2014 - SLE Lecture

Systemic Lupus Erythematosus
(SLE)
4
th
year, General Medicine, 2014

DIFFUSE CONNECTIVE TISSUE
DISEASES

1. SYSTEMIC LUPUS ERYTHEMATOSUS : SLE

2. SCLERODERMA ( scleroderma : Scl)

3. POLIMYOSITIS (PM)
4.
4. DERMATOMYOSITIS (DM)

5. RHEUMATOID ARTHRITIS (RA)

6. SJGREN SYNDROME :
1. 6.1 primary
2. 6.2. secondary : usually associated with each of the five connective
tissue diseases/ collagen diseases
DIFFUSE CONNECTIVE TISSUE
DISEASES

OVERLAP SYNDROME :
collagen disease with an intricate
simptomatology (RA, SS, SLE)
present in 25% cases of the patients

SLE DEFINITION

Systemic lupus erythematosus (SLE) is an
autoimmune disease in which organs
and cells undergo damage mediated by
tissue-binding autoantibodies and
immune complexes.
EPIDEMIOLOGY
SLE primarily is a disease of young women (90
% of patients are women of child-bearing years);

SLE is usually a postpubertal disease, with onset of
clinical symptoms usually in the 20s to 30s

female : male ratio is 9 : 1

but, people of both sexes, all ages, and all
ethnic groups are susceptible;

EPIDEMIOLOGY
The prevalence varies with race, ethnicity,
and socioeconomic status, but in a
general outpatient population, SLE affects
~ 1 in 2000 individuals;

Prevalence of SLE in the United States is
1550 cases per 100,000;

The highest prevalence among ethnic
groups studied is in African Americans.

PATHOGENESIS AND ETIOLOGY
Interactions between:
susceptibility genes + environmental factors
result in
abnormal immune responses
that generate
pathogenic autoantibodies and immune complexes
that deposit in tissue, activate complement, cause
inflammation, and over time lead to irreversible organ
damage.

Despite the influence of heredity, most cases of SLE
appear sporadic

PATHOGENESIS AND ETIOLOGY:
THE SUSCEPTIBILITY

Like other autoimmune diseases, SLE can
display familial aggregation, with a higher
frequency among first-degree relatives of
patients :

The disease occurs concordantly in approximately
25% to 50% of monozygotic twins and 5% of
dizygotic twins

Moreover, in extended families, SLE may occur
with other autoimmune conditions, such as
hemolytic anemia, thyroiditis, and idiopathic
thrombocytopenia purpura.

An association of human leukocyte antigen
(HLA)-DR2 and HLA-DR3 (and various
subspecificities) with SLE has been commonly
observed, with these alleles producing a relative
risk of disease that ranges approximately from 2
to 5

SLE is also associated with inherited deficiency
of Clq, Clr/s, and C2 :
A decrease in complement activity could promote
disease susceptibility by impairing the clearance of
foreign antigen or apoptotic cells;

THE SUSCEPTIBILITY

THE ENVIRONMENTAL FACTORS

Infectious agents : could induce specific responses by
molecular mimicry and perturb overall immunoregulation;

Stress : can provoke neuroendocrine changes affecting immune
cell function;

Diet : can affect production of inflammatory mediators;

Toxins (including drugs): could modify cellular
responsiveness and the immunogenicity of self-antigens;

Physical agents (e.g. sunlight) : can cause inflammation
and tissue damage.

ABNORMAL IMMUNE RESPONSES
- IMMUNE CELL DISTURBANCES -

These immune cell disturbances appear to promote B-cell
hyperactivity, leading to hyperglobulinemia, increased
numbers of antibody-producing cells, and heightened
responses to many antigens, both self and foreign.
Autoantibody production in SLE occurs in the setting of
generalized immune cell abnormalities that involve the B cell,
T cell, and monocyte lineages.

Another consequence of B-cell and T-cell disturbance in SLE
may be abnormal tolerance. In healthy individuals, anti-
DNA precursors are tolerated by anergy or deletion;
however, people with SLE or animals with SLE models may
retain such precursors, which can be stimulated to generate
high affinity autoantibody responses (15).

