rheum Flashcards
RA
systemic cx: constrictive pericarditis IPF benign nail fold vasculitis Felty's syndrome (splenomegaly, neutropenia, leg ulcers) pyoderma gangrenous peripheral neuropathy
drug induced lupus
- eg TNF-a
- ix; anti-histone ab
Up to 95% of patients have antihistone antibodies, which also are present in more than 50% of patients with SLE.
Antibodies to anti-double-stranded DNA, anti-Smith, antiribonucleoprotein, or anti-Ro/SSA or anti-La/SSB antibodies are typically absent
abs - disease
Microsopic POlyangiitis is associated with anti-MPO antibodies.(pANCA)
Wegener’s: with anti PR3.(cANCA)
Renal limited vasculitis: 70-80% with anti-MPO (pANCA)
Anti Jo-1 + ILD = polymyositis (anti-synthetase syndrome)
symmetric, progressive muscle weakness
Interstitial lung disease may precede myopathy or occur early in the disease, often in association with the presence of antibodies to t-RNA synthetases
limited scleroderma
Anti-centromere Ab
-Centromere antibody protective effect against severe ILD
Cardiac and renal disease is RARE
- Lung disease 30%/ Pulm HT 10%
Telangiectasia is the most common feature
Diffuse scleroderma
Anti-topoisomerase(Scl-70)
-Anti-RNA polymerase III is associated with diffuse cutaneous disease and is the most common immunological marker for renal crisis
Tendon friction rubs is the hallmark feature
systemic sclerosis
NSIP
scleroderma
- common Gi - gord
- ILD –> cyclophosphamide
RA
NO DIP ivlved for RA and SLE
Synovial fluid
RA: WCC 2000-10,000 , PMNs >50%.
septic arthritis: WCC >50,000 and PMNs >75%
Clinical triad of Felty’s syndrome
RA,
Neutropenia (<2.0 x 109/L) and
Splenomegaly.
Hydroxychloroquine
No evidence for slowing of radiographic progression with the use of hydroxychloroquine.
major side effect affecting the eyes and this includes:
1) Maculopathy-reduced visual acuity(dose related)
2) Vortex keratopathy(non dose related)
dermatomyositis
Gottron’s sign heliotrope rash Shawl sign Periungal changes Mechanics hands
3 mandatory fx of PMR
Age >50.
Bilateral shoulder ache.
Abnormal CRP +/- ESR
autoab
Microsopic POlyangiitis is associated with anti-MPO antibodies.(pANCA)
Wegener’s: with anti PR3.(cANCA)
Renal limited vasculitis: 70-80% with anti-MPO (pANCA)
R. factor +ve
Rheumatic disorders:
● Rheumatoid arthritis – 26 to 90 percent
● Sjögren’s syndrome – 75 to 95 percent
● Mixed connective tissue disease – 50 to 60 percent
● Mixed cryoglobulinemia (types II and III) – 40 to 100 percent
● Systemic lupus erythematosus – 15 to 35 percent
● Polymyositis or dermatomyositis – 5 to 10 percent
(high titres in RA, Sjogrens, cryoglobulinaemia)
Nonrheumatic disorders :
● Indolent or chronic infection, as with SBE or with hepatitis B or C virus infection. RF production typically ceases with resolution of the infection in these disorders.
● Inflammatory or fibrosing pulmonary disorders, such as sarcoidosis
● Malignancy, particularly B-cell neoplasms
● Primary biliary cholangitis (previously referred to as primary biliary cirrhosis).
Healthy individuals — Rheumatoid factors have been found in up to 4 percent of young, healthy individuals
seronegative spondyloarthropathies
- ankylosing spondylitis
- psoriatic arthritis
- reactive arthritis
- enteropathic spondylitis
- undifferentiated spondyloarthropathy
biological DMARDs
- Tumor Necrosis Factor: Infliximab Etanercept Adalimumab Golimumab Certolizumab
- T cell activation:
Abatacept - Anti CD-20:
Rituximab - Interleukin-6:
Tocilizumab - Interleukin-1:
Anakinra
Abatacept is a fusion protein of CTLA4 and Fc portion of IgG1
It interferes with T cell activation by preferentially binding to CD80/86 on the APC therefore preventing CD80/86 binding to CD28 on T cells.
In short,
Without Abatacept:
CD28 binds to CD80/86 = T cell activation.
But with Abatacept:
CTLA4 binds to CD80/86 = No T cell activation.
CTLA generates a NEGATIVE signal
genes are associated with risk of developing RA
PADI
STAT4
DR4
PTPN22
predictors of severity (erosive damage) of RA
- High titre of RF
- Presence of anti-CCP ab
- Erosions
- ESR and CRP at presentation
- Swollen joint count
- high disability HAQ score
- Rheumatoid nodules
- HLA DR4
Among all of these, erosion is the best predictor of severity.
Risk factors for RA development:
– Positive anti-CCP
– Smoking
– STAT 4 polymorphism.
Wegeners
renal + pulmonary (URT +/- LRT) involvement
Features
- upper respiratory tract: epistaxis, sinusitis, nasal crusting
- lower respiratory tract: dyspnoea, haemoptysis
- glomerulonephritis (‘pauci-immune’, 80% of patients)
- saddle-shape nose deformity
- also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions
Investigations
- cANCA positive and presence of antiproteinase-3 antibodies > 90%, pANCA positive in 25%
- chest x-ray: wide variety of presentations, including cavitating lesions
- renal biopsy: crescentic glomerulonephritis
Management
- steroids
- cyclophosphamide (90% response)
- plasma exchange
- median survival = 8-9 years
Adult Still’s disease
- typically affects 16-35 year olds
Features
- arthralgia
- elevated serum ferritin
- rash: salmon-pink, maculopapular
- pyrexia
- lymphadenopathy
- rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative
drugs - serum rate
Drugs that raise serum urate concentrations – Diuretics – Tacrolimus – Cyclosporin – Ethambutol – Pyrazinamide – Cytotoxic chemotherapy – Ethanol – Salicylates (low dose) – Levodopa – Ribavirin and interferon – Teriparatide
Drugs that lower serum urate concentrations – Ascorbic acid – Benzbromarone – Calcitonin – Citrate – Oestrogens – Fenofibrate – Losartan – Probenecid – Salicylates (high dose) – Sulfinpyrazone
Basically the diuretics, anti-TB drugs,anti-viral, immunosuppressives and chemo drugs may give rise to increased serum uric acid.
gout
Urate-lowering therapy is indicated for patients with:
1) recurrent gout attacks ( 2 or more attacks per year)
2) chronic arthropathy,
3) tophi
4) gout with uric acid stones (urate nephropathy,urate calculi)
This therapy should be started 1-2 weeks AFTER inflammation has abated because of the risk of acute attack.
First line is allopurinol
Second line is probenecid, sulfinpyrazone,benzbromarone and febuxostat (CI in heart disease).
Febuxostat is a novel xanthine oxidase inhibitor approved for management of gout in the European Union; the two approved doses of 80 mg per day and 120 mg per day are more effective than allopurinol 300 mg per day.
Dose adjustment with febuxostat is NOT necessary in patients with mild renal failure. Side-effects include raised liver enzyme activity and a small increase in the rate of serious cardiovascular events, which precludes
use in patients with ischaemic or congestive heart failure
DO NOT STOP URATE LOWERING THERAPY IF AN ACUTE ATTACK OCCURS!!
