Rheumatology Flashcards
1
Q
define SLE and its epidemiology
A
chronic, multi-systemic autoimmune disease of unknown cause, characterised by presence of ANA (antinuclear) antibodies.
commonly affects women in their reproductive yrs e.g. between 15 and 45.
more common in afro-caribbeans and asians
lupus other than systemic includes drug-induced e.g. isoniazid for TB, discoid and overlap syndromes.
2
Q
factors associated with SLE development?
A
genetic e.g. HLA-DR2, and Dr3, complement levels and hormone levels, and environmental e.g. oxidative stress, infection-EBV, UV light exposure-sun can trigger disease and recurrence of symptoms after medical treatment, drugs.
smoking- linked to SLE development and disease prognosis.
3
Q
charcteristics of AI proliferation in SLE?
A
hyperactive B/Tcell activation, defective immune complex clearance and impaired tolerance
autoantibodies produced: apoptosis and self-exposure, self-recognition and cross-reactivity
4
Q
drugs which may cause drug-induced lupus?
A
phenytoin carbamazepine isoniazid sulfasalazine hydralazine OCP
reversible, and associated with anti-histone antibodies.
5
Q
The ACR has 11 criteria, for which any 4 are required in a pt to diagnose SLE. What are these criteria?
A
SOAP BRAIN MD
- serositis- either pleuritis-pleuritic pain, pleural rubs, pleural effusion, or pericarditis-ECG, pericardial rub or effusion.
- oral or NP ulcers-painless
- arthritis-non-erosive, 2 or more peripheral joints (so not axial), tender, swollen or effusion.
- photosensitivity- rash due to unusual reaction to sunlight
- bloods-haemolytic anaemia with reticulocytes or leucopenia, or lymhopenia (both on 2 or more occasions) or thrombocytopenia in absence of offending drugs.
- renal disorder-persistent proteinuria, cellular casts-red cell, Hb, granular, tubular or mixed.
- ANA +ve
- immunology- 1 of anti-dsDNA, anti-smith, antiphospholipid antibodies.
- neurological disorder-seizures or psychosis
- malar rash-fixed erythema, flat or raised, over malar eminences, spares nasolabial folds
- discoid rash-erythematous raised patches with adherent keratotic scaling and follicular plugging, atrophic scarring may occur in older lesions.
6
Q
considerations in systems review of pt with ?SLE
A
any organ system can be affected!
- MSK: gen. arthralgia with morning stiffness(signif=30mins-1hr), myalgia, small joints of hands and wrist arthritis- symmetrical, polyarticular and NON EROSIVE. deformity=Jaccoud’s arthropathy due to ligament laxity.
- mucocutaneous- oral ulcers, malar rash, alopecia, photosensitivity, nasal and vaginal ulcers, Raynaud’s.
- renal- HTN, haematuria, oedema, weight gain, hyperlipidaemia, may complain of swollen eyelids in nephrotic syndrome
- NS- headache, seizures, aseptic meningitis.
- CVS, Resp- pleuritic pain -sharp, worse on inspiration
- GI-abdo pain, N+V, diarrhoea.
non-specific symptoms= fatigue, malaise, fever, weight loss, myalgia
7
Q
blood tests to be ordered in suspected SLE?
A
FBC-assess anaemia, leucopenia, thrombocytopenia and rarely pancytopenia
ESR/plasma viscosity- elevated-inflam?
Biochemistry: Us and Es-?renal disease- raised urea, K+ (and Na+?), LFTs, CRP-NORMAL, immunology-ANA antibodies, dsDNA, smith antigen
clotting profile:APTT- may be prolonged in those with antiphosholipid antibodies (anti-cardiolipin and lupus anticoagulant)
8
Q
investigations in addition to bloods requested in suspected SLE?
A
urinalysis- haematuria, proteinuria, casts
CXR- pleural effusion- meniscus sign, homogeneous white opacification, infiltrates and cardiomegaly- indicative of pericardial effusion?
X-ray affected joints- but unlikely to show periarticular osteoenia of disease at inital presentation as takes yrs for X-ray changes to develop. Non-erosive.
USS kidneys- AKD or CKD?
ECG if CP symptoms, can exclude other causes of chest pain
echo-investigate pericardial involvement
9
Q
differential diagnoses for SLE?
A
RA
systemic sclerosis
antiphospholipid syndrome
mixed CT disease
10
Q
complications of SLE?
A
atherosclerosis HTN dyslipidaemia DM OP avascular necrosis permanent neuro. damage lymphoma
11
Q
what education must given to pts with SLE?
A
sun exposure- need total sun block
smoking cessation
prompt tment of infections
pregnancy- should be planned, drug therapy reviewed before. Oestrogen pills may exacerbate disease or thrombosis. barrier methods or POP preferred. If SLE well controlled prior to conception, signif. minimises risks assoc with pregnancy.
relapsing and remitting illness.
advise on risk of LT complications, managing other RFs e.g. for CVD- healthy diet, exercise, stop smoking, good BP control, *SLE independent RF for atherosclerosis.
12
Q
how can SLE disease activity be monitored?
A
anti-dsDNA ab titres-high in active disease
C3, C4 reduction, and C3d and C4d increase- these suggest increased activity
ESR
BP, urinalysis- casts and proteins, FBC, Us and Es, LFTs, CRP- usually normal
13
Q
pharmacological management of SLE?
A
high-dose steroids and cyclophosphamide if severe renal, cardiac or neur. involvement, or assoc systemic vasculitis
azathioprine, MTX and mycophenolate as steroid sparing
intra-artic. steroids for joint problems
hydroxychloroquine- anti-malarial with therapeutic effect in rheumatic disease, for skin and joint problems
NSAIDs for arthritis, and pleuritis and pericarditis
CVS risk reduction
bisphosphonates, Ca2+ and Vit D to combat osteoporosis?
14
Q
most sensitive and most specific autoantibodies in SLE?
A
sensitive-ANA
specific- anti-dsDNA
15
Q
what more serious condition usually coexists with polymyalgia rheumatica (PMR)?
A
giant cell arteritis
16
Q
pathogenesis of PMR?
A
cause unknown
contribution of genetic polymorphisms and environ. factors
HLA-DR4 assoc. (also assoc. in RA?)
inflammation central to pathogenesis
17
Q
symptoms of PMR?
