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Book Details
Abstract
Concise and clinically focused, Gout, by Drs. Naomi Schlesinger and Peter E. Lipsky, provides a one-stop overview of recent developments regarding this common form of inflammatory arthritis. Impacting an estimated 8.3 million people in the U.S. alone, gout is seen frequently by both primary care physicians as well as rheumatologists. This resource provides detailed coverage of the epidemiology, causes, diagnosis, management, and treatment of patients with both acute and chronic gout.
- Addresses key topics such as genetics, hyperuricemia, comorbidities of gout, treatment guidelines for acute and chronic gout, classification and diagnosis, and imaging.
- Discusses future outlooks for improving pharmacological and nonpharmacological treatment options, including an overview of drugs in the pipeline.
- Consolidates today’s available information on this timely topic into one convenient resource.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Gout | i | ||
| Gout | iii | ||
| Copyright | iv | ||
| List of Contributors | v | ||
| Preface | ix | ||
| REFERENCE | ix | ||
| Dedication | xi | ||
| Contents | xiii | ||
| 1 - Hyperuricemia and the Silent Deposition of Monosodium Urate Crystals | 1 | ||
| DEFINITION OF HYPERURICEMIA | 1 | ||
| CONSEQUENCES OF HYPERURICEMIA | 1 | ||
| DEPOSITS OF MONOSODIUM URATE CRYSTALS IN PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA | 2 | ||
| Ultrasound | 2 | ||
| Dual-Energy Computed Tomography | 2 | ||
| Relevance of Silent Deposits | 4 | ||
| Pending Agenda | 5 | ||
| DISCLOSURE STATEMENT | 5 | ||
| REFERENCES | 5 | ||
| 2 - Genetics of Hyperuricemia and Gout | 9 | ||
| THE GENETIC BASIS OF HYPERURICEMIA | 9 | ||
| MOLECULAR INSIGHTS INTO URATE CONTROL | 12 | ||
| Renal Uric Acid Excretion | 12 | ||
| SLC2A9 | 12 | ||
| ABCC4 | 15 | ||
| PDZK1 | 16 | ||
| ABCG2 and Gut Uric Acid Excretion | 16 | ||
| Metabolic Loci | 18 | ||
| Glucokinase regulatory protein | 18 | ||
| ALDH2 and ALDH16A1 | 19 | ||
| LRP2 | 20 | ||
| THE GENETIC BASIS OF PROGRESSION FROM HYPERURICEMIA TO GOUT | 20 | ||
| Candidate Gene Studies in Gout | 20 | ||
| TLR4 | 20 | ||
| CARD8 and IL1B | 21 | ||
| PPARGC1B and mitochondrial DNA copy number | 21 | ||
| APOA1 | 21 | ||
| GWAS With Gout as Outcome | 21 | ||
| MENDELIAN RANDOMIZATION: ARE HYPERURICEMIA AND GOUT CAUSAL FOR COMORBID METABOLIC CONDITIONS? | 22 | ||
| PRECISION MEDICINE | 23 | ||
| REFERENCES | 23 | ||
| 3 - Immunoinflammatory Nature of Gout | 29 | ||
