🩻MSK🩻 - Lupus

Question 1

What are the autoimmune connective tissue disorders?

Answer 1

SLE
Sjogren’s syndrome
Systemic sclerosis (scleroderma)
Autoimmune inflammatory muscle disease

Question 2

What is SLE?

Answer 2

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

Question 3

What features are characteristic of autoimmune connective tissue disorders in general?

Answer 3

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

Question 4

Outline Raynaud’s

Answer 4

Intermittent vasospasm of digits
Usually triggered by cold exposure
Typical triphasic colour changes - white, blue, red
Severe Raynaud’s -> tissue ischaemia, ulcers and necrosis

Question 5

What is the epidemiology of SLE?

Answer 5

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

Question 6

Why is there so much variety in SLE presentations?

Answer 6

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

Question 7

How do finger deformities in SLE differ from those in types of arthritis?

Answer 7

SLE-induced deformities show no bony erosions - deformity is due purely to soft tissue damage

Question 8

What are some of the clinical features of SLE?

Answer 8

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

Question 9

What marker is a hallmark of SLE?

Answer 9

Presence of ANA

Question 10

What is ANA?

Answer 10

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

Question 11

What is done after ANA are identified?

Answer 11

Question 12

What is APL?

Answer 12

Antiphospholipid (APL) antibodies
As well as ANA, some SLE patients have antibodies directed to phospholipids on cell membrane
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Question 13

What is the presence of APL antibodies associated with?

Answer 13

Increased risk of thrombosis:
Arterial - stroke
Venous - DVT

Pregnancy loss - miscarriage

Question 14

What is anti-phospholipid antibody syndrome?

Answer 14

Persistent presence of APL + a clinical event
Anti-phospholipid antibody syndrome can also occur in absence of SLE
(‘primary anti-phospholipid antibody syndrome’ )

Question 15

What other autoantibodies are specific for SLE?

Answer 15

Anti-double stranded DNA antibodies (anti-dsDNA) - serum level correlates with disease activity
Anti-Sm antibodies

Question 16

What autoantibodies are associated with RA?

Answer 16

Rheumatoid Factor
Anti-cyclic citrullinated peptide antibody

Question 17

What autoantibodies are associated with SLE?

Answer 17

Antinuclear antibodies (ANA)
Anti-double stranded DNA antibodies (anti-dsDNA)
Anti-phospholipid antibodies
Anti-Smith
Anti-Ro
Anti-La
Anti-RNP

Question 18

Which of SLE’s immunopathogeneses stem from innate immunity?

Answer 18

Overactivity of type 1 interferon pathway
Complement pathway abnormalities

Question 19

Which of SLE’s immunopathogeneses stem from adaptive immunity?

Answer 19

Autoreactive T and B cells

Question 20

How is the immune system generating a response to nuclear antigens?
(should be hidden inside the cell)

Answer 20

the ‘waste disposal hypothesis’

Question 21

What types of investigations would you do for SLE?

Answer 21

Inflammation
Haematology
Renal
Immunological

Question 22

What inflammatory markers would their be in SLE?

Answer 22

High ESR
Normal CRP (unless infection or serositis/arthritis)

Question 23

What might you find in haematological investigations in a patient with SLE?

Answer 23

Haemolytic anaemia
Lymphopenia
Thrombocytopenia

Question 24

What renal signs might you see in SLE?

Answer 24

Urine protein - VERY IMPORTANT
Creatinine
Look at albumin
Kidney biopsy if persistent proteinuria

Question 25

What immunological signs might be apparent upon investigation in SLE?

Answer 25

ANA Anti-dsDNA Low complement (i.e. low C4 and C3) - complement used in immune complexes APL antibodies

Question 26

How can SLE activity be measured?

Answer 26

Combination of clinical signs/symptoms and investigations Unwell Patient with active lupus typically has: Low complement C3 and C4 levels High anti-dsDNA antibodies

Question 27

How can a platelet count be used to measure activity of SLE?

Answer 27

Thrombocytopenia = more active disease More autoimmune destruction of platelets

Question 28

What is the overall aim of SLE treatment?

Answer 28

Remission/low disease activity Prevention of flares

Question 29

What must be carefully balanced in SLE treatment?

Answer 29

Controlling disease vs avoiding iatrogenic harm (especially steroids)

Question 30

What iatrogenic harm can potentially be caused by SLE?

