Date: Fri, 16 Jun 2000

From: USSW

Dear People.,,

Do you think Mayo clinic can diagnose lupus w/just a low C4 complement andsome abnormal Ch50's and Ch100's?

Plus the symptoms of lupus (arthralgia, fibromyalgia, hair loss, sychosis,ibs, tmj, dry eyes but not Sjgorgen's) etc.? and acid reflux disease,carpal tunnel Can lupus be that hard to diagnose?

I have been to :endocriniologist, neursurgeon, neurologist, gastroenterologist and many times to reg. doctors.

Also (one time) I had a sedimentation rate of 53 (would that be cuased by a pregnancy ) or a flare up?

Having lots of hypothyroid type symptoms (many low T3's and high T4's ( or vice versa).. please answer asap... I am due to fly out Thurs !

Have heard former implant ladies don't fair well @ Mayo as far as diagnosing?

Would they truly discriminate because Dow and Plastic Surgeons help fund them (dont' bit e hand that feeds you) ?

Sincerely,

Brenda 

Could you tell me where to get info from FDA regarding copper bracelets etc. being approved for medicinal purposes and other alternative treatments for lupus (incase I don't ever get a formal diagnosis) cause this shit will kill someone..

thanks and happy holydays 

Dear Brenda,

Yes, lupus is typically a very difficult disease to diagnose. The article enclosed at the end of this email discusses the difficulties of diagnosing lupus. I've also enclosed two articles to help you understand laboratory tests. If you haven't already done so, visit our "Living With Lupus" website (http://www.lupus.org/lupus ) and go to the COMMONLY ASKED QUESTIONS section. I believe you'll find questions 11 - 13 helpful in furthering your understanding of the complexities of diagnosing this disease.

A positive ANA by itself is not proof of lupus. If you do not satisfy at least four criteria, it is unlikely you have lupus at this time. Many or even most people who have just a few criterion for lupus never develop this or other connective tissue disease, and either get better or continue as they are.

Learn the signs and symptoms of lupus so that if you develop something new, you can tell your doctor so s/he can determine if you have satisfied enough criteria for a diagnosis.

The sedimentation rate, can be influenced by a number of different things. It can be elevated due to:

-anemia

-hypercholesterolemia

-female sex

-pregnancy

-high room temperature

-inflammatory disease

-chronic renal failure

-obesity

-heparin

-tissue damage

(This list was excerpted from the textbook Rheumatology, by Klippel. Fig. 1.20)

Thyroid disease can occur in lupus, and information is included in a separate email which follows this one.

If after reading the information on our website and the articles enclosed ou have further questions, please feel free to contact us.

Patricia Leisy

Online Health Educator

1300 Piccard Drive, Suite 200

Rockville, MD 20850

U.S.A.

301-670-9292

800-558-0121 (24 hour answering machine)

article follows

DIAGNOSIS CAN BE DIFFICULT

A selection from the Lupus Foundation of America Newsletter Article Library Approved LFA Patient Education Committee

92-035

Research focusing on the nature of lupus (SLE) has accelerated sharply over the past twenty years. It is believed that the symptoms of lupus are the result of an abnormally functioning immune system. What causes the malfunction is not yet known. The normal immune system functions to protect the body against damage by viruses, bacteria and other foreign substances. In lupus, this same immune system appears to react against the body's own healthy

cells forming antibodies against them. This causes inflammation and the subsequent symptoms of the disease. Since the immune system functions throughout the body, the symptoms of lupus can vary widely in type and intensity, depending on the parts of the body being affected.

Most people involved in lupus research and treatment would probably agree that lupus still remains a difficult disease to diagnose. Two reasons account for this difficulty. First, there is no single set of symptoms that are uniformly specific to lupus. Second, there are no laboratory tests yet available that can prove conclusively that a person has or does not have lupus.

