Lupus, also known as lupus erythematosus, is an autoimmune inflammatory disorder that occurs mostly in women.
Lupus produces widely varying symptoms, although joint pain is reported by most patients and skin lesions are common. Lupus can cause short periods of symptoms alternating with healthy periods, or can progress into a life-threatening disorder affecting the heart, kidneys, and other organs.
Why the disease is termed lupus is unknown, but it has been known as a distinct disorder and called lupus by European physicians since at least the tenth century A.D. The term erythematosus was first attached to the disease in the 1850s, and it refers to the patchy congestion of skin capillaries with blood (erythema) that often accompanies the disease.
Between one million and 1.5 million Americans have some form of lupus. The incidence among women is 10–15 times greater than among men, and it is two to three times more common among African Americans, Hispanics, Asians, and Native Americans than among whites. Lupus most often appears for the first time in women between the ages of 15 and 44. Twenty thousand people die of lupus-related causes in the United States annually.
Causes and symptoms
Lupus is an autoimmune disorder, a disease in which the body's immune system turns against the body itself. In a healthy person, the immune system defends against invading organisms but does not, in general, attack the body's own tissues. The cause of lupus is unknown. However, it is known that lupus has a genetic component, which means a predisposition to lupus can be inherited. Approximately 10% of lupus patients have one or more direct relatives with lupus. (Note that this means that 90% of lupus patients have no such relatives; however, it shows a
genetic connection because 10% is a much higher figure for familial lupus than can be attributed to chance alone.) Lupus has been definitely linked to genes on chromosome 1 and less certainly to genes on chromosomes 4 and 6.
Given genetic susceptibility, the disease may either develop spontaneously or be triggered by some environmental factor. Environmental factors known to trigger lupus include infections (e.g., Epstein-Barr virus, which infects 99% of children with lupus, but only 70% of healthy children), antibiotics, ultraviolet light (the rays in sunlight or sunlamp-light that causes sunburn), stress, smoking, certain medications, and hormones (especially estrogen, the female sex hormone).
Lupus manifests as a continuum or spectrum of disorders. However, it is common to divide lupus cases into four categories or groups:
- Systemic lupus erythematosus. This is the most serious form of lupus and affects about 70% of all persons with lupus. It is termed systemic because, in this variety of lupus, the body's immune system attacks one or more essential body systems. Targets may include the brain, kidneys, heart, pancreas, or other organs.
- Discoid or cutaneous lupus erythematosus. This variety of lupus is less severe, in that it attacks the skin only. However, it can be disfiguring, often attacking the skin of the face. The term discoid is derived from the round (disc-shaped) lesions that appear on the skin. About 10–15% of lupus patients have cutaneous lupus.
- Drug-induced or drug-related lupus erythematosus. This term refers to lupus that develops after a patient has taken a medication. Medications that can trigger drug-induced lupus include procainamide or hydralazine. Many of the substances that can potentially trigger lupus fall into the class of aromatic amines, or hydrazines. For example, the aromatic amine paraphenylenediamine is present in certain hair dyes and has been associated with lupus or lupus-like syndrome. Tartrazine (a food coloring, FD&C yellow No. 5), which is present in thousands of foods and medications, has also been associated with lupus. Cocaine abuse can induce lupus and several other connective-tissue diseases, as can exposure to certain metals (e.g., mercury). Between 10,000 and 15,000 people are diagnosed with drug-induced lupus annually in the United States.
- Mixed connective tissue disease. Approximately 10% of patients with lupus also have symptoms of one or more additional connective-tissue diseases.
The symptoms of lupus are quite varied. In discoid lupus, red patches (erythema) appear symmetrically on the cheeks, possibly extending to the face, neck, scalp, and other parts of the body. No organ other than the skin is affected (or the disease is classified as systemic, rather than discoid). Systemic lupus may begin suddenly, signaled by fever, or develop slowly over months or years. Chronic fatigue is a common symptom. Symptoms related to impairment of any organ may occur. The lupus disease process in a given organ is named after that organ; for example, inflammation of the kidneys is termed lupus nephritis, and inflammation of the brain is termed lupus cerebritis. Kidney involvement may be fatal. Over 50% of all systemic lupus patients in the United States presently have some degree of lupus cerebritis; 25–75% have neuropsychiatric symptoms at some time in their illness. Symptoms of lupus cerebritis may include headaches, seizures, stroke, psychosis, dementia, peripheral neuropathy, cerebellar ataxia (failure of muscular coordination, usually on one side of the body), chorea (jerky, involuntary movements), and others. Duration of central nervous system involvement may be transient (as with a migraine headache) or long lasting (as with dementia). Stroke incidence is 3–20% in systemic lupus patients, and is highest in the first five years of the disease. Peripheral neuropathy (carpal tunnel syndrome, for example) occurs in more than 20% of systemic lupus patients and cranial nerve palsies occur in 10–15%.
Exposure to the ultraviolet rays in sunlight can trigger lupus or, in a person who already has the disease, cause it to flare up. Worsening flare-ups of the disease can be life threatening because they can include inflammation and failure of the kidneys. Also, declining memory and mental sharpness with long-term lupus is common.
Lupus is notoriously difficult to diagnose. Many cases are not diagnosed until the patient has suffered irreversible kidney damage; for patients who do not have organ-threatening disease, diagnosis takes an average of two years of searching among physicians and conditions. The telltale erythematous skin lumps or rashes that give lupus erythematosus the latter half of its name eventually appear in 90% of systemic lupus patients and all discoid lupus patients, but may not appear early enough in the course of the disease to guarantee timely diagnosis. Additionally, no single lab test can confirm lupus, although certain antibody tests can help to distinguish lupus from other diseases.
