Connective tissue disorders Flashcards
What is the use of serum antibodies?
May aid diagnosis
Correlate with disease activity
May be directly pathogenic
What is typical of Arthralgia & arthritis in connective tissue disorders?
non-erosive
What is a common sign in Connective tissue disorders?
Intermittent vasospasm of digits on exposure to cold
Typical colour changes – white to blue to red
Vasospasm leads to blanching of digit
Cyanosis as static venous blood deoxygenates
Reactive hyperaemia
Raynaud’s phenomenon is most commonly isolated and benign condition (‘Primary Raynaud’s phenomenon’)
What happens in SLE?
Chronic tissue inflammation in the presence of antibodies directed against self antigens
Multi-site inflammation but particularly the joints, skin and kidney
Which antibodies are involved in SLE?
Antinuclear antibodies
Anti-double stranded DNA
Anti-phospholipid antibodies
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 sometimes arthritis
Serositis (pericarditis, pleuritis, less commonly peritonitis)
Renal disease – glomerulonephritis (‘lupus nephritis’)
Cerebral disease – ‘cerebral lupus’ e.g. psychosis
What is the current 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
Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
What antibodies are present in systemic vasculitis?
Antinuclear cytoplasmic antibodies (ANCA)
what is the significance of the ant-dsDNA antibody in SLE?
Specific for SLE
Serum level of antibody correlates with disease activity
What is the significance of ANA in SLE?
Seen in all SLE cases
Not specific for SLE
What is the significance of Anti-phospholipid 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
Serum level of antibody does NOT correlates with disease activity
What is the significance of Anti-Ro and Anti-La antibodies?
Secondary Sjögren’s syndrome
Neonatal lupus syndrome (transient rash in neonate, permanent heart block)
Which antibodies signify Cerebral lupus?
Anti-ribosomal Antibodies
What are the investigations important in SLE?
Inflammation:
high ESR but C-reactive protein is typically normal unless infection or serositis/arthritis
Haematology:
Haemolytic anaemia, Lymphopenia, Thrombocytopenia
Renal:
very important to measure urine protein (most commonly urine protein:creatinine ratio [uPCR])
look at albumin
Immunological
Antinuclear antibodies
Anti-double-stranded DNA antibodies - highly specific, correlate with disease activity
Complement consumption – e.g. low C4 and C3
Clotting – antiphospholipid antibodies
Lupus anticoagulant and anti-cardiolipin antibodies
In treated patients SOME changes may reflect ADVERSE REACTIONS TO MEDICATION
e.g. abnormal liver function (‘transaminitis’) or fall in neutrophil count (neutropenia)
What does an unwell SLE patient have?
Unwell lupus patient has LOW complement C3 and C4 levels and HIGH levels of anti-ds-DNA antibodies
What is the management for SLE?
Treatment in SLE aims at remission or low disease activity and prevention of flares
Hydroxychloroquine is recommended in all patients with lupus
Maintenance treatment glucocorticoids should be minimised and, when possible, withdrawn.
Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of glucocorticoids
In persistently active or severe disease we use cyclophosphamide and B cell targeted therapies (rituximab and belimumab)
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 Sjogrens syndrome?
Autoimmune exocrinopathy
lymphocytic infiltration of especially exocrine glands and sometimes of other organs (extra-glandular involvement)
Exocrine gland pathology results in;
Dry eyes (xerophthalmia)
Dry mouth (xerostomia)
Parotid gland enlargement
Commonest extra-glandular manifestations are non-erosive arthritis and Raynaud’s phenomenon
Termed ‘secondary’ Sjögren’s syndrome if occurs in context of another connective tissue disorder e.g. SLE
What will a salivary gland biopsy show in sjogrens syndrome?
Salivary gland biopsy will show lymphocytic infiltration predominantly CD4 helper T cells and to lesser extent B lymphocytes
What is Schemer’s test?
Schirmer’s test – 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 are the blood tests for inflammatory muscle disease?
Elevated CPK, abnormal electromyography, abnormal muscle biopsy (polymyositis = CD8 T cells; dermatomyositis = CD4 T cells in addition to B cells)
Associated with malignancy (10-15%) and pulmonary fibrosis
What happens in Systemic sclerosis?
Thickened skin with Raynaud’s phenomenon
Dermal fibrosis, cutaneous calcinosis and telangiectasia
Skin changes may be limited or diffuse
What happens in 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 happens in limited systemic sclerosis?
Fibrotic skin hands, forearms, feet, neck and face
Anti-centromere antibodies
Pulmonary hypertension
Long history of Raynaud’s phenomenon
What is CREST?
CREST describes a sub-type of limited systemic sclerosis.
It stands for Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
What is overlap syndrome?
When features of more than 1 connective tissue disorder are present e.g. SLE and inflammatory muscle disease we can use the term overlap syndrome
What is undifferentiated connective tissue disease?
When incomplete features of a connective tissue disease are present we can use the term undifferentiated connective tissue disease
What is MCTD?
In one instance a 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*
….this condition was termed Mixed Connective Tissue Disease (‘MCTD’)
What are the antibodies involved in Diffuse systemic sclerosis?
Anti-Scl-70 antibody
also termed antibodies to topoisomerase-1
What are the antibodies involved in Limited systemic sclerosis?
Anti-centromere antibodies
What are the antibodies involved in Dermatology/Polymyositis?
Anti-tRNA transferase antibodies
E.g. histidyl transferase (also termed anti-Jo-1 antibodies)
What are the antibodies involved in Sjogrens syndrome?
No unique antibodies but typically see
Antinuclear antibodies - Anti-Ro and anti-La antibodies
Rheumatoid factor
What are the antibodies involved in Mixed connective tissue disease?
Anti-U1-RNP antibodies
