Rheumatoid Arthritis

Question 1

Definition

Answer 1

• CHRONIC SYMMETRIC POLYARTICULAR INFLAMMATORY JOINT DISEASE - primarily affects SMALL JOINTS of HANDS + FEET

	○ CHRONIC, AUTOIMMUNE, SYSTEMIC ILLNESS characterised by SYSTEMIC PERIPHERAL ARTHRITIS + OTHER SYSTEMIC FEATURES

Question 2

Presentation

Answer 2

Symptoms:

• PAIN - VARIOUS JOINTS (INFLAMED SYNOVIUM + JOINT CAPSULE, DESTROYED CARTILAGE)

• STIFFNESS + IMMOBILITY
• POOR FUNCTION

• SYSTEMIC SYMPTOMS

Signs:

• SWELLING
• TENDERNESS
• LIMITED MOVEMENT
• REDNESS
• HEAT
• DEFORMITY e.g. swan-necking (DIP flexion + PIP hyperextension), ulnar deviation, Bouchard’s nodes (PIP swellings, also common on CMC joint of thumb, boggy swelling), rheumatoid nodules

Systemic Signs:

NON-SPECIFIC:

* FATIGUE/LASSITUDE (lack of energy)
* WGT. LOSS
* ANAEMIA

• FATIGUE + REDUCED COGNITIVE FUNCTION (SECONDARY FIBROMYALGIA) - dysregulation of HPA axis

SPECIFIC (can be any system): underlined are v. severe complications

* EYES - dry eyes to scleritis
* LUNGS - interstitial lung disease, fibrosis
* NERVES
* SKIN - cutaneous complications, can lead to vasculitic ulcers
* KIDNEYS (less common)
* LIVER - elevated acute-phase response, anaemia of chronic disease (IL-6 increases hepcidin production - iron regulatory hormone)
* MUSCLES (sarcopenia) - muscle wasting, loss of muscle mass + strength
* BONE - osteoporosis
* SECONDARY SJOGREN'S SYNDROME

• VASCULITIS, NODULES, SCLERITIS, AMYLOIDOSIS (amyloidosis v. rare now) = secondary to uncontrolled chronic inflammation

LONG-TERM:

* CVS - altered lipid metabolism, elevated acute-phase reactants, increased endothelial activation
* MALIGNANCY

Question 3

Classification

Answer 3

1. JOINT INVOLVEMENT
   
   2. SEROLOGY
   3. ACUTE-PHASE REACTANTS (INFLAMMATORY MARKERS - ESR, CRP)
   4. SYMPTOMS DURATION

Question 4

Investigations

Answer 4

Bloods:

• FBC + U&E (illness, infection - diff. WBC)
ESR, CRP

Immunology:

• RHEUMATOID FACTOR (IgG, IgM) - essentially redundant now, antibody to antibody produced, SENSITIVE + NOT SPECIFIC (can be raised in ageing, infection, malignancy, other conditions, in ~ 50% of the normal population)
• ANTI CYCLIC CITRULLINATED ANTIBODIES (ANTI CCP/ACPA) or anti-citrullinated protein antibody

Imaging:

• X-RAY of JOINTS = LOSS of CARTILAGE, BONY DEFORMITIES (these are all late changes, should be managed earlier)
• MR
• DOPPLER = INFLAMMATION ~ JOINTS

Question 5

Management

Answer 5

• ASSESSMENT = DISEASE ACTIVITY SCORE (www.das28.com), HOW DOES PT. FEEL

	○ LOW DAS/DAS < 2.4 = represents CLINICAL REMISSION
	○ HIGH DAS/DAS > 5.1 = represents ELIGIBILITY for BIOLOGIC THERAPY

• RHEUMATOLOGY FOLLOW-UP

	○ EARLY ARTHRITIS CLINIC - NURSE LED

	○ MONTHLY APPT.
	○ MONITORING DISEASE ACTIVITY using DAS28
	○ MONITORING BLOOD TESTS - REGULAR BLOOD TESTS
	○ PT. EDUCATION
	○ MDT e.g. RHEUMATOLOGY PHYSIO, RHEUMATOLOGY SPECIALIST NURSE, RHEUMATOLOGY OT, PHARMACIST, CLINICAL PSYCHOLOGIST, PODIATRIST, ORTHOTICS

EARLY + AGGRESSIVE INTERVENTION to obtain optimal outcomes = EFFECTIVELY SUPPRESS INFLAMMATION (improves symptoms + prevents joint damage &amp; instability)

	HOW EARLY &amp; HOW AGGRESSIVE?

	SEQUENTIAL MONOTHERAPY
	COMBINATION: STEP UP, STEP DOWN, PARALLEL
	TREAT TO TARGET = routine treatment compared to intensive management - latter is much better in achieving low disease activity, so doesn’t matter so much how low disease activity is achieved but that it is achieved

Question 6

Pharmacology

Answer 6

• MEDICINES
• INJECTIONS
• THERAPIES
  1. NSAIDs = SYMPTOMATIC CONTROL
  2. DISEASE MODIFYING ANTI-RHEUMATIC DRUGS (DMARD)
  3. BIOLOGICS
  4. CORTICOSTEROIDS = ORAL, IM, IA

DMARD: SLOW ONSET EFFECT on DISEASE ACTIVITY & DELAY DISEASE PROGRESSION

• METHOTREXATE

EFFECTIVE, WELL-TOLERATED (at doses given for RA, still needs monitoring), CHEAP

CORNERSTONE if COMBINATION TREATMENT (w/ DMARD & BIOLOGIC)

