Rheumatoid Arthritis

Question 1

What is rheumatoid arthritis?

Answer 1

A chronic, systemic, inflammatory, autoimmune disease characterised by inflammation of the synovial joints.

Question 2

What causes rheumatoid arthritis?

Answer 2

Circulating antibodies which damage previously healthy tissue. These include cyclic citrullinated peptide (anti-CCP, specific to RA) and non-specific rheumatoid factor, an antibody which targets IgG antibody.

Question 3

What is a synovial joint?

Answer 3

Freely movable joints in which the bones are encased in smooth cartilage and are separated by a joint cavity which contains synovial fluid (made by synovial membrane). Examples include elbow, hip, wrist, pivot (neck), ankles.

Question 4

What are the risk factors for rheumatoid arthritis?

Answer 4

Genes e.g., HLA gene
Smoking
Gut microbiome
Hormonal factors

Question 5

What are the symptoms of rheumatoid arthritis?

Answer 5

Long-term joint pain accompanied by swelling, heat, and stiffness of the joints, as well as occasionally systemic symptoms including fever and fatigue.

Question 6

What are the main differences between presentation of RA and osteoarthritis?

Answer 6

Symptoms - symmetrical and of small joints vs asymmetrical and of weight-bearing joints.
Systemic symptoms - prominent vs unusual
Morning stiffness - >1 hour vs <30 mins
Worst time of day - morning vs progressive over day
Activity - lessens vs worsens
X-ray - damage and erosions of joints vs joint space narrowing (due to cartilage loss) and subchondral sclerosis (bone thickening).
Blood test - elevated anti-CCP and RF vs no changes

Question 7

What is first line treatment of rheumatoid arthritis?

Answer 7

A DMARD (disease-modifying anti-rheumatic drug).

Question 8

Name 3 DMARDs.

Answer 8

Methotrexate, Sulfasalazine, Leflunomide.

Question 9

How is methotrexate dosed?

Answer 9

7.5mg once weekly.

Question 10

How does MTX work?

Answer 10

Dihydrofolate reductase inhibitor which prevents aspects of nucleic acid synthesis, thus preventing DNA synthesis. This reduces cell division in rapidly dividing cells e.g., immune cells.

Question 11

What are some common side effects of MTX?

Answer 11

Mucositis (pain and inflammation of GIT)
Myelosuppression (reduced blood cell production)

Question 12

What can help reduce MTX side effects?

Answer 12

Folic acid 5mg weekly taken on a different day to MTX

Question 13

What conditions is MTX contraindicated/cautioned in?

Answer 13

Hepatic impairment - avoid
Renal impairment - caution and reduce dose
Blood disorders
Pregnancy

Question 14

What monitoring is required for MTX?

Answer 14

FBC
Renal function
Liver function
All baseline, then weekly until stabilised. Then every 2-3 months.

Question 15

What are some key MTX interactions?

Answer 15

NSAIDs - increase risk of toxicity.

Question 16

How does leflunomide work?

Answer 16

Dihydroorotate dehydrogenase inhibitor which prevents aspects of nucleic acid synthesis, thus preventing DNA synthesis. This reduces cell division in rapidly dividing cells e.g., immune cells.

Question 17

What are some common side effects of leflunomide?

Answer 17

Abdominal pain
Hair loss
GI discomfort
Leucopenia
Weight loss

Question 18

What conditions is leflunomide contraindicated/cautioned in?

Answer 18

Leucopenia
Thrombocytopenia
Anaemia
Pregnancy (teratogenic)
Hepatic impairment (metabolite accumulation)

Question 19

What monitoring is required for leflunomide?

Answer 19

Prior to prescribing: pregnancy test, FBC, LFT.
Repeat FBC and LFTs every 2 weeks for 6 months, then every 8 weeks.
Ensure pregnancy prevention throughout.
Monitor BP.

Question 20

What should be considered when stopping leflunomide?

Answer 20

Active metabolite persists for long time. If starting another DMARD or conception, give cholestyramine or activated charcoal for accelerated elimination.

Question 21

How does sulfasalazine work?

