The Heart in Systemic Autoimmune Diseases

Fabiola Atzeni, Andrea Dorea, Mike Nurmohamed, Paolo Pauletto

• Publisher: Elsevier Science
• Year: 2017
• Print ISBN: 9780128039977
• eBook ISBN: 9780444636690
• Edition: 2
• Topic: Medicine
• Subtopic: Diseases & Allergies

The Heart in Systemic Autoimmune Diseases, Second Edition, provides an overview on our current understanding of major complications relating to the heart and autoimmune diseases. It includes the latest information on the new pathogenetic mechanisms involved, along with clinical manifestations of these important comortbidities. Mortality in autoimmune diseases, in particular, rheumatoid arthritis and SLE, has increased when compared with the general population. This excess mortality is largely due to cardiovascular diseases (CVDs)-particularly those of atherosclerotic origin, such as ischemic heart disease-and is gaining recognition in all branches of medicine, from cardiology, to internal medicine, and from rheumatologists to orthopedics.- Presents an impressive body of well ordered information on the topic of cardiovascular diseases and their relationship to autoimmune illness- Highlights key references- Summarizes the experience of a selected panel of distinguished physician-scientists who are actively involved in the field of cardiovascular disease and systemic autoimmunity

Chapter 1

Cellular Immunity

A Role for Cytokines

D. Lisa Fairweather^∗, M. Afanasyeva^∗ and N.R. Rose^{§ ∗}Johns Hopkins Medical Institutions, Baltimore, MD, United States ^§Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, United States

Abstract

The heart is a remarkably durable and efficient pump that provides all cells of the body with nutrients and removes waste products. Myocarditis is a process characterized by an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with coronary artery disease. Autoimmune heart disease following viral infection involves the production of key cytokines by immune cells such as macrophages and natural killer cells. Finally, if environmental or genetic factors allow overproduction of proinflammatory cytokines, then progression to chronic autoimmune myocarditis may follow. Importantly, myocarditis often precedes the development of dilated cardiomyopathy, which can lead to heart failure and the need for cardiac transplantation.

Keywords

Autoimmunity; Inflammation; Myocarditis; Myocytes; Natural killer

The chapter has been revised and updated by Francesco Caso, Rossella Talotta, and Fabiola Atzeni for the 2016 edition.

Key Points

• Myocarditis is a process characterized by an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with coronary artery disease.

• The development of autoimmune heart disease following viral infection involves the production of key cytokines by immune cells such as macrophages and natural killer cells.

• Environmental or genetic factors allow overproduction of proinflammatory cytokines, then progression to chronic autoimmune myocarditis may follow.

1. Introduction

The heart is a remarkably durable and efficient pump that provides all cells of the body with nutrients and removes waste products. If cardiac dysfunction occurs for any reason, it can have devastating results. Consequently, heart disease accounts for the majority of illness and death in Western populations (Schoen, 1999). Myocarditis or inflammation of the heart muscle is a significant contributor to heart disease, especially in infants, children, and young adults, and its treatment remains problematic (Drory et al., 1991; Rose and Afanasyeva, 2003). Importantly, myocarditis often precedes the development of dilated cardiomyopathy (DC), which can lead to heart failure and the need for cardiac transplantation.

Myocardial inflammation is a major diagnostic characteristic of myocarditis. According to the current histologic definition based on the Dallas criteria, myocarditis is a “process characterized by an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with coronary artery disease” (Aretz, 1987). Although inflammation can also occur as a result of ischemic injury, in myocarditis the inflammatory infiltrate plays a primary role in causing the myocardial damage.

The true incidence of myocarditis in the human population is unknown, but up to 10% of routine post-mortem examinations show histological evidence of myocardial inflammation (Gore and Saphir, 1947; Gravanis and Sternby, 1991). Because myocarditis is often difficult to diagnose with standard cardiologic tests, a definitive diagnosis depends on an endomyocardial biopsy, a relatively insensitive procedure due to the focal nature of the inflammation. Histologically defined disease has been confirmed in only approximately 30% of the patients with clinically suspected myocarditis, and in 30–60% of patients with DC (Marboe and Fenoglio, 1988; Peters and Poole-Wilson, 1991). The wide range in the rate of detection of myocarditis in biopsy specimens probably reflects local differences in diagnostic criteria and patient selection as well as the insensitivity of biopsy in general.