ANTINUCLEAR ANTIBODIES (ANA)
Autoantibody production is the central immunologic
disturbance in SLE.

ANA are directed to a host of self-molecules found in
the nucleus, cytoplasm, or surface of cells. In addition,
SLE sera contain antibodies to such soluble molecules
as IgG and coagulation factors.

SLE is classified as a disease of generalized
autoimmunity because of the wide range of its
antigenic targets.

PATHOGENESIS AND ETIOLOGY
AUTOANTIBODIES IN SLE

1. Antinuclear antibodies : best screening test;
repeated negative tests make SLE unlikely

- Prevalence : 98%
- Ag. recognized : multiple nuclear

2. Anti-dsDNA : high titers are SLE-specific and in
some patients correlate with disease activity,
nephritis, vasculitis

- Prevalence : 70%
- Ag. Recognized : DNA (double-stranded)


1. Anti-Sm : specific for SLE, no definite clinical
correlations

- Prevalence : 25%
- Ag. recognized :Protein complexed to 6 species of
nuclear U1 RNA

2. Antiphospholipid : predisposes to clotting, fetal
loss, thrombocytopenia

- Prevalence : 50%
- Ag. Recognized : Phospholipids, 2 glycoprotein 1
cofactor, prothrombin

1. Antierythrocyte
1. Prevalence : 60%
2. Ag. recognized : Erythrocyte membrane
3. Measured as direct Coombs' test

2. Antiplatelet
1. Prevalence : 30%
2. Ag. Recognized : Surface and altered cytoplasmic antigens in
platelets
3. Associated with thrombocytopenia but sensitivity and
specificity are not good; this is not a useful clinical test

3. Antineuronal
1. Prevalence : 60%
2. Ag. Recognized : Neuronal and lymphocyte surface antigens
3. In some series a positive test in CSF correlates with active
CNS lupus

1. Anti-Ro (SS-A) : not specific for SLE
1. Prevalence : 30%
2. Ag. recognized : Protein complexed to hY RNA, primarily 60 kDa and 52 kDa;
3. associated with sicca syndrome, subacute cutaneous lupus, and neonatal lupus
with congenital heart block; associated with decreased risk for nephritis

2. Anti-La (SS-B): not specific for SLE
1. Prevalence : 10%
2. Ag. Recognized :47-kDa protein complexed to hY RNA
3. Usually associated with anti-Ro; associated with decreased risk for nephritis

3. Antihistone
1. Prevalence : 70%
2. Ag. Recognized : Histones associated with DNA (in nucleosome, chromatin)
3. More frequent in drug-induced lupus than in SLE
DIAGNOSTIC CRITERIA FOR SLE
1. Malar rash;
2. Discoid rash;
3. Photosensitivity : exposure to
ultraviolet light causes rash;
4. Oral ulcers : includes oral and
nasopharyngeal ulcers, observed by
physician
5. Arthritis : nonerosive arthritis of two or
more peripheral joints, with tenderness,
swelling, or effusion
6. Serositis : pleuritis or pericarditis
documented by ECG or rub or evidence of
effusion
7. Renal disorder : proteinuria >0.5 g/d or
3+, or cellular casts
8. Neurologic disorder : seizures or
psychosis without other causes
9. Hematologic disorder :
Hemolytic anemia or
leukopenia (<4000/ L) or
lymphopenia (<1500/ L) or
thrombocytopenia (<100,000/ L) in the absence of
offending drugs
10. Immunologic disorder :
Anti-dsDNA, anti-Sm, and/or anti-phospholipid
11. Antinuclear antibodies : an abnormal titer of
ANA by immunofluorescence or an equivalent
assay at any point in time in the absence of
drugs known to induce ANAs
If 4 of these criteria, well
documented, are present at any time
in a patient's history, the diagnosis is
likely to be SLE. Specificity is 95%;
sensitivity is 75%.
Malar rash : fixed
erythema, flat or
raised, over the malar
eminences;
It is the most classic
of all the rashes in
SLE and it is
categorized among
the acute rashes.
It occurs in 30% to
60% of all patients.

