Rheumatology Flashcards
Osteomyelitis
inflammatory condition of bone caused by an infecting organism, most commonly Staphylococcus aureus.
When to suscept acute osteomyelitis
Most commonly in an unwell child with a limp, or in an immunocompromised patient.
When to suscept chronic osteomyelitis
most commonly in adults with a history of open fracture, previous orthopaedic surgery, or a discharging sinus
Osteomyelitis- signs- acute
Systemic- Fever, rigors, sweats, malaise
Local- tenderness, warmth, erythema, and swelling
Osteomyelitis- signs- chronic
Systemic- Fever, rigors, sweats, malaise
Local- tenderness, warmth, erythema, and swelling
draining sinus tract
deep / large ulcers that fail to heal despite several weeks treatment (DM ulcer)
non-healing fractures
Native vertebral osteomyelitis- signs
Local back pain associated with systemic symptoms, paravertebral muscle tenderness and spasm
Osteomyelitis RFs
previous osteomyelitis
penetrating injury
intravenous drug misuse
diabetes
Osteomyelitis- investigations
FBC- may be raised WBC (chronic is normal)
ESR/ CRP- usually raised
Blood culture- to identify suitable antibiotic
Plain x-ray of affected area
MRI/ CT
Osteomyelitis- investigations- plain x ray
Chronic- cortical erosion,
periosteal reaction,
mixed lucency,
Sclerosis
sequestra
soft tissue swelling
Osteomyelitis- investigations- MRI
marrow oedema from 3-5 days
Delineates cortical, bone marrow and soft tissue inflammation
Osteomyelitis- investigations- definitive diagnosis
Bone biopsy- 2 samples
Positive blood cultures (50% of acute OM)
Osteomyelitis- differential diagnosis
Soft tissue infection (Cellulitis and erysipelas)
Charcot joint
Avascular necrosis of bone (Causes: steroid, radiation, or bisphosphonate use)
Gout (uric acid crystals in joint fluid / more acute presentation)
Fracture
Bursitis
Malignancy
Osteomyelitis- treatment
Surgical- Debridement or Hardware placement or removal
Antimicrobial therapy
Osteomyelitis- treatment- antimicrobial therapy
Initial broad spectrum empiric therapy
Tailored to culture and sensitivity findings
Bone penetration of drug
Prolonged duration (6 weeks<)
Routes of Osteomyelitis
- Direct inoculation of infection into the bone
trauma or surgery,
poly/ monomicrobial - Contiguous spread of infection to bone
- Haematogenous seeding- children (long bones)>adults (vertebrae), monomicrobial
Routes of Osteomyelitis- Contiguous spread of infection to bone
-from adjacent soft tissues and joints, polymicrobial or monomicrobial,
-older adults: DM, chronic ulcers, vascular disease, arthroplasties / prosthetic material
Osteomyelitis- typical microbe causes
Staphylococcus aureus,
coagulase-negative staphylococci,
aerobic gram-negative bacilli
Osteomyelitis- histopathology- acute changes
Inflammatory cells
Oedema
Vascular congestion
Small vessel thrombosis
Osteomyelitis- histopathology- chronic changes
neutrophil exudates
lymphocytes & histiocytes
Necrotic bone ‘sequestra’
new bone formation ‘involucrum’
Pathogenesis of OM – Host factors
Behavioural factors- risk of factors
Vascular supply- arterial disease, DM, sickle cell disease
Pre-existing bone/ joint problem
Immune deficiency
Periprosthetic joint infection
Infectious complication following total joint arthroplasty (TJA)
Periprosthetic joint infection- common causes of infection
Gram‐positive bacterium is still the most common pathogenic bacteria in PJI
Staphylococcus epidermidis and Staphylococcus aureus were the largest in number.
Periprosthetic joint infection- upper vs lower limb
Propionibacteria more sig problems in upper limb
Periprosthetic joint infection- upper limb and propionibacteria
They are colonisers of humans from the above the waist
Can even be shed by blinking the eyes
Therefore may represent more of a threat in upper limb prostheses and Spines
Septic arthritis
Consider in any acutely inflamed joint as it can destroy joint in 24 hrs and has high mortality rate (11%)
Inflammation may be less overt if immunocompromised or underlying joint disease
Commonly affect knee (>50%)
Septic arthritis RFs
Pre-existing joint disease (esp rheumatoid arthritis)
DM, CKD, immunocompromised, recent joint surgery, prosthetic joints, IV drug users, increased age (80<)
Septic arthritis- common organisms- native joints
Staph Aureus (DM)
Streptococci
Neisseria gonorrhoea (young, sexually active, MSM)
Anaerobes (DM)
Mycobacterium/ fungi- immunocompromised
Gonococcal Arthritis
Occurs with disseminated gonococcal infection
Fever, arthritis, tenosynovitis- multiple joints, small + large
Maclopapular- pustular rash (with both flat and raised parts)
Typical clinical presentation of septic joint
Painful, red, swollen, hot joint
Remember children may just not use it
Fever
90% monoarthritis- don’t rule out in polyarticular presentations
Knee > hip > shoulder
Septic arthritis- investigations
Urgent aspiration- synovial fluid microscopy, gram stain, culture + sensitivities and WBC- before starting antibiotic therapy unless urgent
Blood culture
Bloods- for baseline
Pain x ray- not urgent as not diagnostic but baseline investigation
Diagnostic investigation for septic arthritis
Urgent joint aspiration for synovial fluid for microscopy or culture
Septic arthritis- treatment
Long course antibiotics (>6 weeks) guided by aspiration results
Joint washout/ rpt’d aspiration until no recurrent effusion
Rest/ splint/ physio
Analgesia
Stop any immuno-suppression temporarily if possible
Septic arthritis- most common infecting organism overall (native joints)
Staph Aureus
Inflammatory Arthritis
New onset joint SWELLING- Synovial (compressible, tender), Often red, Warm to touch
Worst in morning / inactivity
Stiffness > 30 mins (usually longer)
Constant or intermittent
Inflammatory Arthritis- 3 Ss
Stiffness
Swelling
Squeezing- painful
Causes of Joint Inflammation
Inflammatory Arthritis
*RA
*Seronegative Spondyloarthritis
*Crystal arthrits – gout and pseudogout
Septic Arthritis
