Autoimmune connective tissue disorders Flashcards
Examples of autoimmune connective tissue disorders? General causes?
Polymyositis & Dermatomyositis
Antiphospholipids syndrome
Sjögren syndrome
Systemic sclerosis & scleroderma
Causes of autoimmune disease:
- cancer
- environment
- genetics
What is polymyositis and dermatomyositis?
inflammatory disorder causing symmetrical, proximal muscle weakness & breakdown
T-cell mediated cytotoxic process directed against muscle fibre
Associated w/ malignancy!
May be associated w/ connective tissue disorders e.g. lupus
Dermatomyositis also affects the skin
Epidemiology of polymyositis and dermatomyositis
Middle aged
More common in women
Pathophysiology of polymyositis and dermatomyositis
Muscle fibres are infiltrated by inflammatory cells
There is degeneration, necrosis & phagocytosis of muscle fibres.
PM - main driver of damage = cytotoxic T cells
DM - muscle damage driven by complement-mediated damage of microvasculature
NOTE: do NOT need to know the pathophysiology of autoimmune conditions in any detail
Presentation of polymyositis and dermatomyositis
Gradual onset- weeks to months
Symmetrical proximal muscle weakness +/- tenderness
Raynaud’s
Respiratory muscle weakness
interstitial lung disease
- e.g. fibrosing alveolitis or organising pneumonia
- seen in around 20% of patients & indicates a poor prognosis
- dysphagia, dysphonia, voice change
Can involve: thighs, upper arms, cardiac & GI smooth muscle
Fever & weight-loss
polyarthraliga
myocarditis
vasculitis
Dermatomyositis only- skin:
- purple (heliotrope) rash on cheeks & eyelids
- Gottron’s papules - scaly, purple coloured plaques over PIP, DIP joints, hands & elbows.
- Macular ertheymatous rash - on face, neck, chest, shoulders & hands.
- Periungual telangiectasia - periungual means skin around your nails. Cuticles often thickened & irregular.
- Cutaneous vasculitis - can cause ulceration.
NOTE: view images on notes
Investigations for polymyositis and dermatomyositis
Muscle biopsy:
- look for necrosis, regeneration & inflammatory cell infiltrate
Imaging:
- MRI- can identify muscle oedema & then used to target a biopsy.
- Screen for malignancy- CT, x-ray
Blood tests:
- Raised ESR
- High creatine kinase - PMR has normal!
NOTE: CK may be normal if Low grade inflammation, not enough, or so extensive they’ve leaked all their muscle enzyme out.
Positive autoantibody test - in 60% w/ myositis.
- ANA positive
- Anti-Jo-1 antibodies more common in PM (seen in Raynauds, lung involvement)
- Anti-Mi-2 antibodies specific to DM but less common
Management for polymyositis and dermatomyositis
- High dose oral glucocorticoids e.g. prednisolone.
- With immunosuppressive therapy e.g. methotrexate or MMF first choices.
- Azathioprine is an alternative- steroid sparing agent - Serum CK monitored
- As it falls, the dose of steroid is gradually reduced.
- Maintainanence dose of 5-7.5 mg. - Cyclophosphamide - for patients w/ interstitial lung disease.
- Treat malignancy if found.
What is antiphospholipid syndrome?
Autoimmune disease - antiphospholipid (aPL) antibodies bind to plasma membrane phospholipids causing blood clots.
Characterised by:
- Arterial & venous thrombosis (blood clots)
- Fetal loss
- Thrombocytopaenia (↓ platelets)
- High levels of antiphospholipid antibodies.
- Primary or secondary i.e. to another condition (commonly SLE)
Epidemiology of antiphospholipid syndrome
Associated w/ other diseases! → SLE, RA, SScl, Bechet’s, Giant cell, Sjögren’s, Psoriatic arthritis
More common in women
Mostly of fertile age- 11-55 yr
30% of SLE patients will have aPL antibodies
Pathophysiology of antiphospholipid syndrome
2 main antiphospholipid antibodies are:
- anti-cardiolipin
- lupus anticoagulant
They have a procoagulant effect i.e. promote blood clotting in suseptible individuals.
Associated w/ impaired fibrinolysis (the normal breakdown of blood clots) & increased vascular tone. (refers to the degree of constriction of a blood vessel i.e. more constricted).
- All contribute to clot formation & infarction
Clinical features of antiphospholipid syndrome
Major features:
- Venus thrombosis- DVT & PE most common
- Arterial thrombosis - Cerebral ischaemia e.g. stroke, transient ischaemic attacks (TIA) & peripheral ischaemia.
- Fetal complications- recurrent miscarriage, premature birth
- Thrombocytopenia - reduced platelet count. Not severe to cause haemorrhage.
- Prolonged aPTT - clotting test.
