MSK Flashcards
(279 cards)
1
Q
What are spondyloarthropathies?
A
Group of overlapping conditions that all share certain clinical features
2
Q
What are the similar features of spondyloarthropathies?
A
Axial inflammation - spine and sacroiliac joints
Asymmetrical peripheral arthritis
Absence of rheumatoid factor - seronegative
Strong associated with HLA-B27
3
Q
What is HLA-B27?
A
Human leukocyte antigen
Class I surface antigen - present on all cells except RBCs
Encoded by MHC on chromosome 6
APCs
Plays role in immunity and self-recognition
Essentially a tissue type
Prevalence of it affects prevalence of ankylosing spondylitis
Molecular mimicry whereby an infection triggers an immune response and infectious agent has peptides very similar to HLA-B27 molecules so auto-immune response triggered
4
Q
How do spondyloarthropathies present?
A
Sausage digit (dactylitis) Psoriasis Inflammatory back pain NSAID good response Enthesitis (particularly in heel) Arthritis Crohn's/colitis/elevated CRP HLA-B27 Eye (uveitis)
5
Q
What is ankylosing spondylitis?
A
Chronic inflammatory disorder of spine, ribs and sacroiliac joints
6
Q
What is ankylosis?
A
Abnormal stiffening and immobility of joint due to new bone formation
7
Q
How common is ankylosing spondylitis?
A
More common and more severe in men
Usually presents at 16 -young adult < 30
88% HLA-B27 positive
Women present later and under-diagnosed
Low incidence in African and Japanese people
Native North American have high incidence
8
Q
What can increase your risk of having ankylosing spondylitis?
A
HLA-B27 Environment - Klebsiella - Salmonella - Shigella
9
Q
What is the pathology of ankylosing spondylitis?
A
Lymphocyte and plasma infiltration occurs with local erosion of bone at attachments of intervertebral and other ligamants (enthesitis - inflammation where tendons and ligaments insert into bone), which heals with new bone formation
Syndesmophyte - new bone formation and vertical growth from anterior vertebral corners
10
Q
How does ankylosing spondylitis present?
A
Gradual onset of lower back pain, worse at night, spinal morning stiffness, relieved by exercise
Episodic inflammation of sacroiliac joints in late teen years or early 20s
Pain radiates from sacroiliac joints to hips/buttocks, usually improves towards end of day
Asymmetrical joint pain - oligoarthritis
Loss of lumbar lordosis
Increased kyphosis
Limitation of lumber spine mobility in both sagittal and frontal planes
Enthesistis
11
Q
What are the non-articular features of ankylosing spondylitis?
A
Anterior uveitis Osteoporosis Aortic incompetence Cardiac conduction defects Apical lung fibrosis Amyloidosis IgA nephropathy
12
Q
How is ankylosing spondylitis diagnosed?
A
Bloods - ESR/CRP raised, normocytic anaemia, HLA-B27 positive
X-ray - erosion and sclerosis of margins of sacroiliac joints which can proceed to ankylosis, blurring of upper and lower vertebral rims at throacolumbar junction caused by enthesitits, heals with new bone formation, fusion of sarcoiliac joints
MRI - shows sacrolitis before seen on x-rays
13
Q
How is ankylosing spondylitis treated?
A
Treat quickly to prevent irreversible syndesmophyte formation and progressive calcification
Morning exercise to maintain posture and spinal mobility
NSAIDs
Methotrexate - helps with peripheral arthritis
TNF-alpha blocker - earlier you start the less syndesmophytes form
Local steroid injections for temporary relief
Surgery - hip replacement to improve pain and mobility
14
Q
How common is psoriatic arthritis?
A
Can occur without psoriasis
10-40% with psoriasis
Can present before skin changes
15
Q
What can increase your risk of getting psoriatic arthritis?
A
FHx of psoriasis
16
Q
How does psoriatic arthritis present?
A
Asymmetrical oligoarthritis
Symmetrical seronegative polyarthritis
Spondylitis - unilater/bilateral sacrolitis and early cervical spine involvement
DIPJs involvement only
Adjacent nail dystrophy
Dactylitis
Arthritis mutilans - periarticular osteolysis and bone shortening
Hidden sites - behind/inside ear, scalp, pitting in nails/onokylisis, umbilicus, natal cleft, penile psoriasis
17
Q
How is psoriatic arthritis diagnosed?
A
Bloods and ESR normal
X-ray
- Erosions central to joint
- Pencil cup deformity in intraphalangeal joints - bone erosions create pointed appearance and articulating bone concave
- Skin and nail disease can be mild and may develop after arthritis
18
Q
How is psoriatic arthritis treated?
A
Similar to RA
NSAIDs and/or anagesics for pain - can worsen skin lesions
Local synovitis responds to intra-articular corticosteroid injections
Early intervention with DMARDs can help skin lesions eg methotrexate, sulfasalzine and leflunomide
Methotrexate and ciclosporin used for severe disease
Anti-TNF alpha agents such as stanercept and golimumab highly effective and safe for severe skin and joint disease - used when methrotrexate fails
19
Q
What is reactive arthritis?
A
Sterile inflammation of synovial membrane (synovitis), tendons and fascia triggered by an infection at a distant site, usually gastro-intestinal or genital
Typically affects lower limb
20
Q
How common is reactive arthritis?
A
In men who HLA-B27 positive 30-50 fold increased risk
Women less commonly affected
21
Q
What can cause reactive arthritis?
A
GI infections - Salmonella - Shigella - Yersinia enterocolitica Sexually acquired - Urethritis from chlamydia trachomatis - Ureaplasma urealyticum
22
Q
How does reactive arthritis occur?
A
Bacterial antigens or bacterial DNA found in inflammed synovium of affected joints - persistent antigenic material driving inflammatory response
23
Q
How does reactive arthritis present?
A
Acute, asymmetrical lower limb arthritis Occurring a few days to couple weeks after infection Acute anterior uveitits Circinate balantis Enthesitis HLA-B27 pos - sacrolitis, spondylitis Sterile conjuncitivitis Skin lesions resembling psoriasis Keratoderma blennorrhagica Nail dystrophy
24
Q
How is reactive arthritis diagnosed?
A
ESR and CRP raised Culture stool if diarrhoea Sexual health review Aspirated synovial fluid sterile with high neutrophil count X-ray shows enthesitis
25
How is reactive athritis treated?
Joint inflammation - NSAIDs and corticosteroid injections
Treat persisting infection with antibiotics
Screen sexual partners
Majority of individuals with reactive arthritis single attack that settles, few develop disabiling relapse and remitting arthritis
Relapse cases use methotrexate or sulfasalzine
Severe and persistent disease - TNF-alpha blockers such as etanercept and golimumab
26
What is osteoporosis?
Systemic skeletal disease characterised by low bone mass and a micro architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
Bone mineral density more than 2.5 standard deviations below the young adult mean value
T score < 2.5
27
What is osteopenia?
Pre-cursor to osteoporosis characterised by low bone density
Defined as BMD between 1-2.5 SDs below young adult mean value -1 < T score < 2.5
28
What is osteomalacia?
Poor bone mineralisation leading to soft bone due to lack of calcium (adult form of Rickets)
29
How common is osteoporosis?
More common in women in the over 50s due to natural loss of trabeculae with age
In men, reduced bone formation but numbers of trabeculae more stable so lifetime fracture risk lower
Caucasians and Asians most at risk
Risk increases as we age
1/2 women will get a fracture due to osteoporossi
1/5 men
30
What increases your risk of getting osteoporosis?
Old age
Female
FHx of osteoporosis or fractures
Previous bone fractures
SHATTERED
Steroid use - prednisolone, heparin, ciclosporin, PPIs, anticonvulsants, GnHR analogues, SSRIs, androgen deprivation
Hyperthyroidism and hyperparathyroidism (increases bone turnover)
Alcohol and tobacco
Thin - BMI < 22 (reduced skeletal loading, increased bone resorption)
Testosterone decreases - increased bone turnover
Renal/liver failure
Erosive/inflammatory bone disease - cytokines increase bone turnover
Dietary calcium decrease/malabsorption, T1DM
31
What occurs in osteoporosis?
Peak bone mass around 25
Results from increase bone breakdown by osteoclasts and decreased bone formation by osteoblasts, leading to loss of bone mass
Bone mass decreases with age, depends on peak mass attained in adult life and rate of loss
Genetic factors - multiple genes involved
Nutritional factors, sex hormone status and physical activity
Bone strength determined by bone mineral density, bone size and bone quality
32
What occurs in postmenopausal osteoporosis?
Oestrogen deficiency
Increased numbers of osteoclasts, permature arrest of osteoblastic synthetic activity and perforation of trabeculae with loss of resistance to fracture
High bone turnover
Predominantly cancellous bone loss
33
What changes in trabeculae occur with ageing?
Decrease in trabecular thickness - strain felt on bones head to tail, preferentially preserve vertical trabeculae and lose horizontal
Decrease in trabeculae thickness in connections between horizontal trabeculae resulting in decreased trabecular strength and increased susceptibility to fracture
34
How does osteoporosis present?