Causes of Joint Inflammation- Seronegative Spondyloarthritis examples
-Psoriatic
-Ank Spond
-Reactive Arthritis
-Enteropathic – Crohns and Ulcerative Colitis related
Rheumatoid Arthritis
Symmetrical small joints, hands wrists feet
Big joints involved later, bad prognostic sign if involved at presentation
No spinal involvement
1% of pop
Rheumatoid Arthritis- RFs
Middle age, female, family history, smoking
Seronegative Arthritis
Asymmetrical big joints, with spinal involvement
More common in men
Associated symptoms
Seronegative Arthritis
- Associated symptoms
-Inflammatory bowel, or GI infection, eye inflammation and psoriasis
-Nail involvement predicts arthritis in patients with psoriasis
Psoriatic Arthritis
RA like
Distal interphalangeal involvement
CRP may not be significantly raised
Crystal Arthritis (Gout/Pseudogout)
Typically acute intermittent episodes joint inflammation
Gout
6x more common in men
feet, ankles, knees, elbows, hands
Hyperuricaemia
Gout- RFs
beer, renal impairment, diuretics, aspirin, FH
Pseudogout
3 x more common in women
wrists, knees, hands
Typically on background of OA
Chondrocalcinosis on x ray
Osteoarthritis
Degenerative- slow onset – months to years
Typically weight bearing joints DIPs, PIPs, thumb bases, big toes
Osteoarthritis- signs
Pain and crepitus on movement and back ground ache at rest
Minimal early morning stiffness (gelling)
No variability to joint swelling
Normal CRP
Clear changes on xray
Arthritis- making a diagnosis
Is it inflammatory?
Which joint pattern?
Associated symptoms / risks
Tests- RF (Rheumatoid factors)/CCP+ (RA only), uric acid between attacks ?gout
-X rays
Arthritis-making a diagnosis- is it inflammatory
Visible joint swelling
Elevated CRP
Variable symptoms with flares
Arthritis-making a diagnosis- Associated symptoms / risks
Psoriasis (particularly with nail involvement)
Inflammatory eye / bowel symptoms
Family / Smoking history (RA)
Crystal Arthritis
commonest cause of acute joint swelling
Gout most common in men
Pseudogout in women
Gout
Caused by the deposition of monosodium urate crystals within joint
The immunological reaction initiated to try and remove them, leads to acute pain and swelling
Curable
Gout- causes of hyperuricaemia
Under excretion urate- genetic, drugs
Overproduction of urate- diet, alcohol, metabolic, proliferation
Gout pathogenesis
Hyperuricaemia > crystal formation + shedding > synovial cells > inflammatory response
Gout and Alcohol
Beer / lager / stout equally bad
All rich in guanosine
Small increased risk with spirits
No increased risk with wine
Gout RFs
Renal impairment
Beer
Diuretics
Aspirin
Family History
Fructose
Gout presentation
Acute episodes
Onset often at night
Resolve spontaneously (quicker with treatment)
Usually recur in a predictable pattern of joint involvement
Acute Gout – Most common joint effect
1st MTPJ (metatarsophalangeal joint- big toe joint) 90%
Gout- differential diagnosis
Septic Arthritis
Trauma
Calcium Pyrophosphate Arthritis
Rheumatoid Arthritis
(Osteoarthritis!)
Gout diagnostic investigation
arthrocentesis with synovial fluid analysis- shows negatively birefringent needle-shaped crystals under polarised light
Gout symptoms
severe joint pain, with swelling, effusion, warmth, erythema, and or tenderness of the involved joint
Gout other investigations
FBC (expect raised WCC)
U+E
LFT if concern re alcohol
Serum Uric Acid (often normal during acute attack)
CRP
Xray if recurrent episodes or concern re sepsis
Gout clinical course
> asymptomatic hyperuricemia,
acute/recurrent gout,
intercritical gout,
chronic tophaceous gout
Gout- acute treatment
High dose NSAID unless renal failure, peptic ulcer disease, com pts with asthma
If CI, use colchicine or corticosteroids
+ lifestyle advice
Gout- lifestyle advice
Alcohol
Diet
Weight loss
Adequate fluid intake
Gout- chronic treatment indications
Recurrent attacks
Evidence of tophi or chronic gouty arthritis
Associated renal disease
Normal serum Uric acid cannot be achieved by life-style modifications
Gout- chronic treatment
1st lines- Allopurinol – Xanthine Oxidase Inhibitor (urate-lowering drugs)
2nd line- Febuxostat – more potent Xanthine Oxidase Inhibitor
If CI, use probenecid or sulfinpyrazone (increase renal excretion of uric acid)
Gout- aims of treatment
Aim of chronic gout management is to reduce Uric acid below <300 umol/l
Increase allopurinol every 2-4 weeks until this is met
Engage patient in this – more likely to comply and make lifestyle modification
Chronic Gout – signs
Tophi- chunks of uric acid crystals that accumulate in and around joints
Gout – complications
Disability and misery
Tophi
Renal disease ie calculi
Rheumatology Mantra
Inflammation x time = damage
Inflammation reversible, but damage not
Rheumatoid arthritis- clinical presentation
Pain and Swelling of joints
- Typically small joints hands, wrists, forefeet
Early morning stiffness (often prolonged)
Sudden change in function
Intermittent, Migratory or Additive involvement
Rheumatoid arthritis- physical examination
Decreased grip strength / fist formation
Often subtle synovitis – MCPs, PIPs, MTPs, ankles
DIPs are spared
Usually symmetrical
Deformity unusual at presentation
Rheumatoid arthritis- investigations
rheumatoid factor (RF)- positive
Anti-cyclic citrullinated peptide (anti-CCP) antibody- positive
Radiographs show erosions
Ultrasonography show synovitis of the wrist and fingers
Rheumatoid factor (RF)
Autoantibodies frequently seen in patients with RA but can also be seen in hepatitis C, chronic infections, and other rheumatological conditions
60-70% of RA patients test positive
Anti-cyclic citrullinated peptide (anti-CCP) antibody
Positive in 70% of RA patients
Anti-CCP can be positive when RF is negative, and it seems to play more of a pathogenic role in the development of RA
Rheumatoid arthritis- investigations- X rays
Used as diagnostic, and prognostic tools, and to monitor therapy
Xray changes of RA
