Multi-System Autoimmune Diseases Flashcards
What are connective tissue diseases?
Broad group of disorders that affect connective tissues (cartilage, BVs, bones, tendons etc.)
What are examples of autoimmune connective tissue diseases?
SLE Slceroderma Sjogren's syndrome Autoimmune myositis Mixed connective tissue disease
What is autoimmune vasculitis?
Autoimmune diseases characterised by inflammation of blood vessels (vasculitis) & subsequent ischaemia and damage to organs
What are the autoimmune vasculitides?
Giant cell arthritis
Granulomatosis polyangiitis (Wegner’s)
Microscopic polyangiitis
Eosinophilic granulomatosis polyangiitis (Churg-Strauss)
How do you diagnose an autoimmune vasculitis?
Cardinal clinical features (Ex & Hx)
Immunology
Imaging
Tissue - only way to get a proper diagnosis is via biopsy and microscopy
Exclusion of DDx
What may mimic autoimmune vasculitis?
Drugs Infection Malignancy Cardiac myxoma Cholesterol emboli Scurvy
What drugs may mimic autoimmune vasculitis?
Cocaine (nausea, sweating, unstable HR and BP, chest pain, chills, resp depression)
Minocycline (nausea, diarrhoea, headache, fatigue, myalgia/arthralgia, rash, pruritus)
What infections may mimic autoimmune vasculitis?
HIV - myalgia/arthalgia, fever, generalised rash, generalised non-tender lymphadenopathy, headache
Endocarditis
Hepatitis
TB
What symptoms do you get with endocarditis?
Inflammation of inner lining of heart and valves, usually caused by infections
Fever, chills, generalised malaise, weakness, night sweats, pleuritic chest pain, arthalgia/myalgia
What symptoms do you get with hepatitis?
Malaise, fever, myalgia/arthalgia, jaundice, pruritus
What symptoms do you get with TB?
Wt loss, fever, night sweats, lymphadenopathy, dyspnoea, productive cough
What is a cardiac myxoma and what symptoms do you get with one?
Benign heart tumour
SoB, fever, wt loss, palpitations
What do you get with a cholesterol embolus?
Acute renal failure, purpura, GI and NS involvement, e.g. stroke
What is scurvy? What symptoms do you get with it?
Lack of vit C
Tiredness, sore arms, legs, gum disease, bleeding from skin
What age and gender tend to get SLE?
Young females (9x)
20-22 is peak
Onset: 15-50yo
Oestrogen has a lot to do with the disease (men present when middle aged with diff presentation)
In which race is SLE more common?
Afrocarribeans > Asians >
Caucasians
Also worse in Afrocarribeans
What is the pathophysiology of SLE?
GENETICS & ENVIRONMENT
E.g. girl has susceptibility genes and exposed to UV radiation
UV –> cell DNA damage –> apoptosis –> apoptotic bodies (DNA, histones, proteins released from cells - as these are from the nucleus they are ‘nuclear antigens’)
Susceptibility genes mean immune cells more likely to think nuclear antigens are foreign & make Abs against the NA (anti-nuclear antibodies)
Susceptibility genes also –> less able to clear NAs so –> worse build up of NAs
ANAs present in lost SLE and form complex with NAs
Complexes enter BS and deposit/stick to vessel walls/organs (kidneys, joints, skin, heart)
Deposits cause local inflammation reaction in tissues –> damage via activation of complement system –> fully permeable channels in cells –> cells burst and die
Many patient’s also develop Ab against other cells (RBCs/WBC) and molecules (e.g. phospholipids) and its not fully understood why
What is the clinical presentation of SLE?
SLE can theoretically affect anywhere in the body
Classical presentation: woman, child bearing age, fever, rash, joint point and symptoms specific to where the complexes have deposited
FLARES and REMITTANCE
What classification criteria is used to diagnose lupus?
Don’t need to fufill a criteria to diagnose it
What is the classification criteria for lupus?
