Treatment and prophylaxis

Whereas gout was once considered a disease of the affluent, it now affects all segments of the population due to sedentary lifestyles. Often, chronic courses are seen – although potent and well-tolerated drugs are available.

Along with chondrocalcinosis (pseudogout), gout is one of the most common inflammatory joint diseases. Hyperuricemia, or gout, occurs when the body’s production of uric acid is increased or its excretion is decreased. The uric acid can crystallize and be deposited especially in joints and kidneys.

Epidemiology

The risk of gout attack increases with duration and level of hyperuricemia: at uric acid levels above 535 μmol/l uric acid, the annual incidence of gouty arthritis is reported to be about 5%. About 20-30% of men and 3% of women have elevated uric acid levels [1]. Symptomatic gout occurs in 1-2% of the adult population, with an increasing trend in older age. Before menopause, primary gout is very rare. Hyperuricemia and gout are associated with cardiovascular risk factors and disease, respectively. Whether metabolic disease is an independent risk factor for cardiovascular disease is controversial [2,3].

Causes

The primary form of gout is the most common. It is a congenital metabolic disorder underlying renal dysfunction with impaired uric acid excretion. Very rarely, there is an overproduction of uric acid (e.g., Lesch-Nyhan syndrome).
The secondary form of gout may have the following causes:

Myeloproliferative and lymphoproliferative diseases, psoriasis, tumor lysis syndrome
Medications: ciclosporin, thiazides, loop diuretics, aspirin (up to 1000 mg/day).
renal insufficiency, polycystic kidney, hypertension
Metabolic: hypothyroidism, dehydration, lactic acidosis, ketosis, metabolic syndrome.

Diagnosis of the acute gout attack

Clinical picture: The diagnosis can usually be made clinically, especially if a typical pattern of symptoms is present. Characteristic is an extremely painful monarthritis with redness, hyperthermia and severe swelling that develops within 24 hours. In many cases, provocation factors can be determined from the patient’s medical history (Tab. 1) . The first attack of gout most frequently affects the metatarsophalangeal joint (podagra), followed by the knee and ankle joints. Tendon sheaths, bursae and soft tissues are not infrequently affected. If the inflammation spreads to the skin, the appearance may mimic erysipelas. In the elderly and in women, gout begins less inflammatory and is often oligo- to polyarticular. The joints of the hands can then also be affected [1].

Laboratory: Serum uric acid, differential blood count, CRP/BSR and creatinine should be determined in gout patients. It should be noted that uric acid may be normal or even decreased in the gout attack. CRP and BSR are usually elevated. However, both inflammatory parameters are not suitable for excluding other arthritides. Stress fractures can occasionally produce symptoms of gout, in which case there is no CRP/BSR increase.

Joint puncture: Detection of uric acid crystals in the synovial fluid confirms the diagnosis. However, joint puncture is indicated only in unclear cases. The main differential diagnoses are septic arthritis or chondrocalcinosis (pseudogout).

X-ray: Radiological diagnosis is not necessary in the typical gout attack. In unclear cases, dual-energy computed tomography and arthrosonography can visualize the uric acid deposits [1].

Screening for comorbidities: Gout patients should always be screened for cardiovascular risk factors or diseases (if not already known). This includes renal dysfunction, coronary artery disease, heart failure, peripheral arterial disease, hyperlipidemia, hypertension, and type 2 diabetes. Whether successful treatment of gout affects the outcome of cardiovascular disease is still unknown.

Therapy of the gout attack

In the gout attack, nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs of choice, e.g., naproxen 2× 500 mg/day. Not suitable is acetylsalicylic acid, which is even contraindicated in doses up to 1 g/day because it inhibits uric acid excretion. However, low-dose acetylsalicylic acid taken for cardiovascular prophylaxis need not be discontinued in the treatment of a gout attack.

If NSAIDs are contraindicated in a patient (renal insufficiency!), oral glucocorticosteroids can be used for a short time (e.g., prednisone 20-40 mg/day). Experience has shown that intraarticular steroid injection (e.g., 10 mg triamcinolone and lidocaine), which can be performed during diagnostic joint puncture, for example, is particularly effective. Steroid injection requires a confirmed diagnosis.