| INTRODUCTION | 29 | ||
| MONOSODIUM URATE CRYSTALS TRIGGER THE ACTIVATION OF THE NRLP3 INFLAMMASOME | 29 | ||
| PYROPTOSIS MEDIATED BY MONOSODIUM URATE CRYSTALS | 29 | ||
| INFLAMMATORY SIGNALS INFLUENCING INFLAMMATION AND INFLAMMASOME ASSEMBLY IN GOUT | 31 | ||
| MECHANISMS OF INFLAMMASOME ASSEMBLY IN GOUT | 31 | ||
| IL-1β AN INITIATOR OF INFLAMMATION IN GOUT | 31 | ||
| IL-1 INHIBITION IN GOUT | 32 | ||
| MECHANISMS OF INFLAMMATION RESOLUTION IN GOUT | 32 | ||
| CONCLUSION | 33 | ||
| REFERENCES | 33 | ||
| 4 - Tophi: Clinical and Biological Features | 37 | ||
| INTRODUCTION | 37 | ||
| TOPHUS PATHOLOGY | 37 | ||
| MECHANISMS OF TOPHUS FORMATION | 37 | ||
| CLINICAL FEATURES OF TOPHI | 38 | ||
| TOPHUS IMAGING | 39 | ||
| TOPHI AND URATE ARTHROPATHIES | 41 | ||
| MANAGEMENT | 42 | ||
| DISCLOSURE | 43 | ||
| REFERENCES | 43 | ||
| 5 - Crystal Analysis in Synovial Fluid | 47 | ||
| PREPARATION OF THE SAMPLE | 47 | ||
| MICROSCOPE | 48 | ||
| DIAGNOSING INTERCRITICAL GOUT AND CPP CRYSTAL ARTHRITIS | 53 | ||
| SOME PRACTICAL TIPS | 54 | ||
| OTHER CHARACTERISTICS OF SYNOVIAL FLUID IN CRYSTAL ARTHRITIS | 54 | ||
| OTHER CRYSTALS IN SYNOVIAL FLUID | 55 | ||
| DISCLOSURE | 57 | ||
| REFERENCES | 57 | ||
| 6 - Epidemiology of Gout and Hyperuricemia | 59 | ||
| INTRODUCTION | 59 | ||
| UNITED STATES AND CANADA | 59 | ||
| Hyperuricemia | 59 | ||
| Gout | 60 | ||
| Prevalence | 60 | ||
| Incidence | 60 | ||
| UNITED KINGDOM AND EUROPE | 61 | ||
| Hyperuricemia | 61 | ||
| Gout | 61 | ||
| Prevalence | 61 | ||
| Incidence | 61 | ||
| ASIA AND OCEANIA | 62 | ||
| Hyperuricemia | 62 | ||
| Gout | 63 | ||
| Prevalence | 63 | ||
| Incidence | 64 | ||
| AFRICA AND THE MIDDLE EAST | 64 | ||
| Hyperuricemia | 64 | ||
| Gout | 64 | ||
| Prevalence | 64 | ||
| GLOBAL BURDEN OF GOUT | 64 | ||
| AGE, GENDER, ETHNICITY, AND SOCIOECONOMIC DEPRIVATION | 65 | ||
| Age and Prevalence and Incidence of Gout and Hyperuricemia | 66 | ||
| Sex and Prevalence and Incidence of Gout and Hyperuricemia | 66 | ||
| Race/Ethnicity and Prevalence and Incidence of Gout and Hyperuricemia | 67 | ||
| Socioeconomic Deprivation and Prevalence and Incidence of Gout and Hyperuricemia | 68 | ||
| CONCLUSION | 68 | ||
| REFERENCES | 68 | ||
| 7 - Comorbidities in Gout | 73 | ||
| INTRODUCTION | 73 | ||
| CHRONIC KIDNEY DISEASE | 73 | ||
| CARDIOVASCULAR DISEASE | 75 | ||
| HYPERTENSION | 79 | ||
| HYPERLIPIDEMIA | 80 | ||
| OSTEOPOROSIS | 80 | ||
| OBESITY | 81 | ||
| DIABETES | 81 | ||
| OTHER ASSOCIATIONS | 82 | ||