Fracture only cause of symptoms
Vertebral crush fracture
- Sudden onset severe pain of spin, radiating to front
- Thoracic vertebral fractures may lead to kyphosis
Colles' fracture of wrist typically following falls
Fractures of proximal femur usually occur in older individuals falling on side or back
35
How is osteoporosis diagnosed?
T score - standard deviation score attained using DEXA scan, compared with gender-matched young adult average (peak bone mass)
X-ray for fractures
DEXA scan - low dose radiation, measures important fracture sites
Bloods - Ca, phosphate and alkaline phosphate all normal
36
How is osteoporosis treated?
```
Lifestyle measures - quit smoking and reduce alcohol consumption, weight bearing exercise may increase bone density, calcium and vitamin D deficient diet, balance exercises to reduce falls
Anti-resportive - slow down osteoclasts and reduce bone turnover
- Bisphosphonates
- Strontium ranelate
- Denosumab
- HRT
- Raloxifene
- Testosterone
```
37
What is osteoarthritis?
Cartilage loss with accompanying periarticular bone response
Inflammation of articular and periarticular structure and alteration of cartilage structure
Non-inflammatory degenerative arthritis
Age-related, dynamic reaction pattern of a joint in response to insult or injury
All tissues of joint involved
Articular cartilage most affected
38
How common is osteoarthritis?
Most common condition affecting synovial joints
Majority primary with no obvious factor causing it
Secondary OA occurs in joint disease or other conditions
Prevalence increases with age - uncommon before age 50
Beyond 55 more common in women
39
What can increase your risk of osteoarthritis?
```
Joint hypermobility
Insufficient joint repair
Diabetes
Increasing age - cummulative effect of traumatic insult, decline in neuromuscular function
Gender - more common in women
Genetic predisposition
Obesity - pro-inflammatory state
Occupation - manual labour (small joints of hand), farming (hips), football (knees)
Local trauma
Inflammatory arthritis
```
40
What occurs in osteoartritis?
Matrix of collagen fibres enclosing mixture of proteoglycans and water, smooth surface and shock absorbing
Normal balance between cartilage degradation and wear and production by chondrocytes lost - despite increased synthesis of extracellular matrix, cartilage becomes oedematous
Focal erosion of cartilage develops and chondrocytes die, repair attempted from adjacent cartilage but process disordered leading to failure of synthesis of extracellular matrix so surface becomes fibrillated and fissured
Exposes underlying bone to increased stress producing micro-fractures and cysts
Bone attempts repair producing abnormal sclerotic subchondral bone and overgrowths at joint margins which become calcified
Secondary inflammation
Exposed bone becomes sclerotic - increased vascularity and cyst formation
Metalloproteinases - secreted by chondrocytes degrade collagen and proteoglycan
Interleukin 1 and TNF-alpha - stimulate metalloproteinase production and inhibit collagen production
ILGF-1 and transforming growth factor impairs matrix repair
Gene susceptibility
41
What are the main pathological features of osteoarthritis?
Loss of cartilage
| Disordered bone repair
42
How does osteoarthritis present?
Affects many joints, mechanical pain with movement and/or loss of function
Gradual onset and progressive
Joint pain - made worse after movement and relieved by rest
Joint stiffness after rest
Only transient stiffness - less than 30 mins morning stiffness
DIPJs (Heberden's nodes)
1st carpometacarpal joints
1st metatarsalphalangeal joints
Weight bearing joints
Limited joint movement
Muscle wasting of surrounding muscle groups
Crepitus - crunching sensation when moving joint
Joint effusions
Bouchard's node (PIPJ)
43
What could be a differential diagnosis for osteoarthritis?
RA - differentiated by pattern of joint involvement and absence of systemic features and marked early morning stiffness
Chronic tophaceous gout and psoriatic arthritis affecting DIPJs
44
How is osteoarthritis diagnosed?
Deformity and bony enlargement on exam
CRP elevated
Rheumatoid factor and anti-nuclear antibodies negative
X-rays LOSS
- Loss of joint space
- Osteophytes
- Subarticular sclerosis
- Abnormalities of bone contour
MRI - early cartilage injury and subchondral bone marrow changes
Aspiration of synovial fluid if painful effusion - viscous fluid with few leucocytes
45
How is osteoarthritis treated?
Non-medical
- Exercise - muscle strength, mobility of weight bearing joints, fitness
- Weight loss if obese
- Local heat/ice packs
- Bracing devices, joint supports, insoles for stability, footwear with shock absorbing properties
- Acupuncture, physio, occupational therapy
Paracetamol before NSAIDs
Weak opioids with paracetamol
Intra-articular corticosteroid injections produce short-term improvement when painful joint effusion
Surgery
- Arthroscopy
- Arthroplasty - joint replacements for uncontrolled pain, or significant limitation of function
- Osteotomy - cut bone to change shape/length
- Fusion - usually of ankle and foot to prevent painful grinding of bones
46
What is rheumatoid arthritis?
Chronic systemic autoimmune disease causing symmetrical polyarthritis
Disease of synovial joints
Inflammatory autoimmune arthritis
47
How common is rheumatoid arthritis?
Affects 1% of population worldwide with peak prevalence between 30-50 years
Increased prevalence in smokers
Not seen as much in elderly in contrast to OA
More common in women
48
What can cause RA?
```
Suggested role of female sex hormones
Immune system
- Triggering antigen unknown
- T cells - interferon, IL-2, IL-4
- Macrophages - IL-1, IL-8, TNF-alpha
- Mast cells - histamine and TNF-alpha
Fibroblasts - IL-6
- Local production of rheumatoid factor by B cells and formation of immune complexes with complement activation also maintains chronic inflammation
```
49
What are the factors that can increase your risk of RA?
Female - before menopause women affected 3x more than men, equal incidence post-menopause
Genetics - HLA-DR4 and HLA-DRB1 confer susceptibility and associated with development of more severe erosive disease
Smoking
Immune system
50
What is the pathology of RA?
Predominantly synovial disease and synovitis occurs when chemoattractants produced in joint recruit circulating inflammatory cells
Over-production of TNF-alpha leads to synovitis and joint destruction - interaction of macrophages, T and B lymphocytes drives overproduction
Synovium becomes greatly thickened and becomes infiltrated with inflammatory cells
Generation of new synovial blood vessels induced by angiogenic cytokines and activated endothelial cells produce adhesion molecules forcing leukocytes into synovium where trigger inflammation
Synovium proliferates and grows out over surface of cartilage, producing tumour-like mass called pannus
Pannus of inflammed synovium damages underlying cartilage by blocking normal route for nutrition and by direct effects of cytokines on chondrocytes
Cartilage thins and underlying bone exposed
Pannus destroys articular cartilage and subchondral bone resulting in bony erosions
51
How does RA present?
```
Slowly progressive, symmetrical swollen, painful stiff
MCP, PIP
DIPs normally spared
Metatarsophalangeal of feet
Wrists, elbows, shoulders, knees, ankles
Warm and tender
Symptoms worse in mornings
Morning stiffness lasting more than 30 mins
Symmetrical peripheral polyarthritis
Movement limitation, muscle wasting
Hand deformities - ulnar deviation, swan neck thumb, boutonniere deformity
Fatigue, sleep disturbed
Synovitis and effusions in knees
Tenosynovitis - inflammation of tendons
```
52
What are the extra-articular manifestations of RA?
Lungs - pleural effusions, fibrosing alveolitis, pneuoconiosis, interstitial lung disease, bronchiectasis
Heart - pericarditis, pericardial rub, Raynauds, pericardial effusion
Eyes - dry eyes, episcleritis, scleritis
Neurological - peripheral sensory neuropathies, compression/entrapment neuropathies, cord compression
Kidneys - amyloidosis, nephrotic syndrome, CKD
Skin - subcutaneous nodules
53
How is RA diagnosed?
Bloods - normochromic, normocytic anaemia, ESR/CRP raised in proportion to activity of inflammatory process, positive rheumatoid factor, positive anti-cyclic citrullinated peptide (presents early)
X-ray
- Soft tissue swelling in early disease
- Joint space narrowing in late disease
- Peri-articular erosions
MRI and USS - erosions at joint margins and bones
If effusions present then aspiration of joint
54
How is RA treated?
No cure
Smoking cessation - reduces risk of CVS disease
Reduce weight
Exercise
Surgery - synovectomy to reduce bulk of inflammed tissue and prevent damage
Pain management - NSAIDs relieving joint pain and stiffness, paracetamol w/w/o opioid
Corticosteroids - suppress disease activity but risk of long-term toxicity
DMARDs - methotrexate, sulfalazine, leflunomide
Biological therapy
- TNF-alpha blockers
- B cell inhibitors
- Interleukin blockers
- T cell activation blockers
55
What is gout?
An inflammatory arthritis that is associated with hyperuricaemia and intra-articular monosodium urate crystals
56
How common is gout?
Prevalence increasing especially in developing countries
More common in men
Rarely occurs before young adulthood
Most common inflammatory arthritis in UK
57
What can cause gout?
