What is Lupus?

As many as two million Americans may have lupus, a chronic autoimmune disease that can affect virtually any organ in the body. But many people, when first diagnosed with the disease, do not know what it is. As a rheumatologist, I work with a lot of lupus patients. The first office visit is dedicated to answering their basic questions about the disease, and below, I will outline some of what I tell them.

What is Lupus?
Lupus is a chronic, autoimmune, inflammatory, multisystem disease. Currently, it is not known what causes lupus. The disease most commonly strikes women during their childbearing years, between the ages of fifteen and forty-five. Women are affected ten times more often than men in this age group. However, younger and older individuals can develop lupus. In these less commonly affected age groups (children and individuals over forty-five), females are only twice as likely to be affected than men.

What causes the disease?
Although the cause of lupus is not known, there is a genetic predisposition to developing an autoimmune disease such as lupus. The disease can first become evident when it is triggered by something in the environment, such as an infection, medication, or sun exposure. But most of the time we cannot identify the specific trigger for an individual patient. Sex hormones may contribute to the onset of the disease.

Understanding autoimmune diseases
The immune system is the body's normal defense system against foreign or non-self invaders, such as infections from the environment or tumors from within the body. A normal immune response includes making antibodies and causing inflammation in an effort to rid the body of the foreign intruder. For example, when you are first exposed to chicken pox, your immune system will produce antibodies or proteins to fight the infection. The chicken pox antibodies protect you against having the infection a second time when you are exposed to the virus again.

An autoimmune system breakdown
The autoimmune responses in people with lupus are not regulated properly, and they produce antibodies and inflammatory responses that are mistakenly directed against their own tissues. This mixed up reaction can occur in any organ, so recognizing the range of problems seen in lupus patients can be difficult and confusing. It is best to work with a specialist who can de-code the disease symptoms.

Four Forms of Lupus
There are four different forms of lupus, and each affects the body differently.

Drug-induced lupus: The most common form of lupus in older individuals is induced by drug exposure. It usually causes only a brief illness if the offending medication is identified and discontinued.

Discoid lupus: The second form is called discoid lupus, and occurs only on the skin. It causes a rash that can lead to permanent scarring of the skin. When the rash is in the scalp, it can be associated with permanent hair loss.

Systemic lupus: The third type of lupus is the systemic form, which is the most serious form, as it can affect any organ in the body. The systemic form is almost always associated with antibodies that are detected in the blood, causing the immune system to go haywire.

An overlap syndrome: Systemic lupus can also be part of an overlap syndrome that includes problems from more than one type of rheumatic autoimmune disorder such as lupus and rheumatoid arthritis

Diagnosing Lupus
It can be very difficult to recognize lupus. In fact, people often live for years with the disease before receiving a proper diagnosis, because the symptoms are not always initially associated with the disease. These symptoms can occur at different times or they can occur all at the same time.

Rheumatologists are doctors who specialize in the diagnosis and treatment of arthritis and autoimmune disorders. In order to make a diagnosis of lupus, a rheumatologist must study a combination of clinical symptoms, physical examination results, and certain laboratory tests. Though the range of problems associated with lupus is very broad and each patient is different, there are a number of symptoms characteristic of lupus that a rheumatologist will be looking for.

They include:

• Unexplained fever, weight loss, fatigue
• Arthritis with swollen joints, stiffness, and pain in the joints
• Rashes that may worsen with under one hour of sun exposure
• Recurrent oral or nasal ulcers
• Bleeding from the gums or a prolonged menstrual period
• Red rash on the legs that looks like many little pinpricks
• Swollen legs
• Difficulty urinating or foamy urine
• Chest pain, especially worse when taking a deep breath
• Color changes in hands with exposure to cold
• Muscle weakness
• Blood clots, including stroke and heart attacks in those under the age of 45
• Recurrent pregnancy loss
• Seizures, hallucinations, difficulty with memory, and other neurological problems

The tests
Blood and urine tests serve a number of purposes in the diagnosis and treatment of lupus. They are used as a diagnostic tool, they help to assess organ involvement in the disease, and they can be used to study the effectiveness of treatment. These laboratory tests include a complete blood count that measures your white blood count, your hemoglobin and platelets, and a blood chemistry panel that looks at kidney and liver function, and a urinalysis (examination of the urine), which also assesses kidney function. There are also specific blood tests for lupus such as anti-nuclear and other antibodies, complement levels, and those that indicate an increased risk of blood clots. Sometimes, x-rays, ultrasound examination and biopsies of organ tissues are needed depending on the symptoms and the organs involved.

