Multi-system Autoimmune Disease Flashcards

1
Q

Name some autoimmune connective tissue diseases (5)

A
  • Systemic Lupus Erythematosus
  • Systemic sclerosis
  • Sjogren’s syndrome
  • Auto-immune myositis
  • Mixed connective tissue disease
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2
Q

Name some autoimmune systemic vasculitidies (4)

A
  • Giant cell arteritis
  • Granulomatosis with polyangiitis (Wegeners)
  • Microscopic polyangiitis
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
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3
Q

What are 2 very common presenting symptoms of multi-system autoimmune diseases?

A
  • Arthralgia - joint pain
  • Myalgia - muscle pain
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4
Q

How should you approach a patient who is thought to have a multi-system inflammatory disease?

A
  • 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
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5
Q

What is Systemic Lupus Erythematosus (SLE)?

A

An inflammatory autoimmune connective tissue disease.

  • ‘Systemic’ because it affects multiple organs and systems
  • ‘Erythematosus’ becuase of the red malar rash
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6
Q

What is the classic dermatological sign associated with lupus?

A

Butterfly-shaped rash across the cheeks and bridge of the nose.

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7
Q

Epidemiology of SLE

A
  • Relatively uncommon
  • Affects Females > Males
  • Young/middle aged adults
  • It often takes a relapsing-remitting course
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8
Q

What causes SLE?

A

A mix of genetic, hormonal and environmental factors

Genetics

  • Higher incidence in monozygotic twins and siblings

Environmental

  • UV light
  • Drugs
  • Infections
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9
Q

Describe the pathogenesis of SLE

A

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.

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10
Q

How does SLE present?

A

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
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11
Q

Discoid lupus Erythematosus

A

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
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12
Q

Which examinations are important to check for kidney involvement in SLE?

A
  • Urinalysis - check for proteinuria or haematuria
  • Renal biopsy for further investigation
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13
Q

What is the sensitivity and specificity like for anti-nuclear antibody screening in SLE?

A

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.

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14
Q

What other autoantibodies are specific to SLE?

A
  • Anti-ds DNA
  • Anti - Sm
  • Anti - Ro
  • Antiphospholipid antibodies
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15
Q

What are the 2 major subsets of Systemic Sclerosis?

A
  • Limited cutaneous systemic sclerosis (CREST)
  • Diffuse cutaneous systemic sclerosis
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16
Q

Describe Limited cutaneous systemic sclerosis (previously known as CREST)

A

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

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17
Q

Systemic sclerosis Vs Scleroderma. What’s the difference?

A
  • 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’
18
Q

Describe diffuse cutaneous sclerosis

A
  • 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
19
Q

Aetiology/pathogenesis of Systemic sclerosis

A

Environmental (silica, solvents, viral infection) and genetic factors are involved.

Pathogenesis:

  • Vascular damage
  • Immune system activation/inflammation
  • Fibrosis
20
Q

What is Sjogren’s syndrome?

A

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)

21
Q

Which antibodies are associated with Sjorgen’s syndrome? (2)

A
  • Anti Ro
  • Anti La
22
Q

Clinical features of Sjogren’s syndrome

A
  • Fits
  • Hemiplegia
  • Ataxia
  • Cranial nerve lesions
  • Interstitial lung disease
  • Dysphagia
  • Oesophageal dysmotility
  • Arthralgia
  • Raynaud’s
23
Q

What is the Schirmer test?

A

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
24
Q

What are some complications of Sjogren’s syndrome?

A
  • Lymphoma
  • Neuropathy
  • Cutaneous vasculitis
  • Interstitial lung disease
  • Renal tubular acidosis
25
Q

What are Polymyositis and dermatomyositis?

A

Very rare autoimmune conditions where there is inflammation in the muscles. Predominant symptom = muscle weakness.

  • Polymyositis - chronic inflammation of muscles
  • Dermatomyositis - CT disorder where there is chronic inflammation of the skin and muscles

If left untreated it will progress slowly and the patient may become dependent on a wheelchair. If they have bulbar muscle (muscles of the mouth and throat) involvement then they might develop swallowing and nutrition problems.

26
Q

What are the key investigations for diagnosing myositis?