SLE: PHOTOSENSITIVITY, FACE AND NECK

The most common form of
chronic disease is discoid
lupus (DLE; 15%30) which
can occur as part of the
systemic disease or exist in
isolation in the absence of
any autoantibodies (2%
10% will develop SLE)

Discoid rash :
erythematous circular raised
patches with adherent
keratotic scaling and
follicular plugging; atrophic
scarring may occur

Discoid rash :
erythematous circular
raised patches with
adherent keratotic
scaling and follicular
plugging; atrophic
scarring may occur

Oral ulcer
Oral or nasopharyngeal ulceration, usually
painless, observed by a physician


Nonerosive arthritis involving two or
more peripheral joints,characterized
by tenderness, swelling or effusion
SLE: JACCOUDS ARTHROPATHY (CLINICAL AND
RADIOGRAPH)
At its onset, SLE may involve one or several
organ systems; over time, additional
manifestations may occur
Most of the autoantibodies characteristic of each
person are present at the time clinical
manifestations appear
Severity of SLE varies from mild and intermittent
to severe and fulminant.
Most patients experience exacerbations
interspersed with periods of relative quiescence;
Permanent complete remissions (absence of
symptoms with no treatment) are rare.

SYSTEMIC MANIFESTATIONS
Systemic symptoms :

particularly fatigue and
myalgias/arthralgias, are present most of
the time.

severe systemic illness requiring glucocorticoid
therapy can occur with fever, prostration,
weight loss, and anemia with or without
other organ-targeted manifestations
Musculoskeletal Manifestations
Most people with SLE have :
intermittent polyarthritis, varying from mild to disabling, characterized by
soft tissue swelling and tenderness in joints, most commonly in hands, wrists,
and knees.
joint deformities (hands and feet) develop in only 10%

Erosions on joint x-rays are rare; their presence suggests a non-lupus
inflammatory arthropathy such as rheumatoid arthritis

If pain persists in a single joint, such as knee, shoulder, or hip, a diagnosis of
ischemic necrosis of bone should be considered, particularly if there are no
other manifestations of active SLE. The prevalence of ischemic necrosis of bone is
increased in SLE, especially in patients treated with systemic glucocorticoids

Myositis with clinical muscle weakness, elevated creatine kinase levels, positive
MRI scan, and muscle necrosis and inflammation on biopsy can occur, although most
patients have myalgias without frank myositis. Glucocorticoid therapies (commonly)
and antimalarial therapies (rarely) can also cause muscle weakness; these adverse
effects must be distinguished from active disease
Painful joints are the most common presenting
symptom of SLE, with frequencies reported
between 76% to 100%

In some cases the pain is more characteristic of
arthralgia because it is unaccompanied by the
traditional signs of inflammation

In others the classical signs of a true arthritis,
such as swelling, erythema, heat, and decreased
range of motion, are present.


Although arthritis can affect any joint, it is
most often symmetrical with involvement
of the small joints of the hands (proximal
interphalangeal and metacarpal
phalangeal), wrists and knees, but sparing
the spine

The arthritis can be evanescent, resolving
within 24 hours, or more persistent.

In contrast to RA, the arthritis in SLE is
nonerosive and generally nondeforming

In those patients that do appear to have
deforming features, such as ulnar deviation,
hyperflexion, and hyperextension, the deformities
are generally reducible

These hypermobile digits with reducible
deformities are secondary to involvement of
paraarticular tissues, such as the joint capsule,
ligaments, and tendons, and are referred to as
Jaccoud-like arthropathy.

Jaccoud-like arthropathy in
SLE

Rheumatic complaints localized to the hips should raise serious
consideration of osteonecrosis, the frequency of which has been reported
to be 5% to 10%.

Although the femoral head is the most common site of involvement, other
sites include the femoral condyles, talus, humeral head, and, occasionally,
the metatarsal heads, radial head, carpal bones, and metacarpal bones.

Bilaterality is frequent but not necessarily simultaneous.

Most cases are associated with the use of corticosteroids, but causality has
also been attributed to Raynauds, small vessel vasculitis, fat emboli, or
the presence of antiphospholipid antibodies.