Almost every symptom of lupus can also be easily attributed to other illnesses or disorders. In addition, the symptoms are sometimes vague or they may come and go spontaneously. For instance, fever, weight loss, marked fatigue and weakness which are often experienced by someone with lupus, may also be symptoms of many others disorders, some more threatening, some less so. Likewise if transient joint or muscle pain are the initial problems, here again there are so many causes of such symptoms it may be very difficult to link these to lupus. If pleurisy is a symptom and it spontaneously clears up rather quickly, the physician may assume that a virus was the cause and not necessarily lupus.

The diagnosis of lupus is usually made after a careful review of the patients's medical history, coupled with analysis of blood study results from both routine laboratory testing and some specialized tests related to immune system status. Since symptoms may present themselves slowly and may evolve over months or years, it is important that a physician follow the patient to see what happens. Often it can take years for the diagnosis to be made. This can be a very difficult time for the person seeking relief from numerous symptoms. Only by a comprehensive examination can the probability of lupus be assessed and even then it is sometimes very difficult to be sure. 

The first principle in making a diagnosis of SLE is that the individual has clinical evidence of a multi-system disease (i.e. has shown abnormalities in several different organ systems). The following are typical manifestations which might lead to suspicion of SLE.

Skin: butterfly rash; ulcers in the roof of the mouth; hair loss.

Joints: pain; redness and swelling.

Kidney: abnormal urinanalysis suggesting kidney disease.

Lining membranes: pleurisy; peri-carditis and/or peritonitis (taken together this type of inflammation is known as polyserositis). Blood: hemolytic anemia (the red cells are destroyed by autoantibodies); leukopenia (low white blood cell count); thrombocytopenia (low platelets).

Lungs: infiltrates that may be transient.

Nervous system: convulsions; psychosis; nerve abnormalities that cause strange sensations or alter muscular ability.

The second diagnostic principle is to examine the status of the immune system in individuals having a sus-picious clinical history. In general, physicians now look for evidence of autoantibodies. At this time some commonly used tests of immune status in the diagnosis of SLE are:

1) The anti-nuclear antibody test (ANA): a test to determine if

autoantibodies to cell nuclei are present in the blood.

2) The anti-DNA antibody test: to determine if the patient has antibodies to the genetic material in the cell.

3) The anti-Sm antibody test: to determine if there are antibodies to this substance, a nuclear protein.

4) A variety of tests for the presence of immune complexes in the blood.

5) Tests to examine the total level of serum complement - a group of proteins involved in the inflammation which can occur in immune reactions - and tests to assess the specific level of C3 and C4, two proteins of this group.

6) LE cell prep: An examination of the blood looking for a certain kind of cell which has ingested the swollen antibody-coated nucleus of another cell.

A positive ANA may occur sometime during the course of the illness in about 90 percent of patients with SLE, but it also occurs in a variety of other illnesses and in as much as 5 percent of the normal population. It is a very sensitive test and is now more frequently performed than the LE prep.Sometimes examination of a tissue sample can be helpful in making the diagnosis. A kidney biopsy, for example, can show certain changes characteristic of SLE if the kidney disease is severe. Even in early kidney involvement, examination of biopsy tissue can show deposits of antibodies and immune complexes in the kidney's filtration unit.

A skin biopsy can be helpful in identifying deposits of antibodies and complement proteins found at the junction of the outer skin layer, called the epidermis, and the underlying part of the skin, the dermis. A "positive band test" is significant only when the tissue sample is taken from an area which is not involved by the rash. The results, like those of a kidney biopsy, should be interpreted in combination with the clinical history, as well as all the other tests performed.

In 1982, the American Rheumatism Association published a revised set of criteria to aid physicians in making the diagnosis of Lupus. The new criteria are:

- Malar Rash

- Discoid Rash

- Photosensitivity

- Oral Ulcers

- Arthritis

- Serositis

- Renal disorder

- Neurologic disorder

- Hematological disorder

- Immunologic disorder

- Positive FANA test result

A physician observing a person to have at least 4 out of the 11 criteria, either serially or collectively, should be suspicious to the possibility of lupus being the underlying disorder. However, physicians must also be

Careful in utilizing criteria for an individual case, as other diseases could also conform to the criteria. Presently, the diagnosis of lupus is usually based on these findings:

1) evidence of a multi-system disease (more than one organ involved):

2) the presence of autoantibodies;

3) the exclusion of other diseases and disorders which can mimic the features of lupus.