-Soft tissue swelling
-Periarticular osteopenia
-Joint space narrowing
-Bone erosion
Rheumatoid arthritis- X rays changes
-Soft tissue swelling
-Periarticular osteopenia
-Joint space narrowing
-Bone erosion
Rheumatoid arthritis- treatment aims
To suppress inflammation as completely and quickly as possible once diagnosis confirmed without making our patients ill
Improve symptoms, prevent/reduce damage, prevent premature mortality
Rheumatoid arthritis- treatment
Early use of DMARS improve outcomes
Referral to physio, OT, podiatry as indicated
Escalation to biologic treatment if resistant disease
Connective tissue disease- autoimmune example
Systemic lupus erythematosus (SLE)
Systemic sclerosis
Primary Sjögren’s Syndrome
Dermatomyositis/Polymyositis
Multi-system diseases- causes
Infections
Auto-immune connective tissue diseases
Metabolic diseases
Endocrine diseases
Cancer
Inherited Connective Tissue Diseases
Marfan’s Syndrome
Ehler Danlos Syndrome
Marfan’s Syndrome
being tall
abnormally long and slender limbs, fingers and toes (arachnodactyly)
heart defects
lens dislocation
Ehlers-Danlos syndromes (EDS)
Joint hypermobility
stretchy skin
fragile skin that breaks or bruises easily
Auto-immune connective tissue diseases features
Inflammation leading to scarring in organs affected- can lead to organ failure
Any system can be affected
Inflammation can be treated with immunosuppressive drugs, damage is irreversible
Systemic Lupus Erythematosus
Multisystemic autoimmune disease
Autoantibodies are made against a variety of autoantigens (ANA) which form immune complexes. Inadequate clearance of immune complexes result in host immune responses which cause tissue inflammation and damage
Systemic Lupus Erythematosus- prevalence
More common in women (90% of disease)
More common in Afro-Caribbeans and Asians
4/100 000/year
Genetic association
Systemic Lupus Erythematosus- Pathogenesis
Immune complex mediated> tissue damage
Systemic Lupus Erythematosus- clinical features
Remitting and relapsing illness of variable presentation and course
Often non-specific (malaise, fatigue, myalgia and fever) or organ specific
Systemic Lupus Erythematosus- LE specific skin conditions
Malar “butterfly” rash with sparing of the nasolabial folds- acute
Annular, Psoriasiform- Subacute
Discoid rash, Scarring alopecia, Lupus profundus- chronic
Photosensitive rash
Systemic Lupus Erythematosus- clinical features- organ specific
Rashes, Inflammatory arthritis, Nephritis/ nephrosis, renal failure, pericarditis, acute MI, pleural effusion, PE, Numerous neurology, Psychosis, oral ulceration, recurrent abortions, pregnancy complications, cytopenia, abnormal clotting
Systemic Lupus Erythematosus- arthritis
Symmetrical
Less proliferative than RA
Can be deforming
Non-erosive
Lupus nephritis
Hypertension, proteinuria, renal failure
Systemic Lupus Erythematosus- Auto antibodies
Anti-nuclear antibody: Not specific for lupus (screening test)
Double stranded DNA antibody: Specific
Systemic Lupus Erythematosus- Haematological Features
Anaemia (Haemolytic, Coombs positive)
Thrombocytopenia
Neutropenia
Lymphopenia
Systemic Lupus Erythematosus- Investigations
Antinuclear antibodies (not diagnostic, sign of connective tissue disease), double-stranded (ds)DNA, Smith antigen- positive
ECG/ Chest x-ray for pts presenting with cardiopulmonary symptoms
Urinalysis- to asses renal involvement
Bloods- FBC, U+E, ESR/CRP
Systemic Lupus Erythematosus- Investigations- bloods
FBC- anaemia, leukopenia, thrombocytopenia
U+E- elevated urea and creatinine
ESR/CRP- elevated, shows non-specific inflammation, think infection
Systemic Lupus Erythematosus- diagnosis
Think SLE when multi-system disorder and ESR is raised
Anti-dsDNA antibody titres
Complement- decreased C3+C4
Skin and renal biopsies can be diagnostic
Systemic Lupus Erythematosus- treatment aims
Low disease activity and prevention of flares in all organ systems may be the aim (as full remission is rare)
Systemic Lupus Erythematosus- general treatment
High factor sun block- UV protection
Hydroxychloroquine- reduces disease activity and improves survival
Patient education
Systemic Lupus Erythematosus- maintenance treatment
NSAIDs and Hydroxychloroquine for joint pain
Topical steroids for skin flares
Steroid sparing agents
Monoclonal antibodies for high disease activity
Systemic Lupus Erythematosus- flare treatment
Mild- Hydroxychloroquine and steroid
Moderate- DMARDs or mycophenolate
Severe- Urgent high dose steroids, mycophenolate (immunosuppressive), rituximab (monoclonal antibodies)
Raynaud’s problem
decreased blood flow to the fingers
Can be primary or secondary to other diseases
Raynaud’s problem- secondary
Connective tissue disease- systemic sclerosis, mixed connective tissue, SLE
Drugs
Vascular damage- atherosclerosis, frost bite, vibrating tools
Systemic sclerosis (SSc)
Vasculopathy, excessive collagen deposition, inflammation, auto-antibody production
Systemic sclerosis (SSc)- features
Scleroderma (skin fibrosis), internal organ fibrosis and microvascular abnormalities (ie Raynaud’s phenomenon)
Raynaud’s- management
Physical protection
Vasodilators (Nifedipine, Iloprost, Sildenafil, Bosentan)
Fluoxetine
Sympathectomy- surgery
Systemic sclerosis (SSc)- management
Prevention of renal crisis- (ACEi)
Early detection of pulmonary arterial hypertension- Annual echocardiograms and pulmonary function tests
Treatment of skin oedema
Treatment of pulmonary fibrosis
Sjögren’s Syndrome
Chronic inflammatory autoimmune disease
Primary or secondary to other disease
There is lymphocytic infiltration and fibrosis of exocrine glands
More common in men in 40s/50s
Sjögren’s Syndrome- secondary
SLE
Rheumatoid arthritis
Scleroderma
Primary billiary cirrhosis
Other auto-immune diseases
Primary Sjogren’s Syndrome- clinical features
Dry eyes/mouth
Arthritis
Rash
Neurological features
Vasculitis
ILD
Renal tubular acidosis
Strong association with gluten sensitivity
