Gout (Clinical)

Epidemiology and Etiology

Epidemiology^[2,3]

• In the United States, the general prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is approximately 3%.
• Risk increases with higher body mass index Body mass index An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity): prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is 1%–2% in those with normal body mass index Body mass index An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity), and 5%–7% with class II or class III obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
• Middle-aged to elderly men and postmenopausal women are most often affected.
• Rare in childhood unless there is an inherited enzyme defect or a malignancy Malignancy Hemothorax

Etiology^[1,3,15]

• Hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout ( plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products urate > 6.8 mg/dL) is necessary but not sufficient for the development of gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout.
  • Only 10% of individuals with hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout develop gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout.
  • Elevated uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis (UA) can result from reduced excretion (90%), overproduction, or both.
• Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout can occur in primary or secondary forms:
  • Primary gout Primary Gout Gout (90%):
    • Unknown enzyme defects: usually due to decreased excretion of UA
    • Known enzyme defects: e.g., Lesch-Nyhan syndrome Lesch-Nyhan syndrome An inherited disorder transmitted as a sex-linked trait and caused by a deficiency of an enzyme of purine metabolism; hypoxanthine phosphoribosyltransferase. Elevation of uric acid in the serum leads to the development of renal calculi and gouty arthritis. Purine Salvage Deficiencies and variants of hypoxanthine-guanine phosphoribosyltransferase deficiency (due to increased purine production), glycogen storage diseases Glycogen Storage Diseases A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. Benign Liver Tumors (due to decreased excretion of UA) 
  • Secondary gout Secondary Gout Gout (10%):
    • Increased nucleic acid turnover (e.g., leukemia), due to increased UA production
    • Chronic renal disease (due to decreased excretion of UA)

Risk factors that increase UA levels^[2,3,15,20]

• Diets:
  • Rich in meat and seafood 
  • Beverages containing fruit sugar (fructose), alcohol
• Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
• Medical conditions: untreated high blood pressure, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome, heart and kidney diseases
• Certain medications
  • Thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
  • Low-dose aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) 
  • Anti-rejection/ immunosuppressive drugs Immunosuppressive drugs Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. Organ Transplantation used in organ transplantation Organ Transplantation Transplantation is a procedure that involves the removal of an organ or living tissue and placing it into a different part of the body or into a different person. Organ transplantations have become the therapeutic option of choice for many individuals with end-stage organ failure. Organ Transplantation
• Family history Family History Adult Health Maintenance of gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout
• Age and sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria: higher prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in middle-aged and older men, but UA levels in postmenopausal women approach those of men
• Recent surgery or trauma
• Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration

Mnemonic

Drugs causing acute precipitation of gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout: FACT

F: Furosemide diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication

A: Aspirin/Alcohol

C: Anti-Cancer drugs (e.g., cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants)

T: Thiazide diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication

Pathophysiology

• Purine compounds, whether they are synthesized in the body or come from eating high-purine foods, can ↑ uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis levels.^[1,16,18]
• Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis is excreted mainly through the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy.
• Overproduction or underexcretion (more common) of uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis can lead to hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout → supersaturation → deposition of monosodium urate (MSU) crystals in the tissues
• MSU deposits in the soft tissue Soft Tissue Soft Tissue Abscess and synovium as MSUcrystals (“ tophi Tophi Msu deposit in the soft tissue and synovium. Gout”).
  • Can erode the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and damage other tissues such as tendons and cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology
  • Cause recurrent monoarticular arthritis Monoarticular Arthritis Septic Arthritis and chronic deforming arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis 
• The precise relationship between hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout and gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout is unclear:
  • The majority (90%) of people with hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout do not have gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout.
  • Normal or ↓ serum uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis levels do not rule out gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout.
  • However, all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout will have hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout (> 6.8 mg/dL) at some point, although levels may fluctuate.

Clinical Presentation

Gout flares Gout Flares Gout^[3,4,18,20]

• Typically monoarticular (< 20% are polyarticular)
• Commonly occurs in the lower extremities, most often at the base of the great toe (first metatarsophalangeal [MTP] joint, or podagra) or the knee
• Intensely inflammatory, causing severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, redness Redness Inflammation, warmth, swelling Swelling Inflammation, and disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment
• Peaking within 12–24 hours and resolving within 3–10 days even without treatment
• Onset more often at night

Intercritical gout Intercritical Gout Gout^[3,18]

Upon resolution of an acute gout Acute Gout Gout flare, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship enter an intercritical (between-flares) period.

