24: Inflammatory Rheumatic Diseases

Introduction

The inflammatory rheumatic diseases form a group of disorders that are highly variable in their phenotypic expression. However, they have in common the presence of localized and/or systemic inflammation, which results in characteristic connective tissue and internal organ damage. Among these diseases, the specific clinical and pathologic features of each disorder likely reflect the initiating and propagating stimuli that determine the specific tissues targeted, and the inflammatory effector mechanisms that predominate.

Although the spectrum of inflammatory rheumatic diseases is broad, some general principles provide a framework within which to discuss the pathophysiology of all. One of the most useful constructs is a kinetic one, which focuses on disease initiation, propagation and flares. It is useful for discussion of both acute and chronic diseases. Understanding the stimuli and mechanisms responsible for each of these phases among the different rheumatic diseases permits a deeper insight into these fascinating and complex syndromes.

Overview of Inflammatory Rheumatic Diseases

Acute Diseases

The initiating force of acute diseases (eg, gout, immune complex vasculitis) is often exogenous and clearly recognizable (eg, crystal deposition, new medication, systemic bacterial or viral infection). The disease is self-limited due to the success of the inflammatory response in removing the offending initiating stimulus (eg, crystals in gout; bacterial antigen or drug in immune complex vasculitis; Figure 24–1). Despite resolution of the acute episode, flares may occur upon reexposure to the initiating stimulus.

Chronic Diseases

The initiating force in chronic diseases (eg, systemic lupus erythematosus [SLE], rheumatoid arthritis) is often remote and no longer recognizable once the unique disease phenotype becomes fully established and the diagnosis clear. Propagation of the disease typically occurs as a result of an autoimmune response, inducing a self-amplifying cycle of damage. Conditions leading to the initiation of chronic autoimmune diseases occur rarely, but once a disease is established, flares are frequent. This circumstance probably reflects the abundant capacity of the immune system to “remember” previously encountered antigens and to respond to them with greater vigor when encountered again, even at lower concentrations (Figure 24–1).

Different tissues are affected in various diseases (eg, specific synovial joints in gout and rheumatoid arthritis; skin, joints, kidney, serosal surfaces, nervous system, and blood cell lines in SLE).

Pathogenesis of Inflammation

The nature of tissue damage and joint injury is determined in part by the inflammatory and immune effector functions that predominate. In addition, the pathologic features of the chronic inflammatory disorders reflect the combination of inflammatory damage and the consequences of healing.

Endothelial Activation

Recruitment and activation of specific subsets of inflammatory and immune ...