Epidemiology The world population is around 7.7 billion of which nearly 30% are children less than 18 years of age. The top five most populous countries have 45% of the world population. Asia has 60% of the world population, with India and China each having 1.3 to 1.4 billion people. Africa also has a population of 1.3 billion. Thus, the major burden of pediatric rheumatic diseases…
Introduction Rheumatic diseases in children are frequently multisystem, chronic, and characterized by periods of disease activity and remission. The disease and therapy can have significant impact on the child physically and emotionally. Early diagnosis of disease through thoughtful, thorough, and appropriate investigation is important for prognosis and improved outcomes. The best approach to the management of children with rheumatic disease includes specialized multidisciplinary teams ( Fig.…
Introduction Over the past 85 years the role of laboratory investigation in rheumatic diseases has progressed from reports of curious in vitro phenomena in diseases defined purely on clinical grounds to sophisticated immunopathology testing providing information now essential for disease diagnosis. A corollary of this progress is that rheumatology practice has increasingly involved the clinical interpretation of an expanding array of laboratory tests. To be proficient at…
Introduction Imaging often plays a key role in establishing the presence, severity, and extent of inflammation of musculoskeletal tissues and can also help monitor disease complications, exclude other diagnoses, and assess treatment response. Imaging can provide early diagnosis and visualization of inflammatory abnormalities including synovitis, tenosynovitis, and enthesitis, as well as osteochondral damage. This chapter provides an approach to the imaging investigation of the child with…
Introduction Chronic pain in children and adolescents is commonly defined as any prolonged pain that lasts longer than the expected healing time (arbitrarily defined as greater than 3 months), or any recurrent pain that occurs at least three times throughout a period of 3 months. Chronic pain is a primary symptom of many pediatric rheumatic (e.g., arthritis) and nonrheumatic musculoskeletal conditions (e.g., amplified musculoskeletal pain syndromes,…
Introduction Pediatric rheumatic diseases are a broad group of disorders characterized by chronic inflammation, which may have a profound effect on the child’s well-being and may cause irreversible changes in several organs and systems. The aim of the management of these illnesses is to control objective signs of inflammation, to preserve physical function and health-related quality of life (HRQoL), and to prevent organ damage. The achievement…
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…
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…
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.…
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…
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.…
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…
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…
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…
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…
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…
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…
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…
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,…
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…