Rheumatology Flashcards
What is the HLA allele associated with seropositive rheumatoid arthritis?
HLA - DRB1
What is the main environmental risk factor associated with seropositive rheumatoid arthritis?
Smoking
Combined with HLA-DRB1 -> confers very high risk
Also affects response to treatment
What are the key auto-antibodies involved in seropositive rheumatoid arthritis?
Anti-citrullinated protein antibodies (ACPA)
Rheumatoid factor
Can be detected up to 10 years before clinical disease
What is the “second hit” in rheumatoid arthritis?
The additional insult which promotes the actual migration of circulating cytokines into the synovium which causes clinical disease
What are the 4 kinase signalling pathways implicated in rheumatoid arthritis?
MAPK
SyK
NIK
Jak-Stat (most promising for therapeutics)
MCQ
All of the following have been identified as risk genes for rheumatoid arthritis except \_\_\_? A: STAT4 B: DRB1 C: PADI D: FOXP3 E: PTPN22
D: FOXP3
STAT4: involved in both RA and SLE
PADI: promotes formation of ACPA
PTPN22: if combined with DRB1 leads to early erosive disease
In rheumatoid arthritis, why do bony erosions occur peri-articular?
Bony erosions occur before cartilage erosion in RA.
This is the location where the cartilage no longer protects the bony surface
What are the key cells involved in bony erosions in rheumatoid arthritis?
Osteoclasts
In rheumatoid arthritis, which joints are typically affected first?
Which are spared?
Small joints first, symmetric
DIP sparing
How can arthropathy of rheumatoid arthritis and SLE be differentiated?
SLE: deformities should be passively reversible (unless very severe disease), and non-erosive
Different extra-articular features
What is Felty’s Syndrome?
Triad of rheumatoid arthritis, neutropenia, and splenomegaly
- Rheumatoid arthritis is typically severe, erosive, and seropositive
- Neutropenia is present in all patients
- Splenomegaly
What is rheumatoid factor?
Antibody against Fc portion of IgG
Short-lived, so can be used to monitor disease activity
Name 5 rheumatological conditions other than RA that Rheumatoid factor is positive in
Sjogrens
Cryoglobulinaemia
SLE
Sarcoid
Undifferentiated CTD
What non-rheumatological condition is rheumatoid factor frequently positive in?
Hepatitis B and C
What are some key XR findings in RA?
- Periarticular erosions
- Periarticular osteopaenia / osteoporosis
- Joint pace narrowing
- Deformities
What are the classic hand findings in RA?
- Ulnar deviation of fingers
- Dorsal wrist subluxation
- Boutonniere
- Swan-neck deformities
- Z deformity of thumb
In rheumatoid arthritis, what is the fastest acting medication to reduce inflammation?
Glucocorticoids
- for short-term symptom control whilst awaiting effect of DMARDs
What is the “anchor” medication in treatment of rheumatoid arthritis?
What is it reversed by?
Methotrexate 10-25mg weekly
- competitive folate analogue (need to give with folate)
- improves mortality and prevents flares
SEs: GI upset, myelotoxicity, transaminitis, hepatic fibrosis, pneumonitis
Reversed by folinic acid
What is the main alternative cDMARD to methotrexate in RA?
What is it reversed by?
Leflunomide 10-20mg daily
- can be used in poor renal function
SEs: diarrhoea, myelosuppression
Very long half-life, reversed by cholestyramine
What is the most common cause of premature death in patients with rheumatoid arthritis?
Cardiovascular disease
What are the TNF inhibitors used in rheumatoid arthritis? (5)
Infliximab (Remicade) 3 mg/kg intravenously, as a single dose at 0, 2 and 6 weeks, and thereafter every 8 weeks
Adalimumab (Humira) 40 mg subcutaneously, every 2 weeks
Etanercept 50 mg subcutaneously, once weekly
Golimumab 50 mg subcutaneously, every 4 weeks
Certolizumab pegol subcut 2-weekly (doesn’t cross the placenta)
What are the main risks with TNF inhibitors?
