multisystem disease Flashcards
pathophysiology of autoimmune connective tissue disease?
immune response against self antigen, producing antibodies, immune complexes and cellular activity against self-tissue.
common history complaints of someone with an aCTD
fatigue, anorexia, fever, weight loss
skin changes/rashes, joint paints, muscle pains, dry eyes/mouth, sicca symptoms, raynauds phenomenon
what are sicca symptoms
dry eyes, dry mouth, conjunctivities, episcleritis, vaginal dryness
what can be seen on examination of someone with aCTD
rash, joint pain, pigmentation, alopecia, endocarditis
what are some aCTDs
SLE, antiphospholipid syndrome, systemic sclerosis, polymyositis/myositis, dermatomyositis, mixed CTD
how does SLE happen
failure to clear apoptosed cells, leaving remnants that are ingested by APC who then trigger lymphocyte production of antibodies against self tissue. along with failure of self-regulation, inflammatory state and immune-complex deposition, causes multisystem disease.
systems that can be affected in SLE
CNS, eyes, mouth, joints, skin, heart, lungs, GI, kidneys, vasculature, blood
what are some CNS symptoms in SLE
psychosis, confusion, hemiplegia, ataxia, cranial nerve lesions, fits
what are some eye symptoms in SLE
dry eyes, scleritis, episcleritis, conjunctivitis, optic neuritis
what are some mouth symptoms in SLE
mouth ulcers, dry mouth
what are some joint symptoms in SLE
joint pains, muscle pains,
what are some GI symptoms in SLE
mesenteric vasculitis
what are some skin symptoms in SLE
lupus erythema discoid lupus raynauds phenomenon photosensitive rash butterfly rash livedo
what are some cardiovascular signs in SLE
percarditis
endocarditis
aortic valve lesions
what are some vascular signs in SLE
livedo
raynauds
nail and finger tip lesions
what are some kidney signs in SLE
glomerulonephritis, Proteinuria, haematuria, AKI
what are some haematological signs of SLE
lymphopenia, neutropenia, thrombocytopenia,
anaemia of chronic dz or haemolytic anaemia
low C3, C4
raised ESR (but often normal CRP)
auto antibodies
what are some lung complications of SLE
restrictive lung disease raised hemidiaphrams - "shrinking lung" pleural effusions (exudative) pneumonitis
is the pleural effusion in SLE transudative or exudative?
exudative
what are the antibodies associated with SLE?
anti-dsDNA anti-Sm anti-ro anti-la anti-histone (drug induced SLE) anti RNP
what auto antibody if seen, is specific to SLE?
anti-smith
what is the most commonly seen auto antibody in lupus?
anti dsDNA
what auto antibodies produce a ‘speckled’ sign on immunohistochemistry
anti-RO anti-LA, SCL-70, and RNA polymerase III
what auto antibody is associated with drug induced SLE?
anti-histone
what will ESR and CRP be like in SLE?
high ESR, normal CRP
what can be seen on histology in SLE?
immune-complex deposition in skin and/or kidneys
what does a false +ve VDRL suggest
SLE
what are some life threatening complications of SLE
renal crisis
pulmonary haemorrhage
catastrophic antiphospholipid
what coagulation syndrome is associated with SLE ?
anti-phospholipid syndrome
what antibodies are associate with antiphospolipid syndrome?
lupus coagulant
anti-cardiolipin
anti-b2GP
what is the behaviour of lupus coagulant? in vitro/vivo
in vitro it is antocoagulative
in vivo it is prothrombotic
what is anti-cardiolipin associated with
antiphospholipid syndrome
what syndrome is associated with lupus anticoagulant?
antiphospholipid syndrome
how will antiphospholipid syndrome affect pregnancy?
recurrent miscarriages
what can be seen on bone marrow biopsy in SLE?
lupus erythema cell (LE cell)
what is more worrying of SLE - 1:80 ANA titre found in a 22 year old, or 1:80 ANA titre found in a 79 year old?
the younger patient.