Answer 30

Infection Osteoporosis Avascular necrosis (AVN) - often affects hips. Higher incidence in lupus, ++ in presence of APL antibodies

Question 31

What is used to decide upon the specific choice of treatment in SLE?

Answer 31

Disease severity Organ involvement/manifestations

Question 32

What can be used to expedite the tapering/discontinuation of glucocorticoids in SLE?

Answer 32

Appropriate initiation of immunomodulatory agents

Question 33

What are the most commonly used pharmacological options in SLE management?

Answer 33

Hydroxychloroquine is recommended in all SLE patients Steroids for acute flares - withdraw ASAP

Question 34

What is given for mild SLE?

Answer 34

Hydroxychloroquine alone may be sufficient

Question 35

What is given in more serious SLE?

Answer 35

Hydroxychloroquine + immunomodulatory agents (mycophenolate, **methotrexate**, azathioprine)

Question 36

What is given in SLE with renal disease?

Answer 36

Mycophenolate +/- rituximab

Question 37

What is given in persistently active SLE?

Answer 37

B cell targeted therapies Rituximab = anti-CD20 monoclonal antibody: depletes B cells Belimumab = anti-BAFF antibody (BAFF = a B cell survival factor/cytokine)

Question 38

What is given in severe/life-threatening SLE (e.g. SLE featuring myocarditis)?

Answer 38

iv steroids + iv cyclophosphamide (+/- rituximab)

Question 39

How is an SLE patient identified to have antiphospholipid antibody syndrome?

Answer 39

An episode of clot APL abs positive

Question 40

What should a patient with SLE and antiphospholipid antibody syndrome receive?

Answer 40

Anticoagulants (e.g. warfarin)

Question 41

What is anifrolumab?

Answer 41

Emerging therapy Interferon receptor blockade

Question 42

What must be considered with SLE and pregnancy?

Answer 42

Risk of disease and drugs to both mother and foetus

Question 43

How are the best outcomes achieved with SLE and pregnancy?

Answer 43

Get SLE into remission before pregnancy Pre-pregnancy planning

Question 44

What is a specific consideration for APL abs and pregnancy?

Answer 44

Associated with miscarriage Reduce risk with aspirin/heparin

Question 45

What must be considered with pregnancy and SLE in terms of kidney function?

Answer 45

Pregnancy increases haemodynamic demands - will worsen renal function

Question 46

Other than APL, what is another risk to the foetus in SLE pregnancies?

Answer 46

Ro antibodies - can cause foetal heartblock

Question 47

What drug considerations must be taken into account with pregnancy in SLE?

Answer 47

MMF, cyclophosphamide, methotrexate, warfarin are teratogenic - high risk of severe foetal damage/deformity Hydroxychloroquine, azathioprine, low molecular weight heparin (LMWH) are safe

Question 48

(not in exam) What is Sjogren's syndrome?

Answer 48

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

Question 49

(not in exam) What are the extra-glandular manifestations of Sjogren's?

Answer 49

non-erosive arthritis Raynaud’s phenomenon pleural effusion autoimmune hepatitis

Question 50

(not in exam) What is the autoantibody profile of Sjogren's?

Answer 50

Ro+, La+. RF often + CCP -

Question 51

(not in exam) What is inflammatory muscle disease?

Answer 51

Dermatomyositis = muscle & skin inflammation Polymyositis - (muscle only, no rash)

Question 52

(not in exam) What are the skin changes in dermatomyositis?

Answer 52

Lilac-coloured (heliotrope) rash on eyelids, malar region and naso-labial folds Red or purple flat or raised lesions on knuckles (Gottron’s papules

Question 53

(not in exam) What are the investigations for inflammatory muscle disease?

Answer 53

Bloods - Elevated creatine kinase (CK) Electromyography Muscle biopsy (polymyositis - CD8 T cell infiltrate, ; dermatomyositis - CD4 T cells in addition to B cells)

Question 54

(not in exam) Which other pathologies/diseases are strongly associated with inflammatory muscle disease?

Answer 54

Malignancy (10-15%) Pulmonary fibrosis

Question 55

(not in exam) What is systemic sclerosis (scleroderma)?

Answer 55

Thickened skin with Raynaud’s phenomenon dermal fibrosis cutaneous calcinosis telangiectasia

Question 56

(not in exam) What are the 2 main categories of scleroderma?

Answer 56

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