1b// Lupus and Related Autoimmune Connective Tissue Diseases Flashcards
What are the autoimmune connective tissue disorders?
Systemic Lupus Erythematosus (SLE)
Sjogren’s syndrome
Systemic sclerosis (scleroderma)
Autoimmune Inflammatory muscle disease
*overlap syndromes can occur, especially in children
*NB term “connective tissue disorder” not entirely accurate – often involvement of other organs ‘Multisystem autoimmune rheumatic diseases’ might be better
Give an overview of RA.
What is ankylosing spondylitis?
Chronic spinal inflammation that can result in spinal fusion and deformity
Where is the site of inflammation for ankylosing spondylitis? And what are the antibodies involved?
Site of inflammation includes the enthesis
no autoantibodies
What are the 4 seronegative inflammatory arthritis?
Ankylosing spondylitis
Reactive Arthritis
Arthritis associated with psoriasis (psoriatic arthritis)
Arthritis associated with gastrointestinal inflammation
(enteropathic arthritis)
What is SLE?
Systemic lupus erythematosus (SLE)
Autoimmune disease involving disturbance of both innate and adaptive immune systems
What is the v basic pathogenesis of SLE?
Autoantibodies (antibodies directed against self antigens)
-antibodies to nuclear components
Antibody-antigen (immune complexes) & other mechanisms -> chronic tissue inflammation:
Multi-site inflammation but particularly the joints, skin and kidney
What are the 3 general points of autoimmune connective tissue disorders?
1) Arthralgia and arthritis is typically non-erosive (unlike rheumatoid)
2) Serum autoantibodies are characteristic and…
- Useful diagnostically
- Some correlate with disease activity
- May be directly pathogenic
3) Raynaud’s phenomenon is common in these conditions
What is Raynaud’s phenomenon?
Intermittent vasospasm of digits
Usually triggered by cold exposure
Typical triphasic colour changes
WHITE -> Vasospasm leads to blanching of digit
BLUE -> Cyanosis as static venous blood deoxygenates
RED -> Reactive hyperaemia
What does severe Raynaud’s phenomenon lead to?
Severe Raynaud’s -> tissue ischaemia, ulcers and necrosis
What is the epidemiology of SLE?
What are the skin and mucosal clinical features of SLE?
Malar rash – erythema that spares the nasolabial fold Photosensitive rash
Mouth ulcers
Hair loss
What are the vascular clinical features of SLE?
Raynaud’s
What are the MSK clinical features of SLE?
Arthralgia and sometimes arthritis (usually non-erosive)
What are the internal organs clinical features of SLE?
Serositis (pericarditis, pleuritis, less commonly peritonitis) Renal disease – glomerulonephritis (‘lupus nephritis’) Cerebral disease – ‘cerebral lupus’ e.g. psychosis Myocarditis
What are the haematological clinical features of SLE?
autoimmune thrombocytopenia (low platelets) haemolytic anaemia
Lymphopenia
What are “other” clinical features of SLE? (2)
Lymphadenopathy
Fever in absence of infection
What antibody is a hallmark of SLE?
ANA anti-nuclear antibodies
In who is ANA found?
Found in all SLE patients
Negative ANA effectively rules out SLE
However, ANA is not specific for lupus;
- may be seen in other autoimmune diseases, infection or even healthy people
What will the lab do for ANA?
Lab will do further more specific autoAb tests to identify what ANA are reacting to…
- Anti-ds-DNA antibodies
- Anti-Ro
- Anti-La
- Anti-centromere
- Anti-Smith (Sm)
- Anti-RNP
- Anti-Scl-70
Apart from ANA, what antibody can be found in SLE patients?
As well as ANA, some SLE patients have antibodies directed to phospholipids on cell membrane
What are APLs associated with risk wise?
APL are associated with ↑ risk of:
1) Thrombosis
arterial (e.g. stroke)
venous (e.g. deep vein thrombosis, DVT)
2) Pregnancy loss (miscarriage)
What does persistent presence of APL lead to?
Persistent presence of APL + a clinical event = “anti-phospholipid antibody syndrome”
When can anti-phospholipid antibody syndrome occur asw?
Anti-phospholipid antibody syndrome can also occur in absence of SLE (‘primary anti-phospholipid antibody syndrome’ )
What are the main autoantibodies for SLE?
What are the autoantibodies rheumatology?
What is the immunopathogenesis of SLE?
How is the immune system generating a response to nuclear antigens as it should be hidden inside the cell? (the waste disposal hypothesis)
Why are manifestations of lupus so varied?
it is systemic autoimmunity, so any organ can be affected
unlike hashimoto’s where it’s only the thyroid
From investigations of SLE, what can be seen for inflammation?
high ESR but usually normal C-reactive protein unless infection or serositis/arthritis
From investigations of SLE, what can be seen for haematology?