Any 4 of:
1. malar rash (butterfly) - sparing nasolabial folds, appears after sun exposure
2 - discoid rash (raised, dark, scaley, scarring, permanent marks, alopecia)
3 - photosensitivity
4 - oral ulcers
5 - arthritis (2 joints)
6 - serositis (pleurisy/pericarditis)
7 - renal (significant proteinuria/cellular casts in urine)
8 - neurological (unexplained seizures/psychosis)
9 - haematological (low WCC, platelets, lymphocytes, haemolytic anaemia)
10 - immunological (other Ab and low complement)
11 - ANA
What will SLE arthritis look like on Xray?
No damage to the bone, ligaments have softened up - it is fully reversible!
Why might people with SLE and renal involvement have normal U&Es?
Dipstick will better show protein/blood in urine which are early signs of kidney disease
Why do you get haematological anomalies in SLE?
WCC/platelets/lymphocytes/RCs etc are targeted by immune cells and destroyed
What are the other antibodies as mentioned in 10?
Anti-smith
Anti-dsDNA
Antiphospholipids - anti-cardiolipin, lupus anticoagulant
What is anti-smith an Ab against?
Small ribonucleoproteins
What is anti-dsDNA an Ab against?
Double stranded DNA
What are anti-phospholipids an Ab against?
Proteins attached to phospholipids
Are ANA only found in SLE?
NO
What other things may cause a butterfly like rash?
Rosacea and mitral stenosis
How do you Mx SLE?
Avoid sunlight
Corticosteroids
Immunosupressants
What is scleroderma?
Chronic dx caused by abnormal growth of connective tissue which leads to diffuse thickening and hardening of the skin & often inner organs
What does sclerosis mean?
Thickening
What is characteristic of scleroderma?
Top layer of skin becomes very keratinised and 5x as thick as it should be & loss of skin softness
May also get swelling of hands/feet, joint pain, BV damage –> overreaction to cold/stress (Raynauds)
In which gender/age group is scleroderma most common?
3x F and 30-50yo
What is the pathogenesis of scleroderma?
Inflammatory synthesis of ECM - fibroblast proliferation and synthesis of normal collagen
+ non-inflammatory vasculopathy if more severe dx
What are morphea?
Localised patches of hardened skin
Usually on trunk
Don’t come with over symptoms/pain
What are the types of scleroderma?
Localised and systemic sclerosis
What does localised scleroderma involve?
Morphea/linear scleroderma
What are the types of systemic sclerosis?
Limited
Diffuse
What does systemic sclerosis involve?
Internal organs & skin involved
What does limited systemic sclerosis present like?
90% time Raynauds precedes onset of other symptoms
Skin manifestations usually involve hands, fingers, face - DOES NOT PASS ELBOWS
Extracutaneous organ involvement may occur (e.g. difficulty swallowing, heartburn etc.)
May manifest as crest syndrome
What does diffuse systemic sclerosis tend to present like?
Raynaud’s coinciding/following onset of other symptoms
Skin manifestations spread proximally from trunk –> elbow (thickening and tightening of skin across whole body)
Extracutaneous manifestations common
What extracutaneous manifestations may be present in systemic sclerosis?
Arthalgia/myalgia
GI
Oesophageal dysmotility - dysphagia/reflux
Small bowel dysmotility - bloating, gas, constipation, cramping
Pulmonary dx - pulmonary HTN, interstitial lung dx
Heart dx - myocarditis, pericarditis
Renal - abnormal collagen deposition –> decreased renal BF & therefore function
ETC
What is CREST syndrome?
C- calcinosis (calcium deposits, really painful)
R - Raynaud’s
E - oesophageal dysmotility (gullet thickens, peristalsis is abnormal & can affect sphincter, GORD common complaint)
S - sclerodactyly (sausage fingers)
T - telectangasia (small visible BVs around face & Chest)
ASSOC with limited systemic sclerosis
What is Raynaud’s phenomena?
Vasospasm in BVs of fingers/toes usually due to exposure to cold/stress
What are the complications of limited systemic sclerosis?
Pulmonary hypertension
What are the complications of diffuse systemic sclerosis?
Pulmonary fibrosis
Renal crisis
Small bowel bacterial overgrowth (improper peristalsis)
In which age group/gender is Sjogren’s most common?
9x F
40-50yo
What is Sjogren’s syndrome?
Autoimmune dx characterised by destruction of the lacrimal and salivary glands
What are the clinical features of Sjogren’s?
