1. Rheumatoid arthritis in adults
Gout - Management
Prof. Dr. R V S N Sarma
MD (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
Rheumatoid arthritis in adults
Implementing NICE guidance
ABOUT THIS PRESENTATION:
This presentation has been written to help you raise awareness of the NICE clinical guideline on the management of rheumatoid arthritis (RA) in adults. This guideline has been written for rheumatologists, GPs, other healthcare professionals, people with RA and their carers, patient support groups, commissioning organisations and service providers.
The guideline is available in a number of formats, including a quick reference guide and an ‘Understanding NICE guidance’ version with information for patients and carers. You may want to hand out copies at your presentation so that your audience can refer to them. See the end of the presentation for ordering details.
You can add your own organisation’s logo alongside the NICE logo.
We have included notes for presenters, broken down into ‘key points to raise’, which you can highlight in you presentation, and ‘additional information’ that you may want to draw on, such as rationale or an explanation of the evidence for a recommendation. Where necessary, the recommendation will be given in full.
DISCLAIMER
This slide set is an implementation tool and should be used alongside the published guidance. This information does not supersede or replace the guidance itself.
PROMOTING EQUALITY
Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.
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2. Tissue deposition in excess
Dietary 34%, Endogenous 66%,
Purine nucleotides
hypoxanthine
Allopurinol
Xanthine oxidase (XO)
xanthine
Oxypurinol
Uric acid
1/3
2/3
Urinary excretion
Alimentary excretion
Tissue deposition in excess
Urate crystal
microtophi
NOTES FOR PRESENTERS:
You can download the guidance documents from the NICE website.
The NICE guideline – all the recommendations.
A quick reference guide – a summary of the recommendations for healthcare professionals.
‘Understanding NICE guidance’ – information for patients and carers.
The full guideline – all the recommendations, details of how they were developed, and reviews of the evidence they were based on.
For printed copies of the quick reference guide or ‘Understanding NICE guidance’, phone NICE publications on or and quote reference numbers N1790 (quick reference guide) and/or N1791 (‘Understanding NICE guidance’).
NICE has developed tools to help organisations implement this guideline, which can be found on the NICE website.
Costing tools – a costing report gives the background to the national savings and costs associated with implementation, and a costing template allows you to estimate the local costs and savings involved.
Audit support – for monitoring local practice.
uricosurics
Phagocytosis with acute inflammation and arthritis
colchicine
NSAID

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

4. 1 2 3 4 5 The Spectrum of Gout GOUT Acute Inflammatory Mono Arthritis
Serum hyper uricemia > 7 mg %
GOUT
Tophaceous urate crystal deposit
Interstitial Renal urate deposition
Urolithiasis and Nephropathy

5. Pathophysiology Urate saturates in plasma at 7 mg/dL
Assuming pH, temp, Na are WNL
MSU deposits in less vascular tissue
Cartilage
Tendons and / or ligaments
There is a predilection for peripheral joint / tissue

6. 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

7. Predisposing Factors Heredity Drug usage Renal failure
Hematologic Disease
Trauma
Alcohol use
Psoriasis
Poisoning
Obesity
Hypertension
Organ transplantation
Surgery

8. Signs and Symptoms Acute attack Chronic
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

9. Sequence of Progression
Asymptomatic Hyperuricemia
Acute Gouty Monoarthritis
Interval or Intercritical Gout
Chronic Tophaceous Gout

10. 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

11. Polarizing Light Microscopy
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 Microscopy

12. X-ray Findings in Gout Acute: Soft tissue swelling Chronic
Chronic Tophaceous gouty arthritis, extensive bony erosions are noted throughout the carpal bones
Sclerosis and joint-space narrowing are seen in the first metatarsophalangeal joint, as well as in the fourth interphalangeal joint.
Punched out bony defects
Retained bone density

14. ACR Criteria for Diagnosis
Any 6 of following
More than one attack acute arthritis
Max. inflammation with in 1day
Erythema over joint 4. Podagra 5. H/o of Podagra
6. Unilateral tarsal involvement 7. Tophus
8. Hyperuricemia – serum uric acid > 7 mg%
Asymmetric swelling on X-ray
Subcortical cyst without erosion
Negative Culture for infective arthritis

15. Differential Diagnosis
Septic Arthritis
CPPD – Pseudo Gout
Acute Rheumatic Fever
Palindromic Rheumatism
Psoriatic Arthritis

16. 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 IM/IV or Solumedrol
Opiates and Tylenol for analgesia

17. Treatment Acute Gout NSAIDs Contraindicated? Renal insufficiency
Peptic ulcer disease
Congestive heart failure
NSAID intolerance No
NSAIDs
Anti inflammatory
doses
Yes No
Corticosteroids
Are Corticosteroids
Contraindicated?
Treatment Acute Gout
Yes
# Joints
Involved?
>1 1
Oral Colchicine
Intra articular
PO Steroid
Oral or
Intra articular
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

18. 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

19. 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

20. 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 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

21. 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

22. 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

23. 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

24. 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

25. 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
mg/day orally as a single or divided doses
Moderate to severe - Allopurinol
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

26. 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

27. Newer Drugs for Gout Febuxostat Pegloticase Losartan Fenofibrate
Dietary supplements: Vitamin C

28. Pigloticase Intolerant to Allopurinol & Febuxostat
Do not achieve target serum urate
High baseline serum urate levels
Severe Tophaceous gout
Induction therapy

29. 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

30. Prognosis Generally good Acute attacks subside in 1 - 2 weeks
More severe course when Sx present < 30 y/o
Up to 50% progress to chronic disease if untreated.
Surgical intervention may be required for tophi.
Secondary Osteoarthritis in chronic joint Tophi

31. Hyperuricemia Hyperuricemia is linked to comorbidities Obesity
Hyperlipidemia
Metabolic syndrome
Hypertension
Diabetes mellitus
Renal disease
Heart failure

32. 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.