• Most often entirely asymptomatic
• Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables in duration
• Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship left untreated will develop a recurrent flare within 2 years.
• Monosodium urate crystals Monosodium Urate Crystals Gout may continue to deposit as tophi Tophi Msu deposit in the soft tissue and synovium. Gout in various tissues.

Tophaceous gout Tophaceous gout Nodular deposit of monosodium urate crystals associated with chronic inflammation with a foreign-body giant cell reaction. Gout^[3,4]

• Nodular deposit of monosodium urate crystals Monosodium Urate Crystals Gout associated with chronic inflammation Chronic Inflammation Inflammation with a foreign-body giant cell reaction
• Found in cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology, subcutaneous and periarticular tissues, tendons (e.g., Achilles tendon), olecranon Olecranon A prominent projection of the ulna that articulates with the humerus and forms the outer protuberance of the elbow joint. Arm: Anatomy bursae, ear helix, kidney, and elsewhere
• Can cause destruction of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and soft tissue Soft Tissue Soft Tissue Abscess

Associated renal complications^[3,4,12]

• Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
• Chronic urate nephropathy Chronic Urate Nephropathy Gout

Diagnosis

Assessment^[11]

• Take a detailed medical history and ask about:
  • Current symptoms:
    • Joints affected
    • Symptom severity and speed of onset 
    • Frequency and duration of attacks 
    • Previous attacks and drug intervention 
    • Dietary habits 
    • Ability to mobilize; impact on work and activities of daily living 
    • Family history Family History Adult Health Maintenance of gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout, hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout, nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis, or renal disease 
    • Comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus and risk factors (see above)
• Examine, paying particular attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment to:
  • Warm, red, swollen joints 
  • Tophi Tophi Msu deposit in the soft tissue and synovium. Gout 
• Always rule out the possibility of septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis:
  • Refer immediately to relevant specialists, typically trauma and orthopedics

Evaluation^[3,4,11,20]

• Diagnosis is established via microscopic analysis of the joint aspirate, which shows:
  • Crystals of MSU, which are negatively birefringent (yellow when parallel to compensator filter) and needle-shaped
  • WBC > 2,000/μL with > 50% neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation (an acute inflammatory synovial fluid)
  • Note: MSU crystals MSU crystals Gout can also be seen on aspirates of tophi Tophi Msu deposit in the soft tissue and synovium. Gout.
• Laboratory studies may show:
  • ↑ Serum urate:
    • Hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout is defined as a concentration > 6.8 mg/dL (405 µmol/L)
    • May be normal or ↓ during an acute flare
    • Best to measure 2 weeks after flare
  • ↑ WBC
  • ↑ Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess)
• X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
  • Shows no changes early in the disease
  • As the disease progresses, punched-out erosions Erosions Corneal Abrasions, Erosion, and Ulcers with an overhanging rim of cortical bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types develop.
  • Soft tissue Soft Tissue Soft Tissue Abscess masses (may be calcified) → tophi Tophi Msu deposit in the soft tissue and synovium. Gout
• Ultrasonography:
  • Hyperechoic Hyperechoic A structure that produces a high-amplitude echo (lighter grays and white) Ultrasound (Sonography) enhancement of the surface of articular cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology → MSU crystal deposition
  • MSU crystals MSU crystals Gout may also appear as hyperechoic Hyperechoic A structure that produces a high-amplitude echo (lighter grays and white) Ultrasound (Sonography) foci floating within the joint space

American College of Rheumatology (ACR) criteria^[11,14]

• Entry criterion: ≥ 1 episode of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, swelling Swelling Inflammation, and/or tenderness in a peripheral joint or bursa
• Sufficient criteria (either):
  • MSU crystals MSU crystals Gout in joint fluid
  • MSU crystal identified from tophus 
• If sufficient criteria not met MET Preoperative Care, the following are assessed:
  • Pattern of joint/bursa involvement
  • Characteristics of episodes (e.g., erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, unable to bear touch/pressure, difficulty using joint)
  • Number of episodes meeting time-course criteria
  • Evidence of tophi Tophi Msu deposit in the soft tissue and synovium. Gout
  • Serum urate level
  • Synovial fluid analysis Synovial Fluid Analysis Rheumatoid Arthritis
  • Imaging demonstrating urate deposition
  • Imaging demonstrating joint damage 
• Calculator

Management of Chronic Gout

Management differs for acute and chronic gout Chronic Gout Gout.