A
morning stiffness lasting for more than 1hr
proximal pain- bilateral shoulder or thigh muscle aching pain persisting for 1 month or more (although can strike quite suddenly appearing over a week or 2?)
pain may wake pt at night, but pain and stiffness tend to improve with movement and as the day goes on.
systemic features: weight loss, low grade malaise, symptoms of GCA, appetite loss, depression/anxiety. may also have a slight fever, overwhelming tiredness and muscle pain and stiffness may seem to follow a flu-like illness.
18
Q
how is PMR diagnosis often confirmed at check up 1 wk after presentation?
A
prompt response to corticosteroids
19
Q
features of rapid diagnosis of PMR?
A
age>50yrs, duration>2wks
bilateral shoulder or pelvic girdle aching, or both
morning stiffness duration >45min
evidence of acute phase response e.g. raised CRP
20
Q
features O/E of PMR?
A
normal muscle strength at initial presentation (unlike musc le wkness seen in polymyositis)
may be muscle tenderness proximally- but not like multiple tenderness points seen in fibromyalgia.
temoral artery tenderness suggests coexisting GCA.
21
Q
red flag symptoms and signs of spinal pain?
A
aged outside of 18-55yrs
non-mechanical pain-worse at rest, due to whole body diseases-inflammation AS, ancer and infection.
thoracic pain
night pain
history of trauma
history of previous cancer
history of steroid use, IV drug abuse
systemic features e.g. fever, weight loss
widespread neurology- symptoms cannot be explained by injury to 1 nerve root.
22
Q
investigations in PMR?
A
bloods: FBC- look for anaemia as pt may be fatigued?
ESR- raised to >40mm/hr
BC: Us and Es- kidney function, CRP- raised,
serum protein electrophoresis- measure paraprotein level to exclude multiple myeloma, TFTs.
X-ray- exclude non-erosive joint disease e.g. SLE
if GCA clinically suspected, must do temporal artery biopsy
23
Q
differential diagnoses in PMR?
A
polymyositis- weakness
metabolic bone disease e.g. osteomalacia- movment hindered?
hypothyroidism- won’t be raised inflammatory markers?, no weight loss
elderly onset RA- small joint involvement?
fibromyalgia- multiple tender points, no morning stiffness as non-inflammtory
malignancy e.g. multiple myeloma- serum paraprotein electrophoresis, bence-jones proteins urinalysis- light-chain part of Abs?
24
Q
management of PMR?
A
standardised daily dose 15-20mg oral prednisolone, review in 1 wk where clinical response of >70% expected. inflammatory markers should be normalised in 4 wks.
reduce dose of prednisolone slowly for 3-6mnths, to low maintenance level sustained for 6-12mnths, then grad. reduced over nxt 6 mnths, with aim to stop.
give bisphosphonate and PPI to protect against steroids
if pt persisting on steroids, may consider MTX or azathioprine as steroid sparing, but must monitor for GCA emergence, if occurs need prednisolone 40-60mg/day depending on if eyes involved. must rule out co-existing GCA when taking a history e.g. ask about unilateral headache, scalp tenderness, TA tenderness, jaw claudication- pain on eating?, visual symptoms.
25
what drugs should be given alongside LT steroid tment in PMR?
osteoporosis prophylaxis- bisphosphonate e.g. alendronate
| GORD and gastric ulcer proph- PPI e.g. lansoprazole
26
pathophysiology of fibromyalgia?
cause poorly understood, but though to be abnormal central and peripheral processing of pain, resulting in reduced pain threshold, hyperlagesia- increased pain, and allodynia- pain from non-painful stimulus.
condition is a chronic pain syndrome with presence of hyperalgesic points, and other physical and psychological symptoms. widespread pain and absence of inflammatory symptoms e.g. improvement in pain with exercise, ?duration of morning stiffness.
27
RFs for fibromyalgia?
female
aged 20-50yrs
physical trauma e.g. whiplash type injuries to neck and trunk
psychological trauma e.g. stress, anxiety, depression.
viral infections- may occur as post-viral syndrome.
*diagnosis of exclusion
28
clinical features of fibromyalgia?
FIBRO:
fatigue (chronic)
insomnia, irritability, IBS, irritable bladder
blues-anxiety and depression
rigidity- muscle and morning stiffness
ow- widespread and chronic pain (>3mnths) and others- tender points, paraesthesia, temp changes, migraine, feeling of swollen joints, panic attacks, memory lapses, concentration defecit.
symptoms exacerbated by certain stressors
29
important to consider what in PMH and SH of ?fibromyalgia pt?
PMH- physical trauma e.g. whiplash type injury
IBS, ME, chronic headache syndrome
SH- psychological- anxiety, stress, depression.
30
features O/E fibromyalgia pt?
widespread pain, above and below waist and axial skeleton for at least 3mnths
11/18 tender points
digital palpation using thumb to assess tender points- pressure just enough to blanch examiners nail.
no swelling
normal muscle strength, ROM and reflexes.
31
results of investigations in fibromyalgia?
all normal!
32
differentials for fibromyalgia?
chronic fatigue syndrome (myalgic encephalomyelitis)
hypothyroidism- TFTs abnormal
PMR- not widespread pain, significant number of tender points to palpation and blood tests would show raised inflammatory markers, and pt would improve quickly with corticosteroids.
polymyositis- wkness
33
management of fibromyalgia pt?
MDT required, tment considering pain intensity, function, depression, fatigue and sleep disturbance.
non-pharm: heated pool tment, exercise programmes- individually tailored, includ. aerobic training and muscle strenghtening, beneficial in reducing pain LT, CBT, psycholog. support, relaxation, rehabilitation, physio.
pharm: tramadol, may consider paracetamol and weak opioids e.g. codeine, antidepressants e.g. fluoxetine (SSRI) and amitriptyline (TCA). low dose anti-depressatns can allow more slow wave sleep. SSRIs appear less helpful however, venlafaxine (SNRI) may be helpful but consider ADRs of hypo and hypertension.
pramipexole-dopamine agonist and pregabalin- GABA analogue.
34
what are yellow flag symptoms and give examples
psychosocial RFs for developing persistent chronic pain and long-term disability:
social withdrawal
low mood, anxiety, stress
financial difficulties
belief that passive rather than active tment is beneficial
belief that pain and activity are harmful
demonstration of sickness behaviour e.g. prolonged rest
problems with work, claims for compensation or time off work
overprotective family or social support lack
35
pts with what rheumatological conditions may also develop fibromyalgia?
