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PBL Week 12 > Autoimmune connective tissue disorders > Flashcards

Autoimmune connective tissue disorders Flashcards

1
Q

Examples of autoimmune connective tissue disorders? General causes?

A

Polymyositis & Dermatomyositis

Antiphospholipids syndrome

Sjögren syndrome

Systemic sclerosis & scleroderma

Causes of autoimmune disease:
- cancer
- environment
- genetics

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2
Q

What is polymyositis and dermatomyositis?

A

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

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3
Q

Epidemiology of polymyositis and dermatomyositis

A

Middle aged

More common in women

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4
Q

Pathophysiology of polymyositis and dermatomyositis

A

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

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5
Q

Presentation of polymyositis and dermatomyositis

A

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

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6
Q

Investigations for polymyositis and dermatomyositis

A

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

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7
Q

Management for polymyositis and dermatomyositis

A
  1. High dose oral glucocorticoids e.g. prednisolone.
  2. With immunosuppressive therapy e.g. methotrexate or MMF first choices.
    - Azathioprine is an alternative- steroid sparing agent
  3. Serum CK monitored
    - As it falls, the dose of steroid is gradually reduced.
    - Maintainanence dose of 5-7.5 mg.
  4. Cyclophosphamide - for patients w/ interstitial lung disease.
  5. Treat malignancy if found.
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8
Q

What is antiphospholipid syndrome?

A

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)

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9
Q

Epidemiology of antiphospholipid syndrome

A

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

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10
Q

Pathophysiology of antiphospholipid syndrome

A

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

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11
Q

Clinical features of antiphospholipid syndrome

A

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.

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12
Q

Investigations for antiphospholipid syndrome

A

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

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13
Q

Management of antiphospholipid syndrome

A

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.

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14
Q

Prognosis of antiphospholipid syndrome

A

Severe cases: can cause massive pulmonary embolism, stroke & myocardial infarction.

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15
Q

What is Sjögren syndrome?

A

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

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16
Q

Epidemiology of Sjögren syndrome

A

More common in women

Typically 40s & 50s

Primary or secondary to RA

17
Q

Pathophysiology of Sjögren syndrome

A
  1. Lymphocytic infiltration of organs (salivary, lacrimal glands) causes replacement of functional epithelium
  2. causes fibrosis
  3. leads to reduced secretions in eyes, mouth etc.
18
Q

Presentation of Sjögren syndrome

A

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

19
Q

Investigations of Sjögren syndrome

A

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

20
Q

Management of Sjögren syndrome

A

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

21
Q

Prognosis of Sjögren syndrome

A
  • Not usually life threatening
  • x40 increased lifetime risk of lymphoma
22
Q

What is systemic sclerosis?

A

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.

23
Q

Epidemiology of systemic sclerosis

A

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.

24
Q

Sub-divisions of systemic sclerosis

A
  1. Diffuse cutaneous systemic sclerosis (30% of cases) - skin & organs
    - Anti-Scl-70 antibody
    - More extensive skin involvement than limited SScl
  2. Limited cutanteous systemic sclerosis (70% of cases) - skin
    - Anti-centromere antibody
    - CREST
25
Q

Pathophysiology of systemic sclerosis

A

💡 Main processes are fibrosis (thickening or scarring of tissue) & microvascular occulsion.

  1. T lymphocytes (CD4 helper cells) infiltrate the skin.
  2. There is abnormal fibroblast activation
  3. Leading to increased production of extra-cellular matrix in the dermis.
    - This is mainly type I collagen.
  4. This results in symetrical thickening, tightening & induration (going hard) of the skin- fibrosis
  5. Arteries & arterioles narrow due to perivascular (space around vessel) inflammatory filtrates & intimal (tunica intima) proliferation
  6. The same process obliterates the capillary bed
26
Q

Presentation of systemic sclerosis

A

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!

27
Q

Investigations for systemic sclerosis

A

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

28
Q

Management for Systemic sclerosis

A

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

29
Q

Prognosis of Systemic sclerosis

A

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

30
Q

Name the autoantibody for each connective tissue disease

A

VERY IMPORTANT- LEARN TABLE

https://www.notion.so/PBL-week-12-d2d622ca46c049de861be1b7fb103a1a

PBL Week 12 (7 decks)

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