//fpnotebook.com/
Gouty Arthritis
Aka: Gouty Arthritis, Gout, Podagra
- See Also
- Joint Pain
- Monoarticular Arthritis
- Polyarticular Arthritis
- Purine Containing Food
- Definitions
- Joint and tissue deposition of monosodium urate crystals
- Epidemiology
- Men and post-menopausal women more commonly affected
- Estrogen is protective pre-Menopause by increasing Uric Acid excretion
- Age
- Gout is rare under age 20 years old
- Prevalence
- Men: 3-6%
- Women 1-3%
- Increasing Prevalence in United States related to Obesity and aging population
- Affects 8 million in United States (most common inflammatory Arthropathy)
- Prevalence increases with age (affects 12% of those over age 80 years old)
- Black patients have a higher Prevalence
- Incidence of gout attacks
- Uric Acid 7 to 8.9 mg/dl: 0.5% annual Incidence
- Uric Acid >9 mg/dl: 4.5% annual Incidence
- Pathophysiology
- See Uric Acid
- See Hyperuricemia
- Isolated and asymptomatic Hyperuricemia is common and requires no treatment
- Elevated levels are common, and most Hyperuricemia will not result in gout or other adverse effects
- Gout occurs when Uric Acid levels exceed solubility limits
- Monosodium urate crystals deposit in joints, Kidney, and soft tissues
- Crystal deposition triggers a inflammatory response from Cytokines and Neutrophils
- Joint space is irreversibly injured with ongoing attacks
- Risk Factors
- Most common
- Obesity
- Alcohol use (especially beer)
- Diet high in Purine Containing Food (red meats, turkey and wild game, organ meats, seafood)
- Drinks sweetened with high fructose corn syrup
- Diuretic therapy including Thiazide Diuretics and Loop Diuretics
- Hyperuricemia
- Other risks
- Diabetes Mellitus
- Hyperlipidemia
- Hypertriglyceridemia
- Hypertension
- Atherosclerosis
- Renal Insufficiency
- Myeloproliferative disease
- Tacrolimus (Prograf)
- Ethnicity (indigenous Tiawan, Pacific Islanders, Maori of New Zealand)
- Causes: Triggers for acute gout attacks
- See Hyperuricemia
- See Risk Factors above
- Recent increase in Alcohol or purine intake
- Medication use (Allopurinol stopped or started, Diuretic or Chemotherapy started)
- Acute infection
- Intravenous Contrast dye exposure
- Presentations
- Monoarthritis (most common)
- Acute Bursitis
- Tenosynovitis
- Acute polyarticular gout
- Symptoms
- Associated Symptoms
- Chills
- Fever as high as 104 F (40 C)
- Severity: Very severe pain
- Unable to bear weight
- Too painful to put on socks
- Intollerant to light touch from blankets
- Distribution: Lower extremities
- First Metatarsophalangeal joint of great toe (56-78% of cases, most common)
- Known as Podagra
- Affected in 50% of first gout attacks
- Mid-tarsal joints (25-50% of cases)
- Ankle Joints (18-60% of cases)
- Knee Joints
- Distribution: Upper extremities
- Finger interphalangeal Joints (6-25% of cases)
- Wrists
- Elbows
- Characteristics: Joint Pain
- Excruciating, crushing type pain
- Timing: Joint Pain
- Acute onset of lower extremity Joint Pain, typically peaking in the first 24 hours
- Wakens patient from sleep
- Signs
- Acute
- Joint Inflammation
- Erythema, tenderness and swelling at affected joint
- Pain extends well beyond joint
- Entire foot involved in some cases
- Asymmetric joint involvement
- May only involve one side with the first attack
- Skin over joint is tense and shiny
- Chronic
- Gouty Tophi (develop after 10 years)
- Subcutaneous Nodules of monosodium urate crystals and lipids, proteins and mucopolysaccharides
- May drain chalk-like material
- Common sites include ear, olecranon bursa, fingertips
- Chronic Arthritis
- Chronic deposition occurs with recurrent attacks
- Labs
- Complete Blood Count
- Leukocytosis (may be as high as 40,000 wbc/mm3)
- Serum Uric Acid increased
- Hyperuricemia (typically defined as serum Uric Acid >6.8 mg/dl)
- Normal Uric Acid does not exclude gout
- Uric Acid levels are often suppressed to normal levels during a gout flare
- Schlesinger (2009) J Rheumatol 36(6): 1287-9 [PubMed]