High alcohol intake (highest risk for beer then wine)
Purine rich foods (red meats)
High fructose intakes - reduces uric acid excretion
High saturated fat diet
Drugs - low dose aspirin
IHD
Renal causes - defective gene for URAT1 transporter in kidney
- High insulin levels reduces urate excretion
- Diuretics impair uric acid excretion
Increased production of uric acid
- Increased purine turnover
- Myeloproliferative
- Lymphoproliferative disorders
- Carcinoma and psoriasis - increased cell turnover
- Cell damage - surgery
- Cell death - chemotherapy
FHx
58
What is the pathology of gout?
Purines need to be excreted
Last 2 steps of purine metabolism = hypoxanthine converted to xanthine and xanthine converted to uric acid under enzyme xanthine oxidase
Uric acid excreted via kidneys - if some hyperuricaemia converted to monosodium urate crystals - causes symptomatic gout and pain
Serum uric acid levels higher in men than women
Hyperuricaemia defined as serum acid level greater than 420 micromol/L (M) or 360 micromol/L (F)
Need to have hyperuricaemia to develop gout but doesn't guarantee gout - just increases risk
Serum uric acid levels increase with age, obesity, DM, IHD, hypertension
Monosodium urate crystals tend to form in joints that have had previous trauma and form at lower temps so form in more peripheral joints
Monosodium urate crystals can trigger intracellular inflammation resulting in more pain
59
How does hyperuricaemia present?
Can be asymptomatic or may cause acute/chronic gout or tophaceous gout
60
What is acute gout?
Occurs when monosodium urate crystals form
Typically in middle aged men
Sudden onset agonising pain, swelling and redness of 1st MTP joint
Usually just on joint affected but can be polyarthritis
Attack may be precipitated by excess food, alcohol, dehydration or diuretic therapy, cold, trauma, sepsis
61
What is chronic gout?
Rare
| Except in elderly on long term diuretics in renal failure or have been started on allopourinol too soon
62
What is tophaceous gout?
In people with perisitent hyperuricaemia - monosodium urate crystals form smooth, white deposits (tophi) in skin and around joints, on ear, fingers/achilles tendon
Tophi onion like aggregates of monosodium urate crystals with inflammatory cells
Tophi release local proteolytic enzyme hence erosions to bone - form circular punch like holes
Associated with renal impairment and/or long-term used of diuretics
63
What can gout increase the risk of ?
Urate renal stone formation
Gout also increases risk of hypertension, renal disease, CVS disease, T2DM and osteoarthritic damage to joints
Recurrent gout attacks can lead to renal impairement
64
What could be a differential diagnosis of gout?
Septic arthritis in any acute monoarthropathy
65
How is gout diagnosed?
Joint aspiration and microscopy
- Diagnostic
- Shows long needle shaped crystals that are negatively bifringent under polarised light
Raised serum uric acid
Serum urea and creatinine and eGFR - monitoring for signs of renal impairment
66
How is gout treated?
```
Aim to decrease uric acid level to below normal so crystals reverse
Lose weight
Less alcohol
Avoid purine rich foods
Dairy
Acute
- High dose NSAIDs
- If NSAID not tolerated - colchicine (v toxic in overdose)
IM, oral, intra-articular corticosteroid
```
67
What are the side effects of colchicine?
Diarrhoea
| Abdominal pain
68
How is gout prevented?
Stop diuretics and switch to angiotensin receptor blocker
Allopurinol
Febuxostat - non-purine xanthine oxidase inhibitor, use if allopurinol CI or due to side effects
69
What is pseudogout?
Deposition of calcium pyrophosphate crystals on joint surface
70
Who is most affected by pseudogout?
Elderly women
71
What can increase your risk of pseudogout?
```
Old age
Diabetes
Osteoarthritis
Joint trauma/injury
Metabolic disease - hyperparathyroidism, haemochromatosis
```
72
What occurs in pseudogout?
Deposition of calcium pyrophosphate in articular cartilage and periarticular tissue producing radiological appearance of chonedrocalcinosis
73
How does pseudogout present?
Shedding of crystals into joint produces acute synovitis that resembles acute gout but is more common in elderly women and usually affects knee/wrist
Painful attacks
Acute hot swollen wrist/knee
Can be mistake for septic arithtis
74
How is pseudogout diagnosed?
Joint aspiration and microscopy
- Small rhomboid crystals under microscopy
- Positively bifringent crystals under polarised light
- Joint fluid looks purulent so sent for culture to exclude septic arthritis
X-ray
- Shows chonedrocalcinosis - linear calcifcation parallel to articular surfaces
Bloods
- Raised WCC
75
How is pseudogout treated?
High dose NSAIDs eg naproxen/ibuprofen
Colchicine if NSAID not tolerated
IM/oral/intra-articular corticosteroid
Aspiration of joint reduces pain dramatically
76
What is septic arthritis?
Medical emergency
Acutely inflammed joint which can destroy a joint in under 24 hours
Knee affected in more than 50% cases
Joints become infected by direct injury or by blood-borne infection from an infected skin lesion or other site
77
In which age group is septic arthritis most common?
Incidence increases with age 45% over 65
78
What pathogens cause septic arthritis?
Staph aureus - most common
Streptococci
Neisseria gonorrhoea
Haemophilius influenzae in children (rare due to immunisations)
Gram-negative bacteria eg E coli/P aeruginosa in eldery/v young/systemically unwell/IVDU
79
What can increase your risk of getting septic arthritis?
```
Pre-existing joint disease
DM
Immunosuppression
Chronic renal failure
Recent joint surgery
Prosthetic joints
IV drug abuse
Those over 80 and infants
Recent intra-articular steroid injection
Direct/penetrating trauma
```
80
How does septic arthritis present?
Agonisingly painful, red, hot, swollen joint
In elderly and immunocompromised and RA articular signs may be muted
In children - might not use joint, limping/protecting joint
Fever
Monoarthritis
Most common in knee, hip, shoulder, can occur in any joint
Early infection - wound inflammation/discharge, joint effusion, loss of function and pain
Late disease - presents with pain/mechanical dysfunction
81
What could be a differential diagnosis for septic arthritis?
Gout
| Pseudogout
82
How is septic arthritis diagnosed?
Urgent joint aspiration - urgent gram stain and culture
- Purulent/opaque/thick/pussy fluid due to high WCC
- Normal fluid clear, yellow, thin
- Always aspirate before antibiotics
Polarised light microscopy for crystals - exclude gout
ESR, CRP, WCC raised
X-ray
- No value in septic arthritis
- Loosening/bone loss around a previously well-fixed implant suggests infection
Skin wound swab, sputum and throat swab or urine if gonococcal infection possibility
83
How is septic arthrits treated?
Stop immunosuppressants
Double prednisolone dose if on long term prednisolone
Joint immobilised early followed by early physio to prevent stiffness and muscle wasting
If in doubt - start antibioitics after joint aspiration IV for 2 wks
Joint drainage repeatedly until no recurrent effusion can help relieve pain
NSAIDs for pain
84
What is flucloxacillin used for?
Most gram -ves
85
What is erythromycin/clindamycin used for?
If allergic to penicillin
| Most gram -ves
86
What is cefotaxime used for?
Gram negatives/gonococcal
87
What is vancomycin used for?
MRSA
88
What antibiotics do you give if patient immunocompromised?
Flucloxacillin and gentamycin
89
What is osteomyelitis?
Bone marrow inflammation
Infection localised to bone
Either due to metastatic haematogenous spread or due to local infection
90
How common is osteomyelitis?
Predominantly occurs in children
Increasing incidence of chronic osteomyelitis
Majority of haematogenous acute osteomyelitis occurs in children
Adolescents and adults tend to get osteomyelitis due to infection secondary to direct trauma
Elderly get it due to risk factors
91
What pathogens cause osteomyelitis?
S aureus - most common
Coagulase negative staphylococcus
Haemophilius influenzae
Salmonella - complication of sickle cell anaemia
Pseudomonas aeruginosa and serratia marcesans in IVDU
92
What can increase your risk of getting septic arthritis?
```
DM
PVD
Malnutrition
Inflammatory arthritis
Debilitating disease
Decreased immunity
Sickle cell disease
Prosthetic material
Immunosuppressive drugs
Trauma
```
93
What can increase your risk of haematogenous seeding osteomyeltits?
```
Central line
Dialysis
Sickle cell disease
Urethral catheterisation
UTI
```
94
What are the different ways pathogens can get into bone?
Direct inoculation of infection into bone either via trauma or surgery (easy)
Contiguous spread of infection to bone - w/o breaking skin, infection of adjacent soft tissue spreading into bone, seen in elderly who tend to have DM, chronic ulcers, vascular disease, joint replacements and prostheses
Haematogenous seeding
95
What is haematogenous seeding?
Infection spreading from skin to blood then bone
In children more likely to go to long bones at metaphysis
- Blood flow slower, endothelial basement membrane absent and capillaries lack or have inactive phagocytic lining cells - predisposed to bacteria migrating from blood into bone and growth of bacteria in bone
In adults more likely to go to vertebrae
- Vertebrae become more vascular with age, making bacterial seeding more likely
Occurs mainly in children and adults over 50
Risk in IVDU
96
What is the pathology of osteomyelitis?
