Diagnosis and Treatment

July 11th, 2008 by Cindy Owen

While currently there is no cure for lupus, early diagnosis and proper medical treatment can significantly help control the disease. In fact, for most people with lupus, effective treatment can minimize symptoms, reduce inflammation and pain, help maintain normal functions, and stop the development of serious complications.

Just as the symptoms of lupus vary from one individual to another, its treatment is tailored to the different specific problems that arise in each person. The physician will take into account the seriousness and severity of the symptoms and organs involved, the person’s response to treatment as well as her/his age, health, and lifestyle, and the types and risks of potential side effects from the drugs.

The Health Care Team

For mild cases of lupus, when there is little disease activity and no major organ involved, treatment may be managed by a primary care doctor, such as a pediatrician, for children and teens, a family practitioner, or an internal medicine physician, for adults. However, when lupus is active and the person needs to be watched for complications, he or she should be under the care of a specialist, usually a rheumatologist (a physician specially trained to treat musculoskeletal and joint disease).

If lupus has caused damage to a particular organ, other specialists will be consulted as well: a dermatologist for cutaneous lupus (skin disease), a cardiologist for heart disease, a nephrologist for kidney disease, a neurologist for nervous system involvement, and others as the clinical findings require. An obstetrician or perinatologist who specializes in high risk pregnancies will also be needed when a woman with lupus is considering a pregnancy.

Deciding Which Medications to Prescribe

Doctors use a variety of effective medicines to treat their patients. Some of the medications reduce inflammation which causes pain, fever and swelling, while others suppress the overactive immune system. They range in strength from mild to extremely potent, and often several of these medicines are used in combination to control the disease. However, all medications have side effects that need to be monitored.

Although most of the medicines discussed here have not been specifically approved for use in lupus, all appear to be safe and effective for the treatment of symptoms experienced by people with lupus, and have been successfully used for years by doctors in treating their lupus patients.

It is important to note that the medications chosen by physicians to treat lupus will be based on each person’s individual symptoms. These medications prescribed typically change during a person’s lifetime with lupus. It can take months, and sometimes years, before the health care team finds just the right combination of medicines to keep lupus under control.

The Best Approach to Taking Medications

Good communication between patient and doctor is essential to ensure effective management of the medicines that are prescribed. A very effective way to keep track of a complex disease like lupus is with a daily medical diary or journal. This can be kept by the patient or by a trusted family member or friend who can attend doctor appointments with the patient. Not only can details about medications, like dosage and side effects be recorded, but questions to ask the doctor can be written down to take to the next office visit.

The most important thing to remember, though, is that managing lupus is a team effort between patient and physician. And since there is often not only one but several physicians involved in the care of a person with lupus, good communication is necessary between members of the medical team as well.

How To Prepare For A Doctor's Appointment

In a scene from "Star Trek," Bones, the ship's physician, pulls a device from his pocket, scans his patient and within seconds pronounces the diagnosis. On the popular television series "ER," a patient is rolled into the emergency department while EMTs rattle off a litany of vital signs, history and medications and almost instantaneously the doctor diagnoses, simultaneously commencing treatment.

Neither demonstration accurately depicts the realities of medical diagnosis and treatment today; each ignores the primary element in any diagnosis: the telling of the patient's full story. Accurate diagnosis requires a conversation with the patient, thorough examination, and careful reflection on the facts -- all of which take time. The truth is, arriving at a diagnosis never happens as fast as it does on TV.

In today's managed care environment the time you spend face-to-face with your physician is limited. To get the most from your health care providers (HCPs) you'll need to meet them halfway, and preparation is the key. If you come prepared with the details and history of your problem, anticipate questions, know your medications, and bring medical records you increase the likelihood of an accurate diagnosis. And if you are anxious about doctor appointments, good preparation will go a long way to alleviate that anxiety. The following tips can help you make the most of your appointment.

Organize your history

What is the process of diagnosis? The majority is buried in the history -- a description of the problem. What "Star Trek" and "ER" fail to show is the process of sifting through that description to locate the nuggets of pertinent information. While it's true that additional information is gleaned from the physical exam, laboratory and imaging tests, it is the history that provides direction for the investigation. The more organized your presentation, the easier it will be for your HCP to arrive at a diagnosis. Keeping a journal of your symptoms may be helpful. If you feel it might be necessary, enlist a relative or friend to help you prepare and/or accompany you to the appointment. Physicians appreciate an accurate history whether it comes from the patient or someone who clearly knows the problem. (If someone does accompany you, be sure there's unified agreement to the story. Bickering in the exam room is counterproductive.)

In describing your problem, be specific. Telling the doctor you "feel ill" is not as helpful as, "I feel warm, ache all over, especially in my back, and I'm coughing up yellow stuff." Give as much information as you can. If you have more than one problem, talk first about the one that worries you the most. Prepare a separate history for each problem and strive to make it clear and complete. Present them one at a time so you don't confuse your HCP.

