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Abstract
Scleroderma, or systemic sclerosis, is a chronic connective tissue disease generally classified as one of the autoimmune rheumatic diseases. Hardening of the skin is one of the most visible manifestations of the disease. It’s estimated that about 300,000 Americans have scleroderma. About one third of those people have the systemic form of scleroderma. Since scleroderma presents with symptoms similar to other autoimmune diseases, diagnosis is difficult. This issue will cover: The Genetic Basis of SSc: Genetics, Epigenetics, Mechanisms of Pathogenesis – linking fibrosis, vasculopathy and immune dysregulation, The Role of Autoantibodies in Diagnosis and Prognosis/survival; Managing Raynaud’s phenomenon and ischemic ulcers, managing SSc Lung Disease, Monitoring for and Managing Pulmonary Arterial Hypertension, and many more!
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Scleroderma | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| Contents | vii | ||
| Rheumatic Disease Clinics Of North America \r | xi | ||
| Foreword\r | xiii | ||
| Preface\r | xv | ||
| Genetics, Epigenetics, and Genomics of Systemic Sclerosis | 345 | ||
| Key points | 345 | ||
| Introduction | 345 | ||
| Initial evidence of the genetic influence in systemic sclerosis | 346 | ||
| Ethnic Associations | 346 | ||
| Shared Genetic Background in Autoimmune Diseases | 346 | ||
| Genetic study modalities | 346 | ||
| Candidate Gene Approach | 346 | ||
| Genome-Wide Association Studies, Meta–Genome-Wide Association Studies, and Pan-Meta–Genome-Wide Association Studies | 347 | ||
| Immunochip | 353 | ||
| Known genetic associations with systemic sclerosis | 353 | ||
| Major Histocompatibility Complex Region—Human Leukocyte Antigen Genes | 353 | ||
| Major Histocompatibility Complex Region Non-human Leukocyte Antigen Genes | 353 | ||
| Non-major Histocompatibility Complex Genes | 354 | ||
| Innate immunity and interferon pathway genes | 354 | ||
| Adaptive immunity | 354 | ||
| Cell signaling pathways, cytokines, and chemokines | 354 | ||
| Extracellular matrix genes and others | 354 | ||
| The X chromosome | 354 | ||
| Other sources of genetic variation | 355 | ||
| Intronic and Intergenic Mutations | 355 | ||
| Splicing Mutations | 355 | ||
| Expression Quantitative Trait Locus | 356 | ||
| Epigenetics | 356 | ||
| MicroRNA and long noncoding RNA | 357 | ||
| Other epigenetic mechanisms | 357 | ||
| Gene-Gene Interactions | 357 | ||
| Gene expression profiling | 360 | ||
| Summary | 360 | ||
| References | 360 | ||
| The Pathogenesis of Systemic Sclerosis | 367 | ||
| Key points | 367 | ||
| Introduction | 367 | ||
| Overview of Etiopathogenesis | 368 | ||
| Susceptibility | 369 | ||
| Epidemiology | 369 | ||
| Human Leukocyte Antigen Associations | 369 | ||
| Candidate Gene Studies | 369 | ||
| Genome-wide Association Studies | 369 | ||
| Initiation | 370 | ||
| Chemical Triggers | 370 | ||
| Endocrine Triggers | 371 | ||
| Infective Triggers | 371 | ||
| Neoplastic Triggers | 371 | ||
| Progression | 371 | ||
| Raynaud Phenomenon and the Role of Vasoconstrictors | 372 | ||
| Endothelial Damage in Systemic Sclerosis | 373 | ||
| Adhesion Molecules | 373 | ||
| Immunologic Activity in Systemic Sclerosis | 373 | ||
| The Role of Autoantibodies | 373 | ||
| Cellular Immunity | 374 | ||
| Cytokines and Cell Signaling in Systemic Sclerosis | 374 | ||
| Transforming Growth Factor Beta | 374 | ||
| Connective Tissue Growth Factor (or CCN2) | 375 | ||
| Interleukins and Chemokines | 375 | ||
| Fibroblasts | 375 | ||
| Amplification | 376 | ||
| Future considerations | 376 | ||
| References | 376 | ||
| New Classification Criteria for Systemic Sclerosis (Scleroderma) | 383 | ||
| Key points | 383 | ||
| Introduction | 383 | ||
| Previous systemic sclerosis classification criteria | 384 | ||
| Limitations of previous criteria | 384 | ||
