HISTO: Immune related multisystem disorders – Connective tissue disease, amyloid, sarcoid Flashcards
Give an example of an autoimmune disease which is:
- organ specific with organ specific Ag
- ogran specific without organ specific Ag
- multisystem disease
- organ specific with organ specific Ag - pernicious anaemia
- ogran specific without organ specific Ag - primary biliary cirrhosis
- multisystem disease - RhA, Sjogren’s syndrome, SLE
What are the features of SLE?
- Skin - malar rash, discoid lupus with atrophic centre
- Oral ulcers
- Joints
- Neurological
- Serositis
- Renal - glomerulonephritis
- Haematological - pancytopenia
- Immunological - autoantibodies
What antibodies are commonly found in SLE? Which one is common in drug-related SLE? Which is most specific?
ANA - antinuclear antibodies; titre will be given - this is the highest dilution at which the antibodies are still present
Anti-dsDNA
Anti-smith - against ribonucleoproteins; very specific so you know it’s SLE if present, but not very sensitive
Anti-histone - drug related e.g. hydralazine taken for HTN
What investigations are used for anti-dsDNA detection in SLE?
Crithidia luciliae (shown)- incubate patient’s serum with this protozoa which has a big mitochondrion with double stranded DNA (kinetoplast). If the patient has anti-dsDNA antibodies then they will bind the DNA.
ELISA
Other:
LE cells - old test which looks at neutrophils which have taken up denatured nuceli
What is seen on skin histology in SLE?
- Lymphocytic infiltration of dermis
- Vacuolisation (dissolution of the cells) of basal epidermis
- Extravasation of RBCs causes the rash
Immunofluorescence (antibody to IgG) will show immune complex deposition at the epidermis-dermis junction
Where does immune complex deposition occur in the skin in SLE?
Epidermis-dermis junction as shown using immunofluorescence (antibody to IgG)
What does renal histology show in SLE? (normal glomerulus shown below)
- Glomerular capillaries thick (aka “wire-loop” appearance) - due to deposition of immune complexes in BM
Immunofluorescence - can show immune complex deposition (electron microscopy will also show dark areas of immune complex deposition)
What is Libman-Sacks?
- SLE related-endocarditis
- non-infective
- patients may present with emboli, HF and murmurs
What are the vegetations composed of in Libman-Sacks?
Vegetations = lymphocytes, neutrophils, fibrin strands etc.
What is scleroderma? What is the localised form called?
AKA systemic sclerosis = tight skin due to fibrosis and excess collagen (the localised form is called morphoea in the skin)
What are the types of scleroderma?
Diffuse = involves the trunk
Limited = does NOT involve the trunk (remembered as CREST)
- Calcinosis (i.e. calcium deposit on tip of thumb)
- Raynaud’s phenomenon (white –> blue –> red)
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia (Other: nail fold dilatation)
What antibodies are present in limited vs diffuse scleroderma?
Anti-centromere antibodies = diffuse
Anti-topoisomerase (anti-Scl70) = limited
What is seen on immunofluorescence when ANA test is done in diffuse scleroderma?
Nucleolar pattern of immunofluorescence in DIFFUSE
What feature of scleroderma is shown?
Microstomia
What does skin histology in scleroderma show?
There is increased depth and amount of collagen –> reduced skin elasticity.
What GI problems may occur as a result of scleroderma?
Difficulty swallowing and stomach dysmotility due to excess collagen within the lining –> reduced elasticity
What is shown on vascular histology in scleroderma?
- There is intimal proliferation giving an onion skin appearance
- Lumen effectively obliterated and some small thrombi form
What is seen on immunofluorescence when an ANA test is done in mixed connective tissue disease?
Shows a speckled pattern
This is suggestive of mixed connective tissue disease
What is mixed connective tissue disease?
Characterised by overlap of several connective tissue diseases:
- SLE
- Scleroderma
- Polymyositis
- Dermatomyositis
Name 3 features of dermatomyositis.
- Proximal muscle pain and weakness
- High CK
- Gottron’s papules (erythematous rash over the knuckles)
What is shown and what is this a feature of?
- Gottron’s papules =erythematous rash over the knuckles
- Seen in dermatomyositis
What organs are affected in sarcoidosis?
