Rheumatology Flashcards
(215 cards)
1
Q
RA: define
A
chronic systemic inflammatory disease
synovial joints
symmetrical deforming polyarthritis
2
Q
RA: pathophysiology
A
not fully understood
genetically susceptible individuals + unknown antigen
-> autoimmune response
-> synovitis of joints and tendon sheaths
-> synovial hypertrophy
-> cartilage damage
-> bone destruction
T cells stimulate inflammatory cytokines
-> TNF-alpha, IL-1, IL-6 -> pro-inflammatory state
3
Q
RA: risk factors
A
pre-menopausal women family history smoking infection diet hormonal
4
Q
RA: age of onset
A
20-40 years
5
Q
RA: clinical features
A
Stiffness (morning >1 hour) Symmetrical Swollen joints (polyarthritis) Small joints of the hand and feet Sex (female:male 3:1) Speed: quick onet over weeks of months Specific signs in the hand: - early: swollen MCP, PIP and MTS joints - late: Boutonnieres deformity, swan neck deformity, ulnar deviation, z-deformity of the thumb
6
Q
RA: hand features
A
- early: swollen MCP, PIP and MTS joints
- late: Boutonnieres deformity, swan neck deformity, ulnar deviation, z-deformity of the thumb
7
Q
Boutonniere deformity define
A
flexion of the PIP
hyperextension of DIP
8
Q
Swan neck deformity
A
hyperextension of PIP
flexion of DIP
9
Q
RA: extra-articular manifestations
A
dry eyes, scleritis pulmonary fibrosis lymphadenopathy anaemia rheumatoid nodules Stomach ulcers & renal disease (drug related) vasculitis osteoporosis
10
Q
RA and OA comparison
A
RA symmetrical, OA not RA morning stiffness >1h, OA <30min RA not worse on movement, OA is RA onset at 20-40 year old, OA >50 RA rapid onset, OA takes years RA has systemic symptoms, OA doesn't RA worse in the morning, OA evening
11
Q
RA: diagnosis
A
history 6 weeks + 3+ swollen tender joints, symmetrical positive investigations ( rheumatoid factor, anti-CCP, ESR, CPR
12
Q
RA: investigations
A
rheumatoid factor (high sensititvity, low specificity)
anti-CCP (low sensitivity, high specificity)
ESR
CRP
13
Q
RA: management
A
start within 3 m. of symptom onset
DMARDs (disease modifying anti-rheumatic drugs) combination of 2
- methotrexate
-sulfasalazine
- hyroxychloroquine
Corticosteroids injection/oral for rapid relief
NSAIDS for symptomatic relief and red. inflammation
TNF- alpha inhibitos (infliximab)
B-cell blockers (rituximab)
physiotherapy
rheumatology referral
surgery for pain relief and deformity/function restoration
14
Q
Disease Activity score (DAS) 28: what joints are included
A
MCP, PIP, wrist Elbows Shoulders Knees 28 joints
15
Q
Disease Activity Score (DAS) 28: what disease is it used in?
A
RA
16
Q
Disease Activity score (DAS) 28: what is taken into accont
A
tenderness and swelling at 28 joints
ESR
self-reported symptom severity
17
Q
RA: monitoring
A
CRP
DAS28 (Disease activity score)
18
Q
RA: radiological features
A
LESS Loss of joint space Erosions Soft tissue swelling Soft bones- oseopenia
19
Q
OA: define
A
condition characterised by cartilage damage joint space narrowing -> pain, functional limitation and impaired quality of life any joint
20
Q
OA: pathophysiology
A
metabolically dynamic process
imbalance between breakdown and bone repair
normally, hyaline (articulating) cartilage: collagen and matrix components get degraded and replaced by chondrocyte cells
OA: apoptosis of chondrocytes
-> cytokines (IL-1, TNF- alfa)
-> protease enzymes (metalloproteases)
- > cartilage destruction (thinning and fibrillation)
- > abnormal subchondral bone growth
- > oseophytes and bone custs
21
Q
OA: clinical features
A
joint pain
- worse on movement
- morning stiffness <30mins
- periarticular tenderness
- crepitus
- muscle wasting
- deformity
- instabilityy
- bouchard’s nodes
- heberden’s nodes
22
Q
Difference between bouchard’s and heberden’s nodes ?
A
OA- hard/bony swellings
Bouchard’s nodes: PIP joints
Heberden’s nodes: DIP joints
23
Q
OA: investigations
A
Bloods: ESR, CRP, RF, anti-CCP: all normal or negative
X ray: LOSS
MRI shows early changes
24
Q
OA: X-ray features
A
LOSS Loss of joint space Osteophytes Subchondral sclerosis Subchondral cysts
25
OA: presentation questions
predisposing factors (trauma?)