- Livedo reticularis - reddish-blue pattern of the skin of the trunk, arms of legs.
NOTE: view image on notes
Associated clinical features:
- leg ulcers
- Cardiac valve abnormalities - aortic & mitral valve regurgitation. Can cause myocardial infarctions in young people.
- Chorea- movement disorder that causes involuntary, irregular & unpredictable muscle movements.
- Epilepsy
- migrane
- Haemolytic anaemia - where blood cells are destroyed faster then they can be made.
Investigations for antiphospholipid syndrome
Immunology
- Detection of anti-cardiolipin or positive lupus anticoagulant assay.
- ANA & anti-ds-DNA
- Complement - low C3 and C4
- On at least 2 occasions 12 weeks apart
- The lupus anticoagulant assay measures the ability of the antiphospholipid antibodies to prolong clotting tests.
Blood tests:
- FBC - to check for thrombocytopenia, neutropenia or lymphopenia
- ESR - elevated but discrepancy w/ CRP relatively lower.
Biochemistry:
- U&Es - can show renal involvement
- LFT - can how liver involvement
Management of antiphospholipid syndrome
General recommendations:
- avoid oral contraceptive pill
- don’t smoke
- treat hypertension, high cholesterol & diabetes
Asymptomatic patients:
- Monitor closely
- Those w/ high cardiovascular risk factors or w/ seperate autoimmune disease should receive low-dose aspirin prophylaxis
- During high risk periods e.g. after surgery = low-molecular weight heparin thrombosis prophylaxis.
Venous or arterial thrombosis
- Lifelong warfarin - aim for an INR of 2.5 (range 2-3).
- INR = international normalised ratio.
Recurrent fetal loss
- Stop warfarin before conception!
- SC heparin & aspirin should be given throughout pregnancy.
Prognosis of antiphospholipid syndrome
Severe cases: can cause massive pulmonary embolism, stroke & myocardial infarction.
What is Sjögren syndrome?
autoimmune disorder affecting exocrine glands
Results in dry mucosal surfaces.
May be primary (PSS) or secondary to rheumatoid arthritis or other connective tissue disorders!
- develops around 10 years after initial onset.
There is a marked increased risk of lymphoid malignancy
Epidemiology of Sjögren syndrome
More common in women
Typically 40s & 50s
Primary or secondary to RA
Pathophysiology of Sjögren syndrome
- Lymphocytic infiltration of organs (salivary, lacrimal glands) causes replacement of functional epithelium
- causes fibrosis
- leads to reduced secretions in eyes, mouth etc.
Presentation of Sjögren syndrome
ASSOCIATED W/ RA, SLE, SYSTEMIC SCLEROSIS, POLYMYOSITIS, PRIMARY BILLIARY CIRRHOSIS.
Eye:
- keratoconjunctivitis sicca- dry eyes
- Blepharitis - enflamed edge of eye lid.
- Damage to cornea - more likely to get cataracts
Mouth:
- dry mouth- can lead to dental cavities or swallowing problems (dysphagia)
Other symptoms;
- vaginal dryness
- arthralgia
- Raynaud’s
- myalgia- pain in muscle
- recurrent episodes of parotitis- inflammation of parotid gland (salivary glands)
- renal tubular acidosis (usually subclinical)- accumulation of acid in body when kidney fails to acidify urine
- malignancy
- joint pain- low grade synovitis
Investigations of Sjögren syndrome
rheumatoid factor (RF) positive in nearly half of patients
ANA positive
Positive anti-Ro (SSA) antibodies
Positive anti-La (SSB) antibodies
Schirmer’s test: filter paper near conjunctival sac to measure tear formation
- 6mm+ after 5 mins is normal.
histology: focal lymphocytic infiltration
hypergammaglobulinaemia
low C4
ESR raised
Management of Sjögren syndrome
Hypromellose- eye drops.
Pilocarpine - saliva substitute.
Lubricants- vaginal dryness.
Hydroxychloroquine - (200 mg daily) often used for skin & MSK features & may also help fatigue.
Extra-glandular disease, interstitial lung disease & interstitial nephritis
- Steroids, further immunosuppression
Exclude malignancy
Prognosis of Sjögren syndrome
- Not usually life threatening
- x40 increased lifetime risk of lymphoma
What is systemic sclerosis?
Autoimmune disease affecting SKIN & internal ORGANS.
Caused by collagen accumulation (due to overproduction) in skin & viscera (abdomen & intestines)
Causes fibrosis (thickening & scarring of tissue) affecting skin, internalorgans & blood vessels.
Characterised by: Raynaud’s phenomenon, digital ischaemia, sclerodactyly & cardiac, lung, GI & renal disease.
NOTE: scleroderma means hardening of the skin & is the same disease but w/out organ involvement.