Increased risk of lymphoma
Primary Sjogren’s Syndrome- investigations
Positive ANA, RF, Ro and La
Negative ds DNA
Raised Immunoglobulins
Abnormal salivary glands on ultrasound
Sialadenitis on lip biopsy
Sjogren’s Syndrome- treatment
Tear and saliva replacement
Hydroxychloroquine for fatigue, myalgia, arthralgia, rashes
Corticosteroids/immunosuppressants for organ-threatening extra-glandular disease
Polymyositis
Rare condition characterized by insidious onset of progressive symmetrical proximal muscle weakness and autoimmune-mediated straited muscle inflammation, associated with myalgia +/- arthralgia
Lungs can be affected
Dermatomyositis
Myositis + skin signs
Dermatomyositis- skin signs
Macular rash
Lilac-purple rash on eyelids often with oedema
Nailfold erythema
Gottrons papules- roughened red papules over knuckles (also elbows and knees)
Dermatomyositis/Polymyositis- investigations
Muscle enzymes (CK) elevated
Antibody screen
EMG
Muscle/skin biopsy- diagnostic
Screen for malignancy (PET-CT)- Malignancy associated antibodies
Chest X ray, PFTs, High resolution CT lungs
Dermatomyositis/Polymyositis- management
Steroids
Immunosuppressive drugs
Spondyloarthropathy
Chronic inflammation condition, tend to affect the axial skeleton without a positive rheumatoid factor, hence seronegative with overlapping clinical manifestations and association with the gene HLA-B27
Spondyloarthropathy- examples
Ankylosing spondylitis, psoriatic arthritis, enteropathic arthritis, and reactive arthritis
Clinical features of Spondyloarthritis
inflammatory arthritis of the “axial skeleton”
enthesitis
acute anterior uveitis (irits)
peripheral arthritis
skin psoriasis
May also have (sub-clinical) inflammatory bowel disease
Other clinical features of Spondyloarthritis- SPINEACHE
Sausage digit (dactylitis)
Psoriasis
Inflammatory back pain
NSAID good reponse
Enthesitis (heel)
Arthritis
Crohn’s/ Colitis/ elevated CRP*
HLA B27
Eye (uveitis)
HLA B27
human leukocyte antigen
-present in 90–95% of patients with ankylosing spondylitis, 60–90% of patients with reactive arthritis, 50–60% of patients with psoriatic arthritis or inflammatory bowel disease and spondylitis
Human leukocyte antigens
Proteins that help the body’s immune system tell the difference between its own cells and foreign, harmful substances
Inflammatory arthritis of the “axial skeleton”
Inflammatory arthritis of the spine/ rib cage and hips, which results in new bone formation and “fusion” of the vertebrae/ costovertebral / SIJ
Enthesitis
inflammation of junction between ligament/ tendon and bone
Acute anterior uveitis (irits)
inflammation of the anterior chamber of the eye
Ankylosing Spondylitis (Axial Spondyloarthritis)
Chronic progressive inflammatory arthritis of the spine and rib cage – eventually leading to new bone formation and fusion of the joints (bamboo spine, Syndesmophytes, Sacroiliitis)
Typically starts in late teenage years/ 20s
Affects male and females equally
Syndesmophytes
new bone formation and vertical growth from anterior vertebral corners
Sacroiliitis
Sclerosis, erosions, loss of joint space
Fusion
Ankylosing spondylitis- investigations
pelvic x-ray shows sacroiliitis
MRI shows bone marrow oedema
Spine x rays
Ankylosing spondylitis- investigations- pelvic x ray
sacroiliitis
Ankylosing spondylitis- investigations- MRI
bone marrow oedema on a T2-weighted sagittal short-tau inversion recovery image
Ankylosing spondylitis- investigations- spinal x ray
show erosions, squaring, sclerosis, syndesmophytes or bridging syndesmophytes in the lumbar spine, bamboo spine (late disease)
Final stage of Ankylosing spondylitis
Severe kyphosis (exaggerated, forward rounding of the upper back) of thoracic and cervical spine- patient unable to look ahead walking/ see the sun
Ankylosing spondylitis- treatment
Physio and NSAIDs
Biologics- Anti TNF, IL-17 blockers
Small targeted molecules: JAK inhibitors
Psoriatic Arthritis
PsA occurs in around 25% of patients with psoriasis
Chronic inflammatory MSK disease associated with psoriasis. It manifests with seronegative inflammatory arthritis commonly presenting with skin and nail lesions, peripheral arthritis, dactylitis, enthesitis, and spondylitis
Psoriatic Arthritis vs rheumatoid arthritis
Psoriatic Arthritis can be differentiated from rheumatoid arthritis (RA) by several clinical features
-frequent oligoarticular or monoarticular initial pattern of joint involvement
-distal interphalangeal joint involvement
-Dactylitis (inflammation of a digit) and sacroiliitis are not observed in RA
Hidden sites for psoriasis
under hair, nails, belly button
Psoriatic Arthritis mamagement
Similar to RA
Early intervention with DMARDs + biologics
Reactive Arthritis (ReA)
Sterile inflammation of the synovial membrane, tendons and fascia triggered by an infection at a distant site, usually gastro-intestinal or genital
Reactive Arthritis (ReA)- associated infections
Gut associated infections- Salmonella, Shigella, Yersinia
Sexually acquired infection (NSU)- Chlamydia, Ureaplasma urealyticum
Reactive Arthritis- classic triad
Arthritis- Typically 2 days to 2 weeks post infection
Conjunctivitis
(Sterile) urethritis (inflammation of urethra)
Reactive Arthritis- associated skin lesions
Keratoderma blenorrhagica, Circinate Balanitis
Reactive Arthritis- investigations
ESR/ CRP- elevated
ANA/RF- negative
Urogenital/ Stool cultures- negative
Arthrocentesis with synovial fluid analysis- negative
Imaging- sacroiliitis or enthesopathy
Reactive Arthritis- treatment acute
NSAID- 1st line
Corticosteroid
Reactive Arthritis- treatment chronic
DMARD
Enteropathic Arthritis
Episodic peripheral synovitis occurs in up to 20%
of patients with Inflammatory bowel disease
Management tailored to treat both bowels and joints
Enteropathic Arthritis- characteristics
Asymmetric lower limb arthritis
Usually reflects the disease activity
Remission generally related to suppression of bowel disease.
