Causes and Symptoms
The cause of lupus is unknown, but scientists believe that both genetic and environmental factors are involved. Although there is a genetic predisposition to lupus, and researchers have identified an associated gene in some cases, only 10 percent of lupus patients have a familial connection and only 5 percent of children born to individuals with lupus will develop the disease. People of African, American Indian, Asian, and Hispanic origin seem to develop the disease more frequently than do non-Hispanic Caucasians. Lupus affects both men and women, but the incidence is ten to fifteen times higher in women and between 85 and 90 percent of patients are women. The majority of lupus diagnoses occur in young women in their late teens to thirties. It is possible that hormonal factors play a role in this disparity, because it is known that symptoms in women increase before menstrual cycles and during pregnancy. Environmental triggers include infections, exposure to ultraviolet light, and extreme stress, as well as antibiotic usage (particularly penicillin and those in the sulfa group). Certain other drugs, particularly hydralazine, procainamide, and isoniazid, can also cause lupus, but this type of drug-induced
lupus usually disappears after the offending drug is discontinued.
Symptoms may begin suddenly with fever or may develop gradually over the course of months or years. The clinical course is usually marked by remissions, periods when symptoms are minimal or absent, and relapses (called flare-ups), when the patient experiences an aggravation of symptoms and general malaise.
SLE can affect all organ systems of the body. The production of autoantibodies is the underlying physiologic problem in lupus. These autoantibodies can appear in a great number and variety, differing from patient to patient, thus causing their varying symptoms. General symptoms include fatigue, fever, anemia, weight loss, Raynaud’s phenomenon, and headaches. Joint
inflammation and pain (arthritis) occurs in about 90 percent of patients and is often the earliest manifestation of the disease. It usually occurs intermittently and generally does not cause permanent joint damage or deformity. Skin manifestations are present in most patients and include malar (butterfly) and/or discoid skin rashes; redness on the hands, fingertips, and nails; mucous membrane
ulcers in the mouth and nose; and photosensitivity. Inflammation of the sac around the lungs (pleurisy) or heart (pericarditis) is a frequent occurrence, resulting in pain upon deep breathing or chest pain. On rare occasions, there may be severe complications, such as bleeding into the lungs, which is life-threatening, or cardiac failure. Neurologic complications may also occur, including headaches, thinking impairment, personality changes, seizures, strokes, depression, dementia, and psychosis. Kidney involvement may be either minor or progressive, leading to severe nephritis that can be fatal. Ocular changes sometimes occur, causing conjunctivitis or blurred vision. In rare cases, retinitis, inflammation of the blood vessels at the back of the eye, can occur, leading to blindness if not treated quickly.
SLE is difficult to diagnose, due to its variety of symptoms and similarity to many other diseases. The constellation of symptoms appears and progresses differently for each patient and initially may seem vague and unrelated. Usually, patients will first see their family doctors. Upon diagnosis or the discovery of particular body system involvement, the family doctor may refer the patient on to one or more specialists. There is no single test for lupus. A physician will perform several laboratory tests as part of the differential diagnostic process, including various blood and urine tests and biopsies of the skin and kidney. For a positive diagnosis of SLE, a patient must have at least four of the eleven criteria established by the American College of Rheumatology: malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, hematologic disorder, immunologic disorder, and the presence of antinuclear antibodies (ANA).
Treatment and Therapy
There is no cure for lupus. Treatment is aimed at minimizing symptoms, reducing inflammation, and maintaining normal bodily functions. The treatment approach will vary according to the specific symptoms and organ involvement of the individual patient.
Preventive therapy involves lifestyle strategies aimed at reducing the risk of flare-up episodes. Patients are advised to follow a healthy diet, get adequate rest, and participate in moderate weight-bearing exercise in order to combat fatigue and muscle weakness. Counseling, support groups, and patient education help reduce stress and protect emotional well-being. Other recommendations include smoking cessation, limited alcohol intake, and adequate intake of vitamin D and calcium. Avoidance of excessive sun exposure through the use of protective clothing and sunscreens can reduce the occurrence of skin rashes and possibly systemic disease flares. Patients can learn to recognize the warning signs of an impending flare-up, such as increased fatigue, headaches, dizziness, stomach upset, fever, or the appearance of a rash. Regular laboratory tests can also detect an imminent flare-up. Early treatment of flare-ups can make them easier to control, can prevent tissue damage, and may reduce the length of time that the patient is given high doses of drugs.
Medications are an integral part of the treatment of lupus, and fall into four main categories: nonsteroidal anti-inflammatory drugs (NSAIDs),
corticosteroids, antimalarial drugs, and cytotoxic and immunosuppressive agents.