Typically, patients with osteonecrosis complain of persistent painful motion
localized to a single joint, and symptoms are relieved by rest


Generalized myalgia and muscle weakness, frequently
involving the deltoids and quadriceps, can be accompanying
features of disease fl ares.

Overt myositis with elevations of CPK occurs in <15% of
patients.

Electromyogram (EMG) and muscle biopsy findings range
from normal to those seen in dermato/polymyositis.

Exceptionally high levels of creatine kinase (CPK) are rare.
Patients with SLE can develop myopathy as a consequence
of glucocorticoids or antimalarials.

Mucocutaneous Manifestations
Lupus dermatitis can be classified as :
discoid lupus erythematosus (DLE),
systemic rash,
subacute cutaneous lupus erythematosus (SCLE), or "other.

Only 5% of people with DLE have SLE (although half have positive
ANA);
The most common SLE rash is a photosensitive : worsening of this
rash often accompanies flare of systemic disease.
SCLE : patients with these manifestations are exquisitely
photosensitive; most have antibodies to Ro (SS-A).
Other SLE rashes include recurring urticaria, lichen planuslike
dermatitis, bullae, and panniculitis ("lupus profundus").
Small, painful ulcerations on the oral or nasal mucosa are common
in SLE; the lesions resemble aphthous ulcers.
Mucocutaneous Manifestations
The cutaneous system is one of the
most commonly affected,
approaching 80% to 90%

SLE-specific skin lesions are
classified into three types :
chronic,
subacute
acute

Malar rash
Discoid lupus erythematosus (DLE),
Subacute cutaneous lupus
erythematosus (SCLE)

Subacute
cutaneous lupus
erythematosus
(SCLE) lesions are
seen in 7% to 27%
of patients

erythematosus

erythematosus

Alopecia

Alopecia associated
with SLE may be
diffuse or patchy,
reversible or
permanently scarring
as a result of discoid
lesions in the scalp.

Alopecia
Livedo reticularis
Vasculitis
Vasculitis is another
component of skin
disease in SLE. It may
be manifest as :
urticaria, palpable
purpura,
nailfold or digital
ulcerations,
erythematous papules
of the pulps of the
fingers and palms, or
splinter hemorrhages

Vasculitis
Leziuni tegumentare vasculitice : dermatita
interarticulara a mainilor
Vasculitis: fingers
Vasculitis
Raynauds phenomenon
erythematosus (SCLE)
Renal Manifestations
Nephritis is usually the most serious manifestation of SLE,
particularly since nephritis and infection are the leading
causes of mortality in the first decade of disease

Since nephritis is asymptomatic in most lupus patients,
urinalysis should be ordered in any person suspected of
having SLE

Lupus nephritis tends to be an ongoing disease, with flares
requiring re-treatment over many years.

For most people with lupus nephritis, accelerated
atherosclerosis becomes important after several years of
disease; attention must be given to control of blood
pressure, hyperlipidemia, and hyperglycemia.

Renal biopsy is useful in planning current and near-
future therapies.

Patients with dangerous proliferative forms of glomerular
damage (ISN III and IV) usually have :
microscopic hematuria and proteinuria (>500 mg per 24 h
approximately one-half develop nephrotic syndrome,
and most develop hypertension.

If diffuse proliferative glomerulonephritis (DPGN) is
untreated, virtually all patients develop ESRD within 2
years of diagnosis. Therefore, aggressive
immunosuppression is indicated (usually systemic
glucocorticoids plus a cytotoxic drug), unless damage is
irreversible

Nervous System Manifestations
Approximately two thirds of patients with SLE have neuropsychiatric
manifestations.

