Systemic Lupus Erythematosus Flashcards
What does SLE stand for?
Systemic Lupus Erythematosus
What is SLE?
A chronic autoimmune disease that causes the overreactivity of the immune system, producing auto antibodies, leading to systemic inflammation of multiple organs
What is the famous sign of lupus?
A butterfly rash on the face
Where are rashes localised to?
Sun exposed areas
How long do rashes last for?
Days or weeks
What demographic is most likely to be affected by lupus?
Non-Caucasian females, age 15-45
Why do likely see more cases of lupus amongst women ages 15-45
Sex hormones
Name two possible environmental triggers for lupus.
Hormones and UV light (sun exposure)
Does genetic risk of lupus put you at higher risk for other autoimmune disorders?
Yes
Does lupus have a genetic component?
Yes, although this is complex
How much does your risk for lupus increase if you have a first degree relative with the condition?
6x
What is the laboratory hallmark of lupus?
Antinuclear antibodies (ANA ) - present in 98% of patients
Which autoantibody shows a correlation with lupus disease activity?
dsDNA
Why is dsDNA not the first marker to look for in diagnosing lupus?
Because 30-50% of people with SLE don’t have it.
What might the presence of Sm autoantibodies suggest?
SLE with renal involvement
What is MCTD?
Mixed connective tissue disease - an autoimmune disease that shares features of lupus
What can RNP be used as a marker for?
MCTD and overlapping symptoms such as renal involvement, Raynauds and lung disease
What are Ro autoantibodies associated with?
Sjorgren’s syndrome (dry mouth, salivary issues), skin-related lupus, and neonatal lupus
What are antiphospholipid antibodies associated with?
Thrombosis complications, pregnancy loss, and neurological conditions such as myelitis
What is ribosomal P associated with?
Psychiatric disease
What does APS stand for?
Anti-phospholipid syndrome
What are the three main signs of APS?
Arterial and/or venous thrombosis, pregnancy morbidity, and antiphospholipid antibodies
What is the main treatment for vascular disease in SLE?
Immunosuppression
What is the main treatment for vascular disease in APS?
Anticoagulation
What condition can cause vascular disease that affects small vessels and is vasculitic in nature?
SLE
How does vascular disease in APS differ from that in SLE?
It is a coagulation disorder that affects both the large and small vessels, and is thrombotic in nature
How can SLE cause vascular disease?
Overreactivity of the immune system can cause lesions in the small vessels, damaging them (immune complex mediated)
Can someone have both SLE and APS?
Yes
What is APS?
An immune system disorder where antibodies are created that make much blood more likely to clot
What are some of the most common symptoms of SLE?
▪️Fatigue
▪️Arthritis/arthralgia
▪️Skin signs (e.g rashes)
▪️Fever
▪️Raynaud’s
▪️Swelling of limbs and joints
Can affect all organs!
Are antinuclear antibodies specific to SLE?
No!
What laboratory signs are looked for to diagnose definite APS?
▪️Lupus anticoagulant (LA)
▪️IgG/IgM aCL (medium/high titre)
▪️IgG/IgM anti-b2GPI
What SLE/APS related factors increase risk of stroke?
▪️SLE itself
▪️Antiphospholipid antibodies
▪️Vasculopathy/vasculitis
▪️Accelerated atherosclerosis through prolonged steroid use
▪️Valvular disease
How might an acute confusional state present in SLE?
▪️Fluctuating level of consciousness
▪️Acute onset
▪️Often related to infection/metabolic disturbances
What investigations might you need to investigate acute confusional states in SLE?
▪️LP to exclude infection
▪️EEG
▪️MRI
What MRI findings are commonly seen with acute confusional states in SLE?
White matter hyperintensities
What CSF findings have been associated with acute confusional states in SLE?
High levels of:
▪️IL-6
▪️IgG index
▪️Anti-NR2
▪️Anti-Sm
What are the main problems with understanding neuropsychiatric symptoms of lupus?
▪️Wide spectrum of features
▪️Poor understanding of pathogenesis
▪️Lack of diagnostic tools - largely clinical judgement
▪️Therapeutic approach is difficult
How many neuropsychiatric syndromes have been identified in SLE?
19
What are the six most common NP syndromes in SLE?
▪️Cognitive dysfunction
▪️Mood disorder
▪️Anxiety disorder
▪️Headache
▪️Seizure disorder
▪️Cerebrovascular disorder (Most commonly stroke, less commonly thrombosis)
What are the four uncommon NP syndromes in SLE?
▪️Acute confusional state
▪️Psychosis
▪️Myelopathy
▪️Polyneuropathy
What are some of the rare NP syndromes in SLE?
▪️Aseptic meningitis
▪️Demyelinating syndrome
▪️Guillain-Barre syndrome
▪️Autonomic neuropathy
How does cognitive dysfunction usually present in SLE?
Commonly subtle and subclinical (e.g. Forgetful, brain fog, anomia, difficulties recognising people etc)
Occasionally will be severe and progressive
How do you confirm cognitive dysfunction in SLE?
Formal psychometric testing, usually a 1 hour battery testing all domains
What are the main problems with diagnosing common forms of NPSLE?
▪️Lack of specificity - symptoms common among non SLE patients too
▪️Hard to establish causality (e.g. CNS involvement or secondary functional features of chronic illness?)
Psychosis is ___________ in SLE
Infrequent
Very low incidence!
What else might cause psychosis in SLE?