Diagnosis of systemic lupus is based on a list of 11 criteria listed by the American College of Rheumatology. If four or more of the 11 criteria are met, a patient is deemed to have systemic lupus. The criteria include discoid or macular rash (often in a classic facial butterfly pattern across the nose and cheeks), photosensitivity, ulcers in the mouth, kidney dysfunction, and the presence of various blood factors such as anti-DNA antibody or anti-nuclear antibody (antibody that targets cell nuclei).
Approximately 15% of diagnoses of lupus may be misdiagnoses of other disorders, including fibromyalgia, seronegative spondyloarthropathies such as ankylosing spondylitis or Reiter's syndrome, autoimmune thyroiditis, and multiple sclerosis.
Although diagnosis of lupus cerebritis is particularly difficult, even if a patient has lupus, this does not necessarily mean that the neurological symptoms are due to lupus. Imaging studies cannot necessarily distinguish lupus cerebritis, although magnetic resonance imaging (MRI) studies are considered helpful. Positron emission tomography (PET) imaging has a high sensitivity to changes in the brain resulting from lupus cerebritis.
As with other neurological diseases in which the spectrum of symptoms varies widely, the treatment team must be designed for each individual case of lupus. A dermatologist will be involved if skin lesions are present; a neurologist, if cognitive loss is a possibility; a nephrologist will monitor kidney function; and a rheumatologist is often involved because of the frequency of joint pain. Other specialists will be needed depending on what organ systems are affected.
There is no known cure for lupus. However, there are numerous interventions designed to lessen the severity of the disease. These interventions can be classed as pharmacologic (drug-based) or nonpharmacologic.
Pharmacologic interventions (drug therapies)
Five categories of medication are used to treat systemic lupus patients: sunscreens and steroid lotions, nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., acetaminophen or ibuprofen), corticosteroids (e.g., prednisone to suppress the autoimmune response and control inflammation), anti-malarial drugs, and cytotoxic agents (i.e., chemotherapy drugs that are used for cancer, such as methotrexate, azathioprine, and cyclophosphamide).
Cytotoxic agents are used in order to decrease steroid dosage. Anticoagulants (blood thinners) may also be prescribed. For patients with non-organ-threatening disease, the antimalarial drug hydroxychloroquine is often prescribed; prednisone is often prescribed in cases of organ-threatening disease. New lupus drugs are under investigation; with recent increases in knowledge about the genetic and molecular basis of autoimmune disorders, including lupus, pharmacological treatment breakthroughs are possible at any time.
Nonpharmacologic (non-drug) interventions
All persons with lupus should guard against exposure to the sun and use protective clothing, sunscreen, and common sense when going outdoors. Adequate exercise can protect against fatigue, obesity, osteoporosis (weakening of the bones), and hyperlipidemia (excessive fats in the blood plasma). In some cases, dietary restrictions may be helpful, including especially the avoidance of food allergens and foods that may trigger lupus symptoms (such as alfalfa seeds). Vitamins, minerals, and dietary fatty acids have been shown to moderate lupus symptoms in some cases. On the other hand, some dietary supplements such as melatonin and Echinacea can worsen symptoms of some autoimmune diseases.
For lupus cerebritis, therapy choices include all the above options for alleviating the disorder throughout the rest of the body. Drug therapy can also include psychotropic medications such as antipsychotics, antidepressants, and benzodiazepines to stabilize mood, if this is affected. Unfortunately, long-term use of corticosteroids, one of the mainstays of pharmacological lupus treatment, may itself cause psychiatric symptoms. Experimental investigation of pheresis of cerebrospinal fluid for treatment of lupus cerebritis (cerebrospinal fluid is withdrawn from, filtered, and returned to the patient) was begun in the early 1990s.
As of mid-2004, approximately 25 lupus-related clinical trials were in progress, including investigations of monoclonal antibody therapy, the genetics of lupus, quality-of-life improvement, ultraviolet light therapy, stem-cell transplantation therapy, the mechanisms of kidney and brain damage, and many other aspects of lupus. Updated information on these trials can be found at the National Institutes of Health clinical trials website at <http://www.clinicaltrials.gov> for up-to-date information.
Prognosis for the individual patient depends on the severity of the disease process. Lupus can be fully compatible with a normal lifespan, or can result in fatal organ failure, depending upon the progression of the disorder in each individual.
Before corticosteroids became available, half of all patients with systemic lupus died within two years. Today, half of systemic lupus patients with organ-threatening complications survive for 20 years or longer. However, most systemic lupus patients eventually die from infections or from heart disease complicated by long-term use of corticosteroids.
There is some evidence that lupus may spontaneously resolve in part or whole, or resolve in response to treatment, in some lupus patients who have had the disease long term (i.e., 10 years or more).
Psychological counseling may be helpful, given that a diagnosis of lupus is life altering, and stress and frustration can enhance symptoms while searching for a diagnosis. Genetic counseling may be appropriate, as children of women with lupus have a 10% chance of developing lupus if female and 2% if male, while 20% of offspring overall will develop an autoimmune disorder of some type.
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Lupus Foundation of America. 2000 L Street, N.W., Suite 710, Washington, DC 20036. (202) 349-1155; Fax: (202) 349-1156. <http://www.lupus.org/>.