Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Understanding Clinical Investigations

The critical evaluation of clinical studies is essential for the practice of evidence-based medicine. This chapter will provide readers with sufficient knowledge of study design and data analysis to understand and to begin to assess the quality of clinical investigations. Truth, Levels of Evidence, and Evidence-Based Medicine The aim of research is to discover the truth. In clinical trials, the truth is usually the true effectiveness…

Adaptive Immunity and Autoimmunity

Immune defense against microbes is mediated by sequential and coordinated responses, termed innate and adaptive immunity . Innate immunity represents early response mechanisms that facilitate rapid reaction to invading pathogens in the first few hours or days after infection (see Chapter 4 ). Adaptive immunity, in contrast, provides stronger and more specialized responses, as well as memory of the response, leading to more rapid and effective…

Inflammation and Its Mediators

The immune system, the function of which is to protect against infections, is composed of two branches: a phylogenetically earlier one called innate immunity and a more recently evolved one called adaptive immunity. Innate and adaptive immunity are not two separate compartments but an integrated system of host defense, sharing bidirectional interactions fundamental to both the inductive phase and the effector phase of the immune response.…

Mechanistic Investigation of Pediatric Rheumatic Diseases

Introduction Pediatric rheumatology owes a great debt to meticulous clinical observations. In the 21st century, however, the practice of pediatric rheumatology requires skills beyond obtaining a thorough history and physical examination. In this chapter, we endeavor to build upon the basic concepts of immunology to introduce and contextualize some of the laboratory methods used to investigate, and increasingly to manage, pediatric rheumatic diseases. This chapter will…

Genetics and Pediatric Rheumatic Diseases

Introduction Genetics is the study of the relationships between genetic variation (genotypes) and heritable traits (phenotypes). When these investigations are expanded to explore genotype–phenotype relationships across the entire genome, they are called genomics . Together, genetics and genomics investigations are an important starting point for the study of human disease, seeking to discover genetic variants that are relevant to disease pathophysiology, prognosis, and response to treatment.…

Structure and Function

Rheumatic diseases involve abnormalities of multiple organs and systems, but it is predominantly the musculoskeletal system that is affected. The musculoskeletal system consists of bones, joints, cartilage, tendons, ligaments, muscles, and associated connective tissues. This chapter is an overview of normal musculoskeletal biology. In other sections, pathology of the musculoskeletal system and other systems pertinent to rheumatic diseases, including immune, vascular, and neurological systems, are discussed…

Repositioning drugs for systemic lupus erythematosus

Why try to repurpose/reposition drugs for SLE patients? The term drug repurposing refers to using or testing a drug that has been approved by the regulatory authorities for one disease indication in another disease, in this case systemic lupus erythematosus (SLE). Drug repurposing has a number of other names including repositioning, rescue, reprofiling, retooling, and retasking. Because only five medications have been approved by the United…

New treatments of systemic lupus erythematosus

Although the etiology of systemic lupus erythematosus (SLE) remains unknown, breakthroughs in the pathophysiology of the disease in the last two decades have allowed for the design and testing of several targeted treatments. This has further been facilitated by the standardization of global outcome measures for non-renal SLE; the most helpful outcome measures are the SLE disease activity index (SLEDAI)-based Response Index (SRI) and British Isles…

Treatment of antiphospholipid syndrome

Introduction Antiphospholipid syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity occurring in patients with persistent antiphospholipid antibodies (aPL). Prevention of thrombosis and proper management of women during pregnancy are the major goals of therapy in patients with aPL. Treatment of APS has long been the subject of intense debate, due to the diversity of clinical presentations and medical specialties involved. A consensus document has…

Cytotoxic drug treatment

Introduction Cytotoxic drugs were introduced in medicine as antineoplastic agents for their ability to interrupt nucleic acid and protein synthesis in cancer cells. Immunosuppressive agents, such as calcineurin inhibitors, were first used in renal transplantation. Due to their immunosuppressing and immunomodulating properties, cytotoxic and immunosuppressive drugs were subsequently used for the management of autoimmune diseases, including SLE. General indications for cytotoxic—immunosuppressive drug treatment in SLE are…

Systemic glucocorticoids

Introduction Since their discovery in 1949 by Philip Showalter Hench and coworkers, glucocorticoids continue to be the cornerstone of the treatment of several rheumatic diseases including systemic lupus erythematosus (SLE). In the initial trial of synthetic cortisone in 1949 on patients with rheumatoid arthritis, Hench et al. found that some clinical and laboratory features of rheumatoid arthritis benefited by the daily intramuscular injection with either the adrenal…