The goal of management is to minimize urate deposition in tissues and to prevent disease flares. 

General measures^[10,17]

• Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery to achieve BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity < 25
• Avoid foods with a high purine content (e.g., seafood, meat, alcohol [varies among different beverages])
• Avoid certain medications that cause hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout
  • Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication both increase urate reabsorption and decrease its secretion Secretion Coagulation Studies.
  • Allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs is often administered to control gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout if a diuretic is necessary.

Medical treatment

Indications:^[6,10,21]

• Recurrent attacks (≥ 2 per year)
• Tophi Tophi Msu deposit in the soft tissue and synovium. Gout
• Radiographic evidence of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types damage attributed to gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout
• 1st gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout flare and:
  • Chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease stage 3–5
  • Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis level > 9 mg/dL
  • Urolithiasis 

Mechanism of action for xanthine oxidase Oxidase Neisseria inhibitors:^[4,6]

• ↓ Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis production by inhibiting xanthine oxidase Oxidase Neisseria (an enzyme involved in endogenous purine synthesis Synthesis Polymerase Chain Reaction (PCR)).
• Benefits:
  • Eliminate urate crystals
  • Prevent flares
  • Shrink tophi Tophi Msu deposit in the soft tissue and synovium. Gout 
  • Protect against joint damage

Dosing:^[6,10,17,21] 

• Allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs:
  • Typically, the preferred 1st-line agent
  • Start with 100 mg daily (taken after food).
  • Adjust in 100-mg increments every 4 weeks according to serum urate. 
  • Amounts > 300 mg should be taken in divided doses.
  • In severe renal impairment, either:
    • Reduce daily dose below 100 mg, or
    • Increase dosing interval 
• Febuxostat Febuxostat A thiazole derivative and inhibitor of xanthine oxidase that is used for the treatment of hyperuricemia in patients with chronic gout. Gout Drugs:
  • Starting dose of 40–80 mg or less daily for 2–4 weeks 
  • Increase dose every 2–5 weeks, up to a maximum dose of 120 mg daily 
  • Dose adjustment to a maximum of 80 mg in hepatic impairment 
  • Prescribe for ≥ 6 months 

Considerations:^[6,10,17]

• Offer allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs as 1st-line therapy in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with major cardiovascular disease (e.g., stroke, myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, unstable angina Unstable angina Precordial pain at rest, which may precede a myocardial infarction. Stable and Unstable Angina)
• Initiation recommendations vary:
  • US: ACR conditionally recommends initiating during the gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout flare for certain patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.^[6]
  • UK: Commence at least 2–4 weeks after gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout flare settles.^[10]
• Start with low doses and titrate up based on monthly serum urate concentration.

Monitoring and screening Screening Preoperative Care:^{[6,10,17,19,21]}

• Monitor for hypersensitivity syndrome when starting allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs.
• Consider screening Screening Preoperative Care for HLA-B HLA-B Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., hla-b27, -b7, -b8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes. Organ Transplantation*5801 before starting allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs in subgroups with high prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of the allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics (e.g., Han Chinese, Thai, Korean)
  • Associated with risk of allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs hypersensitivity, Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome, and toxic epidermal necrolysis Toxic Epidermal Necrolysis Stevens-Johnson Syndrome 
  • Do not prescribe to people known to have this allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics. 
• Monitor liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function periodically before and while taking febuxostat Febuxostat A thiazole derivative and inhibitor of xanthine oxidase that is used for the treatment of hyperuricemia in patients with chronic gout. Gout Drugs.
• Monitor serum urate:
  • Aim for target serum urate < 360 µmol/L (6 mg/dL)
  • Consider lower target serum urate (< 300 µmol/L (5 mg/dL)) for people with:
    • Tophi Tophi Msu deposit in the soft tissue and synovium. Gout 
    • Chronic gouty arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis 
    • Ongoing frequent flares
  • Once target urate levels are reached, consider annual monitoring. 

