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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).

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    18-34 35-44 45-54 55-64 65-74 75-84 over 85

    Hyperuricemia Males

    Hyperuricemia Female

    Gout Males

    Gout Females

    P re

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    en ce

    p er

    1 00

    0 in

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  • 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 -<

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    0

    10

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    Allopurinol

    1 0

    -< 1

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    1 2

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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