Immune related multisystem disorders Flashcards
What are the AI multisystem diseases?
cANCA (proteinase 3) - Wegener’s (GPA)
Rheumatoid arthritis
pANCA (myeloperoxidase) - Churg-Strauss (eGPA)
Sjogren’s syndrome
Microscopic polyangiitis
SLE
What are the investigations of CTDs?
ANA
if pos:
dsDNA
ENA
Cytoplasmic
If you have positive ANA and dsDNA what condition is that?
SLE
If you have positive ANA and anti-ro, la, Sm and RNP, which conditions could it be?
SLE
Sjogrens (Ro/ La)
If you have positive ANA and SCL 70 what condition is that?
Diffuse cutaneous systemic sclerosis
If you have positive ANA and anti-centromere what condition is that?
Limited cutaneous systemic sclerosis (CREST)
If you have positive ANA and t-RNA synthetase (Jo1)what condition is that?
Myositis
What does SOAP in SOAP BRAIN MD stand for?
Serositis
Oral Ulcers
Arthritis
Photosensitive
What does BRAI in SOAP BRAIN MD stand for?
Blood (pancytopaenia)
Renal (proteinuria)
ANA
Immunological (anti dsDNA)
What does N MD stand for in SOAP BRAIN MD?
Neurological
Malar Rash
Discoid rash
What is ANA used to screen for?
ANA is used to screen for ANY nuclear antigens – the antibody titre is given as dilution value (e.g. 1:10) - the highest dilution at which you can still see the fluorescence is the titre (i.e. 1:1000 > 1:40)
What are the autoantibodies in SLE?
o Anti-dsDNA – most specific (30% SLE have it), not very sensitive
o Anti-smith (Sm) – very specific (20% SLE have it), not very sensitive
§ However, all anti-ENAs (RNPs: anti-Ro, La, Sm, U1RNP) found in SLE
o Anti-histone (drug-related e.g. hydralazine)
§ Patients who are taking hydralazine for hypertension may develop SLE
How do you measure anti dsDNA?
o Incubate the patient’s serum with Crithidia Luciliae (a protozoa)
§ Crithidia has big mitochondrion with double stranded DNA (kinetoplast)
§ If the patient has anti-dsDNA antibodies it will bind to the DNA
o Measured using ELISA (Enzyme Linked Immunosorbent Assay)
o An old test for SLE involved looking for LE cells (these are neutrophils that have taken up denatured nuclei)
What is skin histology in SLE?
o Lymphocytic infiltration of dermis
o Vacuolisation (dissolution of the cells) of basal epidermis
o Extravasation of RBCs causes the rash
o Immunofluorescence (antibody to IgG) will show immune complex deposition at the epidermis-dermis junction
What is this?
Skin histology in SLE
Which of these renal histology slides shows SLE and why?
The left one
o Glomerular capillaries thick (“wire-loop”) SLE Normal
§ Immune complexes in BM
o Immunofluorescence can be used to visualise the immune complex deposition (electron microscopy will also show dark areas of immune complex deposition)
What is Libman Sacks Endocarditis?
o This is a non-infective form of endocarditis that is associated with SLE
o Patients may present with emboli, heart failure or murmurs
o Vegetations = lymphocytes, neutrophils, fibrin strands etc.
What is the difference between limited and diffuse scleroderma?
o Diffuse = involves the trunk- Anti-topoisomerase (anti-Scl70)
o Limited = does NOT involve the trunk- Anti-centromere antibodies
What does CREST stand for?
§ Calcinosis (i.e. calcium deposit on tip of thumb)
§ Raynaud’s phenomenon (white –> blue –> red)
§ Esophageal dysmotility
§ Sclerodactyly
§ Telangiectasia
What part of diffuse cutaneous systemic sclerosis is seen here?
Nucelolar patter of immunofluorescence
What is seen in skin histology in scleroderma?
