deskmate-斯塔克豪斯
Chapter 289
SYSTEMIC LUPUS
ERYTHEMATOSUS
Peter H. Schur
Systemic
lupus
erythematosus
(
SLE
)
is
a
disease
of
unknown
cause
that
may
produce
variable combinations of fever, rash, hair loss,
arthritis,
pleuritis, pericarditis,
nephritis, anemia, leukopenia,
thrombocytopenia,
and
central
nervous
system
(CNS)
disease.
The
clinical
course is
characterized by periods of remissions and acute
or chronic
relapses.
Characteristic
immune
abnormalities,
especially
antibodies
to
a
number
of
nuclear
and
other
cellular
antigens,
develop
in
patients
with
SLE.
The
diagnosis
is
facilitated
by
determining
whether
the
patient
has
4 of the 11 clinical and/or laboratory
criteria developed for the
classification of SLE
(Table
289-1)
.
EPIDEMIOLOGY.
SLE
can occur at any age but has its onset primarily
between ages 16 and
55.
It
occurs
more
frequently
in
women.
In
children,
the
female-male
ratio
is 1.4 to 5.8:1; in adults, it ranges
from 8:1 to 13:1; and in older
individuals, the ratio is 2:1. The
prevalence of SLE is estimated to be
between
4
and
250
cases
per
100,000
population.
In
theUnited
States,
the
highest incidence is among Asians
inHawaii, blacks, and certain Native
Americans
(Sioux,
Crow,
Arapahoe).
The
risk
of
SLE
developing in
a
black
American
female has been estimated to be 1:250. The
prevalence is about
the
same
worldwide;
the
disease
appears
to
be
common
inChina,
in
Southeast
Asia,
and
among
blacks
in
the
Caribbean,
but
is
seen
infrequently
in
blacks
inAfrica. Limited
observations suggest that the incidence of discoid
lupus erythematosus is the same as that
for SLE.
ETIOLOGY.
The
cause of SLE remains unknown, although many
observations suggest a
role for
genetic, hormonal, immune, and environmental
factors. The
evidence for a genetic
role is summarized in
Table
289-2
. Some of these
genetic
marker
associations
are
found
more
frequently
in
SLE
patients
of
different
races
and
ethnicities.
It
has
been
calculated
that
at
least
four
genes are involved in predisposing
individuals to SLE. Each gene
presumably
affects
some
aspect
of
immune
regulation,
protein
degradation,
peptide
transport
across
cell
membranes,
immune
response,
complement,
the
reticuloendothelial
system (including phagocytosis), immunoglobulins,
apoptosis,
and
sex
hormones.
Thus
combinations
of
dissimilar
gene
defects
may
result
in
distinct
abnormal
responses
and
produce
separate
pathologic
processes and
different clinical expression.
The evidence for hormonal abnormalities
is based primarily on the
observation
that
SLE
is
much
more
common
among
women
in
their
childbearing
years.
In
addition,
SLE
has
been
observed
in
some
males
with
Klinefelter's
syndrome, and
some abnormalities of estrogen metabolism have
been noted
in both men and women with
SLE. However, the clinical expression of SLE
is the same in men and women.
Furthermore, a lupus-like disease ofNew
Zealandmice is more common and more
severe and has an earlier onset in
females--and is ameliorated by
oophorectomy or treatment with male
hormones. However, in other strains of
mice with a lupus-like disease,
this
gender difference is not noted.
Numerous immune abnormalities occur in
patients with SLE, the etiology
of
which remains unclear; nor do we know which are
primary and which are
secondary.
Some
of
these
immune
defects
are
episodic,
and
some
correlate
with disease activity. SLE is
primarily
PATHOGENESIS.
Many manifestations are mediated by
antibodies. The classic example is
that
of diffuse proliferative glomerulonephritis.
Immune complexes,
which consist of
nuclear antigens (especially
DNA
) and high-affinity
complement-fixing IgG (especially IgG1
and IgG3) and ANAs (especially
antibodies to DNA), form in the
circulation and are deposited in the
glomerular
basement
membrane
(GBM)
or
form
in
situ;
histone
may
facilitate
immune complex
deposition. The complement system is then
activated and
chemotactic factors are
generated. These factors induce the attraction
and infiltration of leukocytes, which
then phagocytose immune complexes
and
cause the release of mediators (such as activators
of the clotting
system), which further
perpetuate the glomerular inflammation. With
continuing immune complex deposition,
chronic inflammation may ensue,
ultimately leading to fibrinoid
necrosis and scarring (crescents) and
loss of renal function. In lupus
membranous glomerulonephritis, similar
mechanisms occur, although immune
complex-containing, poorly
complement-
fixing
IgG2
and
IgG4
form
primarily
in
situ
on
the GBM;
there
is no cellular infiltrate. The
mechanism for the GBM protein leakage,
which
results
in
the
nephrotic
syndrome,
is
not
clear.
In
lupus
mesangial
glomerulonephritis, mesangial cells
(macrophage-like
PATHOLOGY.
Few
unique
pathologic
features
are
associated
with
SLE
.
In
patients
with
arthritis, the synovial histopathology
tends to be non-specific, with
superficial fibrin-like material and
local or diffuse cell lining
proliferation.
Vascular
changes
include
perivascular
mononuclear
cells,
lumen obliteration,
enlarged endothelial cells, and thrombi, but
fibrinoid
necrosis
is
uncommon.
