Connective Tissue Diseases Flashcards
What are connective tissue diseases?
They are characterized as a group by the presence of spontaneous over activity of the immune system.
They are often associated with specific auto-antibodies which can help define the diagnosis.
What is SLE?
Systemic AI disease that can affect any part of body. Can often mimic or is mistaken for other illnesses
What is the epidemiology of SLE?
F:M 9:1. Higher in asians, afro-americans/caribbeans and hispanic americans. Commoner in asian indians than caucasians in UK.
What genetic factors lead to SLE?
High concordance in monozygotic twins-increased incidence amongst relatives, identification of gene abnormalities predisposing to lupus
What hormonal factors lead to SLE?
Incidence increased with higher oestrogen exposure-early menarche, on oestrogen containing contraceptives and HRT
What environmental factors lead to SLE?
Viruses e.g. EBV. UV light may stimulate skin cells to secrete cytokines stimulating B-cells. Silica dusk may increase risk
What is the pathogenesis of SLE?
Due to loss of immune regulation. Increased/defective apoptosis. Necrotic cells release nuclear material which acts as potential autoantigen. Autoimmunitu possibly results by extended exposure to nuclear/intracellular autoantigens. B/T cells stimulated, autoantibodies produced
What are the constitutional symptoms of SLE?
Fever, malaise, poor appetite, weight loss, fatigue
What are the mucocutaneous features of SLE?
Photosensitivity, malar rash, discoid lupus erythematosus, subacute cutaneous lupus
What are the MSK features of SLE?
Non-deforming polyarthritis/arthralgia (RA distribution- no radiological erosion), deforming arthropathy-Jacoud’s, erosive arthritis, myopathy -weakness, myalgia, myositis
What are the pulmonary features of SLE?
Pleurisy Infections Diffuse lung infiltration and fibrosis Pulmonary hypertension Pulmonary infarct
What are the cardiac features of SLE?
Pericarditis
Cardiomyopathy
Pulmonary hypertension
Libman-Sachs endocarditis
What is the presentation of glomerulonephritis in SLE?
Proteinuria Urine sediments Urine RBC and casts Hypertension Acute renal failure Chronic renal failure
What are the neurological features of SLE?
Depression/psychosis Not always related to disease activity Migranous headache Cerebral ischaemia TIAs or stroke Cranial or peripheral neuropathy Cerebellar ataxia
What are the haematological features of SLE?
Lymphadenopathy (25% patients). Leucopenia, anaemia (haemolytc, normochromic, normocytic), thrombocytopenia
What are the intrinsic factors making SLE patients susceptible to infection?
Low complements
Impaired cell mediated immunity
Defective phagocytosis
Poor antibody response to certain antigens
What are the extrinsic factors making SLE patients susceptible to infection?
Steroids
Other immunosuppressive drugs
Nephrotic syndrome
What are the screening tests for suspected SLE?
Full blood count Renal function tests including urine examination Anti-nuclear antibody Anti-double stranded DNA antibodies ENA Complement levels
In what conditions will ANA be found?
RA, other AI conditions such as SLE, HIV, Hep C
In what percentage of SLE patients will ANA be +ve?
95% in titre of 1:160 or greater
When should a positive ANA test be taken seriously?
If other antinuclear antibodies are positive Anti-dsDNA Anti-Sm Anti-Ro Anti-RNP
When the patient presents with CTD features
Describe anti-double stranded DNA antibody in SLE
Occurs in ~60% patients. Highly specific for SLE-titre correlates with disease activity. May be associated with lupus nephritis
Describe Anti-ENA’s associations
Anti-Ro (60%) Usually associated with anti-La Associated with cutaneous manifestations Secondary Sjogren’s features Congenital heart block and neonatal LE
Are Anti-Sm autoantibodies highly or not highly specific?
Highly (10-20% cases). Probably association with neuro involvement
What conditions are associated with anti-RNP?
Sclerodermatous skin lesions, Raynaud’s, low grade myositis, SLE (30%)
What investigations other than bloods can be used in SLE?
CXR Pulmonary function tests CT chest Urine protein quantification Renal biopsy Echocardiogram Nerve conduction studies MRI brain
What is done in SLE activity monitoring?
Clinical assessment incl. BP. Anti-dsDNA level +vely correlates with activity. C3/4 levels -vely correlate. Urine exam incl protein, cells and casts. FBC, blood biochemistry
What drug treatment is used in SLE?
NSAIDs, analgesia, anti-malarials (hydroxychloroquine), steroids, immunosuppressives (azathoprine, cyclophosphamide, methotrexate, mycophenolate mofetil), biologics (rituximab, belimumab)
What auto-antibody does Rituximab target?
Anti-CD20
What auto-antibody does Rituximab target?
Anti-Blys
What clinical features or test findings are needed to make a diagnosis of anti-phospholipid syndrome?
