rheumatology Flashcards
RA: define
An auto-immune inflammatory synovial joint disease.
A chronic systemic AUTOIMMUNE disorder causing a SYMMETRICAL
POLYARTHRITIS
RA: epidemiology?
common affecting 1% of the population worldwide with a peak prevalence between 30-50 yrs
- Prevalence is increased in smokers
- Not seen as much in the elderly in contrast to OA
- More common in FEMALES than males
RA: aetiology?/rf!!
- Gender: Women
- Before menopause women are affected 3x more than men with an equal sex incidence post-menopause
- suggesting aetiological role for sex hormones
- Genetic factors:
- Human leucocyte antigen; HLA-DR4 & HLA-DRB1 confer susceptibility to RA and are associated with development of more severe erosive disease
- Environmental Factors - eg cigarette smoke, pathogens eg gut bacteria
RA: pathophysiology?
also what is rheumatoid factor?
synovitis (inflammation of the synovial lining) occurs when chemoattractants produced in the joint recruit circulating inflammatory cells
In RA the synovium becomes greatly thickened and becomes infiltrated by inflammatory cells
In synovial fluid: you have macrophages that secrete
- IL-1 & IL-8/6
- TNF-alpha -
These cytokines stimulate fibroblast-like synoviocytes - they become activated and proliferate
→ they stimulate RANKL expression —→ stimulates osteoclast activity = leads to bone erosion
→ the fibroblast like synoviocytes also secrete proteases → they cause cartilage to break down
→ the fibroblast like synoviocytes can migrate from joint to joint = symmetrical arthiritis
The synovium proliferates and grows out over the surface of the cartilage (past the joint margins), producing a tumour-like mass called ‘pannus’
pannus of inflamed synovium DAMAGES the underlying cartilage
and erodes bone
DESTROYS the articular cartilage and subchondral bone
resulting in bony erosions
THENNN → the inflammatory cytokines can escape synovial joints and reach diff parts of body and - EXTRA-ARTICULAR SYMPTOMS like brain = fever
RF = An antibody against the Fc portion of IgG.
RA: symptoms?
- symmetrical
- Pain
- Swelling
- Nodules
- Stiff
- Slowly progressive—> hand involvement - early in disease = small joints of the hand; metacarpophalangeal (MCP), proximal interphalangeal (PIP)
Other joints such as:- Metatarsophalangeal (MTP) of the feet
- Wrists, elbows, shoulders, knees and ankles
- Most cases many joints are involved (but DIPS usually spared)
- Swan neckDIPs flexed and PIPs hyper-extended
- Boutonniere deformityDIPs hyper extended and PIPs flexed
- Z thumbUlnar deviation
- Joints usually warm and tender
- Symptoms worse in the morning and in the cold - Morning stiffness lasting MORE than 30 minutes
- SYMMETRICAL peripheral polyarthritis
- Movement limitation and muscle wasting
RA: investigations?
- Bloods for inflammatory markers; ESR and CRP will be raised.
- Test for anaemia.
- Test for RF and anti-CCP.
-
X-ray:
- Soft tissue swelling in early disease - Joint space narrowing in late disease - PERI-ARTICULAR EROSIONS - decreased bone density - bony erosions
RA: management?
- NSAIDS. —-> e.g. IBUPROFEN and COX inhibitors e.g. ASPIRIN - relieve joint pain & stiffness - does not slow disease progression
- Corticosteroids. eg oral prednisolone - Suppress disease activity but risk of long term toxicity
- DMARDs.- - Inhibit inflammatory cytokines - thereby suppress immune system and thus carry risk of INFECTION
- Used early to reduce inflammation and slow development of joint erosions and irreversible damage
eg METHOTREXATE (oral):
GOLD STANDARD DRUG used for more active disease - Contraindicated in pregnancy
- Biological agents.B-cell inhibitors:RITUXIMAB (IV): or Interleukin blockers: - TOCILIZUMAB: or TNF-alpha blockers: INFLIXIMAB (IV): or T cell activation blocker: - ABATACEPT:
RA: complications?
- kidneys
Amyloidosis. - osteoporosis
RA is an Inflammatory disease. There are high levels of IL-6 and TNF; these are responsible for increased bone resorption. - soft tissues.
- Nodules.Bursitis.Muscle wasting.
- eyes.
- Dry eyes.Scleritis.Episcleritis.
- neurological effects.
- Sensory peripheral neuropathy.Entrapment neuropathies e.g. carpal tunnel syndrome.Instability of cervical spine.
- haematological effects.
- Palpable lymph nodes.Splenomegaly.Anaemia.
- pulmonary effects.
- Pleural effusion.