PMH (secondary causes: RA, Paget's disease)
Family hisotry
Occupation
26
OA: non-pharmacological management
education
exercise
weight loss
transcutaneous nerve stmulation (TENS)
Aids and devices: footwear, insoles, bracing
physiotherapy
Surgery: replacement, arthroscopic debridement
27
OA: pharmacological management
Paracetamol +/- topical NSAIDs
add wezak opioid (codeine)
add oral NSAID + PPI (red. inflammation)
intra-articular CS injections
28
Septic arthritis: define
```
acute infection (usually bacterial) of a native or prosthetic joint
-> rapid joint destruction
knee and hip most commonly affected
```
29
Septic arthritis: cause
haematogenous spread (respiratory or UTI)
local tissue infection (cellulitis and osteomyelitis)
penetrating trauma
inoculation
30
Septic arthritis: pathophysiology
bacteria in the joint
- > cytokines release
- > proteoglycans and collagen hydrolysis
- > cartilage destruction
- > bone loss
31
Septic arthritis: causative bacteria
gram +ve cocci:
-streptococcus aureus
-staphylococcus epidermis (in prosthetic joints)
gram-ve cocci:
- neisseria gonorrhae
gram -ve bacilli
- rara, mainly in diabetics, eldery and IV drug users
32
Septic arthritis: risk factors
```
prosthetic joint
RA
DM
IV drug use
Osteomyelitis
Intra-articular injection/aspiration
```
33
Septic arthritis: clinical features
```
Red flags:
-extremely painful
-erythema
-acutely swollen joint
Muscle spasm/joint immobility
systemic features: tachy, fevel, rash, malaise, anorexia
loosening of the implant
```
34
Septic arthritis: investigations
```
joint aspiration +/- USS -> gram staining, WCC, culture, polarised light microscopy (ex: gout, CPPD)
blood culture
blood tests (sepsis)
X-ray (normal/undelying joint disease)
```
35
Septic arthritis: management
```
Empiric/S.aureus:
flucloxacillin IV -> PO/ Vancomycin
Strep. pneumoniae:
Benzylpenicilin IV -> Amoxivilin PO / Vancomycin IV -> Doxycycline PO
Gram negative:
ceftaxime IV
```
up to 14 days
Athocentesis, lavage, debridement
immobilisation -> physiotherapy
Monitoring w/ WCC, CRP, LFT’s, U&E’s
36
Spondyloarthopathies: conditions
```
PEAR
Psoriatic arthritis
Enteropathis spondyloarthropathies
Ankylosing spondylitis
Reactive arthritis
```
37
Spondyloarthropathies overlapping features
rheumatoid factor negative- seronegative
HLA-B27 association
axial arthritis
Asymmetrical large joints
Mono- or oligo-arthritis (<5 joints)
Enthesitis (inflam. of tendon or ligment insertion)
Dactylitis (sausage digit)
Extra articular manifestations like IBD or iritis
38
Psoriatic arthritis: define
chronic inflammatory arthritis
seronegative spondyloarthropathy
small joints of the hand
variable disease patterns
39
PsA: pathophysiology
```
poorly understood
genetically susceptible indiv. exposed to an environmental trigger
-> T-cell infiltration
-> chemokine/cytokine release
->angiogenesis and cellular infiltration
```
40
PsA: risk factors
Psoriasis, usually before (70%), at the same time (5%) or after (25%)
family history (HLA-B27)
trauma
HIV
41
PsA: clinical features patterns
DR SAM
```
DIP joint disease
Rheumatoid pattern (seronegative and lack of nodules)
Spondyloarthritis (may be w/ usilated sacriliitis, typical or atypical AS)
Asymmetrical oligoarthritis of large joints
Mutilans arthritis (rare, severe form, osteolysis -> small joint destruction-> digits shorthening)
```
42
PsA: general clinical features
```
joint pain
morning stiffness >30 mins
Dactylitis (sausage digits)
Enthesitis- pain at tendon/ligaments insertions into the bone
Psoriatic rash
naul changes (pitting, hyperkeratotis)
```
43
PsA: diagnosis
CASPAR criteria
```
Current psoriasis- 2pts
History of psoriasis- 1pt
Fam history of psoriasis- 1pt
Dactylitis- 1pt
Juxta-articular new bone formation -1pt
RF neg -1pt
Nail changes- 1pt
```
44
PsA: investigations
X-rays: soft tissue swelling, DIP joint erosion, periarticular new bone formation, oseolysis, pencil in cup deformity (advanced)
Bloods: ESR and CRP (normal or raised in active disease), RF, anti-CCP and ANA negative
45
PsA: management
```
NSAIDs
DMARDs (Trial of 3m): Methotrexate + ciclosporin/ sufasalazine
Intra articular CS injecitons
Anti-TNF alpha theraphy (infliximab)
Physiotherapy
```
46
Ankylosing spondylitis: define
chronic inflammatory disorder of the sacroiliac joints and spine
commonest seronegative spondyloarthropathy
other features: peripheral arthritis, enthesitis and extra-articular organ involvement
ankylosis = joint fusion
47
Ankylosing Spondylitis: pathophysiology
Genetic and environmental factors
HLA-B27 association
inflammation of sacroiliac joints
- IV disc, multiple joints and ligmaments involved
early: subchondral granulation tissue -> erosion -> fibrocartilage -> ossification at ligamentous and capsular attachement sites (enthesitis)
late: annulus fibrosis calcification -> bony bridge formation between verderbae (syndesmophytes)-> fusion
48
Syndesmophytes
bony bridge between vertebrae
| seen in Anklylosing Spondylitis (annulus fibrosis calcification)
49
Ankylosing Spondylitis clinical features
dull back pain
stiffness >6 m
- both worse at night and early morning
- worse with rest
- better with exervise
reduced motion in lumbar spine (Schober's test) and cervical spine
Question mark ? posture: loss of lumbar lordosis, thoracic kyphosis and neck hyperextension
50
Ankylosing Spondylitis extra-articular features
A- factor
```
Atlanto-axial subluxation
Anterior uveitis
Apical lung fibrosis
Aortic incompetence
AV node block
Achilles tendinitis
Amyloidosis (rare, late complication)
```
51
Question mark posture where is it seen?
Ankulosing sponylitis
52
Schober's test, what is it and what does it signify?