RA
| SLE
36
what is pregabalin?
an antiepileptic drug, analogue of GABA- inhibitory NT
37
what is scleroderma?
an AI CT disease (non-inflammatory) that affects skin and other organs
2 types= localised (morphoea) and systemic sclerosis
systemic may be limited (CREST syndrome) or diffuse-sudden and aggressive onset, Raynauds not initially, diffuse skin oedema, telangiectasia.
38
pathophysiology of scleroderma?
immune system activation and development of autoimmunity, ANA +ve in 90% of those with systemic sclerosis, ANA also +ve in SLE.
cytokine upregulation contributing to overproduction and accumulation of collagen with fibrosis, causing skin and tissue hardening and contraction
systemic sclerosis extends to small blood vessels, which can cause Raynaud's, digital ulcers, renal crisis (+HTN), pulmonary HTN, and abnormalities in nail fold capillaries.
vasculopathy, NOT vasculitis, -atrophy and proliferation of tunica intima and degeneration of tunica media.
39
leading cause of mortality in pts with limited systemic sclerosis?
pulmonary HTN due to blood vessel damage
| =exertional dyspnoea, syncope and RV strain-ECG shows T wave inversion V1-V4, and tall R waves V1 and V2
40
RFs for scleroderma?
female
1st degree FH of systemic sclerosis
+ve ANA
older adults- systemic sclerosis, localised more common in children and young adults
CMV and chemicals may trigger, silica dust exposure assoc. with limited systemic sclerosis.
41
features of limited systemic sclerosis (CREST syndrome)?
slow onset, affecting skin of head and extremities-face, forearms and legs up to knee
C= calcinosis, typically underneath fingertips
R= Raynaud's, usually 1st obvious sign
E=oesophageal dysmotility- GORD or dysphagia
S=sclerodactyly- stiff fingers, prayer sign- palamr surfaces don't come together
T=telangiectasia- dilated small blood vessels
42
what to look for O/E in suspected scleroderma?
Raynauds- digits change colour from white, to blue, to red, as result of transient vasospasm of peripheral arterioles causing hypoxia. finger tip digital ulcers?
hand swelling and stiffness, worse in morning and causing reduced ROM- prayer sign?, skin pinch test for tightness
note extent of skin involvement
SC calcinosis and telangiectasia
CVS- chest auscultation for crackles of pericardial effusion, murmurs?(RHF?-result of pulmonary HTN), foot swelling?
RS-pulmonary crackles-ILD-fine bibasal inspiratory?
43
investigations in scleroderma?
bloods: FBC- us normal, though WCC may be raised, and may be anaemia of chronic disease-due to raised hepcidin
CRP not raised?
ESR may be raised
US and Es- elevated in renal impairment, and can US kidneys
immunology: ANA, anti-topoisomerase-1- lung fibrosis and renal disease in systemic sclerosis, specific for diffuse systemic sclerosis, anti-centromere ab- CREST-found almost only in limited systemic sclerosis and although increased pulm HTN risk, protection from lung fibrosis and kidney involvement, anti-RNA polymerase- diffuse scleroderma, espec. kidney involvement
PFTs-yrly in systemic sclerosis and echos, CXR-ILD-ground glass opacification?, enlarged As or RV enlargement, HRCT-ILD
Echo-raised PA pressure and RV dysfunction
barium swallow- oesophageal dysmotility
barium enema- wide mouth colonic diverticula due to large intenstine hypomotility
rpt schilling test following antibiotics-small bowel bacterial overgrowth-malabsorption, bloating, weight loss.btest for vit B12 deficiency look at excretion in urine, normalises if then give Abx which allows ileal vit B12 absorption.
44
managment of scleroderma?
symptomatic management
skin-low dose MTX or pred (if assoc. synovitis)
vasc- avoid triggers to Raynauds e.g. stress, can give vasdilators e.g. Ca2+ blockers and prostacyclin agonists-IV, give if secondary before onset of symptoms, but ADRs e.g. hypotension- dizziness
GI-PPIs, avoid food 2-3hrs before bed and caffeine, Abx if infection signs, H2 antagonsit if failure of PPIs
renal-ACEI if at risk of renal crisis-oliguria, headache, oedema, fatigue, proteinuria, microscopic haematuria, regular BP monitoring as can occur at BPs not defined as HTN but above normal for pt, careful monitoring in pregnancy
cardiac- if effusion, oral pred and close BP monit. for cardiac tamponade-cause of mechanical shock, Beck's triad-raised JVP, hypotension and muffled heart sounds.
pulm HTN-endothelin receptor antagonist, prostacyclin agonist
resp- cyclophosphamide in ILD, but increases infection risk.
45
examples of seronegative spondyloarthropathies (inflammatory arthropathies)?
psoriatic arthritis
reactive arthritis
AS
enteropathic arthritis
46
clinical features in common with the seronegative spondyloarthropathies?
-ve for RF
HLA-B27 assoc.
axial arthritis- spine and SI joints
asymmetrical large joint oligoarthritis or monoarthritis
enthesitis-inflam of tendon or ligament insertion points e.g. Achilles tendinitis
dactylitis- entire digit inflammation as result of soft tissue oedema, and tenosynovial and joint inflammation
EA manifestations e.g. IBD, iritis-inflammtion of the iris-thin contractile diaphragm for focusing light on retina.
47
patterns of joint involvement recognised in psoriatic arthritis?
```
DIP joint disease- men more, and strongly assoc. with onycholysis-sep of nail plate from nail bed
rheumatoid patt (25%)- symmetrical small joint, part. MCP, wrist and PIP, but lack nodules and -ve for RF
spondyloarthritis- isolated sacroiliitis, tyical or atypical AS
asymmetrical oligoarthritis (50%)- large joint, e.g. ankle, knee, wrist or shoulder
mutilans arthritis- destruction of small joints of digits with shortening due to osteolysis.
```
48
how does calcinosis, seen in systemic sclerosis and SLE, apear?
Generally as multiple, firm, whitish dermal papules, plaques, nodules, or subcutaneous nodules found in a distribution characteristic for the specific disorder. May be studded with a yellow-white, gritty substance. Not infrequently, the lesions spontaneously ulcerate, extruding a chalky, white material. Most lesions are asymptomatic, though some may be tender, and others may restrict joint mobility.
