Iperuricemia nell’anziano: dal danno articolare al ... ... Iperuricemia nell’anziano: dal danno

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

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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

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4

4 -<

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6 -<

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fl a re

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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

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3 0

-< 3

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3 2

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3 4

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3 6

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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