Anticipate what the doctor needs to know

Let's say that, for example, you have pain. (If you have more than one type of pain you may need to describe each pain separately.) You should be prepared to answer the following questions:

• Where is the pain most severe?
• When did it start?
• Does anything trigger it?
• Is there anything you could do to bring it on, make it better, make it worse?
• Is it present every day, or do you have pain free days?
• Is it worst in the morning, as the day goes on, or constant?
• On a scale of 1-10, how severe is the pain?
• Is it constant or off and on?
• Do you have any other symptoms with it, such as chest pain, shortness of breath?
• Does the pain stay in one area or spread to other areas?
• Does it interfere with your daily routine?
• What has been its course? (Is it stable, or getting worse?)
• Is this a new symptom or a recurrence of a previous problem?

These questions apply to most problems or symptoms. If you've thought about how you would answer them ahead of time you'll be prepared, your response time will be shortened and this may leave more time to discuss your concerns before the end of the appointment.

Know your medications

Another aspect of preparation is knowing what medications you take. Although you may recognize your pill as "the little blue one," there are probably hundreds of pills that are little and blue. The likelihood of your doctor being able to identify your blue pill is slim. Put ALL your medications -- prescription, non-prescription, vitamins, herbs, minerals, each in its original container -- in a bag and take them with you to your appointment. This way the doctor will know the medication, dosage, frequency and your need for refills. If you take medications chronically, keep an updated card in your wallet or purse with the names of the drugs, dosage and frequency. This is important if drug interactions are to be avoided. It's not uncommon for patients to be seen by several specialists each of whom prescribes different medications. Each doctor needs to know what drugs you are taking, including those prescribed by other physicians. They assume you will be able to list all medications you currently take. If you can't tell them, you may put yourself at risk.

Medical records

If you have any copies of medical records from other physicians bring them with you. Also bring X-rays or MRI's with you if appropriate. If you are being referred by another physician, try to expedite the exchange of medical records. Very often, you'll need to consent to your records being released to the new physician. Not every doctor's office will anticipate this or contact you beforehand to arrange for the transfer of records. To make the most of the appointment, call ahead and ask how these arrangements should be made. A transfer of your records may help you avoid repeat diagnostic tests which carry their own risk and expense. Also, if your H.M.O. (health maintenance organization) allows a consultation with a specialist, your first visit may be your only one with that doctor, so it helps to be as prepared as possible.

Request a verbal summary

In the stressed and compressed time of a doctor's appointment it's very common for communication to be impaired. A recent survey of how much patients recalled following a general exam revealed that most could not remember more than of the medical problems their doctor diagnosed! Would you consult your banker, tax preparer or clergyman and leave the meeting without making sure you understood what was discussed? While many HCPs are aware of the need to restate treatment plans or medication adjustments, others may not do so. Sometimes time restrictions decrease the amount of verbal reinforcement the doctor can offer. Ask for a brief summary to make sure all points are covered and necessary prescriptions filled out. Ask what kind of follow-up is needed. Be prepared to take notes.

Questions you should ask during a visit with your HCP:

• What is this problem likely to be, among the possibilities?
• Is further diagnostic evaluation necessary?
• What can I expect from the natural course of this problem?
• Is there treatment available to modify the course?
• How long before I should see the effects of the medication?
• Under what circumstances should I notify the doctor?

If your expectation is that all you have to do is show up for an appointment and the doctor will do the rest, your visit is likely to be a frustrating one, and you may put yourself at risk for misdiagnosis. Remember, unlike "Bones," your doctors don't have scanners they can pull out of their pockets to miraculously diagnose your problem. They need your help. The doctor's appointment is your opportunity to discuss medical problems and concerns. By preparing for the appointment you will be less likely to waste the opportunity, and more likely to gain a degree of satisfaction from the visit.

Laboratory Tests

Symptoms, Signs and Tests

Because many symptoms of systemic lupus erythematosus (SLE) mimic those of other illnesses, lupus can be a difficult disease to diagnose. Diagnosis is usually made by a careful review of three factors:

• the individual's entire medical history
• an analysis of the results obtained in routine laboratory tests and
• some specialized tests related to immune status.

To make a diagnosis of SLE, an individual must show clinical evidence of a multi-system disease (i.e. has shown abnormalities in several different organ systems). Typical symptoms or signs that might lead to suspicion of SLE are:

Skin: Butterfly rash across the cheeks; ulcers in the mouth; hair loss.
Joints: Pain; redness, swelling.
Kidney: Abnormal urinalysis suggesting kidney disease.
Lining membranes: Pleurisy (inflammation of the lining of the lung); pericarditis (inflammation of the heart lining); and/or peritonitis (inflammation around the abdomen). Taken together, these types of inflammation are known as polyserositis.
Blood: Hemolytic anemia (the red cells are destroyed by autoantibodies); leukopenia (low white blood cell count); thrombocytopenia (low number of platelets).
Lungs: Infiltrates (shadowy areas seen on a chest x-ray) that come and go
Nervous system: Convulsions (seizures); psychosis; nerve abnormalities that cause strange sensations or alter muscular control or strength.

