224 - Rheumatoid Arthritis Flashcards
define rheumatoid arthritis?
chronic systemic inflammatory disorder that is autoimmune in nature, attacks synovial joints with pannus formation and extra articular manifestations (lungs/pleura, pericardium, sclera, subcut tissue)
what are the 7 features of the ACR scoring system and how many are required for an RA diagnosis?
4 of morning stiffness, swelling in 3 or more joints, swelling of hand joints, symmetrical joint swelling, erosions on hand in xray, rheumatoid nodules, abnormal serum rheumatoid factor
who does RA tend to affect and what causes it?
35-45 y/o F:M 3:1 genetic factors (HLA-DR4 and PTPN 22), non genetic factors (infections) and smoking
what causes inflammation in RA?
abnormal proliferation and activity of T cells, fibroblasts, osteoclasts, neutrophils and Bcells proliferate and produce Rheumatoid Factors (autoantibodies). This leads to abnormal production of cytokines and inflammatory mediators (TNF-alpha, IL-6, IL-8) causing acute phase response and liver produces CRP (acute phase reactants)
what is a pannus formation?
membrane of granulation tissue composed of synovium and bone marrow derived cells. Stimulates cytokine production and immune cell infiltration (macrophages, T and B lymphocytes) leading to cartilage, bone and ligament damage. Synovium also fills with neutrophils.
How does RA usually present (not systemic features)?
gradually starting small peripheral joints.
- articular features - pain, stiffness, synovitis, joint effusion, restriction of movement, deformity (swan neck and ulnar deviation)
- tendon rupture and contractures (tendons pull joints out)
- constitutional symptoms (fever, fatigue, weight loss)
- rheumatoid nodules in RF+ve - on pressure areas overlying bone. Subcut, firm non tender. Due to small cell vasculitis - shell of fibrous tissue surrounding fibroid centre)
how can RA present systemically?
- Rheumatoid vasculitis - occlusion and ischaemia
- Pulmonary effusions, nodules, fibrosis, cryptogenic organising pneumonia
- pericarditis and pericaridal effusions, valvular disease
- *keratoconjunctivitis sicca, (epi)scleritis, scelromalaecia
- entrapment neuropathies, mononeuritis multiplex
- anaemia, felty’s syndrome (RA +splenomegaly+leukopaenia)
- amyloidosis (incr. serum amyloid A protein levels) in organs
what investigations should be carried out to investigate for RA?
- inflammatory markers ESR and CRP
- Anti-CCP (cyclic citrillunated peptide) - predicts onset
- Rheumatoid Factor (80%)
- x-ray for erosions
- USS/MRI for synovitis
- CXR for pulmonary symptoms
what drugs can be prescribed in RF?
- analgesia
- NSAIDs
- steroids
- DMARDS (disease modifying anti-rheumatic drugs) best in combination
- methotrexate (Tcell inhibitor and purine metabolism inhibitor)
- sulfasalazine (5-ASA compound supresses TNF and IL-1 and inhibits immune cells
- Leflunomide (inhibits pyrrimidine synthesis and th. lymphocyte proliferation
- Biologic agents - anti TNF agents
- monoclonal antibodies (infliximab, adalimumab)
- soluble receptor proteins (etanercept)
what is vasculitis?
inflammation and necrosis of a blood vessel with impairment of circulation and damage to vessel integrity
what causes vasculitis?
immune cell infiltration into vessel wall esp. neutrophils. Causes fibrinoid necrosis of tissue and leukocytoclasis (WBC destruction). This causes endothelial damage, thrombosis, occlusion of vessel and vessel perforation and haemorrhage
how might vasculitis present?
- palpable purpura
- livedo reticularis (mottled purple discolouration of legs)
- ulcers or digital infarction
- urticaria
what investigations should be carried out for suspected vasculitis?
- tissue biopsy is gold standard
- angiogram
- inflammatory markers CRP and ESR
- FBC for anaemia, ↑WCC, eosinophilia
what is the most common vasculitis and who does it affect?
Giant Cell Arteritis (Temporal artertis). Affects >55s and more women by 3:1
what are the signs/symptoms of giant cell arteritis and how would you treat?
*jaw claudication
*localised headache
*constitutional symptoms (fever, fatigue, anorexia)
*temporal artery enlargement and tenderness
*may lead to blindness
treat with high does prednisolone
what is wegener’s granulomatosis also known as and who does it commonly affect?
granulomatosis with polyangitis
affects european middle aged men
what causes wegener’s granulomatosis?
cellular and humoral factors resulting in necrotising vasulitis, necrotising granulomatous inflammation of resp tract, necrotising glomerulonephritis
what are the signs/symptoms of wegener’s granulomatosis?
- constitutional
- ENT -saddle nose deformity, epistaxis, sinusitis, otitis media, hearing loss
- LRT - pulm. infiltrates, SOB, haemoptysis
- renal failure - haematuria, rbc casts
what investigations would be useful for wegener’s granulomatosis?