Colchicine remains one of the first-line agents according to current international guidelines [4,6]. However, the substance is not commercially available in Switzerland.
The interleukin-1 antagonist canakinumab may be used in exceptional cases (off-label use) when the above drugs are contraindicated or ineffective and the patient experiences frequent seizures [4,6].

During the gout attack, the affected limb should be elevated and cooled if possible.

Seizure prophylaxis in chronic gout

Pharmacological uric acid lowering: asymptomatic hyperuricemia does not require specific treatment. In the case of repeated gout attacks and in certain risk constellations, lowering uric acid with medication is indicated (Tab. 2) [1,4], in order to prevent further gout attacks. Creeping dosing is recommended to reduce the risk of relapse [4]. Therapy should be started only after an attack of gout has subsided.

The xanthine oxidase inhibitor allopurinol remains the standard drug for uric acid lowering (Table 3) . It should be taken daily; intermittent allopurinol therapy has been shown to be less reliable in the long term. If a gout attack occurs during established allopurinol treatment, therapy should not be interrupted.

The new selective xanthine oxidase inhibitor febuxostat is an alternative when allopurinol is not tolerated or is contraindicated [4–6]. Dose adjustment is not required in renal insufficiency. However, febuxostat should be used cautiously in patients at high cardiovascular risk, as doubts about the cardiovascular safety of the drug have not yet been fully resolved [7].

Uric acid lowering can also be achieved by increased renal excretion. In Switzerland, the uricosurics probenecid and lesinurad are available. Probenecid may be used in cases of intolerance to allopurinol or added to it if it is not sufficiently effective. However, it is not indicated in nephrolithiasis and renal insufficiency. Lesinurad is approved only for combined therapy with allopurinol.

Anti-inflammatory prophylaxis: In the first weeks to months after starting uric acid-lowering therapy, gout attacks may occur more frequently. Therefore, the possibility of prophylactic use of low-dose NSAIDs for six months should be discussed with the patient. Studies have shown that prophylaxis reduces the risk of seizures. However, most patients do not relapse during this period even without prophylaxis [4].

Duration of treatment: many patients become symptomatic again or develop tophi after discontinuation. However, weaning tests can be considered in principle. In a prospective cohort study, it was shown that discontinuation can be attempted for at least five years after successful drug-induced uric acid lowering [8].
Other measures: If possible, medications that increase uric acid levels should be discontinued (e.g., loop diuretics, thiazide diuretics, aspirin). In patients with hypertension, it is recommended to switch to losartan because this AT1 antagonist has a uricosuric effect (given adequate renal function) [1,4,6]. Regular intake of vitamin C (500 mg/day) slightly lowers uric acid levels.

Dietary changes: Every gout or hyperuricemia patient should receive lifestyle/dietary counseling. The “gout diet” is intended not only to reduce serum uric acid and thus relapse frequency, but also to target the commonly associated metabolic syndrome and increased cardiovascular risk [9]. The traditional low purine diet is no longer recommended. A high-protein plant-based diet even proves beneficial despite its high purine content [10]. Nutrition recommendations are summarized in the box.

Take-Home Messages

The acute attack of gout often occurs as monoarthritis, and in older people, as less inflammatory oligo- or polyarthritis.
The diagnosis is usually made on the basis of the clinic. Joint puncture is only necessary in unclear cases.
Gout patients should always be screened for cardiovascular risk factors.
In the gout attack, NSAIDs or steroids should be applied as early as possible.
Uric acid-lowering therapy is required for repeated gout attacks and certain risk constellations.

Note: This work is based on the mediX Guideline Gout [11]. mediX Guidelines are discussed by over 600 mediX-associated practicing physicians in quality circles,
continuously improved and regularly updated.

Literature:

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Stack A, et al: Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality. Q J Med 2013; 106(7): 647-658.
Richette P, et al: 2016 updated EULAR evidence-based recommendations for the management of gout. Annals of the Rheumatic Diseases 2017; 76: 29-42.
Sivera F, et al: Interleukin-1 inhibitors for acute gout. Cochrane Database Syst Rev 2014; 9: CD009993.
Shekelle PG, et al: Management of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline. Inn Intern Med 2017; 166(1): 37-51.
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