Inflammatory exudate in marrow leads to increased intramedullary pressuew with extension of exudate into bone cortex
Causes rupture through periosteum and interruption of periosteal blood supply resulting in necrosis
Leaves pieces of separated dead bone called sequestra
New bone forms called involucrum
97
What is the histopathology of osteomyelitis?
Acute changes - inflammatory cells, oedema, vascular congestion, small vessel thrombosis
Chronic changes - necrotic bone sequestra, new bone formation - involucrum, neutrophil exudates, lymphocytes, histocytes
98
How does osteomyelitis present?
Onset over several days
Dull pain at site aggravated by movement
Fever, sweats, rigors, malaise
Acute - tenderness, warmth, erythema, swelling
Chronic - tenderness, warmth, erythema, swelling, deep large ulcers failing to heal despite treatment
Can also present as septic arthritis
- infection breaks through cortex resulting in discharge of pus into joint, more common in infants due to patent transphyseal blood vessels and immature growth plates
99
What could be a differential diagnosis of osteomyelitis?
Charcot joint - damage due to sensory nerves affected by diabetes
Soft tissue infection - cellulitis and erysipelas
Avascular necrosis of bone causes - steroids, radiation, bisphosphonate use
Gout
Fractures
Malignancy
100
How is osteomyelitis diagnosed?
```
Imaging
- plain x-ray showing osteopenia
- MRI show marrow oedema 3-5 days (after x-ray)
- Bone scans
Bloods
- Blood culture to determine aetiology
- ESR and CRP raised
- Acute - raised WCC
- Chronic - can have normal WCC
Bone biopsy and culture to determine cause
```
101
How is osteomyelitis treated?
Immobilisation
Antimicrobial therapy
- Tailored to culture and sensitivity findings
- IV teicoplanin S/E rash, pruritus, GI upset
- IV flucloxacillin
- Oral fusidic acid
- Stop treatment guided by ESR/CRP
102
What is TB osteomyelitis?
Usually due to haematogenous seeding spread from reactivated focus in lungs/GI tract
May be slower onset with systemic symptoms eg malaise, fever, night sweats
Local pain and swelling if pus collected
Biopsy essential
Longer treatment - 12 months with same treatment as for pulmonary TB
103
What is systemic sclerosis?
Multisystem disease with involvement of skin and Raynaud's phenomenon
Distinct from localised scleroderma such as morphea, do not involve internal organ disease and are rarely associated with vasospasm (Raynaud's phenomenon)
104
How common is systemic sclerosis?
```
Highest case-specific mortality compared to any other autoimmune rheumatic disease
Occurs worldwide
More common in women
Peak incidence between 30-50
Rare in children
```
105
What can increase your risk of systemic sclerosis?
Exposure to vinyl chloride, silica dust, adulterate rapeseed oil and tricholoethylene
Drugs such as bleomycin
Genetics
106
What is that pathology of systemic sclerosis?
Widespread vascular damage involving small arteries, arterioles and capillaries early features
Initial endothelial cell damage with release of cytokines, including endothelin-1, causes vasoconstriction
Continued vascular damage and increased vascular permeability and activation of endothelial cells leads to upregulation of adhesion molecules, cell adhesion, migration of cells through leaky endothelium and into extracellular space
Stimulates produciton of cytokines and growth factors which mediate proliferation and activation of vascular and connective tissue cells - particularly fibroblasts
Fibroblasts increase quantities of collagen type 1 and 2 producing fibrosis in lower dermis of skin and internal organs
Uncontrolled and irreverible proliferation of connective tissue and thickening of vascular walls with narrowing of lumen
Damage to small blood vessels also produces widespread obliterative arterial lesions leading to chronic ischaemia
107
How does limited cutaneous scleroderma present?
Begins with Raynaud's phenomenon, skin involvement limited to hands, face, feet and forearms
- Skin tight over fingers, flexion deformities
- Beak-like nose, small mouth
- Painful digital ulcers and telangiectasia
- GI tract involvement
- CREST - calcinosis, Raynauds, esophageal dysmotility/strictures, sclerodactylyl, telenagiectasia
108
How does diffuse cutaneous scleroderma present?
Skin changes develop more rapidly and more widespread than limited cutaneous scleroderma
Early involvement of other organs
- GI - dilation and atony (loss of strength) - heartburn, malabsorption
- Renal - AKI and CKD
- Lung disease - fibrosis, pulmonary vascular disease
- Myocardial fibrosis - arryhthmias and conduction disturbances
109
What is Raynaud's phenomenon?
Spasm of arteries causes reduced blood flow
| Blanched areas of hands
110
How is systemic sclerosis diagnosed?
```
Bloods
- Normochromic, normocytic anaemia
- Microangiopathic haemolytic anaemia
- Urea and creatinine raised in AKI
- Autoantibodies
- Rheumatoid factor
Urinalysis
- If proteinuria - albumin/creatinine ratio
Imaging
- CXR - exclude other pathology
- Hand x-ray - deposits of calcium
- Barium swallow - oesophageal motility
- High resolution CT - confirms fibrotic lung involvement
```
111
How is systemic sclerosis treated?
No cure
Raynauds - hand warmers, oral vasodilators (CCBs)
Nutritional supplementation for malabsorption
Prevention of renal crisis (ACEi)
Early detection of pulmonary hypertension with annual ECHO and pulmonary function tests
Pulmonary fibrosis - immunosuppressant, oral prednisolone
112
What is systemic lupus erythematosus?
Inflammatory, multi-system autoimmune disorder with arthralgia and rashes as most common clinical features, and cerebral and renal disease as most serious problem
Unknown cause
113
How common is lupus?
More common in women
Peak age of onset between 20-40 - typically women of childbearing age
Commoner in African-Caribbean's and Asians
114
What can increase your risk of lupus?
```
FHx
Genetics - HLA genes
Pre-menopausal women
Drugs - hydralazine, isoniazid, procainamide, penicillamine
UV light can trigger flares
Epstein-Barr virus
```
115
What is the pathology of lupus?
Immune complex mediated tissue damage
When cells die by apoptosis, cellular remnants appear on cell surface as small blebs carrying self-antigens
Removal of blebs by phagocytes inefficient so transferred to lyphoid tissues where taken up by APCs
Availability of self-antigens and failure of immune system to inactivated B cell and T cells that recognised self-antigens as foreign leads to
- Development of autoantibodies
- Activation of complement and influx of neutrophils - inflammation
- Abnormal cytokine production - increased IL-10 and interferon alpha resulting in high activity of inflammation
Vascultitis
Synovium of joints can be oedematous and may contain immune complexes
Haematoxylin bodies seen in inflammatory infiltrates and result from interaction of antinuclear antibodies and cell nuclei
116
How does lupus present?
Fatigue, fever, arthralgia, skin problems
Symmetrical small joint arthralgia
Erythema in butterfly distribution on cheeks
Photosensitive rash
Glomerulonephritis with persistent proteinuria
Seizures, psychosis
Mouth ulcers
117
What could be a differential diagnosis for lupus?
```
Acute pericarditis
Antiphospholipid syndrome
B cell lymphoma
Fibromyalgia
Scleroderma
Sjorgren syndrome
```
118
How is lupus diagnosed?
Raised ESR, normal CRP
Bloods
- Leucopenia, lymphopenia, thrombocytopenia
- Anaemia of chronic disease/autoimmune haemolytic anaemia
- Urea and creatinine only raised if renal disease advanced
- Autoantibodies
- Serum complement
Histology to see deposition of IgG and complement
MRI and CT for brain lesions
119
How is lupus treated?
IV cyclophosphamide and high dose prednisolone
Reduce sunlight exposure
Reduce CVD risk factors and give statins
Prevent rashes with high-factor sun cream
Treat BP
NSAIDs
Oral/IM corticosteroids
Antimalarial drugs - help skin disease, fatigue, arthralgia
Immunosuppressives
120
What is antiphospholipid syndrome?
Syndrome characterised by thrombosis and/or recurrent miscarriages with positive blood tests for antiphospholipid antibodies
121
How common is anti-phospholipid syndrome?
Associated with SLE in 20-30% cases
More often occurs as primary disease
More common in women
122
What is the pathology of antiphospholipid syndrome?
Antiphospholipid antibodies play role in thrombosis by binding to phospholipid on surface of cells such as endothelial cells, platelets and monocytes
Once bound, change alters functioning of cells leading to thrombosis and/or miscarriage
Antiphospholipid antibodies cause CLOTS
- Coagulation defect
- Livedo reticularis - lace like purplish discolouration of skin
- Obstetric issues eg miscarriage
- Thrombocytopenia
123
How does anti-phospholipid syndrome present?
Thrombosis
Miscarriage
Ischaemic stroke, TIA, MI
Deep vein thrombosis, Budd-Chiari syndrome
Thrombocytopenia
Valvular heart disease, migraines, epilepsy
124
How is anti-phospholipid syndrome diagnosed?