To further complicate diagnosis, myocarditis can be induced from many different agents including infections, immune-mediated reactions, or drugs (Table 1.1). Viral infections, such as Coxsackievirus B3 (CVB3) and cytomegalovirus (CMV), are widespread in the population, and most individuals in Western populations will be infected with one or both of these two viruses at some point, although acute viral myocarditis may occur frequently without clinical detection (Forbes, 1989; Grist and Reid, 1993). Advances in molecular techniques, such as genomic hybridization and the polymerase chain reaction (PCR), have confirmed the presence of infectious agents like CVB3 in the hearts of some myocarditis and DC patients, but the high prevalence of these infections in the population makes it difficult to relate infection with disease. Because these viruses are so common, diagnostic tests based on detection of viral antibody tend to be overly sensitive and the viral infection has usually cleared from the blood stream by the time heart disease occurs. Hence, a better understanding of the pathogenesis of disease is needed in order to find measures that both confirm diagnosis and determine whether the disease is at an early viral or later immune-mediated stage. When viruses directly damage myocytes or initiate immune-mediated damage is often unclear (Huber, 1997; Fairweather et al., 2001).

A number of infectious agents other than viruses are associated with myocarditis. Parasites such as Trypanosoma cruzi (the causative agent of Chagas disease) are the primary cause of myocarditis in Latin American populations where parasites are estimated to infect 16 to 18 million people (Table 1.1) (Cunha-Neto et al., 1996). Chagas disease can afflict nearly 50% of endemic populations with 80% of infected individuals developing myocarditis (Schoen, 1999). Likewise, bacterial infection with Streptococcus pyogenes may result in rheumatic heart disease, which remains a major cause of heart disease in many developing countries. Myocarditis has also been associated with systemic autoimmune diseases such as systemic lupus erythematosus and polymyositis.

Table 1.1

Major Causes of Clinical Myocarditis

Infections

Viruses (e.g., Coxsackievirus, CMV, influenza)

Bacteria (e.g., streptococci, Borrelia burgdorferi (Lyme disease), chlamydia)

Protozoa (e.g., Trypanosoma cruzi (Chagas disease))

Immune-mediated reactions

Post-viral

Post-streptococcal (rheumatic fever)

Systemic lupus erythematosus

Drug hypersensitivity (e.g., sulfonamides)

Transplant rejection

Chemical

Drugs (e.g., adriamycin, cocaine, lead)

Physical

Radiation

Hyperpyrexia

Exercise stress

Unknown

Sarcoidosis

Modified from Huber, S.A., 1997. Autoimmunity in myocarditis: relevance of animal models. Clin. Immunol. Immunopathol. 83, 93 and Schoen, F.J., 1999. The heart. Cotran, R.S., Kumar, V., Collins, T. (Eds.), Robbins Pathologic Basis of Disease. W.B. Saunders Co., Philadelphia, pp. 544.

2. Autoimmunity in Myocarditis

Soon after autoimmune diseases were first recognized more than a ce...

Table of contents

• Cover image
• Title page
• Table of Contents
• Handbook of Systemic Autoimmune Diseases
• Copyright
• Dedication
• List of Contributors
• Preface
• Chapter 1. Cellular Immunity: A Role for Cytokines
• Chapter 2. Organ-Specific Autoimmunity Involvement in Cardiovascular Disease
• Chapter 3. Neonatal Lupus Syndromes: Pathogenesis and Clinical Features
• Chapter 4. Subclinical Cardiovascular Damage in Systemic Rheumatic Diseases
• Chapter 5. Atherosclerosis and Autoimmunity
• Chapter 6. Inflammasomes and Inflammatory Cytokines in Early Atherosclerosis
• Chapter 7. Treatment of Lipid Metabolism Disturbances in Autoimmune Diseases
• Chapter 8. Cardiac Imaging Techniques in Systemic Autoimmune Diseases
• Chapter 9. New Cardiac Imaging Tools and Invasive Techniques in Systemic Autoimmune Diseases (Part II)
• Chapter 10. Cardiac Diseases in Rheumatoid Arthritis
• Chapter 11. Cardiac Involvement in Systemic Lupus Erythematosus
• Chapter 12. Cardiac Involvement in the Antiphospholipid Syndrome
• Chapter 13. Cardiac Involvement in Scleroderma
• Chapter 14. Cardiac Involvement in Systemic Vasculitis
• Chapter 15. Cardiovascular Involvement in Ankylosing Spondylitis
• Chapter 16. Cardiovascular Involvement in Psoriatic Arthritis
• Chapter 17. Cardiovascular Involvement in Primary Sjögren's Syndrome
• Chapter 18. Gout and Heart Disease: A Two-Way Street?
• Chapter 19. Heart Involvement in Osteoarthritis
• Chapter 20. Cardiac Effects of Antirheumatic Drugs
• Index