Infection
- can be reactivation
Malignancy
Which rheumatoid arthritis DMARDs are safe in pregnancy?
Hydroxychloroquine
Sulfasalazine
TNF inhibitors
Steroids at low doses
What is the classic histological appearance of IgG4 disease?
Steroeform fibrosis
What are the 6 major diffuse connective tissue disease entities?
Systemic lupus erythematosus (SLE)
Systemic sclerosis / scleroderma
Polymyositis
Dermatomyositis
Rheumatoid arthritis
Primary Sjögren’s syndrome
What is the female to male ratio in SLE?
9:1
What is the most sensitive auto-antibody for SLE?
ANA
- dense, fine speckled pattern
What are the most specific auto-antibodies for SLE?
Anti-dsDNA
Anti-Sm
What are the antiphopholipid antibodies?
Anti-cardiolipin
Anti-beta2glycoprotein
Lupus anticoagulant
What is Jaccoud’s arthropathy?
Arthropathy seen in SLE.
Tenosynovitis, RA-like swan neck deformity and ulnar deviation. However, this deformity is passively correctable unlike RA.
Not erosive
What is the most common cardiac manifestation of SLE?
Pericarditis +/- pericardial effusion
Presents w/ retrosternal, pleuritic chest pain, improved when sitting up
Occurs in ~25% of Pts at some point during their disease course
What is Libman-Sacks endocarditis?
Occurs in SLE
Verrucous sterile valvular lesions typically involving edge of aortic, mitral or tricuspid valves
What are the 6 classes of lupus nephritis?
I: Minimal mesangial
- No or minimal proteinuria
- Normal Cr
II: Mesangial immune deposits
- Microscopic haematuria and proteinuria
III: Focal proliferative (<50% glomeruli)
- May be active, active on chronic or chronic
- Haematuria and proteinuria +/- HTN
- ↓ GFR +/- nephrotic syndrome
IV: Diffuse proliferative (>50% glomeruli)
- As above
V: Membranous
- Nephrotic syndrome +/- haematuria and HTN
VI: Advanced sclerosing
- Slowly progressive renal dysfunction, proteinuria and bland urinary sediment
Which classes of lupus nephritis require active treatment?
What would be the appropriate management?
Classes 3 + 4 (proliferative)
Management =
Induction -> steroids + MMF or low dose cyclophosphamide
Maintenance -> MMF or azathioprine or cyclosporine
What medication should all patients with SLE receive?
What is its major side effect?
Hydroxychloroquine
- reduces flares
Monitor for macular toxicity with annual eye checks
What is the primary presenting feature in inflammatory myositis?
Weakness, usually painless
What are the differentiating features on muscle biopsy of dermatomyositis and polymyositis?
PM -> inflammatory infiltrate is endomysial, with predominance of CD8 cells
DM -> inflammatory infiltrate is perimysial, with predominance of CD4 cells
What are Gottron’s papules and what condition are they classically associated with?
Violaceous papules over extensor MCP/IP
Found in Dermatomyositis
What is the typical facial rash of Dermatomyositis?
Heliotrope eruption -> erythematous to violaceous eruption on the upper eyelids, sometimes accompanied by eyelid edema
Can also have general facial erythema and
What is photodistributed poikiloderma?
Poikiloderma = skin with both hyperpigmentation and hypopigmentation, as well as telangiectasias and epidermal atrophy
Found in DM in any photo-exposed site, most commonly upper back (shawl sign) and the V of the neck and upper chest.
What is anti-synthetase syndrome?
Anti-Jo1 positive myositis with
- ILD
- Raynaud’s phenomenon and mechanic’s hands
- Non-erosive arthritis
What important condition is dermatomyositis associated with>
Malignancy:
- Adenocarcinomas of the cervix, lung, ovaries, pancreas, bladder, and stomach account for approximately 70%
What is the initial treatment for inflammatory myopathy such as DM or PM?
Prednisolone 1mg/kg -> max 80mg with slow taper of 9-12 months
Start a steroid-sparing agent at the same time -> either AZA or MTX
**need PJP prophylaxis with this treatment
What clinical feature is universally present in systemic sclerosis?
