rheumatology and orthopaedics

Question 1

6 chronic overlapping autoimmune diseases including systemic lupus erythematosus (share some features but can be separated based on presentation)

Answer 1

rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, Sjögren’s syndrome

Question 2

spectrum of autoimmune connective diseases (joint -> muscle -> complicated involvement)

Answer 2

rheumatoid arthritis -> Sjögren’s syndrome -> systemic lupus erythematosus -> dermatomyositis -> polymyositis -> systemic sclerosis

Question 3

systemic lupus erythematosus: male:female ratio, presentation, increased ethnic prevalence

Answer 3

1:9, 15-40 years presentation, increased in Afro-Caribbean, Asian and Chinese, rare

Question 4

what does systemic lupus erythematosus principally affect

Answer 4

joints, skin

Question 5

3 other things systemic lupus erythematosus affects

Answer 5

lungs, kidneys, haematology

Question 6

polygenic associations suggesting systemic lupus erythematosus susceptibility: missing genes

Answer 6

competent genes e.g. C1q and C3

Question 7

polygenic associations suggesting systemic lupus erythematosus susceptibility: over-represented genes

Answer 7

Fc receptors, HLA genes

Question 8

5 clinical presentations of systemic lupus erythematosus

Answer 8

[usually young woman complaining of] malaise, fever (pyrexia), fatigue, weight loss, lymphadenopathy [with chronicity]

Question 9

4 specific features of systemic lupus erythematosus

Answer 9

butterfly rash (spare nasolabial folds with no puss, with permanent scarring if deep epidermal), alopecia, arthralgia, Raynaud’s phenomenon

Question 10

3 other severe features of systemic lupus erythematosus

Answer 10

inflammation of kidney, CNS, heart and lungs; accelerated atherosclerosis; vasculitis (systemic lupus erythematosus causes predisposition)

Question 11

what is ACR criterion for systemic lupus erythematosus based on

Answer 11

multi-system chronic auto-immune inflammatory disease

Question 12

pathogenesis pathway of systemic lupus erythematosus

Answer 12

genetic predisposition and environmental triggers -> activates innate and adaptive immunity -> chronic immune complexes (due to circulating autoantibodies) -> irreversible and vicious cycle of tissue damage with deficient clearance of apoptotic cells

Question 13

6 functions of B cells

Answer 13

activate antigen presenting cell function; regulate T cell activation, anergy or differentiation; produce cytokines; regulate FDC differentiation and lymphoid organisation; antigen presentation; antibody production

Question 14

how are B cells affected in systemic lupus erythematosus

Answer 14

genetic factors cause B cell hyperreactivity, directly resulting in autoantibody production and end organ damage; also increases B cell capacity to enhance function of variety of other cells contributing to B cell responses

Question 15

how do genetic factors in systemic lupus erythematosus enhance B cell responsiveness indirectly

Answer 15

genetic factors directly alter function of T cells and APCs, as well as cytokine production/availability of endogenous antigens, contributing to likelihood that enhanced B cell responsiveness will lead to autoimmunity and end organ damage (vicious cycle)

Question 16

pathophysiology: autoantibody formation pathway in systemic lupus erythematosus

Answer 16

abnormal clearance of apoptotic cell material -> dendritic cell uptake of autoantigens and activation of B cells -> B cell Ig class switching and affinity maturation -> IgG autoantibodies -> immune complexes -> complement activation (e.g. causing rash), cytokine generation etc.

Question 17

8 laboratory tests for systemic lupus erythematosus

Answer 17

antinuclear antibodies (first step), anti-dsDNA and Sm (second step), increased complement consumption, anti-cardiolipin antibodies, lupus anticoagulant, B1 glycoprotein, haematology, renal

Question 18

laboratory tests indicating systemic lupus erythematosus: antinuclear antibodies specificity and what they bind to

Answer 18

antinuclear antibodies are relatively non-specific, but pattern of fluorescent tag is important; homogenous antibody binding to nucleus DNA

Question 19

laboratory tests for systemic lupus erythematosus: anti-dsDNA and Sm (anti-Sm is diagnostic) specificity and senstivity

Answer 19

more specific but less sensitive

Question 20

laboratory tests for systemic lupus erythematosus: what diseases are anti-Ro and/or La present in

Answer 20

common in subacute cutaneous lupus erythematosus, but also in neonatal lupus syndrome and Sjögren’s syndrome

Question 21

laboratory tests for systemic lupus erythematosus: haematologic discoveries

Answer 21

lymphopenia or normochromic anaemia (due to haemolysis); leukopenia, AIHA, thrombocytopenia

