Crystal-Induced Arthritis Rajesh Kataria, D.O. Southern Ohio Rheumatology
Disclosures Speaker: Rajesh Kataria, D.O. Relationships with commercial interests: Speakers Bureau - Horizon Presentation will include discussion of medication to treat gout and off label medication used to lower uric acid
Objectives 1. Identify goal uric acid level in chronic gout management & treatment options to achieve the goal 2. Be able to make dietary recommendations to gout patients 3. Be able to list syndromes caused by calcium pyrophosphate dihydrate crystals
Case Presentation JR is a 56 y/o WM admitted to SOMC with worsening fatigue, generalized weakness and ambulatory dysfunction Hospitalized 2 weeks earlier with diabetic foot ulcer and had undergone debridement Rheum consulted regarding R elbow and wrist pain
Case Presentation JR reports pain starting acutely 1 week prior w/o trauma. Had 1 similar episode years ago in the R elbow and was diagnosed with gout by PCP and has been on allopurinol daily Unable to move R wrist without severe pain
Case Presentation R wrist is warm, erythematous and extremely tender with palpation Temp 99.4 DDx?
Differential Diagnosis of Monoarticular Arthritis (Adults) Acute Infectious arthritis: Bacterial, viral Crystal arthritis: Gout, CPPD, BCP Traumatic arthritis Mechanical derangement Reactive arthritis: ARF Hemophilic arthritis Chronic Infectious arthritis: Mycobacterial, fungal, Lyme Crystal arthritis Tendinitis, bursitis Spondyloarthritis Ischemic necrosis Others
Case Presentation What tests/procedures should be undertaken?
Case Presentation ¼ cc of chalky white substance aspirated from R wrist Specimen sent to lab for what tests? Empiric Vancomycin, Decadron and colchicine started
Class III Synovial Fluid: Septic Arthritis Cloudy to Opaque, Low Viscosity >50,000 WBC/ l with neutrophil predominance
Normal Synovial Fluid Clear, Amber, High Viscosity <200 WBC/ l with mononuclear predominance
Case Presentation Gram stain Few wbcs Few gram + cocci Culture MRSA WBCs 16,000
Crystal Deposition Diseases Gout (monosodium urate crystal deposition) Characterized biochemically as extracellular urate supersaturation
Crystal Deposition Diseases Bone Cartilage CPPD crystals Synovium MSU crystals
Crystal-induced Inflammation Crystal Shedding Protein Coating Phagocytosis Release of Inflammatory mediators: PGE 2, O 2 radicals, Enzymes Local inflammation Release of Inflammatory mediators: IL-1, TNF-, others Systemic manifestations
ACR
Gout Screw up the vise as tightly as possible you have rheumatism; give it another turn, and that is gout. Anonymous
Acute Gouty Arthritis Described in 1683 by Thomas Sydenham Gouty patients are, generally, either old men or men who have so worn themselves out in youth as to have brought on a premature old age of such dissolute habits none being more common than the premature and excessive indulgence in venery and the like exhausting passions. The victim goes to bed and sleeps in good health. About two o clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. The pain is like that of a dislocation and yet parts feel as if cold water were poured over them. Then follows chills and shivers and a little fever. The night is passed in torture, sleeplessness.