pathphysiology of systemic sclerosis
endothelial damage leading to immune/inflammatory response, leading to cellular infiltration which causes more damage, ischaemia. also activation of fibroblasts
who is the pathophysiology of fibrosis in systemic sclerosis
inflammation activates fibroblasts which produces more collagen, causing fibrosis in lower dermis and internal organs
common clinical features of systemic sclerosis
raynauds phenomenon lung disease - pulm H/T and/or fibrosis skin tightening - fingers, arms, face, neck GI dysfunction - dysphagia dilated nail capillary loops
how to tell between limited cutaenous Sc and diffused cutanaeous Sc
LcSSc is associated with CREST syndrome. more pulm hypertension, skin sclerosis usually distal to elbows, less systemic symptoms
DcSSc is more associated with fibrotic lung disease, systemic symptoms (fatigue, anorexia, weight loss), more widespread organ involvement, renal impairment, edema, more severe skin sclerosis that can lead to ulceration
difference in autoantibodies found in LcSSc and DcSSc
LcSSc is associated with anti-centromere antibodies
DsSSc is associated with antiSCL70 and antipolymerase
what are auto antibodies are found in systemic sclerosis?
rheumatoid factor (30%) and ANA (95%)
how to investigate systemic sclerosis?
FBC - Nchr Ncyt anaemia, or haemolytic microangiopathy in renal involvement
U&Es, urine dip, microscopy, ACR
autoantibody testing
nail fold capilloscopy
pulmonary function test
ECHO, BNP
imaging - CXR, xray hands, HRCT, barium swallow/OGD
explain what can be found on imaging in systemic sclerosis
CXR - heart enlargement, lung disease
xray hands - calcinosis
HRCT - fibrotic lung disease
barium swallow/OGD - oesophageal dysmotility
U&Es are always derranged in systemic sclerosis - T or F?
F, only if renal involvement
what is anti-topoisomerase antibody AKA?
anti-scl70
which auto antibody is associated with pulmonary hypertension?
anti RNA polymerase antibody
complications of systemic sclerosis?
pulmonary function
renal function
erectile dysfunction
GI dysfunction
why is pulmonary function testing indicated in systemic sclerosis?
monitoring of fibrotic lung disease
what is CREST syndrome?
calcinosis raynauds esophageal dysmotility sclerodactyly telangeictasia
what is morphea and when is it seen?
localised scleroderma - thickening of skin due to increased collagen production
symptoms of sjogrens syndrome
sicca
fatigue
joint involvement
renal tubular acidosis
how does sicca symptoms present
dry eyes
dry mouth/throat - coughing
dry vagina
what cancer is sjogrens associated with
non-hodgkins lymphoma
what antibodies is sjogrens syndrome associated with
ANA
rheumatoid factor
anti Ro, anti LA
how to investigate sjogrens syndrome
auto antibodies ESR (raised) complement (low) immunoglobulins (raised) schirmer's tear test (test how much tears produced) salivary flow test (reduced) parotid and mandibular gland USS lip biopsy (can see inflammation)
how to tell the difference between myalgia secondary to an autoimmune disease VS primary inflammatory myositis?
secondary mylagia usually doesn’t cause weakness, and will have normal muscle enzymes (CK, LDH)
myositis will cause muscle weakness, and raised CK and LDH, usually proximal muscles
clinical features of polymyositis
insidious onset with systemic symptoms (tiredness, weight loss. anorexia, fevers)
muscle weakness and pain (proximal)
describe the course of muscle weakness in polymyositis
starts with proximal weakness, then pain, usually shoulder and pelvis, in later stages, can involvement pharynx, larynx causing dysphonia/dysphagia, then respiratory muscles become affected causing respiratory failure
facial and hand muscles are not commonly involved in polymyositis - T or F
T
what is dermatomyositis associated with
cancer
what are signs of dermatomyositis
myositis + skin involvement
gottron's papules shawl sign (photosensitive rash) heliotropic rash (around eyes)
periorbital edema
what are gottron’s papules
purplish/red lichenoid rash around fingers, knucles, extensor surfaces
how to investigate (dermato/poly)myositis
bloods - commonly raised ESR/CRP, muscle enzymes (CKD, LDH, Trop T). autoantibodies
EMG, MRI, muscle biopsy
cancer screen in dermatomyositis
what autoantibodies are commonly found in polymyositis
ANA
anti-Jo-1
why is having sjogrens in pregnancy dangerous for the fetus?
sjogrens is associated with anti-Ro antibodies which can cross the placenta to cause heart blocks
pathogenesis of antiphospholipid syndrome?
