Session 8 RA Flashcards
Rheumatic diseases are characterized by inflammation connecting or supporting structures of the body — most commonly the joints. Give examples:
Osteoarthritis (most common arthritis) - affects and destroys cartilage
Rheumatoid arthritis (AID) - synovium
Fibromyalgia - a chronic condition marked by tender points and localized pain throughout the musculoskeletal system
Systemic lupus erythematosus (AID) - joints, skin, kidneys, blood, lungs, heart, and brain
Gout - a type of arthritis, uric acid deposit in the joints (big toe)
Infectious arthritis (arthritis that’s caused by an infection) e.g. Lyme disease or Neisseria gonorrhoeae,
Psoriatic arthritis (a type of arthritis) that affects the fingers and toes and is associated with psoriasis
Ankylosing spondylitis, ( most common spondyloarthropathy) , which may affect the hips, shoulders, and knees, in addition to the spine
Reactive arthritis, or Reiter’s syndrome, (spondlyoarthropathy) that develops after an infection of the urinary tract, bowels, or other organs
- Cause of rheumatic diseases?
- Various factors can put you at greater risk for developing one or more rheumatic diseases. For example:
A. Osteoarthritis is more common in older adults than younger adults
B. Women are far more likely than men to develop ?
C. Gout and spondyloarthropathies are more common in men
D. Lupus most often affects African-Americans and Hispanics
E. Obesity and smoking increases your risk for a number of rheumatic diseases
F. Dietary factors may increase or decrease your risk for certain rheumatic diseases — gout is associated with ?
- Gene & environment e.g. for rheumatoid
2B. rheumatoid arthritis, scleroderma, fibromyalgia, and lupus
F. diets high in purines, which are found in various types of meat
- For arthritis, inflammation typically causes one or more symptoms in the joints, including:
- Rheumatic diseases may produce a wide variety of other symptoms, such as:
- What is rheumatism
1. Pain, Stiffness, especially in the morning
Swelling
Warmth and redness
Tenderness
Difficulty using the joint normally
- Fatigue
Eye inflammation or infections
Rashes and sores
Pain in the neck, spine, or back
Difficulty taking a deep breath
Muscle pain
- any disease marked by inflammation and pain in the joints, muscles, or fibrous tissue,
Give examples of autoimmune rheumatoid diseases
- Pain on its own (in joint) =
- Pain and swelling (in joint) =
- What is Palindromic rheumatism (PR) ?
- ARD can mimic?
- Arthralgia
- Arthritis
- attacks of arthritis (in lecture he said attacks can occur in a pattern e.g. shoulder elbow wrist ankle then back up)
- acute pain, redness, swelling, and disability of one or multiple joints
- interval between & the length of an attack is extremely variable from few hours to days.
- no joint damage after attacks.
- It is thought to be an autoimmune disease, possibly an abortive form of rheumatoid arthritis.
- attacks of arthritis (in lecture he said attacks can occur in a pattern e.g. shoulder elbow wrist ankle then back up)
- Malignancy and vice versa
What to check for in history of lupus?
History taking for ARDs (lupus)
• Constitutional symptoms
(Fever, fatigue, weight loss, night sweats, Poor appetite)
• “Glove and sweater” approach
Examination for lupus
Investigations for lupus
Features of lupus
Rheumatoid arthritis (RA) History
- Female to male ratio: 3:1
- Prevalence: 1%
- No race predilection
- Genetic factors/environmental factors
Current symptoms • Pain • Stiffness • Swelling • Pattern of joint involvement
Evolution • Acute or chronic? • Associated events • Response to treatment/Family history
Involvement of other systems • Skin, eye, lung • Malaise, weight loss, fevers, night sweats?
Impact on patient’s lifestyle
Investigations for RA
Anti-Cyclic Citrullinated Peptide
- Ra pathogenesis
- Image
What do you autoantibodies do you find in blood tests?
What other test do you perform for RA
What can occur in the lungs?
Name 2 extra articular manifestations
- What type of hypersensitivity reaction is lupus?
- State the pathogenesis
- Type 3
-
apoptosis (natural or environment)
- Small blebs that carry self antigens e.g. nuclear constituents (e.g. DNA and histones)
- phagocytosis is ineffective - susceptibility genes - not removed from the blood
- transferred to lymphoid tissues, where they can be taken up by antigen-presenting cells
- The self antigens presented to T cells (TH4) -> B cells to produce autoantibodies
-
apoptosis (natural or environment)
The combination of availability of self antigens and failure of the immune system to inactivate B cells and T cells that recognize these self antigens (i.e. a breakdown of tolerance) leads to the following immunological consequences:
- Development of autoantibodies that either form circulating complexes or deposit by binding directly to tissues.
- Activation of complement and influx of neutrophils, causing inflammation in those tissues.
- Abnormal cytokine production
What occurs once the antigen - antibody complexes have been made?
Deposit in various tissues e.g.
What are the main auto-antibody found in blood tests?
What other autoantibodies can occur in SLE?
Antinuclear antibodies (E.g. Anti DNA (or anti double stranded DNA))
Anti-Sm antibodies
Antiphospholipid antibodies
The SKIN is commonly involved? Give three features:
Butterfly rash on face
Photosensitivity
Urticaria
Vasculitis
Purpura
State why SLE may also be seen as a type 2 hyper aswell
What might you find in the full blood count of a patient with SLE?
If there is evidence of haemolytic anaemia what test of the blood might help to confirm the autoimmune nature of the anaemia?
Anaemia, Low white cell count, Low platelet count.
combs test
=DIRECT!
