Connective tissue diseases

Question 1

Which antibodies are typically found in systemic lupus erythematosus?

Answer 1

ANA and anti-DNA antibodies

Question 2

Is SLE more common in women or men?

Answer 2

Women

F>M, 9:1

Question 3

What age are people most likely to develop SLE?

Answer 3

Child-bearing age

Question 4

What is the pathophysiology of SLE?

Answer 4

Antigen-driven immune-mediated disease. Immunoglobulin G antibodies to double-stranded DNA as well as nuclear proteins.
Tolerance to self antigens in the B-cell pool is maintained.
T-helper cell dysregulation of B cells may arise - resulting in autoimmunity.

Question 5

What are the non-specific symptoms and signs of SLE?

Answer 5

Malaise
Weight loss
Myalgia
Fever
Fatigue
Non-tender regional lymph nodes
Seizures
Depression
Cranial nerve issues

Question 6

What are the specific symptoms and signs of SLE?

Answer 6

Malar rash
Discoid rash 
Photosensitivity
Renal failure
Arthritis
Oral ulcers
Serositis

Question 7

What are the diagnosis criteria for SLE?

Answer 7

4 or more criteria, at least one clinical and one laboratory criteria, OR biopsy-proven lupus nephritis with positive ANA or anti-DNA.

Question 8

What are the clinical criteria for SLE?

Answer 8

Acute cutaneous lupus
Chronic cutaneous lupus
Oral or nasal ulcers
Non-scarring alopecia
Arthritis
Serositis
Renal
Neurological
Haemolytic anaemia
Leukopenia
Thrombocytopenia

Question 9

What are the immunological criteria for SLE?

Answer 9

ANA
Anti-DNA
Anti-Sm
Antiphospholipid antibody
Low complement
Direct Coombs test

Question 10

What is the management for an acute flare of SLE?

Answer 10

Hydroxychloroquine if serositis/joint involvement.
Cyclophosphamide and high dose prednisolone if renal involvement/CNS.
NSAIDs

Question 11

What is the long term management of SLE?

Answer 11

NSAIDs
Hydroxychloroquine
Low dose steroids
Azathioprine, methotrexate, mycophenolate.

Question 12

What is the pathophysiology of anti-phospholipid syndrome?

Answer 12

Antibodies to phospholipid binding plasma proteins on platelets and monocytes results in the development of venous, arterial, and microvascular thromboses, and/or pregnancy associated morbidity.

Question 13

How is anti-phospholipid syndrome diagnosed?

Answer 13

If at leaset 1 vascular thrombosis or pregnancy morbidity is present in association with the presence of anti-phospholipid antibodies on 2 or more occasions, 12 weeks apart.

Question 14

How is pregnancy morbidity defined?

Answer 14

The loss of 3 or more embryos before the 10th week of gestation.
And/or 1 or more otherwise unexplained fetal deaths beyond the 10th week of gestation.
And/or the premature birth of a morphologically normal neonate before the 34th week of gestation because of eclampsia, severe pre-eclampsia, or placental insufficiency.

Question 15

Which investigations would be carried out to test for anti-phospholipid syndrome?

Answer 15

Lupus anticoagulant
ANA and anti-double stranded DNA antibodies.
Anticardiolipid antibodies.
FBC may show thrombocytopenia.
Urea and creatinine may be increased if nephropathy.
Doppler/CTPA or MR angio
Echo - heart valve abnormalities

Question 16

How is antiphospholipid syndrome managed?

Answer 16

Treat thrombosis - low molecular weight heparin and then warfarin after.
If incidental finding of APL antibodies then watch and wait unless pregnant and need aspirin.
May need immunosuppression in catastrophic flare ups.

Question 17

What is systemic sclerosis?

Answer 17

Functional and structural abnormalities of small blood vessels, fibrosis of skin and internal organs with production of autoantibodies..

Question 18

What are the features of limited cutaneous systemic sclerosis?

Answer 18

Calcinosis
Reynaud's
Oesophageal and gut dysmotility
Sclerodactyly
Telangectasia

Risk of pulmonary hypertension.

Question 19

What is the vascular involvement of systemic sclerosis?

Answer 19

Raynaud’s phenomenon
Ischaemic digital ulcers
Hypertensive crisis
Pulmonary arterial hypertension

Question 20

Which organs can fibrosis involve in systemic sclerosis?

Answer 20

Lungs
Heart
GI tract

Question 21

How is systemic sclerosis diagnosed?

Answer 21

Primarily clinical
Elevated ESR/CRP
May have raised ANA or RhF
Anti-centromere (skin involvement and better prognosis)
Anti-Scl70 (worse prognosis and lung fibrosis)

Question 22

What is the management of systemic sclerosis?

Answer 22

No cure
Immunosuppressive regimes - cyclophosphamide/methotrexate
Control BP - ACE inhibitor or ARB
Sildenafil or calcium channel blocker
Low dose steroids
Monitor BP and renal function
Annual echo and spirometry

Question 23

What is the pathophysiology of Raynaud’s?

