Musculoskeletal System Flashcards
1
Q
What is HLA B27 associated with?
A
Spondyloarthritis (SpA) such as:
Ankylosing spondylitis
Psoriatic arthritis
Reactive arthritis
2
Q
What is HLA B27?
A
Human Leucocyte Antigen (HLA) B27
Class I surface antigen (all cells, except red blood cells)
Encoded by Major Histocompatibility Complex (MHC) on chromosome 6
Antigen presenting cell
Essentially a tissue type
3
Q
Why is HLA B27 linked with disease?
A
“Molecular mimicry”
Infection → immune response → infectious agent has peptides very similar to HLA B27 molecule → auto-immune response triggered against HLA B27
Mis-folding theory
HLA B27 heavy chain homodimer hypothesis.
Remember not all patients are B27 positive!
4
Q
How does the mis-folding theory work?
A
These unfolded HLA-B27 proteins accumulate in the endoplasmic reticulum (ER).
A proinflammatory stress response called the endoplasmic reticulum unfolded protein response (ERUPR) ensues.
As a result, interleukin 23 (IL-23) is released, activating a proinflammatory response via interleukin-17+ T lymphocytes.
5
Q
How does the heavy chain homodimer hypothesis work?
A
It is suggested that B27 heavy chains can form stable dimers, which tend to dimerize and accumulate in the endoplasmic reticulum.
In turn, this initiates the proinflammatory ERUPR.
In addition, these heavy chains and dimers can bind to other regulatory immune receptors such as the natural killer receptors (NKRs).
This causes the expression and survival of more proinflammatory leukocytes and subsequent production of proinflammatory mediators.
6
Q
WHAT IS ANKYLOSING SPONDYLITIS OR “AXIAL SPONDYLOARTHRITIS”?
A
Inflammatory arthritis of the spine, rib cage and sacroiliac joints
– eventually leading to new bone formation and fusion of the joints.
7
Q
When does ankylosing spondylitis start?
A
Typically starts in late teenage years/ 20s.
More common in Men.
8
Q
What are the clinical features of SpA?
A
_Low back pain – improves with activity not improved with rest
Morning stiffness_
Inflammatory arthritis of the “axial skeleton”, 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) ie inflammation of the anterior chamber of the eye
Peripheral arthritis (often large joint oligoarthritis but in PsA can be small joint just like RA)
Skin psoriasis
May also have (sub-clinical) inflammatory bowel disease
9
Q
What does SPINEACHE help with and what does it represent?
A
Sausage digit (dactylitis)
Psoriasis
Inflammatory back pain
NSAID good reponse
Enthesitis (heel)
Arthritis
Crohn’s/ Colitis/ elevated CRP*
HLA B27
Eye (uveitis)
Symptoms of SpA.
10
Q
What is Syndesmophytes?
A
Bone growth originating inside ligaments.
11
Q
What is Sacroiliitis?
A
Inflammation of one or both of your sacroiliac joints
Sclerosis, erosions, loss of joint space,fusion.
12
Q
What is Kyphosis?
A
Curvature of the spine at the top.
13
Q
What is the proposed method for Ankylosing spondylitis?
A
Delayed damage theory”
ie once inflammation has occurred – new bone formation is inevitable, therefore once treatment started, new bone continues to form for some time after
14
Q
What are the tests for ankylosing spondylitis?
A
Diagnosis is clinical, supported by imaging
MRI is most sensitive and better at detecting early disease.
Sacroiliitis is the earliest X-ray feature, but may appear late: look for irregularities, erosions, or sclerosis affecting the lower half of the sacroiliac joints, especially the iliac side.
Syndesmophytes common later stages on radiography.
‘Bamboo spine’ In later stages, calcification of ligaments with ankylosis lead to this
FBC (normocytic anaemia), increased ESR, increased CRP, HLA B27+ve (not diagnostic).
15
Q
What is the ASAS criteria used for? What does the criteria require?
A
Ankylosing spondylitis.
Confirmation of sacroiliitis on imaging plus more than or equal to 1 SpA feature
or HLA-B27 plus more than or equal to 2 SpA features.
16
Q
What is the treatment for ankylosing spondylitis?
A
Exercise
NSAIDS
Ibuprofen or Naproxen.
TNF alpha blockers
Golimumab
Local steroid injections
Surgery includes hip replacement/spinal osteomy
Bisphosphonates (consider)
Alendronate
There is increased risk of osteoporotic spinal fractures
17
Q
WHAT IS PSORIATIC ARTHRITIS?
A
Psoriatic arthritis is a form of arthritis affecting the joints in people with the skin condition psoriasis
18
Q
What is the epidemology of psoriatic arthritis?
A
1 in 5 people with psoriasis and can present before skin changes.
19
Q
What are the clinical manifestations of disease for Psoriatic Arthritis?
A
Spinal/Axial, (Similar to AS)
Arthritis mutilans
DIPJ only, (Distal interphalangeal joint)
Oligoarthritis (2-4 joints in first 6 months) (Like RA) Large joint
Asymmetrical
Polyarthritis = >5 joints RA like (symmetrical small joint).
Also
Dactylitis
Nail changes
20
Q
What is arthritis mutilans?
A
An extremely severe form of chronic rheumatoid or psoriatic arthritis characterized by resorption of bones and the consequent collapse of soft tissue.
When this affects the hands, it can cause a phenomenon sometimes referred to as ‘telescoping fingers.’
21
Q
What are the investigations for psoriatic arthritis?
A
‘Pencil-in-cup’, erosive changes, with deformity in severe cases.
Nail changes in 80%
Synovitis (dactylitis)
Rashes
Acneiform rashes and palmo-plantar pustulosis.
22
Q
What is the treatment for Psoriatic Arthritis?
A
Similar to RA
NSAIDs
DMARDs
MTX, ciclosporin
DMARDs often help skin disease
Anti TNF drugs
Golimumab, infliximab
IL12/23 blockers
Ustekinumab
23
Q
WHAT IS REACTIVE ARTHRITIS?
https://www.youtube.com/watch?v=dzQwIqc6dQE
A
Sterile inflammation of the synovial membrane, tendons and fascia triggered by an infection at a distant site, usually gastro-intestinal or genital.
24
Q
What is the epidemology of reactive arthritis?
A
Mostly Male
20-40
25
What are some causes of reactive arthritis?
**_Gut associated infections_**
Salmonella
Shigella
**_Sexually acquired infection (NSU)_**
Chlamydia
Ureaplasma urealyticum.
26
What is Reiter’s syndrome?
Classical triad of
Arthritis (large joints)
Urethritis.
Conjunctivitis
CANT PEE, CANT SEE, CANT CLIMB A TREE
27
What are some symptoms of reactive arthritis?
**_Iritis_**
**_Keratoderma blenorrhagica_**
Brown, raised plaques on soles and palms
**_Circinate Balanitis_**
Painless penile ulceration secondary to Chlamydia
28
What are some differential diagnosis of reactive arthritis?
Hot swollen joint
Think
Septic arthritis.
Gout.
29
What are some tests for reactive arthritis?
**_Blood test_**
Raised ESR/CRP
**_Aspirate joint_**
To exclude infection/crystals.
**_Urethral swab, stool culture_**
Show infection.
Contact tracing if necessary.
30
What is the management for reactive arthritis?
**_No specific cure_**
**_Antibiotics_**
**_Splint joints_**
**_NSAIDS or local steroid injections_**
**_Sulfasalazine or methotrexate_**
If symptoms \>6 months. (Consider)
Treating the original infection may make little difference to the arthritis.
31
WHAT IS ENTEROPATHIC ARTHRITIS?
Inflammatory arthritis associated with the occurrence of an inflammatory bowel disease (IBD), the two best-known types of which are ulcerative colitis and Crohn's disease.
32
Where does enteropathic arthritis occur in men and women?