Anticardiolipin test
- Detects IgG or IgM antibodies that bind negatively charged phospholipid cardiolipid
Lupus anticoagulant test - detects changes in ability of blood to clot
Anti-B2 glycoprotein tet - detects antibodies that bind B2-glycoprotein I, a molecule that interacts closely with phospholipids
A persistently positive test in one or more of these tests needed to diagnose
125
How is anti-phospholipid syndrome treated?
Long term warfarin to minimise thrombosis
Pregnant women
- Oral aspirin and SC heparin early in pregnancy
- Reduces chance of miscarriage but pre-eclampsia and poor foetal growth remains common
Prophylaxis
- Aspirin/clopidogrel especially in those with high IgG
126
What is Sjorgren's syndrome?
Chronic inflammatory autoimmune disorder
Characterised by immunologically mediated destruction of epithelial exocrine glands, especially lacrimal and salivary glands
127
What is the difference between primary Sjorgren's syndrome and secondary Sjorgren's syndrome?
Primary - syndrome of dry eyes in absence of RA or any other autoimmune disease
Secondary - associated with connective tissue disease
128
How common is Sjorgren's syndrome?
More common in women
Associated with HLA-88/DR3
Onset 40-50 - mainly affects middle-aged women
129
What is the pathology of Sjorgren's syndrome?
Lymphocytic infiltration and fibrosis of exocrine glands, especially lacrimal and salivary glands
130
How does Sjorgren's syndrome present?
```
Dry eyes - decreased tear production
Dry mouth - decreased saliva production
Salivary and parotid gland enlargement
Dryness of skin and vagina
Systemic symptoms
- Arthralgia, dysphagia, Raynaud's phenomenon, other autoimmune conditions, renal tubular defects, pulmonary diffusion defects and fibrosis, polynephropathy, vasculitis, increased incidence of non-Hodgkin's B cell lymphoma
```
131
How is Sjorgren's syndrome diagnosed?
```
Schirmer tear test
Rose Bengal staining - shows keratitis
Lab tests
- Raised immunoglobulin levels
- Rheumatoid factor positive
- Antinuclear antibodies
- Anti-Ro antibodies
Salivary gland biopsy shows lymphocytic infiltration
```
132
How is Sjorgren's syndrome treated?
Artificial tears and saliva replacement solutions
NSAIDs and hydroxychloroquine - fatigue and arthralgia
Corticosteroids - swelling/neuropathy
133
What is dermatomyositis?
Rare muscular disorder of unknown aetiology in which there is inflammation and necrosis of skeletal muscle fibres - polymyostitis
Dermatomyositis - skin involvement
Lungs can be affected causing interstitial lung disease
134
How common is dermatomyositis?
Very rare
Affects both adults and children
More common in women
135
What can increase your risk of getting dermatomyositis?
Viral infections of coxsackie, rubella, influenza
| Genetic predisposition - HLA-B8/DR3 at higher risk
136
How does polymyositis present?
Symmetrical progressive muscle weakness and wasting affecting proximal muscles of shoulder and pelvic girdle
Difficulty squatting, going upstairs, rising from a chair and raising hands above head
Pain and tenderness uncommon
Involvement of pharyngeal, laryngeal and respiratory muscles lead to pysphagia, dysphonai and respiratory failure
137
How does dermatomyositis present?
Characteristic skin changes - heliotrope (purple) discolouration of eyelids and scaly erythematous plaques over knuckles
Arthralgia
Dysphagia
DM associated with increased incidence
138
How is dermatomyositis diagnosed?
Muscle biopsy - fibre necrosis, inflammatory cell infiltrates
Muscle enzymes - serum creatinine kinase, aminotransferases, lactate dehydrogenase, aldolase all raised
ESR not raised
Serum antibodies - antinuclear antibody positive, rheumatoid factor, myositis-specific antibodies
Electromyography to detect typical muscle changes
MRI to detect abnormally inflamed muscles
139
How is dermatomyositis treated?
Bed rest combined with exercise programme
Oral prednisolone - continued for at least 1 month after clinically and enzymatically inactive, tapered down slowly
Early intervention for clinical relapse
- Oral azathioprine
- Oral methotrexate
- Oral ciclosporin
Hydroxychloroquine or topical tacrolimus
140
What is fibromyalgia?
AKA chronic persistent pain
Widespread musculoskeletal pain after other diseases have been excluded
Symptoms present for at least 3 months and other causes excluded
Pain at 11 of 18 tender point sites on digital palpation
Central non-nociceptive pain - due to a central disturbacne in pain processing, biophysical factors important
141
How common is fibromyalgia?
Can develop at any age but often over 60
More common in women
12% of those with RA have fibromyalgia
142
What can increase your risk of fibromyalgia?
```
Female
Middle age
Low household income
Divorced
Low educational status
Associations - depression, chronic headache, IBS, chronic fatigue syndrome, myofascial pain syndrome
```
143
How does fibromyalgia present?
Chronic pain (more than 3 months) that is widespread
Pain
- Predominantly neck and back
- Aggravated by stress, cold and activity
- Associated with generalised morning stiffness
- Paraesthetisa of hands and feet
- Areas that pain focusses on - lower neck in front, base of skull, upper edge of breast, neck and shoulder, upper inner shoulder, below side bone at elbow, upper outer buttock, hip bone, just above knee on outside
Fatigue often extreme and occurring after minimal exertion
Non-restorative sleep - frequent waking, waking unrefreshed, poor concentration and forgetfulness, low mood, irritable, weepy, lack of non-REM
Anxious and angry - cannot find reason for pain
144
What could be a differential diagnosis of fibromyalgia?
```
Hypothyroidism
SLE
Polymyalgia rheumatics
Hypercalcaemia
Low vit D
Inflammatory arthritis
```
145
How is fibromyalgia diagnosed?
Pain at 11 of 18 tender point sites on digital palpatation
Thyroid function test
ANAs and DsDNA to exclude SLE
ESR and CRP to exclude PMR
Calcium and electrolytes to exclude hypercalcaemia
Vit D
Examine patient and CRP to exclude inflammatory arthritis
146
How is fibromyalgia treated?
Educate patients and family - real symptoms don't always mean damage
Avoid unnecessary investigations
Reset pain thermostat
- Correct non-restorative sleep
- Improve aerobic fitness - tires them out, sleep better
Low dose antidepressants and anticonvulsants
- Induce muscular relaxation and make normal sleeping patterns
- Tricyclic antidepressants
- Anticonvulsants
- May take a month to have effect
NSAIDs and steroids rarely work
147
How common is mechanical lower back pain?
Common, often self-limiting
Often traumatic or work related
Common back pain in young people - 20-55
Associated with heavy manual handling, stooping and twisting whilst lifting, exposure to whole body vibration, psychosocial distress, smoking and dissatisfaction with work
148
What can cause mechanical lower back pain?
Lumber disc prolapse
Osteoarthritis
Fractures
Spondylolisthesis
149
What risk factors are there for mechanical lower back pain?
Psychosocial distress
| Smoking and dissatisfaction with work
150
What are the risk factors for recurrent back pain?
Female
Increasing age
Pre-existing chronic widespread pain - fibromyalgia
Psychosocial factors - high levels of psychological distress, poor self-rated health and dissatisfaction with work
151
What is the pathology of lumbar spondylosis?
Main lesion in intervertebral disc
Changes in discs occasionally start in teenage years or early twenties and often increase with age
Gel changes chemically, breaks up, shrinks and loses its compliance
Surrounding fibrous zone deveops circumferential or radial issues
Initially asymptomatic but visible on MRI as decreased hydration
Circumferential bulging of intervertebral ligaments
Reactive changes develop in adjacent vertebrae - bone becomes sclerotic and osteophytes form around rim of vertebrae
Most common site L5/S1 and L4/5
In young people, disc prolapse produces Schmorl's node on x-ray - painless but may accelerate disc degeneration
Spondylosis may be symptom less but can cause episodic spinal pain, progressive spinal stiffening, facet joint pain, acute disc prolapses, with/without nerve irritation, spinal stenosis
152
What is the pathology of facet joint syndrome?
Lumber spondylosis also causes secondary osteoarthritis of misaligned facet joints
Pain typically worse on bending backwards and when straightening from flexion - lumbar in site, unilateral or bilateral, radiates to buttocks
Facet joints well seen on MRI and may show osteoarthritis, effusion or ganglion cyst
Treatment - direct corticosteroid injections under imaging
Physiotherapy to reducing weight helps
153
What is the pathology of fibrostic nodulosis?
Uni/bilateral lower back pain and buttock pain
Tender nodules in upper buttock and along iliac crest
Local intralesional cortocosteroid injections may help
154
What is the pathology of postural back pain and sway back of pregnancy?
Altered spinal posture and increased ligamentous laxity
Weight control and pre- and postnatal exercises are helpful, pain usually settles after delivery
Analgesics and NSAIDs are best avoided during pregnancy and breast-feeding
Poor posture causes similar syndrome in non-pregnant due to obesity or muscular weakness
155
How does mechanical lower back pain present?