antiphospholipid antibodies bind to a protein which causes inhibition of protein C. protein C is a anticoagulation protein (cleaves factor 5). without which, the system will become prothrombotic
how can antiphospholipid syndrome present?
any clotting event - DVT, stroke, PE
recurrent miscarriages
what is a skin sign of antiphospholipid syndrome
livedo
what are the 2 associated antibodies in antiphospholipid syndrome
anti-cardiolipin
lupus anticoagulant
what pregnancy conditions are women more at risk at if they have an aCTD?
preeclampsia, eclampsia, fetal growth restriction, preterm delivery.
what should be done if a woman with aCTD wants to get pregnant
planning, counselling, disease remission for 6 months before trying.
what should be prescribed prophylactically if someone has an aCTD and is pregnant
low dose aspirin
what DMARDs are safe in pregnancy?
hydroxychloroquine, azathioprine, methylprednisolone, rituximab in 1st trimester.
why might a woman with SLE give birth to a baby with rashes
could be neonatal lupus - self limiting
what autoantibody is mixed CTD associated with
anti-RNP
what conditions is mixed CTD more associated with
joint erosions
pulmonary hypertension
what is anti-Jo-1 associated with
myositis
what conditions can be seen in mixed CTD
rheumatoid arthritis
SLE
scleroderma
myositis
why might someone with dry eyes also complain of a cough?
(sjogrens) dry mouth/throat can cause chronic cough
why might someone with sjogrens complain of swollen lymph nodes?
could be lymphoma
which auto antibodies give a homogenous picture on Immunofluorescence?
anti-dsDNA
anti-histone
pathophysiology of giant cell arteritis?
granulomatous inflammation of large arteries
clinical features of PMR
pain shoulder, hips, lumbar, neck (worse in morning) systemic symptoms (fever, tiredness, weight loss, anorexia)
who gets PMR?
usually >50 and female
investigations to do in PMR?
FBC (CRP, ESR raised, normochromic normocytic anaemia)
raised alk phos and GGT (acute phase reactants)
temporal artery biopsy if indicated
signs/symptoms of giant cell arteritis
severe headache
scalp tenderness
eye symptoms
jaw claudication
what are some occular complications u can get with giant cell arteritis ?
amurosis fugax
blurred vision
diplopia
permanent loss of viseion
what will be seen on a histological biopsy in affected giant cell arteritis
T cell, macrophage, granulomatous inflammation. +/- giant cell
what imaging should be done in someone with GCA?
serial CXR to monitor for AA/AD
what kind of vasculitis is polyarteritis nodosa?
medium sized vessels
who gets polyarteritis nodosa
middle aged men
clinical features of polyarteritis nodosa?
systemic symptoms mononeuritis multiplex abdominal pain GI bleeding acute/chronic renal failure cardiac (mi, pericarditis, heart failure) skin (purpura, livedo, gangrene)
investigations in polyarteritis nodosa?
FBC (anaemia, raised esr, raised wcc) U&Es ECG aniogram biopsy investigation of any affected organ
what is the pathophysiology of a vasculitis?
a trigger causing endothelial damage, causing immune response towards endothelium of vessels, creating antibody-immune complex deposition onto endothelium, causing inflammation and imune destruction of endothelium, causing damage to vessels leading ischaemia, necrosis, gangrene
common symptoms of small vessel vasculitides
systemic symptoms - fever, weight loss, fatigue, myalgia, arthralgia
eye involvement - scleritis, scleromalacia
ENT - sinusitis, epistaxis, nose collapse, stridor
mucus membranes - genitooral ulcers
skin - rash, livedo, purpura, ulceration, necrosis, gangrene
pulmonary - lung haemorrhage, haemoptysis, chest pain, crackles, wheeze
kidney - AKI/chronic kidney disease
abdo - pain, bloody stools, obstruction
difference between GPA and MPA
GPA is more associated with C-ANCA, MPA is more associated with P-ANCA
GPA tends to be more diffused and multisystemic
MPA tends to involve kidneys more
what is the classical presentation of EGPA
late onset asthma with no prior hx of atopy
what is HSP
henoch schoenlein purpura
rash, arthalgia, abdo pain, with possible AKI
what is important to be done in HSP
urine dipstick, kidney involvement testing
which ANCA antibody is HSP associated with?
none
small vasculitic purpuric rashes vs one bigger vasculitic lesion, which is more serious?