Men – axial/spinal (esp.HLA-B27+)
Women – peripheral/limb
33
What are the symptoms of enteropathic arthritis?
Peripheral synovitis
Asymmetric lower limb arthritis
AS occurs in 7% of patients with IBD.
50% of patients with IBD and HLA-B27 +ve develop sacroiliitis
34
What are the treatments for enteropathic arthritis?
No specific cure
Antibiotics
Splint joints
NSAIDS or local steroid injections
Sulfasalazine or methotrexate
If symptoms \>6 months. (Consider)
Treating the original infection may make little difference to the arthritis.
35
What are some examples of inflammatory joints?
Auto-immune.
Crystal arthritis.
Infection.
36
WHAT IS RHEUMATOID ARTHRITIS?
https://www.youtube.com/watch?v=6ylzE5usu7o
Auto-immune inflammatory disease affecting joints and other systems
37
What is the epidemology rheumatoid arthritis?
Common inflammatory arthritis~1% population
**_Women_** more common
38
What are the classical signs of inflammation?
Rubour (red)
Calor (heat)
Tumour (swelling)
Dolor (pain)
39
What are the properties of an inflammatory disorder?
Pain eases with use
Stiffness
Significant (\>60 mins)
Early morning/ at rest (evening)
Swelling Synovial +/- bony
Hot & red?
Pt demographics
Eg young, psoriasis, family history
Joint distribution
Eg hands & feet
Responds to NSAIDs
40
What are the properties of a degenerative disorder?
Pain increases with use
clicks/ clunks
Stiffness
Not prolonged (\<30 mins)
Morning/ evening
Swelling
None, bony
Not clinically inflamed
Pt demographics
Eg older, prior occupation/ sport
Joint distribution
Eg 1st CMCJ, DIPJ, knees
Less convincing response to NSAIDs
41
What does a normal synovial joint look like?
2 articulating bone surfaces
covered with hyaline cartilage
Fibrous capsule lined with synovium
Joint space filled with synovial fluid.
42
What does inflammation of a synovial joint cause?
Arthritis.
43
What is the cause of rheumatoid arthritis?
Genetic and environment
HLA DR1 and 4
Ciagrette smoke or infection
44
What happens when citruillination happens?
Arginine converted into citruline in collagen type 2 and vermentin
Host no longer recognises these as self
Antigens get picked up by antigen presenting cells
Carried to lymph nodes which activate CD4 cells
CD4 cells activate B cells
Generate antibodies against these cells
45
What happens when the antibodies travel in the blood to the joint?
CD4 cells secrete cytokines
Recruit macrophages into joint space
Macrophages also produce cytokines
Stimulate synovial cells to proliferate
This causes a pannus
46
What is a pannus made up of?
Fribroblasts
Myofibroblasts
Inflammatory cells
47
What happens once the pannus is formed in rheumatoid arthritis?
Causes damage to
Cartilage
Other soft tissue
Errode bone
Activates synovial cells also release proteases which break down cartilage
48
What do T cells express on there surface and what does this do?
RANK-L
Activates osteoclasts
49
What antibodies appear in the synovial fluid?
Rheumatoid factor
Anti-CCP
50
What is rheumatoid factor?
Antibody against the Fc portion of IgG
Fc: region within heavy chain, role in modulating immune response
Occurs in many other diseases
51
What is Cyclic citrullinated Peptide?
Marker of disease; not pathogenic itself
Reacts with Filaggrin protein in keratin
52
What do the immune complexes activate?
Activate the complement system
53
What are the symptoms of rheumatoid arthritis?
Joint pain often worse in morning
Morning stiffness-several hours
Loss of function
General-fatigue, malaise
Extra-articular involvement.
| (may improve with activity)
54
What is some signs of rheumatoid arthritis?
Symmetrical small joints
MCP
PIP
More than 5 usually
Ulnar deviation of the fingers.
Boutonnière and swan-neck deformities of fingers or Z-deformity of thumbs occur.
Baker (poploteal cyst)
Larger joints can be involved.
Atlanto-axial joint subluxation may threaten the spinal cord (rare).
55
What other organs can be involved?
Lungs
Heart
Gastrointestinal tract
Skin
Eyes
Kidneys.
56
What soft tissue involvement can there be in rheumatoid arthritis?
Nodules
Bursitis
Tenosynovitis
Muscle wasting
57
What are some eye involvements of rheumatoid arthritis?
Sicca (dry eyes)
Secondary Sjorgren’s syndrome
Episcleritis
Scleritis (corneal ulceration).
58
What are some haematological involvements of rheumatoid arthritis?
Lymph nodes can be palpable
Spleen may be enlarged
Anaemia
59
What are some lung involvements of rheumatoid arthritis?
Fibroblasts causing scar tissue
Decrease gas exchange
Pleural cavities fill with fluid
60
What is vasculitis?
Most common manifestation is small digital infarcts along nailbeds
Abrupt onset of ischaemic mononeuropathy (MMx) or progressive scleritis typical of rheumatoid vasculitis
Seropositive usually, persistently active disease
Can occur when joints inactive
61
What are some investigations for rheumatoid arthritis?
**_Blood tests_**
**Rheumatoid Factor** 80%
**Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibody** c.80%
Anaemia
High ESR/CRP
Anti-nuclear antibody (ANA) \< 50%
Negative for all c.20%
**_X-Ray_**
Soft tissue swelling, juxta-articular osteopenia and loss joint space.
_**Ultrasound
MRI**_
Identify synovitis more accurately, greater sensitivity.
62
What are the managements for rheumatoid arthritis?
**_DMARDS_**
* *_Rituximab_** - B cells
* *_Abatacept_** - T cells
**_Steroids_**
Rapidly reduce symptoms and inflammation. Methylprednisolone
**_NSAIDS_**
Symptom relief, no efect on disease progression.
Paracetamol and weak opiates are rarely effective.
Physio- and occupational therapy, eg for aids and splints.
**_Surgery_**
May relieve pain, improve function and prevent deformity.
There is increased risk of cardiovascular and cerebrovascular disease, as atherosclerosis is accelerated in RA.
**_Manage risk factors_**
Smoking also increases symptoms of RA.
63
WHAT IS VASCULITIS?
https://www.youtube.com/watch?v=ise3cEqmEqU
Inflammation and necrosis of blood vessel walls with subsequent impaired blood flow
64
What is the cause of vasculitis?
Autoimmune disease, confusing part of the blood vessel as foregin
65
What are the different damage pathways of vasculitis?
Molecular mimicry and directly attack it
Medium and large vessel vasculitis
Indirect damage from damage of an overlying pathogen
Small vessel vasculitis
66
What happen in vasculitis after endothelial damage?
Collagen exposed
Platelets adhere to the vessel wall
Blood vessel wall becomes weakend
Anneurysms become more likely
As the vessel heals and fibrin is deposited the wall becomes stiffer
67
What happens in the cells for vasculitis?
Vessel wall infiltration
Neutrophils, mononuclear cells +/or giant cells
Fibrinoid necrosis
Leukocytoclasis (dissolution of leucocytes)
68
How do you classify vasculitis?
**_Size of vessel_**
Small – medium - large vessel disease
**_Target organ(s)_**
**_A_****nti-neutrophil cytoplasmic antibodies** (**_ANCA_**)
Present or not
**_Primary vs secondary_**
69
What are the different classifications of vasculitis?
Large
Medium
Small
ANCA +ve vasculitis
ANCA –ve vasculitis
70
What are the different large vasculitis'?
Giant cell arteritis, Takayasu’s arteritis
71
What are the different medium vasculitis'?
Polyarteritis nodosa, Kawasaki disease
72
What are the different small vasculitis'?
Microscopic polyangitis, Wegener's granulomatosis
73
How does vasculitis present?
