Lupus

Lupus, or more specifically systemic lupus erythematosus, is a chronic inflammatory disease that may affect various parts of the body, especially the skin, joints, blood, and kidneys. Normally, the immune system produces antibodies to protect against viruses, bacteria and other foreign material. However, in lupus, the body’s own immune system abnormally produces antibodies against its own cells and tissues producing injury to tissue.

For most people, lupus is a mild disease affecting only a few organs. For others, more severe and even life-threatening complications may occur.. 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 main types of lupus: discoid, systemic, and drug-induced.

 

Discoid (cutaneous) lupus

Is always limited to the skin. It is identified by a typical rash that may appear on the face, neck, and scalp. Discoid lupus is diagnosed by biopsy of 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 “titer.”

In approximately 10 percent of patients, discoid lupus can evolve into the systemic form of the disease. This cannot be predicted and treatment of discoid lupus will not prevent its progression to the systemic form. Individuals who progress to the systemic form likely had the systemic form at the outset, with the discoid rash as their initial symptom.

 

Systemic lupus

Usually more severe than discoid lupus, and can affect almost any organ or body system. For some, 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 of remission and increased disease activity (“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 associated with drug-induced lupus are hydralazine (used to treat high blood pressure or hypertension) and procainamide (used to treat irregular heart rhythms). Drug induced lupus is more common in men given these medications. Most individuals taking these drugs will not develop drug-induced lupus. Generally, about 4 percent of those taking these drugs will develop the antibodies suggestive of lupus, and only an extremely small number of that 4 percent will develop overt drug-induced lupus. The symptoms usually fade with discontinuation of the medication.

Although drug-induced lupus and discoid lupus share features of systemic lupus, the rest of this brochure primarily discusses systemic lupus.

 

Symptoms

Although lupus can affect any part of the body, most people experience symptoms in only a few organs or body systems.

The following Table Of Symptoms lists the most common symptoms and their relative frequency

 

TABLE OF SYMPTOMS

Symptoms Occurrence
Achy joints (arthralgia) 95%
Fever more than 100 degrees F (38 degrees C) 90%
Arthritis (swollen 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%

 

Causes

The cause(s) of lupus is unknown, however it is thought to involved both environmental and genetic factors. Some 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 set of genes known to cause the illness. Only 10 percent of lupus patients will have a close relative (parent or sibling) with lupus or who may develop lupus. Statistics show that only about 5% of the children born to individuals with lupus will develop the illness.

Lupus occurs about 10-15 times more frequently in women than men. It can occur at any age, but is most common in women of childbearing age. People of African, American Indian, and Asian descent are thought to develop the disease more frequently than Caucasian women. The reasons for this ethnic predilection are not clear.

Hormonal factors may explain why lupus occurs more frequently in females than males. The increase of disease symptoms before menstrual periods and/or during pregnancy support the belief that hormones, particularly estrogen, may somewhat regulate the way the disease progresses. However, the exact reason for the greater prevalence of lupus in women, and the cyclic increase in symptoms, is unknown.

 

Diagnosis

Lupus may be difficult to diagnosis as often times symptoms are vague, may come and go and may mimic other conditions. Diagnosis is usually made after a thorough review of the medical history and physical exam coupled with analysis of blood and urine laboratory testing. Specialized immune blood testing is done to help confirm the diagnosis, however currently there is no single laboratory test that can determine whether a person has lupus or not.

The American College of Rheumatology (ACR) in 1987 issued a list of 11 symptoms or signs that help distinguish lupus from other diseases (see Table 2). This has recently been revised. An individual meeting at least 4 of these symptoms may be suspected of having lupus. The symptoms do not all have to occur at the same time.

 

THE ELEVEN CRITERIA USED FOR THE DIAGNOSIS OF LUPUS

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 Nonerosive 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 lung or heart)
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 Disorder Seizures (convulsions) and/or psychosis in the absence of drugs or metabolic disturbances which are known to cause such effects
Hematologic Disorder Hemolytic anemia or leukopenia (white blood count below 4,000 cells 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 Antibody Positive test for antinuclear antibodies (ANA) in the absence of drugs known to induce it.
Immunologic Disorder Positive anti-double stranded anti-DNA test, positive anti-Sm test, positive antiphospholipid antibody such as anticardiolipin, or false positive syphilis test (VDRL).

 

LABORATORY TESTS USED IN THE DIAGNOSIS OF LUPUS

Initial testing for lupus includes the antinuclear antibody (ANA) test which is positive in virtually all people with systemic lupus, and is the best diagnostic screening test for systemic lupus currently available. If the test is negative, the patient is likely not have systemic lupus. On the other hand, a positive ANA, by itself, is not diagnostic of lupus since the test may also be positive in individuals with:

  1. Other connective tissue diseases
  2. Without symptoms
  3. Being treated with certain drugs, including procainamide, hydralazine, isoniazid, and chlorpromazine
  4. 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.

Because it can be positive in conditions other than lupus, the results of the ANA test have to be interpreted in conjunction with 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 found in blood. A larger titer suggests a high antibody load. Lupus patients often have high titers, particularly due times of active disease or flares.

