The document describes a case of chronic tophaceous gouty arthritis in a 49-year-old male. It discusses the patient's history, physical exam findings, diagnosis, pathophysiology of gout, treatment options including medications, and guidelines for long-term management of hyperuricemia.
The document describes a case of chronic tophaceous gouty arthritis in a 49-year-old male. It discusses the patient's history, physical exam findings, diagnosis, pathophysiology of gout, treatment options including medications, and guidelines for long-term management of hyperuricemia.
The document describes a case of chronic tophaceous gouty arthritis in a 49-year-old male. It discusses the patient's history, physical exam findings, diagnosis, pathophysiology of gout, treatment options including medications, and guidelines for long-term management of hyperuricemia.
The document describes a case of chronic tophaceous gouty arthritis in a 49-year-old male. It discusses the patient's history, physical exam findings, diagnosis, pathophysiology of gout, treatment options including medications, and guidelines for long-term management of hyperuricemia.
1st year IM-SIGH Case • 49/M, Roman Catholic • Known case of gouty arthritis (2018), previously maintained on Colchicine 500mcg/tab 1 tab TID • CC: Joint pain x 3 days History of Present Illness • Patient started to have joint pain on right hand, with 2 days noted soft nodular lesions on MCP joints. No PTC associated fever or chills
• Still with above symptom, now also with pain on both
1 day knees and feet, with associated pain on walking. No PTC medication taken. No consult done.
• Progression of symptoms prompted consult
Consult PMHx: No HTN or DM; with history of acute gouty arthritis in flare (2018), given Colchicine 500mcg/tab
Physical exam: Social Hx:
• Awake, alert, not in cardiorespiratory Smoker, 34 pack- distress years; Alcoholic • 120/80 86 20 36.5 98% beverage drinker, • Anicteric sclerae, pink palpebral binge drinking conjunctivae, no tonsillopharyngeal once a week congestion, no clavicular lymphadenopathies • Symmetrical chest expansion, clear breath sounds • Adynamic precordium, normal rate regular rhythm • Flat, normoactive bowel sounds, non- tender, no masses • Full equal pulses, CRT<2 sec, no pallor, no edema • (+) tophi deposits on left ear, 1st and 2nd MTP joints of left hand, and 2nd and 3rd MTP joint left foot Case • Diagnosis: Chronic Tophaceous Gouty Arthritis in Acute Flare Gout • Middle-aged to elderly men and postmenopausal women • Affects 1.6% of the general adult population in the Philippines • Deposition of MSU crystals in joints, bones, and connective tissue • Hyperuricemia (>6.8mg/dL) Pathophysiology of Gout Examples of Tophi Deposits Conditions Influencing the Deposition of Urate Crystals • Decreased solubility of urate Ø Low temperature Ø Low pH • Disturbance to the joint or soft tissue • Reabsorption of water resulting in supersaturation Risk Factors Phases of Gout CHRONIC ASYMPTOMATIC ACUTE GOUTY INTERCRITICAL TOPHACEOUS HYPERURICEMIA ARTHRITIS GOUT GOUT
M: 7mg/dL Acute inflammation of Intervals Long term gouty
(416 umol/L) the joint caused by between complications of urate crystallization uncontrolled acute flares hyperuricemia F: 6mg/dL (357umol/L) Acute Gouty Arthritis • Acute arthritis is the most common early manifestation • First episode begins at night with dramatic joint pain and swelling • Early attacks tend to subside spontaneously within 3-10 days • Intervals of varying length and no residual symptoms until the next episode Precipitants of Acute Gouty Arthritis • Dietary excess • Trauma • Hospital admission or surgery • Infection • Dehydration • Excessive ethanol ingestion • Medications • Aspirin <1g/day, pyrazinamide, ethambutol, diuretics (Furosemide) • Hypouricemic therapy Chronic Tophaceous Gouty Arthritis • May present with a chronic non-symmetric synovitis after many acute mono- or oligoarticular attacks • Tophi is diagnostic for chronic tophaceous gout which causes significant joint destruction and deformity ACR/EULAR 2015 Gout Classification Criteria
Maximum possible score is 23
A threshold score of >/= 8 classifies an individual as having gout Laboratory Diagnosis • Synovial Fluid Analysis ü Direct visualization under polarized light – GOLD STANDARD - Extracellular and intracellular monosodium urate crystals - Needle-shaped with pointed ends - Strongly negative birefringent ü Inflammatory – WBC 10,000-100,000 (neutrophil predominance) • Serum Uric Acid ü During gout flare, may be high, normal, or low • Urinary Uric Acid • CBC ü Neutrophilic leukocytosis • Blood Chemistry ü Elevated ESR or CRP are common in gout flares Monosodium urate monohydrate crystals from a gouty tophus viewed under polarized light.