49
3 organ systems typically affected in presentation of Wegener's granulomatosis (granulomatosis with polyangitis)?
URT e.g. nose-epistaxis, saddle nose due to cartilage disruption, nasal septal perforation, nasal obstruction and crusting, with rhinorrhoea, hyposmia as mucosal swelling. eyes- epiphora (watering) due to involvement of NL duct and lacrimal sac, scleritis/episcleritis, sinusitis
ears-recurrent otitis media
throat- subglottic stenosis- voice hoarseness
lungs-cavitatory nodules- may be persistent cough- usually unproductive, pyrexia, haemoptysis, dyspnoea, post-obstructive infection.
kidneys- nephritic syndrome- haematuria, proteinuria, HTN, uraemia
50
what kidney disease occurs with wegener's granulomatosis?
crescenteric glomerulonephritis
51
epidemiology of wegener's granulomatosis?
M>F
middle aged, >40yrs
northern europeans, commonly presents in winter following RTI.
52
immunology classical of wegener's granulomatosis?
c-ANCA and anti-proteinase 3
53
management of wegerner's granulomatosis?
aim to induce remission- high dose corticosteroids or cyclophosphamide
gradually reduce steroid once remission achieved, and start steroid sparing agent e.g. MTX or azathioprine
maintain on these whilst being actively monitored
54
features on biopsy of wegener's granulomatosis?
granuloma
vasculitis
necrosis
55
define wegener's granulomatosis
a necrotizing small vessel vasculitis us assoc. with granulomatous inflammation of RT and glomerulonephritis, and c-ANCA and/or p-ANCA +ve.
56
clinical features of wegener's granulomatosis other than those due to URT, lung or kidney disease?
skin rash- palpable purpura
conjunctival haemorrhages
scleritis
57
investigations in wegener's granulomatosis?
```
FBC
ESR
BC: Us and Es
LFTs
CRP
immunology: ANCA espec. c-ANCA
CXR
urine dipstick
USS kidneys
CT- lungs, nose-sinuses?
endoscope nose- gold crusts?
biopsy confirmation e.g. of kidneys or lungs.
```
58
RFs for psoriatic arthritis?
```
psoriasis
age-30-55
FH- 1st degreee relative, HLA-B27 inheritence
joint or tendon trauma
HIV
caucasians
```
59
general symptoms and signs of psoriatic arthritis?
joint pain and stiffness- inflammatory, morning stiffness more than 30 mins which improves with use, recurs with prolonged rest.
dactylitis/sausage digits
enthesitis- pain, stiffness and tenderness of insertions into bone e.g. Achilles tendon, plantar fascia, epicondyles.
EA manifestationss e.g. onycholysis, nail pitting, hyperkeratosis and uveitis.
60
what criteria are used for rapid diagnosis of psoriatic arthritis?
```
CASPAR criteria: established inflammatory articular disease and 3 or more points:
current psoriasis=2
history of psoriasis (without current)=1
FH (without the above)=1
dactylitis=1
nail dystrophy=1
RF -ve=1
juxta-articular new bone formation=1
```
61
results of investigations in psoriatic arthritis?
bloods: CRP and ESR normal or raised
immunology- RF, antic CCP and ANA negative
X-rays: soft tissue swelling
DIPJ erosion and periarticular new bone formation, osteolysis and pencil in cup deformity in advanced disease.
62
differentials for psoriatic arthritis?
```
RA-symmetrical joint involvement
gout-monoarthritic, large joint espec. knee
erosive OA
reactive arthritis
sarcoid dactylitis
```
63
managements of psoriatic arthritis?
NSAIDs
intra-articular corticosteroid injection
DMARDs: MTX,ciclosporin, sulfasalazine and leflunomide-recommended, and is an antiproliferate DMARD
anti-TNF alpha- etanercept, infliximab, adalimumab, golimumab
physio
64
ADRs of methotrexate?
```
methotrexate
immunosuppression-increased infection risk
myelosuppression
mouth ulcers-GI upset
hepatotoxicity-cirrhosis
nephrotoxicity
pneumonitis
pulmonary fibrosis
pulmonary oedema
hypersensitivity
```
65
define reactive arthritis
acute aseptic arthritis, develops in response to extra-articular infection, often from GIT or genitourinary tract.
seronegative spondyloarthropathy
66
classic presentation of reactive arthritis?
asymmetrical oligoarthritis, usually in lower limbs
67
key GI bacteria implicated in reactive arthritis?
salmonella
campylobacter
shigella
yersinia
68
key GU bacteria implicated in reactive arthritis?
chlamydia trachomatis
69
pathophysiology of reactive arthritis?
infectious trigger in genetically susceptible individuals
immune activation and cross-reactivity with self-antigens causing acute inflammation in affected joint and other tissues 2-6wks post initial infection
inflammation also of enthesis, GI tract, skin, axial skeleton, mucous membranes and eyes
HLA-B27- often +ve, and strong RF for disease severity and chronicity
70
RFs for reactive arthritis?
```
infection-GI or GU
male
aged 20-40
caucasian
HLA-B27
```
71
clinical features of reactive arthritis?
acute, asymmetrical large joint arthritis e.g. knee and ankles, 2-6wks post initial infection- may be malaise, fever and fatigue
enthesitis
conjunctivitis- bilateral and painful, anterior uveitis-unilateral
dactylitis-1 or more toes
urethritis and circinate balanitis- ulcers and vesicles surrounding glans penis
lower back pain- sacroiliitis and spondylitis
mouth ulcers
nail dystrophy and keratoderma blennorrhagica
reiter's syndrome- triad of reactive arthritis, conjunctivitis and urethritis.
72
investigations in reactive arthritis?
bloods: raised CRP, ESR, leucocytosis, thrombocytosis
ANA, RF and anti-CCP negative
HLA-B27 positive
X-ray: normal in early stages. marginal erosions, plantar spurs, sacroiliitis, and asymmetrical syndesmophytes in chronic cases.
joint aspirate- rule out crystal arthritis or septic, fluid sterile and cloudy with high WCC.
stool, throat or urine culture-identify cause
serology-chlamydia
MRI- asymmetrical sacroiliitis and enthesitis in chronic stage
73
management of reactive arthritis?
rest and splint joint, consider physio
NSAIDs
corticosteroids-oral or topical, intrarticular
DMARDs if synovitis for >6mnths
Abx-tetracyclines for urethritis caused by chlamydia
74
how is it determined if a pt is benefiting from tment in RA?
reduction in swelling
reduction in morning stiffness
improvements in blood results, inflam markers
*DAS in pts on biologics
75
Give 3 conditions in which Sjogrens occurs secondarily.
