RA and OA Flashcards
What is the most important environmental risk factor for development of RA?
Smoking
What HLA is RA associated with?
HLA DRB1 0404
HLA DRB1 0401
Risk stacks, therefore if have both HLA DRB1 0404 and 0401 pos the high risk
What is the MHC association of RA?
Shard epitope in 3rd hypervariable region
What is the most specific antibody for RA? this antibody is part of a class of RA antibodies called?
Anti CCP
1 of a group of antibodies called ACPAs (anti cetrulinated protein antibodies)
Whst is though to be the main pathogenesis of RA?
There is an environmental stress that causes induction of PAD enzyme
- PAD converts arginine to citrulline (citrullination)
- Autoreactivity to neoepitopes created by protein citrulination leads to teh formation of ACPAs (anti citrulinated protein antibodies) such as anti CCP
Note citrulination occurs all the time, for example in the lungs of smokers
Person without HLA B1 DR3 0404 or 0401 positive will have more resistance to this citrulination process
Where does protein citrulination occur in the development of RA? (where does RA begin)
Mucosal
Gut microbiome
Lungs
Begins in the peripheries, mucosal surfaces
Antigen presentation and T cell activation in the nodes
Then cell mediated joint attack
What is the unifying cytokine that is increase in all connective tissue disease?
TNF-alpha
- thought to be IL15 because this controls production of TNF, however tests show that TNF alpha is the main driver
What is the most common cell in the synovial fluid of RA pts? Why is this the case?
What about the synovium?
Neutrophil are in teh synovial fluid
THere should not be any neutrophils in the synovium, that would not be RA (? infection)
- this is because there is a gradient of IL8 (chemoatractive)
The main cell in the synovium is the T cells (B cells <5%)
What are the two types of fibroblasts in the synovial membrane? what is their role in RA?
Ling layer fibroblasts
- Cause bone and cartilage destructive
Sub lining layer fibroblasts
- produce cytokines for chemoattration
What is the most important cytokine in errosive RA?
IL-1 (increased expression = increased errosive disease)
- IL-17 is in the synovioum and is associated with errosive disease but it is not the cause
Is RA a disease of TH1 or TH2?
TH1, response is maintained by IL18 and 33
Thought that RA pts are deficient in TH2 cells (these are responsible for switching off the immune response)
- TH2 response sustained by IL4 and 13 which are absent in RA
What happen in an RA flare? (cell migration kinda stuff)
Naive B cell exists in the serum before a flare
B cell becomes activated
PRIME cells are recruited
PRIME cells and activated B cells migrate into the joint causing teh flare
Pt comes in with arthralgia. WHat factors would make them more likely to develop RA in teh new 12 months?
Firs degree relative with RA
RF and anti CCP positive
MCP involvement / morning stiffness
What is the main clinical aspect in the diagnostic criteria for RA?
Joint involvement, multiple joints involved is worse
When should RF be performed?
Only do this if you think the person has RA. Very poor specificity meaning lots of false positives
IS RF or anti CCP a better predictor of errosive disease?
Anti CCP
WHat is the earliest change in RA on Hand XR? What are some other features on hand XR and neck XR?
Peri-articular osteoporosis
- Occurs mainly in RA, not in other condition
Errosions are a poor prognostic factor
Atlantoaxial subluxation >4mm needs to be addressed, esp prior to having surgery
WHat is the triad that characterises Feltys syndrome?
RA, splenomegally, neutropenia (due to hypersplenism)
What heart complication can RA pts classically get?
Constrictive pericarditis
What form of eye disease is RA most associated with?
Episcleritis, scleritis
Scleritis is painful and has visual abn
Episcleritis is not painful and nil visual change
- Phenylephrine topically will cause blanching. WIll not cause blanching in scleritis
All RA pts who tolerate it should be on …?
Methotrexate
What medications reduce radiological progression of RA?
MTX, hydroxychloroquine, leflunamide, sulfasalazine
What are the contraindications for MTX?
mild seronegative disease
renal impairment
liver impairment
high eoth intake
Lung disease
Pt with RA, CPC liver disease and ongoing alcohol. Can they have MTX?