PT. STAY ON IT - imp. as life-long disease

FOLATE ANTAGONIST (CI in PREGNANCY)

• SULFASALAZINE - can be used in PREGNANCY
• HYDROCHLOROQUINE (anti-malarial)
• LEFLUNOMIDE

BIOLOGICS: TARGET KEY ASPECTS of IMFLAMMATORY CASCADE (typically large complex proteins - needs to be given PARENTERALLY)

• TNFα INHIBITORS - TNF -alpha is a key marker in the inflammatory cascade = SULFASALAZINE, ETANERCEPT, ADALIMUMAB
• IL-1 INHIBITORS = ANAKINRA
• ANTI-B CELL THERAPIES = CD20, RITUXIMAB
• ANTI-T CELL THERAPIES = ABATACEPT
• IL-6 INHIBITORS = TOCILIZUMAB
• OTHER

Can be used in PREGNANCY
RAPID, generally WELL-TOLERATED
IMP. TOXICITIES (e.g. infections) + EXPENSIVE

EFFICACY = EFFECTIVE ALONE, ENHANCED RESPONSE w/ METHOTREXATE

TOXICITY = MINOR e.g. injection site reaction, INFECTION e.g. minor cold, flu, TB, MALIGNANCY

Question 7

Epidemiology

Answer 7

• F : M = 3 : 1

AGE of ONSET = PEAK AGE ~ 4TH/5TH DECADE, can OCCUR ANY AGE ≥ 16YRS

Question 8

Aetiology

Answer 8

GENETIC = HLA-DRB1, PTPN22

ENVIRONMENTAL:

• SMOKING & BRONCHIAL STRESS - EXPOSURE to SILICA
• INFECTIOUS AGENTS have been ass. w/ RA
  • VIRUSES - EBV, CMV
  • E. COLI
  • MYCOPLASMA
  • PERIODONTAL DISEASE - PORPHYROMONAS GINGIVALIS
  • MICROBIOME - GUT MICROBES

• REPEATED GENETIC INSULTS in GENETICALLY SUSCEPTIBLE INDIVIDUAL would LEAD TO

* FORMATION of IMMUNE COMPLEXES + RHEUMATOID FACTOR (high affinity autoantibody against Fc portion of Ig)
* ALTERED CITRULLINATION of PROTEINS + BREAKDOWN of TOLERANCE w/ RESULTING ACPA RESPONSE

Question 9

Pathophysiology

Answer 9

synovitis causes tissue damage affecting all structures involved in a joint - arginine converted to citrulline, citrullinated proteins are attacked by

* VILLOUS HYPERPLASIA
* INFILTRATION of T CELLS, B CELLS, MACROPHAGEA, PLASMA CELLS
* INTIMAL CELL PROLIFERATION (FIBROBLASTS)
* CYTOKINE + PROTEASE PRODUCTION
* INCREASED VASCULARITY
* SELF-AMPLIFYING PROCESS

Question 10

Complications

Answer 10

• ORTHPAEDIC INTERVENTION = CHRONIC SYNOVITIS, MECHANICAL DEFORMITIES, SECONDARY OA, POOR FUNCTION, PAIN
  
  • EXTRA-ARTICULAR INVOLVEMENT - RHEUMATOID NODULES, INTESTITIAL LUNG DISEASE, VASCULITIS
  • CV RISK
  • SOCIOECONOMIC

Question 11

Functional impairment

Answer 11

• VERTEBRAL # - OSTEOPOROSIS
  
  • SPECIAL ADAPTIVE CUTLERY
  • SPECIAL FOOTWEAR
  • WALKING AIDS
  • WHEELCHAIR for OUTDOORS
  • SUPPORTIVE FAMILIES
  • CARE PACKAGE

Question 12

Rheumatoid joint

Answer 12

• INFLAMED SYNOVIUM SPREADING ACROSS JOINT SURFACE + INFLAMED TENDON SHEATH + CARTILAGE THINNING + BONE EROSION
  
  • RHEUMATOID SYNOVITIS (PANNUS) = characterised by:○ INFLAMMATORY CELL INFILTRATION, SYNOVIOCYTE PROLIFERATION, NEOANGIOGENESIS
  • SYNOVIAL FLUID in JOINT CAVITY contains NEUTROPHILS esp. DURING ACUTE RA FLARE-UPS
  • SYNOVIAL PANNUS = causes BONE + CARTILAGE DESTRUCTIONS (DEFORMITIES)

Question 13

Autoimmunity

Answer 13

• EVIDENCE of AUTOIMMUNITY can be PRESENT in RA for MANY YEARS BEFORE ONSET of CLINICAL ARTHRITIS
• AUTOANTIBODIES e.g. RFs & anti-citrullinated protein, COMMONLY ASS. W/ RA
  
  • RA autoantibodies - RECOGNISE JOINT ANTIGENS e.g. type II collagen/SYSTEMIC ANTIGENS e.g. glucose phosphate isomerase
  • AUTOANTIBODIES can CONTRIBUTE to INFLAMMATION through SEVERAL MECHANISMS incl. ACTIVATION of COMPLEMENT

SERO+VE RA = RHEUMATOID FACTOR (autoantibody to self IgG - Fc portion), ANTI-CITRULLINATED PROTEIN ANTIBODY

SERO-VE RA = still have RA, but DON’T HAVE AUTOANTIBODIES in above list - MAY STILL DEVELOP OTHER AUTOANTIBODIES