creation date: 2026-02-05 21:10
tags: Pathologies
Gout
Background
Definitions
Gout is a prevalent cause of chronic inflammatory arthritis. Gout is more common in older adults and in males.
Gout flare: episode of acute-onset painful inflammation
Intercritical gout: periods of time between gout flare which is typically asymptomatic
Chronic gouty arthritis and tophaceous gout: bone changes and tophi development results in symptomatic arthritis
Etiology and Risk Factors
Etiology of gout is usually multifactorial involving genetics, comorbidities, and dietary influences.
Genetic predisposition
40-50% of patients with gout have a positive family history. Genes associated with gout include those involved in:
- Production of uric acid
- Reabsorption of uric acid in kidneys
- Excretion of uric acid in kidneys
Cormorbidities
Obstructive sleep apnea is pathophysically linked to hyperuricemia (intermittent hypoxia increases uric acid production).
Other conditions that affect urate balance include:
- Obesity
- Hypertension
- Diabetes mellitus
- Chronic kidney disease
Certain medications may also have an effect (eg. diuretics).
Diet
Dietary sources that contribute to hyperuricemia include:
- Seafood (eg. lobster and shrimp)
- Organs (eg. liver and kidney)
- Red meat (eg. pork and beef)
- Alcohol
- Sweetened beverages (incl. those with high fructose corn syrup)
Causes of flare ups
A number of conditions can trigger flare-ups. Conditions include:
- Stress (eg. due to medical illnesses, recent surgical procedure, trauma, dehydration, starvation)
- Dietary choices
- Drugs
Pathogenesis
Uric acid is the final product of purine metabolism. Urate is produced in the liver and, to a lesser extent, in the small intestines. Urate is excreted in the kidneys and manages blood uric levels.
In cases of overproduction (or underexcretion) of uric acid, hyperuricemia may occur. As uric acid predominantly exist in its ionized form, monosodium urate (MSU), deposition of MSU crystals results in gout.
Crystal deposition within the joints for long periods can result in inflammation if microcrystals shed and activate inflammatory pathways resulting in characteristic inflammatory arthritis findings.
In advanced disease, deposits of MSU within tissue results in tophi. These are commonly found in periarticular, articular, and subcutaneous areas. Tophi further contribute to joint damage and bone erosion.
Clinical Presentation
Signs & Symptoms
Inflammation and tissue damage
A range of findings may exist based on the severity of tissue deposition of MSU.
- Joint involvement of distal joints of the lower extremities (but any joint can be affected)
- Periarticular involvement of soft tissue (eg. tendonitis, bursitis)
- Tophi (may be visible or palpable)
- Kidney complications (nephrolithiasis and chronic urate nephropathy)
Gout flares
Flares typically present as:
- Intense, rapid-onset pain and disability (even with light touch)
- Intensely inflammatory (erythema, warmth, swelling)
- May have systemic symptoms (uncommon)
- Location is monoarticular, asymmetric involvement of lower extremity (and rarely upper extremities)
- Onset often occur overnight and early morning
- Resolution occur within few days to several weeks even without treatment
- Following use of diuretic, intake of alcohol, or triggering foods
Tophaceous gout
Tophi may form in any area with connective tissue including articular bone, cartilage, bursae, soft tissues, tendons, ligaments, entheses, and meninges.
This typically occurs following many years of intermittent gout flares but is rare.
History & Physical Exam
Assess the quality, severity, location, and distribution of prior episodes. Potential triggers should be identified. Other component to elicit include:
- Family history of gout
- Medical history of associated conditions
Physical exam should be comprehensive with attention given to MSK and signs of inflammation.
Diagnosis
Criteria
Diagnosis of gout can be made clinically with supportive clinical features.
A definitive diagnosis can be made with synovial fluid aspiration and visualization of MSU crystals.
Work-up
Laboratory workup
Synovial fluid analysis
- May appreciate MSU crystals during flare
- WBC count of 10^5 to 10^6 cells/mm3 with neutrophilic predominance
Blood tests may find:
- Elevated ESR, CRP
- Neutrophilic leukocytosis
- Elevated serum urate (may drop during acute flare)
Imaging
Plain radiograph of affected joint is typically performed. It may also aid in ruling out alternative diagnoses (eg. osteoarthritis).
Ultrasound may allow for early detection but is not routinely ordered.
Differential
The primary diagnoses to exclude urgently are:
- Septic arthritis
- Cellulitis
Other conditions include other forms of inflammatory arthritis.
Red Flags / Complications
Untreated gout can result in chronic gouty arthritis and tophaceous gout.
Generally, managed gout should rarely progress.
Management
Non-pharmacological
Strategies include treatment of comorbid conditions, addressing medications that affect urate balance (aspirin and diuretics), exercise, and modification of diet.
Dietary recommendations
In most patients, the current recommendations are made:
- Reduction of foods that can trigger gout flares (high-purine foods, alcoholic beverages, high-fructose corn syrup)
- Consider specific diets such as DASH and Mediterranean diet
- Ensure dietary protein is sufficient from plant-based and/or low-fat dairy sources
Pharmacological
Management of Gout and Tophi
Long-term management of gout requires maintaining a subsaturating level of serum urate. Pharmacologic options are available in addition to non-pharmacological lifestyle changes.
In general, pharmacological management is indicated in patients with:
- Frequent or disabling gout flares
- Tophi and structural joint damage
- High risk of severe gout (eg. high baseline urate levels, early onset of synmptoms, genetics)
The target urate level used clinically is <360 mcmol/L (urate solubility limit is 405 mcmol/L). Urate-lowering drugs consist of:
- Allopurinol 100 mg PO daily, titrated up until target is met
- Febuxostat 40 mg PO daily
Adjustment of medication dosing and choices may be necessary in patients with CKD.
Treatment of Acute Gout Flareups
Prior to treating a gout flare, it is important to confirm other forms of inflammatory arthritis is not mimicking gout, especially septic arthritis.
During treatment of a flareup, regular maintenance medications (eg. allopurinol) should be continued.
Therapy of gout flareup consist of systemic antiinflammatory. Options include:
- Prednisone 40 mg PO daily until flare resolves then tapered (note: avoid if infection)
- Triamcinolone acetonide (intraarticular glucocorticoid) once
- Naproxen 500 mg PO BID or indomethacin 50 mg PO TID
- Colchicine
- Anakinra
In cases of flareups resistant to treatment, reevaluation of the diagnosis is warranted as well as assessment of adherence.