There is increased depth and amount of collagen -> reduced skin elasticity
§ N.B. difficulty swallowing and stomach dysmotility due to excess collagen within the lining à reduced elasticity
What is seen in vascular histology in scleroderma?
o Top picture is a normal artery with 3 layers
o Bottom picture is a small artery in a patient presenting to A&E with a renal crisis (characterised by very high blood pressure)
§ There is intimal proliferation giving an onion skin appearance
§ Lumen effectively obliterated and some small thrombi for
What is mixed CTD?
Characterised by overlap of several connective tissue diseases:
o SLE Scleroderma
o Polymyositis Dermatomyositis
What pattern does ANA show in mixed CTD?
o Shows a speckled pattern
o This is suggestive of mixed connective tissue disease
What are the fearures of dermatomyositis?
o They will have proximal muscle pain and weakness
o High CK
o Gottron’s papules (erythematous rash over the knuckles)
What areas are affected in sarcoidosis?
o Joints Skin (lupus pernio, erythema nodosum)
o Lungs (fibrosis, lymphocytosis (increased CD4+ cells in BAL)
Lymphadenopathy
o Heart (any layer: pericardium, myocardium, endocardium)
Eyes (uveitis, keratoconjunctivitis)
o Neuro (meningitis, cranial nerve lesions)
Liver (hepatitis, cirrhosis, cholestasis)
o Parotids (bilateral enlargement)
What does this histology show?
Histology = non-caseating granulomata (ball of activated macrophages); composed of…
o Histiocytes (epithelioid cells)
o Multinucleated giant cells of Langerhans (peripheral nuclei) – fused macrophages -> horseshoe appearance
o Lymphocytes
§ There is NO necrosis within the granuloma (i.e. it is non-caseating)
What investigations would you do for sarcoidosis?
o Hypergammaglobulinaemia
o Raised ACE
o Hypercalcaemia (vitamin D hydroxylation (1a-hydroxylase) by activated macrophages)
What type of vasculitis is takayasu’s and GCA?
Large vessel
What type of vasculitis is polyarteritis nodosa and kawasaki disease?
Medium vessel
What are the ANCA associated small vessel vasculitides? (And which is PANCA and CANCA)
Microscopic polyangiitis
Granulomatosis with polyangiitis (Wegener’s CANCA)
Eosinophilis Granulomatosis with Polyangiitis (Churg Strauss- PANCA)
What are the immune complex associated small vessel vasculitises?
Cryoglobinaemic vasculitis
IgA vasculitis (HSP)
Hypocomplementemic urticarial vasculitis (anti C1q vasculitis)
What is the Chapel Hill Criteria?
The Chapel Hill Criteria classifies vasculitides based on the size of the vessel affected
o A palpable purpuric rash is characteristic of vasculitis
o Nail fold infarcts are also a feature of vasculitis
o Vasculitis can be primary (conditions listed above) or it could be secondary to another condition (e.g. infective endocarditis, SLE)
What are the features of polyarteritis Nodosa?
(inflammation of gut/renal vessels):
o Necrotising arteritis -> heals by fibrosis
o Polymorphs, lymphocytes and eosinophils will infiltrate
o Arteritis is focal and sharply demarcated
o Associations:
§ Rosary beads appearance on angiogram (aneurysms)
§ HBV
What are the clinical features of temporal arteritis?
o Needs an ESR -> needs high dose prednisolone
o A temporal artery biopsy is needed for a definitive diagnosis
§ This will show narrowing of the lumen and lymphocytic infiltration of the tunica media (not intima)
What are the clinical features of Kawasaki disease?
Clinical Features:
Fever
Erythema of palms and soles, desquamation
Conjunctivitis
Lymphadenopathy
Coronary artery aneurysms
Self-limiting (otherwise)
What are the 3 Hallmarks of Wegeners?
§ Upper respiratory (ENT) – nosebleeds, sinusitis, saddle nose
§ Lower respiratory (lungs) – haemoptysis, SOB
§ Kidneys – haematuria
o Antibody: C-ANCA (directed against proteinase 3)
What are the 3 Hallmarks of Churg Strauss?
THREE hallmarks:
§ Asthma
§ Eosinophilia
§ Vasculitis
o Antibody: P-ANCA (directed against myeloperoxidase)
What is this?
Polyarteritis Nodosa
What is this?
Scleroderma