Osteoarthritis
Most common condition affecting synovial joints
Age-related, dynamic reaction pattern of a joint in response to insult or injury- all tissues of the joint are involved and changes bone at joint margins
Typically primary but can be secondary to joint disease or other conditions (obesity, haemochromatosis, occupational)
Osteoarthritis- tissue most affected
Articular cartilage
Osteoarthritis- pathogenesis
Metabolically active and dynamic process
Mediated by cytokines (IL-1, TNF-α, NO)
Driven by mechanical forces
Osteoarthritis- Main pathological feature
Loss of cartilage
Disordered bone repair
Osteoarthritis- RFs
Age, Female preponderance (post menopause), genetic factors, obesity, occupation (manual labour= small joints of hands OA, Farming and OA of hips, footballs and OA of knee), local trauma, inflammatory arthritis, abnormal biomechanics
Osteoarthritis and increased age
Due to: -Cumulative effect of traumatic insult
-Decline in neuromuscular function
Of all people aged over 65:
80-90% will have radiographic evidence of OA
50% will have symptoms of OA
Osteoarthritis and obesity
Linear relationship between BMI and risk of hip and knee OA- Not thought to be due to mechanical factors
Also association with OA of non-weight-bearing joints – e.g. hand joints
Obesity is a low grade inflammatory state
Release of: IL-1, TNF, Adipokines (leptin, adiponectin)
Osteoarthritis symptoms
Pain- may not present despite sig changes on X rays
Functional impairment- walking, activities of daily living
Osteoarthritis signs
Alteration in gait
Joint swelling
Other joint abnormalities (limited range of movement, crepitus, tenderness, deformities)
Osteoarthritis signs- joint swelling
Bony enlargement
Effusion
Synovitis (if inflammatory component)
Osteoarthritis- Radiological features
Joint space narrowing
Osteophyte formation
Subchondral sclerosis
Subchondral cysts
Abnormalities of bone contour
Osteoarthritis- Radiological features- LOSS
Loss of joint space
Osteophyte
Subchondral sclerosis
Subchondral cysts
Osteoarthritis- Osteophyte formation
Bone spurs- bony lumps that grow on the bones in the spine or around joints
Osteoarthritis- Subchondral sclerosis
thickening and hardening of bone that happens underneath cartilage in a joint
Osteoarthritis- Subchondral cysts
fluid-filled space inside a joint that extends from one of the bones that forms the joint
Osteoarthritis- investigations
Clinical diagnosis- activity-related joint pain, morning stiffness that lasts no longer than 30 minutes, >45 years of age
X-rays only considered if diagnosis is unclear or an alternative/additional diagnosis is suspected
Bloods- inflammatory markers- normal
No antibodies found
DIP joint
Distal Interphalangeal Joint- located at the tip of the finger, just before the finger nail starts
PIP joint
proximal interphalangeal joint- articulation between the proximal and middle phalanx in the hand
CMC joint
carpometacarpal joint- base of the thumb where it meets the hand
OA of the hands
Relapsing, remitting course over a few years
‘Nodal’ form has a strong genetic component
Often ‘inflammatory’ phase for each joint
Bony swelling and cyst formation
Reduced hand function
3 compartments of knee that OA can affect
Medial (commonest)
Lateral
Patellofemoral
Knee OA
Any may be affected in isolation or in combination
Without significant trauma, evolution very slow
Once established, often remains stable for years
Erosive / inflammatory OA
Subset of OA
Strong inflammatory component
In addition to standard management, DMARD therapy (usually milder agents) often used
Osteoarthritis- Loose body in the knee
Associated with ‘locking’ of knee
Bone or cartilage fragment
The only indication for arthroscopy in osteoarthritis
Osteoarthritis- non-medical management
Patient education- Activity and exercise and Weight loss
Physio/ Occupational therapy
Footwear
Orthoses- external medical device for supporting joint
Walking aids- stick/ frame
Osteoarthritis- Pharmacological management
Topical- NSAIDs, Capsaicin
Oral- Paracetamol, NSAIDs (with caution), Opioids
Transdermal patches- Buprenorphine, Lignocaine
Intra-articular steroid injections- role remains unclear
Osteoarthritis- DMARDs
Role in inflammatory OA
Osteoarthritis- surgical management
Arthroscopy (only for loose bodies)
Osteotomy
Arthroplasty
Fusion- (Usually ankle and foot)
Osteoarthritis- Indications for arthroplasty
Uncontrolled pain (particularly at night)
Significant limitation of function
Age is considered
Fracture treatment- 4 Rs
Resuscitate
Reduce
Retain
Rehab
Orthopaedic X ray- ABCs
Alignment - Dislocation
Bone - Fractures
Cartilage – widened joint
Soft tissues – swelling, effusion
Bone remodelling cycle
1.Resting
2.Resorption
3. Formation
4.Mineralisation
Callus formation
1.Bleeding
2. Soft callus
3.Bony callus
4.Remodelling
Direct bone healing
Gap <1mm
Absolute stability
Compression
Gap healing
No callus
Indirect bone healing
Relative stability
Callus formation
Aim of orthopaedic treatment
Improve pain
Reduce disability
Improve function
Fracture considerations
Intra/Extra articular
Position
Pattern
Condition
Displacement
Fracture- Intra/Extra articular
Intra-articular fracture — A fracture that extends into the joint