The ANA test
The anti-nuclear antibody (ANA) test is a critical test in the diagnosis of lupus. A normal immune system makes antibodies to fight infection, but in those with lupus, the immune system makes antibodies against its own tissues. If you have lupus, you make an antibody directed against the nucleus of a cell that contains important cellular functional components such as DNA. Almost all systemic lupus patients receive a positive ANA test, but not all ANA positive tests point to a lupus diagnosis. This is a very important point. If you get a positive test result, it could be pointing to one of a number of autoimmune problems, or to no autoimmune problem at all. It could be without any clinical consequences. Because the results could mean a number of things, it is critical that a rheumatologist evaluate the test.

If your ANA test is positive, and your rheumatologist suspects a lupus diagnosis, then there are additional specialized tests that should be done. Since lupus is characterized by the production of extra antibodies, blood tests that include a panel of antibodies including double stranded DNA (dsDNA), SSA, SSB, RNP, Sm, and cardiolipin should be performed. When more than one antibody is present in a patient with clinical symptoms like those listed above, the rheumatologist may then consider a diagnosis of lupus. In addition, the specific antibodies may help predict the patients prognosis and offer clues as to which symptoms that patient will experience in the future. For example, if the double stranded DNA antibody is present, the patient should be monitored for kidney disease. If the anticardiolipin antibody is present, the patient may have pregnancy problems or may be at an increased risk of blood clots

Treatment
It is important for patients and their families to be educated about the disease, and treatment should include both education and counseling. Certain lifestyle changes are critical in the lives of lupus patients, and they include: getting enough rest, getting daily exercise, smoking cessation, eating a balanced diet, using sun protection every day, and taking their medication for current symptoms and prevention of new problems.

Drug treatment
There are no specific drugs for the treatment of lupus, so treatment addresses the particular symptoms and organ systems individual to that patient. Non-steroidal anti-inflammatory medications (NSAIDs) are used to control inflammation. If, however, the symptoms are not easily controlled, corticosteroids such as prednisone may be prescribed. An anti-malarial drug called hydroxychloroquine or plaquenil, is used to control skin, fatigue, and joint symptoms and also to prevent subsequent flare-ups. If symptoms are severe or if there are intolerable side effects from the corticosteroids, then immunosuppressive or chemotherapy medications are added. If a patient is at risk of blood clotting, then blood thinners or anticoagulants (heparin, lovenox, or coumadin) or antiplatelet medications (aspirin) may be used.

Prevention
The prevention of lupus-related complications, either from lupus itself or its treatment is considered to be a standard part of therapy. For example, hypertension (high blood pressure), hyperlipidemia (high cholesterol), osteoporosis (thin bones), which are all potential complications of steroids like prednisone, should be treated accordingly. Lupus patients should remember to be diligent about other aspects of their health and have regular, yearly check ups with a primary care doctor, and these visits should include pap smears and breast examinations for women, prostate examinations for men, and an update of vaccination requirements for all lupus patients.

The Future of Treatment
New treatments for lupus are being developed and tested, and there may even be drugs already approved by the FDA for other conditions that will work effectively in the treatment of lupus as well. For example, the use of a transplant anti-rejection medication, called mycophenolate mofetil (Cellcept) is currently under study for treatment of lupus kidney disease. Other transplant medications such as cyclosporine (Neoral) and tacrolimus (Prograf) have also been tested in lupus patients. The safety of estrogens either for oral contraceptive, regulating menstrual function in young women, or estrogen for replacement after menopause is being studied in a large multicenter national study sponsored by the National Institutes of Health. There has long been a concern that estrogen can worsen the symptoms of lupus, so women living with this disease have not been eligible to receive useful estrogen medications. This safety study will provide important information about how these medications might be used safely in these women.

There are a number of clinical trials underway that may also affect lupus treatment. Clinical trials using a synthetic male hormone, dihydroepiandrosterone or DHEA, have been completed, and the FDA is currently reviewing the studies of DHEA in lupus. If this medication is approved, it will be the first medication specifically approved and indicated for lupus in the last 30 years. There are other clinical trials underway using novel approaches to treat lupus using specific immune targets directed against the immunologic abnormalities in lupus. These studies are looking at new ways to treat lupus kidney disease with better efficacy and less toxicity.

Conclusion
We are making a great deal of progress in the diagnosis and treatment of lupus. This is reflected in better survival rates and improved quality of life for those with this chronic illness. I anticipate that major breakthroughs are forthcoming, and that we will do even better with the treatment of this disease in the near future.