What is Lupus?

WHAT IS LUPUS?
 
 
Robert G. Lahita, M.D., Ph.D.
Chairman of Medicine, Newark Beth Israel Hospital, Newark, N. J.  LibertyHealth Campus of Mount Sinai HospitalMedical School
Jersey City, N J
Professor of Medicine
at the New York CollegeUniversity of Medicine and Dentistry of New Jersey
 
Definition
Lupus is a chronic inflammatory disease that can affect various systems of the body, especially the skin, joints, blood, and kidneys.  The body's immune system normally makes proteins called antibodies to protect the body against viruses, bacteria, and other foreign materials.  These foreign materials are called antigens.  In an autoimmune disorder such as lupus, the immune system loses its ability to tell the difference between foreign substances (antigens) and its own cells and tissues.  The immune system then makes antibodies directed against "self."  These antibodies, called "auto-antibodies," react with the "self" antigens to form immune complexes.  The immune complexes build up in the tissues and can cause inflammation, injury to tissues, and pain.  
 
For most people, lupus is a mild disease affecting only a few organs.  For others, it may cause serious and even life-threatening problems.  More than 16,000 Americans develop lupus each year.  It is estimated that 500,000 to 1.5 million Americans have been diagnosed with lupus.  
 
Types of Lupus
There are three types of lupus: discoid, systemic, and drug-induced.  Discoid (cutaneous) lupus is usually, but not always limited to the skin.  It is identified by a rash that may appear on the face, neck, and scalp.  Discoid lupus is diagnosed by examining a biopsy of the rash.  In discoid lupus the biopsy will show abnormalities that are not found in skin without the rash.  Discoid lupus does not generally involve the body's internal organs.  Therefore, the ANA test, a blood test used to detect systemic lupus, may be negative in patients with discoid lupus.  However, in a large number of patients with discoid lupus, the ANA test is positive, but at a low level or strength.  We call this level a titer.
 
In approximately 10 percent of patients, discoid lupus can evolve into the systemic form of the disease, which can affect almost any organ or system of the body.  This cannot be predicted or prevented.  Treatment of discoid lupus will not prevent its progression to the systemic form.  Individuals who progress to the systemic form probably had systemic lupus at the outset, with the discoid rash as a major symptom.
 
Systemic lupus is usually more severe than discoid lupus and can affect almost any organ or system of the body.  For some people, only the skin and joints will be involved.  In others, the joints, lungs, kidneys, blood, or other organs and/or tissues may be affected.  Generally, no two people with systemic lupus will have identical symptoms.  Systemic lupus may include periods in which few, if any, symptoms are evident (“remission”) and other times when the disease becomes more active (“flare”).  Most often when people mention "lupus," they are referring to the systemic form of the disease.
 
Drug-induced lupus occurs after the use of certain prescribed drugs.  The symptoms of drug-induced lupus are similar to those of systemic lupus.  The drugs most commonly connected with drug-induced lupus are hydralazine (used to treat high blood pressure or hypertension), procainamide (used to treat irregular heart rhythms), and Isoniazid (a drug used to treat TB).  Drug induced lupus is more common in men, because they are given these drugs more often, however this may not be the case now because of a resurgence of tuberculosis and the drugs used to treat that disease..  Not everyone who takes these drugs will develop drug-induced lupus and only about 4 percent of the people who take these drugs will develop the antibodies suggestive of lupus.  Of those 4 percent, only an extremely small number will develop the disease which we call drug-induced lupus.  The symptoms usually leave when the medications are discontinued.  
 
Although drug-induced lupus and discoid lupus share features of systemic lupus, the rest of this brochure primarily discusses systemic lupus.  
 
Cause
The cause(s) of lupus is unknown, but there are environmental and genetic factors involved.  While scientists believe there is a genetic predisposition to the disease, it is known that environmental factors also play a critical role in triggering lupus.  Some of the environmental factors that may trigger the disease are: infections, antibiotics (especially those in the sulfa and penicillin groups), ultraviolet light, extreme stress, certain drugs, and hormones.
 
