Multi System Autoimmune Diseases Flashcards
Progression of Wegener’s Granulomatosis
Myalgia/arthralgia ->
Episcleritis ->
Sinusitis ->
Renal failure
Progression of lupus
Arthralgia/myalgia ->
Skin rash ->
Pleurisy ->
CVA
Progression of scleroderma
Arthralgia/myalgia ->
Skin thickening ->
GORD ->
Pulmonary HTN
Progression of sjorgens syndrome
Arthralgia/fatigue ->
Sicca ->
Skin rash ->
Neuropathy
Connective tissue autoimmune diseases
Systemic lupus erythematous (SLE) Scleroderma Sjogrens syndrome Autoimmune myositis Mixed connective tissue disease
Systemic vasculitis autoimmune diseases
GCA
Granulomatosis Polyangitis (Wegeners)
Microscopic polyangiitis
Eosinophilic granulomatosis polyangiitis (churg-straus)
Diagnosis of multi system autoimmune diseases
Cardinal clinical features - history and exam Immunology Imaging Tissue Exclusion of differential diagnosis
What can mimic the multi system autoimmune diseases?
Drugs - cocaine, PTU, minocycline Infection - HIV, Endocarditis, hepatitis, TB Malignancy - lymphoma Cardiac myxoma Cholesterol emboli Scurvy
Who does SLE affect?
Disease of the young - 15-50 years
F > M; 9:1
Afrocarribeans > Asian > Caucasian
Why do more females get affected by SLE than males?
To do with oestrogen
Presentation of SLE
Face - butterfly rash, photosensitivity
Fever
Skin - vasculitis, purpura, urticaria (hives), discoid (scaley centre, dark rim)
Lungs - Pleurisy, Pleural effusion, Fibrosis (pleural)
Raynauds phenomenon
Kidney effects
Joints
- aseptic necrosis of the hips
- arthritis in small joints
Alopecia
Neuro - Fits, Hemiplegia, Ataxia, Peripheral neuropathy, Cranial nerve lesions
Heart - Pericarditis, Endocarditis, Aortic valve lesions
Abdominal pain
Myopathy
Haem - Anaemia, Leukopenia, Thrombocytopenia
Classification criteria for SLE; any 4 of….
malar rash (butterfly rash) Discoid rash (raised, scarring, alopecia) Photosensitivity Oral ulcers Arthritis (at least 2 joints) Serositis (pleurisy or pericarditis) Renal (significant proteinuria or cellular casts in urine) Neuro; unexplained seizures or psychosis Haematological; - low WCC - platelets - lymphocytes - haemolytic anaemia Immunological - Anti ds-DNA - SM - cardiolipin - Lupus anticoagulant - low complement ANA
Immunological features of SLE
Anti ds-DNA Anti-smith Cardiolipin Lupus anticoagulant Low complement ANA
Who gets scleroderma?
30-50 y/o onset
F > M 3:1
Presentation of scleroderma
Morphea; constraints of the skin Thickening limited to hands and forearms calcium deposits Sausage fingers Telectasia
Presentation of diffuse scleroderma
Thickening of the skin can go across the whole body
Mophrea; constriants of the skin
Types of scleroderma
Limited
Diffuse (less common)
Definition of telectasia
Visible blood vessels prominent
usually around neck or chest
Complications of scleroderma
aesthetics Limited; pulmonary HTN Diffuse; - pulmonary fibrosis - renal crisis - small bower bacterial overgrowth
Who gets Sjorgen’s Syndrome?