Despite advances in medical education and technology it is still not uncommon for lupus to be incorrectly diagnosed or require a lengthy period of time to be diagnosed mainly because the symptoms vary so widely, come and go frequently, and because the disease mimics so many other disorders.

An important fact to remember concerning the treatment for lupus is that the diagnosis does not indicate the particular therapy to be used. In the absence of a cure, present-day treatment of lupus is still primarily tailored to symptomatic relief and not to the diagnosis. 

UNDERSTANDING YOUR LABORATORY TESTS

Chaim M. Brickman, M.D.

Director, Lupus Program of Sinai Hospital, Detroit, MI

Teresa H. Doyle, M.S.N., R.N., C.

A selection from the Lupus Foundation of America Newsletter Article library

LFA Patient Education Committee

Approved 92-050

"WHAT DO MY BLOOD TESTS AND URINE TESTS TELL ME ABOUT MY LUPUS?"

Someone asks us this question nearly every day, and we're always glad to answer. We believe that you contribute to your health and well- being when you understand the basics about your illness and your laboratory tests. This article will discuss some of the tests commonly used in the diagnosis and treatment of lupus.

Lupus and the Process of Inflammation

The immune system is designed to protect the body from harmful invaders such as bacteria, viruses, and other "foreign" matter. It does this through a process called inflammation in which the body destroys foreign matter which doesn't belong. We can often tell that there is inflammation in some parts of the body. For example, an inflamed joint readily shows the 'cardinal signs' of inflammation: warmth, redness, swelling and pain that make it difficult to use that body area. Inflammation in another body part such as the kidney may cause few, if any, of these signs early in the inflammation process. An experienced physician using the correct methods--history and physical exam, x- ray, lab tests and others--is able to detect, and treat, this type of inflammation.

Lupus is an inflammatory condition in which the immune system loses its ability to tell the difference between "self" (things that belong in the body). As a result of this confusion, the lupus patient's immune system attacks its own tissues causing wide spread inflammation. Unfortunately, doctors do not have all the answers needed for the cure and prevention of lupus. However, we can identify lupus earlier than ever before, thereby preventing many of its ill effects. Proper use of diagnostic tests-- especially selected tests of the blood and urine-- makes it possible to monitor the disease and its treatment more effectively than ever before.

The Complete Blood Count (CBC) and Differential

Blood consists of two elements which may be tested by your physician: (1) the fluid portion (which is known as plasma or serum) contains many dis-solved proteins such as antibodies and complement and (2) the cell portion which is studied in the CBC. The CBC test includes the number of red blood cells, white blood cells and platelets--all of which can be affected by lupus. This group of tests enables the doctor to monitor important effects of the lupus as well as the body's ability to support basic functions such as oxygen delivery, blood clotting and protection from infection. Red Blood Cells (RBC) - These donut-shaped cells carry hemoglobin, the chemical that transport oxygen from the lungs to all tissues. Special tests tell how many RBC's there are as well as how much hemoglobin they contain. The terms hemoglobin, RBC, and hematocrit all relate to the specific number of RBC's in the blood.

Platelets - Part of the complex mechanism for clotting blood, these cells may increase in numbers when there is active inflammation. Low Platelet counts are occasionally seen in lupus and could lead to unusual bleeding episodes . White Blood Cells (WBC) - The doctor can request a differential, a count of the various kinds of WBC. Among others they include:

Neutrophils: First line of protection in infection. Present early in most inflammation. Also referred to as polys or segs.

Lymphocytes: Major police force in the body.

Includes:

T lymphocytes, which direct the inflammatory attack using information supplied by monocytes.

B lymphocytes, which produce the antibodies that actually attack the invaders or--in lupus--self. Monocytes - Detect foreign materials in the body and alert the rest of the immune system about the 'invasion'. Also known as the mono.