In some patients these are the major cause of morbidity and mortality

Neuropsychiatric systemic lupus includes :
neurologic syndromes of the central, peripheral, and autonomic nervous
systems,
psychiatric disorders

The pathophysiology of this broad clinical category is not well understood;
proposed mechanisms include :
vascular occlusion due to
vasculopathy,
leukoaggregation or
thrombosis,
and antibody-mediated neuronal cell injury or dysfunction
Nervous System
Manifestations
The most common manifestation of diffuse CNS lupus is :

Cognitive dysfunction, including difficulties with memory and
reasoning.
Headaches are also common. When excruciating, they often
indicate SLE flare; when milder, they are difficult to distinguish
from migraine or tension headaches.
Seizures of any type may be caused by lupus; treatment often
requires both antiseizure and immunosuppressive therapies.
Psychosis can be the dominant manifestation of SLE;
Acute confusional state : the syndrome covers a wide
spectrum ranging from mild alterations of consciousness to
coma.
Myelopathy is not rare and is often disabling; rapid
immunosuppressive therapy starting with glucocorticoids is
standard of care.
Nervous System
Manifestations

Examination of the cerebrospinal fl uid is useful to rule out
infection.

Computerized tomography is sufficient for the initial
diagnosis of most mass lesions and intracranial
hemorrhages.

The findings of magnetic resonance imaging (MRI) reflect
the histopathologic findings of vascular injury and may
involve the white or gray matter
Abnormalities on MRI are more likely with focal findings.
Unfortunately, the correlation between MRI fi ndings and
clinical presentation is low.

CARDIOVASCULAR INVOLVEMENT

A variety of cardiac manifestations can be seen in SLE :

Pericarditis is the most common (6% to 45%) : pericardial
effusions may be asymptomatic and are usually mild to
moderate; tamponade is rare, but can occur.
Myocardial involvement is rare (<5 -10% of patients) and
typically occurs in the presence of generalized SLE activity
Endocarditis : LibmanSacks endocarditis
Accelerated atherosclerosis is an important cause of morbidity
and mortality in SLE
The proportionate mortality from myocardial infarction is
approximately 10 times greater in patients with SLE than in the
general age- and sex-matched population.
CARDIOVASCULAR INVOLVEMENT
Pericarditis :
there is a substernal or pericardial pain, a pericardial rub
the electrocardiogram may show the typical T-wave abnormalities,
echocardiography is the best diagnostic test
Importantly, when a young woman presents with shortness of breath
and pleuritic chest pain, the differential diagnosis must include SLE, and
the patient should be tested for ANA.

Primary myocardial involvement (myocarditis):
fever, dyspnea, palpitations, heart murmurs, sinus tachycardia, ventricular
arrhythmias, conduction abnormalities, or congestive heart failure.

Endocarditis
LibmanSacks, is the classic cardiac lesion of SLE
atypical verrucous endocarditis is comprised of verrucous vegetations ranging
from 1 to 4 mm in diameter, initially reported to be present on the tricuspid and
mitral valves
prophylactic antibiotics for surgical and dental procedures have been
recommended for all SLE patients.
Pleura and Lungs
Pleura and lungs are commonly affected in SLE, but are generally not as
life threatening as the renal and central nervous system complications.

Pulmonary involvement includes :
pneumonitis,
pulmonary hemorrhage,
pulmonary embolism,
pulmonary hypertension

Pleurisy is a more common feature of serositis than pericarditis : over
30% of patients have some form of pleural disease in their lifetime
Pleural effusions are most often small and bilateral
The pain of pleuritis can be quite severe and must be distinguished from
pulmonary embolus or infection.
The fluid is usually clear, exudative with increased protein, normal glucose,
white blood cell count <10,000, a predominance of neutrophils or lymphocytes,
and decreased levels of complement.
Antiphospholipid Antibody
Syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease
associated with recurrent arterial or venous thromboses,
pregnancy losses, livedo reticularis, and mild
thrombocytopenia.

Patients who have antiphospholipid antibodies and one of
the above clinical features in the absence of any other
manifestations of SLE are classified as having primary
antiphospholipid syndrome (APS)
Anticardiolipin antibody
Lupus anticoagulant

Alternatively a patient can have these antibodies in the
context of SLE (secondary APS).
Drug-Related Lupus
The term drug-related lupus (DRL) refers to the development of a
lupuslike syndrome which follows exposure to :
chlorpromazine, hydralazine, isoniazid, methyldopa, minocycline,
procainamide, or quinidine, anti TNF

There are no specified ACR criteria for DRL, but in general these
patients present with fewer than four SLE criteria.

