Gout

Study guide:

Definition:

  • Inflammatory monarticular arthritis, caused by the precipitation of monosodium urate crystal into tissue, usually in and around joints.

Epidemiology:

  • Gout has a male predominance at 30-50 years of age.

  • The most common inflammatory joint disease (arthropathy) in men.

  • Male: female 4:1 <65 years of age, and becomes 3:1 >65 years of age 90% of patients are male over 30 years of age.

  • Prevalence differs regionally (i.e. rare in African Americans and very common in

    Asians).

Risk Factors:

  • Age: 30-50 years

  • Sex: Males> females (Risk increases for females after menopause)

  • Hyperuricemia (the main risk factor for gout)

  • Menopause: estrogen plays a protective role by ↑ uric acid excretion

  • Hypertension

  • Obesity

  • Alcohol

    • Beer has high purine content.

    • Kidneys will excrete alcohol instead of uric acid.

  • Drugs: thiazides, loops diuretics, aspirin.

  • Food high in purine: e.g. red meat, fish.

  • Family History (~20% of patients have a family history)

  • Renal failure

  • Hyperlipidemia

  • . Diabetes

Pathophysiology:

  • Uric acid is the end product of purine metabolism in humans

  • At the end of the metabolism cascade: hypoxanthine xanthine Uric acid

  • Both steps require Xanthine oxidase enzyme

  • Hyperuricemia (HALLMARK of the Disease) precedes Gout

  • Hyperurcemia is defined as Serum uric acid >6.8mg/dl

  • This can occur either due to:

    1. Under-excretion of uric acid from the kidneys (accounts for 90% of the causes)

    2. Overproduction/overconsumption of Uric acid

  • Urate crystal which form due to the increase level of uric acid in the blood, will lead to an inflammatory process with neutrophil predominance.

 

Types& causes:

1- Primary (90% of cases):

  1. Idiopathic or due to an abnormal enzyme

    function/production resulting in: under excretion or

    overproduction of uric acid.

  2. Some enzymatic abnormalities resulting in uric acid

    overproduction include:

    1. Lesch-Nyhan Syndrome: Hypoxnathine-guanine

      phosphoribosyltransferase (HGPRT) deficiency.

    2. Superactivity of phosphoribosyl pyrophosphate

      synthetase (PRPP)

    3. Von Gierke’ s disease: Glucocse-6-phosphate

      deficiency .

2- Secondary to:

  1. Medical condition: renal failure, HTN...

  2. Malignancies é cell lysis éuric acid levels

  3. Drugs & toxins: thiazides, Lead poisoning...

*Both types have the same pathophysiological pattern explained earlier.

HGPRT is an enzyme that uses guanine and hypoxanthine to produces purines instead of letting them get metabolized to Uric acid.

PRPP is an important enzyme in producing both purines and pyrimidines.

 

Clinical features and course:

The clinical course of gout is classically divided into 4 stages:

  • Asymptomatic Hyperuricemia:

    • ​↑ levels of uric acid with NO clinical symptoms (10-20 years)

    • Manifests around puberty in males & post-menopausal in females.

    • Almost 90-95% of cases remain in this stage.

  •  Acute gouty arthritis

    • Sudden, excruciating pain appears after years of being asymptomatic

    • Lasts for hours to weeks.

    • Predominantly occurring in men > 40 years of age

    • Initially affecting 1 joint (mono-articular): signs of inflammation +/- mild fever.

    • The most common affected joint is the big toe (first MTP joint) i.e. podagra

  • Intercritical gout:

    • Asymptomatic period following the first attack

    • There is 75% chance of another, poly-articular & more severe

    • attack within 2 years after the initial attack

  • Chronic tophaceous gout

    • In patient with poorly controlled gout for 10-20 years (an average of 10 years after the initial attack)

    • Tophi: built up of uric acid crystals in soft tissue of a gouty joint. causing a characteristic juxtaarticular bone erosions.

      • Common locations of tophi: elbows, knees, pinna of the external ear, & Achilles tendon

Signs and symptoms of an acute gouty attack:

  • Severe pain, redness & joint swelling

  • Limited joint mobility

  • Symptoms last for hours to months & usually subside on their own.

 

Investigation and Diagnosis:

  • Arthrocentesis -> definitive diagnosis test

    • Hallmark of gout needle-shaped crystals with negative birefringent crystals.

  • X-rays, which show: 

    • ​Punched-out lesions with overhanging edges (circle)

    • Tophi as soft tissue swelling (square)

  • Serum uric acid levels are not helpful in the diagnosis.

Psueodogout vs. gout: Pseudogout has rhomboid shaped needles & slightly positive birefringence.

Management:

  • General management: Modifying risk factors.

  • Acute gouty arthritis:

    • NSIADS (indomethacin): 1st line treatment of choice for an acute gouty attack

    • Corticosteroids:

      • Oral: prednisone

      • IV: methylprednisolone

      • IM: betamethasone

    • Colchicine: alternative if NSIADs didn’t work or not tolerated

      • Limited use GI toxicity in up to 80% of patients

  • Long term-prophylactic management (in patients with recurrent gouty attacks):

    • Antihyperuricemic agent (allopurinol): xanthine oxidase inhibitor -> ↓ uric acid production

    • Uricosuric agents (probenecid): ↑ uric acid excretion

      • Contraindicated in renal failure patients.

  • Considerations:

    • Give Colchicine or NSAID for 3-6 months then discontinue and start prophylactic regimen

    • NEVER give prophylactic medications in acute gout makes it worse!

    • Choosing which prophylactic drug depends on the amount of uric acid excreted

      within 24 hours:

      • If >800mg/day indicates overproduction -> use allopurinol

      • If <800mg/day indicates under-excretion -> use probenecid

Complications:

1. Nephrolithiasis:

  1. Represents 10% of kidney stones

  2. Uric acid kidney stones are radiolucent on X-ray

2-Degenerative arthritis

References:

  1.  http://www.msdmanuals.com/professional/musculoskeletal-and-connective- tissue-disorders/crystal-induced-arthritides/gout

  2.  http://emedicine.medscape.com/article/329958-clinical

  3.  http://www.ncbi.nlm.nih.gov/pubmed/15299172

  4. https://www.academia.edu/7726609/Epidemiology_of_gout_An_update

  5. http://www.uptodate.com/contents/treatment-of-acute-gout

  6. Agabegi, Steven S, and Elizabeth D Agabegi. Step-Up To Medicine. Philadelphia: Lippincott Williams & Wilkins,

    2008. Print.Hall, Justin, and Azra Premji. Essential Med Notes 2015.

    Print.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104583/ (gout risk factors)

  7. Fischer, Conrad. Master The Boards. Print.

  8. Sattar, Husain A. Fundamentals Of Pathology. Chicago: Pathoma.com, 2011. Print.

  9. Toronto Notes

  10. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104583/

Written by:       Husam Tahan

Reviewed by:   Haifa Al Issa

                             Abdullah Al Assad

Format Editor: Bayan Alzomaili

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