Dry eyes and mouth
Parotid enlargement
1/3 have systemic upset - fatigue, fever, myalgia, arthalgia
Rarely other organs are involved, e.g. nerves/lungs
What are the complications of Sjogren’s?
Lymphoma Neuropathy Purpura Interstitial lung dx Renal tubular acidosis
What is autoimmune myositis?
Inflammation and degenerative changes in the muscle
Leading to symmetrical muscle weakness and fibrous replacement of muscle
Usually in the limb girdles/proximal thighs
What are the clinical features of auto-immune myositis?
Muscle weakness - symmetrical, diffuse, proximal
Affecting ADLs
What are the types of auto-immune myositis?
Polymyositis
Dermatomyositis
What is dermatomyositis?
Muscle wasting + Gottron’s papules (80%) and heliotrope rash (30-60%)
What are Gottron’s papules?
Erythematous papules on the extensor surfaces of the hand
What is a heliotrope rash?
Erythematous rash on upper eye lids & face
What are the complications of DM/PM?
Cancer/quite often a paraneoplastic syndrome
Interstitial lung disease
What is MCTD?
Overlapping symptoms of systemic sclerosis, SLE, polymositis
Soft tissue swelling
Raynaud’s
Myositis
Arthalgia
What is giant cell arteritis?
Autoimmune vasculitis that causes chronic inflammation of large and medium sized vessels
What are the clinical features of giant cell arteritis?
Temporal arteritis - elderly age, new onset headache around temple, hardened and tender temple artery, jaw claudication
How do you Rx temporal arteritis?
Medical emergency as can lead to loss of vision
Glucocorticoids
What is the GCA classification criteria?
3 of: age at onset 50y+ new headache temporal artery tenderness/reduced pulsation ESR 50+ Abnormal temporal biopsy
What is ANCA?
Antineutrophil cytoplasmic Ab
Target antigens in cytoplasm of neutrophils
Burst inappropriately and when they come into contact with BVs they destroy BVs
What are the ANCA associated vasculitides?
Granulomatosis with polyangiitis (wegner’s)
Microscopic polyangiitis
Eosinophilic granulomatosis with polyangiitis
These affect small BVs
What is involved in Granulomatosis with polyangiitis?
Necrotising granulomatous inflammation
Usually involving upper and lower RT
Affecting small–> med essels
Necrotising GN is common
If someone presents with sinus disease, chest cavities and kidney disease what should you think about?
GPA
What is microscopic polyangiitis?
Necrotising vasculitis with few/no immune deposits affecting small vessels
Necrotising arteritis involving small and medium arteries may be present
Necrotising GN v common
Pulmonary capillaritis often occurs
Granulomatous inflammation absent
similar to GPA without nasopharynx involvement!
What is Eosinophilic granulomatosis with polyangiitis?
Eosinophil rich and necrotising granulomatous inflammation often involving the resp tract
Necrotising vasculitis predominantly affecting small–> med vessels
Assoc with asthma & eosinophilia
ANCa more frequent when GN present
What are some of the major complications with ANCA associated vasculitis?
Nerve damage Malignancy Lung damage ESRD Hearing loss
What conditions are assoc with ANA?
SLE - 99% Systemic sclerosis - 97% PM/DM - 40-80% Sjogrens - 48-96% MCTD - 100% Drug induced lupus - 100%
Asymptomatic people may also have ANA, may also be present in RA, MS and infection
What ANA antibodies are present in SLE?
Anti-dsDNA
Anti-Ro
Anti-Sm
What ANA antibodies are present in scleroderma?
Anti-Scl-70
Anti-centromere
What ANA antibodies are present in polymositis?
Anti-Jo1
What ANA antibodies are present in Sjogren’s?
Anti-Ro
Anti-La
What Ix might you do in multi-system autoimmune dx?
Radiology (PET, MRI, CT)
Biopsy, e.g. of kidneys, temporal arteries
What are the classes of lupus nephritis?
1 - minimal mesangial 2 - mesangial proliferation 3 - focal 4 - diffuse 5 - membranous 6 - advanced sclerosing
What are the treatments for multi-system autoimmune diseases?
Mild - hydroxychloroquine
Mod - azathioprine, methotrexate, mycophenolate
Severe - cyclophosphamide, rituximab