RA
SLE
Scleroderma
76
Define Sjögren's syndrome
AI disorder of unknown cause characterised by salivary and lacrimal gland inflammation (and other exocrine glands).
77
Pathophysiology of Sjögren's syndrome?
Immune induced Inflammatory response to environmental or endogenous antigens occurs in susceptible people.
Particular lymphocytic infiltration and gland fibrosis producing dry eye-xerophthalmia, xerostomia and partoid gland enlargement.
Close link between primary Sjogrens and SLE so primary Sjogrens pathogenesis is likely to be similar to lupus.
78
RFs for Sjogren's?
```
female
age 30-50 yrs and after menopause
RA
SLE
scleroderma
FH
HLA class II markers
```
79
clinical features of sjogren's?
D's: dry eyes-keratoconjunctivitis sicca
dry mouth-xerostomia
parotid swelling
vaginal dryness and dyspareunia, dry cough and dysphagia
```
systemic features: polyarthritis
arthralgia- rather than swelling that occurs with inflammatory arthropathies e.g. SLE, RA and psoriatic
Raynaud's
lymphadenopathy
vasculitis
lung, kidney and liver involvement
peripheral neuropathy
myositis
fatigue
```
80
which disease are pts with sjogren's at an increased risk of?
non-Hodgkin's B-cell lymphoma
81
what may be found O/E of pt with sjogren's?
eyes: dilatation of conjunctival vessels, corneal lesions, pull down lower eyelid to assess tear pool, blepharitis-edges of eyelids red and swollen, may be present.
mouth: dry, wooden tongue depressor may stick to tongue, oral candidiasis, dental caries, enlarged SM glands, bilateral enlargement of parotids.
features of other AI diseases e.g. SLE, RA and scleroderma.
82
investigations in sjogren's?
bloods: raised ESR/plasma viscosity as high Igs-hypergammaglobulinaemia
immunology: Abs to ribonuceloproteins-anti-Ro and anti-La, +ve ANA and RF
schirmer's test- filter paper placed in lower conjunctival sac, +ve test if after 5 mins, less than 5mm of paper wetted.
salivary gland or lip biopsy-lymphocyte infiltration
lissamine green test and rose Bengal staining- keratitis
S.gland scintigraphy- reduced gland function
parotid sialography- gross distortion of normal pattern of ductules, and signif. retention of contrast.
83
differentials for sjogren's?
```
RA
SLE
scleroderma
sarcoidosis
salivary gland tumour
```
84
management of sjogren's?
manage clinical features:
dry eyes- artificial tears, opthalmic ciclosporin, humidifiers, advise pts to take regular breaks while reading.
dry mouth- drink plenty, salivary substitutes, cholinergic drugs e.g. pilocarpine and cevimeline.
vaginal lubricants
emollients- for dry skin
hydroxychloroquine- for arthralgia and skin symptoms
85
what can be used to assess systemic involvement in primary sjogren's?
the systemic clinical activity index (SCAI)
| analyses factors such as fatigue, MSK involvement and Raynaud's.
86
causes of Raynaud's?
primary (idiopathic)- most common
| and secondary e.g. in RA, SLE, Sjogren's, scleroderma, malignancy-lymphoma, vasculitis.
87
how does gout develop?
gout progresses from an asymptomatic hyperuricaemia to being symptomatic when urate crystals are deposited in the synovial fluid of joints, causing an acute inflammtory response.
after an acute gout attack, a pt is asymptomatic before the next attack, and if hyperuricaemia remians untreated, chronic symptoms can occur.
urate crystals are a purine product. Metabolism produces xanthines which are converted to urate via xanthine oxidase-inhibited by allopurinol.
urate can build up due to impaired renal excretion, overproduction of uric acid and/or by overconsumption of purine-rich foods meteabolised to urate.
88
crystals in gout?
monosodium urate
89
crystals in pseudogout?
calcium pyrophosphate
90
cytokine pivotal in the acute inflammtory response of gout?
IL-1
91
gout RFs?
hyperuricaemia
male-oestrogen is strongly protective*
middle aged
diet-meat espec. red and seafood espec. shellfish
alcohol- metabolised to ketones that compete with urate for renal excretion, AND increases gout risk through dehydration allowing urate crystal precipitation.
drugs- thiazide and loop diuretics, aspirin, ciclosporin, laxatives.
CRF-can't excrete urate
obestity, HTN, FH, CHD and DM also all increase risk.
92
clinical features of gout?
acute gout suggested by a single peripheral joint in excruciating pain (often nocturnal), red, hot and swollen.
1st MTP-most common joint affected=podagra. Mid-tarsal joints, hand, knee and elbow can also be affected.
chronic gout suggested by polyarthritis, tophi-nodular SC deposition of uric acid crystals, fever and malaise.
93
key qns to ask pt with suspected gout?
```
1st time? Onset and duration? Painful when socks worn? Night attacks?-painful with bed covers?
FH of gout/other arthritic conditions?
PMH: DM, HTN or kidney problems?
DH: water tablet?
recent tests, including dye injection?
ever been told serum urate levels high?
diet?-red meat, seafood?
alcohol?
```
94
gout investigations?
joint aspiration and synovial fluid analysis- polarised light microscopy shows negatively birefringent MSU crystals.
serum urate measurement- often elevated, but not always-urate has moved into joints and inflammtion reduces urate.
radiographs- soft tissue swelling early, and possibly punched-out erosions well demarcated later.
95
differentials in gout?
septic arthritis
pseudogout
acute OA flare
cellulitis
96
acute gout management?
NSAIDs
colchicine if NSAIDs CI or ineffective
corticosteroids-short course oral if NSAIDs and colchicine not used. Can give intra-articular if no more than 2 joitns affected.
paracetamol for analgesia
97
gout prevention management?
reduce body weight, reduce consumption of high purine foods, reduce alcohol, take regular exercise, stop smoking
allopurinol- start 1-2wks after inflammation settled and titrate dose until uric acid serum level less than 300 micromol/L. Co-prescribe NSAID or colchicine low dose for at least 1 mnth (possibly up to 3) to prevent acute attack.
febuxostat-2nd line if allopurinol CI. or anakinra-IL-1 antagonist.