A
  • Creatinine kinase blood test - a raised CK level indicates breakdown of muscle cells.
    • Normal CK level = <300 U/L
    • In myositis and dermatomyositis the result is usually >1000 U/L
  • Muscle biopsy - ‘gold standard’
27
Q

Which auto-antibodies are associated with polymyositis and dermatomyositis?

A
  • Anti-Jo-1 antibodies - polymyositis
  • Anti-Mi-2 antibodies - dermatomyositis
28
Q

What are the cutaneous manifestations of myositis?

A
  • Gottron’s papules - 80% - see image
  • Heliotrope rash
29
Q

What is Mixed connective tissue disease (MCTD)?

A

A rare autoimmune disorder that is characterised by features commonly seen in all 3 different connective tissue disorders: systemic lupus erythematosus, scleroderma, and polymyositis.

These patients present with clinical pictures of a range of CT disorders:

  • Arthralgia
  • Myositis
  • Soft tisue swelling/sclerodactyly
  • Raynaud’s
30
Q

What are the vasculitides?

A

A group of autoimmune diseases, all characterised by vasculitis and subsequent ischaemia and damage to organs supplied by these vessels.

3 different groups depending on vessel size:

  • Small - ANCA-associated vasculitis, Granulomatosis with Polyangitis, Eosinophilic Granulomatosis with Polyangitis
  • Medium
  • Large - Giant Cell Arteritis
31
Q

Giant Cell Arteritis

A
  • Common
  • Aetiology is unknown
  • Common in 70+ but can appear in those over 50
  • White population
  • RF: Female, Age

Common presentation

  • >50 y/o
  • New headache
  • Temporal artery tenderness/reduced pulsation
  • ESR > or equal to 50
  • Abnormal temporal biopsy
32
Q

What is the ‘gold standard’ investigation for Giant Cell Arteritis?

A

Temporal artery biopsy

  • If +ve should show inflammatory infiltrate in the artery wall as well as intimal hyperplasia and luminal occlusion
33
Q

What investigations are done for GCA?

A
  • Temporal artery biopsy
  • USS doppler
  • CT angiogram, MR angiogram
  • FDG PET scan
34
Q

How is GCA treated?

A

Urgent initation of high dose Prednisolone

Bone protection

35
Q

Complications of GCA (4)

A
  • Irreversible visual loss
  • Aortic aneurysm
  • Arterial stenosis and limb ischaemia
  • Stroke
36
Q

What is ANCA associated vasculitis?

A

A group of diseases that affect small vessels.

Encompasses

  • Granulomatosis with polyangiitis (Wegener’s)
  • Microscopic polyangiitis
  • Eosiniphilic granulomatosis with polyangiitis
37
Q

Microscopic polyangiitis (MPA)

A
  • Necrotising vasculitis, with few or no immune deposits, predominantly affecting small vessels
  • Granulomatous inflammation is absent
  • Renal and pulmonary involvement common
  • pANCA, anti MPO antibodies
38
Q

Describe Granulomatosis with polyangiitis (previously known as Wegener’s)

A
  • Necrotising granulomatous inflammation
  • Usually involves URT and LRT
  • Hearing loss, sinusitis and haemoptysis
  • cANCA and anti PR3 antibodies associated with this
39
Q

Eosinophilic Granulomatosis with Polyangiitis

A
  • Eosinophil rich and necrotising granulomatous inflammation often involving the respiratory tract
  • Late onset asthma, nasal polyps and eosinophilia
  • Neurological involvement
  • 40-60% anti MPO antibodies positive
40
Q

Case scenario

  • 45 year old F with 3-day history of breathlessness and R-sided chest pain worse with deep inspiration
  • CXR confirms right pleural effusion
  • Treatment with antibiotics makes no difference
  • FBC showed persistently low WCC of 3.0 then 3.2 and low platelets of 100
  • Over the last year she has been experiencing intermittent pain and swelling in her joints and recurrent facial rash after sun exposure
  1. What is the likely diagnosis?
  2. Which bedside assessment would you prioritise?
  3. Which immunological tests would support your clinical suspicion?
A
  1. Systemic lupus erythematosus
  2. Urine dipstick
  3. Positive anti dsDNA antibodies, Reduced complement levels, Positive anti Smith antibodies and Positive anti-nuclear antibodies