No single typical presentation
Systemically unwell
Fever
Arthralgia/arthritis
Rash
Weight loss
Headache
Footdrop
Major event eg stroke, bowel infarction.
74
What must be excluded to ensure correct diagnosis of vasculitius?
Sepsis-SBE, hepatitis
Malignancy
Other-eg cholesterol emboli
75
What are some common tests for vasculitis?
ESR/CRP increase. ANCA may be +ve.
Increase in Creatinine if renal failure.
Urine: proteinuria, haematuria, casts on microscopy.
Angiography ± biopsy may be diagnostic.
76
What is the usual treatment for vasculitis?
Cyclophosphamide.
77
What is ANCA-associated vasculitis?
**_Antineutrophil cytoplasmic antibodies_**
Small/medium vessel vasculitis
Specific antibodies for antigens in cytoplasmic granules of neutrophils and monocyte lysosomes.
78
What are the investigations for ANCA-associated vasculitis? What are the two major patterns?
Detected with indirect immunofluorescence microscopy
**_Two major patterns_**
Cytoplasmic ANCA (c-ANCA) Major antigen Proteinase 3
Peri-nuclear ANCA (p-ANCA) Major antigen Myeloperoxidase (MPO)
79
WHAT IS GIANT CELL (TEMPORAL) ARTERITIS?
https://www.youtube.com/watch?v=ise3cEqmEqU
Granulomatous arteritis of aorta + larger vessels-extracranial branches of carotid arteries
80
What is the epidemology of Giant cell arteritis?
Primarily\>50yrs old
Incidence increases with age
Twice as common in women
81
How does giant cell (temporal) arteritis present?
Headache
Scalp tenderness
Jaw claudication
Acute blindness
Non specific malaise
82
What does the American College of Rheumatology Diagnostic criteria require?
3 or more of:
Age\>50
New headache
Temporal artery tenderness or decreased pulsation
ESR \> 50 mm/h
Abnormal artery biopsies showing necrotizing arteritis with mononuclear infiltrate or granulomatous inflammation
83
What do giant cell arteritis temporal arteries look like?
Palpable
Tender
Reduced pulsation.
84
What is AION(Arteritic) anterior ischemic optic neuropathy ?
Sudden, painless, monocular and severe visual loss.
May be preceded by transient visual loss
The optic disc becomes pale and swollen, often with flame-shaped haemorrhages at the margin.
85
What are the tests for giant cell arteritis?
ESR & CRP increase
Platelets increase
Alk phos increase
Hb lower
Get a temporal artery biopsy within 7 days of starting steroids.
Skip lesions occur, so don’t be put off by a negative biopsy (up to 10%).
86
What is the treatment for GCA?
**_Corticosteroids_**
Prednisolone
**_Steroid sparing agents_**
Eg Azathioprine/Methotrexate/biologics
**_Prophylaxis of osteoporosis_**
Lifestyle advice
Calcium/Vitamin D + Bisphosphonate
DEXA scan
87
WHAT IS POLYARTERITIS NODOSA (PAN)?
https://www.youtube.com/watch?v=ise3cEqmEqU
PAN is a necrotizing vasculitis that causes aneurysms and thrombosis in medium-sized arteries
Leading to infarction in affected organs, with severe systemic symptoms.
88
What is the cause of polyarteritis nodosa?
Some associated with Hep B
Others unknown
89
What is the epidemology of polyarteritis nodosa?
Women more than men.
Rare in UK
90
What is the pathology of polyarteritis nodosa?
Immune cells confuse the vessel wall with hep B virus
Causes transmural inflammation
All layers die
Fibosis as vascular wall heals
This process is fibrinoid necrosis
Anneurysms occur through weakness of artery
91
What are the symptoms of polyarteritis nodosa?
**_Typically systemic features_**
**_Skin_**
Rash and ‘punched out’ ulcers
**_Renal_**
Hypertension
**_Cardiac_**
Angina or MI
**_GI_**
**_GU_**
92
What are the tests for polyarteritis nodosa?
Often WCC increase
Mild eosinophilia (in 30%)
Anaemia
ESR increase
CRP increase
ANCA –ve.
**_Angiography_**
String of beads
93
What is the treatment of polyarteritis nodosa?
**_Control BP_**
**_Corticosteroids_**
Prednisolone
**_Cyclophosphamide_**
Hepatitis B should be treated with an antiviral after initial treatment with steroids.
94
WHAT IS POLYMYALGIA RHEUMATICA (PMR)?
Polymyalgia rheumatica is a disease of the muscles and joints characterized by muscle pain and stiffness, affecting both sides of the body, and involving the shoulders, arms, neck, and buttock areas.
95
What disease is common with polymyalgia rheumaticia?
PMR and GCA share the same demographic characteristics and, although separate conditions, the two frequently occur together
96
What is the epidemology of polymyalgia rheumatica (PMR)?
Over 50 years olds
Women more than men
97
What is the pathogenesis of Polymyalgia rheumatica (PMR)?
Unknown
98
What are the symptoms of polymyalgia rheumatica?
Tenderness and morning stiffness
Bilateral aching
Tenosynovitis
Carpal tunnel syndrome
B symptoms
99
What are the investigations for polymyalgia rheumatica?
CRP increased,
ESR increased
ALP is increased
Note creatinine kinase levels are normal (helping to distinguish from myositis/myopathies)
MRI
Ultrasound
100
What are the differential diagnosis for polymyalgia rheumatica?
Recent onset RA
Polymyositis
Primary muscle disease
Malignancy or infection
Osteoarthritis
Spinal stenosis
101
What are the treatment options for polymyalgia rheumatica?
**_Corticosteroids_**
Prednisolone
102
What is osteoarthritis?
https://www.youtube.com/watch?v=sUOlmI-naFs&t=63s
A non inflammatory disorder
Deterioration of articular cartilage
Formation of new bone of the joint surfaces and margins
103
What is the cause of osteoarthritis?
Unknown but risk factors have a big impact
104
What is the prevalence of osteoarthritis?
Commonest joint disorder
M=F
\<45yrs prevalence greater in males
\>55yrs prevalence greater in females
Common in Caucasians
105
What are the different classifications of osteoarthritis?
**_Primary or idiopathic_**
No identifiable predisposing cause
**_Secondary_**
When an underlying cause is implicated
106
What are the predisposing factors for oesteoarthritis?
Genetic.
Trauma.
Deformities.
Occupation.
Obesity
Bone density.
107
What is the basic pathogenesis for osteoarthritis?
Articular cartilage failure
Friction
Inflammation
Pain
108
What do chondrocytes produce?
**_Type 2 collagen_**
**_Proteoglycans_**
Hyularonic acid
Keratin Sulphate
109
What is the pathogenesis for osteoarthritis?
Chondrophytes release degredation enzymes and synthetic enzymes
Something tips balance in favour of degredation enzymes
Articular cartilage failure trigger chondrcytes
Less proteoglycans made and more type 1 collagens made
Chondrocytes then die
Synovium cells take in dead cells, macrophages release inflammatory mediators
110
What cells are involved with the pathogenesis of osteoarthritis?
**_Proteases_**
Metalloproteases
**_Catabolic cytokines_**
IL-1, TNF- alpha
**_Anabolic cytokines_**
Insulin like growth factor, TGF – beta
**_Inflammation_**
111
What in a history would indicate osteoarthritis?
**_Pain_**
Insidious and increases over months or years
Aggravated by activity
Relieved by rest
May be referred pain
Swelling
Stiffness
112
What does osteoarthritis look like on examiantion?
Swelling
Muscle wasting
Deformity
Decreased ROM
Crepitus (cracking or clicking of joint movement)
Osteophytes palpable
Joint instability (later on)
Heberdens
Bouchards
113
What are Heberdens and Bouchards?
