Rheumatoid arthritis in adultsImplementing NICE guidance

Prof. Dr. R V S N SarmaMD (Med), MSc (Canada), FCGP, FIMSA

Senior Consultant Physician and

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.indrsarmaji YouTube

www.drsarma.indrsarmaji YouTube

Purine nucleotides

hypoxanthine

xanthine

Uric acid

Xanthine oxidase (XO)

Alimentary excretion

Urinary excretion

Tissue deposition in excess

Urate crystal microtophi

Phagocytosis with acute inflammation and arthritis

uricosurics

colchicine NSAID

Allopurinol

Oxypurinol

Dietary 34%, Endogenous 66%, Dietary 34%, Endogenous 66%,

2/32/3 1/31/3

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

Serum hyper uricemia > 7 mg %Serum hyper uricemia > 7 mg %

Acute Inflammatory Mono ArthritisAcute Inflammatory Mono Arthritis

Tophaceous urate crystal deposit Tophaceous urate crystal deposit

Interstitial Renal urate deposition Interstitial Renal urate deposition

Urolithiasis and NephropathyUrolithiasis 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

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

• 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

Polarizing Light MicroscopyPolarizing Light Microscopy

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

Tre

atm

ent

Acu

te G

ou

t NSAIDs Contraindicated? Renal insufficiency Peptic ulcer disease Congestive heart failure NSAID intolerance

NSAIDs Contraindicated? Renal insufficiency Peptic ulcer disease Congestive heart failure NSAID intolerance

Are Corticosteroids Contraindicated?

Are Corticosteroids Contraindicated?

NSAIDsAnti inflammatory

doses

NSAIDsAnti inflammatory

doses

CorticosteroidsCorticosteroids

Oral ColchicineOral Colchicine

Oral orIntra articular

Steroid

Oral orIntra articular

Steroid

No

# Joints Involved?# Joints

Involved?

Yes

No

Yes

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

Intra articularPO Steroid

Intra articularPO Steroid

>11

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