Rheumatoid Arthritis (& other types)

Question 1

What is rheumatoid arthritis?

Answer 1

• a chronic, systemic inflammatory autoimmune disorder that primarily affects the joints
• it can also manifest with extraarticular features
• it is idiopathic with unknown aetiology

Question 2

Who tends to be most affected by rheumatoid arthritis?

Answer 2

• incidence is highest in women over 65 years of age

Question 3

What are the risk factors for rheumatoid arthritis?

Answer 3

• genetic disposition - associated with HLA-DR4 and HLA-DR1
• environmental factors (e.g. smoking)
• hormonal factors
  
  • premenopausal women are at the highest risk, suggesting a role of female sex hormones
• infection
• obesity
• family history of RA
• Remember “ a DRone with 4 propellers and 1 camera”*
• it is associated with HLA-DR4 and HLA-DR1*

Question 4

What is the pathophysiology involved in rheumatoid arthritis?

Answer 4

• certain interstitial tissue proteins undergo a post-translational modification that involves conversion of arginine to citrulline
  
  • this is citrullination
• citrullinated proteins are recognised as foreign by antigen-presenting cells that present them to CD4+ T-cells
• activation of CD4+ T cells

Question 5

How does activation of CD4+ T-cells result in inflammation?

Answer 5

• IL-4 production, which leads to B-cell proliferation and differentiation
• this leads to production of anticitrullinated peptide antibodies
• this produces a type II and type III hypersensitivity reaction
• CD4+ T cells then migrate to synovial joints and secrete cytokines (IFN-y & IL-17)
• there is recruitment of macrophages and secretion of cytokines (TNF-a, IL-1, IL-16) which leads to inflammation and proliferation

Question 6

How is there destruction of cartilage and bone in rheumatoid arthritis?

Answer 6

• bouts of inflammation, angiogenesis and proliferation lead to production of proliferative granulation tissue with mononuclear inflammatory cells
• this produces pannus and synovial hypertrophy
  
  • ​pannus is a growth of granulation tissue from the inflamed synovium into the joint space
  • it can destroy other intra-articular structures such as cartilage
• this leads to invasion, progressive destruction and deterioration of cartilage and bone

Question 7

What particular detectable antibodies are produced in rheumatoid arthritis and what does their presence suggest?

Answer 7

• antibodies against the Fc portion of IgG are produced
• these are called rheumatoid factors
• they are produced to remove autoantibodies and immune complexes
• individuals with positive RF are more likely to develop extraarticular manifestations

Question 8

What are the articular manifestations of rheumatoid arthritis?

Answer 8

• polyarthritis - multiple joints are affected
• there is symmetrical pain and swelling of affected joints (also at rest)
• morning stiffness (often > 30 minutes) that improves with activity
• joint deformities

Question 9

Which joints tend to be affected by rheumatoid arthritis?

Which joints are less commonly affected?

Answer 9

• metacarpophalangeal joints (MCP)
• proximal interphalangeal joints (PIP)
• wrist joints and knee joints
• the distal interphalangeal (DIP) joints tend NOT to be affected

Question 10

What is “rheumatoid hand”?

What 3 deformities is this mainly associated with?

Answer 10

this typically manifests with one or more deformities:

• swan neck deformity
  
  • PIP hyperextension and DIP flexion
• boutonniere deformity
  
  • ​PIP flexion and DIP hyperextension
• Hitchhiker thumb deformity (or Z deformity of thumb)
  
  • ​hyperextension of the interphalangeal joint with fixed flexion of the MCP joint
• there may also be ulnar deviation of the fingers

Question 11

What is the physical examination used in rheumatoid arthritis?

Answer 11

Gaenslen squeeze test

• painful compression of hands (or feet) at the level of the MCP (or MTP) joint
• a painful handshake is an early sign of arthritis
  • compression of the hand leads to lateral pressure on the synovial membrane of MCP joints

Question 12

What are the constitutional symptoms associated with RA?

Answer 12

• low-grade fever
• myalgia (muscle aches)
• malaise
• fatigue
• weight loss
• night sweats

Question 13

What are rheumatoid nodules and which areas of the body are affected by them?

Answer 13

• they are nontender, firm, subcutaenous swellings (2mm - 5cm)
• they commonly occur in areas exposed to higher pressure
  
  • e.g. extensor side of the forearm or bony prominences
• they can also affect the lungs and tend to be bilateral and peripheral

Question 14

What is Caplan syndrome?

Answer 14

• rheumatoid pulmonary nodules that are accompanied by fibrosis and pneumoconiosis
• pneumoconioses are restrictive ILDs associated with the inhalation of certain dusts
  
  • asbestosis and silicosis are the most common
• this occurs in people with RA who have breathed in certain dusts or silica

Question 15

What are the extraarticular manifestations of RA affecting the lungs and eye?

Answer 15

Lungs:

• pleuritis (causing pleuritic chest pain)
• pleural effusions
• interstitial lung disease

Eyes:

• keratoconjunctivitis sicca (“dry eye” disease)
• scleritis
• episcleritis

Question 16

What is the consequence of RA affecting the endocrine and exocrine glands?

How does this present?

Answer 16

secondary Sjögren syndrome

• autoimmune disease characterised by inflammatory destruction of the lacrimal and salivary glands
• patients present with xerophthlamia (dry eyes) and xerostomia (dry mouth)

Question 17

What are the haematological extraarticular manifestations of RA?