If an individual has several of these symptoms, the physician will then usually order a series of tests to examine how well the individual's immune system is functioning. In general, physicians look for evidence of autoantibodies. Although there is no one test that can definitely say whether or not a person has lupus, there are many laboratory tests which aid the physician in making a lupus diagnosis.

Routine clinical tests which suggest that the person has an active systemic disease include:

• sedimentation rate (ESR) and CRP (C-reactive protein) binding, both of which are frequently elevated in inflammation from any cause
• serum protein electrophoresis which may reveal increased gammaglobulin and decreased albumin
• routine blood counts which may reveal anemia and low platelet and white cell counts
• routine chemistry panels which may reveal
  • kidney involvement by increases in serum blood urea nitrogen and creatinine
  • abnormalities of liver function tests
  • increased muscle enzymes (such as CPK) if muscle involvement is present.

These kinds of abnormalities alert the doctor to the presence of a systemic disease with multiple organ involvement.

Commonly used blood tests in the diagnosis of SLE are:

• Anti-nuclear antibody test (ANA) to determine if autoantibodies to cell nuclei are present in the blood
• Anti-DNA antibody test to determine if there are antibodies to the genetic material in the cell
• Anti-Sm antibody test to determine if there are antibodies to Sm, which is a ribonucleoprotein found in the cell nucleus
• Serum (blood) complement test to examine the total level of a group of proteins which can be consumed in immune reactions
• Complement proteins C3 and C4 test to examine specific levels

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The Antinuclear Antibody (ANA or FANA) Test

Positive ANA
The immunofluorescent antinuclear antibody (ANA or FANA) test is positive in almost all individuals with systemic lupus (97 percent), and is the most sensitive diagnostic test currently available for confirming the diagnosis of systemic lupus when accompanied by typical clinical findings. When three or more typical clinical features are present, such as skin, joint, kidney, pleural, pericardial, hematological, or central nervous system findings as described above, a positive ANA test confirms the diagnosis of systemic lupus.

However, a positive ANA test, by itself, is not proof of lupus since the test may also be positive in:

1. other connective tissue diseases, such as:
   • scleroderma
   • Sjogren's syndrome
   • rheumatoid arthritis
   • thyroid disease
   • liver disease
   • juvenile arthritis
2. individuals being treated with certain drugs, including:
   • procainamide
   • hydralazine
   • isoniazid
   • chlorpromazine
3. viral illnesses, such as:
   • infectious mononucleosis
4. other chronic infectious diseases, such as:
   • hepatitis
   • lepromatous leprosy
   • subacute bacterial endocarditis
   • malaria
5. other autoimmune diseases, including:
   • thyroiditis
   • multiple sclerosis
6. as many as 30-40 percent of asymptomatic first-degree relatives of people with lupus (siblings, parents, and children).

Weakly positive ANA
The test can even be weakly positive in about 20 percent of healthy individuals. While a few of these healthy people may eventually develop lupus symptoms, the majority will never develop any signs of lupus or related conditions. The chances of a person having a positive ANA test increases as he or she ages.

Negative ANA
A negative ANA test is strong evidence against lupus as the cause of a person's illness, although there are very infrequent instances where SLE is present without detectable antinuclear antibodies. ANA-negative lupus can be found in people who have anti-Ro (SSA) or antiphospholipid antibodies.

ANA Titers and Patterns
ANA laboratory reports include a titer (pronounced TY-tur) and a pattern.

• The titer indicates how many times the lab technician had to dilute plasma from the blood to get a sample free of the antinuclear antibodies.
  • For example, a titer of 1:640 shows a greater concentration of anti-nuclear antibodies than a titer of 1:320 or 1:160.
• The apparent great difference between various titers can be misleading.
  • Since each dilution involves doubling the amount of test fluid, it is not surprising that titer numbers increase rather rapidly.
  • In actuality, the difference between a 1:160 titer and a 1:320 titer is only a single dilution. This does not necessarily represent a major difference in disease activity.
  • ANA titers go up and down during the course of the disease, and a high or low titer does not necessarily mean the disease is more or less active.
  • Therefore, it is not always possible to determine the activity of the disease from the ANA titer.
  • A titer above 1:80 is usually considered positive.
  • Some laboratories may interpret different titer levels as positive, so one cannot compare titers from different laboratories.
    