Drug-related lupus patients frequently present with constitutional
symptoms such as malaise, low grade fever, and myalgia, which
may occur acutely or insidiously; articular complaints are present
in over 80%, with arthralgia being more common than arthritis

Typically the ANA is a diffuse-homogenous pattern, which
represents binding of autoantibodies to chromatin that consists
ofDNA and histones. Anti-dsDNA and anti-Sm are not
characteristic of DRL.
Neonatal Lupus
This illness of the fetus and neonate is considered a model
of passively acquired autoimmunity, in which immune
abnormalities in the mother lead to the production of anti-
SSA/Ro-SSB/La antibodies that cross the placenta and
presumably injure fetal tissue

The incidence of neonatal lupus in an offspring of a mother
with anti-SSA/Ro antibodies is estimated at 1% to 2%.

The most serious manifestation is damage to the cardiac
conducting system resulting in congenital heart block
(CHB), which is most often third degree.
CHB is generally identified between 16 and 24 weeks of
gestation.
The mortality rate is 20% and
The majority of children require pacing.
LABORATORY FEATURES
Hematologic Abnormalities

ANEMIA :
Autoimmune hemolytic anemia is present in <10% of patients.
A Coombs test can be positive (both direct and indirect) without active
hemolysis.
A nonspecific anemia reflecting chronic disease is present in up to 80% of
patients

LEUKOPENIA :
Leukopenia is seen in over 50% of patients.
Absolute lymphopenia (<1500/mm3)

THROMBOCYTOPENIA :
can be modest (platelet counts of 50,000100,000/mm3), chronic and totally
asymptomatic,
or profound (<20,000/mm3) and acute, with gum bleeding and petechiae.
Moreover thrombocytopenia can be the initial presentation of SLE,
antedating the development of other symptoms or signs by years. Any
young woman presenting with idiopathic thrombocytopenia should be
evaluated for SLE.
LABORATORY FEATURES

The erythrocyte sedimentation rate
is frequently elevated in SLE and is
generally not considered a reliable
marker of clinical activity.

A rise in the C-reactive protein may
be an indicator of infection, but this
has not proven to be absolute.
LABORATORY FEATURES

SEROLOGIC PARAMETERS:

Complement proteins,
Antibodies
Immune complexes
Treatment

Patient education Crucial to optimizing clinical outcomes, as with
any chronic illness.

Identify concomitant conditions Treat conditions that could
contribute to fatigue, particularly hypothyroidism, anemia,
fibromyalgia, and depression.

Photoprotection Patients who are photosensitive should be
instructed to avoid excessive exposure to sunlight and routinely
wear sunscreen and photoprotective clothing.

Review prescription drugs Some can exacerbate photosensitive
reactions and other manifestations of systemic disease.
.
Treatment

Infections Common in lupus; patients should be advised to seek
medical attention urgently for unexplained fevers.

Pregnancies Considered high risk, because of potential disease
flares in the mother and risk to the fetus. Anti-Ro/SSA and
antiphospholipid antibodies are of particular concern.

Cardiovascular disease People with SLE are at increased risk for
coronary artery disease. Attention to risk factors (e.g.
hyperlipidemia, hypertension) and to primary and secondary
prevention measures is important.

Osteoporosis Glucocorticoids and periods of inactivity because of
active disease heighten the risk of poor bone health.

Treatment

NSAIDs
Glucocorticoids
Antimalarials
MTX
Cyclophosphamide
Azathioprine
Mycophenolate mofetil
Treatment

NSAIDs
Used widely for the treatment of
musculoskeletal complaints, pleuritis,
pericarditis, and headache.
Adverse effects of NSAIDs Effects on the
kidneys, liver, and central nervous system
that may be confused with worsening lupus
activity.
Treatment

