SLE Flashcards
What areas are affected in mild SLE?
- Mucocutaneous
- Musculoskeletal
What conditions occur in moderate SLE?
- Serositis
- Cardiopulmonary
- Vasculitis
What conditions occur in severe SLE?
- Nephritis
- CNS lupus
- Thrombosis
What classification criteria is used to classify lupus and how is it used?
ACE/EULAR
- All patients must have ANA ≥ 1:80
- Must have ≥ 10 points to be classified as SLE
What are blood test features of SLE?
- High ESR
- Normal CRP
- Cytopenia (leucopenia)
- Thrombocytopenia
- Low complement C3/C4
What autoantibodies are found in lupus?
1) Antinuclear antibodies (ANA) - almost everyone with lupus has this but not specific
2) Anti-dsDNA antibodies -specific (50-70%)
3) Anti-histone
4) RF?, anti-cardiolipin (aPL)
What antibodies to ENAs are found in lupus?
1) Anti-Ro (anti-SSA) - photosensitivity
2) Anti-La (anti-SSB) - neonatal lupus
3) Anti-Sm - Raynaud’s
4) Anti-RNP
What causes SLE?
- Type III hypersensitivity (immune complexes)
- Complexes of DNA and anti-DNA antibodies become localised in the skin and cause inflammation and rashes and also in other organs e.g. kidneys
- Immune complexes deposit in capillaries in the skin which recruit complement and inflammatory cells e.g butterfly rash bc capillaries are very close to the face
- Abnormal apoptosis exposes nuclear antigens to the immune system which leads to a range of antibodies being exposed
What are environmental factors that can trigger onset/flare ups of lupus?
1) Sunlight
2) Drug
3) EBV in children
4) NETosis (defective apoptosis) leading to autoantigens (and therefore ANAs)
- Something causes the switch from benign to pathogenic autoimmunity
What is the main cytokine in lupus?
Type 1 interferon
What is the pathogenesis of SLE?
- Autoantibody producing plasma B cells produce autoantibodies
- This forms immune complexes with the antigens aided by complement
- The complement/immune complexes bind to tissue
- This causes vascular inflammation and lupus nephritis
What are factors implicated in SLE (cause unknown)?
- Female hormones
- Genetics
- Drugs
- Environmental factors
- Ethnic origin (common in those of African and Asian ancestry)
Describe the link between female gender and SLE
- SLE is 9-10x more common in women
- Disease onset often after menarche
- There is a decline in disease activity with menopause (often can stop treatment)
- Maybe something to do with X chromosomes and double genetic load
Describe the genetics of SLE
- Complex genetics
- Increased risk with sibling or twin
- Key genetic marker is HLA region
- Polymorphism in FCGR2B gene blocks the inhibitory function of this gene
- This leads to B cell activation which protects against severe malaria but gives an increased risk of SLE
What is the peak age of onset of SLE?
15-45 years (peaks in third/fourth decade)
Describe the typical presentation of a patient with SLE (different from RA)
- Young woman
- Fatigue
- Systemic - malaise, weight loss, fever, night sweats (similar to lymphoma)
- Sun sensitive rashes
- Arthritis/aches and pains
- Mouth ulcers
- Hair loss
- Blood clot in leg (?)
What are the clinical features of discoid lupus erythematosus?
- Demarcated, scaly, atrophic, discoid plaques
- Scarring alopecia - can be red and inflamed (acute) or more white and scarred
Describe the rash in subacute cutaneous lupus (SCLE)
Red smooth dots, overlapping, patchy, going up neck and face, hands and wrists
Describe chilblain lupus
- Cold sensitive rash (patients nearly always have Raynaud’s as well)
- Looks like vasculitis but lesions feel cold to the touch rather than hot
- Red, swollen fingers, toes and hands
Describe Jaccoud’s/lupus arthritis (arthropathy)
- Non-erosive
- Due to tendon problems (tendonitis) rather than erosion of bone
- The pattern of arthritis in lupus is similar to the pattern of arthritis in RA
- Persistent, inflammatory symmetrical small joint arthritis (PISA)
- First thing RA then lupus if young woman
- See the same deformities as in RA e.g. swan neck
- However, it is reversible and patients have full hand function
What are the types of lupus vasculitis?
