Systemic Autoimmune Diseases Flashcards
What are the two basic mechanisms of self-tolerance?
-
Central tolerance
- immature lymphocytes that recognize self-antigens in the central lymphoid organs are normally triggered to die via apoptosis
-
Peripheral tolerance
- mature lymphocytes that recognize self-antigens in peripheral tissue either become functionally inactive (anergic), are suppressed by Treg cells, or are triggered to die by apoptosis
What is the fundamental problem with autoimmune disorders?
breakdown in self-tolerance
What are factors that lead to autoimmunity?
susceptible genes (HLA & non-HLA)
infections & tissue injury - expose self antigens & activate antigen presenting cells/lymphocutes in those tissues
What are the 6 organ specific autoimmune disorders mediated by antibodies?
- autoimmune hemolytic anemia
- autoimmune throbocytopenia
- atrophic gastritis of pernicious anemia
- myasthenia gravis
- graves disease
- goodpasture syndrome
What is the systemic autoimmune disease mediated by antibodies?
Systemic Lupus Erythematous
What are the 2 organ specific autoimmune disorders mediated by T-cells?
Type 1 Diabetes Mellitus
Multiple Sclerosis
What are the 3 systemic autoimmune diseases mediated by T-cells?
Rheumatoid arthritis
systemic sclerosis (scleroderma)
Sjogren syndrome
What are the 3 organ specific diseases that are postulated to be autoimune?
inflammatory bowel disease
primary biliary cholangitis
autoimmune hepatitis
What are the 2 systemic diseases postulated to be autoimmune?
polyarteritis nodosa
inflammatory myopathies
SLE is particularly associated with what autoantibodies?
Antinuclear Antibodies (ANA)
- DNA
- Histones
- Non-histone proteins bound to RNA
- Nucleolar antigens
What is the typical clinical presentation of a patient with SLE?
Female patient in 20s/30s
more common in black & hispanic patients
acute or insidious onset
injury to skin, joints, kidneys, & sclerosal membranes
What is the mechanism of injury seen in SLE?
deposition of immune complexes & binding of antibodies to various cells and tissues
What is the pneumonic associated with the diagnostic criteria for SLE?
SOAP BRAIN MD
4+ either serially or simultaneously
- S:erositis
- O:ral ulcers
- A:rthritis
- P:hotosensitivity
- B:lood disorders
- R:enal involvement
- A:ntinuclear Antibodies
- I:mmunologic phenomena
- N:eurologic disorder
- M:alar Rash
- D:iscoid rash
The provided image is an example of what SLE criteria?
Serositis (pleural effusion)
(also includes pericarditis)
chronic interstitial fibrosis & secondary pulmonary hypertension sen in some cases
The provided image is an example of what SLE criteria?
Oral ulcers
(usually painless)
The provided image is an example of what SLE criteria?
arthritis
(non-erosive, involving two or more peripheral joints)
The provided image is an example of what SLE criteria?
Photo sensitivity
(rash in reaction to light exposure)
The provided image is an example of what SLE criteria?
Blood disorders
- neutropenia
- anemia
- lymphocytopenia
- thrombocytopenia
The provided image is an example of what SLE criteria?
Renal Involvement
(persistent proteinuria / cellular casts)
What are the immunologic phenomena associated with SLE?
anti-dsDNA
anti-Smith [Sm] antibodies
anti-phospholipid antibodies
LE cell (outdated test)
The provided image is an example of what SLE criteria?
Antinuclear antibodies (in absence of drugs known to cause lupus-like syndromes)
What neurologic disorders are associated with SLE?
seizure
psychosis
(non-inflammatory occlusion of small vessels – NO vasculitis has been found in CNS)
The provided image is an example of what SLE criteria?
Malar rash
(characteristic “butterfly rash”; fixed erythema, either raised or flat, over malar eminences, usually sparing nasolabial folds)
- similar rash can also be seen on extremities & trunk
The provided image is an example of what SLE criteria?
Discoid Rash
(focal, raised, red patches, with adherent keratotic scaling and follicular plugging; atrophic scarring in older lesions)
Briefly describe the proposed pathogenesis model for SLE
- Susceptibility genes interfere with maintenance of self-tolerance
- External trigger → persistence of nuclear antigens
- antibody response agains self nuclear antigen
- amplified by dendritic cells & B cells
- production of type 1 interferon
**not a testing point, but good to understand
What are the possible contributing factors that lead to the development of SLE?