| SUMMARY | 82 | ||
| REFERENCES | 82 | ||
| 8 - Imaging of Gout | 89 | ||
| IMAGING TECHNIQUES WIDELY USED FOR ASSESSMENT OF GOUT | 89 | ||
| Conventional Radiography | 89 | ||
| Ultrasonography | 90 | ||
| Magnetic Resonance Imaging | 90 | ||
| Conventional Computed Tomography | 90 | ||
| Dual-Energy Computed Tomography | 91 | ||
| IMAGING FOR THE DIAGNOSIS OF GOUT | 92 | ||
| IMAGING FOR ASSESSMENT OF DISEASE SEVERITY | 94 | ||
| IMAGING FOR COMPLICATIONS OF GOUT | 95 | ||
| IMAGING TO MEASURE RESPONSE TO THERAPY | 96 | ||
| IMAGING TO UNDERSTAND MECHANISMS OF DISEASE | 96 | ||
| IMAGING TO ASSIST WITH PATIENT UNDERSTANDING OF DISEASE AND THERAPIES | 97 | ||
| REFERENCES | 97 | ||
| FURTHER READING | 100 | ||
| 9 - Gout Classification and Diagnosis | 101 | ||
| INTRODUCTION | 101 | ||
| CLASSIFICATION AND DIAGNOSTIC CRITERIA | 101 | ||
| EARLY ATTEMPTS AT GOUT CLASSIFICATION: ROME, NEW YORK, AND AMERICAN RHEUMATISM ASSOCIATION CRITERIA | 101 | ||
| THE SUGAR STUDY AND 2015 ACR/EULAR GOUT CLASSIFICATION CRITERIA | 103 | ||
| DIAGNOSTIC RULES ON GOUT | 107 | ||
| CLASSIFICATION OF GOUT FLARES | 109 | ||
| CONCLUSION | 110 | ||
| DISCLOSURE STATEMENT | 111 | ||
| REFERENCES | 111 | ||
| 10 - Clinical Features of Gout and Its Impact on Quality of Life | 113 | ||
| GOUT FLARE | 113 | ||
| GOUTY TOPHI | 115 | ||
| CHRONIC GOUT | 115 | ||
| OTHER MANIFESTATIONS OF GOUT | 116 | ||
| UNUSUAL PRESENTATIONS OF GOUT | 116 | ||
| Early-Onset Gout | 116 | ||
| Gout in Women | 116 | ||
| Spinal Gout | 116 | ||
| IMPACT OF GOUT ON QUALITY OF LIFE | 116 | ||
| DISCLOSURE SUMMARY | 117 | ||
| REFERENCES | 117 | ||
| 11 - Quality of Life | 119 | ||
| GOUT: THE DISEASE AND ITS PREVALENCE | 119 | ||
| QUALITY OF LIFE AND HEALTH-RELATED QUALITY OF LIFE: CONCEPT AND DEFINITIONS | 119 | ||
| WHY MEASURE QUALITY OF LIFE AND HEALTH-RELATED QUALITY OF LIFE WHEN WE HAVE OBJECTIVE DISEASE MEASURES IN GOUT? | 120 | ||
| HOW TO MEASURE QUALITY OF LIFE AND HEALTH-RELATED QUALITY OF LIFE? GENERIC VERSUS DISEASE-SPECIFIC MEASURES IN GOUT | 120 | ||
| PATHWAYS TO THE IMPACT OF GOUT ON HEALTH-RELATED QUALITY OF LIFE AND QUALITY OF LIFE | 121 | ||
| EFFECT OF GOUT ON HEALTH-RELATED QUALITY OF LIFE AND QUALITY OF LIFE | 123 | ||
| PREDICTORS OF HEALTH-RELATED QUALITY OF LIFE AND QUALITY OF LIFE IN PATIENTS WITH GOUT (TABLE 11.2) | 124 | ||
| EFFECT OF GOUT TREATMENTS ON HEALTH-RELATED QUALITY OF LIFE | 131 | ||
| Urate-Lowering Therapies | 131 | ||
| Antiinflammatory Drugs | 132 | ||