1) Cutaneous vasculitis
2) Small vessel vasculitis
3) Digital vasculitis (symmetrical) - ears, elbows, knees, feet
4) Medium/large vessel vasculitis (less common)
5) Digital ischaemia/gangrene (uncommon)
What are the clinical features of small vessel vasculitis?
- Splinter haemorrhages
- Digital infarcts
- Palpable purpura
- Vasculitic ulcers
- Urticarial vasculitis
What are the predictors of poor outcome/mortality in lupus?
- Female
- Black ethnicity
- Infections
- Younger age
- Disease duration < 1 year
- Renal disease
What is the SMR of lupus?
3
What cancer are lupus patients at an increased risk of (others generally lower risk)?
Lymphoma
What would be used to see diffuse multi-vessel coronary artery disease?
Angiogram (can see blocked arteries?)
Why does lupus atherosclerosis occur?
- Vascular damage from inflammation in lupus and cytokines
- This leads to accelerated atherosclerosis
What are lupus patients at increased risk of?
CVD/atherosclerosis
What can peripheral vascular disease in SLE lead to?
- Critical limb/digital ischaemia
- Gangrene
- Amputations
What lung conditions can occur in lupus (90% have abnormal lung function/pulmonary involvement)?
1) Lupus pneumonitis
2) Lupus serositis
Describe pericarditis in lupus
- Common
- Rapidly resolves with corticosteroids
- Rarely leads to tamponade so shouldn’t need to treat it as tamponade
- Rapid onset of pericardial effusion
- ST elevation
Describe myocarditis in lupus
- Common in active SLE
- Arrhythmias (myocardial scarring can be a focus for arrhythmias)
- Conduction disturbance
- Dilated cardiomyopathy
- Cardiac failure
What investigations do you do in myocarditis?
- Troponin-T (sensitive marker of heart inflammation)
- CK-MB
- NT-proBNP - heart failure
- Echocardiography
- Cardiac MRI (useful for diagnosis, can see myocardial scar)
- Endomyocardial biopsy (rare)
Describe endocarditis in lupus
- Most common on mitral valve but can be any
- Not infective
- Due to inflammation (sterile), but can become infection as valve is not functioning properly
- Libman-Sacks endocarditis
Describe features of neuropsychiatric lupus (90% of patients have chronic neuropsychiatric problem due to lupus or living with LTC)
- Psychosis (hallucinations - patients often know they are not real, unlike schizophrenia) - nearly always well treated with anti-psychotics
- Seizures
- Strokes
- Psychological disorders
- Transverse myelitis
- Neurological syndromes e.g. MG
90% of which type of lupus patients present with (glomerulo)nephritis?
Juvenile lupus (young)
What is the prevalence of nephritis in lupus?
40-75% (predictor of poor outcome)
What are the serological features of lupus nephritis (increase risk of nephritis)?
- Anti-dsDNA antibodies
- Low C3 and C4
What are the presenting features of lupus nephritis?
- Asymptomatic proteinuria
- Nephrotic syndrome
- Renal failure
- Rapidly progressive glomerulonephritis (rare) like vasculitis patients
- Typically present with class III or IV
What are features of urine cytology in lupus nephritis (v sensitive for glomerulonephritis/ glomerular disease)
- Dysmorphic/fragmented red cells
- Granular casts
What investigation should you consider in lupus nephritis unless contraindicated?
Renal biopsy - v important to tell severity and how aggressively to treat
Describe all the classes of lupus nephritis
I) Minimal mesangial LN
II) Mesangial proliferative LN
III) Focal LN (active/chronic)
IV-S) Diffuse segmental proliferative LN
IV-G) Diffuse global proliferative LN (most predictive of renal impairment)
V) Membranous LN (heavy proteinuria)
VI) Advanced sclerotic LN (scarred kidney, dialysis)
What are the treatment aims for SLE?
- Induction and maintenance of durable remission
- Minimise toxicity and treatment related damage
- Prevent disease flares - reduces damage
- Avoid long term damage
- Damage accumulation predicts early death
Which drugs are contraindicated in SLE and why?