Answer 21

Amino-salicylate which inhibits leukotriene B4 to reduce synthesis of platelet activating factor an inhibit leucocyte adhesion molecule upregulation i.e., anti-inflammatory and immunosuppressive effect.

Question 22

What are some common side effects of sulfasalazine?

Answer 22

GI discomfort
Cough
Leucopenia
Skin reactions
Headache
Fever

Question 23

What conditions is sulfasalazine contraindicated/cautioned in?

Answer 23

Renal and hepatic impairment - avoid
Pregnancy 3rd trimester - ensure adequate folate supplements taken by mother to prevent neonatal haemolysis.

Question 24

How long do DMARDs take to work? What is the consequence of this?

Answer 24

DMARDs take 2-3 months to provide symptomatic relief, therefore short-term bridging with glucocorticoids (e.g., oral prednisolone) may be prescribed in the meantime.

Question 25

What can be given if a person presenting with RA is waiting for a specialist appointment?

Answer 25

NSAID (ibuprofen, naproxen, diclofenac) or coxib (celecoxib, etoricoxib).
PPI if NSAID is taken long-term.

Question 26

Name 2 types of biologics/anti-TNF alpha therapies used for RA and examples.

Answer 26

Interleukin-1 receptor antagonists - Anakinra.
IgG1l monoclonal antibodies - Infliximab, Adalimumab, Certolixumab.

Question 27

How do anti-TNF alpha therapies work in RA?

Answer 27

Inhibit inflammatory cascade signaling involved in joint erosion.

Question 28

How are anti-TNF alpha therapies administrated?

Answer 28

Anakinra - SC
MABs - IV and/or SC

Question 29

What screening and monitoring do anti-TNF alpha therapies require?

Answer 29

Screen for latent TB and viral hepatitis as they can cause resurgence of dormant diseases.
Monitor neutrophil count before and then monthly.
Monitor FBC, LFTs, renal function, lipid profile, BP, weight. (varies on DMARD)

Question 30

What parameters of DMARD monitoring indicate a referral?

Answer 30

WCC < 3.5 x 10^9/L
Mean cell volume >105fL
Neutrophils <1.6 x 10^9/L
Creatinine increased by >30%
cGFR <60ml/min
Eosinophilia >0.5 x 10^9/L
ALT >100 u/L
AST >100 u/L
Platelet count < 140 x 10^9/L
BP >140/90 mmHg

Question 31

How would a flare up of RA present?

Answer 31

Worsened stiffness, pain and/or swelling in the affected joints, and general fatigue. Also, increased C-reactive protein (marker for inflammation).

Question 32

How should a flare up in RA be dealt with.

Answer 32

1. Rule out septic arthritis (characterised by systemic symptoms and single hot and swollen joint).
2. Seek specialist advice. Give short-term glucocorticoids in the meantime.
3. Specialist - intra-articular glucocorticoid injection e.g., methylprednisolone acetate.
4. Add another DMARD if necessary.

Question 33

What does DAS8 indicate?

Answer 33

Level of disease activity of RA.

> 5.1 = high disease activity. Requires inflixamb treatment.

3.2-5.1 = active disease

<3.2 = low disease activity

<2.1 = disease remission

Question 35

Why should prednisolone and other oral steroids be weaned?

Answer 35

Abrupt withdrawal can cause acute adrenal insufficiency, hypotension or death. It can also lead to relapse.

Question 36

Why should oral steroids such as prednisolone be avoided longterm?

Answer 36

Prolonged use can lead to:
Adrenal suppression
Increase risk of infection
Ulcers
Osteoporosis

Question 37

How should oral prednisolone be weaned?

Answer 37

By 5mg every 3-5 days then stop

OR

If on higher doses, reduce down by 2.5mg every 3-4 days to 7.5mg per day then reduce more slowly e.g., by 2.5mg weekly.

Question 38

What considerations should be taken when putting a patient on a course of oral steroids?

Answer 38

Keep course as short as possible as can cause adrenal suppression.

Wean dose before stopping as risk of adrenal insufficiency and death.

Can cause ulcer if used longer than a month. So consider giving a PPI e.g., lansoprazole 15mg od.

Basal and continuous monitoring of BP, BMI, HbA1c, potassium.

Do they have diabetes or osteoporosis, as this can be worsened.