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Prof. Dr. R V S N Sarma
Rheumatoid arthritis in adults
MD (Med), MSc (Canada), FCGP, FIMSA
Implementing
Senior Consultant
PhysicianNICE
and
guidance
Cardio-Metabolic & Chest Specialist
Hon. National Professor of Medicine
Visiting Professor of Internal Medicine at
Sri Balaji Medical College, Chennai and
Visiting Faculty at Frontier Life Line, Chennai
www.drsarma.in
drsarmaji YouTube
Dietary 34%, Endogenous 66%,
Purine nucleotides
hypoxanthine
Allopurinol
Xanthine
oxidase (XO)
xanthine
Uric acid
Urinary
excretion
2/3
Oxypurinol
1/3
Alimentary
excretion
Tissue deposition
in excess
Urate crystal
microtophi
Phagocytosis
with acute
inflammation
and arthritis
NSAID
uricosurics
colchicine
Gout: Over View
Gout is a systemic illness – a metabolic disease
• Defined as a peripheral arthritis resulting from the
deposition of sodium urate crystals in one or more joints
• deposition of uric acid in soft tissue as mono sodium urate
• deficient purine metabolism – serum uric acid elevation
• Demonstration of intra-articular mono sodium urate (MSU)
crystals -to establish a definitive diagnosis of gouty arthritis
• Prevalence is about 0.8 to 1.5% of the population
• Gout is 5 x more in males than premenopausal women
• Prevalence increases with age and increasing serum UA
• Strong familial predisposition – 80% of family members
The Spectrum of Gout
Acute Inflammatory Mono Arthritis
1
2
Serum hyper uricemia > 7 mg %
3
4
5
Tophaceous urate crystal deposit
Interstitial Renal urate deposition
Urolithiasis and Nephropathy
Etiology of Gout
• Primary gout
• Overproduction: 10%
• Under excretion: 90%
• Secondary gout
• Excess nucleoprotein turnover (lymphoma, leukemia)
• Increased cell proliferation or death (psoriasis)
• Rare genetic disorder Lesch-Nyhan Syndrome (HGPRT)
• Drugs – Thiazides, loop diuretics, PZA, Cyclosporine
• Ethanol abuse – habitual beer drinkers
• Dehydration – fluid deprivation
Signs and Symptoms
Acute attack
• With in few hours - frequently nocturnal
• Excruciating pain – worst pain ever experienced
• Swelling, redness and tenderness
• Podagra: 1st MTP classic presentation
• May effect knees, wrist, elbow, and rarely SI and hips.
Chronic
• Destructive Tophaceous Gout
• Much greater chance if untreated
• Rarely presents as a chronic illness
Sequence of Progression
Asymptomatic
Hyperuricemia
Acute Gouty
Monoarthritis
Interval or
Intercritical
Gout
Chronic
Tophaceous
Gout
Tophaceous Gout
•
•
•
•
Incidence has decreased over last few decades
Seen in 25-50% of untreated patients (after 10-20yrs)
Location: Olecranon, bursae, digits, helix of ear
Damages bone, peri articular structures and soft tissues
Palpable measure of total body urate load
Other Extra articular Complications
Uric acid calculi (seen in10-15% of gout pts)
Chronic urate nephropathy (in those with tophi)
Acute uric acid nephropathy (in pts undergoing chemotherapy)
Hypertensive Renal disease is the most common in gout
Diagnosis
•
•
•
•
Based on history and physical
Polarizing Light Microscopy
Confirmed by arthrocentesis
• Urate crystals: needle-shaped negatively
birefringent either free floating or within
neutrophils & macrophages.
Uric acid level is non specific.
• 30% may show normal level
24 hour Urine collection for urine uric acid estimation
• > 800 mg – Over producer (XO inhibitors)
• < 800 mg - under excretor (uricosuric)
• < 600 mg - purine-free diet
ACR Criteria for Diagnosis
Any 6 of following
1. More than one attack acute arthritis
2. Max. inflammation with in 1day
3. Erythema over joint 4. Podagra 5. H/o of Podagra
6. Unilateral tarsal involvement 7. Tophus
8. Hyperuricemia – serum uric acid > 7 mg%
9. Asymmetric swelling on X-ray
10. Subcortical cyst without erosion
11. Negative Culture for infective arthritis
Treatment
Acute Attack
• NSAID’s in anti-inflammatory doses
• Colchicine 0.5 mg oral every 2 hours, may require 6 mg.
Neutrophil micro tubular assembly inhibitor
Stop with response or side effect (diarrhea, vomiting)
Can be used for chronic disease, risk of BM suppression
• Joint aspiration followed by administration of IAS
• Oral Prednisone 30 – 60 mg/day for 1-2 weeks - taper
• ACTH 40-80 IM/IV or Solumedrol
• Opiates and Tylenol for analgesia
Treatment Acute Gout
NSAIDs Contraindicated?
 Renal insufficiency
 Peptic ulcer disease
 Congestive heart failure
 NSAID intolerance
NSAIDs
Anti inflammatory
doses
No
Yes
No
Are Corticosteroids
Contraindicated?