Haemolytic anaemia, Lymphopenia, Thrombocytopenia
From investigations of SLE, what can be seen/ done for renal?
very important to measure urine protein (urinalysis + quantify with urine protein:creatinine ratio [uPCR])
Creatinine (part of “U&E”, measure of renal function)
look at albumin
Kidney biopsy if persistent proteinuria
From investigations of SLE, what can be seen/ done for immunological?
Antinuclear antibodies
Anti-double-stranded DNA antibodies - highly specific, correlate with disease activity
Complement consumption – e.g. low C4 and C3
antiphospholipid antibodies
In treated patients SOME changes may reflect ADVERSE REACTIONS TO MEDICATION
* e.g. abnormal liver function tests (‘transaminitis’) or fall in neutrophil count (neutropenia)
How do you measure disease activity?
Combination of:
-Clinical symptoms and signs
-Investigations
What does an unwell patient with active lupus typically have (immunology wise)?
Low complement C3 and C4 levels
High anti-dsDNA antibodies
What are the general principles of management of SLE?
- Treatment in SLE aims at remission or low disease activity and prevention of flares
- Balance of controlling disease vs avoiding iatrogenic harm (especially steroids)
- Specific choice of treatment will depend on disease severity and organ manifestations
What are the possible side effects of steroids?
Infection
Osteoporosis
Avascular necrosis (AVN) - often affects hips: higher incidence in lupus, especially in presence of APL Abs
Appropriate initiation of immunomodulatory agents can expedite the tapering/ discontinuation of glucocorticoids
What is recommended for all patients with lupus treatment wise?
Hydroxychloroquine is recommended in all patients with lupus
What is given to treat acute flares in SLE?
Steroids for acute flare but aim to withdraw as soon as safe to do so
What is given as treatment for mild disease SLE?
Mild disease: Hydroxychloroquine alone may be sufficient
What is given for a more serious disease of SLE?
If more serious disease, immunomodulatory agents (mycophenolate, methotrexate, azathioprine)
What is given for renal disease in SLE?
Mycophenolate +/- rituximab usually used for renal disease
What is given in persistently active disease of SLE?
In persistently active disease: 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 for severe or life-threatening disease of SLE?
Severe or life-threatening disease (e.g. myocarditis) : iv steroids + iv cyclophosphamide (+/- rituximab)
What is given to patients with SLE and anti-phospholipid syndrome?
Patients with SLE and antiphospholipid antibody syndrome (i.e. episode of clot + antiphospholipid antibody positive) should be treated with anticoagulation (warfarin)
What is an emerging therapy for SLE?
anifrolumab (interferon receptor blockade)
What should be considered with pregnancy and lupus?
What are the types of autoimmune inflammatory muscle disease?
Polymyositis Dermatomyositis
What are the types of Systemic sclerosis (scleroderma)?
Diffuse cutaneous Limited cutaneous
What is SJÖGREN’S SYNDROME?
Autoimmune exocrinopathy
lymphocytic infiltration of exocrine glands (lacrimal and salivary glands)
What does the exocrine gland pathology result in in SJÖGREN’S SYNDROME?
Dry eyes (xerophthalmia)
Dry mouth (xerostomia)
Parotid gland enlargement
What are extra-glandular manifestations of SJÖGREN’S SYNDROME?
non-erosive arthritis
Raynaud’s phenomenon pleural effusion autoimmune hepatitis
What are autoantibodies involved with SJÖGREN’S SYNDROME?
Ro+, La+. RF often + but CCP -.
What is secondary Sjögren’s syndrome?
Termed ‘secondary’ Sjögren’s syndrome if occurs in context of another connective tissue disorder e.g. SLE
What is inflammatory muscle disease?
Autoimmune-mediated inflammation of muscle
Causes proximal muscle weakness (& sometimes pain)
What is dermatomyositis?
muscle and skin inflammation
What is polymyositis?
(muscle only, no rash)
What are investigations for dermatomyositis?
Investigations:
1) Bloods: Elevated CK (creatine kinase)
2) Electromyography (electrical activity of the muscles)
3) Muscle biopsy (polymyositis = CD8 T cell infiltrate; dermatomyositis = CD4 T cells in addition to B cells)
NB associated with malignancy (10-15%) and pulmonary fibrosis
What is systemic sclerosis?
Thickened skin with Raynaud’s phenomenon
dermal fibrosis
cutaneous calcinosis
telangiectasia
Describe the skin changes in systemic sclerosis.
Skin changes may be limited or diffuse
Describe limited systemic sclerosis.
Fibrotic skin limited to hands, forearms, feet, neck and face
Anti-centromere antibodies
Pulmonary hypertension
Long history of Raynaud’s phenomenon
*CREST describes a sub-type of limited systemic sclerosis.
It stands for Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
Describe 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