Assessment of flexion of the spine
mark at the posterior superior illiac spines and 10cm above
forward spinal flexion to 13.5-15cm (normal)
reduced lumbar spine movement in ankylosing spondylitis
53
Ankylosing Spondylitis: investigations
X-ray: sacroiliitis grade- diagnostic
MRI- early changes
Bloods: CRP, ESR (both in active disease), RF and ANA negative, HLA-B27 testing
USS- enthesitis
54
Ankylosing Spondylitis: X-ray features
```
Sacroillitis grade
- joint irregularity, scerosis,
- joint space narrowing
- joint fusion (anklylosis)
Early changes
- bone erosions
- SI joint widening
- square vertebral bodies with shiny corners
Late changes
- longitudinal lig. ossification
- bamboo spine appearance
```
55
Bamboo spine appearance: where is it seen
Ankylosing Spondylitis
56
Ankylosing Spondylitis: management
```
exercise and physio
NSAIDs -> codeine + paracetamol if insufficient
local CS
anti- TNF- alpha
Surgery: replacements
```
57
Reactive arthritis: define
```
acute aseptic arthritis
response to extra-articular infection (GI/GU tract)
seronegative spondyloarthropathy
asymetrical oligoarthritis
usually in the lower limbs
```
58
Reactive arthritis: pathophysiology
infectious trigger (usually from bacterial GI/GU infection)
in genetically susceptible individuals
->immune activation with self-antigents
-> acute inflammation
usually 2-6 weeks after the initial infection
inflammation of joints, entheses, axial skeleton, mucous membranes, GI tract and eyes
HLA-B27 association
59
Reactive arthritis risk factors
GI/GU infection
Males (in relation to Chlamydia)
HLA-B27 positive
Caucasian patients
60
Reactive arthritis: clinical features
```
arthritis- acute, asymmetrical, large j.
2-6 wks after initial infection
may be accompanied by malaise, fatigue and fever
enthesitis
conjunctivitis
anterior uveitis
dactylitis
lower back pain
mounth ulcers
nail changes
keratoderma blennorrgagica
```
61
Reactive arthritis: what skin condition is it associated with?
keratoderma blennorrhagica
62
Reactive arthritis: what syndrome is it associated with?
Reiter's syndrome:
reactive arthritis
conjuctivitis
urethritis
63
Reiter's syndrome: define
Reactive arthritis
conjuctivitis
urethritis
64
Reactive arthritis: investigations
Bloods
- raised: CRP, EST, leucocytosis and thrombocytosis (acute phase)
- ANA, RF, anti-CCP negative
- HLA-B27 positive in most
X-ray: usually normal +/- erosions, spurs, sacroiliitis
Joint aspirate (r.o cyrstal or septic arthritis) -> sterile, cloudy w/ raised WCC
stool, throat or urine culture- identify causative organism
serology for chlamydia
MRI if chronic
65
Reactive arthritis: management
rest + splint +/- physio
NSAIDS
intra- articular CS
DMARDs: methotrexate, sulfasalizine (for persisten or refractory disease)
Abs: tetracyclines for urethritis by Chlamydia
Anti-TNF alpha (in aggressive cases)
66
Gout; define
inflammatory arthritis
progresses from asymptomatic hyperuricaemia
urate crystals deposition in the synovial fluid
67
Gout: pathophysiology stages
asymptomatic hyperuricaemia (up to 20 years)
acute gout phase (serum lvls reach saturation -> deposition-> inflammatory response)
inter-critical gout phase (asymptomatic period between attacks)
chronic gout phase (chronic symptoms)
68
What is urate crystal?
a purine product
69
Hyperuraemia causes
impaired renal excretion
overproduction of uric acid
over-consumption of purine rich foods (metobalised to urate)
70
Gout: risk factors
hyperuricaemia
males
red meat, shellfish
alcohol -> ketones (compete with urate for renal excretion) also inc. risk via dehydration
Diuretics, aspirin, ciclosporin, laxatives
Chronic renal failure
Other: obesity, HTN, fam history, age, coronary heart disease, DM
71
Gout: clinical features
red flag: single peripheral joint, excruciating pain (oftern nocturnal- bed covers cause pain), red, hot and swollen
1st MTP joint (podargia), small joints of foot (mid-tarsal) and hand, the ankle, knee and elbow
chronic gout: polyarthritis, thopi (nodular subcutaneous urate deposits), fever and malaise
72
Gout of 1st MTP joint: name
podargia
73
Gout: hallmark of chronic gout
thophi
| - nodular subcutaneous deposition of uric acid crystals
74
Gout: investigations
joint aspiration + synovial fluid analysis
-> negatively bifringent crystals under polarized light microscopy
- exclude septic arthritis
serum urate
X-ray: soft tissue swelling, late: punched out erosions
75
Gout: diagnois
Joint aspiration + synovial fuild analysis
| -> negatively bifringent crystals under polarised light microscopy
76