| IS INAPPROPRIATE TREATMENT OF GOUT ASSOCIATED WITH WORSE HEALTH-RELATED QUALITY OF LIFE? | 133 | ||
| ARE THERE DISPARITIES IN THE HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH GOUT? | 133 | ||
| PHYSICAL FUNCTION: A CONCEPT RELATED TO QUALITY OF LIFE/HEALTH-RELATED QUALITY OF LIFE | 134 | ||
| SUMMARY AND CONCLUSIONS | 137 | ||
| FUTURE DIRECTIONS | 138 | ||
| DISCLOSURE STATEMENT | 138 | ||
| REFERENCES | 138 | ||
| 12 - Treatment Guidelines: The Good, the Bad, the Ugly | 141 | ||
| INTRODUCTION | 141 | ||
| WHAT ARE CLINICAL PRACTICE GUIDELINES AND HOW SHOULD THEY BE DEVELOPED? | 141 | ||
| CLINICAL PRACTICE GUIDELINES FOR GOUT | 142 | ||
| ON WHAT DO THE GUIDELINES AGREE? | 145 | ||
| Management of Acute Attacks | 145 | ||
| Prophylaxis When Starting Urate-Lowering Therapy | 146 | ||
| Patient Education | 147 | ||
| ON WHAT DO THE GUIDELINES DISAGREE? | 147 | ||
| Dietary Interventions | 147 | ||
| Indications for and When to Consider Urate-Lowering Therapy | 147 | ||
| Treat-to-Target or Treat-to-Avoid-Symptoms? | 148 | ||
| WHAT ARE THE IMPLICATIONS OF THESE DIFFERENCES IN GUIDELINE RECOMMENDATIONS? | 149 | ||
| CONCLUSION | 149 | ||
| REFERENCES | 150 | ||
| 13 - Nonpharmacologic Treatment of Gout | 155 | ||
| INTRODUCTION | 155 | ||
| TOPICAL ICE ACUTE GOUT | 155 | ||
| EXERCISE | 155 | ||
| WEIGHT LOSS | 155 | ||
| LOW PURINE DIET | 156 | ||
| DIET LOW IN FRUCTOSE | 156 | ||
| HYDRATION | 156 | ||
| DECEASE IN ALCOHOL CONSUMPTION | 157 | ||
| DAIRY PRODUCTS | 157 | ||
| COFFEE | 157 | ||
| FRUITS AND VEGETABLES | 157 | ||
| Fruits | 158 | ||
| Cherries | 158 | ||
| Lemons | 158 | ||
| Vegetables | 158 | ||
| Tofu | 158 | ||
| HIGH-PROTEIN DIETS | 158 | ||
| DIETARY SUPPLEMENTS | 158 | ||
| VITAMINS | 159 | ||
| Vitamin C | 159 | ||
| TRADITIONAL CHINESE MEDICINE | 159 | ||
| SUMMARY | 159 | ||
| REFERENCES | 159 | ||
| 14 - Pharmacologic Treatments: Acute Gout | 163 | ||
| INTRODUCTION | 163 | ||
| NONSTEROIDAL ANTIINFLAMMATORY DRUGS | 164 | ||
| COLCHICINE | 164 | ||
| CORTICOSTEROIDS | 165 | ||
| INTERLEUKIN 1B ANTAGONISTS | 166 | ||
| REFERENCES | 167 | ||
| 15 - Current Pharmacological Treatments of Chronic Gout | 169 | ||
| TREATMENT OF CHRONIC GOUT | 169 | ||
| URATE-LOWERING THERAPY | 169 | ||
| URICOSTATIC DRUGS | 169 | ||
| Xanthine Oxidase Inhibitors | 169 | ||
| Allopurinol | 170 | ||
| Febuxostat | 171 | ||
| URICOSURIC DRUGS | 172 | ||
| Probenecid | 173 | ||
| Lesinurad | 173 | ||
| Losartan | 173 | ||
| Fenofibrate | 173 | ||
| Benzbromarone | 173 | ||
| URICOLYTIC DRUGS | 173 | ||