- heart.
- Pericardial rub.Pericardial effusion.
- You do some investigations on a 30 y/o woman who has presented with painful, red and swollen MCP and PIP joints. The XR shows swelling of soft tissues, deformity and loss of joint space. What auto-antibodies would you expect to see in the serum?
Anti-CCP and RF positive.This patient has rheumatoid arthritis.
OA: define
A non-inflammatory degenerative disorder of moveable joints characterised by the deterioration of articular cartilage and the formation of new bone.
OA: symptoms and signs and
Name 3 joints of the hand that are commonly affected in osteoarthritis.
Nodal osteoarthritis can affect the DIP and PIP joints. What are the two terms used for nodes on these joints?
-
Joint pain - made worse by movement/exercise and relieved by rest
- in severe OA - pain can even occur at rest
- In contrast to inflammatory arthritis there is only transient i.e. LESS than 30 minutes of morning stiffness
- Joint stiffness after rest (gelling) vthus alos reduced joint movement
- ON EXAMINATION: Muscle wasting of surrounding muscle groups
- TENDERNESS ON joint palpation
- May be joint effusions
- Crepitus (grating) - crunching sensation when moving joint due to the disruption of the normally smooth articulating surfaces of the joints
joint swelling and bony enlargement
- Distal interphalangeal joint.
- Proximal interphalangeal joint.
- Carpal metacarpal joint.
- PIP - Bouchard’s nodes.
- DIP - Herbeden’s nodes.
OA: pp?
Chrondrocytes.
prevalence of OA increase with age BC - Due to the cumulative effect of trauma and a decrease in neuromuscular function.
oa: RF?
- Genetic predisposition.
- Trauma.
- Abnormal biomechanics e.g. hypermobility.
- Occupation e.g. manual labour.
- Obesity; pro-inflammatory state.
Increasing age:
• Due to cumulative effect of traumatic insult
• Decline in neuromuscular function
Gender - more common in females
OA: investigations?
-
X-rays = LOSS:
- Loss of joint space
- Osteophytes
- Subarticular sclerosis
- Subchondral cysts
OA: management?
3 types?
- on-medica
• Exercise to improve local muscle strength, improve mobility of weight
bearing joints and general aerobic fitness (regardless of age, severity or
comorbidity)
• Lose weight if obese - particularly if weight bearing joints affected
• Local heat or ice packs applied to affected joint may help
• Bracing devices, joint supports, insoles for joint stability and footwear
with shock-absorbing properties for lower limb OA
• Acupuncture, physiotherapy and occupational therapy
pharm
- NSAIDS (topical better than PO).
- Paracetamol.
- Intra-articular steroid injections.
- DMARDs if there is an inflammatory component.
surgery
- Arthroscopy for loose bodies.
- Osteotomy (changing bone length).
- Arthroplasty (joint replacement).
- Fusion (usually ankle and foot).
Gout: define and epidemiology?
A inflammatory arthritis that is associated with hyperuricaemia (high levels of uric
acid) and intra-articular monosodium urate crystals
You need to have hyperuricaemia to develop gout BUT having
hyperuricaemia DOES NOT GUARANTEE gout - just increases the risk
Gout is most common in men over 75 y/o.
Gout: symptoms?
What joint is commonly affected in gout?
- Hot and swollen joints.
- The toes are commonly effected.
- Usually just one joint affected but can sometimes be polyarthritic
e. g. ankle, foot, small joint of hand, wrist, elbow or knee
The MTP joint of the big toe.
Gout: management?
aim of management?
Name a drug used in the treatment of gout that blocks xanthine oxidase.
aim = to get urate levels below <300 μmol/L.
- Lifestyle modification e.g. diet, weight loss, reduced alcohol.
2. Allopurinol (blocks xanthine oxidase). BUT NOT for pt first gout flare - but start no 3 main treatment w allopurinol for other pt
- Colchicine or NSAIDS or Corticosteroids
- Switch from bendroflumethiazide to cosartan.
- Rasburicase - rapid urate reduction.
—Allopurinol.
Describe the treatment for an acute attack of gout.
- NSAIDs e.g. diclofenac.
- Colchicine if NSAIDs are ineffective.
- Corticosteroids - IM or IA.
Gout: investigations?
What kind of crystals do you see in gout?
- Joint fluid aspiration & microscopy: • DIAGNOSTIC** • Shows long needles shaped crystals that are NEGATIVELY bifringent under polarised light - Should show URATE CRYSTALS - negatively bienfragement crystals!!!! Monosodium urate crystals - negatively birefringent. !!!!