98
ADRs with allopurinol?**
Stevens-Johnson syndrome
hypersensitivity
drug interaction with azathioprine-pancytopenia, due to allopurinol inhibition of xanthine oxidase involved in inactivation of active azathioprine metabolite 6-mercaptopurine.
99
acronym for steroid ADRs?
```
CUSHINGOIDFAM:
cushing's syndrome, cataracts
ulcer-peptic
skin-striae, bruising,thinning
HTN,hyperglycaemia
infection
necrosis
growth restriction
obesity (central), osteoporosis
immunosuppression
diabetes
fluid retention
acute pancreatitis
myopathy
```
100
pathophysiology of giant cell arteritis (GCA) (temporal arteritis most commonly)?
AI reaction against arterial wall (large arteries) in response to an environmental trigger, can affect any branch of aorta (assoc. with thoracic aortic aneurysms).
inflammatory cells stimulate metalloprotease release and ROS, which damage ECM of b.vessel wall.
101
characteristic biospy finding in giant cell arteritis?
granulomas with multinucleated giant cells
*but can have skip lesions producing a negative biospy.
102
RFs for giant cell arteritis?
age-pts over age of 50yrs
gender-female
ethnicity-caucasian
PMR-50% of GCA pts have PMR
103
giant cell arteritis clinical features?
abrupt onset headache, usually unilateral in temporal area, and worse at night
scalp tenderness
temporal artery tenderness and swelling, or decreased pulsation
jaw and tongue claudication-painful jaw on chewing
visual symptoms due to opthalmic artery (from ICA) involvement:
amaurosis fugax-transient loss of vision in 1 eye
blurring and diplopia
partial or complete loss of vision
systemic features of PMR e.g. fatigue, fever, weight loss, muscle aching and pain
104
appearance O/E of eye in GCA?
ophthalmoscope may reveal pale optic disc assoc with severe visual acuity loss
slit-lamp exam may be required
105
results of investigations in GCA?
blds: increase ESR- 50mm/hr or more
FBC-normochromic normocytic anaemia, thrombocytosis.
imaging: USS may reveal thickening of affected blood vessel wall (halo sign)
biospy: intermittent inflammation- giant cell granulomas
should rpt biospy at different sites due to presence of skip lesions.
106
differentials for GCA?
tension headache
migraine
trigeminal neuralgia
107
management of GCA?
high dose corticosteroids- if uncomplicated, start oral pred 40-60mg daily, if complicated- visual loss or history of amaurosis fugax, jaw/tongue claudication then IV methylprednisolone 500mg-1g daily for 3 days, if established visual loss then trial IV methylprednisolone and then at least 60mg oral pred as a starting dose.
then tapering regimen of steroids- 40-60mg pred for 4 wks, then reduce dose by 10mg until 20mg every 2 wks, then by 2.5mg every 2-4 wks to 10mg, then by 1mg every 1-2 mnths.
so 2 yrs of steroids
must give OP prophylaxis- bisphosphonate and Ca2+/Vit D supplementation.
low-dose aspirin (75mg daily) may be recommended to reduce risk of thrombus formation and subsequent visual loss and strokes.
108
define polymyositis and dermatomyositis
AI CT diseases characterised by inflammtion and weakness of skeletal muscle
PM can affect joints, oesophagus, lungs, heart and extension to skin-dermatomyositis.
DM may coexist with other CT disorders e.g. SLE.
109
factors involved in polymyositis and dermatomyositis disease processes?
genetic-HLA markers, and environemtnal-infection and UV light, thought to contribute.
PM- muscle damage predominantly result of cytotoxic T cell damage
DM- muscle damage from complement mediated damage of intra-muscular microvasculature.
110
RFs for poly and dermatomyositis?
age: DM- children and 40-60yrs, PM-40-60yrs
female
black people
HLA subtypes
malignancy-DM may occur secondary to
UV light-DM rash often in sun-exposed areas, may be photosensitivity
infections
111
how is PM diagnosis confirmed?
muscle biopsy
112
clinical features of polymyositis?
muscle pain
insidious, progressive, symmetrical proximal muscle weakness (wks-mnths), difficult walking up stairs or rising from chair
fever, fatigue, weight loss as oesophageal dysmotility
aspiration pneumonia, dysphagia, dysphonia, resp failure
pulmonary fibrosis
113
clinical features of dermatomyositis?
heliotrope rash-violet discolouration of eyelids, possibly with periorbital oedema
gottron's papules-scaly, erythematous eruptions part. over extensor surfaces of MCP, PIP and DIPJs, may be macular erythema (no scaly eruption) in other extensor areas-gottron's sign.
photosensitivity
nail-fold erythema
reddish or blueish-purple patches on sun-exposed areas, may be telangiectasia, rash may be symptomless, burning or itchy
114
features O/E of polymyositis pt?
prox muscle wkness and atrophy
difficult rising from sitting
forced flexion of neck weak
muscles tender on palpation
115
investigations in PM and DM?
blds: CK high
other enzymes e.g. LDH may be high
ESR, CRP and plasma viscosity may be raised
auto-Abs: ANA, anti-mi-2 in DM, anti-jo-1 in PM- assoc. with ILD, Raynauds and arthritis.
MRI-muscle inflammation
EMG
muscle biopsy
116
differentials in PM and DM?
drug induced myopathy e.g. statins
mixed CTD
SLE
hereditary NM diseases
117
non-pharmacological management of PM and DM?
sun-blocking agents
exercise and physio to maintain muscular strength
evaluation of swallowing, may need sppech adn alnguage therapist
monitor CK
screen for malignancy in DM e.g. USS abdo, CT body, myeloma screen, LN biopsy, PSA
118
pharamcological tment of DM and PM?
high dose pred 60-80 mg over 24 hrs, reduce dose gradually based on CK levels
DMARDs and immunosuppressants e.g. azathioprine, MTX and ciclosporin in early resistant cases
IV Igs can help
hydroxychloroquine and tacrolimus can help skin disease
119
Drug NOT to be administered with MTX?
trimethoprim
both folic acid antagonists, would cause significant BM suppression
120
Drug NOT to be administered with azathioprine?
allopurinol
both purine antagonists, would cause significant BM suppression
121
why would a blood test NOT be effective in deciding if the relative of a pt with lupus has lupus themselves?
