Systemic Lupus Erythematosus Flashcards
Describe the spectrum of severity in lupus
- mild
- moderate
- severe
Mild => MSK, mucocutaneous
Moderate => serositis, cardiopulmonary, vasculitis
Severe => nephritis, CNS lupus, thrombosis
What investigation results are typical of lupus
High ESR
CRP = 0
Cytopenia
Low complement
ANA, dsDNA
Anemia, leukocytopenia, thrombocytopenia => direct cytotoxicity
What is the difference between ESR and CRP
ESR => increased fibrinogen
CRP => acute inflammation
What autoantibodies can you find in SLE
-what symptoms arise as a result
ANA (more sensitive marker, but not specific) A dsDNA (more specific to lupus)
ENAs
- Ro => photosensitivity
- La => neonatal lupus
- RNP => Raynaud’s
- Sm => SLE specific
Describe the pathophysiology of SLE
Environmental triggers
- sunlight
- drugs/chemicals/smoking
- viruses
Genetic predisposing factors
- increased apoptosis+ decreased clearance of apoptotic bodies => necrosis, release nuclear antigens
- neutrophil extracellular traps exposes histone complex AG
Leads to clinical disease
- follicular DC, autoreactive B cells => IFNa release
- autoantibody producing plasma cells => complement fixing to immune complexes => organ involvement/damage
Eventually leads to comorbidities
Describe the epidemiology of SLE
Describe the genetic impact
More common in females (due to double genetic load of X)
-common onset after menarche, declines with menopause
African, Asian ancestry
-decreased inhibitory function of FCGR2B gene => protection against severe malaria but increased B cell activation
Genetics => monozygotic significantly increased risk (HLA region C6)
How may a patient with lupus present non specifically
Fatigue Photosensitive rash Inflammatory arthritis/aches, pains Mouth ulcers Hair loss
Describe the different presentations of lupus
-3 possible skin presentations
Discoid
- well demarcated scaly, atrophic, discoid plaques
- face, neck and trunk
Subacute subcutaneous
-well demarcated red, scaly patches on photosensitive regions
Chronic cutaneous
- chilblains on hands and feet
- cold to the touch
Describe the different presentations of lupus
-joints
Jaccoud’s arthritis
- deformation due to tendon inflammation
- swan neck, hitchickers thumb
- have full function of hands (different to RA)
Describe the different presentations of lupus
-vascular
Cutaneous vasculitis
- splinter haemorrhages
- digital infarcts
- palpable purpura
- vasculitic ulcers (inflammation affecting integrity of small vessels)
- urticarial vasculitis (T3 hypersensitivity)
Lupus vasculitis (medium/large vessels) -digital ischemia/gangrene
What are the comorbidities that accompany lupus
CVD
Cancer
Infection
Renal
Describe the pathophysiology behind the 5 cardiovascular comorbidities
Lupus atherosclerosis => accelerated due to inflammatory activity => multivessel disease
Peripheral vascular disease
-digital/limb ischemia => gangrene => amputation
Pericarditis
- rapid resolution with CS
- may lead to tamponade
Myocarditis => scars
- arrythmias/conduction abnormalities
- dilated cardiomyopathy
- HF
Endocarditis
Describe the pathophysiology behind the infective comorbidities
-pulmonary
Lupus pneumonitis, serositis (pleural effusion due to PM inflammation)
What are the presentations of neuropsychiatric lupus
Psychosis/psychological disorders
Strokes/seizures
Transverse myelitis
Describe the investigations that indicate an increased risk of lupus nephritis
How would lupus nephritis present
High anti dsAB
Low C3-4
Damage and scarring found on renal biopsy
Asymptomatic proteinuria
Nephrotic syndrome
Renal failure
Rapid glomerulonephritis
What is a nephrotic syndromes
Symptoms due to kidney damage
- proteinuria
- foamy urine
- hypoalbuminemia
- hyperlipidemia
- HTN
What are the types of lupus nephritis
Minimal mesangial => immune complexes in mesangium
Mesangial proliferative => endocytose circulating AB, stimulates proliferation
Focal
Diffuse
Membranous (thickening of glomerulus and membrane)
Advanced sclerotic (healing of prior inflammatory injury
How would you assess lupus
Use indexes and questionnaries to explore:
Disease activity
Damage
QOL
What are the aims in treatment
Induction and maintenance of remission
Minimise toxicity and treatment related damage
prevent flares
For mild disease activity, what treatments would you use
Sun avoidance, protection
Topical steroids, calcineurin inhibitors, retinoids
Antimalarials
NSAIDS
For moderate disease activity, what treatments might you use
CS (short term, small doses) and HCQ
Azathioprine, methotrexate
What antimalarials could you use
-why can this be used
HCQ, mepacrine, quinacrine => decrease autoantibody production
Long term use well tolerated even in pregnancy
Disease modifying
- decreased relapse rate
- decreased risk of renal flares
- improves lipid, glucose profile
SMOKING REDUCES EFFICACY
How would you treat severe lupus
Renal + extra renal impacts
CS + azathiopurine
Biologics
How does belimumab work
Blocks B lymphocyte stimulator => apoptosis of autoreactive B cells
