1. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. In the Clinic Gout

2. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What are the risk factors for gout?  Hyperuricemia  Male sex  Older age  Obesity  Diet high in animal sources of purines (red meat, shellfish)  Alcohol and high-fructose corn syrup-sweetened drinks  Medications (thiazide or loop diuretics, cyclosporine)  Renal insufficiency  Organ transplantation  Genetic risk factors

3. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What comorbid diseases are associated with gout?  Renal insufficiency  Psoriasis  Hypertension  Diabetes  Hyperlipidemia  Metabolic syndrome  Cardiovascular disease

4. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. Are there effective strategies for prevention?  Dietary changes and weight loss  May lower serum urate levels  Therapy not indicated for asymptomatic hyperuricemia  Not proven to have adverse consequences  Long-term ULT may carry long-term risks  Treatment guidelines may change if there are sufficient evidence to show that hyperuricemia confers increased renal or cardiovascular disease risk

5. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. CLINICAL BOTTOM LINE: Prevention and Screening...  Risk factors  Hyperuricemia  Age, sex, obesity, renal insufficiency, diuretic use, diet  Genetic variants may increase risk  Common comorbidities  Diabetes, CVD, renal impairment, hypertension, metabolic syndrome, hyperlipidemia  Therapy not recommended for asymptomatic hyperuricemia  Lifestyle modifications appropriate in patients with only 1 gout attack and no other indications for ULT

6. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What symptoms and physical examination findings suggest gout?  Acute onset joint pain at night  Swollen, erythematous, warm, exquisitely painful joint  Maximum pain within 24 h and resolves within 2 weeks  First Metatarsophalangeal joint most commonly involved  MSU crystals tend to form in previously diseased joints  With longer-disease duration and unabated hyperuricemia, persistent inflammation may occur  Urate deposition may be evident as subcutaneous nodules  Imaging may reveal tophaceous deposits

7. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What tests can diagnose gout?  Examination of synovial fluid or tophus aspirate  Polarized microscopy, cell count, culture  MSU crystals in synovial fluid or tophus aspiration required to establish diagnosis  Other useful tests in diagnosing gout  Serum urate level  CBC with differential (if considering septic arthritis)  Radiography (to rule out other causes or to look for gouty erosions when symptoms are long-standing)  US or DECT imaging (to identify findings specific for gout)

8. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What is the value of imaging?  Plain radiography  Show gout-related bone erosion, tophi  Show conditions coexisting with or confused for gout  Ultrasonography  Facilitate joint aspiration  Identify articular urate deposition, tophi, inflammation  DECT (not yet used in practice)  Differentiate calcium from urate  MRI (not routinely used in practice)  Show joint inflammation, damage, tophi—but cannot necessarily distinguish gout from CPP arthritis

9. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What are the differential diagnoses?  Calcium pyrophosphate deposition  Septic arthritis  Cellulitis  Rheumatoid arthritis  Osteoarthritis  Psoriatic arthritis  Sarcoidosis

10. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What classification criteria are used for gout in research studies?  MSU in synovial fluid or tophus aspiration is sufficient for classification as gout  ACR/EULAR criteria encompass following parameters:  Pattern of joint involvement during symptomatic episodes  Characteristics of symptomatic episodes  Time course of symptomatic episodes  Clinical evidence of tophus  Highest level of serum urate ever recorded off-treatment  MSU results of synovial fluid analysis  Imaging evidence of urate deposition  Imaging evidence of gout-related joint damage

11. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. CLINICAL BOTTOM LINE: Diagnosis...  MSU crystals in synovial fluid or tophus confirm diagnosis  Joint pain and hyperuricemia alone do not  Aspirate synovial fluid from joint or suspected tophus  Serum urate measurement is helpful but not diagnostic  Examine aspirated material under polarizing microscopy to differentiate gout from CPP-related arthritis  Examine synovial fluid cultures and clinical features to differentiate from septic arthritis  Radiography and ultrasonography: help identify other joint conditions and gout-specific features

12. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. When should clinicians consider hospitalizing a patient with gout?  Gout attacks are one of the most painful conditions  Hospitalization is warranted if:  Patient cannot care for self at home  Septic arthritis is a concern (to diagnose definitively and administer antibiotics promptly to prevent joint damage)  To monitor response to therapy, repeated synovial fluid analysis may be warranted for cell count and culture

13. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What is the role of nonpharmacologic therapy in managing patients who already have gout?  Adjunct to long-term pharmacologic management  Most patients with gout require pharmacologic therapy  Lifestyle changes may help reduce serum urate levels  Reduce consumption of dietary contributors  Weight loss  Adequate hydration  Don’t blame patients for gout  Renal urate underexcretion, with genetic underpinnings, is the major contributor

14. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. What is the role of pharmacologic therapy?  Most patients require pharmacologic therapy  Urate-lowering therapy: cornerstone of management  Prophylaxis: when starting ULT to mitigate expected increased risk for attacks during initial phase  Anti-inflammatory therapy: for gout attacks  Indications for urate-lowering therapy  Frequent attacks (≥2 per year)  Tophus on clinical examination or imaging study  Chronic kidney disease stage ≥2  Past urolithiasis (of any type)

15. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. When should clinicians consider consulting a specialist?  If a septic joint is suspected  To aid with joint aspiration  When gout is difficult to manage  First-line monotherapy insufficient  Contraindication or caution for gout attack management  Features may be related to other forms of arthritis  Patient is young, with possible inherited metabolic disease  Surgery is not indicated except when tophi pose an urgent function- or organ-threatening risk

16. © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 165 (1): ITC1-1. CLINICAL BOTTOM LINE: Treatment...  Pharamcologic treatment  ULT if the patient has a clinical indication  Prophylaxis when initiating ULT  Anti-inflammatory therapy for gout attacks  Patient education  Causes of gout  Management of hyperuricemia  Adjunctive lifestyle modifications  Hospitalization warranted when gout-related pain and functional limitations cannot be controlled