Raynaud’s phenomena
This is complicated by digital ischaemic ulcers in 50% of patients
What are the key features of CREST syndrome?
CREST:
- Calcinosis cutis
- Raynauds
- Eosophageal dysmotility
- Sclerodactyly
- Telangectasia
What differentiates limited from diffuse systemic sclerosis?
Trunk involvement of skin sclerosis
Diffuse disease has poorer prognosis, with increased end-organ damage
What are the two main lung manifestations of systemic sclerosis?
Pulmonary fibrosis
Pulmonary vascular disease -> leads to pulmonary hypertension
What is anti-Scl-70 ab associated with?
Associated with diffuse cutaneous systemic sclerosis and a higher risk of severe interstitial lung disease
What is anti centromere ab associated with?
Associated with limited cutaneous systemic sclerosis
What is anti-RNA polymerase III ab associated with?
Associated with diffuse cutaneous systemic sclerosis, and rapidly progressive skin involvement as well as an increased risk for scleroderma renal crisis
What is the typical clinical presentation of scleroderma renal crisis?
Oliguric AKI, hypertension, bland urinary sediment and microangiopathic haemolytic anaemia
What is the characteristic histological findings in scleroderma renal crisis?
‘Onion-skin’ hypertrophy -> intimal proliferation and thickening that leads to narrowing and obliteration of the vascular lumen, with concentric “onion-skin” hypertrophy
What is the key treatment in scleroderma renal crisis?
Captopril
- Start low and regularly uptitrate until target BP achieved
If malignant HTN -> use sodium nitroprusside in addition
What is first line for treatment of systemic sclerosis-associated pulmonary HTN?
Ambrisentan (endothelin receptor antagonist) + tadalafil (phosphodiesterase-5 inhibitor)
What is the initial management for systemic sclerosis-associated interstitial lung disease?
Mycophenolate, typically for more than 2 years
2nd line -> cyclophosphamide IV monthly for 6 months, or daily PO for 12 months
What is the role of nintedanib in systemic sclerosis?
For systemic sclerosis-associated interstitial lung disease.
Nintedanib is an antifibrotic agent that slows disease progression in idiopathic pulmonary fibrosis, and is now approved for use in SSc-ILD to slow ILD progression
What is the initial management of skin disease in systemic sclerosis?
1st line -> Mycophenolate or methotrexate
2nd line or rapidly progressing disease -> cyclophosphamide
What vasculitis is most commonly associated with PR3-ANCA ab?
What immunofluorescence pattern is associated with this?
PR3-ANCA is most commonly found in GPA -> granulomatosis with polyangiitis
Associated most often with c-ANCA pattern-> cytoplasmic
What vasculitis is most commonly associated with MPO-ANCA ab?
What immunofluorescence pattern is associated with this?
MPO-ANCA is most commonly found in MPA -> microscopic polyangiitis
Associated with p-ANCA pattern -> perinuclear
Which ANCA-associated vasculitis is more likely to relapse?
GPA = granulomatosis with polyangiitis
Which ANCA Ab is more common in ANCA-positive eosinophilic granulomatosis with polyangiitis (EGPA)?
MPO-ANCA is substantially more common among patients with EGPA who are also ANCA positive
QUESTION 2007 A10
In a patient with vasculitis whose serum contains peri-nuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), what is the most likely target antigen for this antibody?
A. Proteinase 3. B. Myeloperoxidase. C. Lactoferrin. D. Cathepsin G. E. Lyzosyme
Myeloperoxidase -> MPO
What are the 3 main reasons to use Plasma Exchange in ANCA vasculitis?
- Advanced kidney dysfunction as a result of glomerulonephritis due to GPA or MPA
- Positive anti-glomerular basement membrane (anti-GBM) autoantibody
- Pulmonary hemorrhage complicated by respiratory compromise or pulmonary hemorrhage that does not respond rapidly to intravenous glucocorticoids
What is the initial treatment for mild forms of ANCA vasculitis?
Corticosteroids + MTX
What is the initial treatment for moderate severity forms of ANCA vasculitis?
