Connective Tissue Disease Flashcards
What are some common connective tissue diseases?
SLE Sjogren's syndrome Systemic sclerosis Dermatomyositis Polymyositis Mixed connective tissue disease Anti-phospholipid syndrome
What are connective tissue diseases?
Spontaneous over actiivty of the immune system that has specific auto-antibodies
What is the epidemiology of SLE?
Females to males 9:1
Prevalence is higher in asians, afro-americans, afro-caribbeans
Uncommon in african blacks
What hormonal factors can lead to SLE?
Incidence increased in those with higher oestrogen exposure - early menarche, on oestrogen containing contraceptives and HRT
What is the pathogenesis of SLE?
Increased and defective apoptosis
Necrotic cells release nuclear material which act as auto-antigens
Autoimmunity results from exposure to nuclear and intracellular auto-antigens
B and T cells stimulated
Autoantibodies produced
How does SLE cause renal disease?
Deposition of immune complexes in mesangium (complexes of nuclear antigens and anti-nuclear antibodies)
Complexes form in circulation then are deposited
Activate complement which attracts leucocytes which release cytokines
Cytokine release perpetuates inflammation which causes necrosis and scarring
What part of the cell is damaged in SLE?
Basement membrane
What is the clinical critera for SLE?
Acute cutaneous lupus Chronic cutaneous lupus Oral or nasal ulcerrs Non-scarring alopecia Arthritis Serositis Renal Neurologic Haemolytic anaemia Leukopenia Thrombocytopenia
What is the immunological critera for SLE?
ANA Anti-DNA Anti-Sm Antiphospholipid Ab Low complement (C3, C4, CH50) Direct coombs test
What are the constitutional symptoms of SLE?
Fever Malaise Poor appetite Weight loss Fatigue
What are the cutaneous features of SLE?
Photosensitivity Macular rash Discoid lupus erythematosus Subacute cutaenous lupus Mouth ulcers Alopecia
What are the MSK features of SLE?
Non-deforming polyarhritis/ polyarthralgia
Deforming rthropathy - jaccoud’s arthritis
Myopathy - weakness, myalgia and myositis
What can serositis cause?
Pericarditis
Pleurisy
Pleural effusion
Pericardial effusion
What renal problems can SLE cause?
Proteinuria of >500mg in 24hrs
Red cell casts
What neurological features can SLE cause?
Depression/ phycosis Migrainous headache Seizures Cranial or peripheral neurpathy Mononeuritis multiplex
What haematological features can SLE cause?
Lymphadenopathy Leucopenia Lymphopenia Haemolytic anaemia Thrombocytopenia
What is anti-phospholipid syndrome?
Venous and arterial thrombosis Recurrent miscarriage Livido reticularis Thrombocytopenia Prolonged APTT
What intrinsic features can make patients with connective tissue disorders more sucepitble to infection?
Low complement system
Impaired cell mediated immunity
Defective phagocytosis
Poor antobidy response to antigens
What extrinsic features can make patients with connective tissue disorders more sucepitble to infection?
Steroids
Other immunosuppressive drugs
Nephrotic syndrome
When should a positive ANA test be taken seriously in SLE?
If other antinuclear antibodies are positive - anti-dsDNA, anti-Sm, Anti-Ro, Anti-RNP
When the patient precents with clinical features
What is anti-double stranded DNA antibody (anti-dsDNA)?
Occurs in 60% of patients with SLE but is highly specific for SLE
Titre correlates with overall disease activity
What condition is anti-dsDNA associated with?
Lupus nephritis
What antibody is Anti-Ro commonly associated with?
Anti-La
What is condition is anti-ro associated with?
Cutaneous manifestations
Secondary sjogren’s features
Congenital heart block and neonatal LE
What condition are anti-Sm antibodies associated with?
SLE but more specificially neurological involvement
What conditions are anti-RNP antibodies associated with?
SLE
Sclerodermatous skin lesions
Raynaud’s phenomenon
Low grade myositis
When SLE is diagnosed what must happen?
Screen for organ involvement: CXR Pulmonary function tests CT chest Urine protein quantification Renal biopsy Echocardiogram Nerve conduction studies MRI brain
How is SLE activity monitored?
Anti-dnDNA levels positevly correlate with activity of disease
C3/C4 levels negatively correlate with activity
Urine examination - protein, cells and casts
FBC
Blood biochem
How is SLE managed?