Although lupus is known to occur within families, there is no known gene or genes which are thought to cause the illness.  There are recent discoveries of genes on chromosomes like number 1 which is associated with lupus in certain families.  Previously, genes on chromosome 6 called “immune response genes” were associated with the disease and studied intensely.  We now know that lupus can involve major genes on many chromosomes and this is an active area of research. Only 10 percent of lupus patients will have a close relative (parent or sibling) who already has or may develop lupus.  Statistics show that only about 5% of the children born to individuals with lupus will develop the illness.  Lupus can occur in identical twins, but the chance of the disease occurring in both twins is about 30%, supporting the idea that origins of the disease are genetic in part, while other factors play a role.
 
Lupus is often called a "woman's disease" despite the fact that many men are affected.  While lupus can occur at any age in either sex, it occurs 10-15 times more frequently among adult females than adult males after puberty; after emergence into sexual maturity.  The symptoms of the disease are the same in men and women.  Women of African, Hispanic, American Indian, and Asian origin are thought to develop the disease more frequently than Caucasian women.  The reasons for this ethnic selection are not clear, but it is important because the death rate for lupus in African American women is higher than that of other races.  The reason for this is unknown.
 
Genetic factors may explain why lupus occurs more frequently in females than in males, although hormones play a role in severity of the illness.  The increase of symptoms before menstrual periods and/or during pregnancy supports the belief that hormones, particularly the estrogens, regulate the severity of the disease. Sex hormones do not cause lupus. However, the exact reason for the greater prevalence of lupus in women and the cyclic nature of symptoms remain unknown.
 

Symptoms
Although lupus can affect any part of the body, most people experience symptoms in only a few organs.  Table 1 lists the most common symptoms of people with lupus.
 
 
TABLE 1
 
TABLE OF SYMPTOMS
 
Symptom Percentage of people who experience
 
Achy joints (arthralgia) 95%
Fever more than 100 degrees F (38 degrees C) 90%
Arthritis (swollen inflamed joints) 90%
Prolonged or extreme fatigue 81%
Skin Rashes 74%
Anemia 71%
Kidney Involvement 50%
Pain in the chest on deep breathing (pleurisy) 45%
Butterfly-shaped rash across the cheeks and nose 42%
Sun or light sensitivity (photosensitivity) 30%
Hair loss 27%
Abnormal blood clotting problems     20%
Raynaud's phenomenon (fingers turning white
   and/or blue in the cold) 17%
Seizures 15%
Mouth or nose ulcers 12%
 
 
Diagnosis
Because many lupus symptoms mimic other illnesses and are vague and come and go, lupus can be difficult to diagnose.  The diagnosis is usually made by a careful review of a person's entire medical history, a physical exam and an analysis of the results obtained in routine and  specialized tests related to immune status.  Currently, there is no single laboratory test that can determine whether a person has lupus or not.  To assist the physician in the diagnosis of lupus, the American College of Rheumatology (ACR) in 1982 issued a list of 11 symptoms or signs that help distinguish lupus from other diseases (see Table 2).  This has recently been revised to include the phospholipid or “sticky blood” antibodies.  A person should have four or more of these symptoms to suspect lupus.  The symptoms do not all have to occur at the same time.
 
When someone has many symptoms and signs of lupus and has positive tests for lupus, physicians have little problem making a correct diagnosis and initiating treatment.  However, a more common problem occurs when an individual has vague, seemingly unrelated symptoms of achy joints, fever, fatigue, or pains.  Some doctors may think the person is neurotic.  Others may try different drugs in the hope of suppressing the symptoms.  Fortunately, with growing awareness of lupus, an increasing number of physicians will consider the possibility of lupus in the diagnosis.  
 
A patient can help the doctor by being open and honest.  A healthy dialogue between the patient and doctor results in better medical care, not only for people with lupus, but for anyone seeking medical treatment.
 
To whom should a person go for a diagnosis of lupus?  Most individuals usually seek the help of their family doctor first, and this is often sufficient unless there is extensive disease.  However, when unresolved questions arise or complications develop a specialist must be consulted.  The choice of specialist depends on the problem.  For example, you would see a nephrologist for a kidney problem or a dermatologist for a skin problem.  Most often, a rheumatologist or clinical immunologist specializing in lupus is recommended.  Referrals can be made through your family doctor, the local medical society, or your local Lupus group like Lupus International.  

