lupus-erythematosus - Monica Richey NP

Patients with suspected or confirmed Systemic Lupus Erythematosus (SLE) undergo laboratory tests for multiple reasons. In her presentation, Ms. Richey explained that physicians and other health care professionals use the information derived from the tests in the following ways.

To Diagnose

To make sure that what is seen clinically is consistent with the lab test findings. Lupus is known as the “great imitator”, meaning that symptoms can often mimic those of other diseases. Healthcare providers want to be sure they are really looking at lupus and not another disease.

Determining the Prognosis

Physicians want to understand how a patient’s disease will progress. Lab tests are used to establish the baseline condition at the time of diagnosis and to help predict whether lupus in an individual patient is more or less likely to become a more serious problem.

To Monitor

Laboratory tests can help assess the severity of the disease, the efficacy of treatment, and if the patient is experiencing any medication-related- toxicity or side effects, especially those that affect organs like the liver and kidneys.

To Guide Therapy

Laboratory test results are used to help make treatment recommendations. Standard laboratory tests for SLE include:

Anti-nuclear antibody (ANA)

The hallmark of lupus is the presence of autoantibodies, antibodies produced by the immune system that attack the body’s own cells. ANA tests for the presence of these autoantibodies. If an ANA result is positive, it is only done once since the patient will generally continue to have a positive result through their lifetime. ANA is not specific to lupus. Positive ANAs are also associated with other conditions such as thyroid disease. A positive ANA can be found in 10% of healthy people. The test is a simple sign of the presence of autoantibodies. Depending on how it is measured, 95-99% of lupus patients will have a positive ANA blood test.

Different types of ANA patterns may indicate different characteristics of lupus. These include:

Homogenous/Rim pattern- seen in systemic lupus

Speckled - non-specific

Nucleolar/centromere- an indication of a possible scleroderma component and a greater likelihood of developing features of scleroderma in the future

Anti-Double Stranded DNA (Anti-DsDNA)

Anti-DsDNA is more specific to lupus than ANA and can be very valuable in making a diagnosis of lupus. The anti-DsDNA test is generally done at every medical visit. This test indicates if the body is making antibodies to - and thus “attacking” - its own DNA. Monitoring anti-DsDNA is very important since levels of this antibody may correspond with disease activity.

If the anti-DsDNA levels are high, the disease is more likely to be active. There is either a current flare or a flare may be imminent.

If the anti-DsDNA levels are low, the disease is more likely to be calm and there is a period of low disease activity.

It is important to note that a positive anti-DsDNA does not always guarantee a diagnosis of lupus. Some people fluctuate between positive and negative anti-DsDNA test results. A diagnosis of lupus is always based on physical presentation and symptoms of the patient in combination with lab test results. In patients diagnosed with lupus the anti-DsDNA will usually remain positive, but the levels can change with the activity of the disease.

Complement level: C3 and C4

Multiple complement components are a part of the immune system that can be visualized as tiny missiles. When bacteria or a virus enter the body the immune system activates these missiles, which perforate the membrane of the bacteria or virus. In the case of lupus, instead of being activated to destroy bacteria or virus cells, the multiple complement component are activated to destroy the body’s own cells.

One of the hallmarks of lupus are low Complement 3 (C3) and Complement 4 (C4) levels. Low C3 is not specific to lupus; low C3 combined with low C4 is what is usually seen in lupus. The patient’s levels of C3 and C4 can indicate the activity of the disease.

When C3 and C4 levels are low, it can suggest that the disease is active and there is either a current flare or a flare is imminent.

When C3 and C4 are normal, the disease is more likely calm. However, it does not mean the patient will not experience a flare.

A consistently low level of C3 can indicate the possibility of developing lupus nephritis in the future. If this is the case, the doctor will watch the kidneys very closely and will ask the patient to return every two/three months to check his or her urine.

Anti-Ro and Anti-La

Anti-Ro and anti-La antibodies stop cells from working properly. The presence of these antibodies is especially important in women of childbearing age. In pregnant women, anti-Ro and anti-La antibodies can cross through the placenta and create complications for the fetus and place the baby at risk for neonatal lupus. Neonatal lupus can manifest as minor issues in which the baby is born with a rash that will eventually disappear or can be more serious and cause heart defects. Women who have positive anti-Ro and anti-La are closely monitored when pregnant and generally have an echocardiogram once a month to monitor the baby’s heart.

People who test positive for anti-Ro and anti-La can also develop Sjogrens syndrome, an autoimmune disorder characterized by dry eyes and dry mouth. In lupus patients, these antibodies are also associated with a higher possibility of developing photosensitivity (sensitivity to the sun.)

Anti-Sm and Anti-RNP

Anti-Sm and anti-RNP antibodies interfere with cell metabolism. For some patients, if the anti-DsDNA is negative, a positive anti-Sm will help to confirm the diagnosis of lupus. Anti-Sm is the antibody most specific to lupus. Anti-RNP can correlate with specific characteristics of lupus, including:

Puffy hands

Raynaud’s disease- areas of the body (such as fingers and toes) become numb and cold in response to cold temperatures or stress

Pulmonary Hypertension- high blood pressure that affects the arteries in the lungs and the right side of the heart. (If this condition is present, doctors will monitor the heart and lungs closely)

Mixed Connective Tissue Disease (MCTD)- lupus mixed with scleroderma, a disease that involves the hardening of the skin and scarring in areas such as the lungs.