Epidemiology of systemic sclerosis
More common in women
Peak age of onset is 40-50 years
Primary or secondary- occurs w/ other autoimmune diseases e.g. myositis or SLE
When occuring w/ myositis & SLE it is called mixed connective tissue disease.
-Most patients have anti-RNP antibodies.
Sub-divisions of systemic sclerosis
- Diffuse cutaneous systemic sclerosis (30% of cases) - skin & organs
- Anti-Scl-70 antibody
- More extensive skin involvement than limited SScl - Limited cutanteous systemic sclerosis (70% of cases) - skin
- Anti-centromere antibody
- CREST
Pathophysiology of systemic sclerosis
💡 Main processes are fibrosis (thickening or scarring of tissue) & microvascular occulsion.
- T lymphocytes (CD4 helper cells) infiltrate the skin.
- There is abnormal fibroblast activation
- Leading to increased production of extra-cellular matrix in the dermis.
- This is mainly type I collagen. - This results in symetrical thickening, tightening & induration (going hard) of the skin- fibrosis
- Arteries & arterioles narrow due to perivascular (space around vessel) inflammatory filtrates & intimal (tunica intima) proliferation
- The same process obliterates the capillary bed
Presentation of systemic sclerosis
Presentation of skin - compare DSScl & LSScl
Phase 1:
- Initially non-pitting oedema(swelling) - fingers &flexor tendon sheaths (tenosynovitis).
- Puffy & tight skin - sometimes.
Phase 2:
- Then skin becomes shiny & taut.
- Sclerodactyly - hardening of skin & hand that causes it to claw.
- Raynaud’s - occurs in every patient w/ SS. Severe disease may cause digital ischaemia, ulcers & gangrene
- Potential capillary loss - due to fibrosis in tissues (unlike SLE).
- Face & neck often involved - thinning of lips + radial furrowing. Beaked like appearance of nose.
- Tethering of skin to underlying structures - common in limited form.
Distribution:
- Diffuse SS - proximal involvement to the knee, elbow & on the trunk e.g. limbs, face, neck & trunk.
- Limited SS - sites distal to elbow & knee (apart from face) e.g. hands, feet, face & neck.
Clinical features specific to limited form- CREST
- Calcinosis - the deposition of insoluable calcium in the skin.
- Raynaud phenomenon.
oEsophageal dysmotility - acid reflux & motor issues that can cause heart burn or dysphagia.
- Sclerodactyly - hardening of the skin of the hand, causing the fingers to curl inward in a claw-like shape
- Telangiectasia - dilated or broken blood vessels located near the surface of the skin.
NOTE: view images on notes
Other features:
- joint stiffness
- arthralgia- joint pain
- Pulmonary hypertension - high blood pressure in the lungs and right side of heart. Can damage right side of ❤️- leads to shortness of breath
- Scleroderma renal crisis - rapidly progressive renal failure.
- Myocardial fibrosis - can cause cardiac failure & arrhythmias.
- Pericarditis - inflammation of the pericardium (sac around heart).
NOTE: internal organ involvement is more common in diffuse form of disease but it is still possible in limited form!
Investigations for systemic sclerosis
Antibodies
- ANA positive
- RF positive
- anti-scl-70 antibodies associated w/ diffuse cutaneous systemic sclerosis
- anti-centromere antibodies associated w/ limited cutaneous systemic sclerosis
Imaging:
- x-ray first
- Echocardiography- fr heart
- Lung function test
- Barium swallow - oesophageal involvement
Blood tests:
- FBC
- U&Es
Management for Systemic sclerosis
Raynaud’s & digital ulcers
- Avoid cold, thermal gloves/socks, high core temp.
- Vasodilators - Ca channel blockers e.g. amlodipine, losarten, fluoxetine, sildenafil, IV prostacyclin, bosentan.
GI complications
- Proton pump inhibitors
Hypertension in renal crisis
- ACE inhibitors e.g. Ramipril
- Ca-channel blockers e.g. Amlodipine
- Bring down the blood pressure!!
Joint involvement
- NSAIDs, analgesia
Progressive pulmonary hypertension
- Bosentan or heart-lung transplant
Interstitial lung disease
- Glucocorticoids
- Cyclophosphamide
SCREENING FOR COMPLICATIONS:
- ECG
- Pulmonary function tests
- Blood pressure- hypertension is a complication of diffuse systemic sclerosis
- renal function
Prognosis of Systemic sclerosis
Poor
Better prognosis for limited SS
Treatment options often lead to undesirable adverse effects.
Most common cause of death is respiratory involvement, which is seen in around 80%: interstitial lung disease (ILD) & pulmonary arterial hypertension
Name the autoantibody for each connective tissue disease
VERY IMPORTANT- LEARN TABLE
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