Rheumatology Flashcards
define SLE and its epidemiology
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.
factors associated with SLE development?
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.
charcteristics of AI proliferation in SLE?
hyperactive B/Tcell activation, defective immune complex clearance and impaired tolerance
autoantibodies produced: apoptosis and self-exposure, self-recognition and cross-reactivity
drugs which may cause drug-induced lupus?
phenytoin carbamazepine isoniazid sulfasalazine hydralazine OCP
reversible, and associated with anti-histone antibodies.
The ACR has 11 criteria, for which any 4 are required in a pt to diagnose SLE. What are these criteria?
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.
considerations in systems review of pt with ?SLE
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
blood tests to be ordered in suspected SLE?
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)
investigations in addition to bloods requested in suspected SLE?
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
differential diagnoses for SLE?
RA
systemic sclerosis
antiphospholipid syndrome
mixed CT disease
complications of SLE?
atherosclerosis HTN dyslipidaemia DM OP avascular necrosis permanent neuro. damage lymphoma
what education must given to pts with SLE?
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.
how can SLE disease activity be monitored?
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
pharmacological management of SLE?
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?
most sensitive and most specific autoantibodies in SLE?
sensitive-ANA
specific- anti-dsDNA
what more serious condition usually coexists with polymyalgia rheumatica (PMR)?
giant cell arteritis
pathogenesis of PMR?
cause unknown
contribution of genetic polymorphisms and environ. factors
HLA-DR4 assoc. (also assoc. in RA?)
inflammation central to pathogenesis
symptoms of PMR?
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.
how is PMR diagnosis often confirmed at check up 1 wk after presentation?
prompt response to corticosteroids
features of rapid diagnosis of PMR?
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
features O/E of PMR?
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.
red flag symptoms and signs of spinal pain?
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.
investigations in PMR?
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
differential diagnoses in PMR?
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?
management of PMR?
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.
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
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.
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
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
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.
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.
results of investigations in fibromyalgia?
all normal!
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
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.
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
pts with what rheumatological conditions may also develop fibromyalgia?
RA
SLE
what is pregabalin?
an antiepileptic drug, analogue of GABA- inhibitory NT
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.
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.
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
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.
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
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?
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.
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.
examples of seronegative spondyloarthropathies (inflammatory arthropathies)?
psoriatic arthritis
reactive arthritis
AS
enteropathic arthritis
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.
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.
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.
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
what kidney disease occurs with wegener’s granulomatosis?
crescenteric glomerulonephritis
epidemiology of wegener’s granulomatosis?
M>F
middle aged, >40yrs
northern europeans, commonly presents in winter following RTI.
immunology classical of wegener’s granulomatosis?
c-ANCA and anti-proteinase 3
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
features on biopsy of wegener’s granulomatosis?
granuloma
vasculitis
necrosis
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.
clinical features of wegener’s granulomatosis other than those due to URT, lung or kidney disease?
skin rash- palpable purpura
conjunctival haemorrhages
scleritis
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.
RFs for psoriatic arthritis?
psoriasis age-30-55 FH- 1st degreee relative, HLA-B27 inheritence joint or tendon trauma HIV caucasians
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.
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
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.
differentials for psoriatic arthritis?
RA-symmetrical joint involvement gout-monoarthritic, large joint espec. knee erosive OA reactive arthritis sarcoid dactylitis
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
ADRs of methotrexate?
methotrexate immunosuppression-increased infection risk myelosuppression mouth ulcers-GI upset hepatotoxicity-cirrhosis nephrotoxicity pneumonitis pulmonary fibrosis pulmonary oedema hypersensitivity
define reactive arthritis
acute aseptic arthritis, develops in response to extra-articular infection, often from GIT or genitourinary tract.
seronegative spondyloarthropathy
classic presentation of reactive arthritis?
asymmetrical oligoarthritis, usually in lower limbs
key GI bacteria implicated in reactive arthritis?
salmonella
campylobacter
shigella
yersinia
key GU bacteria implicated in reactive arthritis?
chlamydia trachomatis
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
RFs for reactive arthritis?
infection-GI or GU male aged 20-40 caucasian HLA-B27