1 lab + 1 clinical feature needed-+ve anti-cardiolipin (phospholipid) antibodies and/or lupus anticoagulant activity and/or anti-beta2-glycoprotein on 2 occasions at least 12 wks apart. Arterial/venous thrombosis. Pregnancy loss (no other explanation) 10-34/40 or 3 losses (no explanation)
What group of people does anti-phospholid syndrome occur in?
Young women M:F 1:3.5
What are other non-diagnostic criteria features of anti-phospholipid syndrome?
Superficial thrombophlebitis and livedo reticularis
Mild/moderate thrombocytopenia
Neurological features – migraine, transverse myelitis
Libman-Sacks endocarditis
Catastrophic anti-phospholipid syndrome
What is the treatment of anti-phospholipid syndrome?
Thrombosis – lifelong anti-coagulation
Pregnancy loss – aspirin + LMWH during pregnancy
Attention to vascular risk factors
What is Sjogren’s syndrome?
AI condition- lymphocyte infiltration of exocrine glands causing xerostomia and keratoconjunctivitis sicca. Can be 1’/2’ to other AI conditions
What is the classification criteria for primary Sjogren’s syndrome
4/6-immunology or biopsy evidence needed: ocular symptoms (daily >3 months), oral symptoms (daily >3 months), ocular dryness, salivary gland involvement, immunology-either Ro, La or both, biopsy evidence of lymphocytic infiltrate
What tests are used in diagnosing Sjogren’s?
Schirmer test(ocular dryness), positive anti-Ro/La and typical features on lip gland biopsy
What other conditions can manifest in Sjogren’s?
Fatigue Arthralgia Raynauds Salivary swelling Lymphadenopathy Skin and vaginal dryness Interstitial lung disease Neuropathy Lymphoma (x40 risk) Renal tubular acidosis Neonatal complete heart block (anti-Ro)
What is the M:F ratio of Sjogren’s?
1:9
What is the treatment of Sjogren’s?
Eye drops, punctal plugs Saliva replacement Pilocarpine Hydroxychloroquine Steroids and immunosuppression Attention to cardiovascular risk factors
What is systemic sclerosis?
AI condition. Presents with vasculopathy- Raynaud’s Syndrome, inflammation, fibrosis causing skin thickening
What are the 2 classes of systemic sclerosis?
Limited, diffuse
What are the features of limited systemic sclerosis?
Previously known as CREST- Calconosis, Raynauds, Esophageal dysmotility, Sclerodactyly, Telangiectasia. Pulmonary HT in 30%. Associated with anti-centromere antibodies
What are the features of diffuse systemic sclerosis?
Skin changes within 1 year of Raynaud’s
Truncal and acral skin involvement
Early significant organ involvement (kidneys, lungs, gut, muscle, joints, heart)
Anti-Scl-70 antibodies
What are the cutaneous features of systemic sclerosis?
Sclerodactyly, calcinosis, ulcerated fingertips, vasculitis
What are the GI manifestations of systemic sclerosis?
Oesophageal hypomobility
Small bowel hypomobility, bacterial overgrowth
Pancreatic insufficiency
Rectal hypomobility
What are the respiratory manifestations of systemic sclerosis?
Interstitial lung disease
Pulmonary hypertension
Chest wall restriction
What are the renal manifestations of systemic sclerosis?
Hypertensive renal crisis, ischaemic
What are the cardiovascular manifestations of systemic sclerosis?
Raynaud’s with digital ulceration
Atherosclerotic disease
Hypertensive cardiomyopathy
Who does systemic sclerosis commonly present in?
Age 25-55, M:F 1:4
What is the treatment for systemic sclerosis?
Calcium channel blockers Prostacyclin (Iloprost) ACE inhibitors Prednisolone Immunosuppression Bosentan, Sildenafil
What is mixed connective tissue disease(MCTD)?
Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. Has major and minor criteria and can present with various combinations of them
What is undifferentiated connective tissue disorder?
‘Connective tissuish’ but usually don’t fit a particular syndrome
Usually a better prognosis
Would expect some antibody positivity
How is systemic sclerosis diagnosed?
Auto-antibodies associated include anti-centromere/Scl-70. Organ screening-includes PFT, echo and monitoring of renal function
What antibodies are associated with MCTD?
Anti-RNP
How is MCTD monitored?
Regular echocardiograms (annually) suggested due to risk of Pulmonary HT, screening for ILD with PFT should take place
How is MCTD managed?
Varies according to presentation, CCBs may help Raynauds. Immunosuppression if significant muscle or lung disease
What is anti-phospholipid syndrome (APS)?
A disorder than manifests clinically as recurrent venous or arterial thrombosis and/or fetal loss. Can occur in association with SLE or other rheumatic/AI condition