33. Hippocrates described gout as “the king of diseases and the disease of kings”

34. “The Management of Gout: It Should Be Crystal Clear”
Robert L. Wortmann
Editorial in J of Rheumatology Oct 2006

35. Case 1
56 yr postmenopausal female with sudden onset of acute pain in her right toe and knee. She had 3 previous episodes of the same symptoms lasting 4-5 days and treated. PM Hx HTN treated with thiazide diuretic and patient is trying to lose weight. BP138/86 BMI 32. PE remarkable for swollen & tender right great toe and knee. UA 8.3mg/dL, aspiration of her knee demonstrated WBC 15K and presence of urate crystals.
Treatment includes all of the following except:
Starting Allopurinol at 300mg/day with an NSAID for acute pain
Discuss risk factors for gout to include obesity, but continue with weight loss and switching of the HTN medication.
C. Start colchicine at 0.6mg bid and start uricosuric Rx. in 4 weeks
D. Start Rx. for acute pain with NSAIDs, but withhold uricosuric Rx.

36. Case 2
50 yr. male with long-standing gouty arthritis. He had several attacks a year treated by OTC NSAIDs. The attacks have become more frequent and the NSAIDs are not controlling the pain. He has HTN for which he takes Captopril. On PE BP 135/85, BMI 31, Temp N. Exam remarkable for a small effusion over right knee and tophi noted over both olecranons. Labs UA 7.5mg/dL, ESR 23mm/hr WBC count N. X-rays of his knees noted narrowing of joint space with effusion.
Best treatment option for this patient is
Start colchicine 0.6mg bid and urate lowering Rx. with allopurinol
Advise patient to discontinue NSAID therapy and use low dose prednisone daily for prophylaxis.
C. Colchicine 0.6 mg bid and uricosuric Rx. with Probenecid
D. Since patient is between attacks, just start urate lowering Rx.

37. Case 3
60 yrs male with persistent gout despite taking allopurinol daily at 100mg/day for the past year. He has a 20 year h/o of gout and was treated with NSAIDs for his acute flairs. However, once the attacks became more common, he was placed on chronic NSAID therapy. PM Hx significant for HTN and chronic renal insufficiency SCr PE: BP 125/73 BMI 34. No acute symptoms. Chronic synovial changes over wrists & left first MTP. Tophi over olecranon. UA 9.5 Best treatment option for this patient is A. Replace NSAIDs with prednisone. Do not change allopurinol dose B. Continue to increase allopurinol despite his renal issues to a dose that keeps UA level below 6.0mg/dL and replace NSAIDs C. Continue NSAID therapy for prophylaxis. Counsel pt. long term NSAID use and HTN can contribute to increasing renal disease. D. Discontinue all current meds and replace them with Colchicine E. None of the above

38. Case 4
A 62 yrs. male comes to you with pain and swelling over left great toe at MTP joint. Exam shows it is erythematous, warm swollen, tender to touch. No h/o previous such attacks. The patient has a history of DM controlled by diet and has HTN. His medications include HCTZ 25mg daily. A CBC and blood chemistry profile are normal except SUA 9.2 mg/dL. Which of the following is true in this situation A. This attack should resolve spontaneously in 2 days B. Allopurinol therapy should be started C. The elevated uric acid level establishes diagnosis of gout D. Intra-articular injection should be avoided E. Stopping the HCTZ may control Hyperuricemia

39. Case 5A
A 32 yrs. male complains of pain of 12 hr duration in the MTP joint of large left toe. He states that the joint is very tender to touch and denies history of trauma. He is on no meds. Exam is within normal limits except for large area of erythema over his left large toe and up onto the dorsum of his foot. No lymphangitis or cellulitis is noted. Which of the following tests help you in a definitive diagnosis A. A gram stain of the fluid aspirated from the joint B. 24hr urine collection for protein C. An X-ray of foot and ankle D. Microscopic examination for crystals in the synovial fluid aspirate E. Intravenous pyelography

40. Case 5B
A 32 yrs. male complains of pain of 12 hr duration in the MTP joint of large left toe. He states that the joint is very tender to touch and denies history of trauma. He is on no meds. Exam is within normal limits except for large area of erythema over his left large toe and up onto the dorsum of his foot. No lymphangitis or cellulitis is noted. Appropriate treatment choices may include which of the following A. Colchicine B. Probenecid C. Prednisone D. Indomethacin E. Allopurinol

41. Case 5C
You are able to aspirate synovial fluid from the joint, to establish diagnosis of gout, which of the following joint findings will establish the diagnosis of gout?
A. Negatively birefringent needle shaped crystals
B. Positively birefringent needle shaped crystals
C. Snowball like aggregate crystals
D. Dumbbell and octahedron shaped crystals

42. Thank you all