C h a p t e r 4 4
Disorders of the Skeletal System: Metabolic and Rheumatic Disorders
1119
Rheumatic Disorders
Arthritis
is a descriptive term applied to more than 100
rheumatic disorders, ranging from localized, self-limit-
ing conditions to those that are systemic immune-medi-
ated processes. The term, which is used to describe any
disorder that affects the joints, oversimplifies the nature
of the varied disease processes, the difficulty in differen-
tiating one form of arthritis from another, and the com-
plexity of treatment of these usually chronic conditions.
These diverse rheumatic conditions share inflammation
of the joint as a prominent or accompanying symptom.
In the systemic rheumatic diseases, such as rheumatoid
arthritis, the inflammation is primary, resulting from an
immune response, probably autoimmune in origin. In
rheumatic conditions limited to a single or few diarthro-
dial joints, such as osteoarthritis, the inflammation is
secondary, resulting from the degenerative process and
joint irregularities.
Systemic Autoimmune Rheumatic
Diseases
Systemic autoimmune rheumatic diseases are a group of
chronic disorders characterized by diffuse inflammatory
vascular lesions and degenerative changes in connective
tissue that share clinical features and may affect many
of the same tissues and organs. They include rheuma-
toid arthritis, systemic lupus erythematosus, and sys-
temic sclerosis, all of which share an immune-mediated
pathogenesis.
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune sys-
temic disease that affects all ethnic groups throughout
the world, with women being affected more frequently
than men. The onset of the disease can occur at any age,
but its peak incidence is between 50 and 75 years of
age.
34
Etiology.
Although the cause of RA remains uncer-
tain, evidence points to a genetic predisposition and
the development of joint inflammation that is immu-
nologically mediated.
3,4,35
It has been suggested that
the disease is initiated in a genetically predisposed
individual by the activation of a T-cell–mediated
response to an immunologic trigger, such as a micro-
bial agent (Fig. 44-5). The importance of genetic fac-
tors in the pathogenesis of RA is supported by the
increased frequency of the disease among first-degree
relatives and monozygotic twins.
4
In addition, specific
major histocompatibility complex (MHC) alleles or
human leukocyte antigen (HLA) types have been asso-
ciated with RA (see Chapter 15). An increased preva-
lence of RA has been associated with specific HLA DR
alleles that share a sequence of amino acids located
in the antigen-binding site of the DR molecule. This
location is presumably the specific binding site of the
immunologic trigger.
3
Cigarette smoking is a strong
risk factor for the development of RA and may also
influence the severity of the disease, especially in those
with the shared epitope (HLA-DR4 marker) and a
positive anti-citrullinated peptide antibody (ACPA)
test, to be discussed.
35,36
Pathogenesis.
The pathogenesis of RA can be viewed
as an aberrant immune response that leads to synovial
inflammation and destruction of the joint architecture.
It has been suggested that the disease is initiated by
the activation of CD4
+
helper T cells, the local release
of inflammatory mediators and cytokines (e.g., tumor
necrosis factor [TNF], interleukin [IL]-1) that destroy
the joint, and formation of antibodies directed against
joint-specific and systemic autoantigens. Approximately
■■
Paget disease is a disorder involving excessive
osteoclastic activity, and bone destruction
and repair, resulting in structural deformities
of the long bones, spine, pelvis, and cranium.
Symptomatic disease may be manifest as skeletal
changes and symptoms related to expansion of
the skull, jaw, clavicle, spine, and long bones of
the leg.
Genetic predisposition (HLA type)
plus
immunologic trigger
T-cell–mediated
immune response
RF antigen/IgG interaction
Complement fixation
Inflammatory
response
Recruitment of
inflammatory cells
Release of enzymes
and prostaglandins
Destruction of articular
cartilage and underlying
bone
Cytokine production
TNF, IL-1
Angiogenesis
in synovium
Synovial
proliferation
Pannus
invasion
FIGURE 44-5.
Disease process in rheumatoid arthritis. IL,
interleukin;TNF, tumor necrosis factor.
