Week 3- clinical presentation and diagnosis

Question 1

what are some of the signs and symptoms of RA?

Answer 1

all patients are different and may experience Fever, malaise(weakness/discomfort), weakness which normally occurs before joint inflammation is visible

Question 2

where can RA occur and what may occur at the joints due to inflammation?

Answer 2

-small synovial lined joints like hands knuckles wrists and feet poly arteritis
- inflammation - pain, tenderness, swelling, stiffness, redness
and joint warmth
-• Inflammation, destruction of bone and cartilage
• Deformity, limited motion, pain on motion

Question 3

what can occur due to progressive articular deterioration?

Answer 3

loss of function

Question 4

what are some general symptoms of RA?

Answer 4

weight loss, fatigue, mental health changes

Question 5

what other organs can RA affect?

Answer 5

lungs= pulmonary fibrosis,
heart= increased cvd, double risk of myocardial infraction
eyes= dry eyes
skin
bones
RA nodules- firm lumps that occur at fingers elbows occur in 20% of patients, these patients have increased severity of disease

Question 6

comorbities can increase the patients risk of what?

Answer 6

• cvd= heart disease= 1/3 deaths in RA, due to inflammation of blood vessles, changes to clotting and chances to cholesterol
• risk of infection
• risk of respiratory disease
• risk of osteoporosis,
• risk of malignancy
• risk of depression

Question 7

what is looked for in blood tests for RA?

Answer 7

• Inflammatory markers

- Immunological parameters

Question 8

what is under inflammatory markers for blood tests when looking at RA signs and symptoms?

Answer 8

• Erythrocyte sedimentation rate (ESR)= shows degree of inflammation within joints, increase within 24-48hrs of inflammation
• C-reactive protein (CRP)= degrees of inflammation produced due to innate Immune responses, 4-6hrs after inflammation

Question 9

what is under immunological parameters for blood tests when looking at RA signs and symptoms?

Answer 9

• Rheumatoid factor (RF)= autoantibody but 30-40% of patients dont have it and other diseases can show positive test, 0 positive shows more servere
• Antinuclear antibody (ANA)=autoantibody only present in 40% of patients shows degrees of disease
• Anti-cyclic citrullinated peptide (anti-CCP)= not all a patients have it

Question 10

what can radiology do for signs and symptoms of RA?

Answer 10

• show damage and inflammation within the joint

- early stages might not

Question 11

what is the motion like for RA patients on examination?

Answer 11

• hard to form first
• limitation due to pain and stiffness
• squeeze tests if gelling if felts shows tenderness in RA patients

Question 12

how is RA diagnosed?

Answer 12

-not one test will provide diagnosis
-complete history taking=morning stiffness for greater than 30mins, Stiffness after quiescence
Family history
Lifestyle,
-clinical presentation= Symmetrical effects
on synovial joints –
symptoms as
discussed
-investigations =Inflammatory markers
Haematological parameters
Immunological parameters
Radiological investigations

Question 13

what does the NICE guidance say for RA for refferal and diagnosis?

Answer 13

-referral to primary care to specialist, refer those with suspected persistent
synovitis(inflammation of joints)
-Diagnosis= If found to have synovitis on clinical examination – Determine
Rheumatoid Factor, consider Anti-CCP antibodies (if negative for RF), x-ray hands
and feet.
-get paitent to fill out Health Assessment Questionnaire (HAQ).

Question 14

how to monitor a patients disease with RA?

Answer 14

use the DAS28= measure of the disease activity for 28 joints
-A measure of disease activity – 4 different measures
• Number of swollen joints (out of 28)
• Number of tender joints (out of 28)
• Measure ESR or CRP
• ‘Global assessment of health’
• Giving overall disease activity score
• Scores:
• DAS 28 = >5.1 = active disease
• DAS 28 = <3.2 = low disease activity
• DAS 28 = <2.6 = remission

Question 15

what is the management for RA and aims?

Answer 15

aims for management is to
• Minimising joint pain and swelling
• Preventing deformity and radiological damage (i.e. erosion)
• Maintaining QoL
• Controlling extra-articular manifestations

Question 16

what is the treatment for RA?

Answer 16

• Analgesia – NSAIDs(not long term) RELIEVE PAIN AND STIFFNES
• DMARDs – Disease Modifying Anti-rheumatic Drug(long term)=Conventional DMARDs (cDMARD) – methotrexate, sulphasalazine, leflunamide
[hydroxychloroquine, azathioprine, penicillamine, gold, ciclosporin
- Main goal of DMARD treatment = remission.
=Biologic DMARD- anti-TNF E.G(Adalimumab, Etanercept, certolizumab, golimumab,
infliximab)
Other biological=Tocilizumab / sarulimab – IL-6 receptor inhibitor
Rituximab – B-cell depletion of lymphocytes
Abatacept – Antibody blocking T-cells
Targeted DMARD= – JAK inhibitors – tofacitinib and baricitinib

Question 17

what is treat to target for RA?

