C h a p t e r 4 4
Disorders of the Skeletal System: Metabolic and Rheumatic Disorders
1125
analysis of bloodwork. The most common laboratory
test performed is the immunofluorescence test for ANA.
The ANA test is not specific for SLE, and positive ANA
results may be found in healthy persons or may be
associated with other disorders. Other serum tests may
reveal moderate to severe anemia, thrombocytopenia,
and leukocytosis or leukopenia.
Treatment of SLE focuses on managing the acute and
chronic symptoms of the disease.
46
Persons with photo-
sensitivity should be cautioned against sun exposure and
should apply a protective lotion when outdoors. Skin
lesions often respond to local application of corticoste-
roids and minor joint symptoms are usually relieved by
rest and NSAIDs.
An antimalarial drug (e.g., hydroxychloroquine) may
be helpful in treating mucocutaneous manifestations,
pleuritis, arthritis, and fatigue. Corticosteroids are used
to treat more significant symptoms of SLE, such as renal
and CNS disorders. High-dose corticosteroid treatment
is used for acute symptoms, and the drug is tapered to
the lowest therapeutic dose as soon as possible to mini-
mize the adverse effects. Immunosuppressive drugs,
such as azathioprine and cyclophosphamide, may be
used in cases resistant to corticosteroids. Biologics, such
as rituximab and belimumab, target B cells and are used
for refractory symptoms.
Systemic Sclerosis/Scleroderma
Systemic sclerosis, commonly called
scleroderma,
is an
autoimmune disease of connective tissues that causes
extensive fibrosis throughout the body.
47–49
The disease
affects women four times as frequently as men, with a
peak incidence in the 35- to 50-year-old age group.
47
The cause of systemic sclerosis is poorly understood,
although there is evidence of both humoral and cellu-
lar immune system abnormalities.
47
Fibroblast activa-
tion with excessive fibrosis is a hallmark of the disease.
Skin involvement is the usual presenting symptom, but
it is the involvement of organs such as the gastrointes-
tinal tract, heart, lungs, and kidneys that produces the
major morbidity and mortality. Microvascular disease is
also present early in the disease, with repeated cycles of
endothelial damage followed by platelet activation and
release of platelet factors that lead to fibrosis and nar-
rowing of the microvasculature and tissue ischemia.
Clinical Manifestations.
Scleroderma presents as two
major clinical subsets: limited and diffuse scleroderma.
The most common subset, which accounts for about half
of the cases, is limited cutaneous scleroderma in which
the skin changes are limited to the fingers, forearms,
and face. Some persons with limited involvement also
develop a condition called the
CREST
syndrome, char-
acterized by a combination of
c
alcinosis (i.e., calcium
deposits in the subcutaneous tissue that erupt through
the skin),
R
aynaud phenomenon (a vascular disorder
characterized by reversible vasospasm of the arteries
supplying the fingers [see Chapter 18]),
e
sophageal dys-
motility,
s
clerodactyly (localized scleroderma of the fin-
gers), and
t
elangiectasia (dilated skin capillaries).
48
Diffuse scleroderma, which accounts for approxi-
mately 35% of persons with scleroderma, is charac-
terized by severe, widespread, and progressive skin
involvement and early onset of organ involvement.
49
The typical person has a “stone facies” due to tight-
ening of the facial skin with restricted motion of the
mouth. Other cutaneous manifestations include hair
loss on the involved skin and telangiectasis on the face,
buccal mucosa, chest, and hands. Almost all persons
with diffuse scleroderma develop Raynaud phenom-
enon. Musculoskeletal involvement is common. Puffy
hands with arthralgia and myalgia may lead to diffi-
culty forming a fist. There are palpable or audible fric-
tion rubs over the extensor and flexor tendons of the
hands, knees, and ankles. Involvement of the esopha-
gus that leads to difficulty swallowing is common, and
malabsorption may develop if the disease affects the
intestine. Pulmonary involvement leads to dyspnea and
eventually respiratory failure. Vascular involvement
of the kidneys is responsible for malignant hyperten-
sion and progressive renal insufficiency. Cardiac prob-
lems include pericarditis, heart block, and myocardial
fibrosis.
Treatment.
Treatment of systemic sclerosis is largely
symptomatic and supportive.
48,49
Advances in treat-
ment, primarily the use of angiotensin-converting
enzyme (ACE) inhibitors in renal involvement, have led
to a substantial decrease in the mortality from hyper-
tensive renal disease.
50
Cardiopulmonary manifestations
of scleroderma, specifically pulmonary hypertension,
can be treated with prostanoids (or endothelial recep-
tor antagonists [bosentan]). Disease modifying agents
such as methotrexate, cyclophosphamide, azathioprine,
and mycophenalate mofetil have been reported effective
in limited case series or randomized controlled trials.
These agents can be used in early diffuse disease.
Seronegative Spondyloarthropathies
The
spondyloarthropathies
are an interrelated group
of multisystem inflammatory disorders that primar-
ily affect the axial skeleton, particularly the spine.
3,4,51
Sacroiliitis is a pathologic hallmark of the disorders.
Typically, the inflammation begins at sites, called
enthe-
se
s, where tendons and ligaments insert into bone rather
than the synovium. There may also be inflammation and
involvement of the peripheral joints, in which case the
signs and symptoms overlap with other inflammatory
types of arthritis.
The spondyloarthropathies are grouped into two
subtypes: the axial spondyloarthropies, which include
ankylosing spondylitis; and the peripheral spondylo-
arthropathies, which include psoriatic arthritis, reac-
tive arthritis, inflammatory bowel disease–associated
arthritis, and undifferentiated peripheral spondyloar-
thritis. Although they differ in terms of factors such as
age and type of onset and extent of joint involvement,
there is clinical evidence of overlap between the various
disorders.
