Week 2 (2) Flashcards
What are SLE, Sjogrens syndrome, systemic sclerosis, dermatomyositis, polymyositis, MCTD and anti-phospholipid syndrome?
Connective tissue diseases
How are connective tissue diseases characterised?
by the presence of spontaneous over activity of the immune system
What part of the body does SLE affect?
Any
Give two pathogenic features of SLE?
- Immune system attacks body’s cells and tissue, resulting in inflammation and tissue damage
- Antibody-immune complexes precipitate and cause a further immune response
What is the female:male ratio for SLE?
9:1
What people is there a higher prevalence of SLE in?
Asians, afro-americans, afro-caribbeans and hispanic americans
In relation to genetic factors for SLE - what is there a high concordance in?
Monozygotic twins
Name a hormonal factor in the aetiology of SLE?
Incidence increased in those with higher oestrogen exposure
Name three environmental factors involved in the aetiology of SLE?
- Epstein-Barr Virus
- UV light
- Silica dust (cleaning powders, smoking)
In SLE pathogenesis - what happens to apoptosis?
Increased and defective
In SLE pathogenesis - what release nuclear material which act as potential autoantigens?
Necrotic cells
In SLE pathogenesis - what does autoimmunity possibly result by?
Extended exposure to nuclear and intracellular autoantigens
Give four mucocutaneous features of SLE
- Photosensitivity
- Malar rash
- Discoid lupus erythematosus
- Subacute cutaneous lupus
Give four musculoskeletal features of SLE?
- Non-deforming polyarthritis
- Deforming arthropathy - Jaccoud’s arthritis
- Erosive arthritis
- Myopathy - weakness, myalgia
Name five pulmonary features of SLE?
- Pleurisy
- Infections
- Diffuse lung infiltration and fibrosis
- Pulmonary hypertension
- Pulmonary infarct
Name four SLE cardiac features
- Pericarditis
- Cardiomyopathy
- Pulmonary hypertension
- Libman-Sachs endocarditis
In SLE - what presents with proteinuria, urine sediments, urine RBC and casts, hypertension, acute and chronic renal failure?
Glomerulonephritis
Give five neurological features in SLE
- Depression/psychosis
- Migraines
- Cerebral ischaemia
- Cranial or peripheral neuropathy
- Cerebellar ataxia
Name four haematological features of SLE
- Lymphadenopathy
- Leucopenia
- Anaemia
- Thrombocytopenia
In SLE, what does low complements, impaired cell mediated immunity, defective phagocytosis and poor antibody response to certain antigens result in?
Susceptibility to infection
Name three extrinsic factors in SLE which increased infection risk?
- Steroids
- Immunosuppressives
- Nephrotic system
Name two main screening tests for SLE?
- FBC
2. Renal function tests including urine examination
Name four immunological tests for suspected SLE?
- Anti- nuclear antibody
- Anti-dsDNA antibodies
- ENA
- Complement levels
Name three conditions other than SLE, where ANA is found in?
- RA
- HIV
- Hepatitis C
Name antibodies which need to be present other than ANA for SLE to be taken seriously?
- Anti-dsDNA
- Anti-Sm
- Anti-Ro
- Anti-RNP
What antibody in SLE is highly specific, titre collerates with overall disease activity and may be associated with lupus nephritis?
Anti-dsDNA
Name two anti-ENA antibodies which are associated with SLE?
Anti-Ro
Anti-La
In SLE - anti-Sm (an anti-ENA) is highly speciic and is probably associated with what?
Neurological involvement
Name an anti-ENA associated with SLE which relates to sclerodermatous skin lesions, Raynauds and low grade myositis
Anti-RNP
In SLE - what does anti-dsDNA positvely correlate with?
Activity
In SLE - what does C3/C4 levels negatively correlate with?
Activity
Are NSAIDs given for SLE?
yes
Name an anti-malarial which is useful for arthritis, cutaneous manifestations and constitutional symptoms in SLE?
Hydroxychloroquine
In SLE - steroids are given, what are small doses for?
Skin rashes, arthritis and serositis
In SLE - steroids are given, what are moderate doses for?
