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
- Oral ulcers
- ANA
- Photosensitivity
- Bloods (low counts)
- Renal (proteinuria)
- Arthritis
- Immunological (anti-dsDNA)
- Neurological (psychiatric, seizures)
- Malar rash
- Discoid rash
NOTE: 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 (against ribonucleoproteins) - most specific but low sensitivity
- Anti-histone - drug-related (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?
A condition characterised by excess collagen in the skin and fibrosis
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
- Raynaud’s phenomenon
- Oesophageal dysmotility
- Sclerodactyly
- 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
What is mixed connective tissue disease?
A condition characterised by the overlap of several connective tissue diseases (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, 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
Which investigations are useful in sarcoidosis?
- Hypergammaglobulinaemia
- High ACE
Hypercalcaemia (due to acitvation of vitamin D by macrophages)