Other immune-based laboratory testing may be done to help confirm the diagnosis or check states of disease activity. Examples include

  • Complement levels – Considered an an “amplifier” of immune function. If the total blood complement level, C3 or C4 are low in an individual with 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 disease.
  • Other antibody testing – Positive testing for anti-DNA antibody, anti-Sm antibody, anti-RNP antibody, and anti-Ro antibody can further help suggest lupus.
  • Antiphospholipid antibodies – Such as anticardiolipin assay or lupus anticoagulant can add diagnostic specificity to lupus, or when occurring blood clots suggest the antiphospholipid syndrome. Presence of these antibodies in the absence of any abnormal clotting may require simple aspirin therapy to mildly thin the blood. However, evidence of abnormal blood clotting may require that the patient take a blood thinner like heparin and later warfarin to prevent blockage of small and large blood vessels. When blockage occurs in the lung or the brain it can be very serious.

 

Important laboratory and diagnostic considerations:

  • 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.
  • 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.

 

A kidney biopsy is sometimes required if urine or blood evaluations show evidence of kidney disease (ie. protein and blood). Kidney abnormalities vary with each patient. A biopsy can elude to the type and degree of kidney involvement by lupus, helping to tailor the specific therapy necessary.

Treatment

For the vast majority of people with lupus, effective treatment can minimize symptoms, reduce inflammation, and maintain normal bodily functions.

 

Preventive measures

May reduce the risk of flares and persistent disease. For photosensitive patients, avoidance of (excessive) sun exposure and/or the regular application of sunscreens will usually prevent rashes. Regular exercise helps prevent muscle weakness and fatigue. Immunizations protect against specific infections. Support groups, counseling, talking to family members, friends, and physicians can help alleviate the effects of stress.

Smoking, excessive consumption of alcohol, too much or too little of prescribed medication, or postponing regular medical checkups should be avoided.

 

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 ongoing medical supervision along with routine medical therapy is essential to for successful treatment and favorable outcomes.

 

Medications are often prescribed for people with lupus, depending on which organ(s) 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): Examples include acetylsalicylic acid (e.g., aspirin), ibuprofen (Motrin), naproxen (Naprosyn), indomethacin (Indocin), etc… These drugs are primarily recommended for muscle and joint pain, and arthritis. Side effect may include stomach irritation and reduced kidney function.

Acetaminophen: Acetaminophen (e.g., Tylenol) is a mild analgesic that can be used for pain. It has the advantage of less stomach irritation than NSAIDs, but it is not nearly as effective at suppressing inflammation.

Corticosteroids: Corticosteroids (steroids) are hormones that have anti-inflammatory and immunoregulatory properties. 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. It is important to address the side effects with your treating physician prior to starting the medication.

Antimalarials: Chloroquine (Aralen) or hydroxychloroquine (Plaquenil), commonly used in the treatment of malaria, may also be very useful in some individuals with lupus. They are most often prescribed for skin and joint symptoms of lupus.. Side effects are rare, and consist of occasional diarrhea or rashes.

Immunomodulating Drugs: Azathioprine (Imuran), mycophenolate (Cellcept) 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 cyclosporine are used to control the symptoms of lupus. Both are immunomodulating drugs which have their own side effects.

Belimumab (Benlysta): The newest medication approved for and indicated in the treatment of lupus. It is given intravenously. It targets a specific component of the immune system which is found to be overactive in lupus patients.

Anticoagulants: These drugs are employed to thin the blood or prevent blood from clotting rapidly. They range from aspirin at very low dose which prevents platelets from sticking, to heparin/coumadin which 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 thrombosis).

 

Patient with lupus should learn to recognize early symptoms of disease activity. 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, the earlier flares are detected, the more easily they can be controlled. Early treatment may decrease the chance of permanent tissue or organ damage and reduce the time one must remain on high doses of medications.

 

Pregnancy and Lupus

The general recommendation for a female with lupus is to cautiously plan a pregnancy. Recommendations to increase the chances of a healthy pregnancy includes timing the pregnancy during times of disease remission and close monitoring by both your rheumatologist and an obstetrician specializing in high risk pregnancies. One with active or prior severe organ involvement (i.e., central nervous system, kidney, or heart and lungs) may be at an increased risk of complications for both the mother and developing fetus. There is some increased risk of disease activity during or immediately after (3 to 4 weeks) pregnancy.

Antiphospholipid syndrome can similarly complicate pregnancy by causing miscarriages.

Some of the lupus medications can lead to fetal malformations. Please discuss all medications taken prior to and during pregnancy to ensure a healthy outcome and avoid a disease flare.

The decision and timing to get pregnant must be discussed in conjunction with your treating rheumatologist.

Prognosis

The prognosis of lupus is much better today than ever before. The key is early diagnosis and treatment by a qualified Rheumatologist that regularly sees Lupus patients. While no cure is currently available, the current methods of therapy frequently allow for patients to live long and healthy lives. Those with non-organ threatening disease can look forward to a normal lifespan if they follow the instructions of their physician, take their medications) 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 requiring hospitalization, most do not.