 
TABLE 2
 
THE ELEVEN CRITERIA USED FOR THE DIAGNOSIS OF LUPUS 
ERYTHEMATOSUS
 
Criterion Definition
 
Malar Rash Rash over the cheeks
 
Discoid Rash Red raised patches 
 
Photosensitivity Reaction to sunlight, resulting in the development of or increase in skin rash
 
Oral Ulcers Ulcers in the nose or mouth, usually painless
 
Arthritis Non-erosive arthritis involving two or more peripheral joints (arthritis in which the bones around the joints do not become destroyed)
 
Serositis Pleuritis or pericarditis (inflammation of the lining of the breast or lung)
 
Renal Disorder Excessive protein in the urine (greater than 0.5 gm/day or 3+ on test sticks) and/or cellular casts (abnormal elements the urine, derived from red and/or white cells and/or kidney tubule cells)
 
Neurologic Seizures (convulsions) and/or psychosis in the absence of drugs or metabolic 
Disorder disturbances which are known to cause such effects
 
Hematologic Hemolytic anemia or leukopenia (white blood count below 4,000 cells 
Disorder per cubic millimeter) or lymphopenia (less than 1,500 lymphocytes per cubic millimeter) or thrombocytopenia (less than 100,000 platelets per cubic millimeter).  The leukopenia and lymphopenia must be detected on two or more occasions.  The thrombocytopenia must be detected in the absence of drugs known to induce it.
 
Antinuclear Positive test for antinuclear antibodies (ANA) in the absence of drugs 
Antibody known to induce it.
 
Immunologic Positive anti-double stranded anti-DNA test, positive anti-Sm test, positive antiphospholipid antibody such as anticardiolipin, or false positive syphilis test (VDRL).
 
Adapted from: Tan, E.M., et. al.  The 1982 Revised Criteria for the Classification of SLE. Arth Rheum 25: 1271-1277.
 
 
Laboratory Tests Used in the Diagnosis of Lupus
The first laboratory test ever devised was the LE (lupus Erythematosus) cell test.  When the test is repeated many times, it is event ually positive in about 90 percent of the people with systemic lupus. Unfortunately, the LE cell test is not specific for systemic lupus (despite the official-sounding name) and is rarely used today.  The test can also be positive in up to 20 percent of the people with rheumatoid arthritis, in some patients with other rheumatic conditions like Sjogren's syndrome or scleroderma, in patients with liver disease, and in persons taking certain drugs (such as procainamide, hydralazine, and others).
 
The antinuclear antibody (ANA or FANA) test detected by a technique called immunofluorescence or now by other means is more specific for lupus than the LE cell prep test, but not good at making the final diagnosis.   This is because the ANA test is positive at some time in virtually all people with systemic lupus, and though it is  a good diagnostic test for systemic lupus it is found in many diseases and even in normal people.  If the test is negative, the patient might not have systemic lupus or have lost the titer during treatment.  On the other hand, a positive ANA, by itself, is not diagnostic of lupus since the test may also be positive in individuals:
 
1.  with other connective tissue diseases; 
2.  without symptoms; 
3.  being treated with certain drugs, including procainamide, hydralazine, isoniazid, and 
     chlorpromazine; 
4.  with conditions other than lupus, such as scleroderma, rheumatoid arthritis, infectious 
     mononucleosis and other chronic infectious diseases such as lepromatous leprosy, subacute 
     bacterial endocarditis, malaria, etc., and liver disease. 
5.  during a normal pregnancy. 
 
Because it can be positive in conditions other than lupus, the results of the ANA test have to be interpreted in light of the patient’s medical history, as well as the current clinical signs and symptoms.
 
ANA test reports include a titer (or strength) of the antibody.  The titer indicates how many times an individual's blood must be diluted to get a sample free of anti-nuclear antibodies.  Thus, a titer of 1:640 shows a greater concentration of anti-nuclear antibodies than a titer of 1:320 or 1:160.  The titer is always highest in people with lupus.  Patients with active lupus have ANA tests that are very high in titer.
 
Laboratory tests which measure complement levels in the blood are also of some value.  Complement is a blood protein that, with antibodies, destroys bacteria.  It is an "amplifier" of immune function.  If the total blood complement level is low, or the C3 or C4 complement values are low, and the person also has a positive ANA, some weight is added to the diagnosis of lupus.  Low C3 and C4 complement levels in individuals with positive ANA test results may also be indicative of lupus kidney, brain or skin disease.  
 