ANA often increased in relatives of pts with rheumatic diseases, despite not having the disease themselves
must do thorough clinical history and examination of the individual.
122
lesions that occur in ankylosing spondylitis?
early lesions include subchondral granulation tissue which erodes the joint and is gradually replaced by fibrocartilage and then ossification. This happens in ligamentous and capsular attachment sites to bone (enthesitis). Later on, outer layer of annulus fibrosis starts to calcify, creating bony bridge between vertebral bodies (syndesmophytes.) These may then fuse with vertebral body above, causing ankylosis.
123
AS RFs?
male
peak age between 17 and 35
HLA-B27 gene- carried by 90% of AS pts
124
AS clinical features?
- dull back pain radiating from SIJs to hips/buttocks and stiffness >6mnths. Worse at night and in early morning, improved by exercise and worsened by rest.
- reduced lumbar spine motion, and globally reduced cervical spine m.ments
- lumbar lordosis loss
- reduced chest expansion due to progressive loss of spinal movements
- thoracic kyphosis and neck hyperextension (question mark posture)- uncommon, occurs in progressive disease.
- peripheral synovitis, typically asymmetrical oligoarthritis, most commonly affecting hip and knee.
- extra-articular features-7As.
125
extra-articular features of AS?
```
atlanto-axial subluxation
apical lung fibrosis
anterior uveitis
aortic incompetence
AV node block
Achilles tendinitis
Amyloidosis
```
126
how can spinal flexion in AS be tested?
Schober's test:
inferior mark at level of PSISs drawn, and 10cm segment above this point marked on pt's back.
increase in distance on max forward spinal flexion with locked knees is measured.
distance should increase to 13.5-15cm at least in healthy adults.
127
differentials for AS?
```
mechanical back pain
other seronegative spondyloarthropathies
degenerative lumbar or cervical spondylosis
trauma
infection
neoplasm
```
128
investigations in AS?
blds: FBC normal, increase CRP and ESR in active disease, RF and ANA negative, HLA-B27 +ve
X-ray: sacroiliitis grade 2 or more bilaterally or 3 or 4 unilaterally, early on: bone erosions, SIJ widening, VBs square with shiny corners-Romanus lesions, late: ossification of L.ligaments of spine producing bamboo spine.
MRI- can identify early sacroiliitis, and early spinal inflammatory changes
USS- help in enthesitis diagnosis
129
AS management?
exercise and physio to strengthen muscle and provide better stability
NSAIDs-1st line for pain and stiffness, may slow rad. progression
other analgesics e.g. codeine for pain
local corticosteroids can temporarily relieve pain
anti-TNF alpha- adalimumab, etanercept or golimumab if persistently high disease activity or failure of NSAIDs
surgery-hip replacements
130
how can disease activity in AS be assessed?
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)- ask 6 qns related to 5 major AS symptoms: fatigue, spinal pain, arthralgia, enthesitis and morning stiffness.
131
why do pts take steroids on a morning?
can cause insomnia
and adrenal insufficiency less at this time
132
symptoms of iritis (anterior uveitis)?
ocular pain
photophobia
cloudy vision
133
signs of iritis?
red eye, espec. adjacent to iris
eye may look normal
need slit lamp exam of anterior chamber to see WBC and protein precipitates
134
causes of iritis?
HLA-B27 arthritis e.g. psoriatic, AS, reactive
Crohn's/UC
juvenile idiopathic arthritis
infections
135
tment of iritis?
topical steroids (non infective cases)
136
causes of keratoconjunctivitis sicca (dry eye)-conjunctival and corneal punctate erosions?
RA
| Sjogren's
137
symptoms and signs of dry eye?
foreign body sensation
dryness
pain
138
how can keratoconjunctivits sicca be investigated?
schirmer's tear test
139
tment of dry eye?
tear replacement
140
MOA of colchicine in gout?
anti-inflammatory
thought to inhibit migration of granulocytes into the inflamed area, reducing release of lactic acid and proinflammatory enzymes that occurs during phagocytosis and breaks the cycle that leads to the inflammatory response.
141
microstomia is a feature of which rheumatological disease?
systemic sclerosis
142
what is the acute phase response?
occurs as result of increase in IL-6 produced by macrophages and adipocytes in response to acute and chronic inflammatory conditions, and this triggers CRP and fibrinogen prod. by liver.
143
role of CRP?
acute phase protein
| activates classical complement pathway, promoting phagocytosis
144
what are rouleaux?
stacks of rbc which stick together due to high proportion of fibrinogen in blood in an inflammatory process
found in lymphoproliferative disease and in high levels of inflammation.
145
RA RFs?
```
female before menopause
age 20-40yrs
smoking, infection, diet, hormonal
FH
genetic- HLA-DR4 and DR1
```
146
RA clinical features?
```
morning stiffness >1hr
symmetrical joint pain
swollen joints
small joints of hand, wrist and feet
quick onest- wks-mnths
```
hands: MCP, PIP, wrist swelling
boutonniere deformity- DIPJ hyperextension, PIPIJ flexion, swan neck deformity- DIPJ flexion, hyperextension of PIPJ, Z-thumb- hyperextension of IPJ, fixed flexion and subluxation of MCPJ, ulnar deviation- subluxation of proximal phalanges towards ulnar side.
147
EA manifestations of RA?
```
rheumatoid nodules
dry eye- keratoconjunctivitis sicca, episcleritis and scleritis
pulmonary fibrosis, pleural effusion
atherosclerosis, myocarditis
anaemia of chronic disease
OP
vasculitic skin rash
hypersplenism-plus neutropenia and RA=felty's syndrome
lymphadenopathy
amyloidosis
```
148
RA differentials?
psoratic arthritis
SLE
reactive arthritis
PMR
149
results of blds in RA?
normocytic normochromic anaemia of chronic disease, increase serum ferritin, thrombocytosis
LFTs-can be deranged? usually normally, as are Us and Es
RF, anti-CCP raised, and CRP and ESR raised
150
components of DAS28?
assesses tenderness and swelling at 28 joints, ESR and patients' self-reported disease severity to calculate disease activity.