the bigger patch, because it indicates a larger vessel involvement
how to tell the difference between a vasculitic purpura VS a thrombotic purpura?
vasculitis involves inflammation which will cause the lesions to be raised - palpable
what does a blue/purple edge of a lesions indicate?
vasculitis, due to start of necrosis
causes of raynauds ?
primary = idiopathic
secondary: SLE, SSC, dermatomyositis/polymyositis, sjogrens, RA, mCTD, takayasu’s arteritis, some drugs
what are some drugs that can cause raynauds
beta blockers, cytotoxic drugs (e.g. bleomycin), sulfasalazine
what does unilateral raynauds imply?
localised vascular problem
what HLA gene is antiphospholipid syndrome associated with?
HLA-DR7
what is the pathophysiology of livedo reticularis?
blocking/obstruction/constriction of capillaries
what are some autoimmune causes of livedo?
SLE, dermatomyositis, rheumatoid arthritis, polyarteritis nodosa
what are some vascular causes of livedo?
antiphospholipid syndrome
thrombocytosis
polycythaemia
cryoglobulinaemia
what is mononeuritis multiplex?
neuropathy of multiple individual nerve trunks
what can cause mononeuritis multiplex
diabetes
autoimmune: SLE, RA
vascular: GPA, MPG, polyarteritis nodosa
what hand signs can be seen in Graves disease?
thyroid acropatchy
what is the pattern of rashes seen in porphyria?
sun exposed areas - blistering, scarring, fragility
which type of porphyria does not exhibit skin signs?
acute intermittent porphyria
which dyslipidaemia condition is tendon xanthoma associated with
familiar hypercholesterolaemia
what underlying condition is eruptive xanthoma associated with?
hypertriglyceridaemia
how to tell the difference between a common viral rash and a rash caused by varicella?
common viral rashes are caused by e.g. measles, they diffused and erythematous, macula papular.
varicella rashes are raised vesicles with umbilication and monomorphic i.e all the same size
what is a sign of primary syphillis infection?
painless chancres at site of infection (mouth, anus, vagina)
what is the secondary sign of syphilis infection
coppery brown rash on the palms and soles
how does lyme disease present?
after tick bite, erythema migrans (red patch), that then becomes an annular rash around the bite
what are 2 skin manifestations of IBD?
erythema nodosum and pyoderma grangrenosum
describe erythema nodosum
erythematous painful nodules usually found on the legs caused my inflammation in fats
what is the rash exhibited in reactive arthritis?
PPPP - palmar plantar pustular psoriasis. or keratoderma blenorrhagica
what other symptoms can be found along side keratoderma blenorrahgica?
urethritis, conjunctivitis, arthritis
what are the symptoms found in behcet’s syndrome
orogenital ulcers, pyoderma, pathergy, uveitis
what inflammatory condition canpathergy be associated with?
Behcet’s disease
what conditions are associated with dilated nail fold capillaries?
raynauds phenomenon
systemic sclerosis
polymyositis/dermatomyositis
mixed CTD
what condition is associated with a sun-exposed geographical shape ring-like rash?
subacute lupus
what condition is associated with beaking of the nose, small tight mouth and telangectasia?
systemic sclerosis
clinical featurs of scurvy ?
corkscrew hairs, perifollicular haemorrhages (small red petichiae), bleeding gums
what are lisch nodules and what are they associated with?
brown streaks around the iris, associated with neurofibromatosis
are lymphocytes raised or reduced in SLE?
reduced
what ENT signs can be seen in small vessel vasculitis?
sinusitis, collapsed nose, epistaxis
what is the triad found in lofgren’s syndrome? and what is it?
erythema nodosum, bilateral perihilar lymphadenopathy, arthralgia
which patient is more worrying, a 19 year old with raynauds or a 52 year old with raynuds?
the 52 year old. the younger the patient presenting with raynauds, the more likely it is to be primary raynouds with no associated conditions. but the older presentation would be more likely to be associated with other autoimmune conditions e.g. SSc or dermatomyositis
what is the difference on examination of between reactive lymphadenopathy and malignant lymphandenopathy?
reactive LNs are more mobile lumps compared to malignant LNs which are more rubbery
what is erythema migrans associated with?
tick bite, lyme disease
what autoimmune condition is associated with dysphagia, dysphonia and loss of finger pulp tissue?
systemic sclerosis