Extra-articular fracture — A fracture that does not extend into the joint
Fracture- pattern
Transverse- fracture run horizontally perpendicular to your bone
Oblique- bone is broken at an angle
Spiral- bone is broken with a twisting motion, causing fracture line that wraps around your bone and looks like a corkscrew
Fracture- condition
Comminuted- broken in three or more places
Segmental- broken in at least two places, leaving a segment of your bone totally separated by the breaks
Impacted- broken ends of the bone are jammed together by the force of the injury
Fracture- Displacement
Length- has the length of the bone overall shortened
Alignment -Translation- movement of fractured bones away from each other
Angulation- two ends of the broken bone are at an angle to each other
Rotation- two ends of bone not on the same plane
Osteoporosis
Systemic skeletal disease characterised by low bone mass
and microarchitectural deterioration of bone tissue, with a
consequent increase in bone fragility and susceptibility to
fracture
Osteoporosis- RFs- SHATTERED
Steroid use
Hyperthyroidism/ parathyroidism/ calciuria
Alcohol and tobacco use
Thin (BMI< 19)
Testosterone decrease
Early menopause
Renal or liver failure
Erosive/ imflammatory bone disease
Dietary low Ca2+/malabsorption or DM
Osteoporosis - epidemiology
18% of females >50
6% of males >50
>300,000 Osteoporotic fractures in UK each year
Pathophysiology of fracture
-Trauma
-Bone strength (Bone mineral density, bone size, bone quality)
Bone mass and age
Peak bone mass between 15-50
Decreases gradually with age for both M+F- menopause causes bone mass to decrease massively
Common Osteoporotic fracture
Hip (most common)
Vertebrae
Colles’ (more common in women)
Colles’ fracture
break in the radius close to the wrist
Factors that affect bone mineral density
Peak bone mass, rate of bone loss
Factors that affect bone strength
Bone size
Factors that affect bone quality
Bone turnover, architecture, mineralisation
Bone remodelling cycle
Quiescence> Resorption > Formation > Quiescence
Postmenopausal osteoporosis
-Loss of restraining effects of oestrogen on bone turnover
-Preventable by oestrogen replacement
-Characterized by high bone turnover (resorption > formation), predominantly cancellous bone loss, microarchitectural disruption
Postmenopausal osteoporosis- pathophysiology
Quiescence -> increased resorption -> insufficient formation Remodelling imbalance:
net loss of bone
Osteoporosis- Changes in trabecular architecture with ageing
- Decrease in trabecular thickness, more
pronounced for non load-bearing
horizontal trabeculae - Decrease in connections between
horizontal trabeculae - Decrease in trabecular strength and
increased susceptibility to fracture
Osteoporosis- gold standard investigation
dual-energy x-ray absorptiometry (DXA)- bone mineral density (BMD) measurements diagnostic for osteoporosis
Dual-energy x-ray absorptiometry (DXA)
Bone mineral density (BMD) is compared with that of a gender- matched, healthy young adult average.
The T score represents no SD the BMD is from the youthful average
Dual-energy x-ray absorptiometry (DXA)- results
T score >0- better than reference
T score 0 to -1- no evidence of osteoporosis
T score -1 to -2.5- Osteopenia
T score < -2.5- osteoporosis (+fracture= severe osteoporosis)
Osteopenia
Bone density is lower than the average adult, but not low enough to be diagnosed as osteoporosis, risk of later osteoporosis
Offer lifestyle advice
Osteoporosis and inflammatory disease
Inflammatory cytokines increase bone resorption- ie RA, seronegative arthritis, connective tissue disease, inflammatory bowel disease
Osteoporosis and endocrine disease
Thyroid hormone and parathyroid hormone
increase bone turnover
Cortisol increases bone resorption and induces (Cushing’s syndrome)
osteoblast apoptosis
Oestrogen/ testosterone control bone turnover
Osteoporosis and reduced skeletal loading
Reduced skeletal loading increases resorption
o Low body weight
o Immobility
Osteoporosis and drugs
Can be caused by certain drugs
* Glucocorticoids
* Depo-provera
* Aromatase inhibitors
* GnRH analogues
* Androgen deprivation
Osteoporosis- drugs aims
Anti-resorptive- Decrease osteoclast activity and bone turnover
Anabolic- Increase osteoblast activity and bone formation
Osteoporosis- Anti-resorptive drugs drugs
o Bisphosphonates
o HRT
o Denosumab
Osteoporosis- Anabolic drugs drugs
o Teriparatide
o Romosozumab
Osteoporosis- first line treatment
Bisphosphonates (typically oral alendronic acid)
Bisphosphonates known side effect
Have to be taken with plenty of water while standing upright for >30 mins and wait 30 before eating/ drinking
Photosensitivity, GI upset, oesophageal ulcers- stop if any dysphagia, abdo pain
Osteoporosis- Denosumab
- Rapid acting and very potent anti-resorptive
- Good fracture risk reduction
- Rebound increase of bone turnover when stopped
Osteoporosis- Teriparatide
- PTH analogue
Useful for people who have suffered more fractures after previous treatment, Increased risk of renal cancer
Osteoporosis- HRT
Can prevent osteoporosis in post menopausal women, risk of breast cancer is slightly increased
How do bones grow?