| Pegloticase | 173 | ||
| URATE-LOWERING THERAPY DRUGS ARE EFFECTIVE | 174 | ||
| POOR ADHERENCE TO URATE-LOWERING THERAPY | 174 | ||
| TREATMENT OF CHRONIC GOUT IS NOT JUST ABOUT URATE-LOWERING THERAPY | 174 | ||
| Prophylaxis | 174 | ||
| Colchicine | 174 | ||
| Nonsteroidal Antiinflammatory Drugs | 175 | ||
| Interleukin-1 Inhibitors | 175 | ||
| POOR ADHERENCE TO PROPHYLAXIS | 175 | ||
| CONCLUSION | 175 | ||
| REFERENCES | 175 | ||
| 16 - Treat to Target | 179 | ||
| ORIGINS OF THE TREAT-TO-TARGET CONCEPT | 179 | ||
| EVIDENCE FOR TREAT-TO-TARGET APPROACHES | 179 | ||
| Treat to Target in Gout | 179 | ||
| Symptom-Focused Approach: The Natural History of Gout | 180 | ||
| Serum Urate–Focused Approach: Impact on Outcomes | 180 | ||
| SERUM URATE TARGETS IN GOUT | 180 | ||
| Therapeutic Serum Urate Targets | 181 | ||
| Preventive Serum Urate Target | 181 | ||
| How Fast, How Low, How Long Should We Lower Serum Urate Level? | 181 | ||
| DISCLOSURE STATEMENT | 182 | ||
| REFERENCES | 182 | ||
| 17 - Drugs in the Pipeline | 185 | ||
| INTRODUCTION | 185 | ||
| NEW ANTIINFLAMMATORY STRATEGIES | 185 | ||
| Targeting Interleukin-1β in Acute and Chronic Gout | 185 | ||
| Anakinra | 186 | ||
| Canakinumab | 187 | ||
| Rilonacept | 187 | ||
| Other Novel Antiinflammatory Strategies | 187 | ||
| Dapansutrile (OLT-1177) | 187 | ||
| Bucillamine | 187 | ||
| NEW APPROACHES TO SERUM URATE LOWERING | 187 | ||
| Agents That Inhibit Urate Synthesis | 188 | ||
| Topiroxostat | 188 | ||
| Ulodesine | 189 | ||
| Agents That Promote Urate Degradation | 189 | ||
| Pegloticase | 189 | ||
| Pegsiticase | 189 | ||
| Rasburicase | 190 | ||
| Agents That Promote Urate Excretion | 190 | ||
| Lesinurad | 190 | ||
| Verinurad | 192 | ||
| UR-1102 | 192 | ||
| Tofisopam | 192 | ||
| Drugs with incidental uricosuric benefits | 192 | ||
| DRUGS WITH MIXED MECHANISMS | 192 | ||
| Arhalofenate | 192 | ||
| Tranilast | 193 | ||
| RLBN1001 | 193 | ||
| BEYOND THE PIPELINE: POSSIBLE FUTURE STRATEGIES? | 193 | ||
| CONCLUSION | 193 | ||
| DISCLOSURE STATEMENT | 194 | ||
| REFERENCES | 194 | ||
| Epilogue | 197 | ||
| REFERENCES | 197 | ||
| Index | 199 | ||
| A | 199 | ||
| B | 200 | ||
| C | 200 | ||
| D | 200 | ||
| E | 201 | ||
| F | 201 | ||
| G | 201 | ||
| H | 202 | ||
| I | 203 | ||
| J | 203 | ||
| K | 203 | ||
| L | 203 | ||
| M | 203 | ||
| N | 204 | ||
| O | 204 | ||
| P | 204 | ||
| Q | 205 | ||
| R | 205 | ||
| S | 205 | ||
| T | 206 | ||
| U | 206 | ||
| V | 207 | ||
| W | 207 | ||
| X | 207 | ||
| Y | 207 |