Connective Tissue Disorders Flashcards
What are the key CTDs?
- SLE
- Sjogren’s synfrome
- Autoimmune inflammatory muscle disease
- Systemic sclerosis (scleroderma)
- Overlap syndromes
What are the types of autoimmune inflammatory muscle disease?
- Polymyositis
* Dermatomyositis
What are the types of scleroderma?
- Diffuse cutaneous
* Limited cutaneous
What is RA?
Chronic joint inflammation that can result in joint damage
What is the site of inflammation in RA?
synovium
What are the associated autoantibodies in RA?
- Rheumatoid factor
2. Anti-cyclic citrullinated peptide (CCP) antibodies
What is ankylosing spondylitis?
Chronic spinal inflammation that can result in spinal fusion and deformity
What is the site of inflammation in ankylosing spondylitis?
enthesis
What are the antibodies in ankylosing spondylitis?
No autoantibodies (‘seronegative’)
What are the seronegative spondyloarthropathies?
- Ankylosing spondylitis
- Reactive Arthritis (Reiters syndrome)
- Arthritis associated with psoriasis (psoriatic arthritis)
- Arthritis associated with gastrointestinal inflammation (enteropathic synovitis)
What is SLE?
chronic tissue inflammation in the presence of antibodies directed against self antigens
Where does SLE affect?
multi-site inflammation but particularly the joints, skin and kidney
What are the associated auto-antibodies in SLE?
- Antinuclear antibodies
- Anti-double stranded DNA antibodies
- Anti-phospholipid antibodies
What are connective tissue diseases?
- Systemic lupus erythematosus
- Sjogren’s syndrome
- Autoimmune Inflammatory muscle disease
- Systemic sclerosis (scleroderma)
- Overlap syndromes
What type of disease are typically non-erosive?
arthralgia and arthritis
Why are serum autoantibodies useful?
- May aid diagnosis
- Correlate with disease activity
- May be directly pathogenic
What is Raynaud’s phenomenon?
- in CTDs
- intermittent vasospasm of digits on exposure to cold
What are the colour changes in Raynaud’s phenomenon?
- Typical colour changes – white to blue to red
1. Vasospasm leads to blanching of digit
2. Cyanosis as static venous blood deoxygenates
3. Reactive hyperaemia
Is Raynaud’s usually isolated?
most commonly isolated and benign condition (‘Primary Raynaud’s phenomenon’)
When is SLE usually diagnosed?
prototypic autoimmune disease typically diagnosed in female aged between 15 – 45 years
What are the wide-ranging clinical manifestations for SLE?
- Malar rash – erythema that spares the nasolabial fold
- Photosensitive rash
- Mouth ulcers
- Hair loss
- Raynaud’s phenomenon
- Arthralgia and sometimes arthritis
- Serositis (pericarditis, pleuritis, less commonly peritonitis)
- Renal disease – glomerulonephritis (‘lupus nephritis’)
- Cerebral disease – ‘cerebral lupus’ e.g. psychosis
What is the current paradigm 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
- Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
What are the key autoantibodies in RA?
1, Rheumatoid Factor
2. Anti-cyclic citrullinated peptide antibody
also termed antibodies to citrullinated peptide antigens (ACPA)
What are the key autoantibodies in SLE?
- Antinuclear antibodies (ANA)
- Anti-double stranded DNA antibodies (anti-dsDNA)
- Anti-phospholipid antibodies
also termed anti-cardiolipin antibodies and associated with risk of arterial and venous thrombosis in SLE; may also occur in absence of SLE in what is termed the ‘primary anti-phospholipid antibody syndrome’
What are the key autoantibodies in OA?
none
What are the key autoantibodies in Reactive Arthritis?
none
What are the key autoantibodies in gout?
none
What are the key autoantibodies in ankylosing spondylitis?
none
What are the key autoantibodies in systemic vasculitis?
antinuclear cytoplasmic antibodies (ANCA)
If ANA is positive the clinical laboratory what further tests to determine which type of ANA it is – typically these include screening for?
- Anti-Ro
- Anti-La
- Anti-centromere
- Anti-Sm
- Anti-RNP
- Anti-ds-DNA antibodies
- Anti-Scl-70
What are cytoplasmic antibodies?
- Anti-tRNA synthetase antibodies
2. Anti-ribosomal P antibodies
What is the significance of ANA in SLE?
- Seen in all SLE cases
2. Not specific for SLE
What is the significance of anti-dsDNA in SLE?
- Specific for SLE
2. Serum level of antibody correlated with disease activity
What is the significance of anti-phospholipid antibodies (also termed anti-cardiolipin antibodies) in SLE?
- associated with risk of arterial and venous thrombosis in SLE
- may also occur in absence of SLE in what is termed the ‘primary anti-phospholipid antibody syndrome
What is the significance of anti-sm antibodies in SLE?
- Specific for SLE
2. Serum level of antibody does NOT correlate with disease activity
What is the significance of Anti-Ro and Anti-La antibodies in SLE?
- Secondary to Sjogren’s syndrome
2. Neonatal lupus syndrome (transient rash in neonate, permanent heartblock)
What is the significance of anti-ribosomal P antibodies in SLE?
