Histo: Connective tissue disease, amyloid, sarcoid, Immune related multisystem disorders Flashcards
Give an example of an autoimmune disease that is:
- Organ-specific with a specific antigen
- Organ-specific without a specific antigen
- Multisystem disease
- Organ-specific with a specific antigen: pernicious anaemia
- Organ-specific without a specific antigen: primary biliary cirrhosis
- Multisystem disease: rheumatoid arthritis, Sjogren syndrome, SLE
What are the main features of SLE?
SOAP
- Serositis
- Oral ulcers
- ANA
- Photosensitivity
Brain
- Bloods (low counts)
- Renal (proteinuria)
- Arthritis
- Immunological (anti-dsDNA)
- Neurological (psychiatric, seizures)
MD
- Malar rash
- Discoid rash
SOAP BRAIN MD
What units are used for ANA levels?
It is a titre - the highest dilution at which you can see the fluorescence (e.g. 1:1000 is a higher level than 1:10)
List three autoantibodies found in SLE. Which is most specific?
- Anti-dsDNA
- Anti-Smith (Sm, against ribonucleoproteins) - most specific but low sensitivity
- Anti-histone - drug-related (e.g. hydralazine)
How is anti-dsDNA measured?
ELISA
Crithidia luciliae
- Incubate the patient’s serum with Crithidia Luciliae (protozoan)
- It has a big organism with dsDNA (kinetoplast) so if the patient has anti-dsDNA antibodies it will bind to the dsDNA in the kinetoplast
What can be seen on blood film in SLE?
LE (lupus erythromatosus) cell - neutrophil or macrocyte that has engulfed nuclear material of another cell
Describe the appearance of skin histology in SLE.
What would immunofluorescence show?
- Lymphocytic infiltration of the dermis
- Vacuolisation (dissolution of the cells) of the basal epidermis
- Extravasation of blood causes a rash
NOTE: immunofluorescence will show immune complex deposition at the epidermis-dermis junction
Describe the appearance of renal histology in SLE.
Thickened pink glomerular capillaries (wire-loop capillaries) due to immune complex deposition.
NOTE: immune complex deposition can be visualised by immunofluorescence
This is what a normal glomerulus looks like
What is the name of non-infective endocarditis associated with SLE?
Libman-Sacks endocarditis
NOTE: the vegetation is made up of fibrin, lymphocytes, neutrophils, histocytes
What is scleroderma?
An autoimmune condition characterised by excess collagen deposition and fibrosis
What is the localised skin-only form of scleroderma called?
Morphoea (sclerosis of skin only)
What are the two types of scleroderma?
Name the antibodies that they are associated with.
Diffuse
- Involves the trunk and proximal limbs
- Anti-Scl70 antibodies (anti-topoisomerase)
Limited (CREST syndrome)
- Only affects skin distal to the elbows and knees
- Anti-centromere antibodies
What are the main features of limited cutaneous systemic sclerosis (CREST syndrome)?
- Calcinosis
- Raynaud’s phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
What pattern of ANA immunofluorescence is seen in scleroderma?
Nucleolar
Describe the skin histology in scleroderma.
Increased depth and amount of collagen (results in reduced skin elasticity)
How does scleroderma cause gastric and oesophageal dysmotility?
Collagen deposition (fibrosis) with the submucosa - affects muscle contraction
Describe the vascular histology in scleroderma.
Intimal proliferation gives an onion skin appearance.
What is a major consequence of vascular damage in scleroderma?
Renal hypertensive crisis
What is mixed connective tissue disease?
A condition characterised by the overlap of several connective tissue diseases including SLE, scleroderma, polymyositis and dermatomyositis
What ANA immunofluorescence pattern is seen in mixed connective tissue disease?
Speckled
What is dermatomyositis?
A condition characterised by proximal muscle pain and weakness and skin changes
Which marker would be raised in the blood in dermatomyositis?
Creatine kinase
What signs would be seen on the skin in dermatomyositis?
- Gottren’s papules
- Heliotrope rash
- Facial rash
- Systemic v-shaped rash
What is sarcoidosis of the skin called?
Lupus pernio
List some features of sarcoidosis.
What is the pathological hallmark of sarcoidosis?
Non-caseating granuloma
Langhans giant cell, epitheloid macrophages, lymphocytes
What are some biochemical changes seen the blood in sarcoidosis?
- Hypergammaglobulinaemia
- Raised ACE
- Hypercalcaemia (due to 1-alpha hydroxylase expression by granuloma macrophages)
What criteria is used to classify vasculitides based on the size of the vessel?
Chapel Hill Criteria
What is polyarteritis nodosa? What are its main features?
- A necrotising arteritis which is focal and sharply demarcated
- It heals by fibrosis and mainly affects the renal and mesenteric vessels
- May present with gut ischaemia or renal impairment
- It produces a rosary beads (nodular) appearance on angiography due to multiple aneurysms
Which infection is polyarteritis nodosa associated with?
Hepatitis B
What is a characteristic feature of vasculitis?
Palpable purpuric rash
How is temporal arteritis diagnosed and treated?
Diagnosis
- Clinical
- High ESR
- Temporal artery biospy
Treatment
- High dose prednisolone
What will be seen on temporal artery biopsy in temporal arteritis?
Lymphocytic infiltration of the tunica media
What is Kawasaki disease? What are the main clinical features?
Medium vessel vasculitis
Fever lasting longer that 5 days accompanied by:
- Conjunctivitis
- Rash
- Adenopathy
- Strawberry tongue
- Hand and feet skin desquamation
What is a complication of Kawasaki’s?
Coronary artery aneurysm (screen using echocardiogram)
What are the main features of granulomatosis with polyangiitis (Wegner’s)?
- ENT - nosebleeds, sinusitis, saddle nose
- Lungs - haemoptysis, SoB
- Kidneys - haematuria
Which antibody is associated with granulomatosis with polyangiitis?
cANCA - directed against proteinase 3
What are the main features of eosinophilic granulomatosis with polyangitis (Churg-Strauss)?
- Asthma (1st stage)
- Eosinophilia (2nd stage)
- Vasculitis (3rd stage)
Which antibody is associated with Churg-Strauss syndrome?
pANCA - directed against myeloperoxidase
