Gout
- Derangement in purine metabolism resulting in hyperuricaemia, monosodium urate crystal deposits in tissues (tophi), synovium (microtophi)
Epidemiology:
- Most common in males >45 years, Extremely rare in premenopausal women
- Mainly occurs and in a younger age in Men (40-50yo) c/w Women (60+)
- Acute attack is very painful with excruciating pain
- Tender to even fine touch Skin over the affected joint is red, swollen, hot, shiny
- Can be precipitated by EtOH excess, starvation, recent surgery, or diuretics Relief with colchicine, NSAIDs and Steroids
- Can subside 3-10days without treatment
- Usually a monoarthritis in 90% of attacks (MTP joint greater toe 75%)
Hyperuricemia: Due to dietary excess, overproduction of urate (<10% of cases) or relative under-secretion of urate (>90% of cases)
- Primary: Most due to idiopathic renal under-secretion (90%) but some are due to overproduction or abnormal enzyme production/function
- Secondary:
- Undersecretion: Renal failure, drugs (diuretics, ASA, ethanol, cyclosporine, levodopa, vitamin B12, nicotinic acid), conditions (sarcoidosis, hypothyroidism, hyperparathyroidism, trisomy 21, preeclampsia)
- Overproduction – ↑ nucleic acid turnover (haemolysis, myeloprolifeative disease, psoriasis, rhabdomyolysis, exercise, exercise, obesity)
- Most people with hyperuricaemia do not have gout and low or normal uric acid levels does not rule out gout. Sudden changes in uric acid levels, temperature & pH are more important than actual levels
- Common precipitants: Alcohol, dietary excess, dehydration, trauma, illness, surgery, TLS
- Associated conditions: HTN, obesity, diabetes, starvation
- Disease progress
- Acute gout 🡪 remission 🡪 acute gout 🡪 remission 🡪 … 🡪 prolonged attacks + incomplete remission 🡪 chronic gout 🡪 tophi (pinna, tendon, jt, eye) + jt destruction
Risk factors of hyperuricemia and gout
| Modifiable risk factors | Nonmodifiable risk factors |
| Hypertension | Age |
| Obesity | Genetic variants |
| Hyperlipidemia | Gender |
| Diabetes mellitus | Ethnicity |
| Cardiovascular disease | |
| Alcohol | |
| Medications altering urate balance | |
| Chronic kidney disease | |
| Dietary factors |
Causes of Hyperuricemia
| Clinical disorders leading to urate and/or purine overproduction | Drug, diet, or toxin-induced urate and/or purine overproduction | Inherited enzyme defects leading to purine overproduction (rare monogenic disorders) | Causes of hyperuricemia due to decreased uric acid clearance |
| Malignancies | Cytotoxic drugs | Glucose-6-phosphatase deficiency (glycogen storage disease, type I) | Diabetic or starvation ketoacidosis |
| Hemolytic disorders | Ethanol | Hypoxanthine-guanine phosphoribosyltransferase deficiency | Lactic acidosis |
| Myeloproliferative disorders | Fructose (high fructose corn syrup) | Phosphoribosylpyrophosphate synthetase overactivity | Chronic renal insufficiency of any form |
| Lymphoproliferative disorders | Ethylamino-1,3,4-thiadiazole | Lead nephropathy (saturnine gout) | |
| Tissue hypoxia | Vitamin B12 deficiency | Hyperparathyroidism | |
| Down syndrome | Pancreatic extract | Sarcoidosis | |
| Psoriasis | Excessive dietary purine ingestion | Chronic beryllium disease | |
| Glycogen storage diseases (types III, V, VII) | 4-amino-5-imidazole carboxamide riboside | Hypothyroidism | |
| Obesity | Preeclampsia | ||
| Insulin Resistance syndrome | Effective volume depletion (e.g., fluid losses, heart failure) |
Clinical presentation
- Trigger:
- stress
- medical illness especially cardiovascular illnesses
- surgical procedure
- recent trauma
- dehydration
- starvation
- dietary factors
- high purine foods such as organ meats or seafood, beer, wine, and spirits
- drugs
- aspirin, diuretics, or even allopurinol).
- stress
- Acute gouty arthritis
- Painful, usually involving lower extremities (e.g. 1st MTP joint)
- Precipitation of urate crystals in the joint space
- Involvement of big toe (“podagra”)
- May progress to mimic cellulitis, but in cellulitis will be able to move joint
- Attack will subside on its own within several days to weeks and may or may not recur
- Tophi
- Urate depositions in cartilage, tendons, bursae, soft tissues and synovial membranes
- Common sites: 1st MTP, ear helix, olecranon bursae, tendon insertions, pressure points
- Painless, but may limit joint mobility
- Kidney
- Gouty nephropathy
- Uric acid calculi
Diagnosis:
- A normal or low serum urate does not exclude the diagnosis of acute gout
- because the concentration may not be elevated during an acute attack
- Losartan, atorvastatin, fenofibrate and calcium channel blockers falsely lowers uric acid levels
- Low-dose aspirin and thiazide diuretics falsely increase uric acid levels
- Joint aspirate
- needle-shaped monosodium urate (MSU) crystals
- negatively birefringent under polarized light.
- Imaging:
- dual-energy CT scan
Differential Diagnosis
- Septic Arthritis
- Critical to distinguish (especially in large joints: Shoulder, elbow, hip and knee)!
