Diagnosis of Autoimmune Conditions Flashcards
What is the process behind why an autoimmune disease develops?
The immune system should be tolerant to self antigens
i.e. Not identify them as something that needs to be attacked
any part of the immune system that could attack self antigens should be eliminated
if it is not eliminated, then autoimmune disease results
What types of tests are needed to identify autoimmune diseases?
Tests are needed to detect which autoantibodies are present in the patient’s blood
various laboratory techniques are used to identify these antibodies
What are the stages in working out which autoimmune disease that a patient has?
Why is it important to achieve the correct diagnosis?
- Take the clinical history
- Examine the patient
- Perform some blood tests
different autoimmune diseases can have similar symptoms
acheiving the correct diagnosis leads to correct management
What is sclerodactyly?
localized thickening and tightness of the skin of the fingers or toes
it often leads to ulceration of the skin of the distal digits
It is often accompanied by atrophy of the underlying soft tissues
What is livedo reticularis?
Mottled reticulated vascular pattern that appears as a lace-like purple discolouration of the skin
it is caused by swelling of the venules, leading to construction of the capillaries by small blood clots
What is scleroderma (diffuse systemic sclerosis)?
Chronic autoimmune condition that affects the skin, connective tissue and internal organs
It results in hard, thickened areas of skin and sometimes problems with internal organs and blood vessels
What is scleroderma caused by?
the immune system attacking the connective tissue under the skin and around internal organs and blood vessels
What tests would be performed to confirm diagnosis of scleroderma?
ANA
ANCA
CK
Rheumatoid factor
Anti-CCP antibody
Complement
FBC, U&Es, LFTs, CRP
Why are diagnostic tests performed?
They are used to answer specific questions and/or to support a clinical diagnosis
They are NOT used as screening tools
What can improve the ability of the tests to distinguish between health and disease?
The ability of the tests to correctly discriminate between health and disease is improved when they are used in the appropriate population
What is meant by sensitivity?
A measure of how good the test is in identifying people with the disease
How is sensitivity worked out from this table?
[a / (a+c)]
a = true positive
b = false positive
What is meant by specificity?
A measure of how good the test is at correctly defining people without the disease
How is specificity worked out from this table?
[d / (b + d)]
b = false positive
d = true negative
What is meant by positive predictive value?
The proportion of people with a positive test who have the target disorder
How is positive predictive value worked out from this table?
[a / ( a + b )]
What is meant by negative predictive value?
The proportion of people with a negative test who do not have the target disorder
How is negative predictive value worked out from this table?
[d / (c + d )]
What are the missing labels regarding testing
What are the 2 types of diagnostic tests?
Non-specific:
- inflammatory markers
Disease specific:
- autoantibody testing
- HLA typing
What are the non-specific markers of systemic inflammation?
- ESR
- CRP
- Ferritin
- Fibrinogen
- Haptoglobin
- Albumin
- Complement
What are antinuclear antibodies (ANA)?
Antibodies in the patient’s blood that bind to the cell nucleus
How can antinuclear antibody testing (ANA) be made more specific?
By identifying subtypes of antibody that bind to different bits of the cell nucleus
How is the ANA test performed?
- A blood sample is taken from the patient’s arm
- An ANA test is performed by testing the blood in the laboratory
- The antibodies in the serum of the blood are exposed in the laboratory to cells
- It is then determined whether are not antibodies are present that react to various parts of the nucleus of cells
Fluroescent techniques are used to detect the antibodies in the cells
What does a positive ANA test suggest?
That an autoimmune disease is present
This does not make a specific diagnosis, it just suggests that some form of autoimmune disease is present
What is meant by the detection of DSDNA and ENAs?
Anti dsDNA is a type of antinuclear antibody that is present in SLE
Extractable nuclear antigens (ENAs)
An ENA panel tests for autoantibodies against 6 or 7 proteins in the cell nucleus
What technique is used in detection of ENAs?
Immunoblots
this technique involves the detection of specific proteins in a sample of tissue to homogenate or extract
antbodies with fluorescent tags are used to identify specific proteins
What does ELISA stand for?
What is this test used for?