- Synovial Fluid Exam (critical if Septic Arthritis is considered)
- Polarizing Light Microscopy
- Negatively birefringent
- Needle shaped Uric Acid crystals
- Gram Stain and Culture
- Rule out Septic Arthritis
- Urine Uric Acid (24 hour collection)
- May be considered
- Imaging
- See XRay Changes in Rheumatic Conditions
- Xray Findings
- Nonspecific and asymmetric swelling is often the only XRay finding
- Subcortical cysts without bony erosions
- Joint Ultrasound findings (any of three findings are consistent with Gouty Arthritis)
- Double contour sign
- Tophus
- Snowstorm appearance
- Ogdie (2017) Arthritis Rheumatol 69(2): 429-38 [PubMed]
- CT Joint
- Conventional CT identifies Gouty Tophi and bony erosions
- Dual-Energy CT detects monosodium urate deposits
- Bongartz (2015) Ann Rheum Dis 74(6): 1072-7 [PubMed]
- Diagnosis: Requires one of the following
- Monosodium urate crystals in Synovial Fluid OR
- Test Sensitivity: 84%
- Test Specificity: 100%
- Gouty Tophi with urate crystals identified on Nodule aspirate OR
- Test Sensitivity: 30%
- Test Specificity: 99%
- Minimum of 6 criteria present from the following list
- Plain radiograph demonstrates subcortical cysts without erosions
- Plain radiograph demonstrates asymmetric swelling within a joint
- Test Sensitivity: 42%
- Test Specificity: 90%
- First metatarsophalangeal joint tender or swollen
- Test Sensitivity: 96%
- Test Specificity: 97%
- Hyperuricemia
- Test Sensitivity: 92%
- Test Specificity: 91%
- Unilateral first metatarsophalangeal joint Arthritis
- Unilateral tarsal joint Arthritis
- Inflammation peaked within one day
- Monoarthritis episode
- More than one acute Arthritis attack
- Effected joints with overlying redness
- Gouty Tophi suspected (but not yet confirmed by aspirate)
- Synovial Fluid culture negative for organisms during an Acute Monoarthritis attack
- References
- Wallace (1977) Arthritis Rheum 20(3): 895-900 [PubMed]
- Differential Diagnosis
- Septic Arthritis
- Critical to distinguish (especially in large joints: Shoulder, elbow, hip and knee)!
- Concurrent infection with gout history may occur (esp. knee, and to lesser extent in ankle, Shoulder, wrist)
- A red, warm, edematous joint is only proven not septic by Joint Aspiration (do not assume gout)
- Pseudogout (calcium pyrophosphate deposition disease)
- Differentiate from gout based on Joint Fluid analysis
- Trauma
- Trauma may also precipitate a gout flare
- Other conditions
- Bacterial Cellulitis
- Reactive Arthritis
- Rheumatoid Arthritis
- Osteoarthritis
- Sarcoidosis
- Neuropathic Arthritis (e.g. Charcot Joint)
- Management: Acute attack
- NSAIDs (any are effective if adequately dosed)
- Avoid in elderly, renal or liver disease, Heart Failure, or Peptic Ulcer Disease
- In these cases, use Corticosteroids instead
- Indomethacin (historically has been preferred NSAID in gout)
- Start: 50 mg orally three times daily for 2-3 days
- Then: 25 mg orally three times daily for 4-10 days
- Naproxen 500 mg orally twice daily for 4-10 days
- Sulindac 200 mg orally twice daily for 4-10 days
- Colchicine (Colcrys)
- Less viable option (too expensive) now that generic preparations were removed from the market
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm227796.htm
- Other disadvantages
- Gastrointestinal adverse effects (Nausea, Vomiting, Diarrhea) at treatment doses
- Avoid in severe liver or Kidney disease
- Requires adjusted dosing in renal disease
- No intrinsic Analgesic effect
- Dosing
- Single bolus at onset (2 dose one hour apart)
- Colchicine 1.2 mg now, then additional 0.6 mg orally in one hour
- Take at onset of symptoms
- As effective as high dose protocols
- Terkeltaub (2010) Arthritis Rheum 62(4): 1060-8 [PubMed]
- May consider 0.6 orally daily to twice daily taken as adjunct to NSAID (see above)
- Most beneficial if started within first 24 hours of attack
- May be ineffective if started >3-4 days after symptom onset
- Corticosteroids
- Precautions
- Rule-out Septic Arthritis first!