In lupus a person's immune system can attack any of the components of the blood. This an cause anemia (low red blood cell count, thrombocytopenia (low platelet count) or leukopenia (low white count leading to a tendency to develop infections). Keep in mind that there can be many others causes of these conditions as well.

Antinuclear Antibody (ANA)

This phrase literally means "substance against the cell nucleus." Since the nucleus is the "headquarters" of the living cell, the ANA can actually damage or even destroy cells and tissues. ANA reports include a number (or titer) and a pattern. The titer tells us how many times the technician had to mix fluid from the patient's blood to get a sample free of ANA's. Thus, a titer of 1:640 shows a greater concentration of ANA than 1:320 or 1:160, since it took 640 dilutions of the plasma before the ANA was no longer detected. 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 titers increase rather rapidly. In actuality, the difference between a 1:160 titer and a 1:320 titer is but 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 the titer may or may not reflect disease activity. Therefore, it is not always possible to tell from the titer the severity of a person's lupus. A titer 1:80 or below is usually considered "negative" or not present.

The ANA pattern is studied by microscope. The technician examines a specially-prepared slide that shows where antibodies attack the nucleus. Certain antibodies attack certain areas of the nucleus, producing four specific patterns. The rim (peripheral) pattern is the most specific pattern for lupus while the homogeneous (diffuse) pattern is the most common pattern seen. The remaining patterns are the speckled and nucleolar patterns. In some cases the pattern helps the doctor decide which of the autoimmune diseases is causing the problem and which treatment program is appropriate.

VDRL

Sometimes the antibodies produced in lupus interact with chemicals used to test for other diseases. One test for syphilis, the VDRL, sometimes becomes falsely positive for this reason. In this case, the VDRL does not mean that person has syphilis; instead it aids in diagnosing lupus. Just to make sure,another more specific syphilis test is used to confirm the doctor's suspicions.

Complement

The blood also contains proteins known as complement proteins, used by the immune system as 'ammunition' for destroying the cells that it has identified as "enemies". When inflammation is very active, the complement is used up, resulting in lower blood levels. Determination of complement levels hereforehelps the doctor evaluate the intensity of the inflammation. Complementproteins are identified by the letter 'C' and a number. The most frequently studied complement tests are C3, C4, and CH50.

Urine Tests

Urinalysis, the urine test most commonly requested, enables the doctor to evaluate the effects of infection, lupus or medications on the kidneys.

The job of the kidney is to rid the body of unneeded waste material. If the kidney becomes inflamed, it may become ineffective. RBC's, WBC's, and proteins such as albumin may pass through the filtering system into the urine; or they may stay in the kidney for a while before being released as "casts" of certain kidney areas. If a urinary tract infection is suspected the physician may request a culture and sensitivity in order to help him decide which antibiotic would be most effective.

If considerable protein is found in the urine, the doctor will order a 24-hour collection to determine how much is being lost in one day. At the same time a creatinine is done to determine how well the kidney is working.

Biopsy

The biopsy is one of the best ways to evaluate an organ or tissue. The procedure involves removal of a small sliver of tissue, followed by examination under the microscope. The biopsy enables the doctor to identify >the amount of inflammation and damage to the tissue. Furthermore, tests can be performed on the specimen in order to determine whether the problem is due to lupus or due to some other factor such as infection, medication, etc. Just about any tissue can be biopsied; the most common sites biopsied are skin and kidney.

Anti-Phospholipid/Anti-Cardiolipin Antibodies

Approximately 30-50% of lupus patients have antibodies in their blood directed against certain chemicals in their body known as phospholipids. One type of phospholipid is called cardiolipid because it is found in many tissues including heart (cardiac) tissue. Patients with these antibodies may have abnormal laboratory tests for clotting (called PT and PTT tests). Some patients with these antibodies may develop clotting problems, problems with recurrent loss of pregnancies, false positive VDRL tests (see VDRL above) or heart valve problems.

