Systemic lupus erythematosus (SLE)

DEFINITION: A chronic, inflammatory autoimmune disease in which the immune system attacks the body’s own structures; can affect any organ or body system, especially the skin, joints, blood vessels, and kidneys; distinct from two other forms of lupus: drug-induced lupus, which is caused by certain prescription medications, and discoid lupus, which primarily affects the skin

ALSO KNOWN AS: Lupus

ANATOMY OR SYSTEM AFFECTED: All

CAUSES: Unclear; possibly related to paramyxoviral infection

SYMPTOMS: Red or purple facial lesions, joint pain and swelling, fatigue, low-grade fever

DURATION: Chronic

TREATMENTS: None; alleviation of symptoms

Causes and Symptoms

The cause of lupus is unknown, but scientists believe that both genetic and environmental factors are involved. There is a genetic predisposition to lupus, and researchers have identified an associated gene in some cases; however, even an identical twin of someone with lupus has only a 25 to 50 percent chance of developing the disease as well. People of African, American Indian, Asian, and Hispanic origin develop the disease about three to four times more frequently than do White Americans not of Hispanic descent. Lupus affects both men and women, but the incidence is twelve times higher in women than in men. 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, such as by the Epstein-Barr virus, exposure to ultraviolet light, and extreme stress, as well as antibiotic usage (particularly penicillin and those in the sulfa group). Celiac disease also appears to be associated with an increased risk of developing lupus. Certain other drugs, particularly hydralazine, procainamide, isoniazid, and oral contraceptives, 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 and pain (arthritis) occurs in the majority 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 ulcers in the mouth and nose; and photosensitivity. Inflammation of the sac around the (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 or blurred vision. In rare cases, retinitis, inflammation of the blood vessels at the back of the eye, can occur, leading to 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 and muscle weakness. Counseling, support groups, and patient education help reduce stress and protect emotional well-being. Other recommendations include smoking cessation, limited 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 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 (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 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 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 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 is a potential 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 of lupus patients. Cyclophosphamide (Cytoxan) and azathioprine (Imuran) are both used in the treatment of lupus nephritis and are also effective in combating blood cell deficiencies, bleeding, vasculitis, and disease. Imuran is less potent but causes fewer side effects than does Cytotoxan. Methotrexate, mycophenolate mofetil (CellCept), cyclosporine, chlorambucil, and nitrogen mustard are other cytotoxic agents that have been used in the management of lupus. Intravenous injections are given to some patients to increase the production of blood platelets. Side effects of cytotoxic drugs include nausea, loss, increased risk of certain cancers, increased risk of infection, sterility, and suppression. Intravenous belimumab (Benlysta) may also be given in conjunction with NSAIDs, corticosteroids, antimalarials, and immunosuppressants, in order to diminish abnormal B cell production, which may in turn reduce the severity of flareup symptoms.

Pregnancy in a lupus patient requires special care and is considered high risk. Doctors recommend planning pregnancy during times of remission. Newer 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.

Some women with lupus experience preeclampsia during their pregnancy. This is a serious condition in which there is a sudden increase in and/or protein in the urine requiring immediate treatment of the patient and delivery of the baby.

Women with lupus may 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 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.

Many 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. Rarely, women with lupus will have a baby with a syndrome called neonatal lupus. This syndrome consists of a transient 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 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. According to the Lupus Foundation of America, about 10 to 15 percent of those with lupus will die prematurely from the illness. The Foundation also reported in 2021 that an estimated 1.5 million people in the United States and about 5 million people worldwide have some form of lupus. According to the CDC, about 204,000 US adults had SLE.

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. For instance, in 2024, scientists believed that they identified a potential cause and cure for lupus after using various methods, including CRISPR technology, to examine and modify genetic data within blood samples taken from those with the disease.

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