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Iperuricemia nell’anziano: dal danno articolare al deterioramento cognitivo
Giovambattista Desideri Unità Operativa e SS di Geriatria
Università degli Studi Dell’Aquila
Epidemiology of gout and hyperuricaemia (SUA >6 mg/dL) in Italy during the years 2005–2009
Trifirò G, et al. Ann Rheum Dis (2011).
0
50
100
150
200
250
300
350
400
450
18-34 35-44 45-54 55-64 65-74 75-84 over 85
Hyperuricemia Males
Hyperuricemia Female
Gout Males
Gout Females
P re
v al
en ce
p er
1 00
0 in
h ab
it an
ts
Gout: The Fashionable Disease
"the disease of kings”
"rich man's disease”
Ann Rheum Dis 2006;65:1301–1311
Likelyhood ratio for various features in the diagnosis of gout - EULAR
Gout in the elderly: (a)tipical features
Tophi can supervene on Heberdenʼs and
Bouchardʼs nodes.
Gout is one of the most painful type of arthritis, but in the elderly tend to be more indolent while gout flares tend to be more polyarticular
Given the chronicity of gout, elderly patients tend to have an increased incidence of tophi, especially of the elbows and hands
The presence of tophi in the hands and the upper extremities can be mistaken for rheumatoid nodules.
Musculoskeletal US can be able to visualize intraarticular crystal deposits with a characteristic hyperechoic enhancement of the outer surface of the hyaline cartilage, known as the “double contour sign.”
Asymptomatic articular damage in hyperuricemia
Hyperuricemia and gout: time for a new staging system?
Dalbeth N et al. Ann Rheum Dis 2014
A proposed revised staging system for
hyperuricaemia and gout, based on the American
Heart Association heart failure staging system.
Presence of
strong CYP3A4
P-glycoprotein
inhibitors
Treat as early as possible
Severe renal
failure
Avoid colchicine
Contra-indications to
cochicine, NSAIDS and
corticosteroids (oral and
injectable)
Education about the disease
Individualised lifestyle advice
Screening for comorbidifties
and current medications
Therapeutic options
Depending on the severity, the
number of affected joints and
duration of attack
Colchicine
(1 mg followed 1
hour later by 0.5 mg)
NSAID
(classic or coxibs +
PPI if appropriate)
Prednisolone
(30-35 mg/d for 5
days)
IA
Injection of
corticosterod
Combination therapy
(for istance colchicine
+NSAID or corticosteroids)
Resolution of flares Educate to self medicate
Consider initiation of ULT
(together with flare profilaxys)
Avoid cochicine
and
NSAIDS
Consider IL-1 blockers
Management of
acute flare
Ann Rheum Dis 2016;0:1–14.
2016 Eular Recommendation for the Management of Hyperuricemia in Patients with Gout
Richette P, et al. Ann Rheum Dis 2016;0:1–14. doi:10.1136/annrheumdis-2016-209707
The greatest concern with the use of allopurinol in patients with renal failure is the
development of serious cutaneous adverse reactions (SCARs), which includes drug
rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and
toxic epidermal necrosis. Allopurinol was found to be the most common drug associated
with SJS or toxic epidermal necrolysis in Europe
Allopurinol-induced SCARs are rare, the incidence rate being about 0.7/1000 patient-
years in allopurinol initiators in the USA,but the mortality rate is high (25%–30%
Renal failure has been associated with an increased risk of SCARs and poor
outcome. Decreased renal function results in decreased clearance and higher serum
levels of oxypurinol, which could induce a cytotoxic T-cell respons and trigger
hypersensitivity reactions in SCARs.
Febuxostat has been found more effective in patients with CKD than allopurinol
given at doses adjusted to creatinine clearance and therefore can be used in these
patients.
Data do not support any cross-reactivity between the two drugs.
Clinical Efficacy and Safety of Successful Longterm Urate Lowering with Febuxostat or Allopurinol in Subjects with Gout: EXCEL study
Becker MA, et al. J Rheumatol 2009; 36:1273-1282.
