Painful Joints

Question 1

What is Gout?

Answer 1

Most common inflammatory arthritis in men and older women – caused by the deposition of monosodium urate monohydrate crystals in and around synovial joints

Question 2

What are the risk factors for gout?

Answer 2

1. Sex - Men
2. Age
3. Increased serum uric acid (SUA) levels - Hyperuricaemia - defined as an SUA of more than 2 standard deviations from the mean (increases with age, BMI and sex - males)
4. Other diseases - General Osteoarthritis - reduction in levels of proteoglycan and other inhibitors of crystal formation

Even though, Hyperuricaemia is a strong risk factor for Gout, only a minority of Hyperuricaemia individuals develop gout

Increased prevelance in affluent socities - increased levels of obesity and metabolic syndrome.

Question 3

Describe the metabolism of uric acid in the body.

Answer 3

1/3 of uric acid pool derived from the diet (purine intake), whereas the other 2/3 derived from endogenous purine metabolism

Network of enzymes involved in uric acid production – main one - xanthine oxidase catalyses the conversion of hypoxanthine to xanthine and xanthine to uric acid

Product of purine metabolism - Adenosine and guanine

Concentration of uric acid in body fluids depends on the balance between endogenous synthesis, and elimination by the kidneys (two-thirds) and gut (one-third)

Question 4

What is the main cause of hyperuricaemia?

Answer 4

Main cause of hyperuricaemia (90% of patients) is reduced uric acid excretion from the kidney – genetically determined + also occurs during renal failure

Attached image shows the different potential drivers/causers of high hyperuricaemia

Regardless… build up of uric acid crystals – drives activation of inflammation

Question 5

How does gout present clinically?

Answer 5

Classical presentation – acute monoarthritis - affects the first metatarsophalangeal in 50% of cases (big toe)

Other common sites include… ankle, midfoot, knee, small joints of hands, wrist and elbow. Axial skeleton and large proximal joints are rarely involved

Typical feature – presents as ‘attacks’
a) rapid onset, reaching maximum severity in 2–6 hours, and often waking the patient in the early morning
b) Severe pain, often described as the ‘worst pain ever’
c) Extreme tenderness, such that the patient is unable to wear a sock or to let bedding rest on the joint
d) Marked swelling with overlying red, shiny skin
e) Self-limiting over 5–14 days, with complete resolution.
f) After attack subsidies – pruritus (itchy dry skin) & desquamation (skin peeling)

• Possibility of accompanying fever, malaise and even delirium – larger joints involved like the knee

Question 6

Can people develop chronic gout?

Answer 6

Yes, people with continuous attacks may end up suffering from chronic gout

Tophi – feature of longstanding gout – crystal deposition in joints and tissue as irregular soft nodules

Question 7

What is the differential diagnosis for gout?

Answer 7

Differential diagnosis - septic arthritis, infective cellulitis or reactive arthritis

Question 8

What type of investigations are performed to confirm the presence of gout?

Answer 8

Gout can be confirmed by identifying urate crystals in the aspirate of a joint, bursa or tophus.

Appearance
- Acute gout – synovial fluid appears turbid – presence of neutrophils
- Chronic gout – variable presentation – occasionally fluid appears white due to urate crystal presence

Biochemical screen should be performed…
- renal function, uric acid, glucose and lipid profile – note during an attack serum urate levels may be normal as they drop when in an inflammatory state
- Acute gout – elevated levels of ERP (erythrocyte sedimentation rate) and CRP (C-reactive protein)

X-ray
- X-rays normally look normal but high levels of joint erosion is apparent in chronic and tophaceous gout

Question 9

How is gout managed (general terms)?

Answer 9

Focus on dealing with the acute attack and then introducing prophylaxis to lower SUA and prevent further episodes.

Question 10

What treatment is used in an acute attack of gout?

Answer 10

Acute episode
- First choice of treatment – Colchicine – inhibits microtubule assembly in neutrophils. Note oral NSAIDs are also effective but are typically not used as patients have other conditions (cardiovascular, cerebrovascular or chronic kidney disease)
- Oral prednisolone (15–20 mg daily) or intramuscular methylprednisolone (80–120 mg daily) for 2–3 days - effective for elderly patients that have increased risk of toxicity towards colchicine and NSAIDs
- Local ice packs help alleviate symptoms
- Joint aspiration coupled with intra-articular glucocorticoid injection

Question 11

What type of prophylatic treatment is used for gout?

Answer 11

Prophylaxis – more than 1 attack in 12 months – consider prophylaxis treatment – goal reduce levels of serum uric acid

a) Allopurinol – first drug of choice - inhibits xanthine oxidase – reducing uric acid levels
b) Febuxostat – given when there is an inadequate response to allopurinol
c) Lifestyle measures – equally as important - lose weight where appropriate, reduce excessive alcohol intake, examine patient’s current drug use as some can elevate SUA and avoid the consumption of high amounts of seafood and offal

Question 12

What is septic arthritis?

Answer 12

Septic arthritis is an infection in the joint (synovial) fluid and joint tissues

Most rapid and destructive bone disease

Associated with significant morbidity and mortality – 10%, for which the most important risk factor is age

Question 13

What is the pathogenesis of septic arthritis?

Answer 13

Normally occurs via the haematogenous (blood) spread from infections of the skin or upper respiratory tract

Infection from direct puncture wounds or joint aspiration is less common

Question 14

What are the risk factors for septic arthritis?

