Multi-system autoimmune disease Flashcards
Examples of connective tissue disease (4)
systemic lupus erythematosus
systemic sclerosis
sjogre’s syndrome
auto-immune myositis
Examples of systemic vasculitides
- giant cell arteritis
- granulomatosis with polyangiitis
- microscopic polyangitis
- eosinphillic granulomatosis
Common presenting symptoms
myalgia/arthalgia
Approach to multi system inflammatory disease (6)
- Cardinal clinical features:
- bedside investigations - o2, bp, temperature, tracheal analysis
- History & Exam
- Immunology - lab tests
- imaging
- tissue diagnosis - biopsy , skin, renal, lung, temporal artery
possible systemic autoimmune rheumatic disease - mimics/differential diagnosis
Drugs - cocaine, minocyline, PTU
Infection - HIV, endocarditis, Hepatitis B and C, TB
Malignancy - lymphoma
Cardiac myxoma
Cholesterol emboli
Scurvey
Minocyline can induce
lupus
Systemic lupus erythematosus (SLE) - what is this
multi system disorder - encompasses almost all organs and tissues
mallar rash in SLE?
across the nasal bridge and cheeks, spares the nasal folds
SLE is more common in?
when is the onset?
male
- 15-50 years
Aetiology of SLE (3)
genetic and environmental components
- hormonal components (prolactin) - modulate incidence of SLE
Examples of environmental factors for SLE
UV light
drugs
infections
Examples of genetic factors for SLE (3)
high rate in monozygotic twins
- sibling risk
- polygenic mode of inheritance
SLE: pathogenesis (4)
- describe the process from autoantigens to cytokines
- immune response against endogenous nuclear antigens
(- autoantigenes - related by apoptotic cells - T cell
- Activated T cells help B cells produce autoantibodies - Cytokine)
- immune complex formation
- complement activation
- tissue injury
SLE: clinical presentation (many examples)
varied
- alopecia
- neuro involvement - Pn, CNL, ataxia, fits
- rash
- photosensitivity
- pleurisy, pleural effusion, fibrosis
- pericarditis, endocarditis,
- abdo pain
- Raynaud’s
- arthritis in small joints, aseptic necrosis of the hip and the knee
- myopathy
- blood - leukopenia, anaemia
Classification criteria (any 4 of 11) - what would you look for
1) Malar rash (butterfly rash)
2) Discoid rash (raised, scarring, permanent marks, alopecia) - keratotic scaling in centre
3) Photosensitivity
4) Oral ulcers
5) Arthritis (2 joints at least)
6) Serositis (pleurisy or pericarditis)
7) Renal (significant proteinuria or cellular casts in urine) 0.5g per 24hr
8) Neurological (unexplained seizures or psychosis)
9) Haematological (low WCC, platelets, lymphocytes, haemolytic anaemia)
10) Immunological (anti ds-DNA, SM, cardiolipin, lupus anticoagulant, low complement)
11) ANA
arthritis with SLE
must involve 2 joints
(charcot’s arthroy)
bilateral symmetrical involvement
non-erosive
Kidney with SE - should check (lupus nephritis)
Urinalysis for proteunira and haematuria
classes of lupus nephritis
I- minimal mesangial II - mesnagial proliferation III- focal IV - diffuse V - membranous VI - advanced sclerosing
When to consider diagnosis of SLE (women)
women of childbearing age - present with fever, weight loss fever, severe fatigue, malaria rash, stomatitis photosensitivity
- mouth ulcers
- arthritis (joint pain)
- pleuritic chest pain
- dip stick for protein and blood
- cytopenia
Autoantibodies in SLE
ANA (antinuclear antibodies)
- high specificity 99% in SLE
- seen in inflammatory, infectious and neoplastic diseases
Specific Autoantibodies in SLE
Anti- D’s DNA
Anti- Sm
Autoantibody with strongest association with nephritis
anti-d’s DNA
other antibodies in lupus (2) - what are they associated with?
ANTI- Ro
- fetal congenital heart block (monitoring in pregnancy)
- neonatal lupus
antiphospholoipid antibodies
- associated with miscarriages
- venous/areterial thrombus
antiphospholoipid antibodies associated with arterial/venous thrombosis?
anti-cardiolipin, lupus anticoagulant
Scleroderma - defintion
onset??
fibrosis of the skin and internal organs, alterations in microvasculature and cellar immunity
30-50 years
Classification of scleroderma (2)
what is the difference?
- localised scleroderma
- systemic sclerosis
- CREST, diffuse cutaneous
what is the difference between localised scleroderma and systemic sclerosis ?
localised scleroderma - restricted to fibrotic skin and subcutaneous tissue
- systemic = ALSO affects the internal organs
Systemic sclerosis affects
internal organs
CREST - limited cutaneous SS is defined by?
skin involvement distal to the elbows and knees
Diffuse Cutaneous SS is denied by?
skin thickening proximal to knees and elbows
Aetiology of scleroderma
Environmental
- silica, solvents, viral infections
- genetic predisposition
- pathogenesis
(vascular damage, inflammation, fibrosis)
Scleroderma: limited - management/ clinical signs
long and careful follow up
- whitening of the fingers, rash, blood vessels
gangrene changes , can trigger soft tissue infections
Scleroderma: limited - management/ clinical signs
Complications?
long and careful follow up
- whitening of the fingers, rash, blood vessels
gangrene changes , can trigger soft tissue infections
- pulmonary hypertension
- GI involvement
Complications of Scleroderma: Diffuse
fast progression of skin sclerosis in weeks/months with int organ involvement - lungs
- rapid interstitial lung disease
Pulmonary fibrosis
Renal crisis
Small bowel bacterial overgrowth
Scleroderma: limited - autoantibody?