Gout: management of acute gout
NSAIDs naproxen (+PPI)
Colchicine if NSAIDs contraindicated/not tolerated
Intra-articular CS (NSAIDs, Colchicine c/indicated, eg renal impairment)
Paracentamol +/- codeine- pain relief
77
Gout: management, prevention of acute atacks
Lifestyle changes (weight loss, reduce purines in diet, alcohol, regular exercise and stop smoking)
Allopurinol 1-2 weeks after acute phase
Febuxostat if allopurinol c/indicated
78
Pseudogout/CPPD: define
inflammatory arthritis
calcium purophosphate cristals deposition in the joint space
coexist with OA
most common cause of chondrocalcinosis
79
CPPD: pathophysiology
calcium pyrophosphate formed extracellularly
inorganis pyrophosphate reacts with calcium
-> deposits in cartilage (fibrocartilage and hyaline cartilage)
-> inflammation
-> chondrocalcinosis
80
CPPD: risk factors
```
age >40
OA
Hypothyrodism
Hyperparathyrodism
Trauma/injury
Diuretics
Acromegaly
Hypomangesaemia
Wilson's disease
Haemochromatosis
```
81
CPPD: clinical features
asymptomatic, accidental finding on X-ray
Red flag: acute tender, red, hot, swollen joint -> acute CPPD (pseudogout)
severe pain and swelling takes 6-24 wks to reach maximum
82
CPPD: investgations
bloods: WCC, ESR, CRP increased in acute attacks
X-ray: chondocalcinosis, OA changes (LOSS)
USS: CPP deposiion
Aspirate -> positive birefingement rhomboid- shaped crystals under polarized light microscopy
83
CPPD management
```
treat underlying cause
rest, ice packs -> gradual mobilisation
NSAIDs
colchicine
CS injections
```
84
Gout and CPPD comparison: aspirate and joints affected
aspirate: Gout- negatively birefringent cristals, CPPD- positively
joints affected: Gout: usually small joins, CPPD: lage joints
85
Vasculitis: define
group of heterogenus diseases
inflammation of blood vessels
-> compromise of the vascular lumen
-> ischaemia
86
Vasculitis: pathophysiology
```
usually primary
-> idiopathic autoimmune disorders
secondary
- infection (hep B&C, TB, syphilis)
- connective tissue disease (e.g. SLE)
- drugs (sulphonamides, beta-lactams, quinolones, hydralazine, propylthiouracil)
```
87
Vasculitis: Takayasu's arteritis
```
large arteries
granulomatous inflammation
large arteries
arm, head, neck, and heart (aortic arch syndrome)
young women
-> arm claudication
-> >10mmHg variation between arms
```
88
Vasculitis: Polyarteritis nodosa
medium arteries
necrotizing arteritis
w/o glomerulonephritis
-> aneurysm, thrombosis and infarction
89
Vasculitis: Wegner's granulomatosis
```
small arteries
necrotizing vasculitis
usually w/ granulomatous inflammation
c-ANCA- specific for WG
respiratory tract (nasal obst, epistaxis, sceritis, snusitis, recurrent otitis media, sublotic stenosis -> hoarsenes of voice, single cavitating nodue on rediological ix)
glomerulonephitis
```
90
Vasculitis: Churg- Strauss syndrome
small arteries
eosinophil rich and necrotizing granulomatous inflammation
associated with asthma and eosinophilia
mesenteric arteritis -> abdo pain
91
Vasculitis: anti-GBM disease
anti- glomerular basement membrane disease
small vessel
glomerular capillaries, pulmonary capillaties or both
w/ deposition of anti-basement membrane autoantibodies
part of Goodpasture's syndrome (anti-GBM antibodies, glomerulonephiris and pulmonary haemorrhage)
92
Vasculitis: Henoch-Schonlein purpura
```
small vessel
IgA dominant immune deposition
small vessle
skin, GI tract
frequently causes arthritis
-> palpable purpuric rash over buttock/lower leg
-> abdo pain
-> asymmetrical arthiris
-> follows URTI
```
93
Vasculitis: Behcet's syndrome
variable vessel vasculitis
almost any organ can be affected
common in those of Turkish descent, very rare in UK
-> oral/ genital ulceration, ocular involvement, erythema nodosum, papulopustular rash, arthritis (mono- or oligo-), diarrhoea, anorexia, encephalitis, confusion, cranial nerve palsy
skin pathergy test- very specific
94
Vasculitis : investigations
```
Bloods: FBC, U&E, creatine, LFTs
Immunology (c-Anca-> WG, p-Anca -> Churg-Strauss syndrome)
Urine dipstick (glomerulonephritis)
CXR- lung involvement
ECG - cardiac abnormalities
Angiogram (aneurysm, stenosis and post stenotic dilatations in Takayasu's and Polyarteritic nodosa
Biopsy
Skin pathergy in Behcet's syndrome
```
95
Vasculitis: management
induce remission: high dose steroids and/or cyclophosphamide
Then: steroids grad. reduced to low dose and methotrexate or azathioprine started instead
96
Vasculitis: Giat cell arteritis
temporal artery vasculitis
| usually extra- cranial branches of carotid a.
