tissue and often develop around hands, feet, elbows and ears

    • High uric acid levels (hyperuricaemia) is a risk factor gor gout

    • Causes for hyperuricaemia → genetic tendency, increasing intake of puring rich foods or reduced excretion e.g. due to kidney failure

    • Clinical features:

      • Abrupt onset

      • Usually monoarthritis

      • Big toe 1st MTPJ (metataophalangeal joints) most commomly affected

    • Investigations

      • Bloods: high c-reactive protein and high serum urate

      • X-rays - usually normal initially. If recurrent attacks/long-standing gout, juxta-articular erosions can develop

      • Joint aspiration and synovial fluid are best for definitive diagnoses

  • Pseudogout

    • Caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystals which cause inflammation

    • Risk factors: background osteoarthritis, elderly patients, intercurrent infection

  • Joint aspiration and synovial fluid analysis

    • Key investigation for any acute monoarthritis

    • Needle inserted into the joint and fluid is aspirated

    • Fluid is sent to lab for

      • Microbiology (gram stain, culutre and sensitivities)

      • Polarising light microscopy to detect crystals

  • Gout Treatment

    • Acute attack - reduce inflammation

      • Non-steroidal anti-inflammatory drugs (NSAIDs)

      • Glucocorticoids (steroids)

    • Chronic - need to reduce uric acid levels

      • Lifestyle - avoid purine rich food, beer

      • Pharmacological: allupurinol, febuxostat (xanthine oxidase inhibitors)

IMMUNE MEDIATED INFLAMMATORY JOINT DISEASE

  • Autoimmune - immune system attacks body’s own tissues - joint inflammation

  • 3 main categories

    • Rheumatoid arthritis

    • Serognegative inflammatory arthritis

    • System lupus erythematosus (aka SLE or lupus)

Rheumatoid Arthritis

  • RA = chronic autoimmune disease

  • Primary site of pathology is in the synovium

  • Synovitis - inflammation of the synovial membrane

  • Synovium is found at

    • Synovial joints,

    • Tenosynovium surrounding tendons

    • Bursa

  • Chronic, polyarthritis

  • Common feature is early morning stiffness in and around joints

  • May lead to joint damage and destruction → joint erosion on radiographs

  • Auto-antibodies usually detected in blood

  • Extra-articular disease can occur

    • e.g. ocular inflammation, interstitial lung disease, nodules and vasculitis

  • Rheumatoid arthritis: pattern of joint involvement

    • Symmetrical

    • Affects multiple joints (polyarthritis)

    • Affects small and large joints, but particularly hands, wrists and feet

    • Mostly affects (MCJPs, PIPJs, wrists, knees, ankles and MTPJs)

  • Pathogenesis

    • Healthy synovial membrane contains macrophage like (type A) and fibroblast like (type B synoviocyte) cells, type I collagen and maintenance of synovial fluid

  • In RA synovium becomes a proliferated mass of tissue due to

    • Neovascularisation

    • Lymphangiogenesis

    • Inflammatory cells (activated T and B cells, plasma cells, mast cells, activated macrophages)

  • Recruitment activation and effector functions of these cells is controlled by a cytokine network

  • Excess of pro-inflammatory cytokines compared to anti-inflammatory cytokine imbalance can also cause this

  • TNF-alpha: cytokine tumour necrosis factor alpha, is the dominant pro-inflammatory cytokine in the rheumatoid synovium

  • Its pleotropic actions are detrimental in this setting

    • Dominant detrimental role of TNF-alpha in rheumatoid arthritis validated by the therapeutic succes of TNF-alpha inhibition

    • TNF-alpha inhibition is achieve via vintravenous infusion or sub-cutaneous injection of antibodie or fusion proteins

Blood Test: RA vs OA and SA

  • Haemoglobin - decreased or normal in RA, normal in OA and SA

  • Mean Cell Volume - normal for RA, OA and SA

  • WCC is usually normal in RA, normal in OA but increased (leucocytosis in SA)

  • Platelet count is normal or high in RA and SA but normal in OA

  • ESR (erythrocyte sedimentation rate) is usually high in RA, normal in OA and normal or high in SA

  • C-reactive protein is high in RA, normal in OA and high in SA

Autoantibodies

  • Two types of antibodies are found in the blood of RA patients

  • Rheumatoid factor - antibodies that recognise the Fc protion of IgG as their target antigen

    • Positive in approximately 80% of RA patients

    • Can also be found positive in other conditions

  • Antibodies to citrinulated protein antigens (ACPA)

    • Clinicl test = anti-cyclic cirtrulinated peptide antibody anti-CCP antibody

    • Anti-CCP antibodies are more specific for RA than RF

    • Anti-CCP Ab positivity is associated with more aggressive/erosive diseases

  • Citrulination = post-translational modification where arginine gets converted to citrulline by PADs

X-Ray

  • Radiographic features of RA

    • Soft-tissue swelling

    • Peri-articular osteopeniai

    • Bony erosions - only occur in established disease. The aim of modern therapy is to treat early before erosions (permanent damage) has occurred

    • Essentially if you are finding out about this through the X-Ray then it’s probably too late.

