What is lupus? What are the types of lupus?
Lupus is an autoimmune diseasecharacterized by acute and chronic
inflammation of various tissues of the body. Autoimmune diseases are
illnesses that occur when the body's tissues are attacked by its own
immune system. The immune system is a complex system within the body
that is designed to fight infectious agents, such as bacteria and other
foreign microbes. One of the ways that the immune system fights infections
is by producing antibodies that bind to the microbes. Patients with lupus
produce abnormal antibodies in their blood that target tissues within their
own body rather than foreign infectious agents. Because the antibodies and
accompanying cells of inflammation can affect tissues anywhere in the
body, lupus has the potential to affect a variety of areas. Sometimes lupus
can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous
system. When only the skin is involved, the condition is called lupus
dermatitis or cutaneous lupus erythematosus. A form of lupus dermatitis
that can be isolated to the skin, without internal disease, is called discoid
lupus. When internal organs are involved, the condition is referred to as
systemic lupus erythematosus (SLE).
Both discoid and systemic lupus are more common in women than men
(about eight times more common). The disease can affect all ages but most
commonly begins from 20 to 45 years of age. Statistics demonstrate that
lupus is somewhat more frequent in African Americans and people of
Chinese and Japanese descent.
What causes lupus? Is it hereditary?
The precise reason for the abnormal autoimmunity that causes lupus is not
known. Inherited genes, viruses, ultraviolet light, and certain medications
may all play some role.
Genetic factors increase the tendency of developing autoimmune diseases,
and autoimmune diseases such as lupus, rheumatoid arthritis,
andautoimmune thyroid disorders are more common among relatives of
patients with lupus than the general population. Some scientists believe
that the immune system in lupus is more easily stimulated by external
factors like viruses or ultraviolet light. Sometimes, symptoms of lupus can
be precipitated or aggravated by only a brief period of sun exposure.
It also is known that some women with SLE can experience worsening of
their symptoms prior to their menstrual periods. This phenomenon, together
with the female predominance of SLE, suggest that female hormones play
an important role in the expression of SLE. This hormonal relationship is an
active area of ongoing study by scientists.
More recently, research has demonstrated evidence that a key enzyme's
failure to dispose of dying cells may contribute the development of SLE.
The enzyme, DNase1, normally eliminates what is called "garbage DNA"
and other cellular debris by chopping them into tiny fragments for easier
disposal. Researchers turned off the DNase1 gene in mice. The mice
appeared healthy at birth, but after six to eight months, the majority of mice
without DNase1 showed signs of SLE. Thus, a genetic mutation in a gene
that could disrupt the body's cellular waste disposal may be involved in the
initiation of SLE.
What is drug-induced lupus?
Dozens of medications have been reported to trigger SLE. However, more
than 90% of this "drug-induced lupus" occurs as a side effect of one of the
following six drugs:hydralazine (used for high blood
pressure),quinidine and procainamide (used forabnormal heart
rhythms), phenytoin (used forepilepsy), isoniazid ([Nydrazid, Laniazid] used
for tuberculosis), d-penicillamine (used for rheumatoid arthritis). These
drugs are known to stimulate the immune system and cause SLE.
Fortunately, drug-induced SLE is infrequent (accounting for less than 5% of
all patients with SLE) and usually resolves when the medications are
What are the symptoms and signs of lupus?
Patients with SLE can develop different combinations of symptoms and
organ involvement. Common complaints and symptoms include fatigue,
low-grade fever,loss of appetite, muscle aches, arthritis, ulcers of the mouth
and nose, facial rash("butterfly rash"), unusual sensitivity to sunlight
(photosensitivity), inflammation of the lining that surrounds the lungs
(pleuritis) and the heart (pericarditis), and poor circulation to the fingers and
toes with cold exposure (Raynaud's phenomenon). Complications of organ
involvement can lead to further symptoms that depend on the organ
affected and severity of the disease.
Skin manifestations are frequent in lupus and can sometimes lead to
scarring. In discoid lupus, only the skin is typically involved. The skin rash
in discoid lupus often is found on the face and scalp. It usually is red and
may have raised borders. Discoid lupus rashes are usually painless and do
not itch, but scarring can cause permanenthair loss. Over time, 5%-10% of
patients with discoid lupus may develop SLE.
