Connective Tissue Diseases Flashcards
List some common connective tissue diseases
SLE Sjogren’s syndrome Systemic sclerosis Dermatomyositis Polymyositis
What are connective tissue diseases
NOT diseases of connective tissue
Spontaneous over activity of the immune system involving specific auto-antibodies
Can change with time and occasionally cause organ failure and death
Which parts of the body can SLE affect
Any part of the body
Which factors contribute to the aetiology of SLE
Genetic - can occur amongst relatives
Hormonal - linked to higher oestrogen exposure
Environmental
Immunological
Describe how autoimmunity arises in SLE
Loss of immune regulation Increased and defective apoptosis Necrotic cells release nuclear material which act as auto-antigens This stimulates T and B cells Autoantibodies are produced
How does SLE lead to renal disease
Immune complexes of nuclear antigens and antibodies are deposited
This activates compliment system which attracts leucocytes
Leads to release of cytokines which cause inflammation, necrosis and scarring
Leads to glomerulonephritis
List some constitutional symptoms of SLE
Fever Malaise Poor appetite Weight loss Fatigue
List the mucocutaneous features of SLE
Photosensitivity Malar rash - butterfly shape on face, sparing nasolabial folds Discoid lupus erythematosus Subacute cutaneous lupus Mouth ulcers Alopecia - patchy
What effect can SLE have on the heart and lungs
Pericarditis
Pericardial effusion
Pleurisy
Pleural effusion
Pulmonary hypertension - do echo
Interstitial lung disease - do CXR and pulmonary functions
List the neurological features of SLE
Depression/psychosis Migrainous headache Seizures Cranial or peripheral neuropathy Mononeuritis multiplex
List the haematological features of SLE
Lymphadenopathy Leucopenia Lymphopenia Haemolytic anaemia Thrombocytopenia
What is anti-phospholipid syndrome
Syndrome associated with SLE and other autoimmune conditions
Causes unprovoked venous and arterial thrombosis, pre-eclampsia, recurrent miscarriage and thrombocytopenia
When should a positive ANA test be taken seriously
When the other anti-nuclear antibodies are also positive
AND
the patient is presenting with symptoms of a connective tissue disease
Which antibody test is the most specific for SLE
Anti-double stranded DNA antibody
However, not very sensitive - only 40-50% SLE patient have it
List the 3 main anti-phospholipid antibodies
Anti-cardiolipin antibody
Lupus anticoagulant
Anti-beta 2 glycoprotein
Can have just one or all 3 (all 3 increases risk of thrombosis)
Aside from antibody tests, what investigations may you do in an SLE patient
Depends on symptoms
Chest: CXR, pulmonary function tests or CT
Urine protein tests
Renal biopsy - if urine positive for protein or red cell casts
Echo - look for pulmonary hypertension
Nerve conduction study
MRI of brain
Describe the general (non drug) management of SLE
Counselling
Regular monitoring
Avoiding excessive sun-exposure
List some immunosuppressives used in the treatment of SLE
Methotrexate - good for synovitis
Azathioprine
Cyclophosphamide
Rituximab
What are some risks of immunosuppressive treatment
Can cause bone marrow suppression
Increased susceptibility to infection
Potentially teratogenic
Which treatments are used for mild SLE
Hydroxychloroquine - all patients start on this
Topical steroids
NSAID’s - to treat joint pain
Which treatments are used in moderate SLE
Oral steroids
Azathioprine
Methotrexate
Which treatments are used in severe SLE
Steroid - IV, high dose or prolonged courses
Cyclophosphamide
Biologics - Rituximab, Belimumab
In general what causes an autoimmune disease
The immune system attacks self antigens as a result of breakdown of tolerance to autoreactive immune cells
Involves the adaptive immune system
Often has genetic, environmental and/or an infectious trigger
Which group are more likely to have autoimmune disease
Women
Which core clinical features would make you suspect an autoimmune disease
Arthralgia Muscle pain or weakness Photosensitivity Raynaud's Mucosal ulcers Alopecia Unexplained thrombosis SOB Neurological symptoms Recurrent pregnancy issues/ miscarriages
What is the general screening test for all autoimmune diseases
Screen for ANA
If positive you then look for specific ones for certain conditions
Do a ENA extractable nuclear antigens test - connective tissue screen
Includes anti-ro, la, sm, RNP, SCl70, centromere etc.