Need to take blood from fetus
RBC with bound rhesus positive antibody bound
add combs antibodies will agglutinate
What is the indirect combs test and when do we do it ?
prenatal screening - i think after the women has the first child she has been sensitised so will produce rhesus + antibodies (D antigen is present on Rhesus positive RBC)
take serum of mother and donor blood which is rhesus positive
Then add combs reagent
= agglutination
Give three other body organs/systems that can be involved
MOA of type 2 hypersensitivities
Autoantibody in MS?
clinical feature?
important facts
– Extraocular muscles – commonest presentation – Bulbar involvement – dysphagia, dysphonia, dysarthria – Limb weakness – proximal symmetric – Respiratory muscle involvement
Treatment of MS
Antimuscarinic side effect –
Drugs effects MS
Plasmapheresis for myasthenia crisis
– miosis and the SSLUDGE syndrome:
» Salivation, » Sweating,
» Lacrimation
» Urinary incontinence
» Diarrhea,
» GI upset and hypermotility
» Emesis
Pyridostigmine
• Prevents breakdown of ACh in NMJ • ACh more likely to engage with remaining receptors • Onset 30min; peak 60-120min; duration 3-6hr
• Aminoglycosides • Beta-blockers, CCBs, quinidine,
procainamide • Chloroquine, penicillamine • Succinylcholine • Magnesium • ACE inhibitor
- Name two autoantibodies in Hashimoto’s disease
- What is a biopsy of the thyroid likely so show in Hashimoto’s disease
- What is the treatment for hypothyroidism and how is it monitored?
- Anti-thyroglobulin antibody
Anti-thyroid peroxidase antibody
- Infiltrate of lymphocytes (CD4+ and CD8+)
Plasma cells (with is a mature B cell producing a single antibody).
- Treatment:
- Oral Thyroid hormone.
- T4 used since longer half-life
- Normally ~50-200 µg/day in single dose.
The TSI causes all of the classical
signs and symptoms of thryotoxicosis, however the additional unique
features of Graves’ disease are:
– Exopthalmos (it is possible to have the exopthalmos alone)
– Pre-tibial myxoedema (confusing because nothing to do with
hypothyroidism/myxoedema!)
increase TSI more thyroid hormone more sympathomimetic effect???
Medication we give for ARDS
Immunosuppressants
- Corticosteroids
- Azathioprine
- Ciclosporin
- Tacrolimus
- Mycophenolate mofetil
Other disease-modifying anti-rheumatic drugs (DMARDs)
• Methotrexate
• Sulphasalazine
• Anti-TNF agents
• Rituximab
• Cyclophosphamide (cytotoxic)
What is first line treatment for RA?
Use:
MOA:
PK:
DDI:
ADR:
MOA: competitively and reversibly inhibits dihydrofolate reductase (DHFR)
No conversion of dihydrofolate to the active tetrahydrofolate
Azathioprine
Feature:
Use:
MOA:
Pharmocodynamics:
Use:• SLE & vasculitis -as maintenance therapy
- RA - weak evidence
- Inflammatory bowel disease
- Atopic dermatitis
- Bullous skin disease
MOA : antimetabolite (6-MP) reduce DNA & RNA synthesis
PD: Low/absent TPMT levels = risk of myelosupression
Therefore test TPMT activity before prescribing
Sulfasalazine:
Use:
MOA:
ADRs:
Practice:
PK:
PK: Poorly absorbed -main activity is within intestine, therefore effective in IBD
cleavage of sulfasalazine
ADRS:
• Bone marrow suppression
– Monitor FBC
• Increased risk of malignancy
– Esp transplanted patients -NHL
• Increased risk of infection
• Hepatitis
– Monitor LFT
Use & ADRS of Mycophenolate mofetil
MYOCOPHENALATE MOFETIL
PK
MOA
• Is a prodrug derived from fungus Penicillium stoloniferum
• Inhibits inosine monophosphate dehydrogenase
(required for guanosine synthesis)
• impairs B- and T-cell proliferation
• spares other rapidly dividing cells
(due to guanosine salvage pathways in other cells)
Cyclophosphamide
MOA:
PD:
indications:
Cyclophosphamide PK and ADR
• Significant toxicity
– increased risk of bladder cancer, lymphoma and leukaemia
– infertility risk relates to cumulative dose and patient age
– monitor FBC
– adjust dose in renal impairment
• Mycophenolate mofetil safer and as effective in lupus nephritis
We can give monoclonal antibodies
TNF - a blocker what we must do before we prescribe and why ?
TB reactivation is a risk
TNFα is released by macrophages in response to M TB infection
TNFα is essential for development + maintenance of granulomata
Screen for latent TB before anti-TNF treatment
Rituximab indications and MOA
binds specifically to a unique cell- surface marker CD20, which is found on a subset of B cells but not on stem cells, pro-B cells, plasma cells or any other cell type
B cells: present antigen to T cells produce cytokines produce antibodies
Rituximab causes B cell apoptosis Very effective in RA. Good safety data
Calcineurin inhibitors in practice
e.g.
indications
S/e
DDI
MOA
E.g.:
Ciclosporin & tacrolimus
Indications:
- widely used in transplantation
- atopic dermatitis & psoriasis
- Not often used in rheumatology -renal toxicity -> Check BP and eGFR regularly
DDI:
metabolited in liver -> Multiple drug interactions are possible (cytochrome P-450)
MOA:
active against helper T cells, preventing production of
IL-2 via calcineurin inhibition
Drugs to treat Rheumatoid Arthritis:
Methotrexate, Sulfasalazine, Infliximab, Rituximab, Adalimumab.
