SLE SYSTEMIC LUPUS ERYTHEMATOUS 09112013 SLE q An

SLE SYSTEMIC LUPUS ERYTHEMATOUS 09/11/2013

SLE q An autoimmune disease of the body's connective tissues, primarily the immune system attacks parts of the cell nucleus q It is a Type III hypersensitivity reaction caused by antibody-immune complex formation. q SLE causes tissue inflammation and blood vessel problems.

q Systemic inflammation, q Affects the kidneys. The tissues of the kidneys, including the blood vessels and the surrounding membrane, become inflamed (swollen), and deposits of chemicals produced by the body form in the kidneys. These changes make it impossible for the kidneys to function normally. q The inflammation of SLE can be seen in the lining, covering, and muscles of the heart. The most common problem is bumps and swelling of the endocardium, which is the lining membrane of the heart chambers and valves. q SLE also causes inflammation and breakdown in the skin. Rashes can appear anywhere, but the most common spot is across the cheeks and nose. q The disease occurs nine times more often in women than in men, especially in women in child-bearing years ages 15 to 35, and is also more common in those of non-European descent.

Causes of SLE: q There is no one specific cause of SLE. q There are, however, a number of environmental triggers and a number of genetic susceptibilities.

Symptoms of SLE: q The symptoms of SLE come on in waves, called flares or flare- ups. q Patients may have almost no symptoms. q SLE patient suffers from general discomfort, q Extreme fatigue, q q Fever, and Weight loss at some point. q In addition to these general symptoms, SLE produces different symptoms in different body systems.

Skin: q Rashes caused by SLE are red, itchy, and painful. q The rash can show up on any part of the body. q The most typical SLE rash is called the butterfly rash, which appears on the cheeks and across the nose. q SLE also causes hair loss. The hair usually grows back once the disease is under control. q People with SLE tend to be very sensitive to sunlight. Being in the sun for even a short time can cause a painful rash. q Some people even get a rash from fluorescent lights at work.

Muscles and bones: q Any joint can be affected, but the most common spots are the hands, wrists, and knees. q Usually the same joints on both sides of the body are affected. q Joint Pain, The pain can come and go, or it can be long lasting. q The soft tissues around the joints are often swollen, but there is usually no excess fluid in the joint. q Many SLE patients describe muscle pain and weakness, and the muscle tissue can swell. q In its late stages, SLE can cause areas of bone tissue to die, called osteonecrosis, which can cause serious disability. q It can be caused at least in part by using high doses of corticosteroids over a long time. q Corticosteroids help control the symptoms of SLE.

Kidneys: q People with SLE usually don't notice any problems with their kidneys until the damage is severe. q Sometimes kidney problems aren't noticed until the kidneys are actually failing.

Heart: q A person with SLE may have inflammation of various parts of the heart, such as pericarditis, myocarditis, and endocarditis. q The endocarditis of SLE is characteristically noninfective (Libman-Sacks endocarditis), and involves either the mitral valve or the tricuspid valve. q Atherosclerosis also tends to occur more often and advances more rapidly than in the general population.

Pregnancy: q Because so many SLE patients are young women, pregnancy is a major concern. q The disease can be managed during pregnancy if it has already been brought under control. q However, the chances of miscarriage, premature birth, and death of the baby in the uterus are high.

Clinical Symptoms: q Fever q Arthritis q Skin rash q Fatigue q Abortion q Infertility q Hypertension

Laboratory diagnosis of SLE: q Elevated ESR. q Normochromic normocytic anemia. q Thrombocytopenia. q Leukopenia. q Rheumatoid factor (20%). q Antinuclear antibody (ANA). q Complement system level, liver enzymes, electrolytes and renal function tests. q Antismooth antibody ( ASMA) q Anticytoplasmic antibody ( ANCA ) q Antimitochondirial antibody (M 2)

Antinuclear antibody (ANA). q Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE. q Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence. The pattern of fluorescence suggests the type of antibody present in the patient's serum. q ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals.

q Subtypes of antinuclear antibodies include q anti-Smith and anti-double stranded DNA (ds. DNA) antibodies (which are linked to SLE) and q anti-histone antibodies (which are linked to drug-induced lupus). q Anti-ds. DNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0. 5% of people without SLE. q The anti-ds. DNA antibody titers also tend to reflect disease activity, although not in all cases. Other ANA that may occur in SLE sufferers are anti-U 1 RNP (which also appears in systemic sclerosis), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome). q SS-A and SS-B confer a specific risk for heart conduction block in neonatal lupus.

• Antinuclear antibodies (green, FITC-labeled) from systemic lupus patients attacking human epithelial cells (HEp-2), counterstained with Evans' Blue (red). Note the homogeneous nuclear staining pattern. Submitted by Charles Murphy, California State University, Sonoma

• Sometimes when performing the ANA test, the substrate cells demonstrate particular patterns of staining. This is the socalled "rim" pattern that is more characteristic of systemic lupus erythematosus (SLE) than other autoimmune diseases.

• These are Crithidia organisms, whose sole purpose for existence is to serve as a substrate for the double stranded DNA test. Here the little critters have brightly fluorescing kinetoplasts indicative of a positive test. A positive double stranded DNA test strongly suggests a diagnosis of SLE.

• This is the so-called "speckled" pattern of antinuclear antibody test staining which is more characteristic of the presence of autoantibodies to extractable nuclear antigens (ENA), particularly to ribonucleoprotein. This pattern is not very specific, but may be seen with an entity called "mixed connective tissue disease" (MCTD) which is an "overlap" condition that is a mix among SLE, scleroderma, and polymyositis features, but without serious renal or pulmonary disease. The autoimmune diseases are very hard to classify, even for the experts

• This is the so-called "nucleolar pattern" of staining in which the bright fluorescence is seen within the nucleoli of the Hep 2 cells. This pattern is more suggestive of progressive systemic sclerosis (scleroderma).

• Here is the famous "LE cell" test which has value only in demonstrating how the concept of autoantibodies work. The pink blobs are denatured nuclei. Here are two, with one seen being phagocytozed in the center by a PMN. This test is not nearly as sensitive as the ANA which has supplanted the LE cell test. Therefore, NEVER order an LE cell test. [Image contributed by Elizabeth Hammond, MD, University of Utah]

• This young woman has a malar rash (the so-called "butterfly" rash because of the shape across the cheeks). Such a rash suggests lupus. Discoid lupus erythematosus (DLE) involves mainly just the skin and is, therefore, relatively benign compared to systemic lupus erythematosus (SLE). In either case, sunlight exposure accentuates this erythematous rash ("photosensitivity"). A small number (5 to 10%) of DLE patients go on to develop SLE (usually the DLE patients with a positive ANA). [Image contributed by Elizabeth Hammond, MD, University of Utah]

ANA Staining Pattern

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