```
Back stiff
Scoliosis when patient standing
Muscular spasm visible and palpable - local pain and tenderness, lessens when sitting/lying
Pain often unilateral and helped by rest
Episodes generally short-lived and self-limiting
Sudden onset
Pain worse in evening
Morning stiffness absent
Exercise aggravates pain
```
156
What could be a differential diagnosis of mechanical lower back pain?
In elderly - ESR and CRP will distinguish mechanical back pain from polymyalgia rheumatica
157
How is mechanical lower back pain diagnosed?
Spinal x-ray - for red flags
MRI more preferable than CT as better for bone pathology
Bone scans
158
How is mechanical lower back pain treated?
Urgent neurosurgical regerral if any neurological deficity
Analgesia eg paracetamol, NSAIDs to allow normal mobility
Combined with physiotherapy, back muscle trainmen regimens and manipulation
Acupuncture helps some
Excessive rest avoided
Re-education in lifting and exercise to prevent further attacks of pain
Comfortable sleeping position using a mattress of medium firmness
159
What are the red flags for serious spinal pathology?
Age of onset less than 20/greater than 55
Violent trauma
Constant, progressive, non-mechanical pain
Thoracic pain
Systemic steroids, drug abuse, HIV
Systemically unwell, weight loss
Persisting severe restriction of lumbar flexion
Widespread neurology
Structural deformity
160
What is osteomalacia?
Normal amount of bone but mineral content low - excess of uncalcified osteoid and cartilage - defective mineralisation
Reverse of osteoporosis - mineralisation unchanged but overall bone loss
Defective mineralisation after fusion of epiphyses
(Rickets - defective mineralisation during bone growth at epiphyses)
161
What is clinical manifestation of profound vitamin D deficiency?
As required for calcium and phosphate absorption and thus incorporated into bone
162
What can cause osteomalacia?
Hypophosphataemia - due to hyperparathyroidism secondary to vitamin D deficiency
Vitamin D deficiency
Renal disease - inadequate conversion of 25-hydroxyvitamin D to 1,25-hydroxyvitamin D
Drug induces - anticonvulsants induce liver enzymes leading to increased breakdown of 25-hydroxyvitamin D, rifampicin
Liver disease
Tumour induced osteomalacia
163
How does osteomalacia present?
Muscle weakness - waddling gait, difficulty climbing stairs and getting out of chair
Widespread bone pain - dull ache worse on weight bearing and walking
Bone pain and tenderness
Fractures of femoral neck
164
How does Rickets present?
Growth retardation, hypotonia
Knock knees, bowed legs
Widened epiphyses at wrists
Hypocalcaemia tetany
165
How is osteomalacia diagnosed?
```
Bloods
- Low calcium and phosphate
- Raised serum alkaline phosphatase
- Elevated PTH
- Low 25-hydroxyvitamin D
Biopsy - incomplete mineralisation
X-ray - defective mineralisation, Looser's pseudofractures/zones - low density bands extending from cortex inwards in shafts of long bones
```
166
How osteomalacia treated?
Vitamin D replacement
- In dietary insufficiency - calcium D3 forte
- In malabsorption/hepatic disease - oral ergocalciferol or IM calcitriol
In renal disease - alfacidol or calcitriol
Associated with increased risk of T2DM, several cancers, CVD
167
What are the most common tumours of bone?
Most common are metastatses from bronchus, breast and prostate
Primary tumours rare - only seen in children and young adults
168
What cancers can cause bone pain?
```
Multiple myeloma
Lymphoma
Primary tumour of bone - rare, only seen in young
- Osteosarcoma
- Fibrosarcoma
- Chondrosarcoma
- Ewing's tumour
Metastatses (osteolytic)
- Lungs (bronchus)
- Breast
- Prostate (often osteosclerotic too)
- Thyroid
- Kidney
```
169
How do bone tumours present?
Unremitting pain that is worse at night
Weight loss
Ill-health
Usually related to anatomical position on tumour with local bone pain
Systemic symptoms - malaise, pyrexia, aches, pains
Occasionally related to hypercalcaemia
170
How are bone tumours diagnosed?
Skeletal isotope scan - shows bony metastases as hot areas before radiological changes occur
X-rays
- May show metastases as osteolytic areas with bony destruction
- Osteosclerotic metastases are characteristic of prostatic carcinoma
MRI - vertebral lesions
Serum alkaline phosphatase usually raised
Hyperclacaemia occurs in 10-20% with metastatic malignanies
PSA raised in presence of prostatic metastases
171
How are bone tumours treated?
```
Analgesics and anti-inflammatory drugs
Local radiotherapy to bone metastases relieves pain and reduces risk of pathological fracture
Chemo
Hormone dependent = hormonal therapy
Bisphosphonates can help symptomatically
```
172
What is osteosarcoma?
Most common primary bone malignancy in children
Usual peak onset 15-19 years
Associated with Paget's disease in adult life
Occurs in metaphyses of long bones
Common sites are knee/proximal humerus
Often presents as relatively painless tumour
Destroys bone and spread into surrounding tissue
Rapidly metastasises to lung
X-ray - bone destruction and formation, soft tissue calcification produces sunburst appearance
173
What is Ewing's sarcoma?
Arises from mesenchymal stem cells
Very rare
Average onset age 15
Presents with mass/swelling, most commonly in long bones of arms, legs, pelvis and chest - occasionally in skull and flat bones of trunk
Painful swelling, redness in area surrounding tumour, malaise, anoreixa, weight loss, fever, paralysis and/or incontinence if affecting spine, numbness in affected limb
174
What is chondrosarcoma?
Cancer of cartilage
Most common adult none sarcoma
Associated with dull deep pain, affected area swollen and tender
Common sites affected - pelvis, femur, humerus, scapula, ribs
175
What is systemic vasculitis?
Inflammation of vessel wall
Inflammation and necrosis of blood vessel walls with subsequent impaired blood flow resulting in
- Vessel wall destruction - aneurysms, rupture, stenosis
- Endothelial injury - thrombosis, ischaemia/infarction of dependent tissues
Seen in many diseases including RA, SLE and polymyositis and some allergic drug reactions
176
How is systemic vasculitis classified?
By size of blood vessel involved and presence/absence of anti-neutrophil cytoplasmic antibodies
177
What are the large vessel vasculitises?
Aorta and major tributaries
Giant cell arteritis/polymayalgia rheumatic
Takayasu's arteritis
178
What are the medium vessel vasculitises?
Medium and small sized arteries and arterioles
Classic polyarteritis nodosa
Kawasaki's disease
179
What are the small vessel vasculitises?
Small arteries, arterioles, venules and capillaries
ANCA-associated - microscopic polyangitis, granulomatas and polyangitis
ANCA-negative - essential cryoglobulinaemia, cutaneous leucocyticlastic vasculitis
180
What conditions are associated with vasculitis?
```
Anaemia and raised ESR
Infective - subacute infective endocarditis
Non-infective
- Vasculitis with RA
- SLE
- Scleroderma
- Polymyositis/dermatomyositis
- Good pastures syndrome and IBD
```
181
What is giant cell arteritis?
Inflammatory granulomatous arteritis of larger cerebral arteries as well as other large vessels
182
How common are large vessel vasculitises?
Only affect patients older than 50
| Two separate conditions but normally co-exist
183
How common is polymyalgia rheumatica?
Systemic disease of elderly
Affects those over 50
More common in women
Pathogenesis unknown
184
How common is giant cell arteritis?
Primary in those over 50
Incidence increases with age
More common in women
185
What can increase your risk of polymyalgia rheumatica?
SLE
| Polymyositis/dermatomyositis
186
What can increase your risk of giant cell arteritis?
Over 50
Female
RA, SLE, scleroderma
187
What is the pathology of giant cell arteritis?
Arteries become inflamed, thickened and can obstruct blood flow
Cerebral arteries affected in particular - temporal artery
Ophthalmic artery can also be affected potentially resulting in permanent or temporary visual loss
188
How does polymyalgia rheumatica present?
Sudden onset of severe pain and stiffness of shoulders and neck and of hips and lumbar spine
Symptoms worse in morning - lasts from 30 mins to several hours
Mild polyarthritis of peripheral joints
Fatigue, fever, weight loss, depression
189
How does giant cell arteritis present?
Severe headaches (temporal pulsating)
Tenderness of scalp or temple
Claudication of jaw when eating
Tenderness and swelling of one or more temporal or occipital arteries
Sudden painless vision loss - emergeny
Malaise, lethargy, fever
Dyspnoea, morning stiffness, unequal/weak pulses
190
What could be a differential diagnosis for polymyalgia rheumatica?
RA, spondyloarthropathies, SLE, polymyositis/dermatomyositis
Osteoarthritis, malignancy
Chronic pain syndrome eg fribromyalgia and depression
191
What could be a differential diagnosis for giant cell arteritis?
Migraine, tension headache, trigeminal neuralgia, polyarteritis nodosa
192
How is polymyalgia rheumatica diagnosed?