- Use with caution in Diabetes Mellitus
- Effective alternative to NSAIDs (less risk of peptic ulcer)
- Efficacy
- Prednisolone 35 mg daily is equivalent to Naprosyn 500 mg twice daily
- Janssens (2008) Lancet 371(9627):1854-60 [PubMed]
- Systemic agents
- Intravenous
- Methylprednisolone 40 mg (consider if NPO in hospital)
- Intramuscular
- Depo-Medrol 80 to 120 mg single dose IM
- Oral
- Start: Prednisone 40 mg orally daily for 5 days
- If persistent symptoms, continue as taper (not needed in many cases)
- Next: Prednisone 20 mg orally daily for 5 days
- Next: Prednisone 10 mg orally daily for 5 days
- Intra-articular Corticosteroid
- Large single joints and refractory cases to other treatment
- However, no evidence to support their use in acute Gouty Arthritis
- Wechalekar (2013) Cochrane Database Syst Rev (4): CD009920 +PMID:23633379 [PubMed]
- Other non-medication palliative measures
- Ice Therapy
- Avoid exacerbating or unhelpful measures
- See Prevention below (including purine avoidance)
- Aspirin in small doses aggravates disorder
- Acetaminophen not helpful
- Phenylbutazone risks outweigh any benefits
- Bone Marrow suppression
- Aplastic Anemia
- Prevention: Prophylactic Medications
- Typically start concurrently with NSAIDs, Corticosteroids or Colchicine (see below)
- Contraindications
- Do not use in acute attack (however, see Allopurinol for caveats)
- Indications
- Recurrent Gout
- Two gout attacks per year or
- One gout attack per year if Chronic Kidney Disease stage 2
- Tophaceous gout
- Nephrolithiasis
- Therapy goal
- Serum Uric Acid <5-6 mg/dl
- Some protocols recheck Uric Acid every 2-4 weeks and increase medication doses if not at target
- Xanthine Oxidase Inhibitors
- First-line agents for prevention
- Originally targeted at Uric Acid over-producers based on 24 hour Uric Acid
- Now used for under-excreters and over-producers
- Allopurinol (preferred)
- See Allopurinol for dosing guidelines, contraindications
- Standard Dosing (GFR>30 ml/min)
- Start 100 mg orally daily and advance to 300 mg daily
- In severe Uric Acid elevation, may be titrated every few weeks up to a max of 800 mg/day
- Doses higher than 300 mg/day should be divided and taken after meals
- May also add probenacid or Lesinurad to reach adequate Uric Acid control
- Renal Dosing (GFR <30 ml/min)
- Start 50 mg/day (reduces Hypersensitivity Reaction riskl)
- Titrate to maximum of 300 mg/day
- Genetic Testing (HLA B5801)
- Obtain prior to use if risk of severe Hypersensitivity skin reaction (Hans Chinese, Thai, Korean)
- See Allopurinol for initiation protocol (start with antiinflammatory agent to prevent triggering gout attack)
- Stop medication and seek medical attention for signs of Hypersensitivity Reaction (e.g. rash, Pruritus)
- Febuxostat (Uloric)
- Dose: 40 mg daily (up to 80 mg/day if Uric Acid still >6 mg/dl after 2 weeks of therapy)
- Contraindicated with Azathioprine (Imuran) or mercaptopurine
- Much more expensive than Allopurinol
- Increased risk of cardiovascular related death in known CV disease (NNH 91)
- White (2018) N Engl J Med 378:1200-10 [PubMed]
- Other preventive agents
- Colchicine
- Dose: 0.6 mg orally daily to twice daily
- Pegloticase (Krystexxa)
- Dose: 8 mg IV every 2 weeks
- Indicated in severe, refractory gout (but costs $5000 per dose)
- Intravenous, pegylated recombinant uric-oxidase enzyme (uricase)
- Converts Uric Acid to inactive water soluble form
- Mechanism related to Uric Acid metabolism to allantoin
- Probenacid
- Dose: 250 mg orally twice daily, gradually increased to up to 2 grams daily
- Originally targeted at Uric Acid under-excreted (based on 24-hour Urine Uric Acid)
- Now rarely used (replaced by Allopurinol used in over-production and under-excretion)
- May be used as adjunct to Allopurinol or febuxostat in refractory Hyperuricemia
- Significantly increased risk of Nephrolithiasis
- Maintain hydration and use Potassium citrate to prevent Nephrolithiasis
- Avoid in combination with Methotrexate or Ketorolac
- Lesinurad (Zurampic)
