GOUT

BUI DUC LUONG MD.

 INTRODUCTION
• Systemic disease
• The deposition of monosodium urate crystals (MSU) in tissues
• 5% of people with hyperuriceamia above 9 mg/dL develop gout
• Gout: MSU crystals by joint fluid aspiration or in tophi aspirate.
EPIDEMIOLOGY

• The general prevalence of gout is 1–4% of the general population

• Men 2–6 folds more than women.
• Worldwide incidence of gout increases gradually: poor dietary habits, lack of
exercises, increased incidence of obesity and metabolic syndrome
PATHOGENESIS OF HYPERURICEMIA
PATHOGENESIS OF HYPERURICEMIA
PATHOGENESIS OF HYPERURICEMIA

• Urate crystals deposition in tissues starts to occur when serum uric acid level
rises above the normal threshold (>6.8 mg/dL)
• Lost balance between production and excretion
• 10%: increased production while 90% are caused by under-excretion
• Factors affecting SUA levels include age and gender. (old > young, male >
female)
CLINICAL SYMPTOM
CLINICAL SYMPTOM: 4 STAGES

1. Asymptomatic hyperuriceamia:
- no symptoms or signs
- accidentally discovered when measuring SUA (serum level greater than
7 mg/dL).
CLINICAL SYMPTOM

2. Acute gout
- Painful condition.

- The big toe, knee, or ankle joints are most often

affected.
- Throbbing, crushing, or excruciating pain
- Joint appears warm and red, fever
- After a first gouty attack, 50% no symptoms.
CLINICAL SYMPTOM

3. Chronic gout
- Joint damage
- Loss of motion in the joints
- Joint pain and other symptoms most of the time,
throughout the day
- Tophi below the skin around joints or in other places
CLINICAL SYMPTOM

4. Advanced Chronic Tophaceous Gout

- Tophi may be seen clinical or x-ray
- Tophi in articular cartilage, subchrondral bone, synovial membrane,
capsule, tendon sheaths and peri articular tissues.
- Tophi formation can also occur over eyelids, nasal cartilage, cornea,
tongue, vocal cords and penis
CLINICAL SYMPTOM

4. Advanced Chronic Tophaceous Gout

- The tophaceous nodules consists of multicentric deposition of urate crystals and
intra cellular matrix and foreign body granulomatous
reaction.
- As they enlarge in size, calcify, they can cause pressure symptoms.The tophi are
firm yellow in colour and occasionally discharge a chalky
material.
DIAGNOSIS: COMPARISON WITH EXISTING CRITERIA
DIAGNOSIS :
(1977 ACR CRITERIA FOR ACUTE GOUT)

- The presence of characteristic urate crystals in the joint fluid

- Or tophus proved to contain urate crystals by chemical means
- Or Polarized light microscopy,
- Or the presence of 6 of the following 12 clinical, laboratory, and radiographic phenomena:
1. More than one attack of acute arthritis
2. Maximum inflammation developed within 1 day
3. Monoarthritis attack
4. Redness observed over joints
1977 ACR CRITERIA FOR ACUTE GOUT
5. First metatarsophalangeal joint painful or
swollen
6. Unilateral first metatarsophalangeal joint
attack
7. Unilateral tarsal joint attack
8. Tophus (proven or suspected)
9. Hyperuricemia
10. Asymmetric swelling within a joint on xray/exam
11. Subcortical cysts without erosions on x ray
12. Joint fluid culture negative for organisms
during attack
2015 ACR-EULAR Gout Classification Criteria
2015 ACR-EULAR GOUT CLASSIFICATIONCRITERIA
DIAGNOSIS: ULTRASOUND
DIAGNOSIS: DUAL-ENERGY CT (DECT)
DUAL-ENERGY CT (DECT)
GOUT TREATMENT GUIDELINES
• 2016 ACP Guideline on Management of Acute and Recurrent Gout

• 2012 ACR Guidelines for Management of an Acute Gout Attack

• 2012 ACR Baseline Recommendations and Overall Strategic Plan for
Patients with Gout

• 2016 EULAR Recommendation for the Management of Flares in Patients

with Gout
• 2016 EULAR Recommendation for the Management of Hyperuricaemia in
Patients with Gout

• 2017 BSR Guideline for the Management of Gout

PHASES OF GOUT AND TREATMENT
GOALS
DIETARY PRESCRIPTIONS FOR GOUT AND
HU
TREATMENT GOUT
EULAR 2016
recommendation for the
management of flares in
patients with gout
 2012 ACR
Guidelines for
Management of
an Acute Gout
Attack
Acute Gout Management
Corticosteroid or Nonsteroidal Anti-inflammatory Drugs for the Treatment of Acute Gout: A Systematic Review
of Randomized Controlled Trials
CA Billy, RT Lim, M Ruospo, SC Palmer, GFM Strippoli. The Journal of Rheumatology August 2017, jrheum.170137

“There is no evidence that corticosteroids and NSAID have different efficacy in managing pain in acute gout, but corticosteroids appear to
have a more favorable safety profile.”

Does the initiation of urate-lowering treatment during an acute gout attack prolong the current episode and
precipitate recurrent attacks: a systematic literature review
F Eminaga, J Le-Carratt, A Jones, A Abhishek. Rheumatology International 2016; Vol 36, Issue 12, pp 1747–1752

“There is moderate-quality evidence that the initiation of ULT during an acute attack of gout does not increase pain severity and risk of ULT
discontinuation.”
EULAR 2016 recommendation
for the management of
hyperuricemia in patients with gout
 2017 BSR
Guideline for the
Management of
Gout
FDA-APPROVED
URATE-LOWERING AGENTS
 The Differences in the Mech
anisms of Action Between All
opurinol and
Febuxostat

(+) Uricosurics
XANTHINE OXIDASE INHIBITOR VS URICOSURIC

High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress
and not by lowering uric acid
J George et al. Circulation 2006; 114(23):2508-16

Allopurinol and Xanthine Nephropathy

JB Wyngaarden. N Engl J Med 1970; 283:371-372

Uricosuric Drugs: The Once and Future Therapy for Hyperuricemia?