Tests of individual antigen antibody reactions have been developed which are very helpful in the diagnosis of SLE.  These include the anti-DNA antibody test, the anti-Sm antibody test, the anti-RNP antibody test, the anti-Ro antibody test, and tests which measure serum complement levels.  These tests can be further explained by your physician.
 
Detection of antibodies to phospholipid, such as the anticardiolipin assay or a positive lupus anticoagulant can be cause for concern especially if the patient has evidence of blood clots (thromboses) anywhere in the body.  The most common manifestation of this is deep vein thrombosis (DVT), phlebitis or inflammation of the vessels in the calves of the legs.  The presence of these antibodies in the absence of any clotting problem may require no treatment.  However, evidence of abnormal blood clotting may require that the patient take a blood thinner like heparin and later warfarin (Coumadin) to prevent blockage of small and large blood vessels.  When blockage occurs in the lung or the brain it can be very serious.  This condition and the antibodies associated with it is called “the sticky blood syndrome”
.
 
Laboratory tests are most useful when one remembers the following information.  If an individual has signs and symptoms supporting the diagnosis of lupus (e.g., at least four of the American College of Rheumatology criteria), including a positive ANA, the diagnosis is confirmed and no further testing is necessary.  If a person has only two or three of the ACR criteria, including a positive ANA, then the ANA supports but does not confirm the diagnosis.  In these cases, unless more specific tests are positive (e.g., anti-DNA, anti-Sm, anti-Ro) the diagnosis of lupus is uncertain until more clinical findings develop or other more specific blood tests, as cited above, become positive.  
 
Many patients may present with vague symptoms and only a positive antiphospholipid (APL) antibody or a lupus anticoagulant.  A person may only have positive antiphospholipid antibodies and be diagnosed with primary antiphospholipid syndrome instead of lupus.  People with primary APL syndrome might still have problems with premature clotting of blood and require treatment. 
 
Physicians will sometimes also perform skin biopsies of both the individual's rashes and his or her normal skin.  These biopsies can help diagnose systemic lupus in about 75 percent of patients.
 
A kidney biopsy is sometimes required if urine or blood evaluations show evidence of kidney disease. Kidney abnormalities vary with each patient.  A biopsy and special preparation of the biopsy sample is required to give the doctor an idea of the degree and type of kidney injury. Using the biopsy results the doctor can tailor therapy for each individual.  
 
The interpretation of all these positive or negative tests, and their relationship to symptoms, is frequently difficult.  A test may be positive one time and negative another time, reflecting the relative activity of the disease or other variables.  When questions cannot be resolved, consult an expert in lupus.  
 

Flares (What Triggers Lupus?)
What triggers an attack of lupus in a susceptible person?  Scientists have noted common features in many lupus patients.  In some, exposure to the sun causes sudden development of a rash and then possibly other symptoms.  In others an infection fails to improve and then complications arise and these may be the first signs of lupus.  In still other cases, a drug taken for some illness produces the symptoms that suggest an autoimmune disease.  In some women, the first symptoms and signs develop during pregnancy.  In others, they appear soon after delivery.  Many people cannot remember or identify any specific factor that triggered their illness.  Obviously, there are many unrelated factors that can trigger the onset of the disease.
 

Treatment
For the vast majority of people with lupus, effective treatment can minimize symptoms, reduce inflammation, and maintain normal bodily functions. Preventive measures can reduce the risk of flares.  For photosensitive patients, avoidance of (excessive) sun exposure and/or the regular application of sun screens will usually prevent rashes.  Regular exercise helps prevent muscle weakness and fatigue.  Immunization protects against specific infections.  Support groups, counseling, talking to family members, friends, and physicians can help alleviate the effects of stress.  Needless to say, negative habits are hazardous to people with lupus.  These include smoking, excessive consumption of alcohol, too much or too little of prescribed medication, or postponing regular medical checkups.
 
Treatment approaches are based on the specific needs and symptoms of each person.  Because the characteristics and course of lupus may vary significantly among people, it is important to emphasize that a thorough medical evaluation and ongoing medical supervision are essential to ensure proper diagnosis and treatment.
 