Over half of the patients with SLE develop a characteristic red, flat facial
rash over the bridge of their nose. Because of its shape, it is frequently
referred to as the "butterfly rash" of SLE. The rash is painless and does not
itch. The facial rash, along with inflammation in other organs, can be
precipitated or worsened by exposure to sunlight, a condition
called photosensitivity. This photosensitivity can be accompanied by
worsening of inflammation throughout the body, called a "flare" of the
Typically, this rash can heal without permanent scarring with treatment.
Most patients with SLE will develop arthritis during the course of their
illness. Arthritis in SLE commonly involves swelling, pain, stiffness, and
even deformity of the small joints of the hands, wrists, and feet. Sometimes,
the arthritis of SLE can mimic that of rheumatoid arthritis (another
More serious organ involvement with inflammation occurs in the brain, liver,
and kidneys. White blood cells and blood-clotting factors also can be
characteristically decreased in SLE, known as leucopenia
and thrombocytopenia, respectively. Leucopenia can increase the risk of
infection and thrombocytopenia can increase the risk of bleeding.
Inflammation of muscles (myositis) can cause muscle pain and weakness.
This can lead to elevations of muscle enzyme levels in the blood.
Inflammation of blood vessels (vasculitis) that supply oxygen to tissues can
cause isolated injury to a nerve, the skin, or an internal organ. The blood
vessels are composed of arteries that pass oxygen-rich blood to the tissues
of the body and veins that return oxygen-depleted blood from the tissues to
the lungs. Vasculitis is characterized by inflammation with damage to the
walls of various blood vessels. The damage blocks the circulation of blood
through the vessels and can cause injury to the tissues that are supplied
with oxygen by these vessels.
Inflammation of the lining of the lungs (pleuritis) and of the heart
(pericarditis) can cause sharp chest pain. The chest pain is aggravated
by coughing, deep breathing, and certain changes in body position. The
heart muscle itself rarely can become inflamed (carditis). It has also been
shown that young women with SLE have a significantly increased risk of
heart attacks from coronary artery disease.
Kidney inflammation in SLE can cause leakage of protein into the urine,
fluid retention, high blood pressure, and even kidney failure. This can lead
to further fatigue and swelling of the legs and feet. With kidney failure,
machines are needed to cleanse the blood of accumulated poisons in a
process called dialysis.
Involvement of the brain can cause personality changes, thought disorders
(psychosis),seizures, and even coma. Damage to nerves can cause
numbness, tingling, and weakness of the involved body parts or
extremities. Brain involvement is referred to as lupus cerebritis.
Many patients with SLE experience hair loss (alopecia). Often, this occurs
simultaneously with an increase in the activity of their disease. The hair
loss can be patchy or diffuse and appear to be more like hair thinning.
Some patients with SLE have Raynaud's phenomenon. In these patients,
the blood supply to the fingers and/or toes becomes compromised upon
exposure to cold, causing blanching, whitish and/or bluish discoloration,
and pain and numbness in the exposed fingers and toes.
How is lupus diagnosed?
Since patients with SLE can have a wide variety of symptoms and different
combinations of organ involvement, no single test establishes the diagnosis
of systemic lupus. To help doctors improve the accuracy of the diagnosis of
SLE, 11 criteria were established by the American Rheumatism
Association. These 11 criteria are closely related to the symptoms
discussed above. Some patients suspected of having SLE may never
develop enough criteria for a definite diagnosis. Other patients accumulate
enough criteria only after months or years of observation. When a person
has four or more of these criteria, the diagnosis of SLE is strongly
suggested. Nevertheless, the diagnosis of SLE may be made in some
settings in patients with only a few of these classical criteria, and treatment
may sometimes be instituted at this stage. Of these patients with minimal
criteria, some may later develop other criteria, but many never do.
