Path 6 Flashcards
Features of SLE
can affect any organ!!
fever, fatigue, weight loss - flare ups
skin - e.g. malar rash
oral ulcers
joints (arthritis)
neurological (e.g. seizures, psychosis)
serositis (e.g. pericarditis, pleuritis; recurrent abdo pain)
renal (glomerulonephritis, protein +)
haematological (pancytopenia)
immunological (autoantibodies)
40yo female with pancytopenia and proteinuria - dx?
SLE
Antoantibodies in SLE
ANA - used for screening, does not show which antibody specifically is involved
Anti-dsDNA
Anti-Smith (ribonucleoprotiens) - most SPECIFIC (if +ve, v likely to have SLE) but not very sensitive (30% people with SLE have it)
Anti-histone (seen in drug induced lupus e.g. hydrazalazine
What medications can cause drug induced lupus?
Which antibody is positive?
hydralazine
procainamide
anti histone antibody
if a number is stated along with ANA, what does it mean?
the dilution of the serum at which the test is +ve, e.g. with 1/1000 dilution -> significantly high ANA
What is the underlying skin histology in a malar rash/SLE skin?
lymphocytic infiltration of the upper dermis
basal epidermis has undergone vacuolisation
red cells extraposition in the dermis
Immunofluorescence: immune complex deposition at epidermis-dermis junction
SLE skin - where are immune complexes deposited?
How can you see them (method)?
epidermis dermis junction
seen with immunofluorescence (Immunoglobulin binding)
What histological changes can you see lupus nephritis?
- thickening of glomerular capillaries (thick wall, wire loop pathology appearance) - due to immune complex deposition in BM
What causes wire loop pathology in lupus nephritis?
deposition of immune complexes in the BM leading to thickening of glomerular wall
can be seen on immunofluorescence or electron microscopy
What is Libman sacks?
non-infective endocarditis seen in SLE
How does Libman sacks endocarditis present?
emboli
stroke
murmurs
the vegetations on the valves are lymphocytes, neutrophils, eosinophils, fibrin strands etc.
What is the problem in Scleroderma?
fibrosis and excess collagen in the skin
what is the localised form of scleroderma called?
morphoea in the skin (patch of tight skin)
What are the 2 types of systemic sclerosis/scleroderma?
diffuse
limited
are scleroderma and systemic sclerosis synonymous?
yes
What is the difference between diffuse and limited scleroderma/systemic sclerosis?
diffuse - trunk is involved
What is more common, diffuse or limited scleroderma?
limited is more common
What autoantibodies are diffuse and limited scleroderma associated with?
Diffuse: anti-scl70 (antibodies to DNA topoisomerase)
Limited: anticentromere
What is CREST syndrome?
Term no longer used!!
describes limited scelroderma
CREST - what does it stand for?
Calcinosis
Raynauds
Oesophageal dysmotility
Sclerodactyly
Telegiectasia
oder of colour change in raynauds?
white
blue
crimson
What is sclerodactyly?
thinkening of the skin of the fingers+hand causing them to curl inwards causing a claw deformity and limitation in movement
seen in scleroderma
What pattern can be seen on IF in scleroderma?
nucleolar pattern
How common is raynauds in the general population (females)?
1 in 10
feautures of systemic sclerosis
calcinosis
raynauds
oesophageal dysmotility
sclerodactyly
telangiecstasia
nail fold capillary dilatation
microstomia (difficulty opening small mouth)
onion skin - intimal proliferation of arterioles +/- obliteration of the lumen. may have thrombi.
What causes skin tightening in scleroderma?
excess collagen deposition in the dermis
stomach changes in scleroderma
excess collagen and fibrosis -> causes oesophageal dysmotility
What is mixed connective tissue disease?
Patients have features of:
SLE
scleroderma
polymyositis
dermatomyositis
OVERLAP
What enzyme is elevated in poly/dermatomyositis and why?
CK
it is leaking out of inflamed muscle
What pattern of ANA can you see in mixed connective tissue disease?
speckled pattern
ANA - speckled pattern - dx?
mixed connective tissue disease
ANA - nucleolar pattern - dx?
scleroderma
ANA - entire nucleus stained pattern - dx?
