Gout

The term gout is derived from the Latin gutta, which means a drop. In the 13th century, it was thought that gout resulted from a drop of evil humor affecting a vulnerable joint.

Causes of hyperuricemia

Increased production

¤ Nutrition: food rich in purine and fructose, fasting

¤ Myelo- and lymphoproliferative syndromes

¤ Psoriasis, tumor lysis syndrome

Reduced excretion

¤ Drugs: loop and thiazide diuretics, cyclosporine, ASS

¤ Renal: chronic renal failure was different. Aetiology

¤ Metabolic/endocrine: obesity, dehydration,hypothyroidism, lactic acidosis, ketosis

Combined

¤ Alcohol, shock

Gout is a disease in which tissue deposition of monosodium urate (MSU) crystals occurs as a result of hyperuricemia (MSU supersaturation of extracellular fluids), resulting in one or more of the following manifestations:

Gouty arthritis
Tophi (aggregated deposits of MSU occurring in articular, osseous, cartilaginous, or soft tissue areas)
Gouty nephropathy
Uric acid nephrolithiasis

Gout is the most common cause of inflammatory arthritis in men over 40 years of age.
Hyperuricemia and gout are strongly associated with obesity and the metabolic syndrome.
Dietary and lifestyle modifications are recommended for the management of gout.
The rheumatologist should always look for gout in all undiagnosed joint conditions even if the serum uric acid level is normal, the involved joint is atypical, and the flare is chronic and polyarticular.
The patient’s comorbid medical conditions should be assessed, including renal and hepatic function, to guide the safest treatment options for acute gout and chronic symptomatic hyperuricemia, with a serum uric acid goal of <6.0 mg/dL.
Prevalence - depending on country - at 0.9-2.5
Hyperuricemia, with or without crystal deposits, is associated with an increased risk of developing renal, cardiovascular and metabolic complications and increased cardiovascular and all-cause mortality

Joints involved in gout:

The joints of the lower limbs are typically involved more often than those of the upper limbs. The first metatarsophalangeal (MTP) joint of the great toe is involved in >50% of initial attacks and over time is affected in >90% of patients.

Acute gout of the first MTP is termed podagra. In order of frequency of involvement after the MTP joints are the instep, ankle, heel, knee, wrist, fingers, and elbow, spine, soft tissue.

Radiographic features:

Joints
- Joint effusion (earliest sign)
- Preservation of joint space until late stages of the disease
- Absence of periarticular osteopenia
- Eccentric erosions
- Typical appearance “punched-out” erosions with sclerotic margins in a marginal and juxta-articular distribution, with overhanging edges
Bone
- Punched-out lytic bone lesions
- Overhanging sclerotic margins
- Avascular necrosis
- Mineralisation is normal
Surrounding soft tissues
- Tophi: pathognomonic
- Olecranon and prepatellar bursitis
- Periarticular soft tissue swelling due to crystal deposition in tophi around the joints is common
- Soft tissue swelling may be hyperdense due to the crystals, and the tophi can calcify (uncommon in the absence of renal disease)

Diagnostics: Detection of urate crystals in the joint point or from tophus material: Needle-shaped, negative in the polarization microscope birefringent crystals

Ultrasound: Double contour is very specific. While there can be variation in appearance, tophi tend to be hyperechoic, heterogeneous, have poorly defined contours. They can be multiple grouped and surrounded by anechoic halos.

DUAL-CT: Imaging of the crystals

MRI (not necessary):Signal characteristics of gouty tophi are usually: T1: isointense T2: variable, majority of lesions are characteristically heterogeneously hypointense T1 C+ (Gd): tophus often enhances

Management of acute attacks of gout

non-steroidal anti-inflammatory drugs (NSAIDs)
peroral steroids at a dosage of 20-40 mg prednsion equivalent for 3-6 days or prednisone per os: 0.5mg/kg bw/d for 3-5 days, followed by a period of 7-10 days > Option for severe renal failure
Colchicine (Colchicine: (not authorised in Switzerland). Dosage: 1mg immediately, 0.5mg after 1 hour, then from the 2nd day: 2x0.5mg per day. Dose adjustment for renal failure (GFR 30-60), hepatic failure Child A/B, weak CYP3A4 inhibitors: 1mg first day, 1x0.5mg from day 2. For therapy with strong CYP3A4 inhibitors: avoid colchicine)
Infiltration of corticoids
Interleukin-1 inhibitors (Anakinra or Canakinumab) for Patients with frequent attacks and contraindication for NSAIDs, colchicines, steroids: IL-1 Blocker: Anakinra (not approved in CH) 100mg s.c. 1x/d (approx. Fr. 60/injection). Canakinumab (approved for CAPS, syst. Juvenile idipath. Arthritis) 150mg s.c. every 3 months (approx. Fr. 14'000/injection)