The 11 criteria used for diagnosing systemic lupus erythematosus are
• malar (over the cheeks of the face) "butterfly" rash,
• discoid skin rash (patchy redness with hyperpigmentation and
hypopigmentation that can cause scarring
• photosensitivity (skin rash in reaction to sunlight [ultraviolet light]
• mucous membrane ulcers (spontaneous ulcers of the lining of the mouth,
nose, or throat
• arthritis (two or more swollen, tender joints of the extremities
• pleuritis or pericarditis (inflammation of the lining tissue around the heart
or lungs, usually associated with chest pain upon breathing or changes of
• kidney abnormalities (abnormal amounts of urine protein or clumps of
cellular elements called casts detectable with a urinalysis
• brain irritation (manifested by seizures [convulsions] and/or psychosis),
• blood-count abnormalities (low counts of white or red blood cells, or
platelets, on routine blood testing
• immunologic disorder (abnormal immune tests include anti-DNA or anti-
Sm [Smith] antibodies, falsely positive blood test for syphilis,
anticardiolipin antibodies, lupus anticoagulant, or positive LE prep test),
• antinuclear antibody (positive ANA antibody testing [antinuclear
antibodies in the blood]).
In addition to the 11 criteria, other tests can be helpful in evaluating patients
with SLE to determine the severity of organ involvement. These include
routine testing of the blood to detect inflammation (for example, tests called
the sedimentation rate and C-reactive protein), blood-chemistry testing,
direct analysis of internal body fluids, and tissue biopsies. Abnormalities in
body fluids and tissue samples (kidney, skin, and nerve biopsies) can
further support the diagnosis of SLE. The appropriate testing procedures
are selected for the patient individually by the doctor.
What is the treatment for systemic lupus?
There is no permanent cure for SLE. The goal of treatment is to relieve
symptoms and protect organs by decreasing inflammation and/or the level
of autoimmune activity in the body. Many patients with mild symptoms may
need no treatment or only intermittent courses of antiinflammatory
medications. Those with more serious illness involving damage to internal
organ(s) may require high doses of corticosteroids in combination with
other medications that suppress the body's immune system.
Patients with SLE need more rest during periods of active disease.
Researchers have reported that poor sleep quality was a significant factor
in developing fatigue in patients with SLE. These reports emphasize the
importance for patients and physicians to address sleep quality and the
effect of underlying depression, lack of exercise, and self-care coping
strategies on overall health. During these periods, carefully prescribed
exercise is still important to maintain muscle tone and range of motion in
Nonsteroidal antiinflammatory drugs(NSAIDs) are helpful in reducing
inflammation and pain in muscles, joints, and other tissues. Examples of
NSAIDs include aspirin, ibuprofen (Motrin), naproxen (Naprosyn),
and sulindac (Clinoril). Since the individual response to NSAIDs varies
among patients, it is common for a doctor to try different NSAIDs to find the
most effective one with the fewest side effects. The most common side
effects are stomach upset, abdominal pain,ulcers, and even ulcer bleeding.
NSAIDs are usually taken with food to reduce side effects. Sometimes,
medications that prevent ulcers while taking NSAIDs, such
asmisoprostol (Cytotec), are given simultaneously.
Corticosteroids are more potent than NSAIDs in reducing inflammation and
restoring function when the disease is active. Corticosteroids are
particularly helpful when internal organs are affected. Corticosteroids can
be given by mouth, injected directly into the joints and other tissues, or
administered intravenously. Unfortunately, corticosteroids have serious side
effects when given in high doses over prolonged periods, and the doctor
will try to monitor the activity of the disease in order to use the lowest doses
that are safe. Side effects of corticosteroids include weight gain, thinning of
the bones and skin, infection, diabetes, facial puffiness, cataracts, and
death (necrosis) of the tissues in large joints.
Hydroxychloroquine (Plaquenil) is an antimalarial medication found to be
particularly effective for SLE patients with fatigue, skin involvement, and
joint disease. Consistently taking Plaquenil can prevent flare-ups of lupus.
Side effects are uncommon but includediarrhea, upset stomach, and eye-
pigment changes. Eye-pigment changes are rare but require monitoring by
an ophthalmologist (eye specialist) during treatment with Plaquenil.
Researchers have found that Plaquenil significantly decreased the
frequency of abnormal blood clots in patients with systemic lupus.