Steroids + either cyclophosphamide OR rituximab
What is the tetrad of IgA Vasculitis (HSP)?
- Palpable purpura (75-90%) – LL predominance, normal platelets and coags
- Abdominal pain – diffuse, acute onset
- Renal – proliferative GN with predominant IgA deposition
- Arthritis – acute onset
What is the initial management of IgA vasculitis?
- Proteinuria >0.5/day – ACEI/ARB
- Proteinuria >0.75g/day or crescenteric GN – IV methylpred pulse then 6mth pred taper
- Persistent inflammation on repeat 4-6mth biopsy – either cyclophosphamide or MMF
What is the first line treatment for IgG4-related disease?
Glucocorticoid monotherapy
What is the second line treatment for IgG4-related disease, after steroids?
Rituximab
What is the only approved targeted therapy for SLE?
Belimumab - human monoclonal antibody that inhibits the soluble form of a B-cell survival factor known as BLyS or BAFF. Levels of BLyS are elevated in some patients with SLE, and it may play a role in the pathogenesis of lupus by promoting the formation and survival of memory B cells and plasmablasts making autoantibodies
Recommended use (UTD): active musculoskeletal or cutaneous disease that is unresponsive to standard therapy with glucocorticoids or other immunosuppressive agents
What autoantibodies are associated with polyarteritis nodosa?
None!
Blood tests can determine organ involvement.
ANCA should be NEGATIVE.
Diagnosis is made with angiography +/- biopsy of affected organ
Diabetic neuropathic arthropathyis most likely to affect which of the following areas? A. Knee B. Mid-foot C. 1st metatarsophalangeal joint D. Elbow E. Ankle
B. Mid-foot
Where do patients with osteoarthritis of the hip most commonly report pain? A. Groin B. Medial thigh C. Lateral thigh D. Knee E. Buttock
A. Groin
**Lateral thigh pain is likely to be trochanteric bursitis, or gluteal tendinopathy
Best indicator of future erosive joint disease in RA? A. Swollen joint count B. Tender joint count C. Weight loss D. CRP
D - CRP
CRP correlates closely with changes in inflammation/disease activity, radiological damage, progression, functional disability
What is the difference between inclusion body myositis and polymyositis? A. Bilateral ptosis B. Weak long finger flexors C. Weak deltoids D. Weak quadriceps E. Truncal weakness
B. Weak long finger flexors
38 year old woman presents with a six-week history of increasing shortness of breath while playing tennis and a two-week history of increasing muscle weakness. She reports mild symmetrical polyarthralgiaof the hands, wrists & knees for six months and Raynaud’s phenomenon during the recent winter. Examination: proximal muscle weakness, a hyperkeratotic rash with fissuring on the palmar and lateral surfaces of the fingers on both hands. Investigations: serum creatinekinase level of 890 (16-139), an interstitial pulmonary infiltrate on HRCT of the chest. Autoantibody tests show the following results: ANA titre 1:2560, speckled; anti-ENA Jo-1 positive, anti-DNA Ab negative. The most likely diagnosis is:
A. Progressive systemic sclerosis
B. Dermatomyositis
C. Polymyositis (anti-synthetase syndrome)
D. SLE
E. Sjogren’ssyndrome
C. Polymyositis (anti-synthetase syndrome)
Characteristic clinical picture of myositis and/or interstitial lung disease and/or chronic articular involvement.
Raynaud’s phenomenon common
Severity and type of pulmonary involvement determines outcome of disease
What is the classic antibody finding in anti-synthetase syndrome?
Anti-ENA Jo-1
Patient with well-managed rheumatoid arthritis (on methotrexate and statin), presents for review, describing increasing lethargy. Nil evidence of active joint inflammation –oral ulcers on examination.FBE: Hb102, WCC2.5, Neut1.2, Platelets 90
What is the drug of choice to manage these findings?
A. Folic Acid
B. FolinicAcid
C. Cholestyramine
D. G-CSF
B - Folinic acid
Has vitamin activity equivalent to folic acid, but does not need the action of dihydrofolatereductase for its conversion.