Value of antimalarial drugs in the treatment of lupus

Introduction Antimalarial agents are now used as the standard of care for the treatment of systemic lupus erythematosus (SLE). The first documented use of antimalarial medications dates back to the sixteenth century, when powder from the cinchona bark tree, which grows in the Andes, was used successfully to treat malaria and was distributed through Europe by the Jesuits. In the nineteenth century, chemical analysis showed that…

Nonsteroidal antiinflammatory drugs in systemic lupus erythematosus

Introduction Nonsteroidal antiinflammatory drug (NSAID) use in systemic lupus erythematosus (SLE) dates back to the early 1950s, when phenylbutazone, the first nonsalicylate NSAID, was used to treat “subacute” lupus in 1953. Aspirin or acetylsalicylic acid (ASA) was the first NSAID to be introduced in 1899 and later, nonASA NSAIDS were introduced including indomethacin in 1964 and ibuprofen in 1969. NSAIDS to date have different classifications including,…

Clinical manifestations

Introduction Antiphospholipid syndrome (APS) is a systemic autoimmune disease, and its most critical manifestation is acquired thrombogenicity. It is classified by at least one clinical and one laboratory criterion ( Table 60.1 ). Vascular thrombosis and pregnancy morbidity are the manifestations for the clinical criteria. The presence of at least one antiphospholipid antibody (aPL)—lupus anticoagulant (LA), anticardiolipin (aCL) and/or anti-β2 glycoprotein I antibodies (aβ2GPI) —on two separate…

Antibodies and diagnostic tests in antiphosholipid syndrome

Antiphospholipid syndrome as an autoantibody–mediated disease Antiphospholipid syndrome (APS) is the most recent example of an autoantibody-mediated disease. Indeed, antibodies directed against phospholipid (PL)-binding proteins—the antiphospholipid antibodies (aPL)- not only are significantly associated with both vascular and obstetric manifestations of the syndrome but also mediate pathogenic pathways. aPL trigger thrombotic events only occasionally and in association with additional thrombophilic factor, suggesting that a “second hit” is…

Pathogenesis of antiphospholipid syndrome

Introduction The presence of antiphospholipid antibodies (aPL) is the defining feature of antiphospholipid syndrome (APS), a systemic disorder clinically characterized by widespread thrombosis and obstetric complications. Despite their name, the majority of aPL associated with APS are directed against phospholipid-binding plasma proteins, among them β2-glycoprotein I (β2GPI) and prothrombin are recognized as the most relevant antigenic targets. In the laboratory, aPL can be broadly categorized into…

Vasculitis in lupus

Prevalence and associated features of vasculitis in lupus It is difficult to obtain exact figures for the prevalence of vasculitis in lupus, as the definition of what constitutes vasculitis differs between different authors. A recent review cites a prevalence of 11% to 36%. Most of the evidence comes from large retrospective studies in single centers. Drenkard et al. in 1997 reported on a cohort of 540 Mexican…

Drug-induced lupus

Introduction and historical perspective Typical drug-induced lupus (DIL) was first reported by Morrow and coworkers in which a late onset “collagen disease” resembling systemic lupus erythematosus (SLE) developed in 17 out of 211 hydralazine-treated patients and by Dustan and coworkers in which 13 out of 139 patients on hydralazine developed constitutional and rheumatologic symptoms. Eight years later Ladd reported a patient who developed lupus-like features after…

Lupus in children

Childhood-onset disease represents a substantial portion of systemic lupus erythematosus (SLE). Although pathophysiology, disease manifestations, and treatment strategies are generally similar to those of adult patients, there are some unique considerations in the diagnosis and management of pediatric lupus. Epidemiology Among all patients with SLE, it is estimated that 10%-20% have onset in childhood. Definition of childhood-onset, or pediatric SLE (pSLE), however, varies by study as…

Incomplete lupus syndromes

Definition Classification criteria for systemic lupus erythematosus (SLE) have been widely utilized in the study of this disease, enabling clinical trials, and new drug approvals. Although not intended to be used as diagnostic criteria, these lists of clinical and laboratory findings are often referred to in clinical practice when trying to determine if a patient has SLE. The starting point for most of these patients is…