Answer 23

Vasospasm brought on by cold temperataures causes digits to change colour to white from lack of blood flow.
Affected areas subsequently turn blue due to de-oxygenation and/or red due to reperfusion.

Question 24

What percentage of the population is affected by Raynaud’s?

Answer 24

1-3%

Question 25

Is Raynaud's more common in men or women?

Answer 25

Women

Question 26

What is secondary Raynauds?

Answer 26

Associated with underlying connective tissue disease. Upregulation of inflammatory cytokines increased in secondary. Diffuse scleroderma have increased adrenoreceptor activity. May pre-date connective tissue disease.

Question 27

What are the investigations of Raynauds?

Answer 27

``` If the patient has new onset Raynaud's, is >40 years old and/or has features from history or exam that suggest secondary causes: ANA with titre and pattern FBC ESR Serum creatinine Urinalysis ```

Question 28

Which features that may be found in Raynaud's are predictive for scleroderma?

Answer 28

Anti-centromere antibody | Dilated capillaries at the peri-ungal region.

Question 29

How is Raynaud's treated?

Answer 29

``` Aspirin Statin Calcium channel blockers May need sildenafil is severe secondary NSAIDs for analgesia ```

Question 30

What is Sjogren's?

Answer 30

Chronic inflammatory and auto-immune disorder characterised by diminished lacrimal and salivary gland secretion (sicca complex) due to lymphocytic infiltration.

Question 31

How does sjogren's present?

Answer 31

With fatigue, dry eyes and dry mouth.

Question 32

How is Sjogren's diagnosed?

Answer 32

Positive ANA's, Ro and anti-La auto-antibodies, decreased saliva and tear production, lymphocytic infiltration in labial salivary gland biopsy.

Question 33

What is the treatment for sjogren's?

Answer 33

Mainly symptomatic, unless vasculitis/MSK involvement, in which case steroids and immunosuppression

Question 34

Which additional symptoms may be present in Sjogren's?

Answer 34

``` Dry skin Dry nose Dry throat Dry vagina Arthralgia Myalgia Peripheral neuropathies Pulmonary, thyroid and renal disorders Lymphoma ```

Question 35

What is the pathophysiology of polymyositis?

Answer 35

Major histocompatitibility complex-1 mediate cytotoxicity by CD8 T cells. Immunological synapses form between CD8 T cells and MHC-1 expressed on muscle fibres - inflammation and necrosis.

Question 36

Which malignancies are associated with polymyositis?

Answer 36

Non-Hodgkin's lymphoma Lung cancer Bladder cancer

Question 37

What is the biggest risk factor for dermatomyositis?

Answer 37

UV radiation intensity

Question 38

What is the pathophysiology of dermatomyositis?

Answer 38

Primary antigen target consists of components of the vascular endothelium of the larger endomysial blood vessels. Lymphatic response results in capillary necrosis, microinfarction, inflammation and cell then spread into muscles.

Question 39

What are the characteristic skin lesions of dermatomyositis?

Answer 39

Heliotrope rash with eyelid oedema Facial rash Gottron's papules (erythema of knuckles accompanied by a raised violaceous scaly eruption) Erythematous rash over the knees, elbows, malleoli, and at the base of the neck and upper chest, forming a V sign. Nail fold changes such a dilation of capillary loops of periungual area.

Question 40

Which cancers are associated with dermatomyositis?

Answer 40

Ovarian cancer Pancreatic cancer Non-Hodgkin's lymphoma

Question 41

What are the clinical features of inflammatory polymyopathies?

Answer 41

Proximal symmetrical muscle weakness. Increased difficulties in performing motor tasks predominantly requiring proximal muscles - e.g. getting up from a chair, climbing steps, combing hair. Find motor tasks that depend on distal muscles affected - e.g. sewing, knitting, writing (late in the course of disease)

Question 42

What are the extramuscular symptoms of polymyopathies?

Answer 42

``` Arthralgia Dysphagia Shortness of breath Palpitatins Syncope Weight loss Fatigue Skin lesions MI symptoms Pain and muscle tenderness ```

Question 43

How is diagnosis of inflammatory polymyopathies confirmed?

Answer 43

Elevated serum muscle derived enzymes (CK) 25% have anti Jo antibodies Typical EMG findings Inflammation and necrosis on muscle biopsy.

Question 44

What are the investigations for polymyopathies?

Answer 44

``` Creatinine kinase Anti Jo antibodies EMG Muscle biopsy Lactate dehydrogenase Myoglobin Aspartate aminotransferase Alanine aminotransferase ```

Question 45

What is the management of inflammatory polymyopathies?

Answer 45

Corticosteroids - first line treatment. IV or oral depending on severity of presentation. IV immunoglobulin, methotrexate, and azathioprine are used as second-line therapy or if life threatening attacks. Third line therapies include cyclophosphamide, mycophenolate, ciclosporin and tacrolimus