Multi-system Autoimmune Disease Flashcards
Name some autoimmune connective tissue diseases (5)
- Systemic Lupus Erythematosus
- Systemic sclerosis
- Sjogren’s syndrome
- Auto-immune myositis
- Mixed connective tissue disease
Name some autoimmune systemic vasculitidies (4)
- Giant cell arteritis
- Granulomatosis with polyangiitis (Wegeners)
- Microscopic polyangiitis
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
What are 2 very common presenting symptoms of multi-system autoimmune diseases?
- Arthralgia - joint pain
- Myalgia - muscle pain
How should you approach a patient who is thought to have a multi-system inflammatory disease?
- Cardinal clinical features: history & examination
- Bedside investigations – O2 sats, BP, temp, Urinalysis
- Immunology
- Imaging
- Biopsy for tissue diagnosis - ‘gold standard’ in many CT diseases - skin, renal, lung or temporal artery
- Exclusion of differential diagnoses - CT diseases are rarer and can mimic other diseases
What is Systemic Lupus Erythematosus (SLE)?
An inflammatory autoimmune connective tissue disease.
- ‘Systemic’ because it affects multiple organs and systems
- ‘Erythematosus’ becuase of the red malar rash
What is the classic dermatological sign associated with lupus?
Butterfly-shaped rash across the cheeks and bridge of the nose.
Epidemiology of SLE
- Relatively uncommon
- Affects Females > Males
- Young/middle aged adults
- It often takes a relapsing-remitting course
What causes SLE?
A mix of genetic, hormonal and environmental factors
Genetics
- Higher incidence in monozygotic twins and siblings
Environmental
- UV light
- Drugs
- Infections
Describe the pathogenesis of SLE
SLE is characterised by anti-nuclear antibodies/autoantibodies. These antibodies create an immune response by targeting ‘self’ nuclear antigens (proteins within the persons own cell nucleus).
- This activates the immune system and generates an inflammatory response
- Immune complex formation – amplify and sustain immune response
- Complement activation - innate immunity - enhances (complements) the ability of antibodies and phagocytic cells to clear immune complexes, microbes and damaged cells
- Tissue damage is mediated by recruitment of inflammatory cells, reactive O2, modulation of the coagulation cascade etc.
This inflammation in the body leads to symptoms of the condition. Sustained inflammation against tissues in the body causes injury/problems.
How does SLE present?
Non-specific symptoms
- Fatigue
- Weight loss
- Photosensitive malar rash - meaning it is triggered by sunlight exposure
- Arthralgia
- Myalgia
- Fever
- SOB
- Lymphadenoapthy and splenomegaly
- Pleuritic chest pain
- Arthritis
- Renal disease
- Hair loss
- Mouth ulcers
- Raynaud’s
Discoid lupus Erythematosus
Non-cancerous chronic skin condition. DLE only affects the skin where as SLE affects internal organs + systems too.
- Women > men
- Associated with a small increased risk of developing systemic lupus erythematosus
- Lesions are photosensitive (made worse by exposure to sunlight)
Lesions appear:
- Dry
- Inflamed
- Crusty
- Erythematous
- Patchy
Management:
- Sun protection
- Topical steroids
- Intralesional steroid injections
Which examinations are important to check for kidney involvement in SLE?
- Urinalysis - check for proteinuria or haematuria
- Renal biopsy for further investigation
What is the sensitivity and specificity like for anti-nuclear antibody screening in SLE?
ANA is highly sensitive for SLE - it is seen in 95% of cases
But it is not specific for SLE as these auto-antibodies (the antibodies that target “normal” proteins within the nucleus of a cell) are seen in many inflammatory, infectious and neoplastic diseases. It can also be seen in 5-15% of the healthy population.
What other autoantibodies are specific to SLE?
- Anti-ds DNA
- Anti - Sm
- Anti - Ro
- Antiphospholipid antibodies
What are the 2 major subsets of Systemic Sclerosis?
- Limited cutaneous systemic sclerosis (CREST)
- Diffuse cutaneous systemic sclerosis
Describe Limited cutaneous systemic sclerosis (previously known as CREST)
It is the more limited/milder version of systemic sclerosis. Slower progression of skin involvement and very late internal organ complication (i.e 10 to 15 years)
- Anti centromere antibodies are associated with limited SSc.
- Can cause pulmonary hypertension and GI problems.
CREST
Calcinosis - calcium deposits under the skin - commonly affects fingertips.
Raynaud’s
oEsophageal dysmotility - CT dysfunction - swallowing difficulties, acid reflux + oesophagitis
Sclerodactyly - skin changes in the hands. Skin tightens around joints and restricts the motion in the joint. As the skin hardens and tightens further the fat pads on the fingers are lost and the skin can break and ulcerate.
Telangiectasia - dilated small blood vessels in the skin
Systemic sclerosis Vs Scleroderma. What’s the difference?
- The terms systemic sclerosis and scleroderma are often used interchangeably.
- Most patients with scleroderma have systemic sclerosis, however, there is a localised version of scleroderma that only affects the skin.
- Systemic sclerosis is an autoimmune inflammatory and fibrotic connective tissue disease.
- Scleroderma translates directly to ‘hardening of the skin’
Describe diffuse cutaneous sclerosis
- This is the opposite to limites SSc. Diffuse cutaneous systemic sclerosis includes the features of CREST syndrome plus it affects internal organs i.e heart, lungs, kidneys.
- Patients develop fast progression of skin sclerosis (weeks/months) and have early organ involvement
- Anti-Scl70 antibodies are most associated with diffuse cutaneous systemic sclerosis
- Can result in pulmonary fibrosis, renal crisis or small bowel bacterial overgrowth
Aetiology/pathogenesis of Systemic sclerosis
Environmental (silica, solvents, viral infection) and genetic factors are involved.
Pathogenesis:
- Vascular damage
- Immune system activation/inflammation
- Fibrosis
What is Sjogren’s syndrome?
A systemic autoimmune disease that affects exocrine glands i.e salivary and tear glands.
- It is quite common (1 in 100).
- Affects Males > Females.
- Commonly starts in patients 40-60 y/o
- Primary - common
- Secondary - lupus, rheumatoid arthritis, systemic sclerosis.
Presenting feature = dry eyes, mouth and vagina.
1/3 have systemic upset (fatigue, fever, dry skin etc)
Which antibodies are associated with Sjorgen’s syndrome? (2)
- Anti Ro
- Anti La
Clinical features of Sjogren’s syndrome
- Fits
- Hemiplegia
- Ataxia
- Cranial nerve lesions
- Interstitial lung disease
- Dysphagia
- Oesophageal dysmotility
- Arthralgia
- Raynaud’s
What is the Schirmer test?
It is a test for Sjogren’s syndrome. It involves inserting a folded piece of filter paper under the lower eyelid with a strip hanging out over the eyelid. This is left for 5 minutes and the distance along the strip that becomes moist is measured.
- Normal, healthy adult - 15mm
- Less than 10mm is significant
What are some complications of Sjogren’s syndrome?
- Lymphoma
- Neuropathy
- Cutaneous vasculitis
- Interstitial lung disease
- Renal tubular acidosis
