Histopathlogy 5: Connective Tissue Disorders Flashcards
List 3 auto-antibodies seen in SLE ?
- Anti-dsDNA
- Anti-Smith (most specific but not very sensitive - only 30% with SLE have)
- Anti-histone (drug related)
NB ANA (Anti-nuclear antibody) is just a screening test which tells you that the patient has antibodies that bind to nuclear antigens (it does NOT tell you which antigens it binds to)
What type of hypersensitivity reaction is seen in SLE ?
Type 3 hypersensitivity reaction
What is the HLA association with SLE ?
HLA DR3
Name the heart condition that can be caused by SLE ?
- Libman-sack endocarditis
- This is a NON-INFECTIVE form of endocarditis (inflammatory form of endocarditis)
List the signs and symptoms of SLE using the mnemonic SOAP BRAIN MD
Serositis (inflam of serous tissue - surround organs)
Oral ulcers
Arthritis
Photosensitivity
Blood disorders- AIHA, ITP
Renal involvement - Type 2 RPGN
ANA +ve
Immune- anti-dsDNA, anti-smith
Neuro symptoms
Malar rash
Discoid rash
Which auto antibodies are seen in Diffuse scleroderma ?
Anti-scl70 - this is the antibody to DNA topoisomerase
Which autoantibodies are seen in limited scleroderma (CREST) ?
Anti-centromere (ANCA)
Which HLA is associated with scleroderma ?
HLA DR5
List the signs and symptoms of limited scleroderma (CREST) ?
- Calcinosis
- Raynauds phenomenon
- Esophageal dysmotility
- Sclerodactily
- Telangiectasia
No involvement of the trunk
Aetiology of scleroderma effect in skin
- EXCESS deposition of collagen
- resulting in reduced skin elasticity
Which autoantibodies are seen in Polymyositis and dermatomyositis ?
anti- Jo1
Patient has proximal muscle weakness. Their bloods show increased CK and abnormal EMG. No rash is seen.
Most likely diagnosis?
Polymyositis
Patient has proximal muscle weakness. Their bloods show increased CK and abnormal EMG. A heliotrope rash is seen on the eyelids. There are Gottron papules on the knuckles
Most likely diagnosis?
Dermatomyositis
Japanese lady with absence of pulse and Claudication (pain in muscles).
The Rheumatologist says that its a large vessel arthritis.
Most likely diagnosis ?
Takayasu’s arteritis
Elderly man presents with a temporal headache, jaw claudication and scalp tenderness.
Most likely diagnosis?
Temporal arteritis
(Large vessel vasculitis)
A man presents with abdo pain and signs of renal impairment. Angiogram shows “rosary beads” because of multiple aneurysms.
Most likely diagnosis?
Associated with which disease?
Polyartheritis nodosa (medium vessel arteritis) Hepatitis B
A heavy smoker with ulceration of the toes and fingers has an angiogram which shows a “corkscrew appearance”.
Most likely diagnosis?
Buerger’s disease
List the triad of features seen in Polyangitis with granulomatosis ?
Saddle nose
Pulmonary haemorrhage
Glomerulonephritis (Crescentic)
Which ANCA is associated with Granulomatosis with polyangiitis (Wegener’s Granulomatosis) ?
C-ANCA
directed against proteinase 3
List 3 characteristic features of Eosinophilic granulomatosis with polyangitis (Churg-Strauss syndrome) ?
- Asthma
- Eosinophilia
- P-ANCA vasculitis
NB this is small vessel disease
List 3 features of Microscopic polyangitis?
Pulmonary haemorrhage (haemoptysis)
Glomerulonephritis (Pauci immune RPGN)
P-ANCA small vessel vasculitis
Which type of amyloidosis is seen in multiple myeloma ?
AL amyloidosis (primary)
With free light chains, monoclonal Ig and Bence jones proteins in the urine
List some causes of AA amyloidosis? (4)
- Rheumatoid arthritis
- Chronic TB infection
- IBD
- Hodgkin’s lymphoma
Name one familial amyloidosis ?