In Conclusion

We are often asked why many of the above tests are performed even when the patient feels fine. Experience has shown that lupus activity is often not recognized by the patient; laboratory tests can warn of problems that are unfelt or are still rather small. Since most patients with lupus take medication, the doctor must monitor the effects of these medications by means of specific blood tests. Finally, laboratory testing has an important role in the detection, treatment, and monitoring of lupus and related conditions. However, it is not the only available technique. Laboratory data supplements other information obtained via the medical history, the physical examination and other diagnostic tests. If you do not understand the meaning of any of your laboratory tests, ask your doctor. A well-informed patient is better able to make good health decisions and to cooperate in a safe, health-enhancing treatment program.

INTERPRETATION OF LABORATORY TESTS

Peter H. Schur, M.D.

Professor of Medicine, Harvard Medical School Director, Lupus Clinic, Lupus Research Lab, Clinical Immunology Lab Brigham & Women's Hospital, Boston, MA

A selection from the Lupus Foundation of America Newsletter Article Library (originally appeared in Lupus News, Volume 10, Number 3)

LFA Patient Education Committee

Approved

92-037 

Many tests are done on patients with suspected lupus in order to establish a diagnosis. In patients with systemic lupus erythematosus (SLE), tests are performed to determine which organs are involved, to what extent, and also to determine the degree of activity of the lupus.

Diagnosis

1. Anti-nuclear antibody tests (ANA, ANF): This test determines whether a patient has antibodies to the nuclear portion of cells. As a source of nuclei one uses either a cell line (called Hep-2) or micro-thin sections of rat or mouse liver or kidney. The reaction is examined under a microscope. If the reaction is positive, serial dilutions are made of sera. The last dilution of serum still giving a positive reaction is referred to as the titer (e.g., 1/10, 1/40, 1/160, etc.) Only 14 of 10,000 SLE cases have a negative ANA test. Thus over 99% of SLE patients have a positive ANA test. Only 1 of three people with a positive ANA test done with rodent tissue have SLE - the higher the titer the more likely one has SLE. Only 1 of six people with a positive ANA using Hep-2 cells have SLE - the higher the titer the more likely one has SLE.Because of variation in technique, results (e.g. titer) may vary from lab to lab - even negative and positive.

2. Anti-double-stranded DNA antibody (anti- DNA, anti-dsDNA): This test is performed in different labs by different techniques called radioimmunoassay (RIA, Farr), Crithidia, or enzyme immunoassay (EIA, ELISA). Each lab determines a range of units observed in normals; anything above this range is considered abnormal or positive.

About 75% of patients with SLE have antibodies to dsDNA.

About 95% of patients with antibodies to dsDNA have SLE.

3. Anti-Sm antibody (Anti-Smith): Anti-Sm antibodies recognize a unique nuclear RNA- protein complex. This test is performed by either hemagglutination (resulting in a titer), counterimmunoelectrophoresis (usually listed as positive or negative - occasionally as a titer), and most recently by EIA (ELISA) - and reported usually as positive or negative.

About 25% of patients with SLE have anti-Sm.

Between 75 and 95% of patients with anti-Sm have SLE.

4. Anti-RNP (anti-U1-RNP): Anti-RNP antibodies recognize another unique nuclear RNA-protein complex. This test is performed in a fashion similar to anti-Sm.

About 40% of patients with SLE have anti-RNP.

About 50% of patients with anti-RNP have SLE; others may have MCTD (mixed connective tissue disease), scleroderma, rheumatoid arthritis, Sjogren's syndrome, or related forms of undifferentiated forms of connective tissue disorders.

5. Anti-Ro (SS-A): Anti-Ro antibodies recognize another unique nuclear RNA- protein complex. This test is performed by counter immunoelectro phoresis or EIA.

About 40% of patients with SLE have anti-Ro.

If a patient has anti-Ro one generally considers that the patient has either SLE, Sjogren's syndrome, or photosensitivity.

6. Ant-La (SS-B): Anti-La antibodies recognize another unique RNA-protein complex. This test is performed in a manner similar to anti-Ro.

About 30% of SLE patients have anti- La.

If a patient has anti-La one considers SLE or Sjogren's syndrome.

As different labs use different methods for detecting anti-Sm, RNP, Ro and La, results may vary from lab to lab. Furthermore, results of these tests, as well as all others mentioned here, vary over time.