-
Serum uric acid is raised:
• If it is not, it should be rechecked several weeks after the attack, as level
fall immediately after an acute episode - Serum urea and creatinine and estimated glomerular filtration rate (eGFR) -
to monitor for signs of renal impairment
Pseudogout: pp?
Calcium pyrophosphate crystals are deposited on joint surfaces. The crystals elicit an inflammatory response.
Deposition of calcium pyrophosphate in articular cartilage and periarticular
tissue producing the radiological appearance of chonedrocalcinosis (linear
calcification parallel to the articular surfaces)
Pseudogout: risk factors / aetiology?
- Hypo/hyperthyroidism.
- Diabetes.
- Haemochromatosis.
- Magnesium levels.
other risk factors?
joint trauma / injury
old age
- Old age
- Diabetes
- Osteoarthritis
- Joint trauma/injury
-
Metabolic disease:
• Hyperparathyroidism
• Haemochromatosis
Pseudogout: define
Deposition of Calcium Pyrophosphate crystals on joint surface
presents in a similar way to gout bc
- join pain
- swelling
- redness
Pseudogout: symptoms?
Acute, hot and swollen joints. Typically the wrists and knees./
- Shedding of crystals into a joint produces acute synovitis that resembles
ACUTE GOUT but is more common in elderly women and usually affects the
knee or wrist - The attacks are very painful
- Acute hot swollen wrist or knee
- Since presents with hot joint and fever - can be MISTAKEN for septic arthritis
(if steroid given effects can be DEVASTATING) - REMMEBR IN GOUT will affect joints like MTP big tow WHEREAS PSEUDOGOUT will affect LARGER JOINTS like knee
Pseudogout: investigations?
- Aspiration: fluid for crystals and blood cultures.
Small rhomboidal crystals under microscopy
• Positively bifringent crystals under polarised light - REMEMBER since
Pseudogout = Positively bifringent
RMEMEBR in gout crystals are long needl-eshaped and NEGTAtively bifringent here they are small rhomboidal and positively brifringent under polarised light• - X-rays: can show chondrocalcinosis.
Shows chonedrocalcinosis - linear calcification parallel to the articular
surfaces - bloods = raisd wcc
Pseudogout: management?
joint accessible then - IM, oral or intra-articular (most effective, but can be painful) corticosteroid e.g PREDNISOLONE
if joints inaccessible
- High dose NSAIDs e.g. NAPROXEN or IBUPROFEN or COX inhibitor e.g.
ASPIRIN
- If NSAID not tolerated well or due to contraindication due to renal
impairment then COLCHICINE:
• Very toxic in overdose
• Side effects; diarrhoea and abdomen pain - Aspiration of the joint reduces pain dramatically
Ankylosing spondylitis: define
and risk factors?
Chronic inflammatory disorder of the spine, ribs and sacroiliac joints / baso vertebral joints
Ankylosis = abnormal stiffening and immobility of joint due to new bone
formation
- HLA-B27 - most individuals have the gene HLA-B27 - encodes for a specific type of MHC
- Environment:
• Klebsiella
• Salmonella
• Shigella
Ankylosing spondylitis: pp?
Inflammation of spine -> erosive damage -> repair/new bone formation -> irreversible fusion of spine.
you have inflammation of intervertebral discs and facet joints of spine
→ inflammation DESTROYS intervertebral joints, facet joints, and sacroiliac joints
fibroblasts replace destroyed joint w fibrin - this FIBROUS BAND AROUND JOINTS limits the range of motion
- EVENTUALLY osteoblasts are ACTIVATED = OSSIFICATION - WHEN fibrous tissue turns into bone
- syndesmophytes (small bony outgrowths) will form → MAKES SPINS IMMOBILE
OTHER parts of body can also be affected!!! - eg eye = anterior uveitis and aortic valve = aortic regurgitation bc valve can get inflamed and damaged and inflammation of tendons = enthesitis
Ankylosing spondylitis: symptoms?
- BACK PAIN!
- Morning stiffness.
- Waking in the second half of the night.
- Buttock pain. - if sacroiliac joints = buttock pain
- Insidious onset.
- Usually <40y/o at onset.
BC IS SYSTEMIC thus = weight loss, fever, fatigue
if cervical / thoracic region = neck or back pain/stiffness → can cause shortness of breath
OTHER parts of body can also be affected!!! - eg
- eye = anterior uveitis and
- aortic valve = aortic regurgitation bc valve can get inflamed and damaged and
- inflammation of tendons = enthesitis —-• E.g. Achilles tendinitis, plantar fasciitis (under heel) and tenderness around the pelvis and chest wall
- Non-articular features:
• Anterior uveitis - inflammation of middle layer of eye
• Associated with osteoporosis
• Rarely; aortic incompetence, cardiac conduction defects and apical
lung fibrosis, amyloidosis and IgA nephropathy
Ankylosing spondylitis: investigations? diagnostic criteria(3)?