```
Clinical history normally diagnostic
ESR/CRP raised
ANCA negative
Serum alkaline phosphatase raised
Mild normocytic anaemia
Temporal artery biopsy shows GCA
```
193
How is giant cell arteritis diagnosed?
```
Diagnostic criteria of 3 or more
- Over 50
- New headache
- Temporal artery tenderness/decrease pulsation
- ESR raised
- Abnormal artery biopsy - inflammation infiltrates present
Normochromic, normocytic anaemia
Raised ESR
ANCA v high
CRP v high
Serum alkaline phosphatase raised
Temporal artery biopsy - definitive diagnostic test, before/within 7 days starting high dose corticosteroids, patchy lesions so need a lot, granulomatous inflammation of intima and media
Breaking up of internal elastic lamina
```
194
How is polymyalgia rheumatica treated?
Corticosteroids produce dramatic reduction of symptoms within 24-48 hrs starting
Decrease dose slowly
If no improvement question diagnosis
Use long term - GI and bone protection (lasoprazole, alendronate, Ca2+ and vit D)
195
How is giant cell arteritis treated?
High dose corticosteroid rapidly - prednisolone to stop vision loss - gradual reduction of steroids over 12-18 months
Used long term so give GI and bone protection
Monitor treatment progress by looking at ESR/CRP
196
What is ANCA-associated vasculitis?
Rare, life-threatening, multisystem diseases causing damage to predominantly small arteries
Anti-neutrophil cytopasmic antibodies are implicated in pathogenesis and can be measured
197
What are the key conditions associated with ANCA-associated vasculitis?
Granulomatous with polyangitis
Eosinophilic granulomatous with polyangitis
Microscopic polyangitis
198
What is the pathology of ANCA-associated vasculitis?
Pathogenic anti-neutrophil cytoplasmic antibodies - activated primed circulating neutrophils
Vasculitis - neutrophil driven necrotising inflammation causing direct vessel wall damage
Granulomatous inflammation - extravascular chronic inflammatory lesions containing macropahes and multi-nucleated giant cells
199
How does granulomatous with polangitis ANCA-associated vasculitis present?
Variable presentation from limited to generalised multi-system disease
Epistaxis, crusts, stuffiness, hearing loss, hoarseness, stridor
Iritis, diplopia
Cough, dysponea, haemoptysis
Rash
Numbness, tingling, foot/wrist drop
Joint pain/swelling
200
How is granulomatous with polyangitis ANCA-associated vasculitis diagnosed?
```
History and exam
ANCA testing
Renal tissue biopsy
CT thorax
Urine protein/creatinine ratio
CT head/sinuses/neurophysiology
Birmingham vasculitis activity score
Vasculitis damage index
```
201
How is granulomatous polyangitis ANCA-associated vasculitis treated?
```
Induction of remission
- Cyclophosphamide or rituximab
- Glucocorticoids
- Plasma exchange
Maintenance of remission
- DMARD
- Rituximab
- Glucocorticoid taper
```
202
What is Paget's disease?
AKA osteitis deformans
| Focal disorder of bone remodelling
203
How commin Paget's disease?
Incidence increase with age - rare under 40
Affects up to 10% individuals by age 90
More common in Europe and Northern England
UK has highest prevalence worldwide
More common in women
204
What causes Paget's disease?
Unknown
Possible result of latent viral infection (canine distemper virus, measles or respiratory syncytial virus) in osteoclasts in genetically susceptible individuals
205
What can increase you risk of getting Paget's disease?
FHx
206
What is the pathology of Paget's disease?
Increased osteoclastic bone resorption followed by formation of weaker new bone, increased local bone flow and fibrous tissue
Ultimately, formation exceeds resorption but new woven bone weaker than normal bone - leading to deformity and increased fracture risk
Disease doesn't spread but can become symptomatic at previously silent sites
207
How does Paget's disease present?
Common sites - pelvis, lumbar spine, femur, thoracic spine, skull, tibia
60-80% asymptomatic
Bone pain
Joint pain - when involved bone close to joint leading to cartilage damage and osteoarthritis
Deformities - bowed tibia and skull changes
Neurological complications
- Nerve compression - deafness from CN8 involvement, paraparesis
- Hydrocephalus due to blockage at aqueduct of Sylvius
High output HF and myocardial hypertrophy due to increase bone blood flow
Osteosarcoma
208
How is Paget's disease diagnosed?
Increased serum alkaline phosphatase with normal calcium and phosphate - reflects increased bone turnover
Urinary hydroxyproline excretion raised - marker of disease activity
X-ray
- Localised bony enlargement and distortion
- Sclerotic changes (increased density)
- Osteolytic areas (loss of bone and reduced density)
Isotope bone scans
- Useful to determine extent of skeletal involvement but unable to distinguish between Paget's disease and sclerotic metastatic carcinoma
209
How is Paget's disease treated?
Bisphosphonates - IV/oral zolendronate/oral alendronate which inhibit bone resorption by decreasing osteoclast activity
NSAIDs for pain
Disease activity monitored by symptoms and measurement of serum alkaline phosphatase or urinary hydroxyproline
210
What is acute disc disease?
Prolapse on intervertebral disc resulting in acute back pain
211
What is chronic disc disease?
Associated with degenerative changes in lower limb lumbar discs and facet joints
212
How common is acute disc disease?
Disease of younger people (20-40) since disc degenerates with age and in elderly - no longer able to prolapse
In older patients sciatica more likely to be result of compression of nerve root by osteophytes in lateral recess of spinal canal
213
How does acute disc disease present?
Sudden onset of severe back pain - often following strenuous activity
Pain often clearly related to position and aggravated by movement
Muscle spasms lead to sideways tilt when standing
Radiation of pain and clinical findings depend on disc affected - lower 3 discs most commonly affected
214
What signs do you get if S1 is affected?
Pain - buttock down back of thigh to ankle/foot
Ankle jerk reflex lost
Diminished straight leg raising
215
What signs do you get if L5 is affected?
Pain - buttock to lateral aspect of leg and top of foot
Diminished straight leg raising
No reflexes lost
216
What signs do you get if L4 is affected?
Pain - lateral aspect of thigh to medial side of calf
Knee jerk lost
Positive femoral stretch test
217
How does chronic disc disease present?
Pain usually mechanical type - aggravated by movement
| Sciatic radiation may occur with pain in buttocks radiating into posterior thigh
218
How is acute disc disease diagnosed?
X-rays often normal
| MRI in those surgery being considered
219
How is acute disc disease treated?
Acute stage - bed rest on firm mattress, analgesia and epidural corticosteroid injection (severe disease)
Surgery only for severe or increasing neurological impairment eg foot drop/bladder symptoms
Physio in recovery phase - helping correct posture and restore movement
220
How is chronic disc disease treated?
No cure
Long-standing pain
Surgery done when pain arises from single identifiable level - do fusion at this level with decompression of affected nerve roots
NSAIDs, physio, weight reduction
221
How do you deal with fractures?
Reduction
Immobilisation
Rehabilitation
222
How do fractures heal?
Haematoma - activation of coagulation cascade, changes in local environment, inflammatory cells and molecules released
Inflammation - recruitment and activation of inflammatory and osteoprogenitor cells, clearance of necrotic tissues
Callus formation - soft and hard, differentiation of MSCs according to mechanical environment, initial stabilisation of fracture, then replaced by calcified tissue
Granulation tissue - active proliferation of osteoprogenitor cells, angiogenesis, extracellular matrix production
Remodelling - long process, resorption of remaining cartilage, resoration of Haversian system, no scar formed
223
What are the different types of fractures?
```
Transverse
Linear
Obliques/non-displaced
Oblique/displaced
Spiral
Greenstick
Comminuted
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224
What complications of fractures can there be?
Damage to surrounding structures
Contamination (open fracture)
Compartment syndrome
Early systemic - fat embolus, shock, crush syndrome, PE, pneumonia
Late - delayed union, non-union, mal union, avascular necrosis, stiffness, arthritis, osteomyeltitis
225
What is polyarteritis nodosa?
Medium vessel vasculitis
226
How common is polyarteritis nodosa?
Rare in UK
Usually occurs in middle aged men
More common in men
Associated with Hep B
227
What can increase your risk of polyarteritis nodosa?
Male
Hep B
RA, SLE, scleroderma
228
What is the pathology of polyarteritis nodosa?
Necrotising vasculitis that causes aneurysms and thrombosis in medium sized arteries leading to infarction in affected organs
Sever systemic symptoms
229
How does polyarteritis nodosa present?
Fever, malaise, weight loss, myalgia
Neurological - mononeuteritis multiplex due to arteritis of vasa nervorum - numbness, tingling, abnormal/lack of sensation and inability to move part of body
Abdominal - pain due to arterial involvement of abdominal viscera, mimicking acute cholecystitis, pancreatitis, appendicitis, GI haemorrhage
Renal - presentation with haematuria and proteinuria, hypertension and acute/chronic kidney disease occurs
Cardiac - coronary arteritis causes myocardial infarction and HF
Skin - subcutaneous haemorrhage and gangrene occur
Lung involvement rare
230
What could be a differential diagnosis of polyarteritis nodosa?
