Case 4

Martha, a 50-year-old lady, presents to your surgery complaining of a 5-month history of stiff painful wrists, and of swelling in her hands. She tells you the hand stiffness is worse when she wakes, and that she also has morning foot pain and a feeling of walking on marbles. Martha also tells you that she can move freely after being awake for a few hours. You suspect Martha has a form of arthritis.

a) Define arthritis

‘A disease causing painful inflammation and stiffness of the joints’.


b) What is osteoarthritis? Summarise the disease process

Osteoarthritis is the most common joint disease and most commonly affects the knees, hips and small joints of the hands. It is caused by a complex interaction between genetic, metabolic, biochemical and biomechanical factors. It is characterised by inflammation affecting cartilage, subchondral bone, ligaments, menisci, synovium and the joint capsule.

Osteoarthritis can be further subdivided into primary and secondary.

Primary osteoarthritis is due to genetic factors and occurs in the absence of a precipitating insult.

Secondary osteoarthritis is more common and occurs as a sequela of joint pathology, e.g. trauma, infection, joint defects, inflammatory conditions.


Destruction and repair of articular cartilage occurs alongside each other, but destruction predominates leading to progressive degeneration of the joint. Destruction is driven by interleukin-1 and tumour necrosis factor release.


There are 3 pathological stages in the disease progression:

  1. Proteolytic degradation of the cartilage matrix.
  2. Fibrillation (splitting) of the cartilage surface – ulceration of the cartilage in this stage exposes underlying bone, producing microfractures and cysts. Attempts to repair the damage lead to subchondral sclerosis and osteophyte formation.
  3. Chronic synovitis – triggered as cartilage particles are engulfed by phagocytes associated with the synovium. Synovitis causes a thickening and fibrosis of the joint capsule that increases joint stiffness and deformity.


c) What is rheumatoid arthritis? Summarise the disease process.

Rheumatoid arthritis is an autoimmune condition whereby the IgM auto-antibody forms immune complexes found in joint synovium, fluid and elsewhere. Secondary changes then occur in the cartilage:

  • Wayward immune response causes synovial inflammation
  • Recruitment of PMNs, macrophages and lymphocytes
  • Phagocytosis of immune complexes and release of lysosomal enzymes
  • Destruction of joint cartilage and recruitment of further inflammatory cells
  • Vasodilation causes redness and swelling
  • Hyperplasia of synovium and angiogenesis: vascular granulation tissue – pannus
  • Inflammatory cells in pannus destroy cartilage and bone and cause anylosis (stiffening and fusion)


d) What differences in symptoms would patient’s report between rheumatoid arthritis and osteoarthritis? Which form of arthritis do you think Martha has?


  • Usually begins after 40 years
  • Develops slowly, over many years
  • Usually affects weight bearing joints such as knee, hip, lower spine, may be uni or bilateral.
  • Pain begins with the use of joints, inflammatory signs are less common
  • Morning stiffness usually lasts <20 mins
  • Does not cause a general feeling of unwellness



  • Can begin as young as 25 in some cases
  • Develops within weeks or months
  • Usually symmetrical, primarily affects small joints, may involve large joints like the elbow
  • Signs of inflammation present (in Martha’s case, swelling!
  • Morning stiffness often > 1 hour
  • Generalised symptoms such as fatigue, weight loss and anaemia may be present


Judging by her symptoms, Martha is more likely to have rheumatoid arthritis due to her onset of symptoms, bilateral distribution, inflammation and prolonged morning stiffness.


e) What blood tests can you perform to aid in your diagnosis of rheumatoid arthritis?

  • FBC – anaemia
  • ESR/CRP – moderately raised
  • Immunology – Rheumatoid factor (raised in ~70% of cases), Anti-cyclic citrullinated peptide antibodies (Anti-CCP) (positive in ~60% cases)
  • Liver profile – increased ALP, decreased albumin


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