Answer 14

• Risk factors include….
  a) Increasing age
  b) Pre-existing joint disease (principally RA)
  c) Diabetes mellitus
  d) Immunosuppression (by drugs or disease)
  e) Intravenous drug misuse.

Question 15

What are the clinical features of septic arthritis?

Answer 15

1. Acute or subacute monoarthritis
2. Joint is usually swollen, hot and red, with pain at rest and on movement
3. Fever
4. Commonly Knee and hip joint

Responsible organism - Staphylococcus aureus (most common), gonococcus (- Young, sexually active adults), Gram-negative bacilli or group B, C and G streptococci (edlerly and intravenous drug users)

Question 16

What investigations are performed to confirm the presence of septic arthritis?

Answer 16

1. Joint aspiration – if the joint is not accessible, this should be performed under imaging guidance in theatre –> Synovial fluid sent for gram stain and culture – cultures are positive in 90% of cases, whereas gram stains are positive in 50% of cases
2. Blood cultures should also be taken
3. The synovial fluid is usually turbid or blood-stained but may appear normal.
4. Blood panel - Leucocytosis (elevation in white blood cell count) with raised ESR and CRP in most patients - may be absent in eldelry and immunocompromised

Question 17

What is the treatment/management for septic arthritis?

Answer 17

Medical emergency - Patient should be admitted to hospital

• Intravenous antibiotic - Flucloxacillin - antibiotic of choice
• Pain releif - oral and/or IV intravenous analgesics - consider ice pack use.

Question 18

What is rheumatoid arthritis?

Answer 18

Rheumatoid arthritis - auto-immune inflammatory arthritis - causing pain, swelling and stiffness in joints

Occurring throughout the world and in all ethnic groups

Prevalence of 0.8-1% and it is more common in women

Chronic disease characterized by exacerbations and remissions

Stiffness for 1-2 hours in the morning

Question 19

Outline the pathophysiology of RA?

Answer 19

Interplay between genetic and environmental factors

GWAS - 100 loci associated with RA - strongest association with HLA variants

Current theory – environmental stimulus (infection) triggers an autoimmune response by modulating host surface proteins

Disease characterized by infiltration of the synovial membrane with lymphocytes, plasma cells, dendritic cells and macrophages

Evidence for a strong role for T and B cells
a) T-cells produce cytokines
b) B-cells produce auto-antibodies
c) macrophages also involved
Net result inflammation

Question 20

What are the clinical features of RA?

Answer 20

Typical presentation is with pain, joint swelling and stiffness affecting the small joints of the hands, feet and wrists in a symmetrical fashion.

Large joint involvement, systemic symptoms and extra-articular features may also occur

Characteristic deformities may develop with long-standing uncontrolled disease, although these have become less common over recent years with more aggressive management

Question 21

What are some systemic features associated with RA?

Answer 21

• Anorexia, weight loss and fatigue may occur throughout the disease course
• Osteoporosis is a common complication and muscle-wasting may occur as the result of systemic inflammation and reduced activity.
• Extra-articular features are most common in patients that have a longstanding history with the condition - this includes…

a) Nodules
b) Vasculitis
c) Ocular Involvement
d) Serositis (inflammation of the serous – lining of the lungs, heart and abdomen)
e) Cardiac involvement
f) Pulmonary involvement
g) Peripheral neuropathy
e) Spinal cord compression

Question 22

What investigations are performed for a RA diagnosis?

Answer 22

Clinical diagnosis - The process of identifying a disease, condition, or injury from its signs and symptoms.

Assess patient history - multiple joints with pain and tenderness, symmetrical and symptoms for weeks to months

Investigations are useful to confirm the diagnosis and assess disease activity
a) ESP and CRP are usually raised
b) Tests for ACPA (Anti-citrullinated peptide antibody)
c) RF (Rheumatoid factor) is also elevated - less specific than ACPA
d) X-ray used to assess the amount of damage towards joints

Question 23

What are the pharmacological and non-pharmacological therapies used for RA?

Answer 23

Pharmacological

Disease modifying antirheumatic drugs (DMARD) – should be introduced for all patients as this improves disease outcome, main ones
a) Prednisolone
b) Methotrexate
But a range of others can be used if these are shown to be ineffective

Suppress inflammation using…
a) Nonsteroidal anti-inflammatory drugs
b) Corticosteroid

Biologic treatment also a possibility - TNF inhibitors

Transient flares can be treated with glucocorticoids but if sustained flares appear than changes in systemic DMARD or biologic therapies need to be considered.

Non-Pharmacological therapy
Physical and occupational therapy play important roles

Question 24

Is surgery an option for RA?

Answer 24

Surgery

• Synovectomy can be considered if DMARD fails - refers to the destruction or surgical removal of the membrane (synovium) that lines a joint.
• Joint replacement surgery may be required but the need for this has diminished over recent years

Question 25

What is the difference between incidence and prevelance?

Answer 25

Prevalence: Number of people in a population who have a disease or other health outcome at one point in time

Incidence: Number of people in a population who develop a disease or other health outcome over a period of time (i.e. new cases over a period of time)

What’s the difference?
Prevalence includes all cases, both new and pre-existing, in the population at the specified time, whereas incidence is limited to new cases only.

Question 26

What are the clinical symptoms associated with sepsis?

Answer 26

Question 27

What should you do if you have an acute hot, inflammed, tender joint?

Answer 27

Exclude septic arthritis!

Aspirate joint, send blood cultures