    
• The pattern of the ANA test can sometimes be helpful in determining which autoimmune disease is present and which treatment program is appropriate.
  • The homogeneous, or smooth pattern is found in a variety of connective tissue diseases, as well as in people taking particular drugs, such as certain antiarrhythmics, anticonvulsants or antihypertensives.
  • This homogenous pattern is also the one most commonly seen in healthy individuals who have positive ANA tests.
  • The speckled pattern is found in SLE and other connective tissue diseases
  • The peripheral, or rim pattern is found almost exclusively in SLE.
  • The nucleolar pattern, with a few large spots, is found primarily in people who have scleroderma.

Because the ANA is positive in so many conditions, the results of the ANA test have to be interpreted in light of the person's medical history, as well as his or her clinical symptoms. Thus, a positive ANA alone is never enough to diagnose lupus. On the other hand, a negative ANA argues against lupus but does not rule out the disease completely.

A Positive ANA Does Not Equate to Having a Disease
The ANA should be looked at as a screening test. If it is positive in a person who is not feeling well and who has other symptoms or signs of lupus, the physician will probably want to conduct further tests for lupus.

If the ANA is positive in a person who is feeling well and in whom there are no other signs of lupus, it can be ignored. If there is any doubt, a consultation with a rheumatologist should clarify the situation.

Other Autoantibodies

In those individuals with a positive ANA, additional tests can be done for certain particular antibodies that may better establish a diagnosis of SLE. The knowledge of which particular antibody is responsible for the positive ANA test can sometimes be helpful in determining which autoimmune disease is present.

• Antibodies to DNA (the protein that makes up the body's genetic code) are found primarily in SLE.
• Antibodies to histones (DNA packaging proteins) are usually found in people with drug-induced lupus (DIL), but may also be found in those with SLE.
• Antibodies to the Sm antigen are found almost exclusively in lupus, and often help to confirm the diagnosis of SLE.
• Antibodies to RNP (ribonucleoprotein) are found in a number of connective tissue diseases. When present in very high levels, RNP antibodies are suggestive of mixed connective tissue disease (MCTD), a condition with symptoms like those of SLE, polymyositis, and scleroderma.
• Antibodies to Ro/SS-A are found in people with either lupus or Sjogren's syndrome, and are almost always found in babies who are born with neonatal lupus.
• Antibodies to Jo-1 are associated with polymyositis.
• Antibodies to PM-Scl are associated with certain cases of polymyositis that also have features of scleroderma.
• Antibodies to Scl-70 are found in people with a generalized form of scleroderma.
• Antibodies to the centromere (a structure involved in cell division) are found in people with a limited form of scleroderma which tends to have a chronic course.

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Complement

Laboratory tests which measure complement levels in the blood may also be helpful to the physician in making a diagnosis of SLE.

• Complement is a blood protein that destroys bacteria and also influences inflammation.
• Complement proteins are identified by the letter "C" and a number.
• The most common complement tests are C3, C4, and CH50.

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 a positive ANA may signify the presence of active disease, especially kidney disease.

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Biopsy

Sometimes examination of a tissue sample (biopsy) can be helpful in making a diagnosis. The biopsy is one of the best ways to evaluate an organ or tissue. The procedure involves removal of a small sliver of tissue, which is then examined under a microscope.

• The doctor can use the biopsy to identify the amount of inflammation and damage to the tissue.
• Further tests can be performed on the specimen to determine whether the problem is due to lupus or is caused by some other factor such as infection or medication.
• Almost any tissue can be biopsied. The most common sites biopsied in lupus are the skin and kidney.
• The results of the biopsy, like any other laboratory test, should be examined in combination with the individual's medical history and clinical findings.

Tests to Assess Disease Activity

When a person diagnosed with lupus develops new or recurring symptoms, laboratory testing of blood or urine can help determine if the symptoms are due to an increase in lupus activity.

Disease activity correlates with a rise in:

• CRP (C-reactive protein) binding
• ESR, or sedimentation rate
• Anti-DNA
• Liver and kidney function tests (AST, ALT, BUN, creatinine)
• CPK (muscle enzyme)
• Urine protein or cellular casts

Disease activity also correlates with a fall in:

• CBC or complete blood count (white blood cell count, hemoglobin, platelets)
• Complement components
• Serum albumin

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Putting It All Together

The interpretation of all these tests, and their relationship to symptoms, can be difficult. When a person has many symptoms and signs of lupus and has positive tests for lupus, it is easier for physicians to make a correct diagnosis and begin treatment. However it is more common for an individual to report vague, seemingly unrelated symptoms of achy joints, fever, fatigue, or pain, and to have negative or borderline test results.

Fortunately, with growing awareness of SLE, an increasing number of physicians will consider the possibility of lupus in the diagnosis. While these tests are useful only when their strengths and limitations are understood, in the hands of skilled physicians these are important tools that assist in diagnosing lupus.