What type of hypersensitivity reaction is Grave's disease and what are the autoantibodies for this disease?
- Type 2
- TSH receptor antibodies
Why do patients get exophthalmos in Grave's disease?
The antibodies are attacking muscles of the eye as the muscles contain TSH receptors. This causes swelling and increased hyularonic acid in the eye so increased osmotic pressure
How is Grave's disease treated?
- Carbimazole: inhibits thyroid peroxidase but be careful as tetarogenic
- Surgery to remove
- Radioactive iodine
- Beta blockers to help symptoms
What type of hypersensitivity reaction is Hashimoto's disease and what autoantibodies are present?
Anti TPO and Anti TG
How can we diagnose Hashimoto's disease?
- Fine needle biopsy to see infiltration of TH1 lymphocytes
- Serum autoantibodies
How do we treat Hashimoto's disease?
Give Levothyroxine and monitor TSH/T4 levels
How is the secretion of thyroid hormone regulated?
How does carbimazole work?
What are the general actions of thyroid hormone and what are the tissue specific effects?
What are some common symptoms of SLE and RA?
- Pain: pleuritic chest pain, joint pain (especially hands and wrists)
What is the epidemiology of SLE?
- More common in young Afro-Caribbean females
- Genetic factors important
- Environmental factors like smoking and UV light can be a trigger
At what age do most autoimmune diseases develop?
Child bearing aged females 15-45 apart from type I diabetes
How do we take a history for autoimmune rheumatic diseases?
- Constitutional symptoms e.g weight loss, fever, night sweats etc
- Glove and Sweater approach
What areas of the body should be examined when suspecting an ARD and what should you be looking for?
What are some investigations that should be carried out when you suspect SLE?
- Often normal CRP
- Even if bloods normal treat the clinical presentation!!!
How should we commence treatment once there is a diagnosis of SLE?
What are the 11 criteria for SLE?
A RASH POINTS MEDICAL DIAGNOSIS
What is the epidemiology of RA?
- More common in females 3:1
- No race preference
- 1% prevalence
- Genetic and environmental factors (e.g smoking and bad dentition)
What is the S factor in rheumatoid arthritis?
What tests are done once you suspect RA and what are some autoantibodies in this disease?
How is RA treated once it is diagnosed?
Sooner the better to slow progression
What are some differentials for this case and what would be the course of treatment if you found of the CRP level was raised?
- Interstitial lung disease due to methotrexate
- Cancer metastases
- Rheumatoid lung nodules
- Do CXR, D dimers (rule out PE), FBC
- Would most likely be pneumonia, don't give amoxicillin as immunocompromised so can cause C.Diff!!! Give IV co-amoxiclav
What are the autoantibodies in rheumatoid arthritis?
- Anti RF: against the rheumatoid factor (Fc part of immunoglobulin G)
- ACPA: anti citrullinated cyclic peptide
Antibodies cause persistent synovitis with systemic inflammation but norma CRP
What are some non-articular manifestations of rheumatoid arthritis?
IMPORTANT!!! Rheumatic lung nodules
What mediators cause the articular manifestations of rheumatoid arthritis?
- Progressive, symmetrical, peripheral polyarthritis
- Synovitis and destruction of joints due to the over production of TNF-a. This over production is due to interaction of macrophages and T/B lymphocytes
- TNF-a causes an over production of IL-6. Blocking TNF-a and IL-6 can improve synovitis and systemic malaise
What information does a D-dimer test provide?
- Used to measure the extent of clotting, it is a breakdown product of fibrin
- Raised: PE, DVT, malignancy, pregnancy, recent surgergy, infection, stroke, MI
- Negative: rules out PE
What are the differential diagnoses? (especially if when you do a urine dipstick there is blood, protein and nitrates)
- Lupus nephritis
- AKI secondary to NSAIDs
- Lupus flare
- Issue with glomerulus (blood)
Most likely complicated UTI as immunocompromised due to result on dipstick
What autoimmune condition does this patient have and why are they more at risk of systemic complications?
- Lack of complement so immune complexes not being opsonised and cleared so more likely to be deposited over the body, e.g kidneys, causing damage
What is the pathogenesis involved in SLE and what autoantibody is produced?
Anti DS-DNA, anti-Ro/La, anti-Sm/RNP
When cells apoptose the cell remnants appear on the cell surface as blebs containing self antigens (e.g DNA and histones)
In SLE removal of blebs by phagocytes in inefficient so they are transferred to lymphoid tissues where they are taken up by APCs that present self antigens to T cells that activate B-cells
What is lupus nephritis?
Occurs in 1/3 of SLE patients and 25% of these reach end stage CKD in 10 years
Immune deposits in glomeruli and mesangium (IgG, IgM, IgA, C3, C1q, C4) can be seen on staining and immunofluorescence