Who gets primary Raynaud’s
Teenagers
No underlying autoimmune disease
Benign condition typically seen when it is cold
Who gets secondary Raynaud’s
Older age group
Have underlying autoimmune disease - systemic sclerosis
More likely to get associated ulcers or gangrene
Seen all year round
How do you treat Raynaud’s
Keep digits warm
Vasodilators - e.g. calcium channel blockers
What are the 2 subtypes of systemic sclerosis
Diffuse cutaneous - has skin involvement above and below the elbows and knees (everywhere basically)
Limited cutaneous - skin involvement only on face and below knees and elbows
Previously called CREST syndrome
What is calcinosis
calcium deposits in the skin
what is sclerodactyly
thickening and tightening of the skin on fingers and hands
What is telangiectasia
Dilation of capillaries causing red marks on the surface of the skin
How is systemic sclerosis managed
Yearly ECHO and pulmonary function tests
Treat symptomatically:
- treat Raynaud’s
- treat reflux with PPI etc
- immunosuppressive for pulmonary fibrosis and skin involvement
- tight control of blood pressure
What are some symptoms of Sjogren’s syndrome
Dry, gritty eyes Dry mouth - drinking lots, struggling to swallow Dry cough Tooth decay Vaginal dryness
How do you diagnose Sjogren’s syndrome
Antibody tests - ANA positive, look for Anti-Ro and Anti-La (La is the most specific)
May also have RF - not specific
If antibodies negative do salivary gland ultrasound and biopsy.
Normally have raised ESR, plasma viscosity and IgG
How do you treat Sjogren’s syndrome
Eye drops, salivary supplements and vaginal lubricants
Good dental hygiene
Hydroxychloroquine - treats fatigue/arthralgia
Immunosuppressants if there is major organ involvement
What criteria must be met to diagnose anti-phospholipid syndrome
Presence of antiphospholipid antibodies on 2 occasions 12 weeks apart-
How do you treat anti-phospholipid syndrome
Lifelong anticoagulation if there is thrombosis - warfarin
Pre-pregnancy LMWH and aspirin (or when pregnancy confirmed)which continue throughout pregnancy until 6 weeks post-partum
Why should you do an urinalysis on someone with SLE
Risk of glomerulonephritis - presents with haematuria (red cell casts in particular) and proteinuria
Urine often changes before bloods do
Do a dip and if more than a trace of protein you do a protein creatinine ratio and if blood send to micro to look for casts
How can SLE affect pregnancy
Active disease is associated with poor maternal and fetal
outcomes - advised not to conceive until disease is stable for at least 6 months
Some of the immunosuppressants are teratogenic - must modify drugs so safe (azithio or low dose hydroxy)
Anti-Ro antibodies can congenital heartblock in 2- 5% of foetuses so montior baby if present
Associated with anti-phospholipid which has high miscarriage risk
Which antibodies may be positive in SLE
ANA - 98% of patients Anti- double stranded DNA Anti-Ro Anti-smith - high titres only are suggestive RNP
Anaemia and cytopenia’s are common in autoimmune diseases - true or false
True
Which autoimmune conditions can cause a raised IgG
Autoimmune liver diseases
Sjogren’s
Photosensitivity is a sign of which autoimmune disease
SLE - will develop a rash days after exposure and it will last for weeks
Different to prickly heat
What is sicca
Another name for Sjorgren’s!!
Symptoms of waking up with dry mouth, eyes feeling gritty, difficulty swallowing dry food without water, vaginal dryness
What are the symptoms of limited systemic sclerosis
Calcification Raynaud's Oesophageal dysmotility - reflux Sclerodactyly Telangiectasia - including abnormal nailfold capillaries
Raynauds + reflux makes you think of which condition
limited systemic sclerosis
Mucosal ulceration is a sign of which autoimmune disease
SLE
Alopecia is a sign of which autoimmune disease
SLE
Can get male pattern baldness and patchy alopecia