SLE
What ANA patterns can you see and what conditions are they suggestive of?
What type of test is ANA?
whole nucleus involved - SLE
nucleolar pattern - scleroderma
speckled pattern - mixed connective tissue disease
ANA is a screening test, you would want to do further testing for autoantibodies.
What are Gottron’s papules and what condition are they a feature of?
erythematous rash over knuckles on dorsal aspect of hands
dermatomyositis
Dermatomyositis features
Tender, inflamed muscles
raised CK
Gottron’s papules
Features of sarcoidosis
Joints (e.g. back pain)
skin (nodules, papules, lupus pernio, erythema nodosum)
lungs (BHL, fibrosis, cough, lymphocytosis - CD4+ on BAL)
lymphadenopathy
parotids (bilateral enlargement)
heart
eyes (uveitis, conjunctivitis)
neuro (meningitis, cranial nerve lesions)
liver (hepatitis, cirrhosis, cholestatis )
What is the pathological hallmark of sarcoidosis?
non-caseating granulomas
What conditions give you erythema nodosum?
sarcoidosis
IBD
Bechets
Causes of bilateral parotid enlargement
Infection: mumps
Inflammation: sarcoidosis, Sjorgens syndrome
alcoholism
BHL
bilateral hilar lymphadenopathy
histopathological features of sarcoidosis
non-caseating granulomas
epithelioid looking cells (with elongated nuclei)
Langhans cells (multinucleate giant cells with horse shoe appearance/distribution of nuclei; multiple macrophages fusing)
what does non-caseating mean?
there is no necrosis occurring
Test findings in sarcoidosis?
- hypergammaglobulinaemia
- raised ACE due to abnormalities of capillaries in the lungs where ACE is made
- hypercalcaemia (vit D hydroxylation by activated macrophages)
What causes hypercalcaemia in sarcoidosis?
increased Vitamin D3 hydroxylation by activated macrophages
Types of vasculitis (3)
large vessel
medium vessel
small vessel
types of large vessel vasculitis
Giant cell arteritis
takayasus arteritis
types of medium vessel arteritis
kawasaki’s
polyarteritis nodosa
types of small vessel vasculitis
Immune Complex SVV
- cryoglobulinaemic vasculitis
- IgA vasculitis (Henoch Schonlein)
- Hypocomplementeric urticarial vasculitis
ANCA-associated SVV
- microscopic polyangiitis
- granulomatosis with polyangiitis (Wegener’s)
- eosinophilic granulomatosis with polyangitis (Churg-Strauss)
What infection is polyarteritis nodosa associated with?
Hep B
What vasculitis is Hep B infection associated with?
polyarteritis nodosa (medium vessel vasculitis)
What can be seen on angiogram in polyarteritis nodosa?
multiple beads (small aneurysms)
What kind of rash is characteristic of vasculitis?
palpable purpuric rash
can be seen in any type of vasculitis
primary and secondary vasculitis
primary vasculitis (large, medium, small vessel)
OR
secondary to infective endocarditis, RA, SLE…
histology of temporal arteritis
narrowing of lumen
granulomas
multinucleate giant cell with horseshoe arrangement of nuclei
lymphocytic infiltration of tunica media
Histopath of polyarteritis nodosa
necrotising arteritis
inflammatory cell infiltrates around vessels: polymorphs, lymphocytes and eosinophils seen
arteritis is focal and sharply demarcated
heals by fibrosis
what vessels are most commonly affected by polyarteritis nodosa?
renal and mesenteric arteries
3 hallmarks of granulomatosis with polyangitis
ENT
Lung
kidneys
What antibody to test for in ?GPA
C-ANCA (cytoplasmic ANCA) directed against proteinase 3
What does C-ANCA bind to?
proteinase 3
When is C-ANCA positive?
GPA
small vessel ANCA vasculitis
ENT, lung and kidney issues
(used to be called Wegeners)
What is the triad of sx in eosinophilic granulomatosis with polyangitis?
asthma
eosinophlia
vasculitis
What ab is +ve in eosinophilic granulomatosis with polyangitis?