Medications are often prescribed for people with lupus, depending on which organs are involved, and the severity of involvement.  Effective patient-physician discussions regarding the selection of medication, its possible side effects, and any changes in doses, are vital.  Commonly prescribed medications include:
 
Non-steroidal Anti-inflammatory Drugs (NSAIDs):  These medications are prescribed for a variety of rheumatic diseases, including lupus.  Examples of such compounds include acetylsalicylic acid (e.g., aspirin), ibuprofen (Motrin), naproxen (Naprosyn), indomethacin (Indocin), nabumetone (Relafen), tolmetin (Tolectin), and a large number of others.  These drugs are usually recommended for muscle, joint pain, and arthritis.  Aspirin and NSAIDs may cause stomach upsets for some people.  This effect can be minimized by taking them with meals, milk, antacids, or prostaglandins such as misoprostil (Cytotec).  Newer NSAIDs contain a prostaglandin in the same capsule (Arthrotec).  The other NSAIDs work in the same way as aspirin, but may be more potent, and patients often require fewer pills per day to have the same effect as aspirin.  Many NSAIDs are now available in “over the counter” forms.  Patients should be cautious about taking too much aspirin or NSAID since too many of these can reduce the blood flow to the kidney and cause problems.
 
Acetaminophen:  Acetaminophen (e.g., Tylenol) is a mild analgesic that can often be used for pain.  It has the advantage of less stomach irritation than aspirin, but it is not an anti-inflammatory drug.  Acetaminophen is a pain medicine.
 
Corticosteroids:  Corticosteroids (steroids) are hormones that have anti-inflammatory and immunoregulatory properties.  They are normally produced in small quantities by the adrenal gland.  This hormone controls a variety of metabolic functions in the body.  Synthetically produced corticosteroids are used to reduce inflammation and suppress activity of the immune system.  The most commonly prescribed drug of this type is Prednisone.  
 
Because steroids have a variety of side effects, the dose has to be regulated to maximize the beneficial anti-immune/anti-inflammatory effects and minimize the negative side effects.  Side effects occur more frequently when steroids are taken over long periods of time at high doses (for example, 60 milligrams of Prednisone taken daily for periods of more than one month).  Such side effects include weight gain, a round face, acne, easy bruising, "thinning" of the bones (osteoporosis), high blood pressure, cataracts, onset of diabetes, increased risk of infection, stomach ulcers, hyperactivity, and an increase of appetite.  This medication should never be stopped abruptly because you might become very ill.  The physician should guide the patient who wishes to lower their dose of corticosteroid in any manner.
 
Antimalarials:  Chloroquine (Aralen) or hydroxychloroquine (Plaquenil), commonly used in the treatment of malaria, may also be very useful in many individuals with lupus.  They are most often prescribed for skin and joint symptoms of lupus.  It may take months before these drugs demonstrate a beneficial effect.  Side effects are rare, and consist of occasional diarrhea or rashes.  Some antimalarial drugs, such as quinine and chloroquine, can affect the eyes.  Therefore, it is important to see an eye doctor (ophthalmologist) regularly.  The manufacturer suggests an eye exam before starting the drug and one exam every six months thereafter.  However, your physician might suggest a yearly exam is sufficient.
 
Immunomodulating Drugs:  Azathioprine (Imuran) and cyclophosphamide (Cytoxan) are in a group of agents known as cytotoxic or immunosuppressive drugs.  These drugs act in a similar manner to the corticosteroid drugs in that they suppress inflammation and tend to suppress the immune system.  The side effects of these drugs include anemia, low white blood cell count, and increased risk of infection.  Their use may also predispose an individual to developing cancer later in life.
 
Other agents like methotrexate and cyclosporin are used to control the symptoms of lupus.  Both are Immunomodulating drugs which have their own side effects.  These drugs are still in the investigational phase for lupus.  Some of these agents are used in conjunction with apheresis, a blood filtering treatment.  Apheresis has been tried by itself in an effect to remove specific antibodies from the blood but the results have not been promising.
 