Moreover, the effect seemed independent of immune suppression, implying
that Plaquenil can directly act to prevent the blood clots. This fascinating
study highlights an important reason for patients and doctors to consider
Plaquenil for long-term use, especially for those SLE patients who are at
some risk for blood clots in veins and arteries, such as those with
phospholipid antibodies (cardiolipin antibodies, lupus anticoagulant, and
false-positive venereal disease research laboratory test). This means not
only that Plaquenil reduces the chance for re-flares of SLE, but it can also
be beneficial in thinning the blood to prevent abnormal excessive blood
clotting. Plaquenil is commonly used in combination with other treatments
For resistant skin disease, other antimalarial drugs, such
as chloroquine (Aralen) orquinacrine, are considered and can be used in
combination with hydroxychloroquine. Alternative medications for skin
disease include dapsone and retinoic acid (Retin-A). Retin-A is often
effective for an uncommon wart-like form of lupus skin disease. For more
severe skin disease, immunosuppressive medications are considered as
Medications that suppress immunity (immunosuppressive medications) are
also calledcytotoxic drugs. Immunosuppressive medications are used for
treating patients with more severe manifestations of SLE, such as damage
to internal organ(s). Examples of immunosuppressive medications
include methotrexate (Rheumatrex,
Trexall),azathioprine (Imuran), cyclophosphamide (Cytoxan), chlorambucil (
Leukeran), andcyclosporine (Sandimmune). All immunosuppressive
medications can seriously depress blood-cell counts and increase risks of
infection and bleeding. Other side effects are specific for each drug. For
examples, Rheumatrex can cause liver toxicity, while Sandimmune can
impair kidney function.
In recent years, mycophenolate mofetil (Cellcept) has been used as an
effective medication for lupus, particularly when it is associated with kidney
disease. Cellcept has been helpful in reversing active lupus kidney disease
(lupus renal disease) and in maintaining remission after it is established. Its
lower side-effect profile has advantage over traditional immune-
In SLE patients with serious brain or kidney disease, plasmapheresis is
sometimes used to remove antibodies and other immune substances from
the blood to suppress immunity. Rarely, SLE patients can develop seriously
low platelet levels, thereby increasing the risk of excessive and
spontaneous bleeding. Since the spleen is believed to be the major site of
platelet destruction, surgical removal of the spleen is sometimes performed
to improve platelet levels. Other treatments have included plasmapheresis
and the use of male hormones. Plasmapheresis has also been used to
remove proteins (cryoglobulins) that can lead to vasculitis. End-stage
kidney damage from SLE requires dialysis and/or a kidney transplant.
Most recent research is indicating benefits of rituximab (Rituxan) in treating
lupus. Rituximab is an intravenously infused antibody that suppresses a
particular white blood cell, the B cell, by decreasing their number in the
circulation. B cells have been found to play a central role in lupus activity,
and when they are suppressed, the disease tends toward remission. This
may particularly helpful for patients with kidney disease.
At the 2007 national Rheumatology meeting, there was a paper presented
suggesting that low-dose dietary supplementation with omega-3 fish
oils could help patients with lupus by decreasing disease activity and
possibly decreasing heart-disease risk.
How can a lupus patient help prevent disease activity (flares)?
SLE is undoubtedly a potentially serious illness with involvement of
numerous organ systems. However, it is important to recognize that most
patients with SLE lead full, active, and healthy lives. Periodic increases in
disease activity (flares) can usually be managed by varying medications.
Since ultraviolet light can precipitate and worsen flares, patients with
systemic lupus should avoid sun exposure. Sunscreens and clothing
covering the extremities can be helpful. Abruptly stopping medications,
especially corticosteroids, can also cause flares and should be avoided.
Patients with SLE are at increased risk of infections, especially if they are
taking corticosteroids or immunosuppressive medications. Therefore, any
unexpected fever should be reported and evaluated.
The key to successful management of SLE is regular contact and
communication with the doctor, allowing monitoring of symptoms, disease
activities, and treatment of side effects.
How can lupus affect pregnancy or the newborn?
Patients with SLE who become pregnant are considered "high risk."