-
Genetic Factors
- MHC & non-MHC
-
Environmental factors
- UV light
- Drugs
- Sex hormones & gene on X chromosome
-
Immunologic factors
- Self-tolerance failure for nucleosomal antigens
- TLR engagement by nuclear DNA / RNA
- Type 1 interferons - lymphocyte activation
- other cytokines
What drugs are most commonly associated with drug-induced lupus?
hydralazine
isoniazid
procainamide
d-penicillamine
Anti-hypertensive & anti-fungal medicines are the most common culprits
What is the most commonly-use method to detect antibodies?
Indirect Immunofluorescence - positive for some type of ANA is positive in virtually every patient with SLE
What is the most commonly-use method to detect antibodies?
Indirect Immunofluorescence
What protozoan is us commonly used for test substrate in immunofluorescence testing? Why?
Crithidia luciliae
kinetoplast stains positive in patients with antibodies to dsDNA - ideal for testing due to its high concentration of dsDNA and lack of other human antigens
Are tests for ANA sensitive or specific for SLE?
sensitive - positive in almost all
but not specific because they are also positive in patients with other autoimmune conditions
SLE is what type of hypersensitivity reaction? Leading to what type of injury?
Type III
tissue injury is caused mainly by deposition of immune complexes & binding of antibodies
acute necrotizing vasculitis & fibroid deposits
What is the pathogenesis involved with peripheral blood cytopenias in patients with SLE?
autoantibodies specific for erythrocytes, leukocytes, & platelets - will opsonize these cells & promote their phagocytosis and lysis
What is the difference between LE bodies & LE cells?
-
LE bodies
- nuclei damaged cells react with ANAs - lose chromatin pattern & become homogeneous
- in vivo phenomenon
-
LE cells
- any phagocytic leukocyte that has engulfed & denatured nucleus of an injured cell
- ONLY seen in vitro when blood is agitated - Outdated
What is antiphospholipid syndrome?
This syndrome is associated with what risks?
autoantibodies (lupus anticoagulants) are directed against phospholipid-associated proteins
may raise the risk of venous & arterial thrombosis
What substances are commonly found in the blood vessels in patients with SLE?
immunoglobulin, dsDNA, C3
perivascular lymphoid infiltrate
The provided image is a characteristic feature of what autoimmune condition?
SLE
fibrous thickening and luminal narrowing
Where are SLE immune deposits found within the kidney?
mesangium
basement membrane
What kidney problems are seen in patients with SLE & how does this present clinically?
cellular infiltration, microvascular thrombosis, vascular wall deposition
hematuria, proteinuria, hypertension, renal insufficiency
** don’t have to differentiate the types via images
SLE can cause what effect on the cardiovascular system?
- pericarditis (common)
- myocarditis (less common)
- valvular involvement
- Coronary artery disease due to atherosclerosis
SLE can cause what effects on the spleen?
moderate splenomegaly
follicular hyperplasia
What are the most common causes of death in patients with SLE?
renal failure & incurrent infection
What the provided immunofluorescence image is characteristic of what condition?
Skin manifestation of SLE
Ig & complement along DE junction
What type of skin manifestations are seen in SLE?
- liquefactive degeneration of the basal layer
- Dermis
- edema
- perivascular mononuclear infiltrates
- vasculitis and fibrinoid necrosis of the vessels
What condition is shown in the provided image? It is most common on what areas of the body?
Discoid Lupus Erythematosus
face & scalp
plaques with varying degrees of edema, erythema, scaliness, follicular plugging & sin atrophy - surrounded by erythematous, elevated border
rare to have systemic symptoms
What is a laboratory test that can help differentiate SLE from chronic discoid lupus erythematosus?
antibodies to dsDNA are rarely present in discoid lupus
What pathology is is shown int he provided image?
Discoid Lupus Erythematosus
Hyperkeratosis, flattened epidermis, perivascular and periadnexal chronic inflammation
What are the key difference in antinuclear antibodies seen in SLE compared to drug-induced lupus?
antibodies for dsDNA are rare in drug-induced
high frequency of antibodies for histones
Do people with drug-induced lupus have the same systemic symptoms as people with SLE?
most do not, but some do
renal & CNS involvement is rare
What genetic factors are associated with Rheumatoid arthritis?
HLA-DR4,
HLA-DR1,
HLA-DR10,
HLA-DR14
What joints are most commonly affected by rheumatoid arthritis?
metacarpaophalangeal & proximal interphalangeal joints of hands & feet
elbows
knees
ankles
spine (uncommon)
What percent of patients with RA are positive for RF?
