Autio-immune Connective Tissue Diseases Flashcards
What is connective tissue?
Tissue that connects, supports, binds, or separates other tissues or organs
Typically having relatively few cells embedded in an amorphous matrix, with collagen and other fibres
Adipose tissue, cartilage, bone, blood, muscle
Loose connective tissue: fascia under skin
Fibrous connective tissue: tendons, ligaments
What are the main auto-immune connective tissue diseases?
Systemic Lupus Erythematosus (SLE) Systemic Sclerosis Sjogren's Syndrome Dermatomyositis + Polymyositis Anti-phospholipid Syndrome
What is SLE?
Systemic Lupus Erythematosus
A systemic inflammatory disease
Characterised by the presence of auto-antibodies in the serum
Who gets SLE?
90% of patients are women
Present between age 14-64
More prevalent in afro-carribbeans
What causes SLE?
Hereditary
Genetics: certain HLA types
Links with oestrogen, hence more common in females
Drugs
UV light can trigger flares
Exposure to EBV virus
What drugs cause SLE?
Once they have caused it, is it permanent?
Hydralazine: smooth muscle relaxant
Isoniazid: antibiotic
No, once the drug is withdrawn often the SLE goes away
What is the pathogenesis of SLE?
Apoptotic cells and cell fragments are not cleared up efficiently by phagocytes
These fragments containing auto-antigens are taken up by APCs and presented to the T cells
These stimulate B cells to produce antibodies against these antigens - autoantibodies
Autoantigen-autoantibody complexes form and are deposited in areas around the body
This activates the complex system, influx of neutrophils, an inflammatory response occurs
What are the clinical features of SLE?
So many!!
Non-specific malaise
Fatigue
Myalgia
Fever
Lymphadenopathy Weight loss Alopecia Skin rashes Haematological disorders Recurrent abortion Neuro-psychiatric features
What skin rashes occur in SLE?
Butterfly (malar) rash
Photosensitive rash
What haematological disorders occur in SLE?
Anaemia Thrombocytopenia: platelet deficiency Neutropenia Lymphopenia Venous + arterial thrombosis Vasculitis
Why do SLE patients get recurrent abortion?
Clots form in the placenta
What neuro-psychiatric features occur in SLE?
Many…
Aseptic meningitis
Cerebrovascular disease
Psychosis
Depression
The American College of Rheumatology set out a guideline of what symptoms you need to see before being able to diagnose SLE.
How many symptoms on the list must the patient have?
4
Investigation of SLE?
Blood:
- anaemia
- neutro/lymphopenia
- thrombocytopenia
- raised ESR
- serum autoantibodies
Biopsy of skin or kidney
- see deposition of autoantobody-autoantigen complexes + complement
Is CRP usually raised in SLE?
Not usually, unless they have a concurrent infection
Which serum autoantibodies are involved in SLE?
Anti-dsDNA (specific for lupus)
Anti-nuclear
Anti-La and Anti-Ro
Many more!
On a blood test, which serum autoantibody is only seen in SLE?
Anti-dsDNA
Management of SLE?
Advise on avoiding risk factors
Drug treatment:
- NSAIDs
- Steroids
- Immunosuppressives
- Biologics
Plasmapheresis
Stem cell transplants
Monitor the patient for any major organ involevement that may arise
What risk factors would you advise an SLE patient avoid?
Excessive sunlight
Reduce cardiovascular risk:
- stop smoking
- healthy diet
- exercise
These things will reduce the risk of a flare-up
What is plasmapheresis?
Like dialysis
Use a machine to wash the autoantibodies out of the blood
Most patients with SLE can live a full life.
True or false?
True
What is anti-phospholipid syndrome?
A condition featuring antibodies against phospholipids
Occurs on its own or as in association with another autoimmune condition
What does anti-phospholipid syndrome cause?
CLOT
C - coagulation defect
L - livedo reticularis (mottled skin rash
O - obstetric problems (recurrent miscarriage)
T - thrombocytopenia
Investigation of anti-phospholipid syndrome?
Blood tests:
you will see the anti-phospholipid antibodies
Management of anti-phospholipid syndrome?
Warfarin to prevent clotting
Or aspirin as prophylaxis
What is livedo reticularis?
A mottled skin rash, caused by capillary dilation and blood stasis in skin venules
What is Sjogren’s syndrome?
An autoimmune disorder where epithelial exocrine glands are destroyed, especially the lacrimal and salivary gland
Who gets Sjogren’s syndrome?
Often middle aged women
40s-50s
What causes Sjogren’s syndrome?
Primary: just happens
Secondary: as a result of other autoimmune conditions
- SLE
- RA
- Scleroderma
- Primary Biliary Cirrhosis
Clinical features of Sjogren’s syndrome?
Sicca complex:
- dry eyes
- dry mouth
- enlarged salivary glands
Systemic features:
- inflammatory arthritis
- neuropathies
- vasculitis
What is the ‘sicca complex’?
Dry eyes and dry mouth
What does xerostomia mean?
Dry mouth
What does keratoconjunctivitis sicca mean?
Dry eyes
Investigation of Sjogren’s syndrome?