Febuxostat 80 mg
Febuxostat 120 mg
0 -<
2
2 -<
4
4 -<
6
6 -<
8
8 -<
1 0
p ro
p o
rt io
n o
f s
u b
je c
ts re
q u
ir in
g g
o u
t
fl a re
tr e a tm
e n
t
Time (months)
0
10
20
30
40
50
Allopurinol
1 0
-< 1
2
1 2
-< 1
4
1 4
-< 1
6
1 6
-< 1
8
1 8
-< 2
0
2 0
-< 2
2
2 2
-< 2
4
2 4
-< 2
6
2 6
-< 2
8
2 8
-< 3
0
3 0
-< 3
2
3 2
-< 3
4
3 4
-< 3
6
3 6
-< 3
8
3 8
-4 0
Maintenance of SUA < 6.0 mg/dl resulted in progressive reduction to nearly 0 in proportion of
subjects requiring gout flare treatment
≈40%
treated ≈20%
treated
≈60%
treated
Total health care resource costs during 6 months from index date according to ULT
Degli Esposti L et al, submitted
euros
D20%
1.00
1.99 (1.77-2.24)
1.24 (1.08-1.41)
1.21 (1.09-1.35)
IRR (95% CIs) [Ref. ≤ 6 mg/dl]
> 6 ≤ 7 mg/dl
> 7 ≤ 8 mg/dl
> 8 mg/dl
1.75 (1.65-1.85)
1.24 (1.18-1.32)
1.10 (1.05-1.15)
IRR (95% CIs) [Ref. ≤ 6 mg/dl]
> 6 ≤ 7 mg/dl
> 7 ≤ 8 mg/dl
> 8 mg/dl
1.00
[Ref. ≤ 6 mg/dl]
> 6 ≤ 7 mg/dl
> 7 ≤ 8 mg/dl
> 8 mg/dl
1.00
2.12 (1.98-2.27)
1.20 (1.11-1.29)
0.98 (0.92-1.04)
HR (95% CIs)
SUA levels and Hx for kidney disease
SUA levels and Hx for CVD
SUA levels and total mortality
Degli Esposti L et al, NMCD 2016
Chaudhary K et al Cardiorenal Med 2013;3:208–220
Hyperuricemia and Cardiorenal Metabolic Syndrome
Low uric acid levels in patients with Parkinson’s disease: evidence from meta-analysis
Shen L, Ji H-F. BMJ Open 2013
Parkinson Controls
Alexander the great, Darwin, Harvey, Newton, Sydenham, ….
This association cannot be mere co-incidence….
Study of Serum Uric Acid and its Correlation with Intelligence Quotient and Other Parameters in
Normal Healthy Adults
Patil U et al. International Journal of Recent Trends in Science And Technology 2013
100 medical students in the age group of 17 to 20 years
Lessons from comparative physiology: could uric acid represent a physiologic alarm signal gone
awry in western society?
Johnson RJ et al. J Comp Physiol B. 2009 179(1): 67–76.
Uric acid having similar structure to that of caffeine and theobromine acts as a cerebral stimulant and thought to be responsible for better development of brain and more intelligence.)1.
Uric acid can increase locomotor activity in rats2
Uric acid increases with emotional or physical stress3
1 Orowan E. Nature 1955;175:683–684.
2 Barrea CM et al. Pharmacol Biochem Behav1989;33:367–369.
3 Rahe RH et al. Psychosom Med 1974;36:258–268.
caffeine
SUA and cognitive function and dementia
Euser SM et al. Brain 2009: 132; 377–382
The mean age of the total sample of 4618 participants
was 69.4 years, 61% were female and the mean
serum level of uric acid was 322.3 mmol/l.
Shah A, et al. Curr Rheumatol Rep (2010) 12:118–124
Gout, Hyperuricemia, and the Risk of Cardiovascular Disease: Cause and Effect?
Odi et amo….
quare id faciam fortasse requiris…
SUA, oxidative stress and cardiovascular disease:
a comprehensive hypothesis
XO-overactivity (genetic, induced)
XO-”overfeeding” (food, fructose, purines)
HTN, CKD
CV disease
Serum Uric Acid
Cellular entry of
Uric Acid
Intracellular Uric
Acid
i.c. oxidative stress ( eNOS)
mitochondrial dysfunction
RAAS activation
Oxidative stress
High TG,MS,TOD
Gout
Borghi C, Desideri GB, Hypertension 2016