Other medication options:^[6,10,17,21] 

• Probenecid Probenecid The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Gout Drugs:
  • Uricosuric drug that inhibits tubular reabsorption of urate → ↑ urinary uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis excretion and ↓ serum urate concentration 
  • Unlicensed in the UK and available only off-license to named patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship under the care of a rheumatologist.
  • In the US, a trial of probenecid Probenecid The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Gout Drugs can be started if allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs and febuxostat Febuxostat A thiazole derivative and inhibitor of xanthine oxidase that is used for the treatment of hyperuricemia in patients with chronic gout. Gout Drugs are not tolerated or are contraindicated.
    • Note: This is not recommended for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with moderate-to-severe CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease (stage ≥ 3).
    • An initial dose of 500 mg 1–2 times daily is conditionally recommended.
• Pegloticase Pegloticase Gout Drugs:
  • A recombinant pegylated (i.e., linked to methoxy polyethylene glycol Polyethylene Glycol Laxatives) uricase → uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis metabolized to allantoin → less likely to precipitate
  • Not currently recommended by NICE 
  • ACR and European League Against Rheumatism (EULAR) recommend pegloticase Pegloticase Gout Drugs in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe, treatment-refractory gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout (> 2 flares per year or nonresolving tophi Tophi Msu deposit in the soft tissue and synovium. Gout).
  • Warnings against high cost and adverse effects
  • Should not be used as a 1st-line agent

Antiinflammatory prophylaxis Prophylaxis Cephalosporins:^[6,10,17]

• Concomitant therapy with antiinflammatory medications is recommended to prevent flares during initiation of urate-lowering therapy.
• Choice should be based on patient factors, but may include:
  • Colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs
  • NSAIDs NSAIDS Primary vs Secondary Headaches
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids (e.g., prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants or prednisolone Prednisolone A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. Immunosuppressants)
• Recommended duration of 3–6 months after initiating urate-lowering therapy with ongoing reevaluation (continue prophylaxis Prophylaxis Cephalosporins if flares continue)

Patient education:^[6,10] 

• Therapy is continued indefinitely, even after target serum urate level is achieved. 
• Usually requires lifelong treatment 
• Seek advice for acute flares 

Differential Diagnosis

The following conditions are differential diagnoses of gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout:

• Septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: an infection of a joint with extremely high WBC counts in synovial fluid (> 100,000 cells/mL) are most supportive of a diagnosis of septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis. Gram stain Gram stain Klebsiella and synovial fluid culture are performed for diagnosis.
• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes pyrophosphate crystal deposition disease (CPPD, pseudogout): positively birefringent crystals in synovial fluid. Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes pyrophosphate crystal deposition disease also has a characteristic radiographic appearance of chondrocalcinosis Chondrocalcinosis Presence of calcium pyrophosphate in the connective tissues such as the cartilaginous structures of joints. When accompanied by gout-like symptoms, it is referred to as pseudogout. Gitelman Syndrome. 
• Trauma: a stress fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures or traumatic process in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types or joint can mimic a gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout flare.
• Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis: a common and painful bacterial skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions infection that affects the deeper layers of the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions and subcutaneous tissue Subcutaneous tissue Loose connective tissue lying under the dermis, which binds skin loosely to subjacent tissues. It may contain a pad of adipocytes, which vary in number according to the area of the body and vary in size according to the nutritional state. Soft Tissue Abscess. Typical signs of acute inflammation Acute Inflammation Inflammation ( rubor Rubor Inflammation, dolor Dolor Inflammation, calor Calor Inflammation, tumor Tumor Inflammation) are present but joint mobility is usually preserved.
• Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: an autoimmune inflammatory polyarthritis Polyarthritis Rheumatoid Arthritis. Tophi Tophi Msu deposit in the soft tissue and synovium. Gout may be mistaken for rheumatoid nodules Rheumatoid Nodules Rheumatoid Arthritis but the clinicoradiological presentation and the lack of crystals in the nodular lesions can differentiate the 2 conditions.
• Dactylitis Dactylitis Ankylosing Spondylitis: severe bacterial inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the finger and toe joints that can resemble tophaceous gout Tophaceous gout Nodular deposit of monosodium urate crystals associated with chronic inflammation with a foreign-body giant cell reaction. Gout with acute flare. The condition can usually be distinguished from gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout based on the history and physical examination.
• Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis: an infection (usually bacterial) of the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types. Diagnosis is made by noting deep bony tenderness and clinical signs of acute systemic inflammation Systemic Inflammation Surgical Site Infections; CBC and magnetic resonance imaging (MRI) are helpful if routine radiologic findings are not supportive.
• Basic calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes (BCP) crystal disease (hydroxyapatite ( HA HA Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia) crystal deposition disease): painful and probably underdiagnosed periarthritis or arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis due to the deposition of BCP crystals in the synovium. The condition can cause severe joint damage, as in the Milwaukee shoulder syndrome seen in elderly women.