NSAIDs are used to control symptoms and reduce muscle and joint pain and inflammation. Commonly used NSAIDs include acetylsalicylic acid (aspirin), ibuprofen, naproxen, indomethacin, sulindac, nabumetone, tolmetin, and ketoprofen. Since these drugs can cause stomach upset, patients are usually advised to take them with meals or to take antacids or prostaglandins as well. Some NSAIDs have a prostaglandin added to the capsule. Patients taking NSAIDs must be monitored because of the potential adverse effects to the liver, kidney, and central nervous system.
Corticosteriods are synthetic hormones that have excellent anti-inflammatory and immunoregulatory effects and reduce symptoms promptly. They are used to treat a spectrum of lupus manifestations, especially in cases when organs are threatened. Prednisone is the most commonly used, followed by hydrocortisone, methylprednisolone, and others. Topical formulations are used for skin rashes, and oral doses are given for systemic involvement. Dosages are monitored carefully and tapered after initial inflammation reduction is achieved in order to reduce possible side effects. Corticosteroids may also be administered by injection into the skin or joint. For severe cases, intravenous administration of large doses of methylprednisolone (called pulse
steroids) for three days is given. Unfortunately, high doses of corticosteroids over long periods of time can produce unpleasant side effects, such as weight gain, rounded face, acne, emotional lability, hypertension, hyperlipidemia, increased risk of infection, diabetes, and osteoporosis.
Antimalarial drugs are frequently used in the management of skin rashes, joint inflammation, and serositis, though it may take months before their beneficial effects become apparent. They also help protect against the damaging effects of ultraviolet light. The most common agents are hydroxychloroquine (Plaquenil), chloroquine (Aralen), and quinicrine (Atabrine). These medications can be taken in combination with NSAIDs and other drugs to increase their effectiveness. They are particularly helpful when used with corticosteroids in order to decrease the amount of steroid needed. Damage to the retina is a potential side effect and is dose-related. Patients must be evaluated by an ophthalmologist twice a year.
Cytotoxic and immunosuppressive agents are potent drugs utilized in cases requiring aggressive therapy to protect major organs. They are used in conjunction with, or in place of, corticosteroids in order to spare the patient the side effects of the corticosteroids. Cytotoxics are not approved by the Food and Drug Administration (FDA) for use in the treatment of SLE; however, they are considered part of standard practice. These drugs target autoantibodies, thus suppressing the overactive immune response of lupus patients. Cyclophosphamide (Cytoxin) and azathioprine (Imuran) are both used in the treatment of lupus nephritis and are also effective in combating blood cell deficiencies, pulmonary bleeding, vasculitis, and central nervous system disease. Imuran is less potent but causes fewer side effects than does Cytoxin. Methotrexate, mycophenolate mofetil (CellCept), cyclosporine, chlorambucil, and nitrogen mustard are other cytotoxic agents that have been used in the management of lupus. Intravenous immunoglobulin injections are given to some patients to increase the production of blood platelets. Side effects of cytotoxic drugs include nausea, hair loss, increased risk of certain cancers, increased risk of infection, sterility, and bone marrow suppression.
Pregnancy in a lupus patient requires special care. Even though more than 50 percent of lupus pregnancies follow a normal course, all lupus pregnancies are considered high risk. Doctors recommend planning pregnancy during times of remission. Recent studies contradict the traditional belief that pregnancy increases the chance of flare-ups and also suggest that most flare-ups during pregnancy are mild, consisting only of rashes, fatigue, and arthritis. Frequent doctor visits are a necessity in order to detect and treat any problems early. The obstetrician will regularly check the baby’s growth and heartbeat in order to detect any abnormalities that might signal problems. Some lupus medications, such as prednisone, are safe to take during pregnancy because they do not cross the placenta. Others, such as cyclophosphamide, need to be used with caution or discontinued during the pregnancy.
About 20 percent of women with lupus experience preeclampsia during their pregnancy. This is a serious condition in which there is a sudden increase in blood pressure and/or protein in the urine requiring immediate treatment of the patient and delivery of the baby.
About one-third of women with lupus have antiphospholipid antibodies. These antibodies cause blood clots, which puts the patient at risk for developing them in the placenta, interfering with the nourishment of the baby. Since these blood clots usually form in the placenta in the second trimester, often the baby has developed enough to be delivered prematurely. The mother can be treated with heparin, which reduces the chance of clots and miscarriage.