Its function as a vitamin is not affected by inhibition of this enzyme by drugs such as methotrexate
→ so useful in treatment of MTX overdose
A patient presents with back pain. Which feature is most suggestive of spinal canal stenosis? A. Pain on prolonged weight-bearing B. Paraesthesia on weight-bearing C. Osteoarthritic changes on X ray D. Loss of deep tendon reflexes E. Loss of vibration sense in feet
B. Paraesthesia on weight-bearing
When differentiating between vascular and neurogenic claudication, which is relieved by walking flexed?
Neurogenic
When differentiating between vascular and neurogenic claudication, which is relieved by standing erect?
Vascular
When differentiating between vascular and neurogenic claudication, which is worsened by walking up stairs or hills?
Vascular
27 year old male presents with an 18 month history of back pain, heel pain and a swollen knee. Has restriction in spinal flexion, is HLA-B27 positive and CRP is 25.In addition to physiotherapy, what is the most appropriate initial pharmacologic management? A. Prednisone B. Naproxen C. Methotrexate D. Etanercept E. Salazopyrin
B - Naproxen
1st line is NSAID + exercise
Arthritis in which of the following joints is most suggestive of haemachromatosis? A. Knee B. Ankle C. Distal interphalangeal D. Metacarpophalangeal E. Metatarsophalangeal
D - MCP
A 49-year-old female presents with a five week history of symmetrical polyarthralgia. Laboratory results are: Antinuclear antibody (ANA) positive, titre: 1/80, pattern: speckled Antibodies to extractable nuclear antigens (ENAs) negative Anti-double stranded DNA antibody (anti-dsDNA) 7 IU/mL [0-5] Anti-cyclic citrullinatedpeptide (anti-CCP) positive.Rheumatoid factor (RF) < 20 [0-20] Which of the following is the most likely diagnosis? A. Rheumatoid arthritis B. Systemic lupus erythematosus C. Mixed connective tissue disease D. Viral polyarthritis E. Osteoarthritis
A. Rheumatoid arthritis
ACPA Ab are very specific
What is the main constituent of amyloid fibrils in dialysis amyloidosis?
Beta2 microglobulin
What is the only treatment shown to halt progression of dialysis amyloidosis?
Kidney Transplant
Which of the following is most likely to exacerbate gout? A. Beer B. Dairy products C. High purine vegetables D. Red meat E. Fish
Beer
An 82-year-old man presents with difficulty walking due to osteoarthritis in his right hip. When prescribing a cane as a walking aide for him, the most appropriate instruction regarding use of the cane is:
Hold the cane:
A. in the right hand and advance the cane with the right leg.
B. in the right hand and advance the cane with the left leg.
C. in the left hand and advance the cane with the right leg.
D. in the left hand and advance the cane with the left leg.
E. in the right hand and advance the cane after both feet have advanced.
C. in the left hand and advance the cane with the right leg.
Hold stick in contralateral hand, advance with affected leg
A 56yo man presents with right knee swelling after a long walk. He has a history of obesity and psoriasis of 12 years. Right knee xrayshows loss of cartilage in the medial compartment with chondrocalcinosis.Serum urate 0.55 (0.24 –0.44)Synovial analysisViscosity: normal, Clarity: normalWCC: 900mm3 (<200), Differential: 90% mononuclearCrystals : occasional extracellular urate crystalsWhat is the cause of this man’s right knee swelling? A. Pseudogout B. OA C. Gout D. Psoriatic arthritis E. Medial meniscal tear
B - OA
28 yowoman who is otherwise well presents with Raynaudsof fingers. ANA +ve1/80 titer. The most likely diagnosis is: A. SLE B. CREST C. Systemic sclerosis D. Primary Raynaud's
D - Primary Raynauds’s
In which part of the vertebral column are syndesmophytesfirst seen in ankylosing spondylitis? A. Cervical B. Cervical/thoracic C. Thoracic D. Thoraco-lumbar E. Lumbar
D - Thoraco-lumbar
A 44 year old female has a 20 year history of systemic lupus erythematosus. She was previously on cyclophosphamide but is now on prednisolone and hydroxychloroquine for skin manifestations. Past history includes type II diabetes. She now presents with ventricular fibrillation and dies. What is the most likely underlying reason for this presentation?