Management of hyperuricemia

Limit the consumption of purine-rich foods such as meat or seafood
give preference to low-fat milk products as sources of protein
avoid alcohol (especially beer and spirits) and sweet drinks containing fructose and fruit juices as far as possible
drink enough water
Regular consumption of coffee and cherry juice is protective
For obesity reduction diet
Does the patient have medication that causes hyperuricemia?aspirin, diuretics (thiazide diuretics, loop diuretics), cyclosporine and other cytotoxic/cytostatic drugs, ethambutol/pyrazinamide, levodopa, nicotinic acid. Consider switching to drugs with uric acid-lowering effects: Losartan, calcium antagonists.

Drug therapy of hyperuricemia

Consider the use of urate lowering therapy (ULT) for every patient with a definitive diagnosis of gout. Objective: Prevention of the formation of urate crystals, dissolution of crystals, tophi. Correctly performed prophylaxis can prevent further gout attacks.
ULT is indicated in patients with two or more attacks of gout per year and in the presence of tophi, urate arthropathy and/or kidney stones
Target value <360μmol/l (= 6 mg/dl)
lower target value (<300 μmol/l) for severe gout (tophi, chronic arthropathy, frequent attacks)
ULT especially in younger patients (<40 years), in case of very high uric acid levels (>480 μmol/l) and/or comorbidities (impaired renal function, hypertension, coronary heart disease, heart failure)
Start ULT after the acute gout flare has subsided (e.g. after one week) and adjust the low dose until the target value is reached.
Do not pause if gout occurs below ULT, do not pause ULT
In principle, continue therapy in the long term
advise patients that initiating ULT may cause acute attacks (often in the first three to six months of therapy)
In the first three to six months of ULT use prophylaxis with NSAID, colchicine (0.5-1 mg daily) or low-dose corticosteroids p.o.
ad Colchicine: dose adjustment is necessary in renal and liver failure
ad Colchicine: interaction with cytochrome 3A4 inhibitors such as protease inhibitors, calcium antagonists and antimycotics type triazoles
By gradually increasing the ULT dose, seizure rates can be reduced and, in the case of allopurinol, the occurrence of allergic side effects can be minimized

Xanthine oxidase inhibitors (allopurinol, febuxostat)

prefer allopurinol in patients without impaired renal function
Start dose of Allopurinol at 100mg/day, increase by 100 mg/day (up to 900mg) every two to five weeks until the uric acid target value is reached. Only 28% reach therapy goal with 300mg but 78% with 600mg!
Adjust allopurinol dose to creatinine clearance in case of impaired kidney function
If kidney function improves under Allopurinol, increase dosage
If serum uric acid target value is not reached with allopurinol, switch to febuxostat (febuxostat reaches uric acid target value more frequently): Non-purine-based XO inhibitor. No dose adjustment for renal failure (KreaCl≥30). Dosage: 40mg 1x/d, after 2-4 Wo increase to 80mg/d if uric acid >360umol/l
Febuxostat can be used without dose adjustment in patients with mild or moderate kidney function impairment.

Uricosurics

(Probenecid, Lesinurad) recommended as second-line therapy alone or in combination with allopurinol
Not for kidney stones
Probenecid (Santuril®): also possible as monotherapy. Dose initial 2x250mg, after 1 Wo 2x500mg/d. Contraindicated for renal insufficiency/nephrolithiasis
Lesinurad in combination with allopurinol is indicated if serum uric acid targets are not achieved with allopurinol alone, dose of Lesinurad is 200 mg 1 × daily (morning), only in combination with allopurinol. Lesinurad (Zurampic®): URAT1 inhibitor, approved in combination with allopurinol Dose 200mg/d, no therapy start for creatinine clearance <45

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