Acute Gouty Arthritis >90% of patients are males over 30 years of age Usually presents as an acute monoarthritis 50% of initial attacks occur in the 1 st MTP Podagra Almost always involves peripheral joints Acute onset with maximum pain in several hours Joint swelling, erythema, tenderness, pain on ROM Systemic symptoms of fever and chills may be present
Gout: A Progressive Condition Gout is the most common form of inflammatory arthritis, estimated to affect 8.3 million (3.9%) Americans. Adapted from Edwards NL. Gout. A. Clinical features. In: Klippel JH, Stone JH, Crofford LJ, White PH, eds. Primer on the Rheumatic Diseases. 13th ed. New York: Springer; 2008:241-249. 1. Edwards NL, Crystal-Induced Joint Disease in ACPMedicine Textbook, 2012. 2. Zhu Y, etal. Arth. & Rheumatism. 2011;63(10): 3136 3141
American College of Rheumatology (ACR) Preliminary Criteria for Gout Diagnosis Presence of MSU crystals in the joint fluid, or Tophus proved to contain MSU crystals by chemical or polarized light microscopy, or The presence of 6 of the following 12 clinical, laboratory, and radiographic criteria:
American College of Rheumatology (ACR) Preliminary Criteria for Gout Diagnosis - > 1 attack of acute arthritis - Maximal inflammation developed within 1 day - Attack of monoarticular arthritis - Joint redness observed - First MTP joint painful or swollen - Unilateral attack involving first MTP - Unilateral attack involving tarsal joint - Suspected tophus - Hyperuricemia - Asymmetric swelling within a joint on X-ray - Subcortical cysts without erosions on X-ray - Negative culture of joint fluid for microorganisms during attack of joint inflammation
Surgery Trauma Precipitation of Acute Gouty Arthritis Medical illness: MI, CHF, CVA Alcohol ingestion Medications: diuretics, cyclosporine Sudden change in urate concentration or solubility
Risk Factors & Co-Morbid Conditions Risk Factors Modifiable 1-6 Obesity Serum urate High-fructose corn syrup Purine-rich diets* o Meats (organ meats), Seafood Alcohol consumption Medications o Diuretics, Low-dose aspirin, Cyclosporine, Ethambutol Non-modifiable 7 Age Gender o Male o Postmenopausal females Co-Morbid Conditions Metabolic Syndrome 8 (63%) Hypertension Diabetes Mellitus Obesity Cardiovascular Disease Myocardial Infarction Peripheral artery disease Congestive heart failure Impaired Renal Function 9-11 1. Bieber JD, Terkeltaub RA. Arthritis & Rheumatism. 2004;50(8):2400-2414 2. Choi HK et al. Arch Intern Med. 2005;165:742-748. 3. Choi HK et al. Lancet 2004:363:1277-81. 4. Choi HK et al. NEJM 2004;350:1093-101 5. Choi HK et al. Ann Intern Med. 2005;143:499-516. 6. Choi et al. BMJ. 2008;336(7639):309-12 7. Wallace KL et al. J Rheumatol. 2004;31:1582-1587. 8. Choi et al. Arthritis Rheum. 2007;57:109 9. Keenan RT, et al. Am. J. Med. 2010;124: 155-163. 10. Becker MA, et al. New Engl. J. Med. 2005;353(23):2450-2461. 11. Emmerson BT. NEJM. 1996;334:445-51
Common Sites of Acute Gout Attacks Elbow Olecranon Bursa Wrist Fingers Knee Ankle Midfoot First Metatarsophalangeal (MTP) joint (eventually affected in ~ 90% of individuals with gout) Edwards NL. In: Goldman A, Schafer AI. Goldman s Cecil Medicine. 24th ed. Philadelphia, PA: Saunders Elsevier; 2011.
Chronic Tophaceous Gout Occurs with longstanding untreated gout and results in tophi Collections of solid urate in connective tissue Typically not painful Can cause bone erosions
Harcourt
ACR
Class II Synovial Fluid: Crystal Arthritis Cloudy, Yellow, Low Viscosity 2,000-75,000 WBC/ l with neutrophil predominance
ACR
ACR Strongly negative birefringent crystals appear bright yellow when parallel with the axis of the compensator using polarizing light microscopy.
Harcourt
Treatment of Gout Acute gouty arthritis NSAIDs Intra-articular or systemic corticosteroids P.O. colchicine (1.2 mg followed by 0.6 mg 1 hour later, then 0.6 mg qd-bid for 7-10 days) I.M. ACTH Prophylaxis Low dose colchicine Low dose NSAIDs/corticosteroids
Treatment of Gout Control of hyperuricemia Xanthine oxidase inhibitors: allopurinol, febuxostat Uricosuric agents: probenecid, lesinurad, (losartan, fenofibrate*) Combination therapy: lesinurad/allopurinol Uricase (urate-oxidase): pegloticase
Indications for Urate Lowering Therapy Frequent attacks Tophaceous deposits Recurrent nephrolithiasis Urate nephropathy
Urate-Lowering therapies (ULTs) target different stages of purine metabolism Purines Humans Almost All Other Mammals Hypoxanthine xanthine oxidase X allopurinol febuxostat Xanthine xanthine oxidase X allopurinol C febuxostat Urate pegloticase uricase* H 2 O + O 2 H 2 O 2 Allantoin *Uricase is present in all mammals except man and higher apes. probenecid lesinurad Urinary Excretion Urinary Excretion Edwards NL. In: Goldman A, Schafer AI. Goldman s Cecil Medicine. 24th ed. Philadelphia, PA: Saunders Elsevier; 2011.
