Rheumatoid arthritis

Question 1

Rheumatoid arthritis : Pathophhysiology

Answer 1

1. Autoimmune system activation : cause by;
   * Environmental exposure : modifies body’s antigen
   * Genetic predisposition : HLA-DR1, HLA-DR4
   Body’s own cells are recognised as ‘foreign’
2. Auto antibodies produced;
   * Rheumatoid factor
   * Anti-ACPA antibody

2 . Joint inflammation -> Release of cytokine which cause;
* Synovial cell activation
* Synovial membrane thickening : stimulate synovial cells to proliferate, causing it to become thick and swollen
* Secrete proteases which break down articular cartilage

• . Increase in RANKL expression on T cells
• Allows the T-cells to bind RANK, a protein on the surface of osteoclasts
• Osteoclasts are therefore stimulated to start breaking down bones

4 . Inflammatory cytokines enter the blood stream and reach multiple organ systems leading to extra articular problems

Question 2

Rheumatoid arthritis : Clinical features

Answer 2

1. Slow insidious onset of pain, swelling, stiffness
2. Symptoms improve with movement
   * Worst in the morning
3. Joint distribution :
   * Involves multiple joints >5 joints
   * Symmetrical joints on both sides of the body
   * Affects smaller joints - Metacarpophalengeal, proximal interphalangeal joints of hands and feet - avoids DIP.

Question 3

RA : The spine

Answer 3

• Cervical spine (not lumbar) : affected by RA,

Atlantoaxial subluxation
* MOA : Synovitis and damage to the ligaments
* Partial dislocation : C2 / C1
* Complication: Subluxation can cause spinal cord compression and is an emergency

Question 4

RA : Extra articular manifestations

Answer 4

Inflammatory cytokines enter the blood stream and reach multiple organ systems leading to extra articular problems

1. Skeletal muscles : leads to formation of rheumatoid nodules
2. Vasculitis - inflammation of blood vessels, increases risk of developing atherosclerosis, increases risk of CVS disease
3. Lungs - activates fibroblasts results in pulmonary fibrosis
4. Liver - in response to inflammatory cytokines
   * Liver starts to produce high volume of hepcidin
   * Hepcidin which decreases serum iron levels by inhibiting its absorption from the gut - resulting in anaemia

5 . Felty syndrome : RA + Splenomegaly + Low WCC count - can lead to life threatening infections

Question 5

RA : Eye manifestation

Answer 5

1. Dry eye syndrome (keratoconjunctivitis sicca)
2. Episcleritis / Scleritis / Keratitis } Inflammation of sclera + cornea
3. Cataracts - secondary to Steroids
4. Retinopathy - secondary to Hydroxychloroquine

Question 6

Rheumatoid arthritis : X-ray findings

Answer 6

1.X-ray : Hands and feet
* Loss of joint space : inflammation and destruction of synovial lining of the joint, leading to reduced space between the bones
* Juxta-articular osteoporosis : loss of bone density of joints
* Soft-tissue swelling : swelling secondary to inflammation of the synovial lining
* Subluxation : partial dislocation due to severe bone destruction

Question 7

Rheumatoid arthritis : Blood test findings

Answer 7

Blood test
1. Antibody test
* First line : Rheumatoid factor
* Second line : Anti-CCP antibody

2. Acute phase reactants
   * CRP and ESR - raised

Question 8

RA : Diagnosis

Answer 8

1. Clinical diagnosis
2. American college of rheumatology criteria : 6/10 points required
   * Small joint involvement (4-10)
   * Serology of RF and ACPA } 1 x to be positive
   * ECR/CRP } abnormal
   * Duration of sx > 6 weeks

Question 9

RA : Management

Answer 9

1. First line : DMARD monotherapy +/- bridging prednisolone
   * Methotrexate, Sulfasalazine, Hydroxychloquinine

If two inadequate response to 2x DMARDS;

2 . Second line : TNF inhibitors
* Etarnecept, infliximab, adalimunab

1. Monitoring response to treatment : CRP and composite score such as DAS28 to assess response to treatment
2. Flares : Corticosteroids and analgesia

Question 10

DMARDS : Side effects

Answer 10

• Leflunomide :

1 . Hypertension
2 . peripheral neuropathy

• Sulfasalazine:
  1. Orange urine and male infertility (reduces sperm count)
  2 . Allergy to aspirin - can cause cross sensitivity
  3. Pneumonitis/Lung fibrosis
  Safe in pregnancy and breast feeding
• Hydroxychloroquine:
  1 . Retinal toxicity,
  2 . blue-grey skin pigmentation and hair bleaching
• Anti-TNF medications: Reactivation of tuberculosis
• Rituximab: Night sweats and thrombocytopenia

Question 11

Methotrexate : MOA + SE

Answer 11

MOA : inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines

Side effects :
* Mucositis - inflammation of mouth and gut
* Myelosuppression,
* Liver cirrhosis,
* Pneumonitis (non productive cough, dyspnoea, malaise, fever)
* Pulmonary fibrosis

Question 12

Methotrexate : Administration

Answer 12

1. Folic acid co prescribed - 24 hours after dose of methotrexate
2. Monitoring : FBC, U+E, LFTs prior to starting treatment, repeated weekly until therapy is stabilised - monitored every 2-3 months
3. Interactions : avoid px trimethoprim due to risk of bone marrow suppression, high dose aspirin increases risk of methotrexate toxicity secondary to reduced excretion.

Question 13

Sjogren’s syndrome : Definition

Answer 13

s an autoimmune disorder affecting exocrine glands resulting in dry mucosal surfaces.

It may be primary (PSS) or secondary to rheumatoid arthritis or other disorders

Question 14

Sjogren’s syndrome : Incidence

Answer 14

1. Sjogren’s syndrome is much more common in females (ratio 9:1).
2. There is a marked increased risk of lymphoid malignancy (40-60 fold)

Question 15

Sjogren’s syndrome : Clinical features

Answer 15

• dry eyes: keratoconjunctivitis sicca
• dry mouth
• vaginal dryness
• arthralgia
• Raynaud’s, myalgia

Question 16

Sjogren’s syndrome : Ix

Answer 16

• rheumatoid factor (RF) positive in nearly 50% of patients
• ANA positive in 70%
• anti-Ro (SSA) antibodies in 70% of patients with PSS

Question 17

Sjogren’s syndrome : Mx

Answer 17

• artificial saliva and tears
• pilocarpine may stimulate saliva production