Strong birefringence, needle shaped morphology Extracellular and intracellular monosodium urate crystals. These crystals are needle-shaped with pointed ends, strongly negative birefringent under compensated polarized light microscopy
NSAIDS Indomethacin 25-50mg TID • Used most often in individuals without
Naproxen 500mg BID complicating comorbid conditions Ibuprofen 800mg TID • Resolution of signs & symptoms usually occurs Diclofenac 50mg TID in 5-8 days Celecoxib 800mg then 400mg 12 h later, then 400mg BID
Colchicine • 0.6mg tablet q8 with • Traditional and effective treatment if used
subsequent tapering early in an attack • 1.2 mg followed by 0.6 • Must be at least temporarily discontinued mg in 1h with promptly at the first sign of loose stools subsequent day dosing • Used as prophylaxis in doses 0.6mg OD-BID depending on response along with hypouricemic therapy • The safe use of Colchicine in patients with severe renal impairment (GFR <30mL/min) has not been established REGIMEN COMMENTS
Glucocorticoids Prednisone 30-50mg/day Initial dose and gradually tapered with the resolution of the attack can be effective in polyarticular gout
Prednisolone 35mg/day for 5 • Found to be equivalent to Naproxen
days 500mg/tab BID for treating flare • Has analgesic effectiveness equivalent to that of Indomethacin
Intraarticular Injection of • Good safety profile
Corticosteoids (Triamcinolone • Should be considered particularly in Acetonide 20-40 mg or patients with monoarthritis of an easily Methylprednisolone 25-50 mg) accessible joint
IL-1 blocker Canakinumab 150mg SQ • Used in patients with frequent flares
Anakinra 100mg SQ x 3 days and contraindications to colchicine, Rinolacept 320 mg NSAIDs, and corticosteroids (oral and injectible) • Contraindicated to those with current infection because of the risk for sepsis Prophylaxis for Gout Attack Hypouricemic Therapy • The minimum serum urate target is <6mg/dL (360umol/L) - For patients on ULT - Below the saturation point for MSU to dissolve all crystal deposits
• Serum urate lowering below 5mg/dL (300umol/L) may be
needed to improve gout signs and symptoms - Tophi - Chronic Arthropathy - Frequent attacks
• Serum urate <3mg/dL is not recommended in the long
term • Some studies have suggested that uric acid might protect against various neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, or amyotrophic lateral slerosis 2016 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF HYPERURICEMIA Indications for Pharmacologic Urate Lowering Therapy (ULT): • Tophus or tophi by clinical exam or imaging study • Frequent attacks of acute gouty arthritis (>/=2 attacks/year) • CKD Stage 2 or worse • Past Urolithiasis
• Recommended to be initiated close to the time of first diagnosis
for the following conditions: • Young age (<40 y/o) • High serum uric acid level (>8mg/dL or 480 umol/L) • Comorbidities (renal impairment, hypertension, IHD, heart failure)
• Pharmacologic ULT could be started during an acute gout
attack, provided that effective anti-inflammatory management has been instituted REGIMEN COMMENTS
Xanthine ALLOPURINOL • First line in patients with normal kidney function
Oxidase 100mg initially and increasing • SE: TEN, systemic vasculitis, BM suppression, Inhibitor by 100mg increments every 2-4 granulomatous hepatitis, renal failure weeks if required
FUBUXOSTAT • Potent, non-purine selective XOI
40 to 80mg OD • Metabolized in the liver and renal excretion is not a major route of elimination • More effective in patients with CKD than allopurinol given at doses adjusted to creatinine clearance Uricosuric PROBENECID • Used in patients with good renal function who underexcrete Agents Initiated at 250mg BID and uric acid with <600mg in 24-h urine sample increased gradually as needed • Not effective in patietns with serum creatinine >177 umol/L up to 3g/day (2mg/dL)
BENZBROMANE • More potent than probenecid
50-200mg/day • Not recommended for use In patients with eGFR <30mL/min but can be used in patients with moderate renal impairment LESINURAD • Approved only in patients on a xanthine oxidase inhibitor as an adjuvant at 200mg/day
LOSARTAN, FENOFIBRATE, • Mild uricosuric effects
AMLODIPINE Pegloticase • Pegylated uricase, produced by a genetically modified strain of E. coli • Catalyzes the oxidation of uric acid into allantoin, a more soluble end product • Used in patients with crystal-proven, severe debilitating chronic tophaceous gout and poor quality of life, in whom SUA target cannot be achieved by any other available drug at maximal dosage • No firm agreement with regards to the duration of treatment • However, there was a consensus to consider a switch, if feasible, toward an oral ULT once all tophi had disappeared References • 2012 American College of Rheumatology Guidelines for Management of Gout • 2016 Updated EULAR Evidence-Based Recommendations for the Management of Gout • 2015 Gout Classification Criteria: An ACR/EULAR Collaborative Initiative • Harrison’s Principles of Internal Medicine 20th Edition