Resistant serositis, haemoatologic abnormalities and class V GN
In SLE - steroids are given, what are high doses for?
Severe/resistant haematologic changes, diffuse GN and major organ involvement
Name two side effects for immunosuppressives used in SLE (azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil)?
All can cause bone marrow suppression
All potentially teratogenic
Name two biologics used in SLE?
Anti-CD20 (Rituximab)
Anti-Blys (Belimumab)
For mild SLE - waht 3 drugs are give?
HCQ, topical steroids and NSAIDS
For moderate SLE - what three drugs are given?
Oral steroids, azathioprine and methotrexate
For severe disease - what three drugs are given?
IV steroids, cyclophosphamide and rituximab
What do you need to have to be diagnosed with anti-phospholipid syndrome?
Positive anti-cardiolipin (anti-phospholipid) antibodies and/ or lupus anticoagulant activity and/or anti-beta2-glycoprotein on 2 occassions at least 12 weeks apart
Is arterial/venous thromosis and pregnancy loss with no other explanation a feature of anti-phospholipid syndrome?
Yes
Who does anti-phospholipid syndrome occur in?
Young women
Name five clinical features of anti-phospholipid syndrome?
- Superficial thrombophlebitis and livedo reticularis
- Mild/moderte thrombocytopenia
- Neurological features - migraine, transverse myelitis
- Libman-Sacks endocarditis
- Catastrophic anti-phospholipid syndrome
Give two treatments for anti-phospholipid syndrome?
Life-long anticoagulation
Aspirin and heparin during pregnancy
What connective tissue disease involves lymphocyte infiltration of exocrine glands causing xerostomia and keratoconjunctivitis sicca?
Sjogrens syndrome
What two antibodies are found in Sjogrens?
Anti-Ro
Anti-La
What ocular test is done in Sjogrens syndrome?
Schirmer
What is the peak age for primary sjogrens syndrome?
40-60 (m:f = 1:9)
What are five treatment options for Sjogrens syndrome?
- Eye drops
- Saliva replacement
- Pilocarpine
- Hydroxychloroquine
- Steroids and immunosuppression
What connective tissue disease is characterised by vasculopathy (Raynauds syndrome), inflammation and fibrosis?
Systemic sclerosis
What is systemic scerosis also known as?
CREST
What is CREST?
Calconosis Raynaud's Esophageal dysmotility Sclerodactyly Telangiectasia
What antibodies are associated with systemic sclerosis?
Anti-centromere antibodies
What antibody is in diffuse systemic sclerosis?
Anti-Scl-70
What two features characerise diffuse systemic sclerosis?
- Skin changes within 1 year of Raynauds
2. Truncal and acral skin involvement
What is the peak age and M:F ratio for systemic sclerosis?
25-55
1:4
Name 6 treatments for systemic sclerosis?
- Calcium channel blockers
- Prostacyclin
- ACE inhibitors
- Prednisolone
- Immunosuppression
- Bosentan, Sildenafil
Give five major criteria for MCTD?
- Severe myositis
- Pulmonary involvement
- Raynauds
- Swollen hands
- Sclerodactyly
What anibody is found >1:10,000 in MCTD?
Anti-RNP
Define vasculitis?
Inflammation of blood vessels, often with ischaemia, necrosis and organ involvement
What does primary vasculitis result from?
Inflammatory response that targets the vessel walls and has no known cause - sometimes autoimmune
What does secondary vasculitis result from?
Infection, drug, toxin or part of inflammatory disorder/cancer
Name two large-vessel vascuslitises?
- Takayasu arteritis
2. Giant cell arteritis
Name two medium-vessel vasculitis?
- Polyarteritis nodosa
2. Kawasaki disease
What class are microscopic polyangitis, granulomatosis with polyangitis (WEgner) and eosinophilic granulomatosis with polyangitis (Churg-Strauss)?
ANCA-associated small-vessel vasculitis
What class are cryoglobulinemic vasculitis, IgA vasculitis (Henoch), hypocomplementemic urticarial vasculitis and anti-GBM disease?
Immune complex small-vessel vasculitis
What can small vessel vasculitis be divided into#?