Heberden's nodes are hard or bony swellings that can develop in the distal interphalangeal joints (DIP)
Bouchard's nodes are hard, bony outgrowths or gelatinous cysts on the proximal interphalangeal joints
114
What are the differential diagnosis to osteoarthritis?
Rheumatoid Arthritis
Gout
Osteonecrosis
Neuropathic Joint
115
What investigations can you do for osteoarthritis?
**_Imaging_**
X-RAY DIAGNOSTIC
**_Laboratory Tests_**
Blood & Synovial Fluid
116
What are you looking for in a X-ray of osteoarthritis?
**_L_**oss of joint space
**_O_**steophytes (bony projection associated with the degeneration of cartilage at joints.)
**_S_**ubarticular sclerosis (denser area of bone just under the cartilage in your joint, appearing as abnormally white bone along the joint line)
**_S_**ubchondral cysts (The cartilage tries to repair itself, the bone remodels, the underlying (subchondral) bone hardens, and bone cysts form.)
117
What labratory tests could you do for osteoarthritis?
**_Blood_**
ESR, FBC, Rh Factor, Calcium, ALP, Electrophoresis
All Normal
**_Synovial Fluid Analysis_**
Non specific in OA
118
What are the different types of management of osteoarthritis?
Conservative / Non surgical
Injection
Surgical
119
What is the conservative / non surgical management of osteoarthritis?
**_Exercise_**
**_Topical Products_**
Capsaicin decreases pain by depleting stores of substance P
**_Tablets_**
Analgesics and Glucosamine
Paracetamol and NSAIDs
Cox-2 inhibitors
**_Lifestyle Modification_**
**_Splints and Orthotics_**
**_Physiotherapy_**
120
What do Glucosamine & Chondroitin sulfate do in osteoarthritis?
Important constituents of proteoglycans (matrix) which resists compression forces in the joint.
121
What injections can be given for osteoarthritis?
**_Steroid - short term_**
Methylprenisolone
**_Viscosupplementation agent_**
Hyaluronic Acid
122
What surgical managements can you do of osteoarthritis?
Debridement of Joint
Realignment Osteotomies
Joint Excision
Joint Fusion (arthrodesis)
Joint Replacement (arthroplasty)
123
WHAT IS SYSTEMIC LUPUS ERYTHEMATOSUS?
https://www.youtube.com/watch?v=0junqD4BLH4
SLE is a multisystemic autoimmune disease in which autoantibodies are made against a variety of autoantigens (eg ANA).
124
What is the epidemology of systemic lupus erythematosus?
Women of child bearing age
Genetic Association:
HLA: DR2, DR3
C4 A Null Allele
125
What happen in systemic lupus erythematosus?
UV light or other trigger causes death of cell
Nucleic contents spill out
Antibodies made against these
Complex sticks to vessel wall and cuases damage
Type 3 hypersensitivity
126
What are the clinical features of SLE?
Malaise, fatigue, myalgia and fever.
Arthritis
**_Skin rashes_**
Butterfly, Discoid, photosensitive rash.
Mucosal ulceration
Pleurisy
Pericarditis
Raynaud’s phenomenon
Glomerulonephritis
127
What are some classic distuingishers of SLE?
Butterfly rash
Dicoid rash
Photosensitive rash
Alopecia
Mouth ulcers
Lupus nephritis
128
What does SLE arthritis look like?
Symmetrical
Less proliferative than RA
Can be deforming
Non-erosive
129
What immunology/testing can be done for SLE?
**_Anti-nuclear antibody_**: Not specific for lupus (screening test)
**_Double stranded DNA_** antibody: Specific
Other antibodies:
**_Rheumatoid factor_**
Cardiolipin antibodies, Anti Ro, La, Sm, RNP
ESR increase but normal CRP
130
What does the SLE : ACR 1982 Classification Criteria
require for diagnosis of SLE?
Four or more of the following.
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder
Neurological disorder
Haematological disorder
Immunological disorder
Anti-nuclear antibody
131
What is the management for SLE?
**_Topical steroids and s_****_unblock_**
Rashes
**_NSAIDS_** and **_hydroxychloroquine_**
Joint and skin symptoms.
**_Steroids_**
Suppress immune system
**_Immunosupressants_**
Azathiprine, methotrexate and mycophenolate are used as steroid-sparing agents.
Rituximab.
Belimumab
132
What is antiphospholipid syndrome?
Antibodies against protein in the phospholipid membrane
Associated with Lupus
133
What does antiphoshpholipid syndrome cause?
Antiphospholipid antibodies (anticardiolipin & lupus anticoagulant) cause CLOTS:
**_C_**oagulation defect
**_L_**ivedo reticularis (mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin)
**_O_**bstetric (recurrent miscarriage)
**_T_**hrombocytopenia (reduced platelets)
134
How do you diagnose antiphospholipid syndrome?
**_Lupus anticoagulant_**
And/or
**_Cardiolipin Antibodies_**
Positive on 2 occasions 12 weeks apart
135
How can you treat antiphospholipid syondrome?
Aspirin
Warfarin
136
WHAT IS RAYNAUD'S PHENOMENON?
https://www.youtube.com/watch?v=n809IRTYYeU
Discoloration of the fingers and/or the toes
After exposure to changes in temperature or emotional events.
137
What are the colour changes of Raynaud's?
Fingers or toes ache and change colour:
pale (ischaemia) to
blue (deoxygenation) to
red (reactive hyperaemia)
138
How is Raynaud's phenomenon caused?
**_Primary_**
Raynaud's disease
**_Secondary_**
Connective tissue diseases
Drugs
Vascular damage
Raynaud's syndrome
139
How is Raynaud's phenomenon caused connective tissue diseases?
**_Secondary_**
**_Connective tissue diseases_**
Systemic sclerosis
Mixed connective tissue disease
SLE
140
How is Raynaud's phenomenon caused drugs?
**_Drugs_**
Beta-blockers
141
How is Raynaud's phenomenon caused vascular damage?
**_Vascular damage_**
Atherosclerosis
Frost bite
Vibrating tools
142
What happens in raynaud's when there is a change in temperature?
Nerves oversitimulated
Leading to vascontrction of blood vessels
143
What are the symptoms of raynaud's?
Colour changes
Numbness, tingling and pain
Could cause tissue death
144
What is the diagnosis of raynaud's phenomenom?
Description of episodes
Explore underlying condition
Nailfold capillary microscopy
145
What is the treatment for Raynaud's phenomenon?
**_Avoid triggers_**
**_Stop smoking_**
**_Vasodilators_**
Nifedipine or sildenafil
**_Surgery_**
146
WHAT IS SYSTEMIC SCLEROSIS?
https://www.youtube.com/watch?v=ErchMUH0oXY
Autoimmune disease of the connective tissue
Thickening of the skin caused by accumulation of collagen
And by injuries to small arteries
147
What are the different types of systemic sclerosis?
Limited and diffuse
148
What does limited systemic sclerosis show?
**_C_**alcinosis (calcium deposits form in the skin)
**_R_**aynaud’s phenomenon
O**_e_**sophageal reflux, strictures
**_S_**clerodactyly (localized thickening and tightness of the skin of the fingers or toes)
**_T_**elangectasia (widened venules (tiny blood vessels) cause threadlike red lines or patterns on the skin.)
Pulmonary arterial hypertension
149
What is the antibody for limited systemic sclerosis?
Anticentromere
150
What does diffuse (skin) systemic sclerosis show?
Additional features:
Proximal scleroderma
Pulmonary fibrosis
Bowel involvement
Myositis
Renal crisis: hypertension
151
What is the antibody for diffuse systemic sclerosis?
Antibodies: Scl-70, nucleolar, RNA polymerase
152
What is the pathogenesis of systemic sclerosis?
Vasculopathy
Excessive collagen deposition
Inflammation
Auto-antibody production
153
What is the management of systemic sclerosis?
