connective tissue disorders

Question 1

what is ankylosing spondylitis

seronegative

Answer 1

chronic spinal inflammation that can result in spinal fusion and deformity
site of inflammation includes enthesis
no autoantibodies = seronegative.

Question 2

what is systemic lupus erythematosus

Answer 2

chronic tissue inflammation in presence of autoantibodies directed against self antigens

• multi site inflammation - particularly joints,skin and kidney
• associated with autoantibodes; anas,anti dsDNA antibodies and antiphospholipid antibodies.

Question 3

connective tissue disorders key points

Answer 3

• arthralgia and arthritis (typically non erosive) may be present
• serum antibodies are characteristic and may aid diagnosis, correlate with disease activity and may be diretly pathogenic
• raynauds phenomenon common with these conditions

Question 4

what is raynauds phenomenon

Answer 4

intermittent vasospasms of digits on exposure to cold
typical colour changes = white -> blue -> red
vasospasm leads to blanching of digit, cyanosis as static venous blood deoxygenates
reactive hyperaemia
* raynauds phenomenon is most comonly isolated and benign condition

Question 5

what group does sle usually affects

Answer 5

female aged between 15-45 yrs

Question 6

what are some of the wide ranging clinical manifestations of sle

Answer 6

malar rash - erythema that spares nasolabial fold
photosensitive rash
mouth ulcers
hair loss
raynauds phenomenon
arthalgia and sometimes arthritis
serositis( pericarditis, pleuritis, less commonly peritonitis)
renal disease - glomerulonephritis
cerebral disease - cerbral lupus e.g psychosis

Question 7

pathogenesis of sle

*dont need to know

Answer 7

apoptosis leads to translocation of nuclear antigens to membrane surface -> impaired clearance of apoptotic results in enhanced presentation of nuclear antigens to immune cells -> b cell autoimmunity -> tissue damage by antibody effector mechanism e.g complement activation and fc receptor engagement

Question 8

why are antiphospholipid antibodies serious in sle

Answer 8

associated with risk of arterial and venous thrombosis

*may occur in absence of sle in what is termed ‘primary antiphospholipid antibody syndrome’

Question 9

what are some investigations and findings for sle

Answer 9

inflammation - high esr but crp is typically normal unless infection/serotitis/arthritis
haematology - haemolytic anaemia, lymphopenia, thrombocytopenia
renal - measure urine protein and urine protein: creatinine ratio, look at albumin too
immunological - anas,adsDNA, complement consumption
clotting - antiphospholipid antibodies

Question 10

disease activity in sle….

Answer 10

unwell lupus patient has low complement c3 and c4 levels and high levels of anti-ds DNA antibodies
= serologically active lupus

Question 11

how does lupus nephritis present

Answer 11

low serum albumin(leaking into urine)

egfr normal

Question 12

what are the treatment aims in sle

Answer 12

aims at remission

or low disease activity and prevention of flares

Question 13

management for sle

Answer 13

hydroxychloroquine is recommended in all patients
maintenance treatment glucocorticoid should be minimised and when possible withdrawn
appropriate initiation of immunomodulatory agents e.g methotrexate, azathioprine, mycophenonite can expedite discontinuation of glucocorticoids

Question 14

what can be given to patients with persistently active/severe sle disease

Answer 14

cyclophosphamide targeted therapy and

b cell targeted therapies - belimumab and rituxumab

Question 15

what should be assessed when sorting management for sle patients

Answer 15

antiphospholipid antibody status
should be assessed for their infectious and cardiovascular diseases risk profile
pregnancy planning

Question 16

what is sjogrens syndrome

Answer 16

autoimmune exocrinopathy - lymphocytic infiltration of expecially exocrine gland and sometimes of other organs - extra glandular involvement

Question 17

what symptoms does exocrine pathology in sjogrens lead to

Answer 17

dry eyes - xeropthalmia
dry mouth - xerostomia
parotid gland enlargement

Question 18

what are the commonest extra glandular manifestations of sjogrens

Answer 18

non erosive arthritis

raynauds phenomenon

Question 19

when is term secondary sjogrens syndrome used

Answer 19

if sjogrens syndrome occurs in context of another connective tissue disorder e.g sle

Question 20

what is inflammatory muscle disease

Answer 20

proximal muscle weakness due to autoimmune mediated inflammation either with rash (dermatomyositis) or without polymyositis

Question 21

what are some skin changes in dermatomyositis

Answer 21

• lilac coloured (heliotrope) rash on eyelids, malar region and nasolabial folds
• red/purple flat or raised lesions on knuckles = gottrons papules
• subcutaneous calcinosis
• mechanics hands (fissuring and crackling of skin over finger pads)

Question 22

what findings would you expect in inflammatory muscle disease

Answer 22

elevated cpk,
abnormal electromyography, abnormal muscle biopsy (polymyositis = cd8 t cells, dermamyo.. = cd4 t cells and b cells)
associated with malignancy (10-15) and pulmonary fibrosis

Question 23

what is systemic sclerosis/scleroderma

Answer 23

thickened skin with raynauds phenomenon

dermal fibrosis, cutaneous calcinosis and telangiectasia

Question 24

what are the skin changes in diffuse systemic sclerosis

Answer 24

• fibrotic skin proximal to elbows/knees
• anti topoisomerase antibodies
• pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
• short history of raynauds phenomenon

Question 25

skin changes in limited systemic sclerosis

Answer 25

fibrotic skin on hands, forearms, feet,neck and face
anti centromere antibodies
pulmonary hypertension
long history of raynauds phenomenon

Question 26

what does crest the subtype stand for in limited systemic sclerosis

Answer 26

calcinosis
raynauds phen
eosophageal dysmobility
sclerodactyl
telangiactasia

Question 27

what is overlap syndrome

Answer 27

features of more than 1 connective tissue disorder are present

Question 28

what is mixed connective tissue disease

Answer 28

patients with features of sle, scleroderma, ra and polymyostitis
identified by presence of atiu1rnp antibody

Question 29

autoantibodies in diffuse systemic sclerosis

Answer 29

anti sci70 antibody

Question 30

autoantibodies in limited systemic sclerosis

Answer 30

anticentromere antibodies

Question 31

key autoantibody in derma/ploymyositis

Answer 31

anti trna transferase antibodies aka antijo1

Question 32

key auto antibodies in sjogrens

Answer 32

no unique abs
but typically see anti ro, anti la
rhematoid factor