Blood:
- serum autoantibodies
- raised ESR
Labial (lip) gland biopsy:
destruction + lymphocyte infiltration
Schirmer test: positive
Which autoantibody is commonly seen in patients with Sjogren’s syndrome?
Antinuclear
What is the Schirmer’s test?
Put a strip of filter paper on the inside of the eyelid
If it doesn’t get wet up to 10mm in 5 mins then the test is positive and there is defective tear production
Management of Sjogren’s syndrome?
Treat symptoms:
- artificial tears
- saliva replacement
Immunosuppression for systemic problems
What is systemic sclerosis?
A multi-system autoimmune disease, with particular involvement of the skin
What is scleroderma?
Another name for systemic sclerosis
What two types of systemic sclerosis are there?
Limited (CREST)
Diffuse
What causes systemic sclerosis?
Genetic predisposition
Triggered by immune activation, infection, environmental toxin
Causes the immune system to produce autoantibodies
Connective tissue cells begin to overproduce collagen, causing fibrosis and thickening of the tissue
What are the clinical features of CREST systemic sclerosis?
C - calcinosis R - Raynaud's phenomenon E - esophageal reflux + strictures S - sclerodactyl T - telangiectasia
PLUS: pulmonary artery hypertension
What is calcinosis?
Lumps of calcium deposited under the skin
What is sclerodactyl?
Tightness, thickening of skin on fingers and toes
What is telangiectasia?
Dilatation of capillaries
They appear as red/purple spidery clusters on skin or organs
What are the clinical features of diffuse systemic sclerosis?
Proximal scleroderma: hardening of the skin
Lung: pulmonary fibrosis
GI tract:
- dilatation of oesophagus
- obstruction of colon
Renal crisis - hypertension
Myositis: inflammation + degeneration of muscle
Heart:
- fibrosis causing arrhythmia
Management of systemic sclerosis?
No proper treatment
Treat the symptoms:
- Raynauds
- Reflux
- Prevent renal crisis
- Treat skin oedema
Monitor organs for early detection, especially pulmonary artery hypertension
What is the most important thing to do when managing a patient with systemic sclerosis?
Monitor regularly for pulmonary artery hypertension
If not it can be serious: SOB, R heart damage, hypoxia
What is dermatomyositis?
Inflammation and necrosis of the skin and skeletal muscle
What is polymyositis?
Inflammation and necrosis of many skeletal muscles, but not the skin
What causes dermatomyositis and polymyositis?
Can just occur
Can be a para-neoplastic syndrome
What should you do if you see someone with dermatomyositis but their serum blood tests showed nothing?
Suspect a malignancy
Clinical features of dermatomyositis?
Skin rash:
- macular rash over back and shoulders
- heliotrope (lilac) rash on eyelids and knuckes
Muscle weakness
Myalgia + arthralgia
Fever
Raynaud’s
Interstitial lung involvement
Myocarditis + arrhythmia
Clinical features of polymyositis?
Muscle weakness
Myalgia + arthralgia
Fever
Raynaud’s
Interstitial lung involvement
Myocarditis + arrhythmia
Investigation of dermatomyositis and polymyositis?
Muscle/skin biopsy to look for signs of inflammation
- inflammatory cell infiltration
- necrosis
Serum muscle enzymes will be raised
Serum autoantibodies:
- anti-JO
- if none suspect malignancy
Electromyography: looks at electrical activity of skeletal muscles
Management of dermatomyositis and polymyositis?
Steroids short term until symptoms have settled
Immunosuppressive drugs: methotrexate
What is Raynaud’s syndrome?
Peripheral digital ischaemia due to paroxysmal (sudden) vasospasm caused by cold weather or emotion
Causes the digits to change colour and ache
Refers to both Raynaud’s disease and phenomenon
What colour(s) do the digits turn in Raynaud’s and why?
First they go white due to ischaemia
Then they go blue due to deoxygenation
Then they go red due to blood rushing black after vasospasm has stopped, reactive hyperaemia
What is the difference between Raynaud’s disease and Raynaud’s phenomenon?
Disease: primary, idiopathic cause
Phenomenon: secondary, a result of an underlying cause
When does Raynaud’s disease (primary Raynaud’s) usually present?
In late teens, early 20s
What are some causes of Raynaud’s phenomenon (secondary Raynaud’s)?
Connective tissue diseases:
- SLE
- Systemic Sclerosis
Drugs
Vascular damage:
- atherosclerosis
- frost bite
- long term use of vibrating tools
Investigation of Raynaud’s syndrome?
Often have to rely on history because in consulting room they will be warm
Look for an underlying cause, like SLE etc.
Management of Raynaud’s phenomenon?
Lifestyle advice:
- keep hands warm
- stop smoking
Treat underlying cause if there is one
Drugs:
- nifedipine
- sildenafil (Viagra)
- fluoxetine (SSRI)
Sympathectomy: chemical or surgical
What is a Sympathectomy?
Surgery where a portion of the sympathetic nerve trunk in the thoracic region is destroyed
This prevents excessive vasoconstriction that occurs in Raynaud’s
What type of drug is nifedipine?
Calcium channel blocker
Prevents vasospasm