Corticosteroids
Yes
1
Oral Colchicine
Intra articular
PO Steroid
Lipsky PE, Alarcon GS, Bombardier C, Cush JJ, Ellrodt AG, Gibofsky A,
Heudebert G, Kavanaugh AF, et al. Am J Med 103(6A):49S-85S, 1997
# Joints
Involved?
>1
Oral or
Intra articular
Steroid
High Purine Foods
• All meats, including organ meats
• Meat extracts and gravies, Sea foods
• Yeast and Yeast extracts
• Beer and other Ethanol containing beverages
• Beans, peas, lentils, oatmeal
• Spinach, Asparagus, Cauliflower, Mushrooms
Treatment
Prophylaxis of Chronic Gout
• Diet low in purine - sea foods, meet
• Will decrease uric acid 1 mg/dL at best
• Weight loss is essential
• Limit consumption of Ethanol
• Modification of medications
• Avoid Salicylates, Diuretics, Niacin
Uric Acid Lowering Therapy (ULT)
• Never useful to treat acute attacks
• Two Approaches if SUA is more than 7 mg%
• Uricosuric therapy – Increasing UA excretion
•
If the 24 hour uric acid excretion is < 800 mg
•
Probenecid 500 mg, Sulfinpyrazone 50-100 mg bid
•
Urine out put of 2000 ml must be maintained
•
Xanthine Oxidase (XO) inhibitors  UA Production
•
Useful in over producers – urinary UA > 800 mg/24
•
Two drugs – Allopurinol, Febuxostat
•
Precipitation of acute attack is problem
Treatment
Chronic
• Uricosuric: for under excretors
Probenecid (Benemid)
Sulfinpyrazone (Anturane) - toxic side effects
Avoid in patients with renal disease
Consider NSAIDs to avoid exacerbation of gout
Benzbromarone is a good agent
Probenecid
Prophylaxis
• Initial
• 250 mg oral twice daily for 1 week
• Maintenance – uricosuric drug
• 500 mg oral twice daily
• If symptoms persist or
• If 24 h urate excretion below 700 mg
• Incrementally increase by 500 mg every 4 wks.
• Maximum of 2000 mg/day
Benzbromarone
• Benzbromarone (Benzarone) retains its uricosuric
effect at doses of 25–150 mg/day in patients who
have a creatinine clearance >25 mL/min.
• Good uricosuric effective and safe
• It is effective in mild to moderate disease
• May cause hepatotoxicity
• Limited availability
Treatment
Chronic
• Indications for Allopurinol (Zyloric, Zyloprim)
Tophaceous deposits
Uric acid consistently > 9 mg%
Persistent Symptoms with moderate UA levels
Impaired renal function
Prophylaxis for tumor-lysis syndrome
• Consider NSAID’s to avoid exacerbation
Allopurinol
• Indications for urate lowering therapy (ULT)
•
Recurrent attacks, tophi, bone / joint damage
•
Renal disease and/or nephrolithiasis,   SUA
• Mild Disease – Allopurinol is the drug of choice
•
100-300 mg/day orally as a single or divided doses
• Moderate to severe - Allopurinol
•
•
400-600 mg/day orally as a single or divided dose
(2-3 times daily); maximum dose 800 mg/day
It is a non selective Xanthine Oxidase (XO) inhibitor
Febuxostat
• It is recent selective XO inhibitor
• (Uloric) given as 80 mg daily single dose
• In those intolerant to Allopurinol
• In Renal insufficiency
• If target serum uric acid is not achieved
• High baseline serum uric acid levels
• Severe Tophaceous gout
Newer Drugs for Gout
• Febuxostat
• Pegloticase
• Losartan
• Fenofibrate
• Dietary supplements: Vitamin C
Pigloticase
• Intolerant to Allopurinol & Febuxostat
• Do not achieve target serum urate
• High baseline serum urate levels
• Severe Tophaceous gout
• Induction therapy
Other Drugs
• Losartan and Fenofibrate
• Hypertension or Hyperlipidemia present
• Mild effect
• Therapy for borderline Hyperuricemia
• Adjuvant therapy while on allopurinol
• Vitamin C
• Mild effect, not replicated instudies
• Borderline Hyperuricemia
Hyperuricemia
Hyperuricemia is linked to comorbidities
• Obesity
• Hyperlipidemia
• Metabolic syndrome
• Hypertension
• Diabetes mellitus
• Renal disease
• Heart failure
Ten Commandments
Fast acting NSAIDs are the drugs of choice for Acute Gout
Anti inflammatory drug Rx. must be continued for 1-2 wks.
Colchicine an effective alternative for NSAIDs. Slow to work
IAS are highly effective in acute mono arthritis of Gout
Oral or parenteral corticosteroids in NSAID intolerance
Allopurinol should not be used in acute attack of Gout
Allopurinol should be continued if the pt. is already receiving
Diuretic use for hypertension to be changed to other agents
Uricose uric Rx. Must be started after a second attack
Newer drugs in refractory cases with high serum UA levels.
Hippocrates described gout as “the king
of diseases and the disease of kings”
THANK YOU ALL