7. Complement (CH50, C4, C3): The complement system represents a group of over 20 serum proteins that are activated by reacting with antibodies and then interact to cause inflamma tion. Thus low levels of complement reflect active disease. The total complement system (CH50) is measured by a hemolytic technique (the release of hemoglobin from specially sensitized sheep red blood cells); C4, and C3 (two of the more important components) are measured by immunodiffusion (reaction of antibody and antigen in agar (a semi- solid medium) - quantitation is determined by the size of a ring of nephelometry (reaction of antibody and antigen in a fluid) - quantitation is determined by optical density). Because of some variations in technique, each laboratory has estab lished a normal range. A low CH50, C4, or C3 level in conjunction with a positive ANA test is highly suggestive but not diagnostic for SLE.

8. CBC (Complete Blood Count): Con sisting of a white blood cell count (wbc), hemoglobin (Hgb), hematocrit (Hct) and platelet count is usually per formed on an automated machine. The normal range is very well standardized internationally. Low levels of any of these counts in the presence of a positive ANA test are highly suggestive of lupus.

Laboratory Tests for the Assessment of Activity of Lupus

1. ANA: Generally speaking if an ANA titer rises (at least four dilutions) it suggests that the lupus may be more active.

2. Anti-DNA: rising titers of anti-DNA are moderately strong indicators that the lupus is becoming more active.

3. Anti-Sm, RNP, Ro, La: there is no evidence that titers (levels) correlate with lupus activity.

4. Complement: Falling (or just low levels) suggest active lupus.

5. CBC: Falling levels of a wbc, Hgb (or Hct), or platelet count suggest active lupus - but other causes (viz. drugs, intestinal bleeding) should be excluded. An elevated wbc suggests either infection or taking moderate to high doses of Prednisone.

6. Kidney: increasing amounts of protein, rbc, wbc, or a falling GFR re flect worsening kidney function, which may be due to lupus. Often a kidney biopsy needs to be performed to distinguish lupus nephritis from other causes of nephritis.

7. Brain: a worsening MRI or EEG sug gests lupus (or other) brain involvement.

Miscellaneous:

1. Anti-cardiolipin antibodies (anti- phospholipid antibodies): This test is either performed as an EIA or as a modified prothrombin time (a blood coagulation test). Very high (but not minimally elevated) levels are associated with phlebitis, small strokes, blood vessel occlusions, low platelet counts, and recurrent miscarriages in the 2nd trimester.

Assessing Organ Involvement

1. Kidney Function Tests

a). Urinalysis: Urine is examined both by dipsticks and microscopically. Normal urine contains no protein, sugar, but may contain up to 5 red blood cells (5 rbc/hpf) or 5 white blood cells (5 wbc/hpf). Presence of protein or more cells suggests inflammation of the kidney, as in lupus nephritis. Absence of urine abnormalities is very strong evidence against the presence of lupus nephritis. The presence of only white blood cells suggests a urinary tract infection.

b). Serum Creatinine: Creatinine (a substance in blood) is normally

cleared from the blood by the kidney. If there is significant impairment of kidney function, then the serum creatinine is increased.

c). 24 Hour Urine: One can determine the amount of protein per 24 hours.

This fluctuates to some degree. Steady increases of urinary protein means wors ening kidney function. One can also determine serum and (24 hour) urine creatinine and calculate a GFR (glomerular filtration rate). This is a sensitive index of kidney function. Normals have values over 100-120.

2. Brain Involvement

a). Magnetic resonance imaging (MRI, NMR) is a sensitive nonradioactive

technique that often will detect neurological abnormalities in SLE patients.

b). CT scan (CAT scan - computerized tomography) may detect abnormalities

in SLE; it has been mostly replaced by the MRI.

c). Brain wave (EEG) - often performed after sleep depriv- ation or with auditory or visual stimulation. The test is used to detect seizure disorders.

d). Psychological testing (e.g. MMPI): To help distinguish neurological from psychological causes of symptoms. If all the above are negative, it is highly unlikely that there is lupus brain involvement.