P-ANCA (perinuclear ANCA)
directed against myeloperoxidase
What is P-ANCA directed against?
myeloperoxidase
What ab to test for in ?eosinophilic granulomatosis with polyangitis (Churg Strauss)
P-ANCA
How do you manage Church Strauss syndrome?
glucocorticoids PLUS cyclophosphamide
Goal is induction of remission
What do 1% of children affected by Kawasaki die off? What happens with the rest?
MI
99% have self limiting course
onion skin - what is it a histopathological feature of?
onion skin - intimal proliferation of arterioles +/- obliteration of the lumen. may have thrombi.
systemic sclerosis
What does anisopoikilocytosis mean?
there is a variation size (aniso) and shape (poikilo) of RBCs
hypersegmented neutrophil - ddx
B12 deficiency
folate deficiency
drugs (e.g. methotrexate, 5-FU, hydroxyurea, hydroxycaarbamide)
def of hypersegemnted neutrophils
> 5 nuclear segments
codocytes
target cells
central area of increased haemoglobin
target cells - ddx
iron deficiency
thalassemia
hyposplenism
liver disease
Howell Jolly bodies - what are they and when are they seen?
remnants of nucleus
usually removed by spleen -> seen in hyposplenism
features of iron deficiency on blood film
microcytosis
hypochromia
anisopoikilocytosis
hyposplenic features on blood film
target cells
Howell jolly bodies
Causes of iron deficiency
blood loss - major cause
other causes:
- poor diet
- malabsorption
- combinations of the above
Causes of megaloblastic change
B12 and folate deficiency
drugs
causes of hyposplenism
absent spleen (therapeutic, trauma)
poorly functioning spelen
IBD
ceoliac disease
SLE
sickle cell disease
Deficiency seen in coeliac
iron
b12
folate
fat
ca
deficiency seen in Crohn’s disease
b12
bile acids
pancreatic disease deficiency
xxx deficiency
where is tissue traanssglutaminase expressed?
endomysosal layer
therefore also called
also check IgA levels (some peeople are IgA deficient)
also check IgA levels (some peeople are IgA deficient)
antibody disappears as people stop eating gluten
Why would you perform an endoscopy in ?coeliac disease?
baseline
Gold standard for coeliac disease diagnosis
(disstal) duodenal biopsy
endoscopy findings in coeliac disease
scalloping of ridges in duodenum (lumps rather than villi)
normal villous : crypt ratio
3-5 : 1
villii are the majority of the biopsy
normal duodenal vili intro epithelial lymphocyte number
20 intraepithelial lymphocytes / 100 epithelial cells
Brunners glands - where are they ?
in the proximal half of the duodenum
they may distort villous architecture
histopathology in coeliac disease
Villous atrophy - villous height is reduced (atrophy)
Crypt hyperplasticity - crypt thickness is increased (hyperplasticity)
increased IEL : >25 IEL / 100 epithelial cells
these changes disappear if they stop eating gluten
Causes of increased IEL
coeliaca
infections
bacterial overgworh
drugs
IBD
Immune dysregulation
most specific test for coeliac disease?
anti-tissue transglutaminase IgA
Long term complications of coeliac disease
- malabssorption
- osteomalacia
- osteoporosis
- neurological disease (epilepsy, cerebral calcification)
- T-cell lymphoma of the bowel
- hyposplenism
Important to stick to the diet to prevent these complications
genetic components of coeliac diesase
HLA-DQ2
increased risk to family members
how often DEXA scan of hip in coeliac disease?
every 3-5 y
b/c of the risk of osteomalacia/osteoporosis
Lambert-Eaton myasthenic syndrome - what malignancy is it associated with?
Small cell Lung cancer
What syndromes is SCLC associated with?
SIADH (15% of patients)
Cushing’s syndrome (5%)
Lambert-Eaton Myasthenic syndrome (3%)
acromegaly
What infection does the presence of galactomannan in the serum of a septic patient suggest?
Aspergillus
Beta-D-Glucan in serum - what does it indicate?
candida
aspergillus
PCP
Glucuronoxylomannan (GXM) in serum - what does it indicate?
cryptococcus