Enzyme-linked immunosorbent assay
An antigen is immobilised on a solid surface and then complexed with an antibody that is linked to an enzyme
detection of a specific protein is accomplished through assessing the conjugated enzyme activity
What other method can be used for antinuclear autoantibody assessment?
Microbead-based immunoassay
What autoantibodies are present in the following conditions:
i. SLE
ii. Sjögren’s syndrome
iii. Neonatal lupus erythrematosis
iv. Diffuse systemic sclerosis
v. limited systemic sclerosis
I dsDNA, Sm
ii. La
iii. Ro
iv. Scl-70
v. Centromere
What auto-antibodies are present in the following conditions?
i. Polymyositis
ii. Dermatomyositis
iii. Rheumatoid arthritis
I. Jo-I
ii. Mi-2
iii. CCP
Which autoantibodies are seen in the following conditions?
i. Diffuse glomerulonephritis
ii. Membranous glomerulonephritis
iii. Neonatal heart block
I dsDNA - SLE with kidney disease
ii. Sm, Ro - SLE with kidney disease
iii. Ro - maternal antibody
Which autoantibodies are present in the following conditions?
i. Raynaud’s phenomenon
ii. Fibrosis alveolitis
iii. Erosive joint damage
I. U1-RNP as part of overlap syndromes
ii. Jo-1 (in polymyositis), U1-RNP
iii. CCP - in RA and overlap syndromes
What is alopecia?
“Spot alopecia”
a condition in which hair is lost from some or all areas of the body
It often results in a few bald spots on the scalp
What would the complement blood results look like in someone with SLE?
What about ANA by indirect immunofluorescence?
C4 and C3 will be low
ANA shows a positive, homogenous pattern
What is the tool used for diagnosing SLE?
American College of Rheumatology Diagnostic Criteria
There are both clinical criteria and immunologic criteria
The requirements are >/= 4 criteria (at least 1 clinical and 1 laboratory criteria)
or a biopsy-proven lupus nephritis with positive ANA or anti-DNA
What is rheumatoid factor?
An antibody (IgM, IgG or IgA) directed against the FC portion of IgG
What types of diseases is rheumatoid factor associated with?
It is commonly found in rheumatoid arthritis but is not diagnostic of the diseases
It can be seen in other diseases in which polyclonal stimulation of B cells is seen
e.g. chronic infections
When is Anti-CCP antibody (ACPA) used as a diagnostic tool?
How sensitive is it?
It is more specific for rheumatoid arthritis than RF
It has similar sensitivity to RF
It is a useful prognostic marker - ACPA positive patients tend to have more severe and erosive disease
What would a joint X ray look like in rheumatoid arthritis?
Peri-articular swelling with effusion of MCP joints
osteopenia
joint space narrowing and erosions
What types of blood test results would be seen in rheumatoid arthritis?
Why is early treatment important?
High rheumatoid factor, CCP and elevated ESR and CRP add to the probability of a definitive diagnosis
Early treatment can prevent joint damage and significant morbidity
When are anti-neutrophilic cytoplasmic antibodies (ANCA) ordered?
They are ordered when vasculitis is queried
e.g. renal or ENT
What are the symptoms of granulomatosis with polyangitis ?
Oral cavity:
- ulceration throughout oral mucosa
Lungs:
- cavities
- bleeds
- lung infiltrates
Skin:
- nodules on the elbows
- purpura
Eye:
- pseudotumours
- conjunctivitis
Nose:
- stuffiness
- nosebleeds
- saddle nose
Heart:
- pericarditis
Kidneys:
- glomerulonephritis
What are the symptoms of granulomatosis with polyangitis caused by?
What test is positive in this condition?
Granulomas and patchy necrosis in blood vessels
there would be a positive anti-neutrophil cytoplasm test
What is the difference between cytoplasmic (c) ANCA and perinuclear (p) ANCA?
Cytoplasmic ANCA:
- Granular fluorescence of neutrophil cytoplasm with nuclear sparing
Perinuclear ANCA:
- apparent fluorescence of the nucleus only
What is the difference between ANCA and anti-PR3/MPO?
ANCA is the pattern
anti-PR3/MPO is the autoantibody causing the condition
What are the target antigens for cytoplasmic and perinuclear ANCA?