ANCA-associated and non-ANCA associated
In a pANCA small vessel vasculitis - if a granuloma is not present what is the diagnosis?
Microscopic polyangitis
In a pANCA small vessel vasculitis - if a granuloma is present, and asthma is too what is the diagnosis?
Churg-Strauss
In a pANCA small vessel vasculitis - if a granuloma is present and thre is no asthma what is the diagnosis?
Wegeners granulomatosis
What is a non-ANCA associated small-vessel vasculitis where there is IgA dominant immune deposit?
Henoch-Schnlein purpura
What large vessel vasculitis predominantly affects those under 40 and is commoner in females and asian populations?
Takayasu arteritis
What large vessel vasculitis affects over 50s and typically causes temporal arteritis but the aorta and other vessels may be affected?
Giant cell arteritis
What are both large vessel vasculitis conditions characterised by?
Granulomatous infiltration of walls of large vessels
What are five clinical findings in large vessel vasculitis?
- Bruit - carotid artery
- BP difference
- Claudication
- Carotodynia or vessel tenderness
- Hypertension
What is temporal arteritis commonly associated with?
Polymyalgia rheumatica
What are three classic symptoms of temporal arteritis?
- Unilateral temporal headache
- Scalp tenderness
- Jaw claudication
What is there risk of in temporal arteritis?
Blindness due to ischaemia of optic nerve
What investigations should be done for temporal arteritis?
- ESR, plasma viscosity and CRP raised
- Biopsy - careful of skip lesions
- MRI - vessel wall thickening
What is the management for temporal arteritis?
Steroids with starting dose of 40-60mg prednisolone
What medium vessel disease is seen in children usually under 5 and can cause vasculitis of coronary arteries where aneurysms can develop?
Kawasaki disease
What medium vessel vasculitiis is characterised by necrotising inflammatory lesions that affect arteries at vessel bifurcations, resulting in micro-aneurysm formation and aneurysms?
Polyarteritis nodosa
What vasculitis is associated with hep B?
Medium vessel
What vasculitis disease has the pathology of: granulomatous inflammation of respiratory tract, small and medium vessels. necrotising glomerulonephritis is common?
Granulomatosis with polyangiitis (GPA) or Wegener’s granulomatosis
What vasculitis disease has the pathology of: eosinophilic granulomatous inflammation of respiratory tract, small and medium vessels and is associated with asthma?
Churg-Strauss syndrome or Eosinophilic granulomatosis with polyangitis (EGPA)
What vasculitis disease has the pathology of: Necrotising vasculitis with few immune deposits, necrotising glomerulonephriotis is very common?
Microscopic polyangiitis (MPA)
At what age does Wegeners or GPA present?
35-55
What are sinusitis, nasal crusting, epitaxis, mouth ulcers, sensorinueural deafness, otitis media and deafness and saddle nose all ENT features of?
Wegeners or GPA
Does Wegeners give cavitating nodules?
Yes
Name two cutaneous features of Wegeners?
Palpable purpura and cutaneous ulcers
What renal condition is seen in GPA or Wegeners?
Necrotising glomerulonephritis
Name three nervous system features of Wegeners or GPA?
- Mononeuritis multiplex
- Sensorimotor polyneuropathy
- Cranial nerve palsy
What condition are conjunctivitis, episcleritis, uveitis, optic nerve vasculitis, retinal artery occlusion and proptosis all ocular features of?
Wenegers or GPA
What is the main difference between Churg-Strauss (EGPA) and Weneger (GPA)?
Presence of late onset asthma and high eosinophil count
What are a group of autoantibodies against antigens in the cytoplasm of neutrophil granulocytes (most common type of white blood cell)?
Anti-neutrophil cytoplasmic antibodies (ANCAs)
What is used to detect ANCA?
Immunofluoresence
What is cANCA found in?
GPA or Wegeners
What is pANCA found in?
MPA and EGPA (Churg-Strauss)
What vasculitis is PR3 found mostly in?
GPA
What vasculitis is MPO found mostly in?
MPA
What is used to treat localised or early systemic ANCA associated vasculitis?