Fever caused by infection
Crohn's
Connective tissue disease
Other vasculitis
231
How is polyarteritis nodosa diagnosed?
Anaemia
WCC raised
ECR raised
ANCA negative
Biopsy of kidney to look for hypertension and other damage
Angiography - micro-aneurysms in hepatic, intestinal or renal vessels
232
How is polyarteritis nodosa treated?
Control BP
Corticosteroids in combination with immunosuppressive drugs
Hep B treated with antiviral after initial treatment with steroids
233
What is a prosthetic joint infection?
Most serious complication of arthroplastic surgery
| Based on hips and knees
234
How common are prosthetic joint infection?
Incidence increasing due to increasing age, diabetes and obesity
235
What can cause prosthetic joint infections?
Staph aureus
Coagulase negative staphylococci
Gram-positives mainly
236
What can increase your risk of prosthetic joint infections?
Poor infection control - prevent using highly aseptic theatre with plastic screen walling off anaesthetist from joint, lamina flow theatres with filtered air blowing out of theatre, antibiotics placed in bone cement and systemic antibiotics pre-op to help minimise risk of infection
Old age, diabetes, obesity
237
How does prosthetic joint infection present?
Majority not acutely infected
Systemically well
Tender, hot, swollen joint
238
How is are prosthetic joint infections diagnosed?
Tissue sample from surgery
X-ray
Both ESR and CRP raised - sign of infection
Alpha defensin
Joint aspiration - identifies organism and antibiotics sensitivities
239
How are prosthetic joint infections treated?
Aim to eradicate sepsis, relieve pain and restore function
Antibiotic suppression - will not eliminate bacteria
Debridement and retention of prothesis - for early post-op infections or acute haematogenous infection, not for chronic infections
Excision arthroplasty - for high risk frail and multiple co-morbidities with uncontrolled infection with antibiotic suppression, not good at restoring function
One-stage arthroplasty exchange - implantation of new prothesis with antibiotics cement
Two-stag arthropasty exchange - radical debridement
Amputation if severe infection and if all else fails
240
Name 2 examples of bisphosphonates
Alendronate
Zolendronate
Disodium pamidronate
241
When are bisphosphonates used?
Alendronate first line treatment for patients at risk of osteoporosis
Severe hypercalcaemia of malignancy
Myeloma and breast cancer bone metastases to reduce pathological fractures and need for radiotherapy or surgery
Paget's disease to reduce bone turnover and pain
242
How do bisphosphonates work?
Reduce bone turnover by inhibiting osteoclasts and promoting apoptosis
Similar structure to naturally occuring pyrophosphate so readily incorporated into bone
Net effect reduction in bone loss and improvements in bone mass
243
What are the main adverse affects of bisphosphonates?
Oesophagitis can occur when taken orally
Hypophosphataemia
Rarely jaw osteonecrosis of atypical femur fractures can occur
Avoid in severe renal impairment and hypocalcaemia and in upper GI disorders
Used with care in patients with dental disease or who smoke
Absorption reduced if taken with calcium containing products such as antacids and iron salts
244
Give 2 examples of calcium and vitamin D drugs
Calcium carbonate
Calcium gluconate
Colecalciferol
Alfacalcidol
245
What are calcium and vit D drugs used for?
In osteoporosis to ensure positive calcium balance when dietary intake/sunlight exposure insufficient
CKD to treat and prevent secondary hyperparathyroidism and renal osteodytrophy
Sever hyperkalaemia ot prevent lifethreatening arrhythmias
Symptomatic hypocalcaemia
Vit D in prevention and treatment of vit D deficiency for Rickets and osteomalacia
246
How do calcium and vitamin D drugs work?
Calcium homeostasis controlled by
- PTH and vitamin D which increase serum calcium levels and bone mineralisation
- Calcitonin which reduces serum calcium levels
Resorting positive calcium balance reduces rate of bone loss and prevents fractures
247
What are the main adverse effects of calcium and vitamin D drugs?
Dyspepsia and constipation
CVS collapse if administered to fast via IV
Do not use in hypercalcaemia
Ca can reduce absorption of iron, bisphosphonates and tetracycline antidepressants
248
Name a xanthine oxidase inhibitor
Allopurinol
249
What are xanthine oxidase inhibitors used for?
To prevent acute attacks of gout
To prevent uric acid and calcium oxalate renal stones
To prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy
250
How do xanthine oxidase inhibitors work?
Blocks metabolism of xanthine (produced from purines) to uric acid
Blocks enzyme xanthine oxidase
Results in lower plasma uric acid concentration and reduces precipitation of uric acid in the joint or kidneys
251
What are the main adverse effects of xanthine oxidase inhibitors?
Skin rash - if severe may indicate hypersensitivity reaction
Not be started during acute gout attacks as may worsen these, and contraindicated in patients with recurrent skin rash in drug
Use with care in renal and hepatic impairment
Azathioprine requires xanthine oxidase for metabolism so allopurinol may increase activity
Use with care with amoxicillin, ACEi or thiazides as increase risk of hypersensitivity
252
Name an example of an anti-gout agent
Colchicine
253
What are anti-gout agents used for?
To prevent acute gout attacks and relieve pain of attack when they do occur
Also used to treat familiar mediterranean fever
254
How do anti-gout agents work?
Inhibit microtubule polymerisation by binding to tubulin, which is essential for mitosis
Inhibits neutrophil motility and activity leading to net anti-inflammatory effect which is useful in acute attacks
255
What are the main adverse effects of anti-gout agents?
GI disturbance
Myalgia, fever
Fatigue occurs due to anaemia in high doses
Peripheral neuropathy due to peripheral nerve damage
Contraindicated in renal impairment
Colchinine toxicity enhanced when using statins
256
Name an example of an anti-metabolite
Methotrexate
257
What are anti-metabolites used for?
Disease modifying treatment for RA
Treat severe psoriatic arthritis that is resistant to other therapies
Also used in peripheral arthritis in spondyloarthropathies
258
How do anti-metabolites work?
Inhibit dihydrofolate reductase which converts dietary folic acid to tetrahydrofolate which is required for DNA and protein synthesis
Lack of FH4 prevents cellular replication
Anti-inflammatory and immunosuppressive effects mediated by IL-6 and TNF-alpha
259
What are the main adverse effects of anti-metabolites?
Sore mouth, GI upset, bone marrow suppression, and rarely hypersensitivity reactions, diarrhoea
Nausea
Long term use can cause hepatic cirrhosis or pulmonary fibrosis
Contraindicated in severe renal impairment and abnormal liver function - abnormal LFTs
Contraindicated in pregnancy
Neutropenia, thrombocytopenia
Renal impairment
260
Name 2 other examples of DMARDs
Sulfasalazine
| Leflunomide
261
When is sulfasalazine used?
For mild/moderate disease
| Used in young and women
262
How do DMARDs work?
Inhibit inflammatory cytokines - suppressing immune system and therefore carry risk of infection
Used early to reduce inflammation and slow development of joint erosions and irreversible damage
Take 6 wks to start working
All have serious side effects so monitoring with blood tests required
263
What are the side effects of sulfasalazine?
```
Nausea
Skin rashes
Mouth ulcers
Neutropenia
Thrombocytopenia
Abnormal LFTs
```
264
How does leflunomide work?
Blocks T cell proliferation
265
What are the side effects of leflunomide?
```
Diarrhoea
Neutropenia
Thrombocytopenia
Alopecia
Hypertension
```
266
How do TNF-alpha blockers work?
Slows/halts erosion formation
TNF bodies fire alarm and produced early on to initiate immune response
TNF regulates other cytokines, stimulates osteoclast development
267
Name 3 TNF-alpha blockers
Infliximab
Etanercept
Adalimumab
268
Which 2 TNF-alpha blockers are monoclonal antibodies?
Infliximab and adalimumab
269
What are the SE of infliximab?
Demyelination and autoimmune syndromes
270
What are the SE of adalimumab?
Hypersensitivity reactions
| HF
271
What is etanercept? What are the SE of etanercept?
Receptor fusion protein
| Infections, hypersensitivity reactions
272
Name a B cell inhibitor
Rituximab
273
How do B cell inhibitor work?
Monoclonal antibodies that target CD20 on B cells preventing to production of rheumatoid factor
Used in those who have failed to respond to anti-TNF agents
274
What are the side effects of B cell inhibitors?
Hypo/hypertension, skin rash, nausea, pruritus, back pain
275
Name an interleukin blocker
Toxilizumab
| Anakinra
276
How does toxilizumab work?
Monoclonal antibody that binds to IL-6 cytokine before it reaches target receptor
IL-6 and -1 are the most important in joint inflammation
Used alongside methotrexate
277
How does anakinra work?
Monoclonal antibody that is IL-1 antagonist
278
Name a T cell activation blocker
Abatacept
279
How does abatacept work?
Blocks T cell activation which mean macrophages and B cells cannot be activated thus reducing inflammation