- Released in 2015 and no longer available in United States due to low demand as of 2019
- Dose: 200 mg/day
- Indicated as adjunct to Allopurinol or febuxostat, for added Uric Acid control
- Contraindicated as mono-therapy to lower Uric Acid (Renal Failure risk)
- Similar to Probenacid, inhibits renal Uric Acid transporters (preventing Uric Acid reabsorption)
- Must be used in combination with Allopurinol or febuxostat (due to risk of renal stones, Renal Failure)
- Very expensive ($12/tablet) and offers little benefit over probenacid (which is one sixth of the cost)
- (2016) Presc Lett 23(10)
- Concurrently start Uric Acid lowering agents with prophylaxis, low dose for 3-6 months
- NSAIDS (avoid in Chronic Kidney Disease, heart disease or liver disease)
- Aleve 220 mg (OTC) orally twice daily or
- Naprosyn 250 mg orally twice daily or
- Indomethacin 25 mg orally twice daily (avoid extended use due to adverse effects)
- Prednisone (if NSAIDs contraindicated)
- Maintenance: 10 mg orally daily, then 5 mg orally daily for 3-6 months
- Acute Exacerbation (start at first symptoms of gout recurrence): 40 mg orally for 1-3 days
- Have available as emergency prescription
- Colchicine
- Colchicine was a first line agent until generic preparations removed from market (now too expensive)
- Colchicine 0.6 mg orally daily to twice daily
- Prevention: General
- Avoid provocative factors (See Hyperuricemia)
- Avoid purine-rich foods (See Purine Content in Foods)
- Especially avoid red meats (beef, lamb, pork), wild game, organ meats and shellfish
- Vegetable/grain high purine foods do not increase risk (nuts, oatmeal, asparagus, legumes, mushrooms)
- Avoid Alcoholic beverages (especially beer)
- Avoid fruit juice and drinks sweetened with high-fructose corn syrup
- Increases Uric Acid as a byproduct of ATP catabolism
- Avoid Thiazide Diuretics
- However Thiazides result in only small Uric Acid increases
- Hueskes (2012) Semin Arthritis Rheum 41(6): 879-89 [PubMed]
- Avoid weight gain
- Weight loss (if Overweight) lowers the gout risk
- Avoid unhelpful or harmful measures
- Vitamin C: 500 mg/day does not appear effective in Gouty Arthritis
- Initially found to lower Uric Acid 0.5 mg/dl, but clinically insignificant benefit
- Huang (2005) Arthritis Rheumatism 52(6):1843-7 [PubMed]
- Stamp (2013) Arthritis Rheum 65(6): 1636-42 [PubMed]
- Adjunctive agents to consider
- DASH Diet (including vegetable sources of protein, soybean)
- Rai (2017) BMJ 357 +PMID:28487277 [PubMed]
- Dairy products (skim milk, low fat yogurt) may be protective
- Choi (2004) N Engl J Med 350:1093-1103 [PubMed]
- Eating cherries lowers serum Uric Acid
- Jacob (2003) J Nutr 133(6): 1826-9 [PubMed]
- Coffee lowers gout attack risk
- However significant decrease only at >3 cups/day
- Choi (2007) Arthritis Rheumatism 56(6): 2049-55 [PubMed]
- Adjunctive Uricosuric medications
- Losartan (Cozaar)
- Not seen with other Angiotensin Receptor Blockers
- Fenofibrate (Tricor)
- Associated Conditions: Other Uric Acid Conditions
- Asymptomatic Hyperuricemia
- Uric Acid Nephrolithiasis
- Occurs in 10-25% of gout patients
- Even higher risk with increasing Uric Acid levels (e.g. 50% Prevalence in those with Uric Acid >13 mg/dl)
- Course
- Gout attack episodes last 5-7 days with or without treatment
- Resources
- Gout risk calculator
- http://www.gp-training.net/rheum/gout_calc.htm
- ACR/Eular Gout Classification Tool
- https://www.mdcalc.com/acr-eular-gout-classification-criteria
- References
- (2020) Presc Lett 27(7): 39
- Klippel (1997) Primer Rheumatic Diseases, p. 230-4
- Papp and Mann (2016) Crit Dec Emerg Med 30(8): 17-23
- Buckley (1996) Am Fam Physician 54(4): 1232-8 [PubMed]
- Clebak (2020) Am Fam Physician 102(9): 533-8 [PubMed]
- Eggebeen (2007) Am Fam Physician 76:801-12 [PubMed]
- Hainer (2014) Am Fam Physician 90(12): 831-6 [PubMed]
- Harris (1999) Am Fam Physician 59(4): 925-34 [PubMed]
- McDonald (1998) Postgrad Med 104(6): 117-27 [PubMed]
- Pittman (1999) Am Fam Physician 59(7):1799-1806 [PubMed]
- Terkeltaub (2003) N Engl J Med 1647-55 [PubMed]