Autoimmune Rheumatic Diseases Flashcards
What is a rheumatologist?
Treats many different organs systems, autoimmune disease and drug to modulate their function
What organs can be affected by rheumatic disease?
Skin, blood vessels, nerves, muscles, bones/joints, internal organs and gut
What is vasculitis (Skin)
Is an inflammatory skin diseases which causes widening of the blood vessels causing things such as stroke, MI’s, abdominal pain, fevers, headaches, nose bleeds, vision loss, weight loss etc.
Do all rheumatoid diseases go into all blood vessels?
No - some will be found in smaller blood vessels, others in larger ones such as the aorta.
What is the symptoms and causes of the skin disease = small vessel vasculitis-henoch schonlein purpura (IgA vasculitis)?
Rashes, stomach aches, arthritics, renal disease and is caused by IgA deposits in the blood vessels of the kidney, skin or gut.
There is expansion of B and T cells
The symptoms of the skin disease kawasaki and cause?
Coronary artery aneurysms, peeling skin around finger nails, red eyes, cracked lips, swelling ankles
Caused by infection associated pyroptosis and oxidative stress which activates innate and acquired immunity leading to arterial wall damage.
What are the symptoms and causes of the nerve disease polyarteritis nodosa?
Medium sized artery disease which causes gangrine in the extremeties and foot drop - where you cannot keep you foot up. It also causes kidney aneurism
What are the symptoms and causes of giant cel arteritis?
The aorta and vessels next to the eye become inflamed (you can see this on their skin) if not treated within 4 weeks causes blindness. Within about 3 days there is no more symptoms and the patient will be fine
What are the symptoms and causes myositis?
Causes rashes, discolorisation on the back, knuckles and under eyes. Also causes muscle weakness. Caused by inflammation surrounds blood vessels and atrophy of fibers near border of fascicle.
This is caused by cancer because your body is trying to fight the cancer. Also, caused by checkpoint inhibitor treatments.
What causes these types of diseases?
You genes, environment, or we dont really know
What are the symptoms of RA?
Swelling of joints
Joint tenderness
systemic malaise
loss of energy
severe morning stiffness
Why would you go early for treatment?
It progresses from feet and hands to all over the body anywhere there is synovial membranes and can be stopped.
What do people with RA develop around their knees?
Pannus which is a swelling full of fibroblasts, plasma cells, endothelium, T lymphocytes, macrophages etc.
Is RA a normal response to injury?
No its a big response to really small injuries this could be because of lack of regulation of the immune response or more cells.
What does the pannus tissue do to bone?
it can eat away at it
Smoking and RA?
Smoking destroys cells in lungs bringing immune system to the lungs. If you are genetically predisposed to RA you are going to have an exagerated immune response. This immune response produces ACPA antibodies which bind harshly to MHC 1 causing good T cell reactions.
What are some extra-articular manifestations of Rheumatoid?
Ocular, heart inflammation, vascular, skin, lungs, neurological (stroke)
Is rheumatoid vasculitis a late complication of RA?
Yes and this can cause gangrine, eyes damage,
How do drugs manage RA?
Systemic DMARDs
Interfere with cytokine function - Anti-TNFalpha and anti-IL-6 (be careful as if someone had TB at some point this may come back).
Inhibit signal (CTLA4-Ig-Abatacept)
Deplete B cells - rituximab
Block Jak stat pathway
How does tofacitinib work?
IL-6 and other cytokines use JAK3-STAT signalling to increase inflammation and this blocks this reducing inflammation
What is psoriatic arthritis?
Can occur in feet, spine, hands etc. Arthritis can get so bad it can melt bones away
Th17 and psoriatic arthritis
Tendons and ligans go into bones and if there is too many Th17 cells this will cause a big immune response to the little hurts these tendons get e.g strain from carrying bags
The IL-17 triggers macrophages, fibroblasts etc which also release inflammatory cytokines
What are biological therapies for psoriatic arthritis?
Anti-TNF
IL-17 inhibitor
IL-12/23 inhibitor which blocks p40 of IL12 and IL23
IL-17 receptor antibody for skin psoriasis
What organs does lupus affect?
Most of them - mouth ulcers, renauts, kidneys failure, hair loss, face rash.
What is the pathophysiology of Lupus?
Triggers cause immune system disregulation or defective apoptosis.
The defective apoptosis causes modified nucleosomal material which is taken up by plasma cells to make Interferons and then either the innate immune response or the adaptive immune response.
The immune system disregulation causes T and B cells and cytokine defects and the adaptive immune response.
What does type 1 interferon do?
Decreases Treg cells, increases NETosis and induces B cells proliferation and loss of tolerance.
What are the biological therapies of lupus?
Rituximab - didnt actually show any significstn benifit.
Belimumab - unhibits the soluble form of a B cell survival factor (BAFF) which normally promotes the formation and survival of memory B cells and plasmablasts making autoantibodies.
IFN - trials show mixed results to date.
What is systemic sclerosis?
Tight fibrosis skin which entirely encases the body it also happens in the gut causing increased bacteria, the lungs (interstitial fibrosis, pulmonary hypertension), cardiac muscles (arythmias, CCF) and renal (accelerated HT, renal crisis)