80% (humoral immunity)
high titers are associated with more severe disease
What infections agents are possibly associated with rheumatoid arthritis?
EBV, parvovirus B19
How does RA affect joints?
non-suppurative proliferative synovitis & may progress to destruction of articular cartilage
What clinical symptoms are commonly seen in RA?
joint pain, swelling, morning stiffness & decreased grip strength
joint deformities
anemia, fatigue, rheumatoid nodules, pleural or pericardial inflammation/effusion, neuropathy, splenomegaly, Sjogren syndrome, vasculitis, inflammation of slcera
The provided histological slides are indicative of what condition?
Rheumatoid Arthritis
- papillary synovial hyperplasia w/ dense inflammatory infiltrate of plasma cells & lymphocytes, and lymphoid nodules
- later a pannus of synovium, inflammatory cells & fibroblasts encroach on the hyaline cartilage leading to destruction
- neutrophils accumulate in synovial surface & in fluid
- osteoclasts are activated, with resulting bone erosion, osteoporosis, and subchrondral cysts
In addition to RF, what other antibodies are commonly seen in RA?
- Antibody to citrullinated peptide (ACPA)
-
anti-CCP antibody (>90% specificity)
- can also be seen in other acute inflammatory states
What is the postulated mechanism by which cellular immunity contributes to RA?
CD4 initiate autoimmune response
they produce cytokines (ie TNF) that stimulate other inflammatory cells to cause tissue injury
What are rheumatoid nodules & in what types of patients do they most commonly occur?
firm, non-tender nodules arising in subcutaneous tissue in areas subject to recurrent pressure & viscera
occur almost exclusively in seropositive (RA, ACPA) patients
What autoimmune disorder is characterized by dry eyes & dry mouth?
Sjogren Syndrome
What immunofluorescence pattern is seen with Sjogren?
speckled
90% of patients with Sjogren have antibodies agains what serologic markers of the disease?
two ribonucleoprotein antigens
SS-A (Ro)
SS-B (La)
What is the clinical manifestation of Sjogren Syndrome?
- older woman
-
keratoconjunctivitis sicca
- blurred vision, burning & itching
- xerostomia
- parotid gland enlargement
- nosebleeds
- bronchitis
Patients with Sjogren’s have a 40-fold increase of developing what pathology?
lymphoma (usually MALT)
What is the clinical picture of a patient with Systemic Sclerosis?
- Woman 50-60
- cutaneous fibrosis
- dysphagia
- Raynaud
- RHF
- GI issues
- renal failure
The etiology of systemic sclerosis is due to what 3 processes?
autoimmunity, vascular damage, fibrosis
What are the two different types of Systemic Sclerosis?
Diffuse scleroderma
Limited scleroderma
What are the characteristic symptoms associated with diffuse scleroderma?
- skin (shiny) involvement at onset (expand proximally)
- rapid progression to chronic inflammation (small vessels & fibrosis)
- early visceral involvement
- Raynaud (may appear years before)
What are the characteristic symptoms associated with limited scleroderma?
- skin is only on fingers, forearms, & face
- late visceral involvement
- CREST Syndrome
- C:alcinosis
- R:aynaud phenomenon
- E:sophageal dysmotility
- S:leroderma
- T:elangiectasia
- Centromeric patterin on immunofluorescence
What immunofluorescence pattern is seen with Limited Scleroderma?
centromeric
What ANAs are commonly seen in Diffuse Systemic sclerosis? Limited Lystemic Sclerosis?
- Diffuse: DNA topoisomerase I
- Limited: Anti-centromere antibody
What pathology is shown in the provided image?
you see infiltration between the glands & within the glands themselves
The skin manifestation shown in the provided image is characteristic of what disease?
Systemic Sclerosis
notice that it is tight & shiny
What can be the result of extensive subcutaneous fibrosis?
claw-like flexion deformity
The provided image shows what pathology?
Systemic Sclerosis
- extensive deposition of dense collagen in the dermis with virtual absence of hair follicle & focal inflammation
- increasing dermal fibrosis
Mixed connective tissue disease is characterized by what high antibody titers?
U1 ribonucleoprotein
What is the clinical manifestation of mixed connective tissue disease?
mixture of those other autoimmune diseases
(SLE, polymyositis, RA, Systemic Sclerosis)
What are the possible complications associated with mixed connective tissue disease?
pulmonary hypertension,
interstitial lung disease,
progressive renal disease