| Other previously proposed systemic sclerosis classification criteria | 384 | ||
| The American College of Rheumatology/European League Against Rheumatism systemic sclerosis classification criteria | 385 | ||
| Using the American College of Rheumatology/European League Against Rheumatism Systemic Sclerosis Classification Criteria | 385 | ||
| Methodological Advances | 386 | ||
| Strengths | 387 | ||
| Weaknesses | 388 | ||
| Definitions of Items in the American College of Rheumatology/European League Against Rheumatism Systemic Sclerosis Classifi ... | 391 | ||
| Cases Examples of Scoring for the American College of Rheumatology/European League Against Rheumatism Systemic Sclerosis Cl ... | 394 | ||
| Case 1 | 394 | ||
| Case 2 | 395 | ||
| Case 3 | 395 | ||
| Case 4: systemic sclerosis overlapping with Sjögren's syndrome | 396 | ||
| Case 5: systemic sclerosis sine scleroderma | 396 | ||
| Case 6 | 396 | ||
| Future considerations/summary | 396 | ||
| References | 397 | ||
| Management of Systemic Sclerosis-Related Skin Disease | 399 | ||
| Key points | 399 | ||
| Introduction | 400 | ||
| Symptoms | 400 | ||
| Skin Sclerosis | 400 | ||
| Nonsclerotic Skin Manifestations | 401 | ||
| Diagnosis | 401 | ||
| Physical Examination | 401 | ||
| Histopathology of Skin Biopsies | 403 | ||
| Differential Diagnosis | 403 | ||
| Natural History | 404 | ||
| Diffuse Cutaneous Involvement | 404 | ||
| Limited Cutaneous Involvement | 407 | ||
| Management of skin sclerosis | 407 | ||
| Existing Therapies | 407 | ||
| Methotrexate | 407 | ||
| Cyclophosphamide | 407 | ||
| Autologous hematopoietic stem cell transplantation | 408 | ||
| Ineffective Therapies | 409 | ||
| Questionable Therapies | 409 | ||
| Experimental Therapies | 409 | ||
| B-cell target therapies | 409 | ||
| Interleukin-6 | 409 | ||
| Intravenous immunoglobulin | 409 | ||
| Mycophenolate mofetil | 410 | ||
| Hyperimmune caprine serum | 410 | ||
| Management of nonsclerotic skin manifestations | 410 | ||
| Raynaud’s Phenomenon | 410 | ||
| Ischemic Ulceration | 411 | ||
| Other Nonsclerotic Skin Manifestations | 411 | ||
| Future considerations/summary | 411 | ||
| References | 412 | ||
| Management of Raynaud Phenomenon and Digital Ulcers in Scleroderma | 419 | ||
| Key points | 419 | ||
| Background | 419 | ||
| Digital ulcers | 424 | ||
| Macrovascular disease in scleroderma | 426 | ||
| Principles of management | 428 | ||
| Case presentations | 429 | ||
| Case One | 429 | ||
| Case Two | 430 | ||
| Case Three | 433 | ||
| References | 434 | ||
| Management of Systemic-Sclerosis-Associated Interstitial Lung Disease | 439 | ||
| Key points | 439 | ||
| Introduction | 439 | ||
| Pathogenesis of SSc-ILD | 440 | ||
| Clinical manifestations | 440 | ||
| Risk factors for the presence and progression of SSc-ILD | 443 | ||
| Treating SSc-ILD | 444 | ||
| Whom and When to Treat | 444 | ||
| How to Treat | 445 | ||
| Immunosuppression | 445 | ||
| Cyclophosphamide | 445 | ||
| Mycophenolate mofetil | 446 | ||
| Azathioprine | 446 | ||
| Rituximab | 446 | ||
| Autologous hematopoietic stem cell transplant | 447 | ||
| Other investigational immunosuppressive agents | 451 | ||
| Antifibrotic therapy | 451 | ||
| Adjunctive therapy | 452 | ||
| General measures | 452 | ||
| Intravenous immunoglobulin | 452 | ||
| Lung transplant | 453 | ||
| References | 453 | ||
| Systemic Sclerosis | 459 | ||
| Key points | 459 | ||
| Introduction | 459 | ||
| Pathophysiology overview | 460 | ||
| Oral cavity | 461 | ||
| Esophagus | 461 | ||
| Diagnosis of Esophageal Involvement | 461 | ||
| Treatment of Esophageal Involvement | 462 | ||
| Stomach | 463 | ||
| Small bowel | 463 | ||
| Small Intestine Bacterial Overgrowth | 464 | ||
| Pseudo-Obstruction | 465 | ||
| Pneumatosis Cystoid Intestinalis | 465 | ||
| Vascular Ectasias in the Small Intestine | 466 | ||
| Malabsorption | 466 | ||