Erythrocyte Sedimentation Rate (ESR)

The ESR is an indirect indication of inflammation and is not specific to lupus. This test is a simple way to measure the presence of disease activity. If the ESR is high, and there are no other reasons for it to be high, such as infection, it usually means the lupus is active. If the ESR is low, there is little inflammation and the disease is calm, although not every person with active lupus has a high ESR. ESR is calculated by measuring the rate at which red blood cells sediment in a test tube in one hour. ESR readings can be affected by many other factors, for example, if the blood sits for longer than one hour before the reading is taken or if the patient is obese or has an infection, the ESR will be higher. This is a non-specific measurement used to quickly gauge the level of disease activity.

Normal Measurements: ◦Women: 0-20 mm/hr; >50 years: 0-30 mm/hr

◦Men: 0-15 mm/hr; >50 years: 0-20 mm/hr

C-Reactive Protein (CRP)

The CRP, like the ESR, is an indirect indication of inflammation, but is more specific in the detection of disease activity, since it is not affected by as many variables. Levels are also higher in the presence of obesity and infection.

Normal Measurement: ◦< 1.0

Both ESR and CRP are used as simple ways to monitor disease activity. ESR and CRP also provide a quick way to help evaluate the effectiveness of treatment. Changes due to treatment may not register for weeks/months with tests such as anti-DsDNA or C3/C4. However, measurements of ESR and CRP will quickly change in response to medications/treatments and can therefore provide doctors with valuable information about the effectiveness of treatment.

It is important to note that some patients with lupus will have normal ESR and CRP levels despite having high disease activity

Complete Blood Count (CBC)

The CBC provides information about multiple components of the blood, including the red blood cell, white blood cell and platelet counts. Lupus can cause a deficiency in many blood components. Common issues associated with low blood cell counts are:

Anemia- low red blood cell count (a common presentation in lupus that can improve when the disease is controlled)

Leukopenia- low white blood cell count (if low enough, the patient can be more prone to infections)

Thrombocytopenia- low platelets (if low enough, the patient is more prone to bleeding, bruising)

Complete Metabolic Panel (CMP)

This panel takes a look at the rest of the body including liver, kidney and lung functions. The test looks at electrolytes in the blood: Na (sodium), K (potassium), and chloride. It looks at the blood glucose. Creatinine and blood urea nitrogen (BUN) levels measure kidney function and aspartate transaminase (AST) and alanine transaminase (ALT) measure liver function.

Urine with Microscopy

Because lupus patients are prone to kidney disease, urine tests are ordered on a regular basis. Urine tests are evaluated for:

Ph – to determine if the urine is acidic or alkaline.

Protein – the level should be 0; if protein is present, it may indicate kidney disease

White Blood Cells (WBC) – only a low number are normally present; a high WBC count in urine may indicate a urinary infection

Presence of Blood – more than a very small number may indicate kidney disease or kidney stones (women should avoid urine test during their periods)

Together CBC, CMP, and urine tests help to monitor disease activity and guide treatment. Doctors are always looking at the whole picture, checking for disease activity, and assessing whether treatments are effective and free of side effects. If the counts for these tests are normal, it suggests that there is not active organ involvement with lupus or major organ side-effect of treatment. If the results are abnormal, further evaluation is likely needed to see if the disease or the treatment are causing problems.

X-rays

X-rays are used to look for damage to joints or bones. Sometimes x-rays can suggest that a patient has thin bones (osteoporosis) which can be due to prednisone therapy, but confirmation would be needed with a bone density study.

Antiphospholipid Syndrome (APS)

Almost ten percent of lupus patients may have antiphospholipid syndrome. This is a complex syndrome especially related to blood clots, but with many other features. About 50% of lupus patients may have antibodies that are associated with the anti-phospholipid syndrome, but don’t have the syndrome itself.

Lab tests that are done to assess for the presence of this syndrome are:

Lupus anticoagulant

Anti-Cardiolipin lgG, lgA, lgM

Beta-2-Glycoprotein I antibodies

If antiphospholipid antibodies (aPL) are found, and the patient has had no clotting abnormality or other symptom or sign of the anti-phospholipid syndrome, then they are noted to have a positive aPL profile only and no treatment is required; however, patients should be aware of the presence of these antibodies and be cautious in situations that can trigger a blood clot (such as prolonged travel). If a positive aPL lab profile is present and the patient has a history of blood clot or other signs or symptoms that meet criteria for the anti-phospholipid syndrome, the patient is diagnosed with Antiphospholipid Syndrome (APS) and anticoagulation (blood thinning) needs to be considered. The duration of the blood thinning will also need to be determined, depending on the individual case.

Ms. Richey ended her presentation by using case scenarios to demonstrate the many ways in which lab tests can be used in combination with other pertinent information to make a diagnosis of lupus. It is important to note that healthcare professionals will take into consideration the whole person when diagnosing and treating lupus. Diagnosis and treatment are based on physical examination, lab tests and other imaging studies. It is also important to note that each person’s lupus is unique, and that no two lupus patients are the same. Lab tests can help complete the puzzle of diagnosis, treatment and monitoring of the disease. Each lab test provides information about different components of lupus. Lab tests can also help doctors better understand the different characteristics of a patient’s lupus. Patients should communicate with their doctors and be sure to ask about their lab test results in order to gain a clearer picture of their disease.

Learn more information about the SLE Workshop at HSS, a free support and education group held monthly for people with lupus and their families and friends.

Posted: 4/20/2015

Summary by Gwyneth Kirkbride, Social Work Intern for Lupus Programs.

Edited by Nancy Novick.