NSAIDs
- They increase risk of stroke and MI and lupus patients are already at increased risk of atherosclerosis
Describe use of corticosteroids in SLE
- Lowest effective dose for shortest period of time
- Prednisolone ≤ 30mg od ± IV/IM methylprednisolone good for anti-inflammation
- Use alongside hydroxychloroquine
- Aim to taper to ≤ 7.5mg od or stop
- Early use of immunosuppressive therapies
Describe antimalarial therapy in SLE
- Hydroxychloroquine
- Combination antimalarials
- Long term use well-tolerated incl. in pregnancy
- 65% decreased risk of cardiac neonatal lupus
- Disease modifying - decreased relapse rate and risk of renal flares
- Improves lipid and glucose profiles for those on steroids
- Anti-clotting effect (thromboprophylaxis)
- Reduces risk of damage and mortality
- Smoking reduces efficacy
What is the first line treatment for all SLE patients?
Hydroxychloroquine (safest anti-rheumatic drug)
What drugs are used in severe SLE (renal and extra-renal) or if people have poor compliance?
- IV methylprednisolone 500mgs x 3
- Fortnightly cyclophosphamide 500mgs (contraindicated in pregnancy)
- Azathioprine
- Mycophenolate 1.5-3g/day (contraindicated in pregnancy)
What is the only licensed biologic for lupus against B cells?
Belimumab (also rituximab which binds to CD20, fixes complement and lyses B cells - B cell depleting antibody, atacicept) and infliximab is also used?
What is the effect of belimumab?
- Anti-BLyS
- Blocks B lymphocyte stimulator so it can’t bind to B cells leading to apoptosis of autoreactive B cells
- Decreases risk of severe SLE flare
- Well tolerated, no serious adverse effects
What things have to be considered in lupus?
- Patient compliance/adherence predicts ESRD in LN
- Minimising/avoiding steroids
- CV risks
- Thrombosis risk
- Glucocorticoid bone loss
- Vitamin D deficiency
- Infection risks/immunisation
- Risks of malignancy
- Non-drug management - fatigue, poor sleep, psychological issues
What type of disease is SLE?
Connective tissue disease incl. vasculitis and inflammation (arthropathy?)
Describe the rash in lupus
- Photosensitive distribution e.g. V of neck, forehead, cheeks (butterfly rash)
- Photosensitive rash can blister
What might you see on a fundus photograph of an eye in someone with SLE?
- Vasculitis in eye e.g. retina
- Patches of yellow = areas of ischaemia where blood supply has stopped
- Blood vessels have become inflamed, stopped supplying blood to that tissue and the retina has died
How do you treat neuropsychiatric lupus syndromes (organic brain syndrome, diffuse disease)?
- Corticosteroids
- Immunosuppression
What makes you more likely to die of lupus?
The more damage you acquire
Which autoantibodies develop early and which ones develop closer to the appearance of symptoms?
- Early = anti-Ro and anti-La
- Later = anti-Sm and anti-dsDNA
What are common patterns of organ involvement in SLE?
1) Skin - diverse patterns, photosensitivity, alopecia
2) Joints - non-erosive arthritis and tendonitis
3) Sicca symptoms - salivary, lacrimal and genital tract
4) Glomerulonephritis - several patterns incl. mesangial, membranous and peripheral
5) Neurological - CNS, eye, PNS
What are the mechanisms of antibody injury in SLE?
1) Direct cytotoxicity (and clearance) e.g. autoimmune haemolytic anaemia, thrombocytopenia
2) Immune complex formation and deposition e.g. skin rashes and glomerulonephritis
3) Trigger pro-inflammatory response in cells carrying Fc gamma receptors e.g. macrophages
4) Promote NK cell activation and/or cytotoxicity
What happens in the immune system in SLE?
1) Complement consumption by immune complexes leading to complement diminishing
2) Excess production of alpha-IFN leading to a state of pseudo-viral infection by immune complexes
3) Activation of TLRs - TLR 7/9 bind to DNA and RNA
4) Recruitment and activation of neutrophils to create tissue damage and inflammation
5) Also involves T helper cells even though antibody mediated