- bloods - normocytic anaemia, ↑neutrophils, ↑ CRP
- serology - ANCA (anti-neurtrophil cytoplasmic antibody) esp. c-ANCA (PR3-ANCA)
- CXR for pulm. nodules
- tissue biopsy
how should wegener’s granulomatosis be treated?
mild - methotrexate/aziothioprine + steroids
severe - cyclophosphamide + steroids
what is polyarteritis nodosa?
multisystem disease. necrotising inflammatory lesion at bifurcations of small/medium muscular arteries producing microaneurysms, rupture with haemorrage and thrombosis. Causes palpable nodules along arteries and organ ischaemia/infarction. Hep B virus associated
what is the progression of churg-strauss syndrome? investigations?
I - allergic rhinitis and asthma
II - eosinophilic infiltrative disease - cough and haemoptysis
III - small/medium vesell vasculitis, peripheral neuropathy, renal failure, arthralgias, purpura, GI pain, myocarditis/ pericarditis
eosinophilia, ↑ creatinine, pANCA, ↑ IgE, CXR for patchy parenchymal opacities
what causes systemic lupus erythematous?
multisystem autoimmune disease caused by tyIII hypersensitivity reaction - apoptotic defect causes increased cell death and display of nuclear and cytoplasmic antigens on cell surface which are picked up by APCs. Bcells produce autoantibodies to attack ANAs (serum anti nuclear bodies) and dsDNA. Large immune complexes are formed and aggregate in microvasculature and basement membranes off kidneys and skin causing rashes
genrtic and environmental causes as well as EBV
who does SLE tend to affect?
women 9x more likely 20s and 30s, afro caribean
how might SLE present?
- constitutional symptoms
- arthritis/arthralgia/myalgia
- malar rash, photosensitivity, discoid rash in sun, alopecia
- renal failure
- epilespy, CVA
- PE
- bowel infarction, oral ulcers
- pericarditis, coronary vasculitis then MI
- Thrombotic Thrombocytopaenic purpura (TTP), miscarriage
- serositis
what investigations should be carried out for suspected SLE?
- clinical exam
- serology - ANAs - if +ve ask for ENA
- anti dsDNA, anti-smith, antiRo/anti La
- inflammatory markers CRP and ESR
- FBC - anaemia, leukopaenia
- urine dipstick - blood and protein
what treatment can be given in LSE?
- prednisolone - systemic symptoms
- hydroxychloroquine + sun block - inhibits eosinophils, neutrophils & antibodies for skin and MSK symptoms
- NSAIDs for arthralgia
- Immunosupressants - cyclophosphamide, mycophenolate motefil, methotrexate, azothioprine
- antidepressants, anticonvulsants
what is scleroderma & what causes it?
systemic skin thickening, tightening and induration. Also fibrosis of lungs, kidneys (+HTN) and vasculopathy. Reynauds phenomenon (episodic cold pale cyanosed extremities including visible dilated nail fold capillaries)
Immune response of Thelper1 cells and autoantibodies resulting in inflammation and excess production & deposition of collagens I and III
clinical features of scleroderma?
CREST
- Calcinosis
- Reynauds
- esophageal syndrome - reflux
- sclerodactyly - skin thickening over fingers
- Telangectasia - dilation of blood vessels
investigations for scleroderma?
auto antibodies
- ANA
- anti-centromere antibody - limited disease
- Anti-scl 70 - diffuse disease
no drugs modify disease - no steroids (renal crisis)
what causes polymyositis/dermatomyositis?
autoimmune reaction by defective CD8 Tcytotoxic cells invading and destroying healthy muscle fibre. In dermatomyositis humoral attack against muscle capillaries and small arterioles
what are the clinical features of polymyositis/dermatomyositis?
slow onset myopathy (poly only adults), symmetrical proximal muscle weakness
dermato -rash skin lesions, bluepurple helitrope discolouration on upper eyelids, extra muscular (cardia, GI, intersitial lung, constitutional)
what investigations for polymyositis/dermatomyositis?
- creatine phosphokinase
- EMG (electromyography) - short duration, low amp, polyphasic waves, muscle irritability
- muscle biopsy confirms diagnosis
- serology - ANAs, trop T, antiJo1
- MRI muscles
treatment for polymyositis/dermatomyositis?
steroids
immuosuppressants - methtrexate, cylcophosphamide, azathioprine, biologics
what are the features of sjogrens syndrome?
*secondary to RA, lymphocytic infiltrates in exocrine organs (thelper and Bcells - lymphoma risk), anti-ro/la antibodies involved
*sicca symptoms eyes and mouth
*parotitis
*reynauds
*althralgia
vasculitis
*renal symptoms
treat with artificial tears/ saliva, chewing gum