Cytoplasmic ANCA:
- PR3 - 90%
- MPO
Perinuclear ANCA:
- MPO - 70%
- PR3
What are the symptoms and features of granulomatosis with polyangitis?
(Wegener’s cANCA anti-PR3 positive)
Histology:
- leukocytoklastic vasculitis
- necrotising, granulomatous inflammation
ENT:
- nasal septum perforation
- saddle nose deformity
- conductive or sensorineural hearing loss
- subglottic stenosis
Eye:
- orbital pseudotumours
- scleritis
- episcleritis
- uveitis (50%)
Lung:
- nodules
- infiltrates or cavitary lesions
- alveoral haemorrhage
Kidney:
- segmental necrotising glomerulonephritis
Heart:
- occasional valvular lesion
Peripheral nerves:
- vascultic neuropathy (58%)
Eosinophilia:
- occasional eosinophilia
What are the signs and symptoms of microscopic polyangitis?
pANCA anti MPO positive
Histology:
- leukocytoklastic vasculitis
- granulomatous inflammation
ENT:
- Absent or mild
Eye:
- Occasional eye disease
- scleritis
- episcleritis
- uveitis
Lung:
- alveolar haemorrhage
Kidney:
- segmental necrotising glomerulonephritis
Heart:
- rare
Peripheral nerves:
- vasculitic neuropathy
Eosinophilia:
- none
What are the signs and symptoms of Churg-Strauss syndrome?
Histology:
- eosinophilic tissue infiltrates and vasculitis
- granulomas have eosinophilic necrosis
ENT:
- nasal polyps
- allergic rhinitis
- conductive hearing loss
Eye:
- occasional eye disease
- scleritis
- episcleritis
- uveitis
Lung:
- Asthma
- fleeting infiltrates
- alveolar haemorrhages
Kidney:
- segmental necrotising glomerulonephritis (rare)
Heart:
- heart failure
Peripheral nerves:
- vasculitic neuropathy
Eosinophilia:
- all
Complete the table for the clinical utility of ANCA testing?
What is the clinical utility of a positive ANCA test?
- Useful in suggesting the diagnosis in the proper clinical setting
- histopathology remains the gold standard for diagnosis in most cases
What do negative ANCA assays not exclude?
Negative ANCA assays do not exclude AASV
10-50% of patients may be ANCA negative
What does persistence of ANCA in the absence of clinical indications suggest?
Persistence of ANCA in the absence of clinical indications of active disease DOES NOT indicate a need for continued treatment
What does reemergence of ANCA positive in a patient who was ANCA negative whilst in remission suggest?
A risk of disease flare
the time to the flare is uncertain
How is autoimmune liver disease screened for?
Why may it be screened for?
It is part of the non-invasive liver screen that is performed if liver tests are deranged
Antibodies are detected by IF screening using rodent tissue block (oesophagus, liver and kidney) and antigen-specific ELISA
What is looked for in the autoimmune liver disease screen for primary biliary sclerosis and autoimmune hepatitis?
Primary biliary sclerosis:
- anti-mitochondrial antibody that is specific for PBS
Autoimmune hepatitis:
- anti-smooth muscle and anti-liver/kidney/microsomal (LKS) antibodies
What are the different types of autoantibodies in type 1 diabetes mellitus?
- Islet cell antibodies
- Anti-GAD65 and anti-GAD67
- Anti-insulinoma antigen 2 (IA-2)
- Insulin autoantibodies (IAA)
What happens to the autoantibodies in type 1 DM with time?
They disappear with progression of disease and total destruction of B-islet cells
Why do we test for the autoantibodies in type 1 DM?
To confirm presence of the disease
to identify relatives and patients at risk of developing autoimmune diabetes
What happens in Addison’s disease?
Which autoantibodies can be detected?
There are clinical features as it impairs production of cortisol
you can detect autoantibodies targeting the adrenal cortex
What antigen is present in pernicious anaemia?
H+K+ - ATPase located in the gastric parietal cells of rodent stomach
What are the clinical presentations of pernicious anaemia?
The antibody is present in more than 90% of patients with pernicious anaemia
What condition can lead to pernicious anaemia?
What is it characterised by?
Autoimmune gastritis
this is characterised by antibodies to GPC and intrinsic factor
