Lupus: The Prototypical Autoimmune Disease
As the prototypical autoimmune disease, lupus occurs when the immune system malfunctions. The immune system is designed to protect the body from foreign invaders, such as bacteria and viruses. It performs this role by producing antibodies, or proteins, to fight off infections. In people with lupus, the immune system loses its ability to distinguish between these foreign substances, called antigens, and the body’s own cells and tissue. For reasons that are not yet fully understood, the immune system then makes antibodies that are directed against "self." The self-antibodies create immune complexes which lodge in the body’s tissue, causing inflammation and organ damage.
No one knows the exact cause of lupus. However, lupus is not infectious. Researchers believe people with lupus are born with a genetic predisposition to the disease. Certain environmental factors also play a role in triggering disease activity. These factors include infections, antibiotics, ultraviolet light, extreme stress, certain drugs, and hormones. Hormonal factors may explain why lupus occurs more frequently in females than in males. Although lupus is known to occur in families, researchers have not identified a specific gene or set of genes believed responsible for the disease. Likely there are many different genes involved in various combinations that make individuals susceptible to developing lupus. The impact of lupus varies widely from person to person.
There are several forms of true lupus. Systemic lupus can affect nearly any organ or organ system of the body. Cutaneous lupus affects the skin. Drug-induced lupus is brought on by certain medications, and resolves when the offending medication is discontinued. Neonatal lupus affects the fetus and can range from a rash that disappears with no ill effects to an irregular heart beat that requires the infant to have a pacemaker. The antiphospholipid syndrome comprises a combination of symptoms and is implicated in recurrent miscarriages and blood clots. Sometimes, people with inconclusive test results for lupus may instead be given a diagnosis of mixed connective tissue disease or undifferentiated connective tissue disease.
There’s More to Lupus Than You Know
Approximately 1.5 million Americans have a form of lupus. Most people with lupus are women (about 90 percent), although men and children also develop lupus. The disease is two to three times more common among African Americans, Hispanics, Native Americans, and Asians than among Caucasians—a health disparity that remains unexplained. In addition, eight of ten new cases of lupus develop among women of childbearing age.
Lupus is more than joint pain, fatigue and skin rashes—common symptoms of the disease. Inflammation caused by lupus can damage the heart, lungs, kidneys and brain, resulting in significant disability or death. Women with lupus have a five- to ten-fold increased risk of coronary heart disease compared to the general population. Between 30 and 50 percent of people with lupus will have kidney disease. And people with lupus are at much greater risk for stroke and seizures than the general population.
The Difficulties of Diagnosing Lupus
What makes the diagnosis of lupus so difficult is that common symptoms of the disease mimic other illnesses and often are dismissed as nothing serious. These symptoms include achy or swollen joints, fevers, extreme fatigue, and skin rashes, all the result of inflammation caused by lupus. Also, disease activity comes and goes over time.
On average, more than half of all people with lupus suffer symptoms for four or more years and visit three or more doctors before they are diagnosed. This is often because the disease develops most often in young adults, and unfortunately, late diagnosis and delayed treatment contribute to the disabling impact of lupus. At present, there is no specific test for lupus.
Once a diagnosis is made, however, people with lupus face another challenge. There is no cure for the disease, and current treatments may cause other health problems that, for many people, can be worse than the primary disease.
Treatment Options Depend on Which Organs Are Affected
Presently, lupus is treated with a number of different medications, depending on the frequency and severity of disease activity and the specific organ systems affected. For people with mild disease, doctors will order non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, or a mild analgesic used for pain, such as acetaminophen.
For people with moderate lupus, treatment may consist of corticosteroids, such as prednisone, or an antimalarial drug, such as Plaquenil. People with serious or organ-threatening lupus usually are treated with immune modulating drugs, such as Imuran and Cytoxan, which suppress the immune system and reduce inflammation. While these medications can be effective in reducing inflammation and preventing or delaying progression of the disease, they can cause other serious health problems, such as osteoporosis and anemia.
Research Offers Promise for New Treatments
It has been nearly 40 years since the U.S. Food and Drug Administration has approved a new therapy specifically for lupus. However, during 2005 both pharmaceutical and biotechnology companies announced encouraging results of several clinical trials of potential new therapies, prestigious medical journals published reports on important research studies, and federal agencies took actions that may lead to better management of the disease. Among the companies working on new treatments for lupus are Aspreva Pharmaceuticals, Bristol-Myers Squibb, Genelabs Technologies, Genentech, Human Genome Sciences, Inc., Immunomedics, La Jolla Pharmaceuticals, MedImmune, Medarex, Teva Neurosciences, and Zymogenetics. Among the year’s highlights are the following:
Orally administered mycophenolate mofetil (CellCept®) was found to be more effective than standard of care intravenous cyclophosphamide in inducing remission of lupus nephritis (lupus kidney disease) among study participants, and had a more favorable safety profile.
Oral contraceptives containing estrogen did not increase the risk of additional disease flares in a study of women with inactive or mildly active lupus, suggesting that some women with lupus might be able to use combined oral contraceptives.
Another study found that women with lupus may benefit from postmenopausal hormone replacement therapy (HRT) without significant increased risk of severe disease flares, although the study found that HRT was associated with a small increased risk in the natural rate of mild to moderate flares.
The Department of Defense provided $2.5 million to support two research studies through the Congressionally Directed Peer-Reviewed Medical Research Program to validate lupus biomarkers, specific biochemicals in the body that make them useful for diagnosing a disease, measuring its progress, or measuring the effects of treatment. Validated biomarkers will expedite clinical trials of new lupus therapies.
The Lupus REACH (Research, Education, Awareness, Communication and Healthcare) Amendments Act of 2005, a federal bill that strengthens the nation's research efforts for lupus, and enhances public and professional awareness and understanding of the disease, was introduced in the United States Senate and U.S. House of Representatives. Introduction of the legislation coincided with the first-ever National Public Policy Summit on Lupus. The Summit, organized by the Lupus Foundation of America (LFA), brought together the nation's top health policy officials, members of Congress, researchers, clinicians, and individuals with lupus and their families to elevate lupus to a prominent place on the nation's healthcare agenda. During the Summit, the LFA also unveiled model bills for state legislatures which authorize state-level research and education programs.
The U.S. Food and Drug Administration (FDA) issued a draft Lupus Guidance Document that, when finalized, will provide a roadmap for industry to follow in establishing clinical trials of potential new therapies for lupus. It has been nearly 40 years since the FDA last approved a new medication specifically for lupus.
The LFA convened a group of leading lupus experts to plan a comprehensive epidemiological study of patients with lupus and related syndromes in the U.S. When completed, the study will determine the true incidence and prevalence of various forms of lupus among different populations. A national-scale epidemiological study is essential for planning and conducting clinical trials for new lupus therapies, other research efforts, patient services, and education programs.
For more information on these and other developments in lupus research and education, visit the LFA website at http://www.lupus.org/. or call the LFA’s national toll-free information request line at 888-38-LUPUS (385-8787).