NO CURE
Treat symptoms
**_Cyclophosphamide_**
Supression of immune system
154
WHAT IS SJÖGREN'S SYDROME?
https://www.youtube.com/watch?v=d3qPMecBrY0
Exocrine glands destoryed
155
Which glands are mainly affected in sjorens?
Lacrimal and salivary glands
156
What are some systemic involvements of sjorens?
Polyarthritis/arthralgia
Raynaud’s
157
What are the features of Sjögren’s Syndrome?
**_Sicca complex:_**
Dry eyes
Dry mouth
Enlarged salivary glands
**_Systemic features_**
InflammatoryArthritis
Rash (sub-acute lupus)
Neuropathies
Vasculitis
Neonatal lupus
158
What would the tests show to diagnose Sjögren’s Syndrome?
**_Schirmer’s test_**
Conjunctival dryness
**_Auto-antibodies_**
ANA (in most)
Rheumatoid factor
Ro
La
**_Raised immunoglobulins_**,
ESR up
**_Biopsy_**
Lymphocyte infiltration in glands
159
What is the Management of Primary Sjogren’s?
**_Tear and saliva replacement_**
Hypromellose
Immuno-suppression for systemic complications
Treat arthralgia
160
WHAT IS DERMATOMYOSITIS/POLYMYOSITIS?
Progressive symmetrical proximal muscle weakness
Autoimmune-mediated striated muscle inflammation (myositis)
Myalgia ± arthralgia.
161
What is affected most in Dermatomyositis/Polymyositis?
Muscle and skin mainly affected: rash and muscle weakness
Lungs can be affected (Interstitial lung disease)
162
What are the autoantibody associations with polymyosits/dermatomyositis?
Jo-1
PM-Scl
Mi-2
163
What are the symptoms for dermatomyositis?
Macular rash
Rash on eyelids
Dysphagia
Dysphonia
164
What investigations can you do for Dermatomyositis/Polymyositis?
Muscle enzymes
EMG
Muscle/skin biopsy
Screen for malignancy
Chest X ray, PFTs, High resolution CT lungs
165
What is the management for Dermatomyositis/Polymyositis?
Steroids
Immunosuppressive drugs
Hydroxychloroquine (skin rash)
166
WHAT IS LOWER BACK PAIN?
Pain of the lower back
167
When does mechanical lower back pain present?
Ages of 20-55.
168
Where is lower back pain?
Located in lumbrosacral region, buttocks and tighs.
169
What does mechanical lower back pain vary with?
Activity and time.
170
What are the red flags for possible serious spinal pathology?
Age on onset less than 20 or greater than 55.
Violent trauma e.g. fall from a heigh
Constant progressive, non-mechanical back pain
Thoracic pain
PMH carcinoma, systemic steroids, drug abuse, HIV
Systemically unwell, weight loss
Persisting servere resistriction of lumbar flexion
Structural deformity
171
What examination would you do for a patient with lower back pain?
With the patient standing, gauge the extent and smoothness of lumbar forward/ lateral flexion and extension.
Clinical tests for sacroiliitis: direct pressure, lateral compression, sacroiliac stretch test (pain on adduction of the hip, with the hip and knee flexed).
Signs of generalized disease—eg malignancy. Examine other systems (eg abdo- men) as pain may be referred.
172
What are the causes of lower back pain?
15–30yrs:
Prolapsed disc, trauma, fractures, ankylosing spondylitis, spondylolisthesis (a forward shift of one vertebra over another, which is congenital or due to trauma), pregnancy.
30–50yrs:
Degenerative spinal disease, prolapsed disc, malignancy (primary or secondary from lung, breast, prostate, thyroid or kidney ca).
\>50yrs:
Degenerative, osteoporotic vertebral collapse, Paget’s, malignancy, myeloma, spinal stenosis.
173
How can a person damage their lower back?
SIngle excessive force
Static loading
Repetative wear and tear
A bit of reality
174
What investigations can you do for back pain?
Arrange relevant tests if you suspect a specific cause, or if red flag symptoms:
**_FBC_**,
ESR and CRP (myeloma, infection, tumour), U&E, ALP (Paget’s), serum/urine electrophoresis (myeloma), PSA.
**_X-rays_**
Exclude bony abnormality but are generally not indicated.
**_MRI_**
Is the image of choice and can detect disc prolapse, cord compression (fig 1), cancer, infection or inflammation (eg sacroiliitis).
175
What is the management for back pain?
For non-specific back pain, focus on education and self-management.
Continue with normal activites and be active.
**_Manage pain_**
Regular paracetamol ± NSAIDS ± codeine
**_Physiotherapy,_** acupuncture or an exercise programme if not improving.
**_Psychosocial issues_**
**_Surgery_**
176
WHAT IS OSTEOMYELITIS?
https://www.youtube.com/watch?v=kta5vCz\_8Lw
Infection localized to bone.
177
What is the epidemology of osteomyelitis?
Children more
Males twice more than women
178
What are the different types of osteomyelitis? Which bacteria are involved?
**_Pyogenic_** (involving or relating to the production of pus)
S. aureus
**_Non-pyogenic_**
M. tb
179
How can the infection of bone take place?
**_Direct_**
**_Contiguous_**
**_Haematogenous_**
180
What are the different microbials for each type of spread?
**_Direct_**
Polymicrobial or monomicrobial
**_Contiguous_**
Polymicrobial or monomicrobial
**_Haematogenous_**
Monomicrobial
181
What are the host factors for osteomyelitis?
**_Behavioural factors_**
I.e. risk of trauma
**_Vascular supply_**
Arterial disease
Diabetes mellitus
Sickle cell disease
**_Pre-existing bone / joint problem_**
Inflammatory arthritis
Prosthetic material
**_Immune deficiency_**
Immunosuppressive drugs
Primary
182
In children where is the most common site for osteomyelitis infection?
**_Long bones_**
**_In metaphysis_**
Blood flow is slower
Endothelial basement membranes are absent
The capillaries lack or have inactive phagocytic lining cells
High blood flow in developing bones in Children
183
In adults where is the most common site for osteomyelitis infection?
**_Vertebrae_**
With age the vertebrae become more vascular, making bacterial seeding of the vertebral endplate more likely
184
What are the acute changes occur to the bone as a result of osteomyelitis?
**_Acute changes_**
–Inflammatory cells
–Oedema
–Vascular congestion
–Small vessel thrombosis
185
What are the chronic changes occur to the bone as a result of osteomyelitis?
**_Chronic changes_**
–Necrotic bone ‘sequestra’
–new bone formation ‘involucrum’
–neutrophil exudates
–lymphocytes & histiocytes
186
How are sequestra and involucrum produced?
Interruption of periosteal blood supply causing necrosis.
Leaves pieces of separated dead bone ‘sequestra’
New bone forms here ‘involucrum’.
187
What are the signs and symptoms of osteomyelitis?
**_Systemic_**:
Fever, rigors, sweats, malaise
**_Local_**:
**_Acute OM_**
Tenderness, warmth, erythema, and swelling
**_Chronic OM_**
Tenderness, warmth, erythema, and swelling
Draining sinus tract
Deep / large ulcers
Non-healing fractures
188
What tests can you do for osteomyelitis?
**_Physical examination_**
**_Laboratory tests_**
**_Imaging_**
189
What are the labratory tests you can do for osteomyelitis?
**_FBC/WCC_**
Rasied or normal
**_CRP/ESR_**
Raised
**_Blood culture_**
**_Bone aspiration_**
190
What are the imaging tests you can do for osteomyelitis?
**_X-Rays_**
Normal
Periosteal evelvation
Osteolysis
**_CT Scan_**
Cortical destruction
Lytic lesions
**_Bone Scan_**
Visulising bone remodelling
191
What are the differential diagnosis for osteomyelitis?
Soft tissue infection
Charcot joint
Avascular necrosis of bone
Gout
Fracture
Bursitis
Malignancy
192
What is the treatment for osteomyelitis?