anti- centromere antibodies
- present with late complications
Scleroderma: diffuse - autoantibody - what does it lead to clinically (3)
anti - Scl70 - pul fibrosis - renal crisis - small bowel bacterial overgrowth (inflammation and fibrosis - malabsorption) (abdo bloating, weight loss)
- GAVE - dilation of small BV in mucosa
Scleroderma: diffuse -treatment
ace inhibitors
- should not get high doses of steroids
abrupt onset of mod /severe hypertension - AKI
- bland urinalysis
Sjogren’s syndrome is characterised by?
lymphocytic infiltrates in the salivary and tear glands
- oral dryness
Sjogren’s syndrome more common in
females (age peak after menopause)
Sjogren’s syndrome symptoms (6/7)
Dry eyes and mouth Parotid gland enlargment 1/3 have systemic upset fatigue fever myalgia arthalgia
Sjogren’s syndrome - antibodies?
Anti RO anti La antibodies
Classification of Sjogren’s syndrome (3)
- ocular dryness for at least 3 months (sensation of sand in the eye)
- oral dryness
- swollen glands in the neck
Sjogren’s syndrome : complications (5)
- Lymphoma
- Neuropathy
- Purpura
- Interstitial lung disease
- Renal tubular acidosis - monitor electrolytes
Auto-immune myositis are?
rare diseases
Auto-immune myositis includes polymyositis and dermatomyositis - describe the epidemiology (4)
Rare
more common in females
peal incidence in 50-60 yo
- increased risk of malignancy
Auto-immune myositis - features
- what is the predominant symptom and what is its distribution?
Muscle Weakness - symmetrical, diffuse, proximal
Polymyositis
Dermatomyositis
Gottron’s papules (80%) - purple link - over hands
Heliotrope rash (30-60%)
antibodies associated with auto-immune myositis?
what condition are patients at risk of getting with this antibody
anti Jo1 antibodies
interstitial lung disease
overlap syndrome of missed connective tissue disease - what do they present with (4)
- raynaud’s
soft tissue swelling/sclerodactyly - myositis
- arthralgia
The vasculitides - large vessel - - what are the 2 types
Takayasu arteritis - asian popualtions
- GCA- older patients
The vasculitides - medium vessel - - what are the 2 types
in children
Polyarteritis Nodosa
Kawasaki disease
small vessel vasculitis - divided into?
small vessel involvement with immune complex deposition
- hyeprsensitivity
- IgA vascualtis
Giant cell arteritis is common in?
patients above 70 year of age
(50-70)
more commonly in women
Giant cell arteritis - classification criteria (5)
Age at onset ≥50 years
New headache (can occur in all areas) - continuous pain, especially at night
Temporal artery tenderness/reduced pulsation
ESR≥50
Abnormal temporal biopsy
– jaw claudication - ischemia of master muscles
- pian brushing hair/ scalp tenderness
- other systemic symptoms
what will a Abnormal temporal biopsy show? (3)
inflammatory infiltrate in artery wall
- intermal hyperplasia
- luminal occlusion
Some patients in GTA will present with?
large vessel involvement
- systemic symptoms
Investigation of GCA? (5)
- temporal artery biopsy
- ultrasound doppler (halo sign)
- CT angiogram - identify evidence of stenosis or aneurysm
- MR angiogram
- FDG PET
GCA - COMPLICATIONS
- irreversible visual loss
- aortic aneurysms
- arterial stenosis and limb ischemia
- stroke
GCA - treatment
high dose steroids straight away - prednisolone
- 40-60mg per day
- PPI
- bone protection
- steroid sparing medication
ANCA associated vasculitis - why is it important (small vessel) - give 3 main examples
used to very high mortality, is now a chronic disease = good survival rate
Granulomatosis with polyangiitis (Wegener’s)
Microscopic polyangiitis
Eosiniphilic granulomatosis with polyangiitis
Granulomatosis with polyangiitis (GPA) (Wegener’s) - what is this?
what does it typically involve?
what vessels does it effect?
Necrotising granulomatous inflammation
Usually involving the upper and lower respiratory tract
Affecting predominantly small to medium vessels
Necrotising glomerulonephritis is common
Symptoms of Granulomatosis with Polyangiitis (Wegener’s) (GPA)
otitis medium hearing loss sinusitis nasal crusting epistaxis, hemoptysis - collapsing of nasal bridge
What us common with GPA
- what antibodies will they have?
Necrotising glomerulonephritis is common
ENT symtoms - cANCA, anti PR3, urine protein
Microscopic polyangiitis (MPA) - what is it ? affects?
What is often absent?
Necrotising vasculitis, with few or no immune deposits, predominantly affecting small vessels.
- Necrotising glomerulonephritis is very common
Pulmonary capillaritis often occurs
Granulomatous inflammation is absent
Microscopic polyangiitis (MPA) - patients present with?
what antibodies? (2)
pulmonary renal syndrome, renal failure, positive line dipstick
pANCA, anti MPO
Eosinophilic Granulomatosis with Polyangiitis (Churg Strauss) (EGPA) - patients will have? late onset of what conditons?
- Eosinophil rich and necrotising granulomatous inflammation often involving the respiratory tract
- late onset asthma, nasal polyps, eosinophilia
ANCA is more frequent when
glomerulonephritis is present
Eosinophilic Granulomatosis with Polyangiitis - involvement of other systems ?
neurological
cardiac, gastrointestinal - poor prognosis
You should avoid this drug in treating SLE
steroids
