(CKD) type 3 and above, advanced heart failure,
high blood pressure, and use of loop diuretics
and thiazide diuretics. Diabetes mellitus and
metabolic syndrome also contribute to the increased
reabsorption of uric acid via hyperinsulinism.
Who is affected by gout?
Gout mainly affects men aged 40 or over. Earlier
onset can be observed, from adolescence and before
the age of 30, and has a definite genetic origin
(mainly the ABCG2 gene).
Gout is uncommon in women before menopause,
because oestrogens have a uricosuric effect, that is,
they increase the urinary elimination of uric acid.
What are the consequences of gout attacks?
Gout attacks usually begin abruptly in the foot,
especially at the joint at the base of the big toe.
Attacks usually trigger at night after a high-fat meal
or after certain beverages. The pain is intense (in
the order of 7–8 on a numerical pain scale of 10)
and becomes maximal in less than 24 hours. Locally,
joint swelling sets in, with often intense, local
redness. Joint function is markedly impaired. The
pain will gradually improve and disappear within
15 days, and medications can reduce the duration or
stop the attack. In early disease, the joint returns to
normal between attacks. Arthritis will repeat itself
at an unpredictable rate, with the time between
each attack gradually becoming shorter. Other joints
can be affected: first, the foot and ankle, then the
knee or, much later, the upper limb. Gout should
be the diagnosis in cases of recurrent acute arthritis
in men.
What are the other manifestations?
Apart from gout attacks, deposits of agglomerated
microcrystals (tophi) can form in a number of sites
including: Achilles’ tendons, patellar tendons, or
even ear cartilage (helix). These clinically visible
deposits reflect the importance of crystal stocks in
the body. They can also be detected through imaging
(joint ultrasound, dual energy scanner or dual
energy CT). 4
Treating the crisis
The mechanism of the gout attack is complex but
the key inflammatory molecule is interleukin-1
(IL-1). There are three standard anti-inflammatory
treatments (standard of care): colchicine; non-
steroidal anti-inflammatory drugs (NSAIDs); and oral/
injectable corticosteroids. 5,6 In any case, the patient
should be advised to start treatment as soon as
possible after the first recognisable signs of the gout
attack. Therefore, it is recommended patients carry
colchicine or NSAIDs with them, ‘in their pocket or
on their bedside table’. 1
Colchicine has good efficacy, particularly in
Table 1
Conditions and comorbidities
associated with gout
• Ageing
• Diabetes mellitus
• Metabolic syndrome
• Hypertension
• Coronary heart disease, myocardial infarction
• Cerebral vascular accident
• Peripheral obliterans arteritis
• Chronic kidney disease
• Atrial fibrillation
4 | 2018 | hospitalpharmacyeurope.com
The mechanism
of the gout attack
is complex, but
the main
inflammatory
molecule involved
in interleukin-1
regards to microcrystalline inflammation, when
it is started early at low doses: 1–1.5mg might be
sufficient on the first day.
Conventional NSAIDs (naproxen, indomethacin)
or COXIBs (etoricoxib) are effective if prescribed
in full doses for a short period of time (3–5
days). They are at risk of adverse reactions and
comorbidities dictate their use or otherwise. They
are contraindicated in cases of renal failure and anti-
vitamin K medication. Naproxen has the advantage
of improved cardiovascular safety.
Oral corticosteroids (prednisone 30mg/day,
for 3–4 days) are also effective. They are useful in
the event of adverse reactions, ineffectiveness or
contraindication to colchicine or NSAIDs. Poorly
controlled diabetes mellitus, heart failure or
hypertension might limit their use.
Canakinumab, an anti-IL-1 monoclonal antibody,
has European marketing authorisation and is
effective in the treatment of difficult-to-treat gout
attacks (classified as patients who have had at least
three gout attacks over a year, who are poorly
relieved by NSAIDs and colchicine, and who are
intolerant to both drugs and cannot be treated
repeatedly with prednisone). However, the long
duration of action of canakinumab (three months),
along within increased risk of infections and its cost
limit its use. Anakinra, an IL-1 receptor antagonist,
is sometimes used off-label; its half-life is short
but the risk of infection exists with prolonged
administration.
What are the comorbidities associated
with gout?
The main difficulty in the management of gout
is related to the associated comorbidities (Table
1). They give rise to contraindications or dose
limitations of so-called ‘standard of care’ drugs
and hypouricaemic drugs. Diabetes mellitus and
its macro- and microvascular complications,
cardiovascular diseases and chronic renal failure
(CKD) are the main comorbidities (see dedicated
articles in this handbook). Some of these
comorbidities such as diabetes and metabolic
syndrome and CKD are also involved in the
development of hyperuricaemia.
Comorbidities are already known to the patient’s
treating physician and pharmacist: in other words,
the occurrence of acute arthritis of the foot in such
a patient must be consistent with the diagnosis of
recent gout.
What is the real treatment for gout?
The cause of the disease is the accumulation of
urate microcrystals due to chronic hyperuricaemia;
and so the real treatment comprises reducing
uricaemia with urate-lowering therapies (ULT) below
the threshold of urate solubility. The threshold is
360µmol/l (6.0mg/dl) for uncomplicated gout and
300µmol/l (5.0mg/dl) for severe gout with tophi.
Two classes of ULT are available: xanthine oxidase
inhibitors (XOIs), which block uric acid synthesis;
and uricosurics, which block the mechanism of
increased reabsorption of uric acid into the renal
tubule.
XOIs
There are two XOIs: allopurinol and febuxostat.
Allopurinol is available at doses of 100, 200 and
300mg (this is the reference treatment in various
treatment guidelines). It is inexpensive and effective,
except in certain circumstances where its effectiveness
may be reduced, such as in CKD, in particular.
The initial dose is 100mg/day, or even 50mg/