C h a p t e r 4 4
Disorders of the Skeletal System: Metabolic and Rheumatic Disorders
1123
principles of joint protection and work simplification.
Some persons need assistive devices to reduce pain and
improve their ability to perform activities of daily living.
Instruction in the safe use of heat and cold modalities
to relieve discomfort and in the use of relaxation tech-
niques are also important.
The classes of drugs used in the treatment of RA
include nonsteroidal anti-inflammatory drugs (NSAIDs)
and selective cyclooxygenase (COX)-2 inhibitors; dis-
ease-modifying antirheumatic drugs (DMARDs); corti-
costeroids; and biologic agents.
38,40
The NSAIDs inhibit
COX-mediated synthesis of prostaglandins, which have
a damaging effect on joint structures (see Chapter 3,
Fig. 3-4).
Corticosteroid drugs interrupt the inflammatory and
immune cascade at several levels, such as interfering
with inflammatory cell adhesion and migration, impair-
ing prostaglandin synthesis, and inhibiting neutrophil
superoxide production. To avoid long-term side effects,
they are used only in specific situations for short-term
therapy at a low dose level. The corticosteroids do
not modify the disease and are unable to prevent joint
destruction. Intra-articular corticosteroid injections can
provide rapid relief of acute or subacute inflammatory
synovitis (after infection is excluded) in a few joints.
They should not be repeated more than a few times
each year.
The DMARDs are a diverse group of therapeutic
drugs that reduce the signs and symptoms of RA as
well as retard progression of the disease. The DMARDs
include hydroxychloroquine, sulfasalazine, methotrex-
ate, and leflunomide. Methotrexate has become the drug
of choice because of its potency, and it is relatively fast
acting (i.e., improvement is seen in 1 month) compared
with the slower-acting DMARDs, which can take 3 to
4 months to work. Methotrexate is thought to interfere
with purine metabolism, leading to the release of adenos-
ine, a potent anti-inflammatory compound. Leflunomide
is a pyrimidine synthesis inhibitor that blocks the prolif-
eration of T cells. All of the DMARDs can be toxic and
require close monitoring for adverse effects, especially
those related to bone marrow suppression.
The biologic agents are structurally engineered ver-
sions of natural molecules (e.g., monoclonal antibod-
ies) designed to target specific pathogenic mediators of
joint inflammation and damage. Etanercept, infliximab,
adalimumab, certolizumab, and golimumab are biologic
response–modifying agents that block tumor necrosis
factor (TNF)-
α
, one of the key proinflammatory cyto-
kines in RA. Abatacept is a recombinant protein that
prevents the co-stimulatory signal that results in full
T-cell activation. Rituximab is a chimeric antibody that
causes B-cell depletion. Tocilizumab prevents IL-6 from
interacting with its receptor and activating cells. The
newest drug used in the treatment of RA is tofacitinib, a
janus kinase 3 inhibitor which interrupts the signal from
the cytokine receptors to the nucleus where inflamma-
tory molecules are made.
41
Surgery also may be a part of the treatment of RA.
Synovectomy may be indicated to reduce pain and joint
damage when synovitis does not respond to medical
treatment. The most common soft tissue surgery is teno-
synovectomy (i.e., repair of damaged tendons) of the
hand to release nerve entrapments. Total joint replace-
ments (i.e., arthroplasty) may be indicated to reduce
pain and increase motion. Arthrodesis (i.e., joint fusion)
is indicated only in extreme cases when there is so much
soft tissue damage and scarring or infection that a
replacement is impossible.
Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic inflam-
matory disease that can affect virtually any organ system,
including the musculoskeletal system. It is a major rheu-
matic disease, with a prevalence of approximately 1 case
per 2000 persons. Systemic lupus erythematosus is pri-
marily a disease of young women, with a peak incidence
between the ages of 15 and 40 years.
42
It is more common
in African Americans, Hispanics, and Asians than whites,
and the incidence in some families is higher than in others.
Etiology and Pathogenesis.
The cause of SLE is largely
unknown. It is characterized by the formation of autoan-
tibodies and immune complexes (type III hypersensitiv-
ity; see Chapter 16).
44
Persons with SLE appear to have
defective elimination of self-reactive B cells with a resul-
tant increase in production of antibodies that can cause
tissue damage. Autoantibodies have been identified
against an array of self-molecules found in the plasma,
cytoplasm, or on the surface of cells, but those directed
against components of the cell nucleus (antinuclear anti-
bodies [ANAs]) are the most characteristic. Antibodies
to double-stranded DNA and a nuclear antigen called
Sm is found in almost all persons with SLE and are part
of the serologic classification of the disease.
The development of autoantibodies can result from
a combination of genetic, hormonal, and environmen-
tal factors.
42
Genetic predisposition is evidenced by the
occurrence of familial cases of SLE, especially among
identical twins, and the increased incidence among
African Americans compared with whites. As many as
four genes may be involved in the expression of SLE.
42
Studies also suggest that an imbalance in sex hormone
levels may play a role in the development of the disease,
especially because the disease is so prevalent among
women. Possible environmental triggers include ultravi-
olet (UV) light, certain foods, infectious agents, and toxic
chemicals, including some drugs.
43,44
Photosensitivity
frequently occurs in SLE.
43
Photosensitive persons may
report a worsening of systemic disease symptoms such
as fatigue and joint pain following sun exposure. Certain
drugs may also provoke a lupus-like disorder in suscep-
tible persons, particularly in the elderly. The most com-
mon of these drugs are hydralazine and procainamide.
Clinical Manifestations.
Systemic lupus erythemato-
sus can manifest in a variety of ways. The disease has
been called the
great imitator
because it has the capac-
ity to affect many different body systems, including the
musculoskeletal system, skin, cardiovascular system,
lungs, kidneys, central nervous system (CNS), and red