- X-ray.
- Sacroiliitis.
- Syndesmophytes (bamboo spine)
• Can be normal or bamboo spine bc of ossification of anulus fibrosus - MRI.
- HLAB27 test.
HLA-B27 positive - NOT DIAGNOSTIC
- diagnostic criteria for ankylosing spondylitis
- > 3 months back pain.2. Aged <45 at onset.3. Plus one of the SPINEACHE symptoms.
Ankylosing spondylitis: management?
- Treat quickly to prevent irreversible syndesmophyte formation and
progressive calcification - Morning exercise to maintain posture and spinal mobility
- NSAIDs e.g. IBUPROFEN or NAPROXEN - useful at night
in severe cases
-
DMARDs like METHOTREXATE to help with peripheral arthritis but NOT with spinal
disease -
Biologics like TNF-alpha blocker:
• Can improve spinal and peripheral joint inflammation, the earlier you
start the less syndesmophytes form
• E.g INFLIXIMAB (IV), ETANERCEPT (SC) or ADALIMUMAB (SC) - Local steroid injections for temporary relief
- Surgery e.g. hip replacement to improve pain and mobility
Osteoporosis: define?
A systemic skeletal disease characterised by low bone mass and micro-architectural deterioration. The patient is at increased risk of fracture.
Bone breakdown > bone formation = resulting in POROUS bones / aka decrease in bone density to point of fracture
Defined as bone mineral density (BMD) MORE than 2.5 standard deviations
BELOW the young adult mean value (T score < 2.5)
Osteoporosis: epidemiology
50% of women and 20% of men over 50 are affected.
The incidence increases with age.
F>m
Osteoporosis: risk factors?
Why is being female one?
- age
- women
Women over 50 are likely to be post-menopausal; they therefore have less oestrogen and so osteoclast action isn’t inhibited. There is a high rate of bone turnover -> bone loss and deterioration -> fracture risk. - SHATTERED
-
Steroid (prednisolone) use:
- Other drugs; heparin, ciclosporin, PPIs, anticonvulsants, GnRH
analogues, SSRIs, androgen deprivation
- Other drugs; heparin, ciclosporin, PPIs, anticonvulsants, GnRH
-
Hyperthyroidism & Hyperparathyroidism:
- Other endocrine diseases e.g. Cushing’s (high cortisol)
- Thyroid hormone and parathyroid hormone INCREASE bone
turnover - Cortisol increases bone resorption (via osteoclasts) and induces
osteoblast apoptosis - Oestrogen/testosterone control bone turnover
- Alcohol and tobacco - bad for bones
-
Thin - BMI < 22:
- Reduced skeletal loading - increases bone resorption e.g. low
body weight (obese people have higher bone density) and
immobility
- Reduced skeletal loading - increases bone resorption e.g. low
- Testosterone decreased - leads to increased bone turnover
- Early menopause - oestrogen drop leading to increased bone turnover
- Renal or liver failure
- Erosive/Inflammatory bone disease e.g. RA/myeloma - cytokines (TNF-
alpha & IL-6) increase bone turnover - Dietary calcium decrease/malabsorption, diabetes mellitus type 1
-
Steroid (prednisolone) use:
Osteoporosis: investigations?
Gold at standard?
- X-ray:
• Demonstrate fractures but insensitive for osteopenia -
Dual energy X-ray absorptiometry (DEXA) scan:
• Low radiation dose and measure important fracture sites (lumbar spine and proximal femur)
• GOLD STANDARD for measuring bone density and diagnosing osteoporosis
• Generates T scores - see above, more than 2.5 standard deviations = osteoporosis -
Bloods:
• Ca2+, phosphate and alkaline phosphate all normal
Osteoporosis: management?
Lifestyle measures:
• Quite smoking and reduce alcohol consumption
• Weight-bearing exercise may increase bone density • Calcium and vitamin D rich diet
• Balance exercises to reduce falls
- Bisphosphonates. (Or denosumab)
- HRT.
Anti-resorptive treatments decrease osteoclast activity.
Teriparatide.
Anabolic treatments increase osteoblast activity.
Psoriatic arthiritis: rf?
- FHx
- HLAB27 associated.
Give 5 conditions that fall under the umbrella term spondyloarthritis.
s.
- Ankylosing spondylitis.
- Reactive arthritis.
- Psoriatic arthritis.
- Enteropathic arthritis.
- Juvenile idiopathic arthriti