Ultrasound

  • Much better for detecting synovitis

    • Synovial hypertrophy (thickening)#

    • Increased blood flow (Seen as doppler signal)

    • May detect early ersosions not seenon plain X-Ray

  • Ultrasound usually of hands and wrists can be performed alongside clinical assessmen in a dedicated early arthritis clinic

Principles of Management

  • Treatment goal: prevent joint damage

  • Requires

    • early recognition of symptoms, referral and diagnosis

    • prompt initiation of treatment, joint destruction = inflammation x time

    • aggressive pharmacological treatment to suppress inflammation

  • Pharmacological treatments

    • Glucocorticoid therapy - useful acutely but avoid long term use because of side-effects

    • DMARD's’ = disease modifying anti-rheumatic drugs

    • Immunomodulatory drugs that halt or slow the disease process

    • First line normally combination of anti-rheumatic drugs, typically methotrexate + hydroxychloroquine an sulfasalazine plus IM or short course of oral steroids

    • If disease still present we will escalate to one of the biological therapies like anti-TNF

    • Historically in the treatment of rheumatoid arthritis nonsteroidal anti-inflammatory drugs like ibuprofen or their stronger cousins like naproxen were used.

      • Less relevant now because they have long term renal damage and cardiovascular risks

RHEUMATOID VS OSTEOARTHRITIS

  • Age at onset: RA happens a bit younger

  • RA onset a lot quicker

  • RA is bilateral and symmetrical, OA is asymmetrical

  • Movement is better with RA

  • RA is common in wrist, ankle and elbow

  • Positive serolody seen with RA

  • Systemic symptoms seen with RA

  • Joint swelling is red, warm and effusion with RA, bony with OA

SERONEGATIVE INFLAMMATORY ARTHRITIS

  • Family of conditions with overlapping clinical features and pathogenesis

  • Unlike rheumatoid arthritis, rheumatoid factors and seronegative and CCP antibodies are not present in the blood, hence called seronegative

  • Still are autoimmune

Psoriatic Arthritis

  • Skin psoriasis assoiated with this arthritis

  • Scaly red plaques on extensor surfaces

  • 10% of people with psoriasis will also have joint inflammation

  • Varied clinnical presentations

    • Classically presents as asymmetrical arthritis involving IPJs (interphalangeal joints)

    • Can also manifest as symmetrical involvement of small joints (rheumatoid pattern)

    • Oligoarthritis of large joints

    • Spinal or sacroiliac joint inflammation

  • Severity of skin not proporitonal to severity of joint disease

Reactive Arthritis

  • Sterile inflammation in joints following infection elsewhere in the body

  • Septic arthritis in the joint, reactive arthritis is an infection elswehere which causes inflammation to the other joint

  • Common triggers are urogenital or STIs or GI infections

  • Inflammation of tendon insertions, skin inflammations or ocular inflammations

  • Reactive arthritis is occasionally the first manifestation of HIV or Hep C

  • Genetic predisposition → young adults with HLA-B27 and environmental triggers such as salmonella infections

SLE (Systemic Lupus Erythematous)

  • Lupus = a multi-system autoimmune disease

  • Multi-site inflammation can affect almost any organ

    • Mainly affects joints, skin, kidneys, haematology, also lungs, CNS and cardiac involvement

    • Associated with antibodies to self antigens (autoantibodies)

      • Different autoantibodies to RA - instead of RF and CCP

      • Autoantibodies are antinuclear antibodies (ANA)

        • Sensitive to SLE not specific

        • A negative test rules out lupus but a positive test doesn’t solely mean Lupus

      • Other autoantibody is the Anti-double stranded DNA antibody (anti-dsDNA abs)

        • High specificity for SLE in the context of appropriate clinical sings

  • More common in females than males (9:1)

  • Presentation usually quite young 15-40 years old

  • Increasd prevalence in African and Asian communities