MH Bach, PA Simkin. Curr Opin Rheumatol. 2014;26(2):169-175

”Urate nephropathy; rare hepatotoxicity”

Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in

patients with gout with an inadequate response to allopurinol
F Perez-Ruiz et al. Annals of the Rheumatic Diseases 2016;75:1074-1080
ALLOPURINOL VS FEBUXOSTAT
ALLOPURINOL VS FEBUXOSTAT
Comparative effectiveness of urate lowering with febuxostat versus allopurinol in gout: analyses
from large U.S. managed care cohort
JA Singh, KS Akhras, A Shiozawa. Arthritis Research & Therapy 2015; 17:120

“Febuxostat was more effective than allopurinol at the currently used doses (40 mg/day for febuxostat in 83% users and 300 mg/day or lower for
allopurinol in 97% users) in lowering sUA in gout patients as demonstrated by post-index mean sUA level, the likelihood of and the time to
achieving sUA goals.”
ALLOPURINOL VS FEBUXOSTAT
Comparative effectiveness of allopurinol versus febuxostat for preventing incident renal
disease in older adults: an analysis of Medicare claims data
JA Singh, JD Cleveland. Annals of the Rheumatic Diseases Published Online First: 05 June 2017. doi: 10.1136/annrheumdis-2017-211210

Ref: Febuxostat 40mg Incident Renal Disease

Hazard Ratio (95% CI) p-value
Febuxostat >40mg 0.97 (0.73 to 1.29) 0.83
Allopurinol <200mg 0.75 (0.65 to 0.86) <0.0001
Allopurinol 200–299mg 0.61 (0.52 to 0.73) <0.0001
Allopurinol ≥300mg 0.48 (0.41 to 0.55) <0.0001
Allopurinol (all doses) 0.61 (0.54 to 0.69) <0.0001

“Allopurinol was more effective than Febuxostat and was associated with greater reduction in the risk of incident kidney disease. The
association of Allopurinol with renal protection was dose-related, and possibly duration-related, with higher reduction of hazard of
incident renal disease with higher Allopurinol doses.”
HLA-B*5801 & ALLOPURINOL-INDUCED SCAR
Severe Cutaneous Allergic Reactions (SCAR)  Presents within first 3 months of starting drug
Stevens Johnson Syndrome (SJS)
Toxic Epidermal Necrolysis (TEN) Median onset 3-4 weeks from drug initiation
Drug Reaction with Eosinophilia & Systemic Symptoms (DRESS)
 Allele frequency in Singapore
 Chinese 1 in 5
 Malay 1 in 15
 Indian 1 in 25

 OR 100:1; PPV 2%, NPV almost 100%

 Other risk factors

 Renal impairment
 High starting dose
HLA-B*5801 & ALLOPURINOL-INDUCED SCAR
2018 Updated EULAR Evidence-based
Recommendations for the Diagnosis of Gout
Summary of recommendations in lay format (1 of 2)

Recommendation *
Every person suspected of having gout should be tested for crystals. Finding ***
MSU crystals allows a definitive diagnosis of gout
Gout should be suspected in any adult with acute arthritis. As well as testing ***
for crystals, gout may be diagnosed by questioning the patients and
examining the joints, particularly the foot and ankle for pain, swelling or
redness
Any person with undiagnosed inflammatory arthritis should have their **
synovial fluid checked for crystals
The diagnosis of gout should not be made based solely on high levels of uric ***
acid in the blood

1 star (*) means it is a weak recommendation with limited scientific evidence; 2 stars (**) means it is a weak recommendation with some scientific evidence; 3 stars (***) means it is
a strong recommendation with quite a lot of scientific evidence; 4 stars (****) means it is a strong recommendation supported with a lot of scientific evidence.
Recommendations with just 1 or 2 stars are based mainly on expert opinion and not backed up by appropriate clinical studies, but may be as important as those with 3 and 4 stars.
51 29/08/2022
Summary of recommendations in lay format (2 of 2)

Recommendation *
When a clinical diagnosis of gout is uncertain and crystal identification is not ****
possible, imaging should be used to look for urate deposits and features of
any alternative diagnosis
X-rays can be used to look for urate arthropathy but cannot always diagnose ****
acute gouty arthritis. Ultrasound scanning or Dual Energy Computed
Tomography (DECT) can aid diagnosis by detecting tophi or urate deposits
People with gout should be checked for risk factors for high uric acid levels, ****
including chronic kidney disease, being overweight, certain medications,
drinking excess alcohol or non-diet sodas, or eating meat and shellfish
People with gout should be checked for linked diseases, including obesity, ****
kidney impairment, heart disease or failure, diabetes, high blood pressure or
high lipid levels in the blood

1 star (*) means it is a weak recommendation with limited scientific evidence; 2 stars (**) means it is a weak recommendation with some scientific evidence; 3 stars (***) means it is
a strong recommendation with quite a lot of scientific evidence; 4 stars (****) means it is a strong recommendation supported with a lot of scientific evidence.
Recommendations with just 1 or 2 stars are based mainly on expert opinion and not backed up by appropriate clinical studies, but may be as important as those with 3 and 4 stars.
52 29/08/2022