Lupus and the Heart-Joint Connection
Often described as the disease with a thousand
faces, systemic lupus erythematosus (SLE) is a chronic autoimmune
disorder. It typically causes fatigue and joint pain, can injure
nearly any internal organ, and increases the risk of cardiovascular
disease. A recent Canadian study in Arthritis and Rheumatism found
that the incidence of heart attack and stroke in SLE patients
was 7 to 17 times higher than what would be predicted based on
traditional cardiovascular risk factors, such as elevated cholesterol,
hypertension, diabetes, and smoking. Although SLE typically strikes
young women in their childbearing years, a large number of older
adults have the condition. About 15% of cases are first diagnosed
after age 55, and more SLE patients are enjoying a lengthy life
thanks to improved drug regimenswith more advances on the
horizon (see box).
What Is Lupus?
Derived from the Latin term for wolf (lupus) and
the Greek word for red (erythematosus), the disorder's name refers
to the red facial rash (which reminded some observers of a wolf
bite) that often develops in lupus patients. Systemic lupus is
an immune system disorder. Normally, the immune system makes
antibodies that protect the body by attacking foreign invaders
such as viruses and bacteria. In SLE, however, the body produces
so-called autoantibodies that attack and destroy normal cells,
causing inflammation, injury, and pain in various tissues and
Although the exact cause of SLE is unknown, genetic
and environmental factors are thought to play a role. In addition
to SLE, there are two other forms of lupus: drug-induced and
cutaneous lupus. Drug-induced lupus may appear after the use
of medications such as hydralazine (an antihypertensive) or procainamide
(used to treat abnormal heart rhythms). Although the symptoms
of this form of lupus are similar to those of SLE, they usually
resolve within a few days to weeks after the offending drug is
stopped. Cutaneous lupus erythematosus, a milder form sometimes
manifested by coin-shaped lesions on the face, neck, and scalp,
evolves into systemic disease in about 10% of patients.
SLE manifests itself in many ways and can affect
virtually any part of the body. Onset may be sudden or gradual
over years. Hallmarks of the disease include:
pain. Frequently accompanied by redness and swelling,
especially in the fingers, hands, wrists, and knees, joint
pain occurs in 90% of patients sometimes years before
disorders. They may be manifested as a butterfly-shaped
rash across the cheeks and bridge of the nose (50% of patients);
coin-shaped lesions, often on the face (25% of patients);
recurrent ulcers in the mouth and nose; and transient hair
loss. About 30% develop Raynaud phenomenon, a disorder marked
by poor circulation in the small blood vessels of the extremities.
or fever. Both occur in 90% of patients. Caused by
inflammation rather than infection, fever is often low grade
but may rise during flare-ups.
involvement. About half of patients develop lupus
nephritis, a persistent inflammation of the kidneys. Such
individuals may eventually experience renal failure and require
dialysis or kidney transplantation.
disorders. Almost 85% of patients experience low red
and white cell and platelet counts or other blood disorders.
Low platelets may cause easy bleeding and easy bruising.
An antibody paradoxically called the lupus anticoagulant
can predispose the blood to clot, raising the risk of venous
and arterial thrombosis, heart attack, and stroke.
involvement. Many patients develop pleurisy (an inflammation
of the membrane lining the lung) and pleural effusion (an
accumulation of fluid between the lung and its lining). Symptoms
include chest pain, difficulty breathing, and coughing.
system involvement. Neurologic disorders affect about
a quarter of patients.
Symptoms typically include anxiety, irritability,
depression, and mild impairment of memory and concentration,
but seizures and psychosis can also occur. For some patients,
the limitations imposed by their disease may also lead to depression.
Flare-ups interspersed with periods of improvement
or remission are typical for SLE. In about 20% to 30% of patients,
symptoms remain mild. Such patients may have only a skin rash
and achy joints but no evidence of major organ involvement. In
about 50% to 75% of patients, however, vital organs such as the
kidney, heart, or lungs are affected. Symptoms can be exacerbated
by infections, ultraviolet light, certain drugs, and hormones,
especially estrogenfor example, symptoms have been observed
to increase before menstruation and during pregnancy. In addition,
both physical and emotional stress may trigger episodes.
According to several recent studies, certain nontraditional
risk factorsincluding low bone density and high homocysteine
levelsmay be tied to heart disease and stroke in people
with lupus. A study in Arthritis and Rheumatism reported
that women with SLE who had decreased bone mineral density had
increased amounts of plaque in their carotid arteries and signs
of calcification in their coronary arteries, raising the risk
of stroke and heart disease.
