Lupus Diagnosis

Because many lupus symptoms mimic other illnesses, are sometimes vague and may come and go, lupus can be difficult to diagnose. Diagnosis is usually made by a careful review of a person’s entire medical history coupled with an analysis of the results obtained in routine laboratory tests and some 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 Collegeof 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. 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.

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

The first laboratory test ever devised was the LE (lupus Erythematosus) cell test. When the test is repeated many times, it is eventually 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 immunofluorescent antinuclear antibody (ANA or FANA) test is more specific for lupus than the LE cell prep test. The ANA test is positive in virtually all people with systemic lupus, and is the best diagnostic test for systemic lupus currently available. If the test is negative, the patient will 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:

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.

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 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). The most common manifestation of this is phlebitis or inflammation of the vessels in the calves of the legs. 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.

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.

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. However, when unresolved questions arise or complications develop, another opinion from a specialist may be advisable. 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 the local Lupus Foundation of America chapter.

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, perhaps a cold or a more serious infection, does not get better, and then complications arise. These complications may be the first signs of lupus. In still other cases, a drug taken for some illness produces the signaling symptoms. 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. Obviously, many seemingly unrelated factors can trigger the onset of the disease.