Biological agents like Retuximab are directed toward specific cells of the immune system.  These include agents which block the production of specific antibodies like those against DNA (Requin), those that inhibit T or B cells (Retuxin) or agents which act to suppress the manufacture of antibodies through other mechanisms (CellCept).  Other modes are intravenous immunoglobulin injections which are given on a regular basis to increase platelets (particles important to coagulation), to treat vasculitis or control Antiphospholipid Syndrome. The use of drugs called cytokine inhibitors require more research.  The drugs used for rheumatoid arthritis patients might not be appropriate for use in lupus at this time.  Many other agents are in clinical studies for use with lupus patients.  These drugs capitalize on our knowledge of the immune system and might be the next “breakthrough”.
 
Anticoagulants:  These drugs are employed to thin the blood, or in actuality to prevent blood from clotting rapidly.  They range from aspirin at very low dose which prevents platelets from sticking to heparin/coumadin which actually prevent the blood from clotting.  The latter requires careful monitoring to insure that the patient is in the “therapeutic range” or that the blood is not excessively “thin."  Generally, such therapy is life-long in people with lupus and follows an actual episode of clotting (embolus or thromboses).  
 
People with lupus should learn to recognize early symptoms of disease activity.  In that way they can help the physician know when a change in therapy is needed.  Regular monitoring of the disease by laboratory tests can be valuable because noticeable symptoms may occur only after the disease has significantly flared.  Changes in blood test results may indicate the disease is becoming active even before the patient develops symptoms of a flare.  Generally, it seems that the earlier such flares are detected, the more easily they can be controlled.  Also, early treatment may decrease the chance of permanent tissue or organ damage and reduce the time one must remain on high doses of drugs.

Nutrition and Diet
Although much is still not known about the nutritional factors in many kinds of disease, no one questions the necessity of a well-balanced diet.  Fad diets, advocating an excess or an exclusion of certain types of foods, are much more likely to be detrimental than beneficial in any disease, including lupus.  Scientists have shown that both antibodies and other cells of the immune system may be adversely affected by nutritional deficiencies or imbalances.  Thus, significant deviations from a balanced diet may have profound effects on a network as complex as the immune system.  
 
There have been suggestions about various foods and the treatment of lupus.  One example is fish oil.  However, these diets have been used only in animals with limited success and should not become the mainstay of a person's diet. In the case of anticoagulation or thinning of the blood, substantial changes of the diet are likely to affect the clotting times and such changes should be avoided.
 
 
Pregnancy and Lupus
A question of concern to many families is whether or not a young woman with lupus should risk becoming pregnant.  The current general view is that there is no absolute reason why a woman with lupus should not get pregnant, unless she has moderate to severe organ involvement (i.e., central nervous system, kidney, or heart and lungs) which would place her (the mother) at risk.  However, there is some increased risk of disease activity during or immediately after (3 to 4 weeks) pregnancy.  If a person is monitored carefully, the danger can be minimized.  A pregnant woman with lupus should be closely followed by both her obstetrician and her "lupus doctor."  
 
As mentioned earlier in the brochure, a condition called the antiphospholipid syndrome can be secondary to lupus and complicates pregnancy.  Antibodies against specific antigens commonly present on coagulation factors can cause blood to clot faster than normal or in some cases, not at all.  Antigens on platelets can also result in an overall decrease in the total platelet count, a condition called thrombocytopenia. Antiphospholipid antibodies can be found in many patients with lupus and pose a particular risk to pregnant lupus patients since their presence is often associated with miscarriages.
 
 
Prognosis
The idea that lupus is generally a fatal disease is one of the gravest misconceptions about this illness.  In fact, the prognosis of lupus is much better today than ever before.  It is true that medical science has not yet developed a  way to cure lupus and some people do die from the disease.  However, with current methods of therapy, deaths from lupus are uncommon and people with non-organ threatening disease can look forward to a normal lifespan if they follow the instructions of their physician, take their medication(s) as prescribed, and know when to seek help for unexpected side effects of a medication or a new manifestation of their lupus.  Although some people with lupus have severe recurrent attacks and are frequently hospitalized, most people with lupus rarely require hospitalization.  There are many lupus patients who never have to be hospitalized, especially if they are careful and follow their physician's instructions.  
 
New research brings unexpected findings each year.  The progress made in treatment and diagnosis during the last decade has been greater than that made over the past 100 years.  It is therefore a sensible idea to maintain control of a disease that tomorrow may be curable.