| Malnutrition | 466 | ||
| Unusual Specific Radiologic Findings | 467 | ||
| Colon | 467 | ||
| Anorectal involvement | 468 | ||
| Liver | 468 | ||
| Pancreas | 468 | ||
| Gastrointestinal involvement, depression, and quality of life | 468 | ||
| Immunosuppressive therapy for gastrointestinal involvement | 469 | ||
| Alternative and future treatments | 469 | ||
| Summary | 469 | ||
| References | 469 | ||
| Scleroderma Renal Crisis | 475 | ||
| Key points | 475 | ||
| Introduction | 475 | ||
| Definition | 476 | ||
| Epidemiology | 476 | ||
| Prevalence | 476 | ||
| Predictive Factors | 476 | ||
| Pathophysiology | 477 | ||
| Blood-Flow Reduction | 477 | ||
| The Renin-Angiotensin-Aldosterone System Involvement | 477 | ||
| Endothelin | 477 | ||
| Drugs | 477 | ||
| Clinical features | 478 | ||
| Normotensive Scleroderma Renal Crisis | 479 | ||
| Scleroderma Renal Crisis Sine Scleroderma | 479 | ||
| Pregnancy and Scleroderma Renal Crisis | 479 | ||
| Differential Diagnosis | 479 | ||
| Laboratory Findings | 480 | ||
| Renal Pathology | 481 | ||
| Vessels | 481 | ||
| Glomeruli | 481 | ||
| Tubular and interstitial lesions | 481 | ||
| Outcomes and Prognoses | 481 | ||
| Treatment | 482 | ||
| Drugs | 482 | ||
| Dialysis and transplantation | 484 | ||
| Prevention | 484 | ||
| Summary | 485 | ||
| References | 485 | ||
| Monitoring and Diagnostic Approaches for Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis | 489 | ||
| Key points | 489 | ||
| Introduction | 490 | ||
| Epidemiology of Pulmonary Hypertension in Systemic Sclerosis | 490 | ||
| Risk Factors for Pulmonary Arterial Hypertension in Systemic Sclerosis | 490 | ||
| Clinical Presentation | 492 | ||
| Monitoring and Screening for Pulmonary Arterial Hypertension in Systemic Sclerosis | 492 | ||
| ItinerAIR screening algorithm | 493 | ||
| Australian algorithm | 494 | ||
| Detection of pulmonary arterial hypertension in systemic sclerosis algorithm | 494 | ||
| Diagnostic Approach for Pulmonary Arterial Hypertension | 494 | ||
| Interstitial lung disease and pulmonary hypertension in systemic sclerosis | 496 | ||
| Exercise-induced Pulmonary Arterial Hypertension | 496 | ||
| Predictors of Mortality in Systemic Sclerosis–Pulmonary Arterial Hypertension | 496 | ||
| Novel Biomarkers | 497 | ||
| Treatment | 497 | ||
| Supportive therapies | 499 | ||
| Prostanoids | 499 | ||
| Endothelin receptor antagonists | 499 | ||
| Phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulator | 499 | ||
| Transplant | 499 | ||
| Future considerations/summary | 500 | ||
| References | 500 | ||
| Musculoskeletal Manifestations of Systemic Sclerosis | 507 | ||
| Key points | 507 | ||
| Articular involvement in systemic sclerosis | 508 | ||
| Definition | 508 | ||
| Prevalence | 508 | ||
| Clinical Features | 508 | ||
| Investigations | 509 | ||
| Laboratory findings | 509 | ||
| Imaging | 509 | ||
| Tendon involvement in systemic sclerosis | 509 | ||
| Calcinosis in systemic sclerosis | 510 | ||
| Bone involvement in systemic sclerosis | 510 | ||
| Myopathy in systemic sclerosis | 513 | ||
| Definition | 513 | ||
| Prevalence | 513 | ||
| Clinical Features | 513 | ||
| Investigations | 513 | ||
| Prognosis | 514 | ||
| Anti-polymyositis Scleroderma Antibody in Systemic Sclerosis Myopathy | 514 | ||
| Therapy for musculoskeletal manifestations of systemic sclerosis | 515 | ||
| Summary | 516 | ||
| Acknowledgments | 516 | ||
| References | 516 | ||
| Psychosocial Aspects of Scleroderma | 519 | ||
| Key points | 519 | ||
| Introduction | 520 | ||
| Depression | 520 | ||
| Anxiety and Fear | 520 | ||
| Fatigue | 521 | ||
| Sleep | 521 | ||
| Pain | 521 | ||
| Pruritus | 522 | ||
| Body Image | 522 | ||
| Sexual Function | 522 | ||
| Clinical management | 522 | ||
| Self-management | 523 | ||
| Support Groups | 524 | ||
| Future considerations and summary | 524 | ||
| References | 525 | ||
| Index | 529 |