97
Giant cell arteritis: pathophysiology
autoimmune disorder
unknown environmental trigger
mononuclear infiltrates or granulomas wth multinucleated giant cells
inflammatory cells infiltrate
-> metalloproteases and ROS stimulation
-> blood vessel wall extracellular matrix damage
98
Giant cell arteritis: risk factors
polymyalgia rheumatica
age >50
females
caucasians
99
Giant cell arteritis: clinical features
Red flags:
abrupt onset headache (unilateral, temporal area)
scalp pain
temporal a tenderness and swelling
visual symptoms
-amaurosis fugax (transient loss of vision in one eye)
jaw and tongue claudication
100
Giant cell arteritis: investigations
bloods: ESR (+50mm/hr), FBC (anaemia, thrombocytosis)
Biopsy (appearance of intermittent inflammation- skip lesions or negative)
USS- halo sign: thickening of the blood vessel wall
101
Giant cell arteritis: management
high dose glucocorticoid once suspected
uncomplicated GCA: oral prednisolone
Complicated GCA (vision loss or jaw/tongue claudication): IV methylprednisolone
Tapering regimen
- prednisolone long term (gradually reducing dose)
Bone protection: bisphosphoneta and calcium/ vitamin D supplements
102
Polymyalgia rheumatica: define
Inflammatory condition causing proximal muscle pain and stiffness (shoulder and pelvic gridle)
103
Polymyalgia rheumatica: associated condition
Giant cell arteritis
104
Polymyalgia rheumatica: pathophysiology
Unknown- inflammation
Genetic predisposition, environmental factors -> increased susceptibility
HLA-DR4 association
105
Polymyalgia rheumatica: risk factors
Age >50
Female
Giant cell arteritis
Family history
106
Polymyalgia rheumatica: clinical features
```
Proximal muscle pain and stiffness:
Bilateral shoulder or thigh muscle
Aching pain 2 months +
Morning stiffness >45 mins
Age >50
```
Red flag systemic symptoms:
-> weight loss, malaise, giant cell arteritis symptoms
Corticosteroids response
107
Polymyalgia rheumatica: diagnosis
```
Proximal muscle pain and stiffness:
Bilateral shoulder or thigh muscle
Aching pain 2 months +
Morning stiffness >45 mins
Age >50
Acute phase response (raised ESR)
```
108
Polymyalgia rheumatica: investigations
Bloods:
- raised inflammatory markers (ESR, CRP, U&Es- kindney function)
- paraprotein level- to exclude multiple myeloma
- thyroid function- to exclude thyroid disease
X-ray- exclusion of non erosive joint disease
+ Giant cell arteritis suspected -> temporal artery biopsy
109
Polymyalgia rheumatica: management
prednisolone- usually clinical response within 1 week
- > inflammatory markers normalisation within 4 wks
- gradual reduction of prednisolone to mainenance for up to 1 year and then gradual reduction to stop
Steroid sparing: methotrexate or azathioprine
bisphosphonates to protect bones +/- PPI
110
Rheumatology: what does SLE stand for?
Systemic lupis erythematosus
111
SLE: define
chronic multi-systemic autoimmune diesease
| characterised y the presence of antinuclear antibodies (ANA)
112
SLE: presence of what immunological factor is characteristic?
Antinuclear antibodies (ANA)
113
SLE: who is commonly affected?
women of reproductive age
114
SLE: pathophysiology
```
genetic susceptibility (HLA DR2/3, complement levels, hormone levels)
environmental susceptibility (UV light exposure, infections, oxidative stress)
```
- > autoimmune proliferation
- hyperactive B-cells and T cell and complement activation
- defective clearance of apoptotic cells and immune complexes -> complement activation
-> autoantibody production
anti-phospholipid antibodies -> anionic phospolipids (within cell membranes) -> antiphospholipod syndrome
115
SLE: risk factors
```
females (10:1)
childbearing age
Afro-Caribbeans and Asians
Drugs
Sun exposure
family history
smoking
```
116
SLE: risk factors: drugs
```
isoniazid
phenytoin
carbamezapine
sulfasalazine
minocycline
terbinafine
```
117
SLE: clinical features/ diagnostic criteria
SOAP BRAIN MD (4+ to diagnose)
Serositis (pleirotos or pericarditis)
Oral/nasopharyneal ulcers
Arthritis 2+ peripheral joints (tenderness,swelling, effusion)
Photosensitivity (skin)
Bloods: haemolytic anaemia w.reticulocytes, leucopenia, lumphopenia, thrombocytopenia
Renal disease- proteinuria
ANA positive
Immunological disorder (anti-dsDNA, Anti-smith, antiphospholipid antibodies)
Neurological disorder (seizures, psychosis)
Malar rash
Discoid rash
118
SLE: skin conditions
Malar rash (fixed erythema over malar eminences, nasolabial folds sparing)
Discoid rash (erythematous raised patches with adherent keratotic scaling and follicular plugging )
119
SLE: manifestations
general: weight loss, fever, fatigue, aching
CNS: seizures, paralysis, psychosis
Eye: retinal exudates, conjuctivitis, blindness
Skin: alopecia, malar rash, raynaud's syndrome, photosensitivity
GI: poor appetite, D & V
Repro: menorrhagia, amenorrhoea, stillbirths
MSK: arthralgias, arthiritis, myalgias
120
SLE: bloods
```
FBC: haemolytic anaemia w/reticulocytes, leucopenia, lymphopenia, thrombocytopenia
ESR and CRP- non specific, raised
ANA antibodies +
anti-dsDNA+ highly specific
anti-Smith+ highly specific
U&E- raised in renal disease
```
121
SLE: investigations (excluding bloods)
Urinalysis- haematuria, proteinuria (renal disease)
CXR- cardiopulmonary symptoms
XR of affected joints- periarticular oseopenia
MRI- suspected CNS lupus
ECG- cardiopulmonary symptoms
Echo- pericardial invovlement
122
SLE: features on x-rays of affected joints
periarticular oseopenia
123
SLE: complications
```
atherosclerosis
hypertension
dyslipidaemia
DM
osteoporosis
avascular necrosis
permanent neurological damage
lymphoma
```
124
Antiphospholipid syndrome: association with...
