Rheumatology Flashcards
What codes for genetic predisposition to RA
HLA DR4 serotype
How does smoking cause RA
Cigarettes cause citrullination of proteins - post translational modification by which arginine is converted to citrulline. Citrullination is a normal process, required for skin formation
In RA, an abnormal autoimmune response develops against citrullinated peptide->anti-cyclic citrilinated protein antibodies
Shared epitope predispose to the development
What is the synovial immunology of RA
Adaptive and innate immune pathways integrate. T cells releasing cytokines which are pro-inflammatory. T cells activating B cells which become plasma cells that release anti-CCP antibodies. In joint lining, innate cells like macrophages (cytokine) and neutrophils (reactive oxygen intermediates) causing damage and inflammation. Activation of the cell within the lining of the join: chondrocytes, fibroblasts, osteoclasts. These activations cause tissue remodelling and damage.
What do osteoclasts do in RA
Osteoclasts are the major driver of bony erosion in rheumatoid - causes breakdown and degradation of bone.
What are the joint signs of RA
Polyarthritis: tender, swollen, stiff, painful
Symmetrical involvement:
Hands - MCP/PIP joints
Feet - MTP joints
Variable large joints involved
How is RA diagnosed
Rheumatoid factor (antibody factor of IgM): classically red cells or latex particles. Currently nephelometry or ELISA anti-CCP antibody: uses ELISA, more specific than RF
What is swan neck deformity
hyperextension of PIJ and flexion of DIJ
What is boutonniere defeformity
PIJ (flexion) bent towards the palm and DIJ (hyperextension) is bent away
How does RA invovle the spine
Lower lumbar spine and thoracic spine is rarely involved.
Atlas and Axis: erosion can occur at odontoid peg. Can cause forward movement of atlas over axis, causing the head to move forward - can cause cord compression.
Define RA nodules
RA nodules are often painless. CCP and rheumatoid factor positive.
Nodules can occur in the chest - rheumatoid lung disease. Can also cause fibrosis of the lungs - pulmonary fibrosis (long standing RA).
What is necrotising slceritis
repeated sclerosis which can cause perforation of the sclera
What is methotrexate
Analogue of folic acid
Inhibits enzyme dihydrofolate reductase (DHFR) reducing folinic acid -> affects purine and pyrimidine metabolism
What are the adverse effects of methotrexate
nausea, bone marrow suppression, hepatoxicity, pneumonitis (inflammation of the lungs, presenting with SOB and fever), embryotoxic
What are TNF inhibitors
monoclonal abx that bind to cytokine TNF. Currently have 5 different TNF inhibitors - Infliximab, Adalimumab (pens given sc), Golimumab, Certolizumab pegol, Etanercept
What is IL-6
most abundant cytokine within RA synovium. Drives acute phase response, mediates chemokine driven lymphocyte trafficking, induction of RANK-L (activates osteoclasts) through JAK/STAT signalling.
What is rituximab
(also treats non-Hodgkin’s lymphoma): monoclonal abx that targets the CD20 molecule expressed on the surface of B cells - depletion of B cell. Efficacy persists long after drug clearance. Only effective in seropositive px
What is tocilizumab
(given sc) binds to IL-6 receptor, preventing IL-6 binding
How is SLE diagnosed
ANA, anti-dsDNA, anti-Sm, antiphospholipid Abs, low complement, direct Coomb’s test
What extractable antibodies are found in lupus
Antibodies to Ro/SSA = photosensitivity
Sm = SLE specific
RNP = Raynaud’s/overlap
La/SB = neonatal lupus
In severe lupus with multisystem disease, prevalence of anti-DNA is 70-80%
What are the ESR and CRP marker levels in lupus
If ESR 100 with CRP 0 = Lupus or related autoimmune disease
CRP>100 in a lupus patient = infection
Cytopenia
Low complement C3/C4
What are the causes of lupus
Environment -> sunlight, drugs (only curable form of lupus) and chemicals, viruses (EBV in paediatric onset lupus)
Genetic -> defective apoptosis (all nuclear antigens become expressed on cell surface in normal apoptosis, but lupus patients fail to clear away the apoptotic bodies)
What is the pathogenesis ofl upus
Autoantigens are processed by follicular dendritic cells in the germinal centre where they are presented to autoreactive B cells. This interaction under the influence of T1 interferons leads on to autoantibody producing plasma B cells -> immune complexes formed between auto-antibodies and antigen. Immune complexes bind to tissue to initiate vascular inflammation and lupus nephritis.
