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, and 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 diseases permits a deeper
insight into these fascinating and complex syndromes.
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 on reexposure to the initiating
Kinetics of acute and chronic inflammatory rheumatic
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
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).
of Inflammation: Introduction
The nature of tissue damage and joint injury is determined in part
by the inflammatory and immune effector functions that predominate.
Additionally, the pathologic features of the chronic inflammatory
disorders reflect the combination of inflammatory damage and the consequences of healing.
Recruitment and activation of specific subsets of inflammatory
and immune cells are essential determinants of the pathologic features.
In this regard, the role of activation of ...