SLE
125
Antiphospholipid syndrome: define
autoimmine
hypercoagulable state
caused by antiphospholipid antibodies
126
Antiphospholipid syndrome: consequences
recurrent arterial and venous thrombosis
| miscarriages
127
Antiphospholipid syndrome: clinical features
```
CLOT
Coagulation defects
Livedo reticularis
Obstetric (recurrent miscarriage)
Thrombocytopenia
```
128
Livedo reticularis: what is it and what is it associated with?
mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin
Antiphospholipid syndrome
129
Antiphospholipid syndrome: diagnosis
Clinical- arterial/venous thrombosis or miscarriages
Lab
- anti-cardiolipin antibodies
- lupus anticoagulant in plasma
130
Antiphospholipid syndrome: management
low dose aspirin or warfarin (recurrent thromboses)
131
SLE: Management
patient education
-sun exposure, smoking cessation, pregnancy planning
Analgesics/NSAIDs- arthritis
intra-articular CS injection
hydroxychloroquine (skin and joint disease)
high dose steroids
or methotrexate or mycophenolate (steroid sparing)
132
SLE: monitoring
anti-dsDNA antibody titres
| C3/4 reduction and C3a/C4a increase -> increased activity
133
Polymyositis: define
Rare autoimmune connective tissue disease
Inflammation and weakness of skeletal muscle
May involve joints, oesophagus, lungs and heart
134
Dermatomyositis: define
Polymyositis with skin involvement
| Coexists with other connective tissue disorders (e.g. SLE)
135
Polymyositis and dermatomyositis: pathophysiology
Genetic factors (HLA markers) and environmental factors (UV light, infection)
-> individual susceptibility
-> autoantibodies
-> B-cell and T-cell infiltration
-> increased pro-inflammatory cytokines
-> muscle damage via cytotoxic T cell damage
In Dermatomyositis: complement mediated damage of muscular microvasculature
-> creatine kinase released
136
Polymyositis and dermatomyositis: risk factors
```
Genetic predisposition- HLA markers
Females
Black people
Malignancy (esp DM)
UV light (DM)
Infections (DM)
```
137
Polymyositis: onset age
40-60 peak
| Rare in childhood
138
dermatomyositis: onset age
Bimodal distribution
5-15
40-60
139
Polymyositis: clinical features
Symmetrical
Proximal muscle weakness
Progressive (weeks-months)
Muscle pain
Systemic features (weight loss due to oesophageal dysmotylity)
->Aspiration pneumonia, dysphagia, dysphonia, resp. failure (respiratory muscle and pharyngeal muscle involvement)
-> pulmonary fibrosis (30%)
140
Polymyositis: pulmonary consequences
```
Respiratory & pharyngeal muscle involvement
-> aspiration pneumonia
-> dysphagia, dysphonia
-> respiratory failure
Pulmonary failure (1/3)
```
141
Dermatomyositis: clinical features
Gotton's papules over MCP, PIP and DIP joints
Gotton's sign over other extensor surfaces e.g. Elbows and knees
Heliotrope rash- violet eyelid discolouration +/- periorbital oedema
Photo sensitivity
Nail fold erythema
142
Polymyositis and dermatomyositis: investigations
Creatine kinase (good indicator of disease activity)
ESR, plasma viscosity and CRP- raised
ANA positive
Anti Mi 2 antibodies- specific for DM, only in 25%
Anti Jo1 antibodies- non specific
MRI -> muscle inflammation
Electromyography - can be normal in 15% of DM
Muscle biopsy- diagnostic (myosotis evidence)
143
Secondary cause of dermatomyositis
Malignancy
144
Polymyositis and dermatomyositis: non pharmacological management
```
sun- blocking agents
increased physical activity -> inc. muscle strength
physiotherapy
occupational therapy
SALT assessment
CK monitorning
```
145
Polymyositis and dermatomyositis: pharmacological management
prednisolone (high dose initially)
DMARDs
steroid sparing drugs if resistnat
IV immunoglobulins
hydroxyvhloroquine & tacrolimus- for skin disease
146
Sjogren's syndrome: define
autoimmune disorder
| characterised by inflammation of the salivary, lacrimal and other exocrine glands
147
Sjogren's syndrome: associated conditions
other autoimmune diseases
| usually RA, SLE or scleroderma
148
Sjogren's syndrome: pathophysiology
environmental or endogenous antigens in susceptible individuals
-> immune induced inflammatory response
lymphocytic infiltration and fibrosis of the lacrimal and salivary glands
-> xerophthalmia (dry eyes)
-> xerostomia
-> enlarged parotid glands
149
Sjorgen's syndrome: risk factors
```
Female
SLE
RA
Scleroderma
HLA markers
family history
```
150
Sjorgen's syndrome: age of onset
bimodal
30-50s
after menopause
151
Sjorgen's syndrome: clinical features
```
D
dry eyes (keratoconjunctivitis sicca)
dry mouth (xerostomia)
```
parotiD swelling
Dry: vagina, cough
Dyspareunia
Dysphagia
Systemic features: polyarthritis, vasculitis, lung, kidney and liver involvement
152
Sjorgen's syndrome: what cancer is it associated with?