Onset 40-50 years
F > M 9:1
Presentation of Sjorgen’s Syndrome
Primarily attacks salivary + lacrimal glands (struggle with QoL)
- dry mouth
- cannot cry
GI - dysphasia, abnormal oesophageal motility
Pulmonary - interstitial lung disease
Neuro - fits, hemiplegia, ataxia, cranial nerve lesions, sensory neuropathy
Renal - renal tubular acidosis
Skin - palpable purpura, raynauds syndrome
mononeuritis multiplex
Parotid gland enlargement
1/3 have systemic upset
- fatigue
- fever
- myalgia
- arthralgia
Complications of sjorgens syndrome
Lymphoma Neuropathy Purpura Interstitial lung disease Renal tubular acidosis
Presentation of autoimmune myositis
tends to be proximal muscles affected NO PAIN weakness - symmetrical - diffuse - proximal - polymyositis - dermatomyositis (Gortons papules, helitrope rash)
Complications of autoimmune myositis
cancer
interstitial lung disease
An overlap syndrome and its features
MCTD
- soft tissue swelling
- Raynauds
- myositis
- arthralgia
Large vessel vasculitis examples
Takayasu arteritis
Giant cell arteritis (GCA)
Buergers disease
Medium vessel vasculitis examples
Polyarteritis nodose
Kawasaki disease
Wegeners
Small vessel vasculitis examples
ANCA associated vasculitis - microscopic polyangiitis - granulomatosis with polyangiitis - eosinophilic granulomatosis with polyangiitis Immune complex SVV - IgA vasculitis - anti-GBM disease
Classification criteria for GCA
3 of the following
- age at onset > 50 years
- new headache around the temporal artery
- temporal artery tenderness/pulsation (occluded arteries
- ESR > 50
- abnormal temporal artery biopsy
What does GCA stand for?
Giant cell arteritis
What does ANCA AAV stand for?
ANCA associated vasculitis
What does ANCA stand for?
Antineutrophil cytoplasmic antibody
Features of ANCA
Antibody
Neutrophils are activated and burst inappropriately when they come into contact with a blood vessel
This destroys the blood vessel
What is another name for Granulomatosis with Polyangitis?
Wegener’s granulomatosis
What are ANCA associated vasculitis?
Wegener’s (Graulomatosis with polyangiitis)
Microscopic polyangiitis
Eosinophilic granulomatosis with polyangiitis
Features of Wegener’s granulomatosis
Necrotising granulomatous inflammation
Usually involving the upper and lower respiratory tract
Affecting predominately small to medium vessels
Necrotising glomerulonephritis common
Features of microscopic granulomatosis
Necrotising vasculitis
Few or no immune deposits
Predominately affecting small vessels
necrotising arteries involving small and medium arteries may be present
necrotising glomerulonephritis very common
Granulomatous inflammation is absent
Features of eosinophilic granulomatosis with polyangiitis
Eosinophil rich and necrotising granulomatous inflammation often involving the respiratory tract
Necrotising vasculitis predominately affecting small to medium vessels
Associated with asthma and eosinophilia
ANCA more frequent when glomerulonephritis is present
What does ANA stand for?
Antinuclear antibody
Conditions where ANA is raised
SLE 99% Systemic sclerosis 97% Poly/dermatomyositis 40-80% Sjorgrens syndrome 48-95% MCTD 100% Drug induced lupus 100% IBD (UC > CD) (usually pANCA) Autoimmune hepatitis (usually pANCA)
What does MCTD stand for?
Mixed connective tissue disease
What is MCTD?
A broader category of rheumatoid “overlap” syndromes, used to describe when a patient has features of more than one classic inflammatory rheumatic disease
Situations where ANA is raised “unhelpfully”
RA
MS
Infection variation
Specific ANA profile of scleroderma
Scl-70
Centomere
Specific ANA profile of SLE
dSDNA
Ro
Sm
Specific ANA profile of polymyositis
Jo-1
Specific ANA profiles of sjorgens disease
Ro
La
Classes of lupus nephritis from biopsy
I - minimal mesangial II - mesangial proliferative III - focal IV - diffuse V - membranous VI - advanced sclerosing
Treatment of multisystem autoimmune diseases
Organ threat mild = hydroxychloroquine
Organ threat moderate
- azathioprine
- methotrexate
- mycophenolate
Organ threat severe
- cyclophosphamide
- Rituximab
What is polyarteritis nodosa?
Vasculitis affecting medium sized arteries with necrotising inflammation leading to aneurysm formation
Who is polyarteritis nodosa common in?
Middle aged men
What is polyarteritis nodosa associated with?