Most grow by getting longer and wider
Modeling is dominant process during skeletal growth- Subperiosteal, Endocortical, Trabecular
Osteogenesis imperfecta
Commonest primary osteoporosis
Defects related to type 1 collagen
Mostly autosomal dominant inheritance
Low bone mass
Increased bone fragility
“brittle bone disease”
Osteomalacia
Normal amount of bone but its mineral content is low (there is excess uncalcified osteoid and cartilage)
Osteomalacia vs osteoporosis
Osteomalacia is low mineral content and normal amount of bone
Osteoporosis is normal mineral content and overall bone loss
Osteomalacia and rickets
Rickets is the result of low mineral content during the period of bone growth
Osteomalacia is the result of this process after the fusion of the epiphyses
Rickets- signs and symptoms
Growth retardation, hypotonia, apthay in infants
Once walking- knovk-kneed, bow-legged + deformities of the metaphyseal-epiphyseal joint (growth plate)
Features of low Ca2+
Osteomalacia- signs and symptoms
Bone pain/ tenderness, fractures (esp femoral neck), proximal myopathy (waddling gait), due to low PO4- and vit D def
Causes of Osteomalacia
Vit D deficiency, renal osteodystrophy (renal failure leads to 1,25(OH)2D deficiency), drug- induced, vit D resistance, liver disease, tumour
Vitamin D and rickets
Defect of mineralisation of growing bone
Failure of apoptosis of hypertrophic chondrocytes
Accumulation of un-mineralised growth plate cartilage and un-mineralised osteoid in the rest of the skeleton
Symptomatic vitamin D deficiency
Bowing of legs
Aches
Hypocalcaemia
Fits
Muscle weakness
Cardiomyopathy
Enamel hypoplasia
Fractures
Radiological Features of Rickets
Cupping
Splaying
Fraying
Osteopaenia
Periosteal elevation
Treatment of rickets
Treat underlying cause of rickets
ie vit D supplement for diet deficiency, vit D2 for malabsorption/ hepatic disease or calcitriol for vit D resistance or renal disease
Phosphate absorption
Small intestinal absorption
Not often limited in diet
Absorb 60-65% dietary content
Can be absorbed passively or actively via stimulation from 1,25OH2vitamin D
X-linked hypophosphataemic rickets
Inherited- due too defect in renal phosphate handling
Rickets develop in early childhood
Plasma PO4- is low
X-linked hypophosphataemic rickets- treatment
Large dose of oral phosphate and calcritiol
Hypophosphatasia
inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity
Generalized Arterial Calcification of Infancy (GACI)
rare, life-threatening inherited. Disorder Patients develop calcifications and intimal proliferation in multiple arteries, often resulting in critical illness and death in utero or early infancy
Skeletal dysplasia
category of rare genetic disorders that cause abnormal development of a baby’s bones, joints, and cartilage
Achondroplasia
Commonest skeletal dysplasia 1 in 15-30 thousand
Diagnosis in early infancy
80% to average stature parents
Affects fibroblast growth factor receptor
Achondroplasia- mean adult heights in US
131 cm males
124 cm females
Achondroplasia- long bones
Disproportionately short-limbs
Bowing of legs and other malalignment
Ligamentous laxity
Achondroplasia- complications
Spinal stenosis, lower extremity misalignment, Hydrocephalus, Cervicomedullary/ spinal cord Myelopathy
Achondroplasia- treatments
Treatment for complications
Monitoring- X-rays to monitor the position of the spine and lower extremities. MRI scans of the brain and spine help doctors spot development of spinal stenosis,
What is a crystal?
Homogenous solid
Stable, hard, high density
Strengthen the skeleton and remove excess ions
Crystal pathology
Pathological in wrong sites
-Nephrolithiasis (kidney stones)
-Crystal arthropathies (gout, pseudogout)
Local inflammatory response leading to tissue damage
Crystal arthropathies
Gout
-Urate crystals
Pseudogout
-Pyrophosphate crystals
Gout
Sudden onset hot swollen joint
Excruciatingly painful
Gout typical joint involvement
Big toe- 76%
Ankle/foot- 50%
Knee- 32%
Finger- 25%
Elbow/Finger- 10%
Most common joint involvement- gout
Big toe
Tophaceous gout
uric acid crystals form tophi of white growths that develop around the joints and tissues that gout has affected.
Most severe form of gout
Tophi
often visible under the skin and tend to look like swollen nodule
Gout Epidemiology
Commonest arthritis in men >40yrs
Rises in post-menopausal women- often related to identifiable trigger eg diuretics
More common in males
Normal uric acid excretion
Uric acid produced by nucleic acids/purine metabolism
Usually excreted by kidneys
Purine metabolism
Purine> Hypoxanthine> Xanthine (catalysed by Xanthine oxidase)> Uric Acid
Gout pathophysiology- uric acid crystal formation
Uric acid not fully excreted by kidneys
Converted in to monosodium urate
Excess coalesces into crystals
Urate serum levels
Serum saturation = 0.3mmol/l
Urate in solution
Serum levels > 0.36mmol/l
Risk of crystal deposition
Plasma concentration >0.42mmol/l
Supersaturation; crystal deposition very likely
RFs for excess Urate in plasma
Too much urate consumed (diet, conditions that cause over–production of uric acid)
Too little urate excreted (renal impairment, drugs)
RFs for Too much urate consumed
Alcohol – especially beer
Fructose sweetened drinks
Excess meat, shellfish, offal
Yeast extract
Myeloproliferative disease
Psoriasis
Tumour lysis syndrome
Lesch-Nyhan syndrome
RFs for Too little urate excreted
Renal impairment
Thiazide diuretics
Low dose aspirin
Tacrolimus, ciclosporin
Ethambutol, pyrazinamide
Dietary causes of gout
Excess consumption of: Alcohol – especially beer
Fructose sweetened drinks
Excess meat, shellfish, offal
Yeast extract
Drug causes of gout
Thiazides – increase fluid excretion so remaining fluid more concentrated, also reduce kidney’s excretion of urate
Aspirin reduces uric acid excretion
Tacrolimus, ciclosporin reduce uric acid excretion
Lesch-Nyhan syndrome and gout
x-linked recessive, neurological and behavioural abnormalities and over-production of uric acid
Gout and metabolic syndrome
association with metabolic syndrome, diabetes, hypertension
Extra fat, body produces more insulin, makes it harder for kidneys to get rid of uric acid
Hypertension and gout
Hypertension damages glomerulus, affects renal excretion of uric acid