non-Hodgkin's B cell lymphoma
153
Sjorgen's syndrome: investigations
Schirmer's test- quantitavely measures tears with filter paper. Positive if <5mm of paper is wet
ribonucleoproteins Ro and La- in 90% of patients
ESR and hypergammaglobulinaemia- raised
ANA and RF positive
Salivary gland or lip biopsy -> lymphocyte infiltration
Salivary gland scintigraphy- decreased salivary gland function
154
Sjorgen's syndrome; management
Dry eyes: artificial tears, opthalmic ciclosporin drops
Dry mouth: increase fluid intake, salivary substitutes, salivary substitutes, cholinergic drugs
Other: vaginal lubricants, emollients, hydroxychloroquine (arthralgia and skin symptoms)
155
Scleroderma: define
'hard skin'
autoimmune connective tissue disease
affects the skin and other organs
types: localised, systemic (if limited- CREST syndrome) or diffuse
156
Sclerodema: types
localised- usually children (Skin and subcutaneous tissue)
| systemic (if limited- CREST syndrome; diffuse)
157
Scleroderma: pathophysiology
not fully understood, 3 agreed processes:
1. immune activation -> autoimmunyty (ANA positive)
2. cytokines up regulation -> overproduction and accumulation of collagen
3. if systemic: small blood vessels inflammation (-> Raynaud's phenomenon)
158
Scleroderma: risk factors
```
family history
famale
environmental factors
- cytomegalovirus
- chemicals
- silica dust exposure (limited SSc)
```
159
Limited scleroderma: clinical features
CREST syndrome
- slow onset, skin and extremities affected
Calcinosis (under fingertips)
Raynaud's phenomenon
E-oesophageal dysmotility (dysphagia or GORD)
Sclerodactylyl (stiff fingers)
Telangiectasia
160
Diffuse scleroderma: clinical features
sudden and aggressive onset
diffuse skin oedema (itchy)
Talangectasia
+/- Raynaud's phenomenon
161
Localised scleroderma: types
morphoea
| linear
162
Morphoea localised scleroderma: clinical features
oval itchy skin patches - waxy red appearance
fingers not involved
dilated nailbed capillaries
163
Linear localised scleroderma: clinical features
thickened line of skin (knife-like scar)
on arms, legs or forehead
childhood
164
Scleroderma: general symptoms
```
Raynaud's phenomenon- esp limited
skin thickness (Starts as swelling and puffiness)
```
165
How does scleroderma affect the lugs?
pulmonary HTN- due to blood vessel damage (limited)
| interstitial lung disease- due to overproduction of collagen (diffuse)
166
How does scleroderma affect the heart?
right heart failure
| pericardial effusion `
167
How does scleroderma affect the kindeys?
renal impairment
168
Raynaud's phenomenon: define and diagnosis
primary or secondary (connective tissue disorders, like scleroderma)
transient vasospasm of the peripheral blood vessels (digits) -> hypoxia
in extreme conditions: ischaemic gangrene and digital ulcers
triggers: stress and cold
diagnosis (clinical) by colour change: white -> blue -> red
169
Scleroderma: investigations
ESR, WCC raised, Anaemia
Immunology
- ANA - postive in majority
- Anti- topoisomerase-1 (Scl 70)- ass. w/ lung fibrosis and renal disease in scleroderma
- ACA (anti- cemtromere antibody) in CREST sydrome
- Anti- RNA polymerase I and III antibody- diffuse sceroderma esp w/ kidney involvement
170
Scleroderma: management
Treat based on organ involved:
Skin- hygiene & emollients + prednisolone/methotrexate
Vascular (Raynaud's phenomenon)- vasodilators (e.g. CCB)
ILD: cyclophosphamide
171
Scleroderma and ILD management
cyclophosphamide
172
Fibromyalgia: define
Syndrome of chronic pain
Presence of hyperalgesic points at specific anatomical points
With other physical and psychological symptoms
With no identifiable organic cause
173
Fibromyalgia: pathophysiology
Poorly understood
Abnormal central na peripheral pain processing
-thought to be responsible for reduced pain threshold, hyperalgesia and allodynia
174
Fibromyalgia: risk factors
Females
Age 20-50
Physical trauma (like whiplash injuries to neck or trunk)
Psychological trauma (stress, anxiety, depression)
Viral infections
175
Fibromyalgia: clinical features
FIBRO
Fatigue (chronic)
Insomnia, irritability, IBS, irritable bladder
Blues- anxiety, depression
Rigidity- muscle and joint stiffness
Ouch- pain, tender points, paraesthesia , migraine, panic attacks
176
Fibromyalgia: tender points general location
```
Over the shoulders
Neck (front)
Sacroiliac joints
Over greater trochanter
Cubical fossa
```
11/18 for diagnosis
177
Fibromyalgia: investigations
All normal
178
Yellow flags: risk factors for developing chronic pain
Belief that pain and activity is harmful
Sickness behaviour
Withdrawal from society
Emotional problems (anxiety, low mood, stress)
Problems/dissatisfaction at work
Problems with claims (for compensation, time off work)
Overprotective family
Lack of social support
Inappropriate expectations of treatment
179
Fibromyalgia: management
Heated pool treatment
Excercise programmes
CBT
Relaxation, rehabilitation, physiology, psychological support
Tramadol, paracetamol, codeine
Antidepressants (fluoxetine and amitriptyline)
Pregabalin
180
Osteoporosis: define
Progressive systemic skeletal disorder
Low bone mass and micro-architectural deterioration of bone tissue
-> bone fragility and fracture susceptibility
Bone mineral density (BMD) > 2.5 standard deviations below young healthy adults
181
Osteoporosis: pathophysiology
1. Osteoclast > osteoblast activity
- > Decreased bone mass and incomplete bone remodelling
2. Oestrogen deficiency (e.g. Menopause)
- > increased production of RANK ligand by osteoblasts
- > increased osteoclast formation, function and survival
- > increased osteoclast activity
182
Ostoeporosis and steroid use pathophysiology
decresed osteoblastic activity
183
Primary osteoporosis: classification
Based on pattern of bone loss and common fractures
Type 1: post menopausal (increased ostoclast activity)
-> distal radius and vertebrae #
Type 2: senile (decrease oseoblast act.)