Antibiotics
Surgical
Splintage
Supportive
193
WHAT IS SEPTIC ARTHRITIS?
https://www.youtube.com/watch?v=Tz07Uqx7\_VY
Inflammation of a joint that's caused by infection.
194
What is septic arthritis caused by? What does it affect?
Bacteria. It can also be caused by a virus or fungus.
Typically, septic arthritis affects one large joint in the body, such as the knee or hip.
195
What are the risk factors for septic arthritis?
Pre-existing joint disease
Vascular e.g. diabetes mellitus,
Immunosuppression
Chronic renal failure
Recent joint surgery
Prosthetic joints, IV drug abuse, age \>80yrs
196
What are the symptoms for septic arthritis?
Fever
Monoarthritis
Irritability
197
What tests can you do for septic arthritis?
FBC/ESR/CRP
Joint aspiration for synovial fluid microscopy and culture
Blood cultures
Plain radiographs and CRP may be normal
198
What are the differential diagnosis for septic arthritis?
Crystal arthropathies.
199
What are the treatment options for septic arthritis?
Antibiotics IV
Joint drainage
**_Flucloxacillin_**
**_Vancomycin_** IV if MRSA
**_Cefotaxime_** IV if gonococcal or Gram –ve or- ganisms suspected.
200
WHAT IS BONE CANCER?
Cancer of the bone
201
What can you find out from the history for bone cancer?
Presenting Complaint
Mass
Pain
Loss of Function
History of Presenting Complaint
Duration of symptoms, including full Pain / Mass history
How issue came to patient’s attention
Past Medical History and Medication History
Family History
Social History
202
What are the red flags signs for a MSK malignancy?
Rest pain
Night pain
Lump present – tender, enlarging, deep to fascia, above 5cm in diameter
Loss of function
Neurological symptoms
Unwell / Weight loss
203
What inital investigations can you do for MSK malignancies?
**_Blood tests_** – FBC, U+E, Ca2+, Alk Phos
**_Plain Xrays_**
**_Ultrasound_**
**_CT Scan_**
Better for assessing bone quality, as well as solid tumours
Staging CT of Chest / Abdo / Pelvis essential if suspect metastases
**_MRI Scan_**
Better for assessing reactive changes of soft tissue / bone marrow
Recent studies assessed full-body MRI to look for metastases
**_Bone Scan_**
Technetium; Tc99. Good for assessing for skeletal metastases
204
What are plain X-rays used for in bone cancer?
Look to see what the lesion is doing to the bone and vise-versa
Definition / Bone density / Zone of Transition / Periosteal reaction
Osteoblastoma vs Osteosarcoma
**_Special Signs:_**
Codman’s Triangle (Osteosarcoma, Ewing’s, GCT, Osteomyelitis, Metastasis)
Sunburst appearance (Osteosarcoma, Ewing’s)
Onion-skin appearance (Ewing’s)
205
What is the ultrasound used for in bone cancer?
Quick, cheap method of assessing soft tissue masses
Real time assessment, no radiation. However operator dependant.
Excellent to differentiate Normal vs Abnormal, Solid vs Cystic
206
What are CTs used for in bone cancer?
Used to perform 3D reconstruction of bony lesions which can help plan resection. Also used for Staging (CT Chest, Abdo and Pelvis)
207
What does an MRI show you in bone cancer?
T1 imaging: anatomy
T2 imaging: pathology
Displays:
Soft tissue involvement of bony mass
Periosteal and Endosteal reaction
Skip Lesions
Soft tissue masses – heterogenous masses are more suspicious of malignancy
208
What is shown on a bone scan for bone cancer?
**_3 Phase Scan_**
Arterial (1 minute)
Blood Delivery
```
Blood Pooling (5 minutes)
Capillary dilation
```
Delayed (2-4 hours)
Uptake within bone
**_Gamma Camera_**
**_Technetium (Tc99-MDP)_**
209
How should staging of a bone cancer be done?
Stage Locally
Xray
Ensure whole bone is imaged
Limb alignment views for lower limb
MRI
Useful to assess for “skip lesions”
Stage Distally
CT Chest / Abdo / Pelvis
Bone Scan
Whole-body MRI scan
210
What is the staging of malignant tumours?
* Enneking system
* G0 = Histologically Benign
* Well Differentiated i.e. resemble cell of origin
* Low mitotic count
* G1 = Low Grade Malignant
* Moderate differentiation; Few mitoses
* Local spread only. Low risk of metastasis
* G2 = High Grade Malignant
* Poorly differentiated; Frequent mitoses
High risk of metastasis
211
What is the staging of benign tumours?
* Enneking Classification
* Grade 1 – Latent
* Well defined margin. Grows slowly then stops
* May heal spontaneously and very low risk of recurrence
* Grade 2 – Active
* Progressive growth limited by natural barriers
* Well defined margin but may expand and thin cortical bone (e.g. ABC)
* Negligible recurrence after marginal resection
* Grade 3 – Aggressive
* Growth not limited by natural barriers (e.g. GCT)
* Metastasis present in 5% patients
* High recurrence following marginal resection (extended resection therefore needed)
212
How do you name the different types of tumour?
* Prefix will be tissue of origin, for example:
* Osteo… = Bone
* Chondro… = Cartilage
* Rhabdomyo… = Skeletal Muscle
* Lipo… = Fat
* Suffix tells you whether it is benign or malignant
* …oma = Benign tumour
* …sarcoma = Malignant connective tissue tumour
* …carcinoma = Malignant epithelial/endothelial tumour
…blastoma = (Malignant) Tumour of embryonic cells
213
Where do tumours normally present?
214
What are osteosarcomas?
•Spindle cell neoplasms that produce osteoid
215
What are the different primary osteosarcomas?
* Intramedullary osteosarcoma (high grade)
* Parosteal osteosarcoma (low grade)
* Periosteal sarcoma (high grade)
* Telangiectatic osteosarcoma
216
What are the different secondary osteosarcomas?
Paget’s, Post-Radiation, Fibrous Dysplasia
Associated with p53 mutation
Also associated with Chondrosarcoma and STS
217
What is a high-grade intramedullary osteosarcoma? Where is it most common?
* “Classic” osteosarcoma
* Most common type
* Location: knee, proximal humerus, proximal femur
* Age: children, young adults
* 90% are high grade and penetrate the cortex early forming a soft tissue mass (IIB lesion)
* 10-20% have pulmonary mets
* X-rays: bone formation with bone destruction
* MRI useful for staging
218
What is secondary osteosarcoma secondary to?
* Paget’s Disease
* Older population only. Pagets present in 0.7-0.9% population, hence this is rare
* Median age 64yrs for onset. High risk for pulmonary metastasis
* Irradiation (60-70% survival for extremity lesions, 27% axial lesions)
* Children treated with high dose radiotherapy at greatest risk
* Tend to be high-grade tumours. High risk of pulmonary metastasis
* Treat as per primary bone tumour guidelines
* Fibrous Dysplasia
* Associated with McCune-Albright syndrome and Polyostic Fibrous Dysplasia
* McCune-Albright = fibrous dysplasia + café-au-lai spots + endocrine abnormalities
219
What is the treatment for an osteosarcoma?
* Initial treatment with multi-agent chemotherapy pre-op 8-12 weeks
* Aims to kill tumour cells, reduce further spread, treat micro-metastases
* Repeat procedures to Stage the Tumour
* Limb Salvage surgery (where possible) + adjuvant chemotherapy
220
What are the treatment options for bone tumours?
* Histological tests help to show sensitivity of tumour to Chemotherapy agents and Radiotherapy
* Chemo/Radio-therapy can be given:
* Neo-adjuvant (i.e. before surgery)
* Adjuvant (at the time/post surgery)
* Radiotherapy: Ewing’s, Myeloma, Lymphoma, STS, Metastasis
* Surgery can either be Limb-Sparing or Limb-Sacrificing
* Local recurrence vastly increases risk of future Amputation
221
What are the different surgical margins that can be achieved during oncologic surgery?