ACR Guidelines for the Management of Gout At minimum, SUA < 6 mg/dl SUA<5 mg/dl for those with tophi and/or CTGA* Durable improvement in signs and symptoms of gout Reduced frequency of flares Clearance of tophi * CTGA: Chronic Tophaceous Gouty Arthropathy Khanna D, Fitzgerald JD, Khanna PP et al. Arthritis Care & Research. 2012;64(10):1431 1446 Single Agent Xanthine Oxidase Inhibitor (XOI) titrated to maximum appropriate dose (Alternative if XOI contraindicated or not tolerated: Probenecid) Serum urate target not achieved, continuing disease activity Add Uricosuric to XOI with both agents titrated to maximum appropriate dose Pegloticase Serum urate target not achieved, continuing disease activity
Treatment of Gout Maintaining serum uric acid < 6 mg/dl is associated with reduced risk of future gout attacks In a clinical study of 267 patients, 86% of patients who achieved a serum uric acid of < 6 mg/dl had no gout attacks during the observation period (> 1 year).
Treatment of Gout ACR guidelines recommend monitoring serum uric acid level every 2-5 weeks during uratelowering therapy titration, then every 6 months once serum uric acid target has been achieved
Treatment of Gout When is the best time to measure serum uric acid? At least 2 weeks post-flare, as serum uric acid levels may be artificially low up to 50% of the time during a flare
Treatment of Gout Lifestyle modifications Weight loss Limiting consumption of purine-rich meat (liver, kidney), seafood (shellfish, sardines, anchovies), and vegetables and legumes (asparagus, cauliflower, spinach, beans, peas, and mushrooms) Reducing alcohol intake, particularly beer Limiting high-fructose corn syrup intake Consuming dairy products Dietary restrictions may reduce urate levels by about 1 mg/dl
Calcium pyrophosphate deposition disease (CPDD) Due to articular deposition of calcium pyrophosphate dihydrate (CPPD) crystals Chondrocalcinosis radiographic calcification of articular fibro- or hyaline cartilage An umbrella term that includes Acute CPP arthritis (pseudogout) OA with CPPD (pseudo-oa) Chronic CPP inflammatory arthritis Pseudo-RA Pseudo-neuropathic
Acute Pseudogout Part of the spectrum of calcium pyrophosphate deposition disease (CPDD) Due to articular deposition of calcium pyrophosphate dihydrate (CPPD) crystals Generally occurs in patients over 50 years of age Slight female predominance Usually presents as an acute monoarthritis >50% of initial attacks occur in the knee Pseudogout is otherwise clinically similar to acute gouty arthritis though generally less intense
Precipitation of Pseudogout Surgery Trauma Medical illness: MI, CHF, CVA Transient decreases in Ca ++ Alteration of equilibrium between CaPP i in joint tissue and solution Increased solubility of CaPP i Crystal shedding
Conditions Associated with CPPD Disease True associations: Hyperparathyroidism, hemochromatosis, hypophosphatasia, hypomagnesemia, aging Probable associations: Hyperthyroidism, renal stones, ankylosing hyperostosis, ochronosis, Wilson s disease, hemophilic arthropathy Possible associations: Diabetes mellitus, hypertension, renal insufficiency, hyperuricemia, gynecomastia, IBD, RA, Paget s disease, acromegaly
Weakly positive birefringent crystals appear blue when parallel with the axis of the compensator using polarizing light microscopy. ACR
Basic Calcium Phosphate Deposition (BCP, Hydroxyapetite) Calcific tendinitis and bursitis Calcific periarthritis Primary Secondary: ESRD, Scleroderma Familial Intra-articular Most commonly involves shoulders and knees Acute arthritis Chronic erosive arthritis: Milwaukee shoulder
Approach to Acute Monoarticular Arthritis Synovial fluid analysis for crystals, gram stain and culture is essential If no crystals are found, generally treat as if septic arthritis even if gram stain is negative If crystals are found, it does not exclude concomitant septic arthritis Therapeutic trial of oral colchicine supports a diagnosis of acute gouty arthritis
Case Presentation 3 days later (Monday) Crystal search + MSU Final Diagnosis: Acute gouty + septic arthritis