-> neck of femur #
184
Ostoeporosis: risk factors
```
SHATTERED
Steroid use/Smoking
Hypo/hyper thyrodism, hyperparathyrodism, hypercalcinuria
Age >50/ Alcohol
Thin (BMI<22)
Testosterone deficiency
Early menopause
Renal / liver failure
Erosive bone disease (RA/ myeloma)
Diabetes/ deficiency of calcium/vitamin D
```
185
Osteoporosis: bloods
```
PTH levels (high)
TFT (low/high)
Serum FSH (high), sex hormones (low), adrognes (low)
Vit D (low)
EST (high in inflammatory disease)
Bone markers (Calcium, alk phos- normal)
```
186
Osteoporosis: diagnosis
DEXA scan
- Bone mineral density of spine and hip
T sore of >2.5 below standard deviation of a young healthy adult
187
DEXA scan results interpretation
>0- BMD better than reference pop.
0 to -1 normal
-1 to -2.5 osteopenia
-2.5 or below osteoporosis
188
Osteoporosis: non pharmacological management
```
smoking cessation
alcohol reduciton
exercises (Weight bearing muscles)
diet: adequate calcium and vit D
physio
occupational therapy- safery and falls risk reduction
```
189
Osteoporosis: pharmacological management
```
bisphosphonates
denosumab
strontium ranelate
teriparatide
Raloxifene
Calcitonin
HRT
```
190
Osteoporosis: bisphosphonates MOA and example
inhibit osteoclasts -> inhibit bone reabsorption
| Alendronic acid
191
Osteoporosis: bisphosphonates side effects
GI symptoms
| oesophagitis (have to stand for 30 mins after taking to reduce risk)
192
Osteoporosis: Denosumab MOA and regime
monoclonal antibody against RANK- lignad (reduced osteoclasts production)
6 monthly injection
193
Osteoporosis: Strontium ranelate MOA (general) and regime
unknown mechanism
stimulate ostoblasts and inhibit osteoclasts
once daily in water at bedtime
194
Osteoporosis: Strotium ranelate side effects
nausea, diarrhoea
headache, dizziness
DVT
thromboembolism
195
Osteoporosis: Teriparatide MOA and regimen
parathyroid hormone analogue
intermittent exposure to parathyroid hormone
-> osteoblast activation
once daily injection into the thigh or abdomen
196
Osteoporosis: Teriparatide limitations
very expensive
| used in very severe cases
197
Osteoporosis: raloxifene MOA
selective oestrogen receptor modulator (SERM)
| - in post-menopausal women
198
Osteoporosis: fracture risk assessment
FRAX
Fracture Risk Assessment Tool
based on clinical risk factors
199
Paget's disease of bone: define
bone disease
characterised by focal increase in bone remodelling (increased osteoclast activity)
-> abnormal bone production
-> mechanically weak bone
commonly affects the pelvis, spine, skull, femur and tibia
200
Paget's disease of bone: pathophsiology and phases
genetic and environmantal factors (viral infections and mechanical stress)
Lytic phase- transient inc. osteoclast act. -> inc reabsorption (marked increase in alk phos)
Mixed- increased levels of bone turnover -> deposition of structurally abnormal bone
Sclerotic phase: chronic (late) phase, predominant osteoblast activity
201
Paget's disease of bone: risk factors
Male
Family history
Rare in Asians
202
Paget's disease:clinical features
```
Usually asymptomatic
Bone pain
Bone deformity and enlargement
Inc. temp over bone (inc. vascularity)
Pathological fractures
Secondary OA
Hearing loss and tinnitus (due to compression of vestibulocochlear nerve from skull bones)
```
203
Paget's disease: investigations/diagnosis
```
ALP increased (can check bone specific ALP if there's liver disease)
X-rays: localised enlargement, patchy cortical thickening with sclerosis and osteolysis, deformity
MTI: suspected spinal stenosis and cord compression
```
204
Paget's disease: management
```
Orthotic devices, sticks and walkers
Adequate intake of calcium and vit D
Bisphosphonates
NSAIDs and paracetamol
Osteotomy for deformities
```
205
Vitamin D deficiency consequences
Inadequate mineralisation of bone
Rickets pain children
Osteomalacia in adults
206
Pathophysiology of vitamin D deficiency in kidney failure
Failure of hydroxylation of
| 25-hydroxyvitamin D (25-OHD) to 1,25-dihydroxyvitamin D
207
Vitamin D deficiency causes
Renal disease (impaired hydoxylation of 25-OHY)
Lack of sunlight (ultraviolet B)
GI malabsorption (coeliac, CF, short bowel syndrome)
Liver disease (impaired hydroxylation of vit D)
Drugs (anticonvulsants, HAART or glucocorticosteroids)
Genetics
208
Vitamin D deficiency progressions of disease
Vit D. Deficiency
- > Reduced serum phosphate and calcium
- > Increased PTH (secondary parathyrodism)
- > Reduced mineralisation of bone
209
Vitamin D deficiency risk factors
```
Dark skin
Children / over 65 yrs
Obesity
routine covering of face and hands
Housebound
Sunscreen
```
210
Bone deformities in Rickets
```
Protruding forehead
Large head
Pigeon chest
Depressed ribs
Curved long bones
Kyphosis
Enlarged epiphysis in ankle
```
211
Osteomalacia x ray features
Psudofractures
Looser zones
Coarse trabecular
Osteopenia
212
Rickets x ray features
Methaphyseal cupping and flaring
Epiphyte also irregularities
Widening of the epiphyte all plates
213
Vitamin D deficiency management
Treat underlying condition
Adequate sun exposure
Adequate diatary intake of vitamin d (oily fish, egg yolk, milk)
Vitamin D and calcium supplements
214
Vitamin D deficiency implications
Increased risk of
T2DM
Cancers (e.g. Prostate)
Cardiovascular factors
215
Paget's disease: serious potential complication
1% -> Paget's sarcoma
