1. HPI A 52 yo male presents to his PCP on a Monday morning with exquisite right knee pain that started overnight. He spent Sunday tailgating with friends. He denies trauma or any previous episodes. What else would you like to know?

2. PMH Medical Hx: hypertension, right ACL repair (1980) Family Hx: Father has gout, Mother has hypertension and hyperlipidemia Social: Former collegiate football player, divorced with 3 children, works as a cook at a diner What is your differential diagnosis?

3. DDx Gout – primary, secondary Chrondrocalcinosis (pseudogout) Infective arthritis (gonococcal) Septic joint Rheumatoid arthritis Osteoarthritis Meniscal Injury Ligamentous Injury (ACL, PCL, MCL, LCL) What do you want to do next?

4. Physical Exam Height, 6’ 5”; Weight, 300 lbs; BMI, 36 Vitals: BP 150/90; T 98.9, HR 70, RR 18 Gen: Patient is cooperative but sitting uncomfortably with right leg slightly flexed HEENT, CV, Respiratory, Abdominal, Neuro, and Psych Exams: wnl Skin: warm, erythematous right anterior knee Musculoskeletal: exam limited by patient’s pain tolerance What labs do you want to order and why?

5. Lab Tests a)Joint aspiration with synovial fluid analysis – Can differentiate gout/pseudogout, osteroarthritis, and septic joint based on number of leukocytes – Can differentiate gout and pseudogout based on crystals b)CBC, ESR, CRP – rule out septic joint, infective arthritis c)Serum uric acid level – limited value, can be high without gout or low during acute attack

6. Lab Results CBC – normal ESR – 24 mm/h CRP – 15 mg/L Serum Uric Acid – 8.5 mg/dL Synovial Fluid – 20,000/mm 3 leukocytes Osteoarthritis 50,000 – See next slide for microscopic view

7. Synovial Fluid negatively birefringent, needle-shaped crystals

8. Overview of Gout “The king of diseases and the disease of kings” – Hippocrates Deposition of monosodium urate crystals in the synovium and periarticular sites creates inflammatory reaction – Painful arthritis/bursitis negatively birefringent, needle-shaped

9. Hallmarks of Gout Monoarticular in most cases – 1 st MTP joint is the most frequent site of involvement Middle-aged men Familial pre-disposition Often precipitated by large meal or alcohol intake – ask about recent diet (red meat, fish) Acute – develops over hours, resolves in 3-10 days

10. Hallmarks of Gout Signs & Symptoms: pain, redness, swelling, fever/chills, malaise Risk Factors: hypertension, hyperlipidemia, obesity

11. Associated Diseases Can be secondary to hyperuricemia due to: 1.Increased cellular turnover – e.g. leukemia, multiple myeloma 2.Decreased urate excretion – e.g. chronic renal disease, medications (diuretics, cyclosporin), toxins (ethanol, lead) 3.Lesch-Nyhan Syndrome – X-linked hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) deficiency – Severe neurologic symptoms, self-destructive behavior

12. Chronic Gout Tophi – large accumulations of urate crystals, usually in ear, PIP joints, and elbow

13. Chronic Gout Tophi are seen as the pale areas of urate crystals surrounded by lymphocytes and macrophages

14. Chronic Gout

15. Treatment Acute gout is treated by reducing pain and inflammation – NSAIDs – 1 st line treatment – Colchicine – 2 nd line treatment due to potential toxicity – Corticosteroids – if patient has contraindications to NSAIDs and colchicine

16. Prevention For patients suffering from recurrent attacks, prophylactic measures to lower serum urate levels may be initiated following the acute phase Lifestyle Modifications: – Decrease dietary protein intake and alcohol consumption – Weight loss Medications: – Colchicine – Allopurinol – Probenecid Stop thiazide diuretics

17. Hallmarks of DDx 1.Chondrocalcinosis (Pseudogout) – Deposition of calcium pyrophosphate dihydrate crystal deposition creating inflammatory reaction – Clinically similar to gout – Associated with previous joint surgery or underlying metabolic condition – Differentiate based on synovial fluid analysis

18. Pseudogout Crystals Positively birefringent, rhomboid-shaped crystals

19. Pseudogout on X-ray Normal KneeKnee with pseudogout (calcified cartilage) and osteoarthritis (decreased joint space)

20. Hallmarks of DDx 2.Gonococcal Arthritis – Neisseria gonorrhoeae infection – Usually monoarticular knee, wrist, or small joints of the hand

21. Hallmarks of DDx 3. Rheumatoid Arthritis – Autoimmune – Bilateral involvement – PIP & MCP joints, knees – Rheumatoid nodules

22. Hallmarks of DDx 4.Osteoarthritis – Degenerative joint disease – Weight-bearing joints – Heberden Nodes at DIP joints – Bouchard Nodes at PIP joints

23. Pearls Podagra = gout in 1 st MTP Crystals under polarized light: – Gout = negatively birefringent, needle-shaped – Pseudogout = positively birefringent, rhomboid- shaped

24. Summary Patient is started on NSAID therapy and counseled on recurrence rates of gout – 78% have a second attack within 2 years Patient states that he will try to start losing weight and cutting back on beer