🩻MSK🩻 - Lupus Flashcards
What are the autoimmune connective tissue disorders?
SLE
Sjogren’s syndrome
Systemic sclerosis (scleroderma)
Autoimmune inflammatory muscle disease
What is SLE?
Autoimmune disease involving disturbance of both innate and adaptive immune systems
Autoantibodies to nuclear components
Antibody-antigen (immune complexes) & other mechanisms -> chronic tissue inflammation
Multi-site inflammation but particularly the joints, skin and kidney
What features are characteristic of autoimmune connective tissue disorders in general?
Arthralgia and non-erosive arthritis
Serum autoantibodies - useful diagnostically, corelates with disease activity, may be directly pathogenic
Raynaud’s phenomenon - intermittent vasospasm of digits - usually triggered by cold exposure
Outline Raynaud’s
Intermittent vasospasm of digits
Usually triggered by cold exposure
Typical triphasic colour changes - white, blue, red
Severe Raynaud’s -> tissue ischaemia, ulcers and necrosis
What is the epidemiology of SLE?
Typical onset between 15 – 45 years
F:M ~9:1
Prevalence and severity varies by ancestry
African > Asian > White European
Clinical manifestations highly variable
Disease can range from mild to life threatening
Why is there so much variety in SLE presentations?
Target of autoantibodies are nuclear components - present in just about every cell
Such a wide variety of potential targets = a huge variety of outcomes and presentations
How do finger deformities in SLE differ from those in types of arthritis?
SLE-induced deformities show no bony erosions - deformity is due purely to soft tissue damage
What are some of the clinical features of SLE?
Skin and mucosa - malar rash, photosensitive rash, mouth ulcers, hair loss
Vascular - Raynaud’s
MSK - Arthralgia and (non-erosive)
Internal organs - serositis (pericarditis, pleuritis etc…), renal disease, cerebral disease, myocarditis
Haematological - autoimmune thrombocytopenia, haemolytic anaemia
Other - lymphadenopathy, fever with no infection
Can be any combination of the above
What marker is a hallmark of SLE?
Presence of ANA
What is ANA?
Anti-nuclear antibodies
Found in all SLE patients (actually some don’t but for the purposes of the exams assume they all do)
Negative ANA rules out SLE, positive doesn’t diagnose however - may be seen in other autoimmune diseases, infections or even sometimes healthy people
What is done after ANA are identified?
What is APL?
Antiphospholipid (APL) antibodies
As well as ANA, some SLE patients have antibodies directed to phospholipids on cell membrane
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What is the presence of APL antibodies associated with?
Increased risk of thrombosis:
Arterial - stroke
Venous - DVT
Pregnancy loss - miscarriage
What is anti-phospholipid antibody syndrome?
Persistent presence of APL + a clinical event
Anti-phospholipid antibody syndrome can also occur in absence of SLE
(‘primary anti-phospholipid antibody syndrome’ )
What other autoantibodies are specific for SLE?
Anti-double stranded DNA antibodies (anti-dsDNA) - serum level correlates with disease activity
Anti-Sm antibodies
What autoantibodies are associated with RA?
Rheumatoid Factor
Anti-cyclic citrullinated peptide antibody
What autoantibodies are associated with SLE?
Antinuclear antibodies (ANA)
Anti-double stranded DNA antibodies (anti-dsDNA)
Anti-phospholipid antibodies
Anti-Smith
Anti-Ro
Anti-La
Anti-RNP
Which of SLE’s immunopathogeneses stem from innate immunity?
Overactivity of type 1 interferon pathway
Complement pathway abnormalities
Which of SLE’s immunopathogeneses stem from adaptive immunity?
Autoreactive T and B cells
How is the immune system generating a response to nuclear antigens?
(should be hidden inside the cell)
the ‘waste disposal hypothesis’
What types of investigations would you do for SLE?
Inflammation
Haematology
Renal
Immunological
What inflammatory markers would their be in SLE?
High ESR
Normal CRP (unless infection or serositis/arthritis)
What might you find in haematological investigations in a patient with SLE?
Haemolytic anaemia
Lymphopenia
Thrombocytopenia
What renal signs might you see in SLE?
Urine protein - VERY IMPORTANT
Creatinine
Look at albumin
Kidney biopsy if persistent proteinuria
What immunological signs might be apparent upon investigation in SLE?
ANA
Anti-dsDNA
Low complement (i.e. low C4 and C3) - complement used in immune complexes
APL antibodies
How can SLE activity be measured?
Combination of clinical signs/symptoms and investigations
Unwell Patient with active lupus typically has:
Low complement C3 and C4 levels
High anti-dsDNA antibodies
How can a platelet count be used to measure activity of SLE?
