Rheumatoid arthritis

1
FREEDOM FROM RHEUMATOLOGICAL DISORDERS
2

• Gout
• An elevated serum urate concentration
• Recurrent attacks of acute arthritis in which
  MSU( monosodium urate) crystals are seen in
  synovial fluid
• Aggregates of MSU crystals (tophi) are deposited
  in around joints leading to deformity
  crippling
• Hyperuricemia
• An elevated level of urate in the blood gt 7mg/dl
  in males and gt6.5mg/dl in females

3
Epidemiology

• The incidence of gout varies in population with
  an overall prevalence of less than 1 to 15.3
• Pathophysiology
• Uric acid is the end product of the degradation
  of purines.
• The accumulation may result from either
  overproduction or underexecreation.

4

• The purines from which uric acid is produced
  originate from three sources dietary
  purine,conversion of tissue nucleic acid to
  purine nucleotides and de novo synthesis of
  purine bases.
• Overproduction of uric acid result from
• Abnormalities in the enzyme system that regulate
  purine metabolism.
• An increase in the activity of phosphribosyl
  pyrophosphate(PRPP) synthatase, a key determinant
  in purine synthesis and thus uric acid
  overproduction.

5

• 3. A deficiency of hypoxanthine-guanine
  phosphoribosyl transferase (HGPRT) may also
  result in the overproduction of uric acid.
• 4. Increased breakdown of tissue nucleic acids,
  as with myeloproliferative and lymphoproliferative
  disorders.
• Drugs that decrease renal clearance
• Diuretics, salicylatelt2g\d, ethanol, L-dopa,
  cyclosporine, ethambutol..

6

• Normal individual produce 600-800mg of uric acid
  daily and excrete less than 600 mg in urine.
  Individual who excrete more than 600 mg on a
  purine-free diet are considered overproducers.
• Hyperuricemic individuals who excrete less than
  600mg per 24 hours on purine-free diet are
  defined as underexcretors of uric acid.
• On regular diet, excretion of gt1000 mg per 24
  hours reflect overproduction , less than this is
  probably normal.

7
Gout once called the Disease of Kings is
also seen in Women, Especially After Menopause
8

• MF - 71 to 91
• Women before menopause- F lt M
• In ages younger than 65- MF- 41 ratio
• In the older age groups gt 65- MF-31 ratio
• After 80 years of age-F gt M

9
URIC ACID METABOLISM MEN Vs WOMEN

• Estrogen have a mild uricosuric effect
  therefore, gout is unusual in premenopausal women
  
• Higher renal clearance of urate in women possibly
  due to their higher plasma estrogen levels
• The declining use of HRT may further increase the
  frequency of gout in women at an earlier age

10
Pathogenesis of Gout

• Hyperuricemia results from urate overproduction
  (10), under excretion (90) or often a
  combination of two
• Gout is mediated by supersaturation and
  crystallization of uric acid within joints
  ultimately, the formation of tophi
• Interactions of MSU crystals with the components
  of the innate immune system trigger acute gouty
  inflammation

11
Triggering Factors-Acute Attack
Alchol ingestion Dietary excess of purine Hemorrhage Acute medical illness Infections Exercise Trauma Surgery Drugs cyclosporine, furosemide, ethambutol, aspirin (Low dose), pyrazinamide, thiazides, nicotinic acids etc
12
Clinical Features in Gout patient
Asymptomatic Hyperuricemia Acute Gouty
Arthritis - Acute monoarticular
arthritis - The attacks begin abruptly
and reach maximum intensity in 8-12
hours - The joints are red, hot, and
exquisitely tender - Untreated, the
first attacks resolve spontaneously
in less than 2 weeks. -
Gout can initially present as a polyarticular
arthritis in 10 of
patients
13
Intercritical gout Chronic tophaceous Gout
- Attacks become more polyarticular -
Inflammation may become less intense -
Proximal and upper-extremity joints involved
- Attacks occur more frequently and last longer
- Tophi in the soft tissues (helix of the ear,
fingers, toes)
14
(No Transcript)
15
(No Transcript)
16
(No Transcript)
17
(No Transcript)
18
(No Transcript)
19
Clinical FeaturesMEN Vs WOMEN

• In women, polyarticular/tophaceous disease is
  often the first manifestation of gout
• A preceding recurrent mono-arthritis is found in
  joints other than the big toe
• The duration of disease before tophi is shorter
• The prevalence of tophi is higher and its
  localization different in female than in male
  patients

20

• Tophi are usually indolent and show little
  surrounding inflammation
• Gout in women has higher frequency of upper limb
  joint involvement in comparison to men
• The articular features of gout are usually
  similar

21

• Definitive diagnosis is best established by
• Aspiration of joint and identification of urate
  crystal
• The triad of acute monoarticular arthritis,
  hyperuricemia
• and dramatic response to colchicines
• Presence of 6 of the below mentioned 12
  clinical,
• laboratory and radiographic criteria

Criteria of Acute Gouty Arthritis
? More than one attack of arthritis
? Maximum inflammation in one day
?Monoarticular arthritis ?Joint
redness ? First metatarsophalangeal
joint involvement ? Unilateral
attack ? Unilateral attack involving
tarsal joint ? Suspected tophus
?Hyperuricemia ? Asymmetric
swelling within joint (radiograph) ?
Subcortical cyst without erosion (radiograph)
?Negative culture of joint fluid for
microorganism
22
Co morbid Conditions

