Crystal induced arthropathy - Rheumatology

Question 1

The two main types of crystal-induced arthritis?

Answer 1

б Distinguished by polarized light with a red filter.
1. Gout: Sodium urate.
2. Pseudo gout: Calcium pyrophosphate.
» Needle-shaped urate crystals, small, intracellular pyrophosphate crystal.
б Compensated polarized light microscopy of synovial fluids (x 400).
A. Monosodium urate crystals show bright negative birefringence under polarized light and needle-shaped morphology.
B. Calcium pyrophosphate crystals show weak positive birefringence under polarized light and are few in number. They are more difficult to detect than urate crystals.

Question 2

Gout definition and Pathogenesis ?

Answer 2

Gout:
» is an inflammatory arthritis associated with hyperuricemia and intra-articular sodium urate crystals, end product of human purine metabolism.
Hyperuricemia:
» Serum uric acid [SUA]: exceedingly approximately 6.8 mg/dL.
» Increase with:
1. age,
2. obesity,
3. and with western diet.

Pathogenesis of gout:
б SUA depends on the balance between:
1. purine synthesis,
2. ingestion of dietary purines
3. and the elimination of urate by the kidney (66%) & intestine (33%).
б 90%→ Impaired excretion of uric.
б 10% → Increased production due to high cell turnover.
б < 1% → Inborn error of metabolism.
б Acute gouty inflammation is initiated by resident synovial cells, including phagocytes, which secrete chemokines and cytokines to attract and activate the neutrophils.

Question 3

Gout examination?

Answer 3

1. Subcutaneous tophi:
   » Subcutaneous tophi along the helix of the ear are uncommon
   » Well-organized collection of monosodium urate crystals and is pathognomonic for gout, as is the destructive arthritis of advanced gout.
2. Large tophi:
   » Involving the distal interphalangeal joints are commonly seen in gouty patients with preexisting Heberden nodes.
   » This is particularly characteristic of late-onset gout.
3. Ulcerated tophus:
   » An ulcerated tophus revealing a Yellowish-white urate deposit.
4. Podagra or acute gout:
   » First metatarsophalangeal joint is Hyperintense erythema with a dusky hue is characteristic.
   » Area of inflammation usually extends beyond the region of the involved joint.
5. Advanced gout:
   » The hands and wrists demonstrate an asymmetric arthritis with articular & interarticular tophi.

Question 4

Gout investigations and management ?

Answer 4

Investigations:
1. Joint fluid microscopy:
» The most specific & diagnostic test but is technically difficult.
2. Serum uric acid:
» Usually raised (>6.8 mg/dL).
» If it is not, it should be rechecked several weeks after the attack, as levels fall immediately after an acute episode.
3. Serum urea, creatinine and eGFR.

Management:
1. NSAIDs or coxibs in high doses rapidly reduces the pain and swelling.
» The first dose should be taken at the first indication of an attack.
2. Naproxen: 750 mg immediately, then 500 mg every 8-12 hours.
3. Diclofenac: 75-100 mg immediately, then 50 mg every 6-8 hours, after 24-48 hours,
» reduced doses are given for a further week
» NSAIDs may cause renal impairment and peptic ulceration.

Alternative treatments include:
б Colchicine: Loading doses will cause diarrhea or colicky abdominal pain, so ( 500 μg 2-3 times/day ) is usually sufficient to terminate attacks without side- effects.
б Corticosteroids: Oral prednisolone or intramuscular or intraarticular depot methylprednisolone is used.

Dietary advice:
б These modifications can reduce serum urate by 15% and delay the need for drugs that reduce serum urate levels
б Reduce:
» Alcohol intake, » Carbonated soft drinks
» Purine-rich foods such as: offal, red meat, shellfish, spinach.

Agents that reduce serum uric acid:
б The aim of treatment is to reduce and maintain the uric acid level:
» below 5.5mg /dL in all patients
» below 5mg /dL in those with severe gout.
1. Allopurinol:
» Allopurinol is a xanthine oxidase inhibitor.
» Never be started within a month of an acute attack and always under cover of NSAIDs or colchicine for the first 2-4 week.
» Dose can be increased gradually from 100 mg every few weeks until uric acid level is below the 5.5 mg/dL level.
» Used at low doses (50-100 mg) in renal impairment.
2. Febuxostat:
» Febuxostat (80-120 mg) is a non-purine analogue inhibitor of xanthine oxidase.
» Well-tolerated and as effective as allopurinol.
» It is safer in renal impairment, as it undergoes hepatic metabolism.
» Allopurinol remains the drug of first choice, unless there are strong contraindications to its use.
3. Pegloticase:
» Pegylated recombinant uricase given intravenously lowers urate levels dramatically but is typically reserved for patients with severe refractory gout.
4. Uricosuric agents:
» Benzbromarone acts on the URAT1 transporter.
» Sulfinpyrazone and probenecid are best avoided in renal impairment.
» Losartan: Angiotensin I receptor antagonist and is uricosuric.