Gout triggers
Most are spontaneous
Direct trauma to the joint
Intercurrent illness
Alcohol or shellfish binge
Surgery
Dehydration
Gout- diagnostic investigation
Arthrocentesis with synovial fluid analysis
shows high WBC, strongly negative birefringent needle-shaped crystals under polarised light
Gout-Arthrocentesis with synovial fluid analysis
Diagnostic- Excludes septic arthritis and differentiates gout from pseudogout
shows high WBC and monosodium urate crystal (strongly negative birefringent needle-shaped crystals under polarised light)
Gout- acute 1st line treatment
NSAIDs
Colchicine- (anti-inflammatory medicine for gout)
Prednisolone- corticosteroid
Gout- chronic- 1st line treatment
Allopurinol- Lower uric acid levels
Gout- chronic- treatment
Allopurinol (1st line)
Febuxostat
Xanthine oxidase inhibitors
Low dose colchicine, NSAID or corticosteroid for up to 6 months to prevent paradoxical risk of flare
Education
Gout- chronic- aim of treatment
Lower uric acid levels
Gout- acute- aim of treatment
Inhibit phagocyte activation and acute inflammation
Pseudogout
Sudden onset hot swollen joint
Knees>wrists>shoulders>ankles>elbows
Resolution in 1-3 weeks
Calcium pyrophosphate (CPP) crystals
Pseudogout- epidemiology
Predominantly a disease of the elderly
Chronic arthropathy overlap with OA
Pseudogout- crystal type
Calcium pyrophosphate (CPP) crystals
Pseudogout- diagnostic treatment
arthrocentesis with synovial fluid analysis
-positively birefringent rhomboid-shaped crystals under polarised light
Pseudogout- arthrocentesis with synovial fluid analysis
Positively birefringent rhomboid-shaped crystals under polarised light
Pseudogout RFs
Haemochromatosis
Hyperparathyroidism
Hypophosphatasia
Hypomagnesaemia
Hypothyroidism
Acromegaly
Pseudogout- acute treatment
NSAIDs
Colchicine- (anti-inflammatory medicine for gout)
Prednisolone- corticosteroid
Pseudogout- chronic treatment
LT low dose Prednisolone
LT low dose colchicine
Typical gout presentation
acute with hot swollen joint(s)
Chronic with joint/tissue damage
Crystal deposition in joints can trigger
acute inflammation
long term damage
Vasculitis
inflammation of a blood vessel, which is characterised by the presence of an inflammatory infiltrate and destruction of the vessel wall
Systemic Vasculitis
autoimmune disorders characterised by inflammation of blood vessels
Giant cell arteritis
Granulomatous vasculitis of large and medium-sized arteries
It primarily affects branches of the external carotid artery
Common form of vasculitis in people aged 50 years or older
Giant cell arteritis- key signs and symptoms
Presence of a new headache in someone with tenderness of the scalp, aching + stiffness, extremity claudication, jaw and tongue claudication
Partial/complete loss of vision (painless) in one or both eyes in up to 20% of patients
Granulomatosis with polyangiitis
Systemic vasculitis that typically involves small and medium vessels.
Classic triad of upper and lower respiratory tract involvement and pauci-immune glomerulonephritis
Granulomatosis with polyangiitis- key signs and symptoms
Upper + lower respiratory tract involvement, renal involvement
Common constitutional effects include fatigue, malaise, fever, night sweats, anorexia, and weight loss
Antineutrophil cytoplasmic antibodies (ANCA) testing
attack healthy neutrophils. This can lead to a disorder called autoimmune vasculitis
strongly correlated with certain forms of vasculitis (like granulomatosis with polyangiitis)
List key indications for antineutrophil cytoplasmic antibodies (ANCA) testing
Signs of inflammatory bowel syndrome
Signs of vasculitis
Systemic vasculitis- investigations
Anti-neutrophil cytoplasmic auto-antibodies (ANCA)- positive, not diagnostic
Biopsy of affected tissue- may be misleading due to sampling error or immunosuppressive therapy
Giant cell arteritis- diagnostic investigations
Vascular ultrasonography and/or a temporal artery biopsy
Giant cell arteritis- treatment
Start treatment with a high-dose glucocorticoid immediately, even while awaiting confirmation of the diagnosis
Granulomatosis with polyangiitis- treatment
Remission induction- high-dose corticosteroid
Remission maintenance- corticosteroids and immunomodulatory therapy
Overview of treatment for systemic vasculitis
Dependent on specific diagnosis and on the severity of the clinical manifestations
Complications of systemic vasculitis
Organ damage, blood clots and aneurysms, vision loss, infections
Polymyalgia rheumatica
inflammatory rheumatologic syndrome that manifests as pain and morning stiffness involving the neck, shoulder girdle, and/or pelvic girdle in individuals older than age 50 years
Treat with 24 to 72 hours with low-dose prednisolone
Polymyalgia rheumatica and giant cell arteritis
About 15% to 20% of patients with PMR have giant cell arteritis (GCA); 40% to 60% of GCA patients have PMR.
Fibromyalgia
syndrome characterised by widespread pain in the body present for at least 3 months and is thought to be related to amplified pain signals in the spinal cord and brain
Aetiology is unknown
Fibromyalgia- clinical diagnosis
No x-ray/lab test- diagnosis is strictly clinical based on clinical criteria- presence of chronic (>3 months), widespread body pain and associated symptoms such as fatigue and sleep disturbance
Fibromyalgia treatment
Non-pharmacological therapies are the cornerstone to the management of fibromyalgia- patient education, self-management, physical activity, physio, Psychological interventions
Polyarteritis nodosa
Necrotising inflammation of medium-sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules
Polyarteritis nodosa and Hepatitis B virus
Very rare since immunisation program
Short course of high-dose corticosteroids, followed by a combination of antiviral therapy and plasma exchange
Non-HBV-related Polyarteritis nodosa treatment
Immunosuppression is the mainstay of treatment
Paget’s disease of bone
chronic bone disorder that is characterised by focal areas of increased bone remodelling, resulting in overgrowth of poorly organised bone
This unbalanced process may lead to osseous deformities, altered joint biomechanics, nerve compressions, and pathological fracture