Familial Mediterranean fever
Congo red staining shows ……………. under polarised light if there is Amyloidosis
apple green birefringence
An Afro Caribbean patient presents with SOB and cough. Examination shows erythema nodosum, lymphadenopathy and hepatosplenomegaly. X-ray shows bilateral hilar lymphadenopathy
Histology shows: non-caseating granulomas
Most likely diagnosis?
Sarcoidosis
Which electrolyte is often elevated in Sarcoidosis?
Ca2+
How to measure anti-dsDNA in SLE
- incubate the patient’s serum with Crithidia Luciliae (protozoan)
- This organism has a big mitochondrion with dsDNA (kinetoplast)
- Also measure with ELISA
Skin histology for SLE
- lymphocytic infiltration (black dots)
- vacuolisation (dissolution of the cells)
- extravasation of the RBCs
How do glomerulus capillaries look in SLE?
- thickened (wire-loop capillaries)
- capillaries are thick due to immune complex deposition in the basement membrane (capillaries are surrounded by basement membranes)
Limited vs diffuse Systemic Sclerosis (scleroderma) in terms of where on the body affected
- Diffuse= involves the truncal skin
- Limited= does NOT involve the trunk (only affects distal to the elbows and knees)
immunofluorescence finding in scleroderma
nucleolar pattern
Effect of trichome staining on muscle and collagen
- Red staining- muscle
- Blue staining- collagen
NB can use this in scleroderma (see XS collagen)
Histological finding in scleroderma
onion skin appearance - due to intimal layer of artery proliferating and obliterating the lumen
Why do ANA test?
Screen for mixed connective tissue disease
Then need to follow-up to look for specific antibodies
Sign on knuckle in dermatomyositis
Gottron’s papules (erythematous purple rash over the knuckles)
Sites affected in sarcoidosis
- Joints (arthralgia)
- Skin (e.g. lupus pernio, erythema nodosum)
- Lungs (bilateral hilar lymphadenopathy, fibrosis, lymphocytosis (increased CD4+ cells in the bronchoalveolar lavage)
- Lymphadenopathy
- Heart (any layer: pericardium, myocardium, endocardium)
- Eyes (uveitis, keratoconjunctivitis)
- Neuro (meningitis, cranial nerve lesions)
- Liver (e.g. hepatitis, cirrhosis, cholestasis)
- Parotids (bilateral enlargement)
pathological hallmark of Sarcoidosis is a non-caseating granulomatous inflammation
Enzyme and electolyte raised in sarcoidosis
- Raised serum ACE levels (due to abnormality in the lungs where ACE is made)
- HyperCa
2 visible features of vasculitis
- palpable purpuric rash
- Nail fold infarcts
Definitive Dx of temporal arteritis
- temporal artery biopsy
- show narrowing of the lumen and lymphocytic infiltration of the tunica media
Tx of Giant Cell Arteritis (Temporal Arteritis)
high dose prednisolone
Example of Medium Vessel vasculitis
Polyarteritis Nodosa
- Necrotising arteritis
- most commonly affecting the renal vessels or mesenteric vessels
- May present with gut ischaemia or renal impairment
- Creates a rosary beads appearance on the angiogram because of the presence of multiple aneurysms
rosary beads appearance on the angiogram due to which vasculitis?
Polyarteritis Nodosa
Polyarteritis Nodosa associated with which infection?
Hep B
Example of Small Vessel vasculitis
Granulomatosis with polyangiitis (Wegener’s Granulomatosis)
- ENT- nosebleeds, sinusitis, saddle nose
- Lungs- haemoptysis, SOB
- Kidneys- haematuria
p-ANCA seen in which small vessel vasculitis?
Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
3 hallmarks:
- Asthma
- Eosinophilia
- Vasculitis
