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LUPUS ERYTHROMATOSUS A TO Z

SOURCE: National Institutes of Health, U.S.Department of Health and Human Services: Link to NIH


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Treatment and Health Maintenance

Improving current treatments for lupus patients and improving the reproductive health of women with lupus are also important elements of ongoing lupus research.

Specifically, investigators are studying ways to

  • minimize the use of immunosuppressives, such as corticosteroids and cyclophosphamide, to decrease unwanted side effects and improve the quality of life for lupus patients;
  • develop new therapies with fewer side effects;
  • correct underlying immune abnormalities; and
  • improve women's reproductive health and evaluate the safety of hOlmone replacement therapy for women with lupus.
Minimize the Use of Immunosuppressives

Corticosteroids, such as prednisone, are a mainstay of lupus therapy because they suppress the immune system and reduce inflammation.

Unfortunately, they also cause some serious side effects, including osteonecrosis, osteoporosis, and coronary artery disease.

Other, less serious side effects can also take a toll on the patient's quality of life.

Scientists are investigating how corticosteroid use can be minimized in such a way that the benefits are retained while the side effects are reduced.

Cyclophosphamide also suppresses the immune system and has anti-inflammatory properties.

Treatment with cyclophosphamide improves many severe manifestations of lupus.

Unfortunately, cyclophosphamide can be toxic. Patients using this drug may experience gastrointestinal complications, alopecia, and an increased risk for infections.

In the long term, cyclophosphamide also may damage gonadal tissue and lead to ovarian or testicular failure.

Other potential long-term complications include hemorrhagic cystitis, bladder fibrosis, and bladder cancer. At this time, scientists are conducting studies to better understand the long-term effects of cyclophosphamide therapy.

In addition, they are exploring the use of additional drugs that might counteract some of the negative side effects of cyclophosphamide, and trying to find the most effective dose regimen that causes the fewest severe side effects.

Scientists are also trying to identify combination therapies that may be more effective than single-treatment approaches.

For example, in lupus nephritis patients with moderate kidney scarring, a combination of cyclophosphamide and prednisone is more effective in preserving renal function than is treatment with prednisone alone.

In these patients, the combination therapy reduces the likelihood of end-stage renal failure.

Develop New Therapies

While some researchers are examining existing drug and treatment practices, other researchers are developing new treatment regimens.

Promising areas of treatment research include biologic agents, hormones, newer forms of chemotherapy, and nitric oxide.

Biologic Agents On the basis of new information about the SLE disease process, scientists are using novel biologic agents to selectively block parts of the immune system.

Developing and testing these new drugs, which are based on compounds that occur naturally in the body, is an exciting and promising new area of lupus research. Scientists hope that these naturally occurring substances will cause few side effects.

In addition, use of these agents may yield clues to the etiology of the disease.

Hormones

Because hormones are believed to influence the course and perhaps even the etiology of lupus, many researchers are interested in testing the effects of hormones on lupus patients.

For example, animal and human studies have shown benefits associated with dehydroepiandrosterone (DHEA) therapy.

DHEA is a naturally occurring hormone present in unusually low concentrations in people with lupus.

DHEA is currently being tested in clinical trials to determine if its use can improve the clinical outcome and reduce the prednisone requirements of lupus patients.

Chemotherapy

Researchers also continue to look for new forms of chemotherapy that work selectively on the immune system. For example, they are testing immunosuppressive drugs, such as cyclosporine and 2 chlorodeoxyadenosine, which strongly suppress immune function.

Preliminary clinical studies suggest that these drugs may be used in treating patients with lupus nephritis.

Nitric Oxide

Recent studies sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have investigated the role of nitric oxide, a natural substance known to promote inflammation.

These studies, using mice that develop a lupus-like autoimmune illness, including joint and kidney inflammation, showed that the animals produce abnormally high levels of nitric oxide.

When the mice were treated with a drug that blocks nitric oxide formation, development of kidney disease was prevented and joint inflammation was reduced.

Additional studies are needed to determine whether nitric oxide plays a role in inflammatory disease in humans and whether drugs that block the formation or action of nitric oxide will be valuable in treating patients with lupus.

Correct Underlying Immune

Abnormalities

Researchers predict that one day it may be possible to correct the underlying immune abnormalities in people with lupus.

Studies are under way to explore the dimensions, risks, and benefits of reconstructing the immune system by bone marrow transplantation and of using gene therapy to treat lupus.

Improve Reproductive Health in Women With Lupus

Because of recent improvements in diagnostic tools for lupus and a better understanding of the disease, doctors can now predict the likelihood of a lupus-related miscarriage and identify women at risk for giving birth to babies with neonatal lupus.

Doctors and lupus patients can now take measures to prevent miscarriages, and doctors can prepare to treat those babies born with neonatal heart block, the most serious complication of neonatal lupus.

Progress is also being made in another important area of reproductive health. In the past, women with lupus have not been able to use oral contraceptives or take advantage of hormone replacement therapy because of concerns that estrogens exacerbate lupus.

However, recent data suggest these drugs may be safe for some women with lupus, and a current study funded by NIAMS, the NIH Office of Research on Women's Health, and the NIH Office of Research on Minority Health is focusing on the safety and effectiveness of oral contraceptives and hormone replacement therapy in women with lupus.

This clinical trial is called the Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA). Researchers hope this study will yield options for safe, effective methods of contraception for young women with lupus as well as options for estrogen replacement therapy for postmenopausal women with lupus.




Source: National Institutes of Health, U.S.Dept of Health and Human Services


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