Counselling
Regular monitoring
Avoid excessive sun exposure
Pregnancy issues
How is SLE treated pharmacologically?
NSAIDs and simple analgesia
Anti-malarials (hydroxychloroquine) for arthritis, cutaneous manifestations and constitutional symptoms
Steroids
Immunosuppressives
When would you give a small dose of steroids in SLE?
Skin rashes
Arthritis
Serositis
When would you give a moderate dose of steroids in SLE?
Resistant serositis
Haematologica abnormalities
When would you give a high dose of steroids in SLE?
Severe/ resistant haematologic changes, renal disease and major organ involvement
What immunosuppresive agens are utilised in SLE?
Azathioprine
Cyclophosphamide
Methotrexate
Mycophenolate mofetil
What are the down falls to immunosuppressives?
Bone marrow suppression
Increased susceptibility to infection
Teratogenic
What biologics are used for SLE?
Anti-CD20 (rituximab)
Anti-Blys (belimumab)
What drugs are used for mild SLE disease?
HCQ
Topical steroids
NSAIDs
What drugs are used for moderate SLE disease?
Oral steroids
Azathioprine
Methotrexate
What drugs are used for severe SLE disease?
IV steroids
Cyclophophamide
Rituximab
Belimumab
What is a positive titre of ANA?
1:160 and over in almost all SLE patients
What are anti-phosphilid antibodies?
Lupus anticoagulants
What are the rhuematological autoimmune diseases?
SLE Sjogrens syndrome Systemic sclerosis Mixed connective tissue disease Inflammatory myositis Anti-phospholipid antibody syndrome
When should an autoimmune disease be suspected?
Arthralgia/ arthritis Muscle pain/weakness Photosensitivity Raynaud's phenomenon Sicca symptoms (dry eyes/mouth/throat/vaginal) Dysphagia SOB Neurological symptoms Recurrent pregnancy loss
What is the main general screening antibody for autoimmune conditions?
ANA - high titres are more importnat e.g ANA titre of 1:640 is more significant that ANA of 1:80
What antibodies are present in RA?
RF, Anti-CCP
What antibodies are present in drug induced SLE?
Anti-histone
What antibodies are present in dermatomyositis?
Anti-Jo 1
What antibodies are present in limited scleroderma?
Anti-centromere
What antibodies are present in diffuse scleroderma?
Anti-Scl 70
What antibodies are present in scleroderma renal crisis?
Anti-RNA polymerase 3
What antibodies are present in sjogren’s syndrome?
Anti-Ro
Anti-SSB
ANA
RF
What antibodies are present in congenital heart block?
Anti-Ro
What antibodies are present in mixed connective tissue disease?
Anti-U1RNP (dsDNA must be negative)
What antibodies are present in microscopic polyangitis?
p-ANCA
What antibodies are present in churg strauss?
p-ANCA and esoniphiliaq
What antibodies are present in wegners granulomatosis?
c-ANCA
What antibodies are present in SLE?
ANA, dsDNA, anti-smith, ribosomal P
What are the specific assosiations with RA?
CCP and erosive disease, extra-articular manifestations, smoking
What are the specific assosiations with SLE?
Antiphospholipid syndrome, ribosomal P and neurophychatric SLE
What are the specific assosiations with drug induced SLE?
Induced by hydralazine, chloropromazine, methydopa, isoniazid, procainamide and anti-TNF
What are the specific assosiations with dermatomyositis?
DM and malignancy
Anti-synthetase (ILD, myositis, mechanics hands)
What are the specific assosiations with scleroderma?
PHT (pulmonary hypertension) ILD (intersitial lung disease) GIT (GI tract problems) Cardiac Renal Renal crisis (hypertension, acute rise in creatning, papilloedema)
What are the specific assosiations with Sjogren’s syndrome?
Sicca symptoms
Risk of lymphoma
What are the specific assosiations with mixed connective tissue disease?
Puffy hands
What are the specific assosiations with churg strauss?
Asthma
Eosinophilia
Atopy
What are the specific assosiations with wegenrs granulmoatosis?
Granulomas in the renal and pulmonary basement membrane
What are the specific assosiations with micrscopic polyangitis?