Thrombocytopenia = more active disease
More autoimmune destruction of platelets
What is the overall aim of SLE treatment?
Remission/low disease activity
Prevention of flares
What must be carefully balanced in SLE treatment?
Controlling disease vs avoiding iatrogenic harm (especially steroids)
What iatrogenic harm can potentially be caused by SLE?
Infection
Osteoporosis
Avascular necrosis (AVN) - often affects hips. Higher incidence in lupus, ++ in presence of APL antibodies
What is used to decide upon the specific choice of treatment in SLE?
Disease severity
Organ involvement/manifestations
What can be used to expedite the tapering/discontinuation of glucocorticoids in SLE?
Appropriate initiation of immunomodulatory agents
What are the most commonly used pharmacological options in SLE management?
Hydroxychloroquine is recommended in all SLE patients
Steroids for acute flares - withdraw ASAP
What is given for mild SLE?
Hydroxychloroquine alone may be sufficient
What is given in more serious SLE?
Hydroxychloroquine + immunomodulatory agents
(mycophenolate, methotrexate, azathioprine)
What is given in SLE with renal disease?
Mycophenolate +/- rituximab
What is given in persistently active SLE?
B cell targeted therapies
Rituximab = anti-CD20 monoclonal antibody: depletes B cells
Belimumab = anti-BAFF antibody (BAFF = a B cell survival factor/cytokine)
What is given in severe/life-threatening SLE (e.g. SLE featuring myocarditis)?
iv steroids + iv cyclophosphamide (+/- rituximab)
How is an SLE patient identified to have antiphospholipid antibody syndrome?
An episode of clot
APL abs positive
What should a patient with SLE and antiphospholipid antibody syndrome receive?
Anticoagulants (e.g. warfarin)
What is anifrolumab?
Emerging therapy
Interferon receptor blockade
What must be considered with SLE and pregnancy?
Risk of disease and drugs to both mother and foetus
How are the best outcomes achieved with SLE and pregnancy?
Get SLE into remission before pregnancy
Pre-pregnancy planning
What is a specific consideration for APL abs and pregnancy?
Associated with miscarriage
Reduce risk with aspirin/heparin
What must be considered with pregnancy and SLE in terms of kidney function?
Pregnancy increases haemodynamic demands - will worsen renal function
Other than APL, what is another risk to the foetus in SLE pregnancies?
Ro antibodies - can cause foetal heartblock
What drug considerations must be taken into account with pregnancy in SLE?
MMF, cyclophosphamide, methotrexate, warfarin are teratogenic - high risk of severe foetal damage/deformity
Hydroxychloroquine, azathioprine, low molecular weight heparin (LMWH) are safe
(not in exam)
What is Sjogren’s syndrome?
Autoimmune exocrinopathy
lymphocytic infiltration of exocrine glands (lacrimal and salivary glands)
Exocrine gland pathology results in
Dry eyes (xerophthalmia)
Dry mouth (xerostomia)
Parotid gland enlargement
(not in exam)
What are the extra-glandular manifestations of Sjogren’s?
non-erosive arthritis
Raynaud’s phenomenon
pleural effusion
autoimmune hepatitis
(not in exam)
What is the autoantibody profile of Sjogren’s?
Ro+, La+. RF often +
CCP -
(not in exam)
What is inflammatory muscle disease?
Dermatomyositis = muscle & skin inflammation
Polymyositis - (muscle only, no rash)
(not in exam)
What are the skin changes in dermatomyositis?
Lilac-coloured (heliotrope) rash on eyelids, malar region and naso-labial folds
Red or purple flat or raised lesions on knuckles (Gottron’s papules
(not in exam)
What are the investigations for inflammatory muscle disease?
Bloods - Elevated creatine kinase (CK)
Electromyography
Muscle biopsy (polymyositis - CD8 T cell infiltrate, ; dermatomyositis - CD4 T cells in addition to B cells)
(not in exam)
Which other pathologies/diseases are strongly associated with inflammatory muscle disease?
Malignancy (10-15%)
Pulmonary fibrosis
(not in exam)
What is systemic sclerosis (scleroderma)?
Thickened skin with Raynaud’s phenomenon
dermal fibrosis
cutaneous calcinosis
telangiectasia
(not in exam)
What are the 2 main categories of scleroderma?
Skin changes may be limited or diffuse
Limited systemic sclerosis:
Fibrotic skin limited to hands, forearms, feet, neck and face
Anti-centromere antibodies
Pulmonary hypertension
Long history of Raynaud’s phenomenon
Diffuse systemic sclerosis:
Fibrotic skin proximal to elbows or knees (excluding face and neck)
Anti-Scl-70 antibodies
Pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
Short history of Raynaud’s phenomenon