Glucocorticoids

Effective in the management of many different manifestations
of SLE.
Topical or intralesional preparations Often used for
cutaneous lesions.
Intra-articular glucocorticoids Used occasionally for arthritis.
Oral or parenteral therapy Used for the control of systemic
disease.
Low dose Oral administration, ranging from 5 mg to 30 mg
prednisone daily, in single or divided doses, is effective in treating
constitutional symptoms, cutaneous disease, arthritis, and
serositis.
Higher dose More serious organ involvement, particularly
nephritis, cerebritis, hematologic abnormalities, or systemic
vasculitis, generally requires high-dose prednisone, 12
mg/kg/day.
Treatment
Antimalarials
Some of the most commonly described
medications for SLE.
Include hydroxychloroquine, chloroquine, and
quinacrine.
Uses Frequently used in the management
of constitutional symptoms, cutaneous and
musculoskeletal manifestations, and in some
cases, serositis.
Treatment
Cyclophosphamide The mainstay of treatment for
severe organ - system disease, particularly lupus nephritis.

Methotrexate Continues to be used most commonly as a
steroidsparing agent for milder manifestations of disease.
Particularly helpful in the arthritis of SLE

Azathioprine Used as an alternative to
cyclophosphamide for treatment of nephritis or as a
steroid-sparing agent for nonrenal manifestations

Mycophenolate mofetil Now preferred to both
cyclophosphamide and azathioprine for the management of
moderate renal disease. Also used empirically for other SLE
manifestations.
Treatment
Methotrexate :

numerous case series and few retrospective
studies have demonstrated success in the
treatment of active cutaneous and/or articular
involvements, allowing corticosteroid taper

the methotrexate is given in the range of 7.5
to 15 mg/week

Methotrexate should therefore be discontinued
6 months prior to pregnancy, regardless of the
patients gender.
Treatment
Cyclophosphamide :
It is reserved for the treatment of
severe SLE, including lupus nephritis,
central nervous system disease,
pulmonary hemorrhage, and
systemic vasculitis
Vascular Occlusions
The prevalence of transient ischemic attacks, strokes, and
myocardial infarctions is increased in patients with SLE. These
vascular events are increased in, but not exclusive to, SLE patients
with antibodies to phospholipids (aPL). It is likely that
antiphospholipid antibodies are associated with hypercoagulability
and acute thrombotic events, whereas chronic disease is associated
with accelerated atherosclerosis. Ischemia in the brain can be
caused by focal occlusion (either noninflammatory or associated
with vasculitis) or by embolization from carotid artery plaque or from
fibrinous vegetations of Libman-Sacks endocarditis. Appropriate
tests for aPL (see below) and for sources of emboli should be
ordered in such patients to estimate the need for, intensity of, and
duration of anti-inflammatory and/or anticoagulant therapies.
Vascular Occlusions
. In SLE, myocardial infarctions are primarily manifestations of
accelerated atherosclerosis. The increased risk for vascular events
is seven- to tenfold overall, and higher in women <45 years old with
SLE. Characteristics associated with increased risk for
atherosclerosis include older age, hypertension, dyslipidemia,
dysfunctional proinflammatory high-density lipoproteins, repeated
high scores for disease activity, high cumulative or daily doses of
glucocorticoids, and high levels of homocysteine. When it is most
likely that an event results from clotting, long-term anticoagulation is
the therapy of choice. Two processes can occur at oncevasculitis
plus bland vascular occlusionsin which case it is appropriate to
treat with anticoagulation plus immunosuppression. The role of
statin therapies in SLE is being investigated.
ILLUSTRATIVE CLINICAL CASE
JG, 24 year old, white female;

She presents with a 3 month history of fatigue
and pain in her wrists, fingers and left knee;