Prolonged steroid use
Why is it important to differentiate lupus psychosis from steroid induced psychosis?
▪️Lupus psychosis treated by increasing steroid dose/awaiting response
▪️If steroid induced, will need to reduce or stop prescription
When are neuropsychiatric events most common in SLE?
Early on
What percentage of NP manifestations in SLE are directly attributable to SLE?
20-30%
What concomitant conditions may contribute to NP manifestations in SLE?
▪️Infection
▪️Hypertension
▪️Metabolic disturbance
▪️Toxic effect of therapy (e.g. steroids)
If someone tests positive for the JC virus and is on aggressive immunosuppressant treatment for lupus, what are they at risk for?
Progressive multifocal leukoencephalopathy
(demyelinating lesions, neurological symptoms following treatment)
What percentage of SLE patients will present with aseptic meningitis?
0.6% - very rare!
What is aseptic meningitis?
Inflammation of the meninges that is NOT caused by bacterial infection
What are the main signs of aseptic meningitis?
▪️Fever, headache
▪️Increased lymphocytes and immune cells in CSF but negative microbiology
Why might SLE lead to aseptic meningitis?
▪️Active lupus
▪️Drug-induced (e.g. NSAIDs, immunosuppressants)
What is PRES?
Posterior reversible encephalopathy syndrome
(vasogenic oedema caused by disruption of BBB)
(Rare NPSLE)
What are the main signs of PRES?
▪️Altered mental state
▪️Cortical blindness
▪️Headache
▪️Seizures
How can you spot PRES on MRI?
▪️Vasogenic oedema (extracellular fluid accumulation due to BBB disruption)
▪️Lesions typically in posterior occipital and parietal lobes
What causes PRES in SLE?
▪️Secondary to autoimmunity
▪️Cytotoxic drugs
▪️Corticosteroids
▪️Hypertension
What is the prognosis of PRES?
Usually good
Reversible with controlled arterial hypertension and step back from immunosuppressants
What neurological complicationsay be seen with PRES?
▪️Endothelial dysfunction
▪️Vasodilation
▪️Hyperperfusion
▪️Haemorrhage
What are the symptoms of idiopathic intracranial hypertension?
▪️Positional headache
▪️Nausea
▪️Vomiting
▪️Papilladema
▪️Visual disturbance
▪️6th cranial nerve palsy (eye movement)
How do you treat idiopathic intracranial hypertension in SLE?
▪️Glucocorticoids
▪️Acetazolamide
▪️Mannitol
Good prognosis!
How does idiopathic intracranial hypertension appear on brain imaging?
Normal
How might you spot idiopathic intracranial hypertension with a lumbar puncture?
Normal CSF but high opening pressure
What percentage of SLE patients present with PRES?
Less than 1%
What percentage of SLE patients present with idiopathic intracranial hypertension?
1%
How common is macrophage activation syndrome in SLE?
Quite rare but risen since covid due to viral infection
More common in children
What is macrophage activation syndrome (MAS)?
▪️Hyperinflammagory condition
▪️Uncontrolled activation and proliferation of white blood cells
▪️Secondary inappropriate reaction to trigger, usually infection (haemophagocytic lymphohistiocytosis)
What are the main symptoms of MAS?
▪️High fever
▪️Liver dysfunction and swelling
▪️Swelling of lymph nodes
▪️Deficiency of all blood cell types
▪️Increased iron stores and triglycerides
▪️Neurological abnormalities and altered mental status
How is MAS treated and what are the problems?
▪️More challenging when it occurs with SLE
▪️Usually requires aggressive immunosuppression and ITU
▪️Aggressive neurosuppression if neurological abnormalities
What are the 3 main proposed mechanisms for the pathogenesis of CNS SLE?
▪️Vascular abnormalities
▪️Local production of cytokines
▪️Direct effects of autoantibodies
What NP symptoms may be indicative of APS?
Focal/thrombotic manifestations such as:
▪️Transient ischaemia attacks
▪️Ischaemic stroke
▪️Cerebral venous thrombosis
If APS is suspected as the cause of NP symptoms, what can you do to confirm this?
Testing for antiphospholipid antibodies (aPL)
What should you test for if a young person presents with a stroke (<50)?
Antiphospholipid syndrome (test for aPL)
When can immunoglobulins be used?
In cases of severe CNS disease in the presence of severe infection so don’t want to use immunosuppression
What is CSF analysis typically used for in NPSLE?
Excluding infection
What is MRI typically used for in NPSLE?
Excluding other diseases
What treatment is best for suspected thrombotic mechanism of NPSLE?
Antiplatelet or anticoagulant therapy
What treatment is best for suspected inflammatory mechanism of NPSLE?
Corticosteroids/immunosuppressants
What treatmemt should be used if someone is symptomatic and persistently positive for aPL?
Antiplatelet or anticoagulant therapy
What treatment should be used for NPSLE if someone is symptomatic with evidence of active lupus?
Corticosteroids/immunosuppressants
What antibodies are associated strongly with chorea and why?
aPL - binding in the basal ganglia?
What antibodies are associated with seizures?
aPL
How do you treat seizures in SLE?
▪️Antiepileptic treatment
▪️Consider steroids and immunosuppression if not improving or signs of CNS inflammation
How do you treat myelitis in SLE/APS?
Anticoagulation and immunosuppression
ASAP to prevent permanent damage
What can you use for refractory NPSLE?
Rituximab (RTX)