- Concurrent infection with gout history may occur (esp. knee, and to lesser extent in ankle, Shoulder, wrist)
- A red, warm, edematous joint is only proven not septic by Joint Aspiration (do not assume gout)
- Pseudogout (Calcium pyrophosphate deposition disease)
- Differentiate from gout based on Joint Fluid analysis
- Trauma
- Trauma may also precipitate a gout flare
Treatment:
ACUTE GOUT
- NSAIDS
- All drugs in this class have equal efficacy.
- Avoid in elderly, renal or liver disease, Heart Failure, or Peptic Ulcer Disease: In these cases, use Corticosteroids instead
- Indomethacin (historically has been preferred NSAID in gout)
- Start: 50 mg orally three times daily for 2-3 days
- Then: 25 mg orally three times daily for 4-10 days
- Naproxen 500 mg orally twice daily for 4-10 days
- Prednisolone
- Oral prednisolone 35 mg daily has been shown to effectively treat the symptoms of acute gout,
- 15–20 mg daily is often recommended
- It can usually be stopped after 3–5 days.
- Colchicine
- 1 mg as soon as possible – Most beneficial if started within first 24 hours of attack
- then 500 micrograms one hour later (maximum 1.5 mg per course)
- May be ineffective if started >3-4 days after symptom onset
- Do not repeat the course within three days
- Synthetic ACTH (Tetracosatrin 1mg IM)
Prophylaxis
- When starting urate-lowering therapy concomitant prophylaxis should be provided for a minimum of six months to prevent flares of gout.
- It is common for flares of gout to occur when starting treatment and when changing the dose.
- Preventing these flares is a goal of treatment
- Firstline:
- NSAIDs
- low-dose colchicine
- 500 mcg of colchicine BD for people with normal renal function
- 500 mcg daily in those with renal impairment, may be considered
- Colchicine is equal to NSAIDs for long-term prophylaxis, however short-term NSAIDs or oral glucocorticoids may be appropriate depending on the patient’s comorbidities and drugs
- Second line:
- low-dose prednisolone is second line
- Firstline:
Urate-lowering therapy
- After management of an acute attack, urate-lowering therapy should be considered in those with gout and at least one of the following:
Tophi ; >2 attacks a year ; Chronic kidney disease (stage 2 or worse); Urolithiasis
- Allopurinol (preferred)
- Start 100 mg orally daily
- Increase the daily dose by 50 mg every 2–4 weeks until the target serum uric acid concentration is reached
- target serum uric acid
- less than 0.36 mmol/L
- less than 0.30 mmol/L if tophi are present
- S/E: nausea or vomiting, rash or flaking of the skin ( rare: Stevens-Johnson syndrome, toxic epidermal necrolysis), eosinophilia, leucocytosis, fever, hepatitis and renal failure)
- Febuxostat
- If unable to tolerate allopurinol
- Febuxostat is metabolised by the liver and renal excretion is not a major route of elimination.
- febuxostat 40 mg = allopurinol 300 mg in efficacy.
- If the serum uric acid is greater than 0.36 mmol/L after 2–4 weeks of therapy, febuxostat 80 mg once daily is recommended.
- Probenecid
- is effective in patients with impaired renal function, contrary to previously held beliefs(NPS)
Prevention:
- Dietary Measures:
- Reduce intake of foods high in purines, such as
- Organ meat (liver, brain, kidneys, sweetbread)
- tinned fish (sardines, anchovies, herrings)
- shellfish and game
- sausages
- Limit intake of sweetened beverages
- Reduce intake of foods high in purines, such as
- Avoid or reduce alcohol consumption
- especially beer and spirits
- avoid drugs such as diuretics (thiazides, frusemide) and salicylates
- Weight Control:
- Losing weight if overweight can help reduce uric acid levels and manage gout.
- A higher body mass index (BMI) is positively correlated with higher serum uric acid concentration and metabolic syndrome.
- Adequate Hydration:
- Proper hydration is important in the treatment of gout.
- Drinking plenty of water can help flush out uric acid and prevent gout attacks.
- Exercise:
- Regular physical activity is beneficial in managing gout.
- Exercise helps in weight management and overall health improvement.
- In patients with recurrent gout: Allopurinol 100mg – 300mg Daily is the drug of choice (Beware renal insufficiency and elderly patients)
Complications
- Tophi, joint deformity, osteoarthritis, bone loss.
- Urate nephropathy and nephrolithiasis.
- Gout might also cause
- ocular complications: conjunctivitis, uveitis, or scleritis from the urate crystal precipitation
Pseudogout
(CPPD – Calcium PyroPhosphate Dihydrate)
- Commonly affects larger joints such as the knee, wrist, and shoulder.
- Symptoms include pain, swelling, and sometimes redness, often less severe than gout.
- Attacks may be less sudden and can last longer.
Occasionally signals underlying disorder:
- OA
- hypoMg
- haemochromatosis
- hypophosphatasia
- hyperparathyroidism
- Wilson’s dx
∴ screening test in young pseudogout px:
- Fe studies – ferritin
- ALP
- Ca
- PO4
- Mg
- PTH
- Diagnosis
- X-ray: chondrocalcinosis
- joint aspirate :
- calcium pyrophosphate dihydrate (CPPD) crystals
- rhomboid-shaped
- positively birefringent under polarized light
- Management
- NSAIDs
- intra-articular steroid injx
- colchicines is less effective than in gout
- Long-Term Management:
- There is no specific long-term medication to prevent pseudogout attacks. Treatment is usually focused on managing symptoms and underlying associated diseases.
- Chronic calcinosis:
- OA-like changes
- more severe
- calcium deposit on x-ray