Methotrexate + steroids
What is used to treat generalised/systemic ANCA associated vascusliits?
Cyclophosphamide + steroids
What is used to treat refractory ANCA associated vasculitis?
IV immunoglobulins
ituximab
Name an acute immunoglobulin A mediated disorder?
Henoch Schonlein Purpura (HSP)
What conditions involves generalised vasculitis involving small vessels of the skin, GI tract, kidneys, the joints and rarely the lungs and CNS?
HSP
Who is commonly affected by Henoch-Schonlein Purpura?
2-11 year old children
What do more than 75% of patients have preceding HSP?
URTI, pharyngeal infection, GI infection - most common group A streptococcus
5 features of presentation in HSP?
- Purpuric rash over buttocks nad lower limb
- Colicky abdo pain
- Bloody diarrhoea
- Joint pain
- Renal involvement
How is HSP managed?
Symptoms resolve within 8 weeks
MUST DO URINALYSIS to screen for renal involvement
In inflammatory arthritis - what are paracetamol, opiate compounds, NSAIDs and atypical analgesics used for?
Symptom relief
Name three DMARDs used in inflammatory arthritis?
- Methotrexate
- Sulphasalazine
- Hydroxychloroquine
What analgesic is commonly used in fibromyalgia?
Amitryptiline
What class of drug is diclofenac?
NSAID
What drugs are NSAIDs which selectively target cyclooxygenase-2, an enzyme responsible for inflammation and pain?
Cox 2 inhibitors
If a patient was at risk of peptic ulcers - what NSAID would you give?
Cox 2 inhibitor
What NSAID increases the risk of CV events?
Cox 2 inhibitors
What drugs used in inflammatory arthritis are slow acting, purely anti-inflammatory with no direct analgesic effect and reduce rate of joint damage?
DMARDs
When using DMARDs for inflammatory arthritis - what must be monitored?
WCC
When should inflammatory arthritis patients be started on DMARDs?
Within 3 months
What is the first choice DMARD in most cases?
Methotrexate
Name a few side effects of methotrexate?
Leucopenia, hepatitis, pneumonitis, rash/mouth ulcers, nausea, TERATOGENIC
What drug must be stopped in males and females at least 3 months before conception - and what must be started instead?
-Methotrexate
Sulphasalasine
What drug is an azo ester of sulfapyridine and 5-aminosalicylic acid and is often used in combination with methotrexate in early inflammatory arthritis?
Sulfasalazine
What are a few side effects of sulfasalazine?
Nausea, rash/mouth ulcers, neutropenia, hepatitis, reversible oligozoospermia
What DMARD used in SLE, Sjogrens syndrome and RA causes irreversible retinopathy?
Hydroxychloroquine
If patients suffer side effects for most DMARDs what other options are available?
Sodium aurothiomalate (gold) IM - bone marrow suppression, GN, rash Penicillamine oral
What type of drugs are licensed for RA, psoriatic arthritis and ankylosing spondylitis but are also mroe effective in combo with DMARDS
Anti-TNF
Give two adverse effects of anti-TNF?
Major infection risk (TB)
Contraindicated in pulmonary fibrosis and heart failure
What is the criteria for use of ANTI-TNF?
High disease activity score and use of previous standard DMARDs
What biologic inhibits IL-6?
Tocilizumab
What biologic inhibits IL-12 and IL-23?
Ustekinumab
What biologic blocks full activation of T cells?
Abatacept
What biologic is monoclonal antibody against B cells?
Rituximab (CD20)
In RA what biologic is NOT used?
Ustekinumab
In psoriatic arthritis what two biologics are used?
Anti-TNF
Ustekinumab
In ankylosing spondylitis what biologic is used/
Anti-TNF
In Connective Tissue Disease -what biologic is used?
Rituximab
Name a xanthine oxidase inhibitor?
Allopurinol
Give an adverse affect of allopurinol?
Rash
Name a few adverse effects of corticosteroids?
Weight gain, muscle wasting, skin atrophy, osteoporosis, diabetes, hypertension, cataract, glaucoma, fluid retention
What should the dose be like for corticosteroids?
Low and for a short time
