Diathesis 171Several forms of onset have been described for RA. Most
commonly, symptoms develop insidiously over weeks or
months, although a small percentage of patients may experi-
ence an acute onset of symptoms (Harris, 1993). As many as
56% of RA patients may experience a course with partial re-
missions, but many (44%) experience a progressive decline
(Eberhardt & Fex, 1998). Due to improvements in pharma-
ceutical technology, the prognosis for RA is considerably
more favorable today than in the past. However, despite
these medical advances, RA remains a progressive disease
resulting in functional decline and a shortened lifespan
(Harris, 1993).
Several demographic and clinical variables have been
associated with poor prognosis in RA. Women appear to be at
particular risk, as RA affects women 2 to 3 times more than
men (Lawrence et al., 1998). Age is also a source of vulnera-
bility. Although incidence of RA increases with age, there
is evidence that an early onset, particularly before age 60, is
associated with more aggressive disease (Harris, 1993).
Furthermore, younger patients with RA are more vulnerable
to developing depression, which itself is a disabling condi-
tion (Wright et al., 1998). Duration of disease is another risk
factor for poor prognosis, as the “rst two years of disease ac-
tivity appear to be the most amenable to treatment effects
(J. Anderson, Wells, Verhoeven, & Felson, 2000). Thus, fe-
male gender, younger age at onset, and longer duration of dis-
ease activity serve as epidemiological and clinical diathesis
factors contributing to course and prognosis in individuals
with RA. Conversely, male gender, older age at onset, and re-
cent diagnosis serve to bene“t RA progression and outcome.
Besides epidemiological and clinical sources of vulnera-
bility, there exist genetic predispositions to developing RA.
For instance, some studies have demonstrated a fourfold in-
crease in risk for developing severe RA in “rst-degree rela-
tives of individuals with RA (Aho, Koskenvuo, Tuominen, &
Kaprio, 1986). Other genetic studies have found heritability
of RA as high as 65% (MacGregor et al., 2000). Genetics have
been hypothesized to in”uence RA disease initiation and pro-
gression via immunological and hormonal processes. First,
due to the autoimmune nature of RA, much genetic research
has focused on the speci“c structure of immune cells in RA
patients. One model is that RA patients inherit genes that pro-
duce immune cells that have a structure very similar to that of
infectious agents such as viruses or bacteria (for review, see
Harris, 1993). As long as the individual is not exposed to the
infectious agent, the autoimmune response is not generated.
However, once an infection occurs, the individual•s immune
system mounts an attack against the infectious agent but
also mistakenly attacks its own immune cells, particularly the
ones that line the synovial joints. The result is full-blown
RA. Another genetic model of RA development suggests that
individuals with RA inherit genes that produce abnormal
hypothalamic-pituitary-adrenal axis (HPA) responses to
stress and in”ammation (Sternberg et al., 1989). As HPA re-
sponses typically inhibit in”ammation, hypoactivity of the
HPA axis may fail to control in”ammation. Thus, when an
individual with this genetic HPA vulnerability experiences in-
”ammation in the initial stages of RA, his or her HPA re-
sponses are insuf“cient to suppress the RA disease process. It
should be clear from both of these models that, although ge-
netics play a role in establishing vulnerability to developing
RA, genetic in”uences alone are insuf“cient to produce RA.
Instead, these genetic models illustrate the utility of applying
a diathesis-stress approach to understanding RA.OsteoarthritisOA is the most prevalent form of arthritis in the United
States, affecting approximately 20.7 million Americans
(Lawrence et al., 1998). Because the prevalence of this con-
dition increases linearly with age, the number of OA cases is
expected to rise considerably as the American population
matures (Mankin, 1993). Although the precise etiology of
OA is currently unknown, the pathogenesis is primarily char-
acterized by cartilage destruction and bone erosions (Kraus,
1997). In individuals without arthritis, the processes of carti-
lage and bone synthesis and destruction operate in concert.
In contrast, in individuals with OA, cartilage repair does not
keep pace with cartilage destruction and bone synthesis. The
levels of enzymes that promote cartilage destruction are
elevated relative to those that promote cartilage synthesis in
individuals with OA. The net result of the imbalance of carti-
lage destruction and synthesis is a reduction in overall carti-
lage in affected joints. Further complicating the process, bone
synthesis continues and eventually encroaches into the joint
space once occupied by cartilage (Kraus, 1997). Eventually,
due to the contact of bone on bone, movement becomes lim-
ited and pain ensues in affected joints.
As in RA, common symptoms of OA are pain and in”am-
mation, limited range of motion, and morning stiffness
(Kraus, 1997). Furthermore, as disease activity progresses,
joint deformity may develop (Mankin, 1993). However, in
contrast to the widespread, symmetrical joint involvement
characteristic of RA, joint swelling and tenderness in OA are
localized to speci“c joints. The weight-bearing joints of the
body, such as hip, knee, and spinal column joints, are those at
most risk of developing OA. In addition, the hand joints are
also affected in OA, particularly in women (Kraus, 1997).
Onset of OA is usually insidious, with disease slowly pro-
gressing over a period of years. However, although OA is a