She has also noted an increased sensitivity to
sunburn and this past winter she experienced
pain in her fingers on exposure to cold,
stating that her fingers turned colors when they
were cold.
PLEURA AND LUNGS
The most common pleuropulmonary
manifestation of SLE is pleuritis.
Pleuritic pain is present in 45% to 60% of
patients and may occur with or without a pleural
effusion. Clinically apparent pleural effusions
have been reported in 50% of patients with SLE
and may be found in 93% of cases at autopsy.
Effusions are usually bilateral, but may be
unilateral, equally distributed between the left
and the right hemithoraces.
Pleural effusions in SLE are invariably exudative,
but with higher glucose and lower lactate
dehydrogenase levels than those found in
rheumatoid arthritis
Past Medical History:
Asthma, currently controlled with theophylline
Spontaneous abortion x2
Febrile seizures as a child, treated with phenobarbital x3 years
Social History:
Smokes 1 pack/day, no Etoh, 3-4 cups of coffee/day
Physical Exam:
WNWD female in NAD
Weight 135lbs
BP 120/75
Malar rash, swelling of wrists and MCPs bilaterally and Left knee
Medications:
Theophylline 300mg tid
LoOvral (started 4 months ago)
Multivitamin qd
Acetaminophen prn for pain
Laboratories:
Hct/Hgb 35/10.2 MCV 92
ANA +1:1280 speckled pattern
+ ds DNA, + anticardiolipin antibody
PTT 50, PT 11.2 (Control 11.6)
UA 1+ protein, negative for glucose/blood/casts

1. What signs and symptoms does she have that are consistent
with SLE?

2. Could her illness be drug-induced?

3. Formulate a treatment plan for this patient, including drugs,
doses and monitoring parameters.

4. What parameters should be monitored in this patient?

-fatigue-Raynaud's
-arthralgias
-+ANA in speckled pattern*/dsDNA Ab*-
malar rash
-photosensitivity
-h/o spontaneous abortion (seen with
"lupus anticoagulant")
with SLE?




Unlikely to be drug-induced lupus because:
Phenobarbital: given too long ago
Theophylline: not associated with SLE or DIL
Lo-Ovral: oral contraceptives are implicated in
unmasking idiopathic lupus but are not thought
to cause drug-induced lupus. Other factors
against this being DIL are the presence of a
speckled ANA pattern (with DIL generally see a
homogenous pattern) and the + ds DNA
antibody (in DIL see ssDNA).
with SLE?




General:
Birth control pills should be discontinued and some alternate form of
contraception initiated since the onset of SLE may have been
triggered/exacerbated by the BCP.
Arthralgias:
can be treated with NSAIDs, e.g. naproxen 375mg tid. Avoid ibuprofen as
first choice NSAID because of association with aseptic meningitis in patients
with SLE. If symptoms do not respond to an adequate trial of NSAIDs,
would consider starting hydroxychloroquine 200mg bid. Systemic steroids
are not indicated for treatment of lupus arthritis alone and patient has no
other indications for systemic steroids at this time.
Raynaud's:
try non-drug measures first: stop smoking, wear gloves/mittens, avoid
cold/precipitating factors. If necessary, nifedipine 10mg bid to tid (or
30mgXL qd) is drug of choice. If symptoms are not constant/severe, patient
may taken nifedipine prn. If patient unable to tolerate nifedipine, can try
diltiazem or isradipine.
Malar rash:
if bothersome to patient can be treated with low potency topical steroid, i.e.
1-2.5% hydrocortisone cream; otherwise need not treat.
Lupus anticoagulant:
patient does not have history of thrombosis. Presence of this antibody
increases risk of stroke or thromboembolism. Patients with strong evidence
(e.g. history of CVA/DVT/PE) can be treated prophylactically with coumadin.
In patients like JG less risky measures are sometimes used, e.g. low-dose
aspirin. Corticosteroids will also decrease risk for these patients by
decreasing antibody formation, but long term toxicity usually precludes their
use. The lupus anticoagulant may also be associated with recurrent
spontaneous abortions. If JG wishes to get pregnant, this should be
addressed prior to conception, due to her past history 2 miscarriages.
Photosensitivity:
use sunblock with SPF > 15 that blocks both UVA and UVB light
Proteinuria:
minimal, doesn't require treatment at this time, however, should be
monitored carefully

with SLE?




Rash
Arthralgias
Proteinuria monitors of disease activity
Fingers for digital ulcers
Anemia
Renal function (BUN/Cr) if on NSAIDs
Eye exams every 6 months if on antimalarials
monitors of drug toxicity
Blood pressure if on drug therapy for Raynaud's

2014 - SLE Lecture

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Systemic Lupus Erythematosus

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