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?
- Serositis - note can cause pleuritic chest pain, abdo pain
- Oral ulcers
- ANA - Anti nuclear antibodies
- Photosensitivity
- Bloods - pancytopenia (low HB, low platelets, low WBC)
- Renal (proteinuria)
- Arthritis
- Immunological (anti-dsDNA)
- Neurological (psychiatric, seizures)
- Malar rash
- Discoid rash
NOTE: SOAP BRAIN MD
What is ANA used for
Anti-nuclear antibody
Used as a screening test –> high sensitivity, low specificity
If -ve –> good at ruling out SLE
If +ve –> means it could be SLE among other things
the higher the titre –> the more +ve
List three autoantibodies found in SLE. Which is most specific?
- Anti-dsDNA -
- Anti-smith (against ribonucleoproteins)
- Anti-histone - seen in drug-related SLE (e.g. hydralazine)
How is anti-dsDNA measured?
- 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
NOTE: it can also be measured with ELISA
Describe the appearance of skin histology in SLE.
- Lymphocytic infiltration of the dermis
- Vacuolisation (dissolution of the cells) of the basal epidermis
- Extravasation of blood causes a rash
- Immunofluorescence will show immune complex deposition at the epidermis-dermis junction
Describe the appearance of renal histology in SLE.
Glomerular capillaries are thickened (wire-loop capillaries) due to immune complex deposition.
NOTE: this can be visualised by immunofluorescence
What is the name of non-infective endocarditis associated with SLE?
Libman-Sacks endocarditis
NOTE: the vegetation is made up of lymphocytes, neutrophils, fibrin etc.
What is scleroderma/systemic sclerosis?
A condition characterised by excess collagen in the skin and fibrosis –> tight skin
What is the localised form of scleroderma called?
Morphoea
What are the two types of scleroderma? Name the antibodies that they are associated with.
- Diffuse - involves the trunk (anti-Scl70 antibodies (aka anti-topoisomerase))
- Limited - only affects distal to the elbows and knees (anti-centromere)
What are the main features of limited cutaneous systemic sclerosis?
- Calcinosis - painful deposits at tip of fingertips
- Raynaud’s phenomenon
- Oesophageal dysmotility
- Sclerodactyly - tight skin over fingers
- Telangiectasia
CREST syndrome
What pattern of ANA immunofluorescence is seen in scleroderma?
Nucleolar
Describe the skin histology in scleroderma.
Increased depth and amount of collagen.
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
Need ACE-inhibitor
What is mixed connective tissue disease?
A condition characterised by the overlap of several connective tissue diseases (SLE, scleroderma, polymyositis and dermatomyositis)
how does dermatomyositis and polymyositis present
proximal muscle weakness + tenderness - affects shoulder + pelvic girdle
can progess to respiratory muscle involvement
Can also get interstitial lung disease
dermatomyositis –> skin manifestations as well:
heliotrope rash in perioorbital
gottron’s papules
what are the bloods in polymyositis and dermatomyositis
raised CK
ANA +Ve
Anti-Jo-1
Anti-Mi-2
What ANA immunofluorescence pattern is seen in mixed connective tissue disease?
Speckled
What is dermatomyositis?
A condition characterised by proximal muscle pain and weakness, high CK and skin changes (e.g. Gottron’s papules - purple rash across the knuckles)
What is sarcoidosis of the skin called?
Lupus pernio
List some features of sarcoidosis.
- Arthritis
- Lupus pernio
- Erythema nodosum
- Bilateral hilar lymphadenopathy
- Pulmonary fibrosis
- Lymphadenopathy
- Inflammation of layers of the heart
- Uveitis
- Meningitis
- Hepatitis, cirrhosis
- Bilateral parotid enlargement
What is the pathological hallmark of sarcoidosis?
Non-caseating granuloma
What is a granuloma?
- A collection of activated macrophages (aka histiocytes)
- The macrophages are sometimes described as epithelioid macrophages
- Some macrophages will fuse to form multinucleated giant cells - with horseshoe nucleus
What is caseating vs non-caseating
caseating has necrosis inside of it
Which investigations are useful in sarcoidosis?
- Hypergammaglobulinaemia
- High ACE
- Hypercalcaemia (due to extra-renal production of 1-alpha hydroxylase by macrophages –> activates vitamin D)
What criteria is used to classify vasculitides based on the size of the vessel?
Chapel Hill Criteria
These are primary, can be secondary e.g. to lupus or infection
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 appearance on angiography due to multiple aneurysms
Which condition is polyarteritis nodosa associated with?
Hepatitis B
What is a characteristic feature of vasculitis?
Palpable purpuric rash
How is termporal arteritis diagnosed and treated?
- High ESR
- High dose prednisolone
What will be seen on temporal artery biopsy in temporal arteritis?
Lymphocytic infiltration of the tunica media
Granuloma with multinulceate giant cells
What is Kawasaki disease? What are the main clinical features?
- A medium vessel vasculitis
- Conjunctivitis
- Rash
- Adenopathy
- Strawberry tongue
- Hands and feet rash
- Fever > 38 degrees for > 7 days
- Coronary artery aneurysms
What are the main features of granulomatosis with polyangiitis?
- ENT - nosebleeds, sinusitis, saddle nose
- Lungs - haemoptysis, SOB
- Kidneys - haematuria
Which antibody is associated with granulomatosis with polyangiitis?
cANCA - against proteinase 3
What are the main features of eosinophilic granulomatosis with polyangitis?
- Asthma
- Eosinophilia
- Vasculitis
Which antibody is associated with eoisinophilic granulomatosis with polyangitis?
pANCA - against myeloperoxidase