No
How does MTX penumonitis typically present? How is it managed?
Soon after starting MTX, pt presents with fever, SOB, dry cough, chest pain
Main DDx is PJP infection
Rx:
Cease MTX
Pred
Supprtive measures
No role for folinic acid
What cancers is MTX associated with?
SKin cancers
B cell lymphomas
Lung cancer (probs due to smoking association)
Should MTX be ceased in periop?
No, generally speaking just continue it
What is the general approach if pt fails MTX alone?
Add sulphasalazine +/- hydroxychloroquine
- COmbination is always better than MTX alone
What is a specific side effect of luflunamide and how is it managed?
P{eripheral neuropathy
- cease and allow drug to wash out
What is the criteria for biologics in RA?
MTX for at least 3 months, combination with another DMARD for at least 3 months
(Basically fail conventional DMARDs)
What is the biologic that is best / safest to use in preg for RA pts?
Certolizumab
What are some of the TNF alpha inhibitors used in RA?
Infliximab
Adalimumab
Etanercept
Golimumab
Certolizumab
DMARDs slow radiological progresion of RA. What effect do teh biologics have on radiological progression?
Cease radiological progression
- this doesnt nec means better patient scores tho
TNF inhibitor are associated with reactivation of which latent infection?
TB
Why is MS an absolute contraindication for TNF inhibitors?
TNF inhibitors can cause demyelination
Aside from teh TNF inhibitors, what other biologics can be used for RA?
Abatercept (Soluble CTLA4 anoligue)
Tocilizumab (IL6 receptor antibody)
Rituxumab (mab for CD20)
JAK inhibitors
- Tofacitinib (JAK1, JKA6)
- Baracitinib (JK1,2)
- Upadacitinib (JK1)
What infectious agent is most implicated in TNF inhibitors?
Herpes zoster
- need to give shingrex
Pt has Hep B, new dx RA> which biologic can he have?
None
Pt has solid malignancy <5yrs, new dx RA. which biologic can he have?
Ritux
How is OA classified?
Primary or secondary
Knee OA vs multiple joint OA (most often Knee + other joints but not always)
What are some common causes of secondary OA?
Anatomical abn
Trauma
Metabolic disorder (ie haemachromatosis)
What is the biggest RF for OA?
Age
Hip OA in younger person. What secondary cause?
Probably hip dysplasia
May also be haemachromatosis
What is the major modifiable RF of OA?
Obesity
its a much bigger RF from knee OA than for hip OA
Is exersise protective or RF for OA?
Normal joint at risk with lack of exersise, at risk with high impact exersise
Abn joints are at risk with exersise
WHat are teh 4 features of OA on XR?
Loss of joint space
Osteophytes
Subchondral cysts
Subchondral sclerosis
Pt with hand OA, has MCP joint involvment. What is Dx?
Cant be standard OA (MCP woulds not be involved)
- Have to think of RA, OA due to secondary cause it haamachromatosis, boxing etc)
Rx of OA? What medications do not work / are not recomended?
Non pharm:
- Loose weight
- Exersise / tai chi
Pharm:
- Paracetamol if nil co-morbidities (First line if niol co-morbidity, not first line if have co-morbidities)
- Non seletective NSAIDs (gastroprotection needed if co-morbidities, not give to pts with significant co-comorbidities)
-> topical NSAIDs short term or for intermitent pain
- Topical capcacin
- Duloxetine - pain management if failure of NSAIDs
- DO not use opioids - unclear benefit and significant risks
- BPs are of unclear benefit at this stage
- Nil good evidence for glucosamine and chondroitin (also beware shell fish allergy)
- Intrarticular injection are not effective in the long term. Similar efficacy to placebo in the short term for symptom relief
What medicaiton is disease modifying in OA?
Doxycycline
- reduces joint space narrowing
Strontium is also Disease modifying, however not used anymore due to risk of thromboemolism