* Intralesional: The plane of surgery goes through the tumour.
* Marginal: The plane of surgery goes through the reactive zone of the lesion (the reactive zone contains oedema, tumour cells, fibrous tissue, and inflammatory cells).
* Wide: The plane of dissection goes through normal tissue.
* Radical: The entire anatomic compartment of the lesion is removed.
222
WHAT IS A CRYSTAL IN CRYSTAL ARTHRITIS?
**_Homogenous solid_**
ions bonded closely in ordered, repeating, symmetric arrangement
**_Stable, hard, high density_**
223
Where are crystals and what do they do?
**_All animals_**
Strengthen endo & exo-skeleton
Remove excess ions (surface binding)
224
Why are crystals common in the gall bladder and kidney?
They are the two routes of excretion of uric aicd.
225
What is the pathway of excretion of uric acid?
Purines -\> HypoXanthine-\> Xathine -\> Uric acid -\> monosodium urate
226
WHAT IS GOUT?
https://www.youtube.com/watch?v=bznoU5bke4U
Monosodium urate crystals deposited in joints
227
What is the epidemology of crystal arthropothies?
Commonest arthritis in men \>40yrs
Uncommon men\<30yrs
Rises in post-menopausal women
Men more than women
Worldwide
228
What is the cause of gout?
Hyperuricemia
Too much uric acid in the blood
229
What is the pathogenesis of gout?
Too much uric acid
Formation of sharp crystals
In areas of slow blood flow
Joints and kidneys
Overtime results in destruction of tissue leading to arthritis
Inflammation from WBC releasing proinflammatory mediators
230
Where does uric acid come from?
When cells are broken down
Purines in DNA are broken down
Into uric acid and excretes into urine
231
How does hyperuricemia happen?
When uric acid exeedes its solubility.
232
What changes happen to uric acid at pH 7.4?
Loses a proton and binds sodium to form monosodium urate crystals.
233
What is the key enzyme in formation of uric acid from purines?
Xanthinine oxidase.
234
How can monosodium urate crystals be formed?
**_Increased consumption_**
**_Increased production_**
**_Decreased clearance_**
Obesity and diabetes
Chemo and radiotherapy
Genetic predisposition
Chronic kidney disease
235
In what food are purines rich?
Shellfish
Anchiovies
Red meat
Organ meat
236
What causes an increased production of purines?
High-fructose corn syrup drinks
237
Where are the most common areas for gout to form?
Occur at the first metatarsophalangeal joint of the big toe
This is called Podagra
Other common joints are the ankle, foot, small joints of the hand, wrist, elbow or knee.
238
What are the symptoms of gout?
Podagra
Pain
Hot
Red
239
What is the differential diagnosis of gout?
Exclude septic arthritis in any acute monoarthropathy.
Then consider haemarthrosis, CPPD and palindromic RA
240
What are the investigations of gout?
**_Polarized light microscopy of synovial fluid_**
Shows negatively birefringent urate crystals
**_Serum urate_**
Raised
**_Radiographs_**
Soft-tissue swelling
‘Punched out’ erosions
There is no sclerotic reaction, and joint spaces are preserved until late
241
How do you treat the acute gout attack?
**_Decrease pain and swelling_**
NSAIDs
Corticosteroids
Colchicine - reduces WBC migration
**_Underlying cause_**
Change in diet
**_Medications_**
Xanthinine oxidase inhibitors
Allopurinol
Uricosuric medication
Probenicid
242
What are the permenant depositis of urate crystals called?
Tophi
243
What are the triggers of the acute attack of pseudogout and gout?
Direct trauma to the joint
Intercurrent illness
Surgery – especially parathyroidectomy
Blood transfusion, IV fluid
T4 replacement
Joint lavage
Most are spontaneous
244
WHAT IS PSEUDOGOUT?
Calcium pyrophosphate deposition in joints
245
Where is pseudogout most common?
Typical distribution – (MCPs), wrists, knees, (ankles)
246
What is the differential diagnosis of pseudogout?
Rheumatoid arthritis.
247
What is the epidemology of pseudogout?
After 30
Peak at 60
248
What are the clincial features of pseudogout?
**_Commonly incidental finding on radiology_**
Severe pain, stiffness, swelling
Marked synovitis, difficult to distinguish from gout
Fever
249
How do you distinguish OA from pyrophosphate arthropathy?
**_Pattern of involvement_**
Wrists, shoulders, ankles, elbows
**_Marked inflammatory component_**
**_Superimposition of acute attacks_**
250
What are the tests for pseudogout?
**_Polarized light microscopy_**
Positively birefringent crystal
It is associated with soft tissue calcium deposition on x-ray.
251
What is the acute management of pseudogout?
**_Acute_**
NSAIDs, analgesia, colchicine
**_Injection_**
**_Physiotherapy_**
**_Immunosuppresants_**
Methotrexate and hydroxychloroquine for chronic pseudogout
252
WHAT IS OSTEOPOROSIS?
Low bone mass and deterioration of bone tissue
Consequent increase in bone fragility and susceptibility to fracture.
253
What are the different types of osteoporosis?
Primary (age)
Secondary (related to a condition)
254
What is the epidemiology of osteoporosis?
1/2 women and 1/5 men over 50
255
What are some causes and risk factors of osteoporosis?
Inflammatory disease
Endocrine disease.
Reduced skeletal loading
Medication.
Alcohol and smoking.
256
What is the pathophysiology of fractures?
257
What is bone density equal to?
Amount of bone you made and how much bone you lost.
258
When does bone density increase and decrease?
Increase in childhood, in puberty increases more then finishes increasing at around 25 then starts to decrease around 30, and woman faster after menopause.
259
What is the normal bone remodelling cycle?
Chemical chnages, osteoclasts break the bone down which sends signals to osteoblasts to build new bone.
260
What happens in 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
Trabecullar bone more because it has more cells on the surface
261
What are the bones mechoceptors?
Osteocytes
262
What is Eular buckling theory?
A structure without horizontal conections will be 16 times weaker than that of one with.
263
What is the importance of high turnover to low turnover in bone remodelling?
The high turnover will be weaker that the low turnover.
264
How do we diagnose osteoporosis?
**_Bone densitometry_**
Dual energy X-ray absorptiometry. (DEXA)
**_Bloods_**
Calcium and Phosphate
265
How does a DEXA work?
Uses to different beams to assess how much calcium is in the bone.
Low radiation dose
Measures important fracture sites
266
What is a T-score?
Standard deviation score, it compares your score with gender-matched young adult average (peak bone mass)
267
What do you use the T-score for?
Diagnose osteoporsis.
\< -1.0
Normal
-1.0 to -2.5
Osteopenia
\> -2.5
Osteoporosis
\> -2.5 plus fracture
Severe osteoporosis
268
What do inflammatory diseases do to bone? What are some common associated conditions?
Inflammatory cytokines increase bone resorption
Rheumatoid arthritis, seronegative arthritis, connective tissue diseases
Inflammatory bowel disease
269
What do endocrine disease do to bone? What are some examples of some diseases?
**_Thyroid and parathyroid hormone increase bone turnover_**
Hyperthyroidism
Primary hyperparathyroidism
**_Cortisol increases bone resorption and induces osteoblast apoptosis_**
Cushing’s syndrome
**_Oestrogen/testosterone control bone turnover_**
Menopause
Male hypogonadism
Anorexia/athletes
270
What happens during reduced skeletal loading? How does this happen?
**_Reduced skeletal loading increases resorption_**
Low body weight
Immobility
271
What medications cause an increase risk of osteoporosis?