What are the risk factor for lupus
female hormones, genetics, drugs, ethnic origin (African and Asian ancestry), environmental factors
Disease onset after menarche in women, decline in disease activity with menopause (oestrogen plays a role)
What is discoid lupus
lesions in chest, face, trunk and back (just pure discoid px very rarely develop SLE)
What is subacute cutaneous lupus
all have anti-Ro antibodies
What is Jaccoud’s arthritis
full normal function of hands (differs from RA) - tendonitis
What is lupus vasculitis
cutaneous vasculitis. Small vessel vasculitis: splinter haemorrhages, digital infarcts, palpable purpura, vasculitis ulcer, urticarial vasculitis
What is Libman-Sacks endocarditis
(development of verrucous vegetation, but it is a sterile endocarditis): affects the mitral valve (treated with warfarin, abx, and corticosteroids)
What is neuropsychiatric lupus
psychosis (hallucinations), seizures, strokes, psychological disorders, transverse myelitis (inflammation of the spinal cord, similar to MS)
What is lupus nephritis
asymptomatic proteinuria, nephrotic syndrome, renal failure, rapidly progressive glomerulonephritis, dysmorphic/fragmented red cells, granular casts
Consider renal biopsy unless contraindicated
How is lupus nephritis diagnosed
low C3 and C4, high anti-dsDNA antibodies
What is the treatment for lupus
NSAIDs are contraindicated due to increased cardiovascular events from lupus
Hydroxychloroquine (first line of treatment), Mepacrine (anti-malaria drug) - main stay of treatment. Downregulates cytokines. Takes 3 months to work. Long term use well tolerated including pregnancy. Decreases risk of cardiac neonatal lupus. Reduce relapse rate and risk of renal flares. Improves lipid and glucose profiles. Thromboprophylaxis.
Smoking reduces anti-malaria efficacy
What do positive APAs inidcate
Anticardiolpin antibodies (aCL), Lupus anticoagulant (LA), anti-beta2 glycoprotein 1 antibodies. If triple positive, more likely to detect obstetric and clotting problems.
What are the signs of cerebral APS
Headache, cognitive dysfunction, ischaemic stroke, transient ischaemic attacks, acute ischaemic encephalopathy, amaurosis fugas, chorea
How is APS treated in pregnancy
No thrombosis í careful monitoring; aspirin
Previous maternal thrombosis -> heparin + aspirin
Recurrent embryonic loss (<10 weeks) -> heparin + aspirin; low dose aspirin
Late fetal death/IUGR/severe pre-eclampsia -> heparin + aspirin
Postpartum -> 6/52 heparin
What is secondary raynuad’s
Asymmetrical, thumb often affected, macroscopic nailfold capillary loops, digital infarcts, autoantibodies. 95% predictive of CTD, SLE, systemic sclerosis
What is scleroderma
diffuse cutaneous systemic sclerosis. Anti-Scl 70: DNA topoisomerase I and anti-RNA polymerase I, III
What is crest syndrome
limited cutaneous systemic sclerosis: anti-centromere antibodies. More likely to have pulmonary hypertension.
What is dermatomyositis
Dermatomyositis (DM) is a rare inflammatory muscle disease that leads to destruction of muscle tissue usually accompanied by pain and weakness.
What is acute anterior uveitis
Inflammation of the middle layer of the eye, causing eye pain and changes to vision. Very similar genetically SpA. HLA-B27 very strong link with both uveitis and SpA. Differs from conjunctivitis with pain.
What is psoriatic arthritis
DIP and PIP synovitis, asymmetric oligoarthiritis, dactylitis (whole digit inflammation, which is not present in RA)
What is ankylosing spondylitis
Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy. It typically presents in males (sex ratio 3:1) aged 20-30 years old.
What are the signs of ankylosing spondylitis
reduced lateral flexion reduced forward flexion reduced chest expansion Apical fibrosis Anterior uveitis Aortic regurgitation Achilles tendonitis AV node block Amyloidosis and cauda equina syndrome
What is psoriasis
presents with red, scaly patches on the skin although it is now recognised that patients with psoriasis are at increased risk of arthritis and cardiovascular disease.
What is psoriatic arthropathy
Psoriatic arthropathy correlates poorly with cutaneous psoriasis and often precedes the development of skin lesions. Around 10-20% percent of patients with skin lesions develop an arthropathy with males and females being equally affected
Treat as RA
What is the genetic association of psoriasis
associated HLA-B13, -B17, and -Cw6. Strong concordance (70%) in identical twins
What is the immunology of psoriasis
abnormal T cell activity stimulates keratinocyte proliferation. There is increasing evidence this may be mediated by a novel group of T helper cells producing IL-17, designated Th17. These cells seem to be a third T-effector cell subset in addition to Th1 and Th2
