table 2
Phenotypes of gout patients
1 MTP1 arthritis in a young male No comorbidity
Positive family history due to
low fractional clearance of urate* Step 1 Often just NSAID offered
Steps 2–3 XOi: Allopurinol 100–300mg
daily
2 MTP1/ankle/knee arthritis in older male
or atypical arthritis in older female Obesity/hypertension/ hyperlipidaemia in
many/ DM in many: Cardiovascular risk
score high Steps 2–3 Will need XOi: allopurinol
escalation regime
3 MTP1/ankle/knee arthritis in older male Low fractional clearance of urate and
obesity due to lifestyle/hypertension/
hyperlipidaemia in many/DM in many:
Cardiovascular risk score high Steps 1–3 Will need personalised
treatment with high-dose XOi or
XOi+US: two MoAs
4 MTP1/ankle/knee arthritis in older man Diminished clearance: glomerular
filtration rate <50
Low fractional excretion of urate
Often advanced stage with tophi Step 1 Will need redefining the
personal target for treatment
depending also on feasibility
5 Gouty arthritis in young females/
hereditary syndrome Females with hypertension and/or
obesity; sporadic attacks Step 1–2 Personalised treatment
MTP1, metatarsophalangeal one; XOi, xanthine oxidase inhibitor; US, uricosuric; MoA, mode of action
*Fractional clearance of urate is a marker of how efficiently urate is being reabsorbed/excreted; average normal value in men is 7.5% and 4.5% in gout (although some gout patients
can have very low levels (1.5–2.0%))
of 17% of all gout patients were in Cluster 2 and
these were only obese; 24% in Cluster 3 had diabetes
and 1 in 3 with liver disorder (39%) plus excessive
alcohol use; 28% in Cluster 4 had dyslipidaemia
and hypercholesterolaemia without cardio-renal
disorders or hepatic disorders; 18% in Cluster 5 with
combined coronary heart disease and heart/renal
failure and often using diuretics. Cluster 5 was about
10 years older and consisted of more women in 28%
and minimal alcohol consumption. Such clusters do
not provide an epidemiologic insight of comorbidity,
but do not help us in clinical practice. In this article,
we describe patient journeys and case studies in five
separate identifyable phenotypes.
Clearly an arthritic patient can be treated for
quite some time with just intermittent NSAIDs
or prednisolone in cases of attacks presenting to
the general practitioner (GP). With crystal proof,
urate-lowering treatment (ULT) is usually initiated
at the second or third attack. In the third step, GPs
either themselves initiate ULT (XOI) or refer to
a specialist; factors involving this decision are GP-
as well as patient-dependent and also dependent
on numbers of comorbidities. An important factor
is the intrinsic motivation for chronic causative
treatment as well as adherence to improved lifestyle,
versus short-term therapy focusing solely on the
attack. Often forgotten as a factor is the rapid
availability of specialised care. Altogether, it might
take some time before the patient reaches stage 4,
that is, a negative urate balance. In step 5, networks
of cooperative care with specialists and GPs enable
patients to be treated for chronic continuation of
ULT in the periphery of care systems. 4 The optimal
patient journey should be chosen by patients and
physicians. 5
Case studies
Some real-life gout patient phenotypes and patient
journeys as presented to our department are
described in the following case studies.
Case study 1
A healthy 40-year-old man with a family history
10 | 2018 | hospitalpharmacyeurope.com
Intrinsic
motivation is
needed for an
improved lifestyle
and, if required,
ULTs
of gout (father had gout) and a three-year period
suffering from an annual gout attack in his big toe,
often presenting during the night. After the last
attack, about six months prior, he suffered from
recurrent flares that responded to colchicine and/or
prednisolone but the attacks still recurred. He had
initiated a healthier lifestyle through participating
in sports and drinking malted beers instead of
regular beer. He wanted to know how to prevent the
distressing attacks.
Physical examination Healthy man with BMI 21.2
with some residual redness over both MTP1 joints at
both sides
Ultrasonography Double contour sign left-sided
MTP1 with grade 1 power Doppler
X-rays forefeet Slight degeneration with
a subcortical cyst.
The Gout Calculator scored 11.5 points: highly
suggestive of gout regarding sensitivity and
specificity.
Laboratory test serum urate (SUA) 440μM
(7.4mg/dl) with glomerular filtration rate
>60; serum creatinine 90 ESR 2 and CRP<1,0;
haemoglobin 8.6mM and urate excretion 4.3mM
(72.28mg/dl); fractional clearance of urate
(FCU) 4.3%
Course Dietary advice (reduce purine ingestion/
stop malted beer and increase coffee intake; only
100g of meat daily) with colchicine 0.5mg twice
daily. This resulted in a slight improvement but
his complaints in feet remained as did his double
contour on ultrasongraphy (US) two months after the
initial measurement. Urate-lowering treatment was
started (allopurinol 300mg daily with a significant
improvement within 4 months; SUA dropped to
250mmol/l (4.2mg/dl). The double contour also
disappeared.
From such cases, it is shown that most diets are
enriched with calories and purines, and specific
families (genetic factors) with a lower urate
clearance due to urate transporters might be prone
to develop a urate accumulation syndrome resulting
in monosodium urate (MSU) deposits on the