**_Glucocorticoids (corticosteroids)_**
GnRH analogues
Androgen deprivation
272
What is FRAX?
A genorator to see how much at risk of a fracture you are?
273
What are the treatment options for osteoporosis?
**_Anti-resorptive_**
**_Decrease osteoclast activity and bone turnover_**
Bisphosphonates
HRT
Denosumab - antibody to RANK
**_Anabolic_**
**_Increase osteoblast activity and bone formation_**
Teriparatide
274
What are benefits and risks of hormone replacement therapy?
**_Benefits_**
Reduce the risk of fractures
Stop bone loss
Prevents hot flushes
Reduces risk of colon cancer
**_Risks_**
Breast cancer
Stroke
Cardiovascular disease
275
When are bisphosphonates used and why? What are some oral and intravenous drugs?
**_First line treatment_**
ORAL
Alendronate (daily or weekly)
Risedronate (daily or weekly)
Ibandronate (monthly)
Etidronate (two weeks of 13)
IV
Ibandronate (3-monthly)
Zoledronate (once yearly)
276
What do bisphosphonates do?
Bisphosphonates inhibit an enzyme in the cholesterol synthesis pathway – Farnesyl Pyrophosphate Synthase
277
What are bisphosphonantes action?
278
What is Denosumab?
Monoclonal antibody to RANK ligand
Switches off bone resorption.
Rebound increase of bone turnover when stopped
279
What is Teriparatide?
**_PTH analogue_**
First anabolic treatment
Increases bone density,
280
WHAT IS OSTEOMALACIA?
Osteomalacia there is a normal amount of bone but its mineral content is low (there is excess uncalcified osteoid and cartilage).
281
What is the cause of osteomalacia?
**_Vitamin D deficiency_**
**_Renal failure_**
1,25-dihydroxy-cholecalciferol deficiency
**_Drug-induced_**
Increased breakdown of 25-hydroxy-vitamin D.
**_Vitamin D resistance_**:
Osteomalacia responds to high doses of vitamin D
**_Liver disease_**
Due to reduced hydroxylation of vitamin D to 25-hydroxy-cholecalciferol and malabsorption of vitamin D, eg in cirrhosis
Tumour
282
What are the signs and symptoms of osteomalacia?
Bone pain and tenderness
Fractures
Proximal myopathy (waddling gait)
283
What are the investigations for osteomalacia?
**_Plasma_**
Mildly decerease Ca2+
Decrease PO43–; alk phos increase; PTH high; 25(OH)-vitamin D low, except in vitamin D resistance.
In renal failure 1,25(OH)2-vitamin D low
**_Biopsy_**
Bone biopsy shows incomplete mineralization.
Muscle biopsy (if proximal myopathy) is normal.
**_X-ray_**
Loss of cortical bone
284
What are the treatments for osteomalacia?
Vitamin D
285
WHAT IS PAGETS DISEASE OF BONE?
Also called osteitis deformans
Increased bone turnover associated with increased numbers of osteoblasts and osteoclasts
With resultant remodelling, bone enlargement, deformity, and weakness
286
What is the epidemiology of Paget's diease of bone?
Rare in the under-40s.
Incidence rises with age (3% over 55yrs old).
287
What are the signs symptoms of paget's disease of bone?
Asymptomatic
Deep, boring pain, and bony deformity and enlargement
Classically a bowed sabre tibia
288
What are the investigations for paget's disease of bone?
**_X-ray_**
Localized enlargement of bone.
Patchy cortical thickening with sclerosis, osteolysis, and deformity
**_Blood chemistry_**
Ca2+ and PO43 normal
Alk phos markedly raised.
289
What is the treatment for paget's disease of bone?
Analgesia
Alendronate
290
WHAT IS FIBROMYALGIA?
https://www.youtube.com/watch?v=Jyl98z07ZHM
Fibromyalgia is a chronic condition affecting fibrous tissue and muscle causing pain
291
What is the epidemology of fibromyalgia?
Female more than men
292
What is the normal pathway of pain?
Pain in finger
Nocicepter converts stimulates into electrical signal
Signal transmitted to cell body in dorsal root ganglion
If strong enough, substance P released
Substance P released onto secondary neuron in dorsal horn
Inhibitory neuron release serotonin and norepinephrine to dampen pain signal
293
What happens at the site of damage for fibromyalgia?
Cells release nerve growth factor
Mast cells release more nerve growth factor
High levels of nerve growth factor
Growth, sensitivity and more nerve growth factor.
294
What is the cause of fibromyalgia?
Unknown
Thought to be caused by the way the brain receieves pain signals
295
What is the pathology of fibromyalgia?
Lower levels of serotonin, this normally decreases pain
Higher levels of substance P
Higher levels of nerve growth factors
BOTH involved with increasing pain
296
What are the risk factors for fibromyalgia?
Genetics
**_Environmental_**
Child abuse
Depression
Anxiety
Negative beliefs
297
What are the symptoms of fibromyalgia?
Widespread pain over the body
298
What are the investigations for fibromyalgia?
Pain location in more than 7 areas with a symptom severity score of 5/12
OR
Pain location in more than 5 areas with a symptom severity score of 9/12
SYMPTOMS must be present for more than 3 months
NOT due to another disease
299
What are the treatment options for fibromyalgia?
Exercise
Relaxation techniques
Sleep hygiene
**_Medications_**
Amitriptyline
Serotonin and nor-adrenaline reuptake inhibitors
Anticonvulsants - Pregabalin - slow nerve impulses
300
WHAT ARE SOME VERTEBRAL DISC PROBLEMS?
Disorders effecting intervertebral discs: herniation, degeneration, infection.
301
What is disc herniation?
Herniation = prolapsed vertebral disc.
302
What is disc degeneration?
Major cause of lower back pain.
Exact cause is known
Could be natural part of ageing
Can occur in young people: genetic, environmental, traumatic, inflammatory, infectious, etc.
May lead to disc herniation.
303
What is the pathophysiology of disc prolapse?
Nucleus pulposus herniates, it can irritate or compress the adjacent nerve root - symptoms of sciatica
304
What is the epidemology of disc prolapse?
More common in under 40s, whereas degeneration is more common in over 40s.
305
What is the presentation of a disc prolapse?
Symptoms of sciatica
Compress cauda equine
Nerve root compression
Symptoms can correspond to the level.
306
What are the investigations for disc prolapse?
Symptoms may settle within 6 weeks
MRI very sensitive
CT
Plain x-rays sometimes useful
307
What is the management for a disc prolapse?
Analgesia
Encourage to keep active
Heat and massage to relieve muscle spasm
Avoid activities that aggravate pain
Physiotherapy
Surgery.
308
What is discitis?
Pyogenic infection of the spine
Rare
Incidence due to life expectancy
309
What is the pathopgysiology of discitis?
Inflammation of vertebral disc space
Can co-exist with osteomyelitis
Most commonly effects lumbar spine
Usually haematogenous spread of infection from other parts of the body
Common sources; urinary tract, lungs, soft tissues
310
What is the epidemology of discitis?
Staphylcoccus aureus is most common pathogen
Most commonly affects males in 50s
311
What are some risk factors to discitis?
Immunosuppressed
IV drug use.
312
What is the presentation of discitis?
Insidious onset
Neck or back pain and localized tenderness
Pain worse on movement
Restricted mobility
Associated fever and weight loss
Neurological deficit.
313
What are the investigations for discitis?
ESR and CRP
WCC may be normal
Blood cultures, sputum, urine
X-ray may show disc space narrowing, calcification
CT and MRI show changes earlier than X-ray
CT guided biopsy.
314
What is the management for discitis?
Antibiotics (adjusted after culture results)
Immobilization (2 weeks bed rest, then immobilization with brace)
Analgesia prescribed as requird
Surgery if neurological deficit, deformity or lack of response tp antibiotics.
