Connective Tissue Disorders Flashcards
What is rheumatoid arthritis?
Chronic joint inflammation can result in joint damage
Site of inflammation = synovium
Associated with autoantibodies (RF and Anti-CCP)
Which autoantibodies are associated with rheumatoid arthritis?
Rheumatoid factor
Anti-CCP
What is the site of inflammation for rheumatoid arthritis?
Synovium
What is ankylosing spondylitis?
- Chronic spinal inflammation that can result in spinal fusion and deformity- spinal fusion is detected on the radiograph as a ‘Bamboo spine’.
- Site of inflammation includes the enthesis
- No autoantibodies (Seronegative).
What are the consequences with ankylosing spondylitis?
Spinal fusion
How is spinal fusion evidently seen on a radiograph?
Bamboo spine
What are the examples of seronegative spondyloarthopathies?
- Ankylosing spondylitis
- Reactive arthritis (Reiter’s Syndrome)
- Arthritis associated with psoriasis (Psoriatic arthritis)
- Arthritis associated with gastrointestinal inflammation (enterohepatic synovitis).
What is SLE?
- Chronic tissue inflammation in the presence of antibodies directed against self-antigens.
- Multi-site inflammation – predominantly in the joints, skin and kidney.
- The formation of immune complexes Type III hypersensitivity.
What type of hypersensitivity is associated with SLE?
Type 3 hypersensitivity -due to formation of immune complexes
Which three main autoantibodies are associated with SLE?
Antinuclear antibodies
Anti-double stranded DNA antibodies
Anti-phospholipid antibodies
Which typeof rash is associated with SLE?
Malar rash
Which sex is mainly affected by SLE?
Female
In which age group is SLE is diagnosed typically?
15-45 years
What are the key features of SLE?
Arthralgias and arthritis are typically non-erosive
Serum autoantibodies are characteristic
What is Raynaud’s phenomenn?
Intermittent vasospasm of digits on exposure to cold
1) Vasospasm - blanching of the digit
2) Cyanosis
3) Reactive hyperaemia
What are the three stages of Raynaud’s?
1) Vasospasm
2) Cyanosis
3) Reactie hyperaemia
What are the colour changes seen in Raynaud’s?
White to blue to red
Why does cyanosis occur after vasospasm in Raynaud’s?
As static venous blood deoxygenates
Why does reactive hyperaemia occur after vasospasm and cyanosis in Raynaud’s?
Transient increase in organ blood flow, as a response to occlusion
What are the clinical manifestations of SLE?
- Malar Rash – Erythema that spares the nasolabial fold
- Photosensitive rash
- Mouth ulcers
- Hair loss
- Raynaud’s phenomenon
- Arthralgia and arthritis (sometimes)
- Serositis (pericarditis, pleuritis, less commonly – peritonitis)
- Renal disease – glomerulonephritis (lupus nephritis)
- Cerebral disease – ‘cerebral lupus’ – psychosis.
What is the pathogenesis of SLE?
Apoptosis leads to translocation of nuclear antigens to membrane surface
Impaired clearance of apoptotic cells results in enhanced presentation of nuclear antigens to immune cells
B-cell autoimmunity
4) Tissue damage by antibody effector mechanisms - complement activation and Fc receptor engagement
What risks are associated with anti-phospholipid (cardiolipin) antibodies in SLE?
There is an increased risk of arterial and venous thrombosis
What autoantibody is present in systemic vasculitis?
Antinuclear cytoplasmic antibodies (ANCA)
Which autoantibodies are screened when ANA positive?
- Anti-Ro
- Anti-La
- Anti-centromere
- Anti-RNP
- Anti-ds-DNA antibodies
- Anti-Scl-70.
What are the two main examples of cytoplasmic antibodies?
Anti-tRNA synthetase
Anti-ribosomal P antibodies
Which antibody is associated in neonatal lupus syndrome?
Anti-La
What is the main clinical risk in a neonate with neonatal lupus syndrome?
Permanent heart block - conduct ECG
What is the significance of anti-ribosomal P antibodies?
Cerebral lupus
What inflammatory markers are raised and normal in SLE?
CRP is normal (Unless infection or serositis)
ESR elevated
What haematological manifestations are found in SLE?
Haemolytic anaemia
Lymphopenia
Thrombocytopenia
What renal investigations are performed in patients with SLE?
Measure urine protein: Creatinine ratio
Albumin
eGFR
What immunological manifestations are found in patients with SLE?
- Antinuclear antibodies
- Anti-double-stranded DNA antibodies – highly specific, correlate with disease activity.
- Complement consumption (Low C4 and C3) – in active disease.