Hepatitis B infection
Presentation of polyarteritis nodosa
Fever Malaise Arthralgia HTN Weight loss Mononeuritis multiplex, sensorimotor polyneuropathy Testicular pain Livedo reticularis Hamaeturia, renal failure (renal disease seen in 70%) Angiography can show saccular or fusiform aneurysms and arterial stenosis ANCA in 20% Hep B serology +ve in 30%
Treatment of raynauds
Nifedipine
Investigations for sjogrens syndrome
RF +ve in 100%
ANA +ve in 70%
Primary disease - anti-Ro and anti-La
Schrimers test (filter paper near conjunctival sac to measure tear formation)
Focal lymphocytic infiltration on histology
What is seen in drug induced lupus?
Not all features of lupus have to be present
Renal and nervous system involvement UNUSUAL
Athralgia
Myalgia
Skin e.g. malar rash
Pulmonary involvement e.g. pleurisy common
Immunology of drug induced lupus
ANA +ve in 100%
dsDNA -ve
Anti-histone antibodies in 80-90%
anti-Ro, anti smith +ve in 5%
Most common causes of drug induced lupus
Procainamide
Hydralazine
Less common causes of drug induced lupus
Isoniazid
Minocycline
Phenytoin
What is Takayasu’s arteritis and what gender gets it?
Inflammatory, obliterative arteritis affecting aorta and branches
F > M
Presentation of takayasus arteritis
Upper limb claudication
Diminished or absent pulses
ESR affected in the acute phase
What is beurgers disease?
Segmental thrombotic occlusions of the small and medium lower limb vessels
Who is beurgers disease common in?
Young male smokers
Presentation of beurgers disease
Proximal pulses usually present but pedal pulses are lost
Acute hypercellular occlusive thrombus usually present
Tortous corkscrew shaped collateral vessels may be seen on angiography
What is antiphospholipid syndrome?
An acquired disorder characterised by predisposition to both venous and arterial thrombosis, recurrent foetal loss and thrombocytopenia
How may antiphospholipid syndrome occur?
Primarily
Secondary to other conditions (most commonly SLE)
What does antiphospholipid syndrome cause an increase in?
APTT
Presentation of antiphospholipid syndrome
Venous / arterial thrombosis recurrent foetal loss livedo reticularis thrombocytopenia prolonged APTT PET PHTN
Management of antiphospholipid syndrome
Initial VTEs - warfarin with target INR 2 - 3 for 6 months
Recurrent VTEs - lifelong warfarin
Arterial thrombosis - lifelong warfarin
What test can assist in diagnosing antiphospholipid syndrome?
+ve anti-cardiolipin antibody
Causes of +ve cANCA
Wegeners granulomatosis (90%) Microscopic polyangiitis (40%)
Causes of +ve pANCA
Microscopic polyangiitis (50-75%)
Churg strauss syndrome (60%)
PSC (60 - 80%)
Wegeners (25%)
What is dermatomyositis?
An inflammatory disorder causing symmetrical, proximal muscle weakness and characteristic skin lesions
Causes of dermatomyositis
Idiopathic
Connective tissue disease
Malignancy
What is usually screened for after a diagnosis of dermatomyositis?
Malignancy
What is polymyositis?
A variant of dermatomyositis where the skin is not involved
Presentation of dermatomyoisitis
Photosensitive Macular rash over back and shoulder Heliotrope rash in periorbital region Gottrons papules Mechanic hands - extremely dry and scaley hands with linear cracks on palmar and lateral aspects of fingers Nail fold capillary dilatation Proximal muscle weakness +/- tenderness Raynauds Resp muscle weakness ILD Dysphagia / dysphonia
What are gottrons papules?
Roughed red papules over extensor surfaces of fingers
Investigations of dermatomyoisitis
80% ANA +ve
30% anti-synthetase Abs
Who gets still disease?
15 - 25 y/o
35 - 46 y/o
Presentation of stills disease
Arthalgia Elevated serum ferritin Salmon pink maculopapular rash Pyrexia (rises in late afternoon / early evening in a daily pattern and accompanies the joint pain and rash) Lymphadenopathy RF and ANA -ve
Criteria used to diagnose stills disease
Yamaguchi criteria
Management of stills disease
NSAIDs 1st line Steriods If persist - Methotrexate - IL-1 - anti-TNF therapy
Antibodies present in drug induced lupus
Anti-histone antibodies (95%)
Patients with sjrogens syndrome are at increased risk of what?
Lymphoid malignancies