• Renal stones
• Urate nephropathy chronic kidney failure
• Hypertension
• Diabetes
• Endothelial dysfunction
• Obesity
• Insulin resistance syndrome
• Atherosclerosis
• Cardiovascular disease related mortality
• Cerebrovascular disease
• Hypothyroidism

23
Treatment of Gout

• Treat acute arthritic attack promptly
• Prevent recurrence of acute gouty arthritis
• Lower urate levels
• Prevent or reverse complications of the disease
  resulting from deposition of MSU crystal in
  joint, kidney, or other sites
• Prevent or reverse co-morbid conditions like
  obesity, HT triglycerdemia renal
  complications

24
Treatment of Acute Gouty Arthritis

• NSAIDs are preferred in patients with
  uncomplicated gout
• Intraarticular corticosteroid for gout affecting
  one or two large joints
• Colchicine is preferred for patients in whom the
  diagnosis of gout is not confirmed
• It is most effective during the first 12-24
  hours of an attack, effectiveness declines with
  the duration of inflammation

25
Long-Term or Prophylactic Therapy

• Lowering uric acid with either allopurinol or
  probenecid can precipitate attacks of gout
• NSAIDs and colchicine are frequently used as
  prophylaxis against recurrent acute gout
• A standard practice is to use low-dose oral
  colchicine (0.6 mg orally twice a day in patients
  with intact renal function) for the first six
  months of antihyperuricemic therapy
• Long-term use of colchicine can lead to a muscle
  weakness with elevated levels of creatine kinase
  particularly in patients with renal insufficiency
  
• NSAIDs can be used for prophylaxis, such as
  indomethacin at 25 mg bid

26
Approaches to Lowering Uric Acid Levels

• Asymptomatic Hyperuricemia
• Rarely an indication for specific drug
  therapy
• Symptomatic Hyperuricemia
• Life long therapy with anti-hyperuricemic
  therapy is indicated in following situation
• gt2 or 3 acute attacks
• Renal stones
• Tophaceous gout
• Chronic gouty arthritis with bony erosions.

27
Antihyperuricemic Therapy

• In many cases, patients who have a first attack
  of gout should undergo therapy with agents that
  lower uric acid
• Some rheumatologists advocate waiting for the
  second attack to begin therapy to lower uric acid
  levels because not all patients have a second
  attack
• Antihyperuricemic therapy should be started a few
  weeks after the attack has resolved and with the
  institution of colchicine to prevent another
  attack

28
Indications for Allopurinol (Xanthine Oxidase
inhibitor)

• Hyperuricemia associated overproducers of uric
  acid
• In patients at risk of tumor lysis syndrome to
  prevent renal
• toxicity during therapy for malignancies
• Uric acid excretion of 1000mg or more in 24 hours
• Hyperuricemia associated with HGPRT deficiency or
  PRPP
• synthetase over activity
• Uric acid nephropathy
• Nephrolithiasis
• Intolerance or reduced efficacy of space
  uricosuric agents
• Gout with renal insufficiency (GFRlt60ml/min)
• Allergy to uricosurics

29
Candidates for uricosuric drugs

• Who is younger than 60 years of age and normal
  renal function (creatinine clearance greater than
  80ml/min)
• Uric acid excretion of less than 800 mg/24 hours
  on a general diet
• No h/o of renal calculi

30
Probenecid

• Reduce serum urate levels by enhancing the renal
  excretion of UA
• Fewer significant adverse effects than
  allopurinol
• Can be used in the majority of middle-aged
• Maintenance dose ranges from 500 mg to 3 g per
  day is administered on twice daily or thrice
  daily schedule
• Precipitation of gout, urolithiasis, and
  impairment of renal function are common side
  effects

31
Sulfinpyrazone

• Sulfinpyrazone is an alternative uricosuric agent
  that has antiplatelet activity but is seldom used
  because of the added risk of bone marrow
  suppression
• Starting dose, 50 mg orally twice daily
  gradually increased to 100-400 mg daily
• Precipitation of gout, urolithiasis, and
  impairment of renal function are common side
  effects

32
Dietary Management of Hyperuricemia

• Alcohol consumption must be avoided
• Diets like butter, red meat, pasta sweets, white
  rice, potatoes, white bread, wine beer, liquor,
  fish poultry and sea food increase the risk of
  gout
• Higher level of consumption of dairy products is
  associated with a decreased risk
• Moderate intake of purine-rich vegetables or
  protein is not associated with an increased risk
  of gout
• Those who consumes milk 1 or more times per day
  have a lower serum uric acid level

33
Recent Advances in Treatment

• Recombinant uricase can promote accelerated
  tophus dissolution
• Oxipurinol is the active metabolite of
  allopurinol. Patients with allopurinol
  hypersensitivity can often tolerate oxypurinol
• Febuxostat is an orally administered selective
  inhibitor of xanthine oxidase. It inhibits both
  the oxidized and reduced forms of xanthine
  oxidase. It is a potential alternative to
  allopurinol for patients with gout.
• Anti-tumour necrosis factor as a new therapeutic
  option

34
Treatment of Co morbid conditions

• The ARBs like losartan, Amlodipine the
  triglyceride-lowering agent fenofibrate -
  Uricosuric effects
• Weight loss is protective
• The amelioration of insulin resistance by either
  a low-energy diet or troglitazone Metformin
  therapy can also lower uric acid and attenuate
  the articular syndrome

35

• Role of HRT in Gout
• The effect of exogenously administered
  oestrogens, produce a fall in plasma uric acid
  concentration through a uricosuric effect
• However, there is no conclusive evidence is
  available for the use of estrogen replacement for
  such cases however it remains the potential area
  of research

36
Good luck