>5.1= high activity
3.2-5.1=moderate
1.2= moderate or good response if score at end point is below 3.2, and 0.6 or less is poor response if score above 3.2 at end point.
151
which joints are examined for tenderness and swelling for DAS28 calculation?
```
the 10 MCPJs
the 8 PIPJs of fingers
the 2 IPJs of thumbs
2 wrist joints
2 elbow joints
2 shoulder joints
2 knee joints
```
152
sulfasalazine ADRs?
```
GI upset- N and V, abdo pain
myelosuppression
hepatitis
rash
reversible azoospermia
```
153
give 2 ways of monitoring response to tment in RA?
DAS28
| CRP
154
clinical features of osteomalacia?
bone pain and tenderness- part. in back, pelvis, and long bones of leg
pathological fractures, espec. femoral neck
proximal myopathy causing proximal weakness and possibly waddling gait
signs of hypocalcaemia- paraesthesia, cramps, seizures
155
RFs for Vit D deficiency?
```
children and those >65yrs
infants exclusively breastfed
dark skin- afro-caribbean, middle eastern and south asians
obesity- BMI>30- fat sequesters Vit D
routine covering of face and hands
housebound
sunscreen
pregnancy- multiple, short interval
```
156
disease involving PIPJs and DIPJs?
OA: more commonly DIP than PIP, bony swelling- Heberden's nodes DIP, and Bouchard's nodes PIP
RA: more commonly PIP, swelling and tenderness, usually symmetrical, alongside swollen and tender MCPJs.
spondyloarthropathy e.g. psoriatic or reactive arthritis: similar pres. to RA but usually asymmetrical, PA can affect both PIJ and DIJ but characteristically affects DIJ. but more common presentation of these is in large joints with an asymmetrical oligoarthritis.
157
causes of dactylitis?
spondyloarthropathy e.g. psoriatic arthritis
sickle cell anaemia
TB
sarcoidosis
158
differentials for thumb base pain?
1st CMC in OA, exam- bony swellings of the joint
De Quervain's tenosynovitis- assoc with chronic overuse such as in jobs and hobbies involving repetitive hand and wrist motions. inflammation of 1st extensor compartment of wrist.
159
causes of Vit D deficiency?
lack of sunlight
renal disease
liver disease
GI malabsorption- coeliac disease, short bowel syndrome, cystic fibrosis
genetic causes
drugs- anticonvulsants, glucocorticoids, HAART, cholestyramine, rifampicin
160
result of blood tests in osteomalacia?
```
reduced 25hydroxyVitD (less than 25nmol/L)
normal or low Ca2+
increase PTH
reduced fasting phosphate
normal or increased ALP
```
161
appearance of osteomalacia on X-ray?
pseudofractures or looser zones- low-density bands extending from cortex inwards in the shafts of long bones.
osteopenia
coarse trabeculae
162
management of osteomalacia?
treat underlying cause
adequate sun exposure
adequate Vit D dietary intake- oily fish/cod liver oil, egg yolk, milk
daily Vit D and Ca2+ tablets-Adcal D3
supplementation: adults- 10,000 IU calciferol daily or 60,000 wkly for 8-12 wks, then 1000-2000 daily maintenance.
if severe malabsorption, give IM calciferol 300 000 IU mnthly for 3 mnths, then yrly maintenance doses.
163
adverse health risk assoc. with Vit D deficency?
type 2 DM
several cancers e.g. prostate
CVD
164
osteoporosis is characterised by what bone mineral density values?
those reduced by more than 2.5 standard deviations below that observed in young healthy adults (T score)
165
commonest OP cause?
oestrogen deficiency post menopause
166
how is OP classified?
primary and secondary- to hormonal, nutritional, drug related or inherited
primary- type 1=post menopausal, distal radius and vertebrae commonly fractures, type 2= senile, age-related, NOF #s more common.
167
RFs for OP?
```
SHATTERED
steroids, smoking
hyper/hypo thyroidism, hyperparathyrpoidism, hypercalcinuria
age>50, alcohol
thin-BMI less than 22
testosterone deficiency
early menopause
renal or liver failure
erosive bone disease e.g. RA, myeloma
deficiency of Ca2+ and/or Vit D, diabetes
```
168
how might a pt with OP affecting spine present?
height loss
kyphosis
resp difficulty
back pain
all may occur if vertebral fracture
169
results of blds in OP?
```
Ca2+ and ALP usually normal
reduced Vit D- deficiency?
raised ESR- inflam- RA or myeloma?
increase serum FSH, decrease sex hormones and androgens- ?deficiency or menopause
TFTs
increase PTH- hyperparathyroidism?
```
170
what does a Z score of less than -1.5 indicate in OP?
raises concern of factors other than ageing contributing to OP
171
why is strontium ranelate, despite its dual action, of limited use in OP?
risk of DVT and thromboembolism
172
tment, other than bisphosphonates for OP?
denosumab- monoclonal Ab against RANKL- produced by osteoblasts and increases osteoclast activity
strontium ranelate
teriparatide-analogue of PTH as intermittent PTH exposure activates osteoblasts more than osteoclasts
raloxifen, calcitonin, HRT
173
define seronegative arthritis?
arthritis not associated with rheumatoid factor production
174
why might malabsorption be a feature of systemic sclerosis?
bacterial overgrowth in small bowel
may present as macrocytic anaemia with vitB12 deficiency, with subsequent abnormal Schilling test and early peak in hydrogen with hydrogen breath test.
175
presentation of behcet's disease?
this is a systemic vasculitis of unknown cause
oral ulceration
genital ulceration
anterior and posterior uveitis or retinal vascular lesions
erythema nodosum or papulopustular rash (cutaneous lesions)
mon or oligo arthritis
GI features e.g. diarrhoea and anorexia
neurological features includ encephalitis, confusion or cranial nerve palsy
176
differences between anterior uveitis (iritis) and episcleritis?
iritis-red eye, painful, severe photophobia, clouding ov vision-haze in front of iris
episcleritis-localised red eye with superficial vessel dilatation, mild pain, no visual loss or light sensitivity, hx of recurrent episodes, 1 drop of phenylephrine causes lesion blanching-based on adrenaline, vasoconstrictor.
also scleritis assoc. with RA and SLE- localised area of dark red, dilated superficial and deep vessel on sclera with aching pain an tenderness.
177
most specific test for limited systemic sclerosis?
anti centromere antibodies