A.Pericarditis and tamponade
B.Coronary artery disease
C.Libmansacks endocarditis
D.Viral myocarditis
E.Coronary vasculitis
F.Antiphospholipid syndrome with large pulmonary embolus
B - CAD
In patients with systemic lupus erythematosus, the prevalence of coronary-artery atherosclerosis is elevated and the age at onset is reduced.
A 52 year old female complains of 3 years of progressive dry eyes. Investigations: positive ANA speckled, 1:640, ENA + Ro and La, ESR 98.She is otherwise well with normal examination apart from Schirmer’stest 1mm, and positive Rose-Bengal staining.The best initial treatment is: A.Prednisolone B.Hydroxyurea C.Methotrexate D.Prednisolone eye drops E.Hypomellosetear substitute
E.Hypomellosetear substitute
A 52 year old woman with RA has inability to extend her 4thand 5th fingers A. Extensor tendon rupture B. Radial nerve palsy C. Dupuytren'scontracture D. Metacarpal joint deformity
A - extensor tendon rupture
Which of the following activities is most likely to cause pain in osteoarthritis of the patello‐femoral joint? A. Walking up stairs B. Jogging C. Walking on flat ground D. Getting out of a chair E. Standing
A - walking up stairs
47 year old male, HIV for past 20 yrs, presents with gradual onset right hip pain over last 3 weeks. He is on emcitrabine, tenefavir, enviranz. Known to have lipodystrophy. No history AIDS defining illness. XR shown right hip/pelvis showing collapse of superior surface femoral head. ANA negative, Rh factor negative, urate 0.52 (normal < 0.44)What is most likely diagnosis? A. Gout B. OA C. Psoriatic arthritis D. Avascular necrosis E. RA
D. Avascular necrosis
In general population, ethanol use and glucorticoiduse account for 90% of cases. Other associated conditions include lupus, sickle cell disease, organ transplantation, antiphospholipid antibodies, trauma, radiation.
In HIV+ patients, incidence is 100x that of general population. Asymptomatic disease found in 6%.
Risk factors include low CD4 nadir, prior AIDS-defining illness, dyslipidemia, and traditional risk factors. Majority of patients exposed to glucocorticoids or megestrol.
A 75 year old lady presents with unilateral temporal headache. Which one of the following is the most specific for temporal arteritis? A. Tenderness over the temporal area on palpation B. Hip and shoulder tenderness C. Jaw (masseter) claudication D. Fever E. Blurring vision F. Elevated ESR G. Proximal weakness
C. Jaw (masseter) claudication
A diabetic labourer sustains an injury to his foot when a brick falls on it. Several weeks later he develops increasing burning pain severely limiting mobility, increasing sweating and sensitivity to touch or cold. The most appropriate diagnostic investigation is:
A. Doppler ultrasound of lower limb vasculature
B. Bone scintigraphy
C. Bone biopsy
D. X-ray
B. Bone scintigraphy
Will show reflex sympathetic dystrophy
What findings are seen on compensated polarised light microscopy in gout?
Negatively birefringent, needle-shaped
What findings are seen on compensated polarised light microscopy in pseudogout?
Weakly positive birefringent, rhomboid shaped
Which 3 conditions does Mixed CTD share features with?
Systemic lupus erythematosus, systemic sclerosis, and polymyositis
What is the specific risk to consider in use of tocilizumab?
Lower intestinal perforation
- avoid with history of diverticulitis
What is the main risk with febuxostat that makes it second line after allopurinol, despite its higher potency?
Cardiovascular risk - caution in HF and IHD
What are the indications for urate-lowering therapy in gout?
Recurrent flares (>1 / year)
CKD or past renal stones
Tophi
What are the targets for uric acid level in gout?
<0.36 in most people
<0.30 in tophaceous gout
What conditions are associated with speckled pattern ANA?
SSc
MCTD
Sjogren’s
