connective tissue disorders Flashcards
what are the key connective tissue disorders?
Systemic Lupus Erythematosus (SLE)
Sjögren’s syndrome
Autoimmune inflammatory muscle disease:
Polymyositis
Dermatomyositis
Systemic sclerosis (scleroderma):
Diffuse cutaneous
Limited cutaneous
Overlap syndromes
what is rheumatoid arthritis?
Chronic joint inflammation that can result in joint damage
Site of inflammation is the synovium
Associated with autoantibodies:
Rheumatoid factor
Anti-cyclic citrullinated peptide (CCP) antibodies
synovitis
what is ankylosing spondylitis?
Chronic spinal inflammation that can result in spinal fusion and deformity
Site of inflammation includes the enthesis No autoantibodies (‘seronegative’)
ENTHESITIS
inflammation where ligaments and tendons enter bones
what is SLE?
Chronic tissue inflammation in the presence of antibodies directed against self antigens
Multi-site inflammation but particularly the joints, skin and kidney
Associated with autoantibodies:
Antinuclear antibodies
Anti-double stranded DNA antibodies
Anti-phospholipid antibodies (increased propensity to
thrombotic events)
comes with a molar
immune complexes
what are connective tissue disorders?
Arthralgia and arthritis is typically non-erosive (can damage ligaments and capsules but not bone)
Serum autoantibodies are characteristic and…
May aid diagnosis
Correlate with disease activity
May be directly pathogenic
Raynaud’s phenomenon is common in these conditions:
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 are some facts about SLE?
Chronic tissue inflammation in the presence of antibodies directed against self antigens
Multi-site inflammation but particularly the joints, skin and kidney
Auto-antibodies: Antinuclear antibodies, Anti-double stranded DNA and Anti-phospholipid antibodies
Prototypic autoimmune disease typically diagnosed in female aged between 15 – 45 years
9:1 F:M ratio
what are the symptoms 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 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 are the autoantibodies in rheumatology?
rheumatoid arthritis:
Rheumatoid Factor
Anti-cyclic citrullinated peptide antibody
SLE:
Antinuclear antibodies (ANA)
Anti-double stranded DNA antibodies (anti-dsDNA)
Anti-phospholipid antibodies
osteoarthritis, gout, reactive arthritis, ankylosing spondylitis:
none
systemic vasculitis:
Antinuclear cytoplasmic antibodies (ANCA)
what are the key investigations done for 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 happens to complement in SLE?
Unwell lupus patient has LOW complement C3 and C4 levels and HIGH levels of anti-ds-DNA antibodies
Low as compliment is being activated, so being depeleated
how do we manage 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 is sjorgrens 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 is inflammatory muscle disease?
Proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) a rash
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)
Elevated CPK (creatine phosphokinase), 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 is systemic sclerosis?
Thickened skin with Raynaud’s phenomenon
Dermal fibrosis, cutaneous calcinosis and telangiectasia
Skin changes may be limited or diffuse
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
Limited systemic sclerosis*: Fibrotic skin hands, forearms, feet, neck and face Anti-centromere antibodies Pulmonary hypertension Long history of Raynaud’s phenomenon
*CREST
Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