Question 22

laboratory tests for systemic lupus erythematosus: renal discoveries

Answer 22

proteinuria, haematuria, active urinary sediment

Question 23

3 stages of assessing systemic lupus erythematosus

Answer 23

identify pattern of organ involvement -> monitor function of affected organs -> identify pattern of autoantibodies expressed

Question 24

assessing systemic lupus erythematosus: renal function monitoring

Answer 24

blood pressure and GFR, urea and electrolytes, urine sediment, protein:creatinine ratio

Question 25

assessing systemic lupus erythematosus: lungs/CVS monitoring

Answer 25

lung function, ECG

Question 26

assessing systemic lupus erythematosus: other organ systems affected

Answer 26

skin, haematology, eyes

Question 27

assessing systemic lupus erythematosus: 2 techniques used to identify renal disease by pattern of autoantibodies expressed

Answer 27

anti-dsDNA, anti-Sm

Question 28

assessing systemic lupus erythematosus: technique used to identify pattern of autoantibodies expressed

Answer 28

anti-cardiolipin antibodies

Question 29

5 clinical features signifying systemic lupus erythematosus activity, which are identified to pre-empt severe attacks

Answer 29

weight loss, fatigue, malaise, hair loss (alopecia), rash

Question 30

3 laboratory markers signifying systemic lupus erythematosus activity

Answer 30

ESR, increased complement consumption (low C3 and C4), increased anti-dsDNA (other antibodies (e.g. antinuclear antibodies) and CRP are poor indicators, as CRP does not increase)

Question 31

3 divisions of systemic lupus erythematosus

Answer 31

mild, moderate, severe

Question 32

features of mild systemic lupus erythematosus

Answer 32

joint (arthralgia) +/- skin (rash) involvement

Question 33

features of moderate systemic lupus erythematosus

Answer 33

inflammation of other organs, pleuritis, pericarditis, mild nephritis

Question 34

features of severe systemic lupus erythematosus

Answer 34

severe inflammation of vital organs (severe nephritis, CNS disease, pulmonary disease, cardiac involvement, autoimmune haemolytic anaemia, thrombocytopenia, TTP)

Question 35

treatment of mild systemic lupus erythematosus

Answer 35

paracetamol +/- NSAID, and monitor renal function; hydroxychloroquine: arthropathy, cutaneous manifestations, mild disease activity; topical corticosteroids if rash on face

Question 36

2 indications of moderate systemic lupus erythematosus

Answer 36

failure of hydroxychloroquine/NSAID; organ/life threatening disease

Question 37

how are corticosteroids administered to treat moderate systemic lupus erythematosus, and side effects

Answer 37

high initial dose and chronic administration; side effects include osteoporosis, hypertension, diabetes, weight gain, immunosuppression

Question 38

2 treatments for severe systemic lupus erythematosus

Answer 38

azathioprine, cyclophosphamide

Question 39

azathioprine for severe systemic lupus erythematosus: risks, monitoring

Answer 39

effective steroid-sparing agent, but 20% neutropenia (incl. bone marrow suppression), so regular FBC and biochemistry monitoring

Question 40

cyclophosphamide for severe systemic lupus erythematosus: administration, risks

Answer 40

i.v. pulsed or oral; severe organ involvement, e.g. nephritis, bone marrow suppression, infertility, cystitis

Question 41

2 novel treatments for severe systemic lupus erythematosus

Answer 41

mycophenolate mofetil, rituximab

Question 42

what is mycophenolate mofetil and how is it used to treat severe systemic lupus erythematosus

Answer 42

reversible inhibitor of inosine monophosphate dehydrogenase (rate-limiting enzyme in de novo purine synthesis), which lymphocytes are dependent on

Question 43

what is rituximab and how is it used to treat severe systemic lupus erythematosus

Answer 43

anti-CD20 (B lymphocyte antigen) monoclonal antibody therapy, leading to depletion of B cells (effective in lupus nephritis)

Question 44

what does monoclonal antibody belimumab target

Answer 44

BLyS on B lymphocyte

Question 45

survival chances of systemic lupus erythematosus if no nephritis vs nephritis

Answer 45

no nephritis 85% vs nephritis 60%

Question 46

in what patients is prognosis of systemic lupus erythematosus worse

Answer 46

if black, male, low socio-economic status

Question 47

bimodal pattern: early systemic lupus erythematosus

Answer 47

active lupus: renal failure (protein in urine as poor glomerular filtration), CNS disease (accelerated atherosclerosis causing trouble); infection

Question 48

bimodal pattern: late systemic lupus erythematosus

Answer 48

myocardial infarction

Question 49

what do clinical features of systemic lupus erythematosus depend on

Answer 49

organ affected

Question 50

3 features of treatments for systemic lupus erythematosus

Answer 50

symptomatic, immune-modulating, immunosuppressive; aggressive treatment for systemic lupus erythematosus and other pre-existing diseases