Biopsies
of
the
malar
erythema
may
reveal
some
minor
basal
layer
abnormalities,
as
well
as
immune
complex
deposits
at
the
dermal-
epidermal
junction.
Discoid
skin
lesions
are
characterized
by
hyperkeratosis,
follicular
plugging,
and
more
basal
cell
layer
changes,
including immune complexes at the
dermal-epidermal junction. Pleura and
pericardium are infiltrated by
mononuclear cells. Lupus pneumonitis is
characterized by alveolar wall injury,
hemorrhage, and edema; hyaline
membrane
formation;
and
immune
complex
deposits.
Coronary
arteries
often
demonstrate premature-onset
atherosclerosis. Libman-Sacks endocarditis
is characterized by the accumulation of
immune complexes, mononuclear
cells,
hematoxylin bodies, and fibrin and platelet
thrombi. Pathologic
examination
of
the
spleen
often
reveals
an
skin
appearance
of
the
splenic
arteries, which is thought to represent healed
arteritis.
RENAL
DISEASE.
Minimal disease
(type IIA mesangial disease) of glomeruli has
immune
complex deposits only in
mesangial cells. Type IIb mesangial nephritis
also
has
mesangial
hypercellularity.
Focal
proliferative
nephritis
(type
III)
has
segmental
proliferation
in
glomerular
tufts
and
in
the
mesangium
and
immune complex deposits in the mesangium and
scattered granular
deposits in the
subendothelial, subepithelial, and intrabasement
GBM.
Active diffuse proliferative
glomerulonephritis (type IV) affects more
than 50% of glomeruli with cellular
proliferation, necrosis,
loops,
the process involves
sclerosis, adhesions, crescents, and (tubular)
atrophy. Extensive
present.
In
membranous
nephritis
(type
V)
diffuse,
uniform
thickening
of
the GBM is seen, with a
fine granular deposition of immune complexes in
the subendothelial region beneath fused
foot processes. Tubular
degenerative
changes
with
interstitial
mononuclear
cells
are
not
uncommon.
Extensive crescent
formation, representing scarring, indicates a poor
prognosis.
The
brain is notable for the paucity of pathologic
changes. Some minor
blood vessel
abnormalities, an occasional microinfarct, and
some
perivascular infiltration have
been noted.
CLINICAL
MANIFESTATIONS.
SLE is
highly variable in onset as well as course. The
initial symptoms
may be non-
specific
(Table 289-4)
and
include myalgia, nausea, vomiting,
headaches, depression, easy bruising,
or more specific symptoms or any
combination thereof. These symptoms may
be mild or severe, fleeting or
persistent.
GENERAL SYMPTOMS.
Fatigue occurs in virtually all
patients with SLE. Fatigue may parallel
the onset of SLE or its relapse but
should be distinguished from the
fatigue associated with other factors
such as increased workload, sleep
disturbance, depression, unhealthful
habits, stress, deconditioning,
anemia,
the use of certain
medications
(including
prednisone),
and
any
intercurrent
disease.
Fever
is
seen
in
80%
of
patients;
it
is
usually
episodic.
Infections,
which
occur
commonly in SLE patients, must always
be considered.
MUSCULOSKELETAL
MANIFESTATIONS.
Arthralgia
and arthritis have been noted in 95% of patients
with SLE.
Symptoms tend to be
asymmetrical and migratory, with complaints in a
particular
joint
often
gone
in
1
to
3
days.
Fingers,
hands,
wrists,
knees,
and less frequently,
ankles, elbows, shoulders, and hips are affected.
Morning
stiffness
is
generally
measured
in
minutes,
in
contrast
to
hours
in
rheumatoid
arthritis.
Although
joint
deformities
are
considered
to
be
more a feature of
rheumatoid arthritis, damage to
periarticula
PULMONARY MANIFESTATIONS.
Pulmonary involvement occurs in most
patients and is manifested as
pleurisy,
coughing,
dyspnea,
abnormal
pulmonary
function
tests,
or
chest
radiographic
abnormalities.
Pleurisy
occurs
in
over
50%
of
patients;
the
most common cause is chest wall pain on
local pressure and/or movement.
Pleuritis (inflammation of the pleura)
also causes pleurisy. It is
diagnosed
by the presence of a pleural friction rub and/or
the
radiographic
presence
of
a
pleural
effusion.
Effusions
typically
have
low
complement
and
protein
levels,
few
WBCs
(the
pleura
has
mononuclear
cells),
glucose
levels
approximating
plasma
levels
(by
contrast,
they
are
low
in
rheumatoid arthritis), and LE cells.
Cough usually represents an
infection,
but pulmonary edema secondary to cardiac or renal
failure or
fluid overload in a patient
receiving corticosteroids should be
considered.
Acute
lupus
pneumonitis
occurs
in
5
to
12%
and
is
characterized
by
fever,
cough
(even
hemoptysis),
pleurisy,
and
dyspnea.
Radiography
shows
diffuse
acinar infiltrates, especially in the
lower lobes. Subsequently,
interstitial
infiltrates and fibrosis may develop, with
pulmonary
function abnormalities. The
prognosis is poor.
Pulmonary
hypertension may complicate
SLE
but is more
frequent with
scleroderma or mixed
connective tissue disease. Raynaud's phenomenon is
common. Late findings include dyspnea,
hypoxemia, restricting lung
disease,
and reduced CO
2
diffusing
capacity.