Answer 17

-target for the patient to reach for disease non-progression,
a strategy which should include frequent review, formal
assessment of joints and escalation of therapy if inflammation is still present until good control is reached.
• Patients have an individual target
• Requiring tight control
-some patients aims are for remission or low disease activity
-reviews can be monthly

Question 18

what is first line for RA?

Answer 18

conventional Disease Modifying Anti-Rheumatic Drug (cDMARD) as
MONOTHERAPY, asap
E.G • Methotrexate (oral)
• Leflunamide
• Sulfasalazine
• [Consider as an alternative hydroxychloroquine (for mild palindromic disease)]
-choice is through drug characterisics, cations, side effects, dosing /
interactions / monitoring requirements and individuals patient

Question 19

after first line what should be consider for the patients medication?

Answer 19

• Escalate dose as tolerated.
  • Consider short term bridging with glucocorticoid therapy when starting a new DMARD for quick inflammation around joints fas cDMARD will take time to work. then it can be stopped

Question 20

what is the step up strategy therapy for RA?

Answer 20

• When the treatment target has not been achieve (despite dose escalation)
• Offer ADDITIONAL cDMARD (oral methotrexate, leflunamide, sulphasalazine or
hydroxychloroquine)
-more intense monitoring monthly and risk of side effects

Question 21

what drug can be added for symptom control of RA?

Answer 21

-COX-2 for stiffness and pain short term
-and PPI due to GI effects
• Lowest affective dose for shortest time

Question 22

what is step-down strategy?

Answer 22

• If maintained for at least 1 year consider step-down strategy
• Return to previous DMARD regime if target no longer met
-can reduce one cDMARD then maybe remove
-could lead to flare ups

Question 23

if DMARD doesn’t bring target that we require what can be done?

Answer 23

In severe disease (DAS28 >5.1) when not responded to combination cDMARD –
bDMARDs and tDARMDs may be considered

Question 24

what is the treatment guidance given by the EULAR (European League
Against Rheumatism)

Answer 24

-METHATREXATE SHOULD BE FIRST TREATMENT
-IF CONTRAINDICATED FOR mtx, leflunomide or sulfasalazine should be
considered as part of the treatment strategy.

Question 25

what is some systemic autoimmune diseases?

Answer 25

Rheumatoid arthritis

Question 26

what is an organ specific autoimmune disease?

Answer 26

• Myasthenia gravis
• Grave’s disease
• Autoimmune diabetes

Question 27

what is RA?

Answer 27

-A chronic, progressive, systemic, inflammatory
disorder affecting synovial joints
-most suffered develop RA between 25 and 50
-more women affected no racial or geographically difference

Question 28

what is the specific genetic predisproportion and 70% of patients express it?

Answer 28

human leukocyte antigen (HLA)-DR4 (mhc)

Question 29

what environemntal factors are affected for the RA?

Answer 29

suggested that tobacco smoke, air pollution, occupational exposure
to mineral oil and silica, infectious agents, and female hormones are involved in
the disease

Question 30

what is the genetic and environmental causes for RA?

Answer 30

-RUNS IN FAMILY
-MHC allele HLA-DRB1 shows relative risk
-more common in women than men (women who have
taken contraceptive pill is around half of women who have never taken it)
-Infections – definite associations lacking, but Mycobacterium,
Streptococcus, Mycoplasma, Epstein-barr virus and Parvovirus have
all been suggested
• Smoking

Question 31

what are the stages of the pathophysiology of RA?

Answer 31

• initiator phase
• Inflammation phase
• Self perpetuating phase
• destruction phase

Question 32

what is the full pathophysiology of RA?

Answer 32

-Initiator phase= Initiating
event unknown and reason
for joint specific localisation
is unknown. APCs and citrillination of
proteins now seen as non-self COULD TRIGGER IMMUNE RESPONSE
-Inflammation phase= self antigens and clonal expansion of T and B cells and insuffiently controlled by REGULATORY t CELLS. ACTIVATED IN THE JOINT
- Self perpetuating phase=casing inflammatory damage in syovium causes self antigens previously ‘unseen’ by immune
system to be exposed, immune response against
cartilage
Infiltration of immune cells
-destruction phase= synovial
fibroblasts and osteoclasts
activated by cytokines (TNF, IL-6)
destruction of bone and
cartilage

Question 33

how is bone lost due to osteoclasts (resorb bone) due to all the different types of cells involved in RA?

Answer 33

• Synovium inflammation is key, but systemic at all stages
(systemic features link in with co-morbidities);
• B-cells – Produce autoantibodies which can activate
complement and also bind to activated macrophages in
synovium. Activated macrophages perpetuate
inflammation.
• Autoantibodies: rheumatoid factor (RF) (directed against Fc fragment of IgG) and anti-citrullinated peptides(anti- CCP) are directed against antigens commonly present outside of the joint. Other autoantibodies too.
• T cells – potentially activate monocytes, macrophages and synovial fibroblasts  produce TNFα, IL-1 and IL-6
• These cytokines induce the production of matrix
metalloproteinases (MMPs) – which degrade the cartilage
• Joint destruction might be caused by CD4 T-cell cytokine:
RANK ligand (belongs to TNF-family), this promotes
osteoclasts (resorb bone)