Women with SLE who are pregnant require close observation during
pregnancy, delivery, and the postpartum period. This includes fetal
monitoring by the obstetrician during later pregnancy. These women can
have an increased risk of miscarriages (spontaneous abortions) and can
have flares of SLE during pregnancy. The presence of phospholipid
antibodies, such as cardiolipin antibodies or lupus anticoagulant, in the
blood can identify patients at risk for miscarriages. Cardiolipin antibodies
are associated with a tendency toward blood clotting. Patients with SLE
who have cardiolipin antibodies or lupus anticoagulant may need blood-
thinning medications (aspirin with or without heparin) during pregnancy to
prevent miscarriages. Other reported treatments include the use of
intravenous gamma globulin for selected patients with histories of
premature miscarriage and those with low blood-clotting elements
(platelets) during pregnancy. Pregnant women who have had a previous
blood-clotting event may benefit by continuation of blood-thinning
medications throughout and after pregnancy for up to six to 12 weeks, at
which time the risk of clotting associated with pregnancy seems to diminish.
Plaquenil has now been found to be safe for use to treat SLE during
Lupus antibodies can be transferred from the mother to the fetus and result
in lupus illness in the newborn ("neonatal lupus"). This includes the
development of low red cell (anemia) and/or white blood cell and platelet
counts, and skin rash. Problems can also develop in the electrical system
of the baby's heart (congenital heart block). Occasionally, a pacemaker for
the baby's heart is needed in this setting. Neonatal lupus and congenital
heart block are more common in newborns of mothers with SLE who carry
antibodies referred to as anti-Ro (or SS-A) and anti-La (or SS-B). (It is wise
for the newborn baby's doctor to be made aware if the mother is known to
carry these antibodies, even prior to delivery. The risk of heart block is 2%;
the risk of neonatal lupus is 5%.) Neonatal lupus usually clears after 6
months of age, as the mother's antibodies are slowly metabolized by the
What does the future hold for patients with lupus?
Overall, the outlook for patients with systemic lupus is improving each
decade with the development of more accurate monitoring tests and
The role of the immune system in causing diseases is becoming better
understood through research. This knowledge will be applied to design
safer and more effective treatment methods. For example, completely
revising the immune system of patients with extremely aggressive
treatments that virtually temporarily wipe out the immune system is being
evaluated. Current studies involve immune eradication with or without
replacement of cells that can re-establish the immune system (stem cell
It should be noted that patients with SLE are at a somewhat increased risk
for developingcancer. The cancer risk is most dramatic for blood cancers,
such as leukemia andlymphoma, but is also increased for breast cancer.
This risk probably relates, in part, to the altered immune system that is
characteristic of SLE.
Women with SLE appear to be at increased risk for heart disease (coronary
artery disease) according to recent reports. Women with SLE should be
evaluated and counseled to minimize risk factors for heart disease, such as
elevated blood cholesterol, quitting smoking, high blood pressure,
DHEA (dehydroepiandrosterone) has been helpful in reducing fatigue,
improving thinking difficulties, and improving quality of life in patients with
SLE. Recent research indicates that DHEA has been shown to improve or
stabilize signs and symptoms of SLE. DHEA is commonly available in
health-food stores, pharmacies, and many groceries.
Landmark research has shown clearly that oral
contraceptives do not increase the rate of flares of systemic lupus
erythematosus. This important finding is opposite to what has been thought
for years. Now we can reassure women with lupus that if they takebirth-
control pills, they are not increasing their risk for lupus flares. NOTE: Birth-
control pills or any estrogen medications should still be avoided by women
who are at increased risk of blood clotting, such as women with lupus who
have phospholipid antibodies (including cardiolipin antibody and lupus
Individuals with SLE can improve their prognosis by learning about the
many aspects of the illness as well as closely monitoring their own health
with their doctors.
Systemic Lupus Erythematosus At A Glance
• Systemic lupus erythematosus (SLE) is an autoimmune disease.
• SLE is characterized by the production of unusual antibodies in the blood.
• SLE is eight times more common in women than men.
• The cause(s) of SLE is (are) unknown, however, heredity, viruses,
ultraviolet light, and drugs all may play some role.
• Up to 10% of patients with lupus isolated to the skin will develop the
systemic form of lupus (SLE).
• Eleven criteria help doctors to diagnose SLE.
• Treatment of SLE is directed toward decreasing inflammation and/or the
level of autoimmune activity.
• Patients with SLE can prevent "flares" of disease by avoiding sun
exposure and not abruptly discontinuing medications and monitoring their
condition with their doctor.