About 50 percent of lupus pregnancies result in birth before full term. The majority of babies born between thirty and thirty-six weeks will grow normally with no problems. Those born before thirty-six weeks are considered premature. Approximately 3 percent of women with lupus will have a baby with a syndrome called neonatal lupus. This syndrome consists of a transient rash and blood count abnormalities and disappears by three to six months of age. Sometimes, a permanent abnormality in the heartbeat also occurs, but it is treatable and the baby is able to grow normally.
Perspective and Prospects
The identification of lupus as a distinct medical entity dates back to the twelfth century, when the term “lupus” (Latin for “wolf”) was used to describe ulcerative facial lesions, because they looked similar to either a wolf’s bite or a wolf’s facial markings. Other descriptions of the various dermatologic manifestations of lupus were noted by physicians over the next several centuries; the first medical textbook illustration occurred in 1856. The Viennese physician Moriz Kaposi, in 1872, was the first physician to recognize and describe the systemic manifestations of lupus, as well as the fact that there seemed to be two distinct forms of lupus, discoid and systemic. This was soon expanded upon by Canadian physician Sir William Osler, who detailed the major organ manifestations. In the late nineteenth century, the usefulness of quinine and salicylates in the treatment of lupus was reported. In the mid-twentieth century, the discovery of the immunologic aspects of lupus were discovered, when the presence of antinuclear antibodies were identified. Around this same time, the first animal models were used for the study of lupus, and the genetic component of lupus was also recognized. A major advance was the discovery of
the effectiveness of cortisone in the treatment of systemic lupus. Corticosteroids remain the primary treatment modality, complemented by antimalarials (for skin and joint involvement) and cytotoxic agents (for severe kidney manifestations and other life-threatening complications).
The prognosis for lupus patients has improved dramatically as a result of earlier diagnosis and better treatment. The long-term prognosis for a given patient is still variable, however, and is often related to the severity and the controllability of the initial inflammation. Also, the morbidity patterns of lupus patients have changed because of the increased usage of corticosteroids and cytotoxic drugs. Infections, accelerated atherosclerosis, and osteoporosis have become significant risk factors. Overall, however, the outlook for survival and quality of life has greatly improved. As of 2005, more than 90 percent of lupus patients lived more than ten years postdiagnosis. Those with organ-threatening disease had a lower rate, with only 60 percent surviving fifteen to twenty years. The Lupus Foundation of America reports that an estimated 1.5 million people in the United States and about five million people worldwide have some form of lupus.
A proliferation of research into the treatment of lupus that began in the 1950s continues and brings much promise for additional insight into the pathogenesis of lupus as well as new treatment modalities and agents. Some focus areas of current research include investigations into patterns of gene activity, the role of the protein interferon-alpha in the progression of lupus, environmental factors, immune ablation, stem cell
transplantation, and the targeting of destructive white blood cells. An intensified effort by the federal government, private industry, and nonprofit organizations, such as the Alliance for Lupus Research and the Lupus Foundation of America, fuels the hope that better treatments, prevention, and ultimately a cure for lupus will be found.
Bibliography:
Alan, Rick. "Systemic Lupus Erythmatosus." Health Library, September 1, 2011.
Hanger, Nancy C. Lupus—The First Year: An Essential Guide for the Newly Diagnosed. New York: Marlowe, 2003.
Kasitanon, Nuntana, Laurence S. Magder, and Michelle Petri. “Predictors of Survival in Systemic Lupus Erythematosus.” Medicine 85, no. 3 (May, 2006): 147–156.
Lahita, Robert G., and Robert H. Phillips. Lupus Q & A: Everything You Need to Know. Rev. ed. New York: Avery, 2004.
Lupus Foundation of America. "Statistics on Lupus." Lupus Foundation of America, 2013.
Meadows, Michelle. “Battling Lupus.” FDA Consumer 39, no. 4 (July/August, 2005): 28–34.
National Institute of Arthritis and Musculoskeletal and Skin Diseases. "Handout on Health: Systemic Lupus Erythrematosus." National Institute of Arthritis and Musculoskeletal and Skin Diseases: Lupus, August, 2011.
Phillips, Robert H. Coping With Lupus: A Practical Guide to Alleviating the Challenges of Systemic Lupus Erythematosus. 4th rev. and updated ed. New York: Avery, 2012.
Seppa, N. “Self-Help: Stem Cells Rescue Lupus Patients.” Science News 169, no. 5 (February 4, 2006): 67–68.
Teitel, Ariel D. "Systemic Lupus Erythmatosus." MedlinePlus, February 2, 2012.
Wallace, Daniel J. The Lupus Book: A Guide for Patients and Their Families. 5th ed. New York: Oxford University Press, 2013.
Zonali, M. “Taming Lupus.” Scientific American 292, no. 3 (March, 2005): 70–77.
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