Pulmonary, renal and segmental necrotizing glomerulonephritis
What is the marker of disease activity in RA, drug induced SLE, scleroderma, sjogren’s syndrome, microscopic polyangitis, chrug strauss and wegners granulomatosis?
ESR/CRP
What is the marker of disease activity in SLE?
Low C4 and C3, anti-dsDNA
What is the marker of disease activity in dermatomyositis?
CK
What is the marker of disease activity in scleroderma renal crisis?
Creatnine and BP
What is the marker of disease activity in congental heart block?
HR
What are the stages of raynaud’s?
Stage 1: ischaemia
Phase 2: cyanosis
Phase 3: rubor
Who can get primary rayauds?
Teenagers - no underlying autoimmune condition
Who can get secondary raynaud’s?
Older age group - underlying autoimmune disease
If ulcer or gangrene it is secondary
What is the treatment for raynads?
Keep hands warm
Vasodilators - CCB, PDE5 inhibitors (sildenafil)
What is sytemic sclerosis?
Skin thickening
90% present with raynaud’s
Can get diffuse or limited
What organs cause systemic sclerosis affect?
Lung
Heart
Skin
What the pattern of distribution of diffuse cutenous SSc?
Skin involvement on extremtities above and below elbows and kness (plus face and trunk)
What the pattern of distribution of limited cutenous SSc?
Skin involvement on extremities and only below elbows and knees (plus face)
What are the symptoms of scleroderma?
CREST
Calcinosis (calcium deposits in skin)
Raynaud’s phenomenon (spasm of blood vessels in response to cold)
Esophageal dysfunction (acid reflux and decrease in oesophagus motility)
Sclerodactyly (thickening and tightening of skin on fingers)
Telangiectasias (dilation of capillaries causing red marks)
What is pulmonary hypertension?
Increased blood pressure in pulmonary artery on right side of heart
What autoimmune condition can cause PHT?
Late complication in limited cutaneous systemic sclerosis
How is systemic sclerosis treated?
Yearly ECHO and PFTs Treat raynaud's Treat reflux with PPI Pulmonary fibrosis - immunosuppression PHT - postacyclin analogues, endothelin receptor antaonists Tight control of BP - ACEI
What are the clinical associations with anti-centromere antibody?
Limited scleroderma
CREST syndrome
PHT
What are the clinical associations with antitopoisomerase?
Diffuse scleroderma
ILD
What is sjogren’s syndrome?
Characterised by lymphocytic infiltration of exocrine glands
Keratoconjunctivitis siccs
What are important questions to ask in the diagnosis of sjogren’s syndrome?
Gritty eyes?
Woken up in the night to get a glass of water?
Found it difficult to swallow bread ot have to drink water to help swallowing?
Any vaginal dryness (pre-menopausal women)?
What are the sympoms of sjogren’s syndrome?
Blepharitis - swollen eyes Salivary gland inflammation Tooth decay Lymphoma Dry cough Multisystem involvement
What are the antibodies, blood markers to diagnose sjogren’s?
ANA positive Anti-Ro and Anti-La Salivary gland ultrasound and biopsy High ESR/PV Raised IgG Cytopaenia
How is sjogren’s treated?
Theraputic spectrum
Artifical tears, salivary supplements and vaginal lubricants
Good dental hygiene - high flouride toothpaste
Hydrocychloroquine for fatigue and arthralgia
Immunosuppression for major organ involvement
What is MCTD a mixture of?
SLE
SSc
PM (polymyositis)
RA
What is antiphospholipid syndrome?
Presence of antiphospholipid antibodies on 2 occassions 12 weeks apart
Anti-cardiolipin antibody (IgG and IgM)
Lupus anticoagulant
What are some symptoms of antiphospholipid antibody syndrome?
Thrombosis
Recurrent miscarriage
Thrombocytopaenia
What can cause secondary antiphospholipid syndrome?
Lupus
What is the treatment for antiphospholipid antibody syndrome?
Lifelong anticoagulation IF thrombosis
What is the treatment for antiphospholipid antibody syndrome pre-pregnancy?
LMWH and aspirin right into the postpartum period
What are the general principles of management for autoimmune conditions?
Assess severity URINALYSIS CXR, Pulmonary function, ECHO Manage CV risk Treatment based on major organ involvement If yes- immunosuppression If no - HCQ and symptomatic management