Answer 17

• normocytic anaemia as a result of anaemia of chronic disease
  
  • this can be normocytic or microcytic with elevated ferritin
  • mediated through hepcidin and cytokines
• microcytic anaemia as a result of NSAIDs causing increased risk of GI bleeding, leading to iron-deficiency anaemia
• macrocytic anaemia due to treatment with methotrexate decreasing folate levels
• neutropenia
• splenomegaly
• lymphoma / large granular lymphocyte leukaemia

Question 18

what are the extraarticular manifestations of RA affecting the musculoskeletal system and the heart?

Answer 18

Musculoskeletal:

• carpal tunnel syndrome
• tenosynovitis and bursitis
  • tenosynovitis is inflammation of a tendon and its synovial sheath

Heart:

• pericarditis and myocarditis
• increased risk of MI, stroke, CHF & AF

Question 19

What are the vascular extraarticular manifestations of RA?

Answer 19

• peripheral vasculitis, which manifests as livedo reticularis
  
  • reddish-blue discolouration of the skin in a net-like (reticular pattern) due to blood vessel spasm
• Raynaud phenomenon
• purpura
  
  • ​a purple-red nonblanchable cutaneous or mucosal lesion due to extravasation of blood into skin or mucous membranes
• vasculitic ulcers
• peripheral neuropathy
  
  • ​peripheral nerve damage characterised by distal sensory loss, burning sensation and/or weakness

Question 20

What criteria is used in the diagnosis of RA?

Answer 20

ACR criteria

• there must be a score of 6 or more points + confirmed presence of synovitis in at least one typical joint
• score is obtained by adding the points from each feature

Question 21

What are the nonspecific parameters that may be present in laboratory tests for RA?

Answer 21

• raised inflammatory markers:
  
  • raised CRP and ESR which correlate with inflammatory activity
  • raised ferritin as an acute phase protein
  • possible leukocytosis and/or thrombocytosis
• anaemia of chronic disease

Question 22

What are the 2 serology tests that can be done in the diagnosis of RA?

Answer 22

Anticitrullinated peptide antibodies (ACPA):

• this is usually anti-CCP
• this test has a specificity of >90%, allowing earlier detection of RA

Rheumatoid factor (RF):

• IgM autoantibodies against the Fc region of IgG
• present in 60-80% patients but low specificity, as it may be raised for other causes of chronic inflammation

Question 23

What is the typical X-ray performed to assess RA?

What are early and late radiological findings?

Answer 23

• dorso-palmar X-ray of both hands
• early changes include soft tissue swelling and juxta-articular demineralisation
• late changes include joint space narrowing, erosions of cartilage and bone, general demineralisation and subchondral cysts

Question 24

What are subchondral cysts?

Answer 24

• marginal erosions seen on imaging that correlate with pannus invasion of bone
• they are fluid-filled spaces inside a joint

Question 25

How is disease activity of RA measured? What is mild disease activity?

Answer 25

* typically there are periods of **minimal / no symptoms** alternating with periods of **increased disease activity**

Question 26

What are the features of moderate disease activity?

Answer 26

Question 27

What are the characteristics of severe disease activity?

Answer 27

Question 28

What are the general measures in the treatment of RA?

Answer 28

* encouraging regular physical activity * application of heat or cold packs as needed * heat reduces pain and relaxes muscles * cold will reduce swelling *

Question 29

What is the main source of acute anti-inflammatory therapy in RA and how long is it given for?

Answer 29

**_glucocorticoids_** * given until the onset of action of DMARD or as a long-term therapy for highly active RA * usually involves **_prednisolone_** systemically or via **intra-articular injection** * **_osteoporosis prophylaxis_** is needed by optimising **calcium** and **vitamin D intake**

Question 30

What is an alternative acute anti-inflammatory therapy used in RA that does not improve prognosis?

Answer 30

* **_NSAIDs_** and **_selective COX-2 inhibitors_** provide symptomatic relief * comedication with a **_PPI_** is recommended as combining glucocorticoids with NSAIDs substantially **_increases risk of GI ulcers_**

Question 31

Who should not be given NSAIDs for symptomatic relief of RA?

Answer 31

* patients \> 60 years * impaired renal function * on antiplatelet agents or blood thinners * history of or active peptic ulcer disease

Question 32

What are DMARDs? When should they be given to RA patients and what are the benefits?

Answer 32

* disease-modifying antirheumatic drugs * they **_induce immunosuppression_**, leading to potential **remission** of RA * they should be given to anyone with RA, regardless of disease activity * DMARD therapy **_slows progression_** of disease, **_preserves joint function_** and limits RA complications

Question 33

Why are glucocorticoids still given initially with DMARD therapy?

Answer 33

* DMARDs have a **_slow onset of action_** (6 weeks or more) * symptomatic treatment with glucocorticoids and/or NSAIDs is often required

Question 34

What is the drug of choice to use as a DMARD? What must be checked before starting this, and what other medication is recommended?

Answer 34

**_methotrexate_** * check **FBC** and **LFTs** before starting * methotrexate can cause pancytopenia due to bone marrow suppression and hepatotoxicity * **_folic acid_** should be given **24-48 hours after** taking methotrexate to minimise side effects * NSAIDs should not be taken on the same day as MTX as they can worsen side effects by inhibiting renal excretion