Michelle Petri, M.D., an Associate Professor of
Rheumatology at Johns Hopkins, and colleagues had previously
uncovered a link between high homocysteine levels and an increased
risk of stroke and arterial clots among patients with SLE. "Homocysteine
levels are high in about 30% of lupus patients and should be
checked," notes Dr. Petri.
And a recent Swedish study, reported in Circulation,
also found that high homocysteine levels and osteoporosis (very
low bone density) appeared to increase the risk of heart disease
and stroke in people with SLE. The study also identified two
other nontraditional risk factors for cardiovascular disease:
the lupus anticoagulant and antibodies to oxidized low density
lipoprotein (LDL, or "bad") cholesterol.
Long-term corticosteroid therapy, often needed
to control disease symptoms, may also contribute greatly to the
higher cardiovascular risk among SLE patients. High doses of
corticosteroids for long periods can raise blood pressure, increase
lipid levels, cause weight gain, and raise the risk of diabetes
down the road-all factors that put lupus patients at greater
risk for heart disease and stroke. In addition, prolonged corticosteroid
therapy can lead to low bone density, cataracts, and mood swings.
According to Dr. Petri, "The adverse effects of prolonged
corticosteroid therapy are probably the number one cause of organ
damage among patients with systemic lupus."
Conservative measures that discourage episodes
include avoiding excessive sun exposure and using a sunscreen
with a Sun Protection Factor (SPF) of at least 15. All patients
with lupus should obtain sufficient rest (8 to 10 hours of sleep
nightly and a nap, if needed, during the day), exercise regularly
to help fend off muscle weakness and fatigue, and follow a healthy
diet. Because lupus patients have limited energy, they should
pace themselves by spreading out work and other activities over
a longer period of time and slowing down before they become too
tired. Immunizations to protect against influenza and pneumonia
are generally recommended, and prompt treatment of infections
is essential. Stress management is also important.
Early diagnosis and treatment can greatly improve
outcome. With treatment, the 20-year survival rate is about 80%,
and many individuals can look forward to a normal life span.
Regular monitoring of organ function and heart disease risk factors
is necessary. Patients with traditional and nontraditional risk
factors should receive aggressive treatment to ward off cardiovascular
Patients should generally be followed by a rheumatologisteven
when they feel well. Although there is no cure, combination therapy
can control symptoms. For some patients with mild disease, the
only medication needed may be aspirin or a nonsteroidal anti-inflammatory
drug (NSAID) to relieve muscle and joint pain and arthritis.
For others with more severe symptoms, stronger medications may
be required, at least on a short-term basis. They include:
which reduce inflammation and suppress the immune system.
They are used to control severe or life-threatening complications
such as kidney disease, central nervous system involvement,
and hemolytic anemia. Some people need corticosteroids for
brief periods; others may require long-term therapy. Combining
corticosteroids with other drugs can sometimes reduce the
risk of serious side effects because the corticosteroid dose
can be reduced.
drugs, which also suppress immune function and are most commonly
used to manage widespread lupus flares and to treat serious
kidney, neurologic, and arthritic symptoms. They can, however,
produce anemia, a low white blood count, and an increased
risk of infection; they may also increase the risk of cancer
later in life, although the risk appears to be very small.
drugs, which are frequently given to treat the skin and joint
symptoms associated with lupus. Side effects, though rare,
include diarrhea and rashes. Because about 1 of every 5,000
people taking hydroxychloroquine may develop retinal changes,
periodic eye examinations are recommended.
For more information: Lupus
Foundation of America
A Promising Future
Researchers are investigating more targeted
SLE therapies that can avoid the potentially dangerous
side effects associated with current treatments. Medications
currently being investigated include dehydroepiandrosterone
(DHEA), a mild male hormone; bromocriptine, which reduces
prolactin levels (a pituitary hormone that is elevated
in SLE); LJP 394 and leflunomide (Arava), which zero in
on particular aspects of the immune system (such as the
antibodies responsible for lupus kidney disease or the
immune cells responsible for inflammation); genetically
cloned (monoclonal) antibodies to immune system proteins,
which are thought to play a role in triggering SLE; and
transplantation of blood-forming stem cells (which produce
red and white blood cells and platelets) in conjunction
with cyclophosphamide (Cytoxan), a cytotoxic drug. It now
appears that short-term high-dose cyclophosphamide therapy
can be effective without stem cell transplantation.
From The Johns Hopkins Medical Letter:
Health After 50, April 2002.