Which parameter in SLE is suggestive of active disease?
Complement consumption and anti-dsDNA antibodies
Which auto-antibody is associated with thrombosis and clotting?
Anti-phospholipid antibodies
How is proteinuria detected in SLE, using serum measurements?
Decreasing serum albumin (also a negative acute phase protein so responds to inflammation)
Why does platelet count decrease in active SLE?
Due to excessive thrombotic activity
Why does haemoglobin decrease as SLE progresses?
Due to autoimmune haemolytic anaemia in lupus
What happens to the reticulocyte count in lupus?
Rises as a compensatory mechanism to the immune complex mediated erythrocyte destruction
What is the recommended management for lupus?
Hydroxychloroquine
What is the maintenance treatment in lupus?
Glucocorticoids
What treatment is available for acute settings of lupus?
Glucocorticoids
Which immunomodulatory agents are used in lupus?
Methotrexate, azathioprine and mycophenolate
How should glucocorticoids be withdrawn?
Tapered
What treatment is recommended in active and severe SLE disease?
Cyclophosphamide
B-cell targeted therapies (rituximab and belimumab)
What is Sjogren’s syndrome?
Autoimmune exocrinopathy - lymphocyte infiltration of exocrine glands
What are the exocrine related manifestations of Sjogren’s syndrome?
Dry eyes
Dry mouth
Parotid gland enlargement
What is xerostomia?
Dry mouth
What is xerophthalmia?
Dry eyes
What are common extra-glandular manifestations of Sjogren’s syndrome?
Non-erosive arthritis and Raynaud’s phenomenon.
What is secondary Sjogren’s syndrome?
Context of another connective tissue disorder (SLE)
What does a salivary gland biopsy reveal in Sjogren’s glands?
Lymphocyte infiltration predominantly CD4 helper T-cells and to lesser extent B lymphocytes
What is Schirmer’s test?
A test to assess tear production.
• Filter paper is placed under the lower lid -extent of wetness measured after 5 minutes.
• Abnormal <5mm after 5 minutes
What is inflammatory muscle disease?
Proximal muscle weakness due to autoimmune-mediated inflammation either with dermatomyositis or without polymyositis (rash).
What skin changes occur in dermatomyositis?
Lilac coloured rash on eyelids (heliotrope), malar region and naso-labial
What colour are Gottron’s papules?
Red-brick
• Red or purple flat or raised lesions on knuckles (Gottron’s papules).
What are the cutaneous manifestations of dermatomyositis?
- Skin changes in dermatomyositis.
- Lilac-coloured (heliotrope) rash on eyelids, malar region and naso-labial folds.
- Red or purple flat or raised lesions on knuckles (Gottron’s papules).
- Subcutaneous calcinosis
- Mechanic’s hands (fissuring and cracking of skin over finger pads).
Which serum markers are elevated in dermatomyositis?
Creatine phosphokinase
Which cell is associated with polymyositis?
CD8 T-cells
Which cell is associated with dermatomyositis?
CD4 T cells, in addition to B-cells
What is systemic sclerosis?
Thickened skin with Raynaud’s phenomenon
Dermal fibrosis - cutaneous calcinosis and telangiectasis
What are the manifestations of diffuse systemic sclerosis?
- Fibrotic skin proximal to elbows or knees (excluding face and neck)
- Anti-topoisomerase-I (Anti-Scl-70) antibodies.
- Pulmonary fibrosis, renal (thrombotic microangiopathy) involvement.
- Short history of Raynaud’s phenomenon.
What are the manifestations of limited systemic sclerosis?
- Fibrotic skin hands, forearms, feet, neck and face
- Anti-centromere antibodies
- Pulmonary hypertension
- Long history of Raynaud’s phenomenon.
Which antibodies are associated with CREST and limited systemic sclerosis?
Anti-centromere antibodies
What is CREST?
CREST describes a sub-type of limited systemic sclerosis.
Calcinosis, Raynaud’s phenomenon, Oesophageal dysmotility, Sclerodactyly, Telangiectasia
What is overlap syndrome?
- When features of more than 1 connective disorder are present: SLE and Inflammatory muscle disease.
- Incomplete features of a connective tissue disease are present we can use the term undifferentiated connective tissue disease
Which auto-antibody is associated with mixed connective tissue disorder?
Anti-U1 RNP antibody
Which auto-antibody is associated with diffuse systemic sclerosis?
Anti-Scl-70
What are anti-centromere autoantibodies associated with?
Limited systemic sclerosis
Which autoantibodies are associated with polymyositis?
Anti-tRNA transferase