Joints
Skin e.g. lupus pernio- lesions affecting the nose, erythema nodosum
Lungs e.g. BHL, fibrosis, lymphocytosis (increased CD4+ cells in BAL)
Lymphadenopathy
Heart - any layer: pericardium, myocardium, endocardium
Eyes e.g. uveitis, keratoconjunctivitis
Neuro e.g. meningitis, cranial nerve lesions
Liver e.g. hepatitis, cirrhosis, cholestasis
Parotids - bilateral enlargement
Other than sarcoidosis, what are 3 causes of bilateral parotid enlargement?
- mumps,
- alcohol,
- Sjogren’s syndrome
What is a pathological hallmark of sarcoidosis?
non-caseating granulomata (macrophage clustures)
What are non-caseating granulomas composed of in sarcoidosis? What does non-caseating mean?
- Histiocytes (epithelioid cells)
- Multinucleated giant cells of Langerhans (peripheral nuclei) – fused macrophages form a horseshoe appearance
- Lymphocytes
Non-caseating = there is NO necrosis within the granuloma NB: Caseating are seen in TB
What is this type of sarcoidosis called?
Lupus pernio
What is this feature of sarcoidosis?
Erythema nodosum
What do laboratory investigations show in SLE?
- Hypergammaglobulinaemia
- Raised ACE
- Hypercalcaemia (vitamin D hydroxylation (1a-hydroxylase) by activated macrophages)
How are vasculitides classified?
Based on Chapel Hill Consensus Criteria based on size of vessel
Name the large vessel vasculitides.
- Takayasu arteritis
- Giant cell arteritis
Name the medium vessel vasculitides.
- Polyarteritis nodosa
- Kawasaki disease
Name the ANCA-associated small vessel vasculitides.
- Microscopic polyangitis
- Granulomatosis with polyangitis (Wegener’s)
- Eosinophilic granulomatosis with polyangitis (Churg-Strauss)
Name the immune complex small vessel vasculitides.
- Cyroglobulinemic vasculitis
- IgA vasculitis (Henoch-Schonlein)
- Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)
Anti-GBM is another type of small vessel vasculitis.
What is this characteristic feature of vasculitis?
Palpable purpuric rash = characteristic of any vasculitis
What is this feature seen in vasculitis?
Nail fold infarcts
What is this feature of vasculitis?
Temporal arteritis - needs biopsy and measurement of ESR
What is meant by a primary vs secondary vasculitis?
Primary = conditions listed below
Secondary= to another condition e.g. infective endocarditis, SLE
What is polyarteritis nodosa?
- Medium vessel vasculitis - usually causes inflammation of gut/renal vessels
- Polyarteritis - affects several vessels
- A necrotising polyarteritis - heals by fibrosis
Association with HBV
What are the histological features of polyarteritis nodosa? What is seen on angiography?
- Polymorphs, lymphocytes and eosinophils will infiltrate
- Arteritis is focal and sharply demarcated
Rosary beads appearance on angiogram i.e. aneurysms
How is temporal arteritis diagnosed?
Definitive - temporal artery biopsy
ESR - needs high dose prednisolone to treat
What is seen on histology in temporal arteritis? Which layers are affected?
- Narrowing of the lumen
- Lymphocytic infiltration of the tunica media (not intima)
What type of vasculitis is Kawasaki disease?
Medium vessel vasculitis
Affects children
What are the clinical features of Kawasaki disease?
Clinical Features:
- Conjunctivitis
- Rash
- Adenopathy
- Strawberry tongue
- Hands - erythema of palms and soles, desquamation
- Burn - Fever
+ coronary artery aneurysms
Self limiting.
What are the hallmarks of granulomatosis with polyangiitis (GPA)?
aka Wegener’s granulomatosis
- Upper respiratory (ENT) – nosebleeds, sinusitis, saddle nose
- Lower respiratory (lungs) – haemoptysis, SOB
- Kidneys – haematuria
What antibody is diagnostic in GPA? What is it directed against?
C-ANCA = cytoplasmic ANCA, directed against proteinase 3
What are the hallmarks of eosinophilic granulomatosis with polyangitis (EGPA)?
- Asthma
- Eosinophilia
- Vasculitis
What antibody is diagnostic in EGPA? What is it targeted against?
P-ANCA = perinuclear ANCA, directed against myeloperoxidase
This histology is consistent with:
- SLE
- Scleroderma
- Sarcoidosis
SLE
This histology is consistent with:
- SLE
- Scleroderma
- Sarcoidosis
Scleroderma
This histology is consistent with:
- SLE
- Scleroderma
- Sarcoidosis
Sarcoidosis