Cerebral lupus
What are the investigations for inflammation in SLE?
- high ESR
2. C-reactive protein is typically normal unless infection or serositis/arthritis
What are the investigations for haematology in SLE?
- Haemolytic anaemia
- Lymphopenia
- Thrombocytopenia
What are the investigations for renal in SLE?
- very important to measure urine protein (most commonly urine protein:creatinine ratio [uPCR])
- look at albumin
What are the investigations for immunological in SLE?
- Antinuclear antibodies
- Anti-double-stranded DNA antibodies - highly specific, correlate with disease activity
- Complement consumption – e.g. low C4 and C3
What are the investigations for clotting in SLE?
-antiphospholipid antibodies
•Lupus anticoagulant and anti-cardiolipin antibodies
What can happen with SLE investigations in treated patients?
- In treated patients SOME changes may reflect ADVERSE REACTIONS TO MEDICATION
- e.g. abnormal liver function (‘transaminitis’) or fall in neutrophil count (neutropenia)
What are the complement C3 and C4 levels in unwell lupus patients?
- Low complement C3 and C4
2. High levels of anti-ds-DNA antibodies
What is the aim of treatment in SLE?
remission or low disease activity and prevention of flares
What medication is used in SLE treatment?
- Hydroxychloroquine recommended in all patients with lupus
2. Maintenance treatment glucocorticoids should be minimised and, when possible, withdrawn
What can help discontinuation of glucoricosteroids in SLE?
- initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate)
- expedite the tapering/discontinuation of glucocorticoids
What medication is used in persistently active or severe disease?
use cyclophosphamide and B cell targeted therapies (rituximab and belimumab)
What else is needed in the management of SLE?
- Patients with SLE should be assessed for their antiphospholipid antibody status
- Patients with SLE should be assessed for their infectious and cardiovascular diseases risk profile
- Pregnancy planning
What happens in Sjogren’s syndrome?
- Autoimmune exocrinopathy
2. lymphocytic infiltration of especially exocrine glands and sometimes of other organs (extra-glandular involvement)
What does the exocrine pathology is Sjogren’s syndrome result in?
- Dry eyes (xerophthalmia)
- Dry mouth (xerostomia)
- Parotid gland enlargement
What is the commonest extra-glandular manifestation in sjogren’s syndrome
- non-erosive arthritis
- Raynaud’s phenomenon
When is it called ‘secondary’ sjogren’s syndrome?
occurs in context of another connective tissue disorder e.g. SLE
What does a salviary gland biopsy in sjogren’s syndrome show?
lymphocytic infiltration predominantly CD4 helper T cells and to lesser extent B lymphocytes
What is schimer’s test in sjogren’s syndrome?
- a test to assess tear production
- filter paper is placed under lower eyelid and extent of wetness measured after 5 minutes
- abnormal is <5mm after 5 minutes
What is inflammatory muscle disease?
proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) a rash
What are the 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)
What is the histopathology of inflammatory muscle disease?
- Elevated CPK (creatine phosphokinase)
- abnormal electromyography
- abnormal muscle biopsy (polymyositis = CD8 T cells; dermatomyositis = CD4 T cells in addition to B cells)
What is inflammatory muscle disease associated with?
malignancy (10-15%) and pulmonary fibrosis
What is crest?
- sub-type of limited systemic sclerosis
- Calcinosis
- Raynaud’s phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
What is systemic sclerosis?
- Thickened skin with Raynaud’s phenomenon
* Dermal fibrosis, cutaneous calcinosis and telangiectasia
What are the features of diffuse systemic sclerosis?
- Fibrotic skin proximal to elbows or knees (excluding face and neck)
- Anti-topoisomerase-1 (anti-Scl-70) antibodies
- Pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
- Short history of Raynaud’s phenomenon
What are the features of limited systemic sclerosis?
- Fibrotic skin hands, forearms, feet, neck and face
- Anti-centromere antibodies
- Pulmonary hypertension
- Long history of Raynaud’s phenomenon
What is overlap syndrome?
features of more than 1 connective tissue disorder are present e.g. SLE and inflammatory muscle disease
What is undifferentiated CTD?
incomplete features of a connective tissue disease are present
What is mixed connective tissue disease?
- group of patients with features of seen in SLE, scleroderma, rheumatoid arthritis, and polymyositis were identified by the presence of an autoantibody:
- Anti-U1-RNP antibody*
What are the key autoantibodies in diffuse systemic sclerosis?
Anti-scl-70 antibody (also termed antibodies to topoisomerase-1)
What are the key autoantibodies in limited systemic sclerosis?
anti-centromere antibodies
What are the key autoantibodies dermato-/polymyositis?
- Anti-tRNA transferase antibodies
2. . E.g. histidyl transferase (also termed anti-Jo-1 antibodies)
What are the key autoantibodies in sjogren’s syndrome?
- No unique antibodies but typically see
1. ANA (anti-Ro and anti-La antibodies)
2. RF
What are the key autoantibodies in mixed connective tissue disease?
Anti-U1-RNP antibodies
