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Systemic Lupus Erythematosus

Pathology || Signs and Symptoms || Diagnosis || Treatment || Overview ||
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Pathology





Systemic lupus erythematosus (SLE) is an autoimmune condition in which the body literally attacks itself. It can affect almost any organ system, and is believed to be related to the immune system releasing antibodies that bind to molecules with the nucleus of a cell. These molecules include, but are not limited to, histone proteins and double stranded DNA binding proteins, which are normal components of a cell's nucleus. For unclear reasons, in systemic lupus erythematosus, the body forms antibodies against these normal molecules.

However, the real damage in lupus occurs when these auto-antibodies bind to their target proteins (ie: antigens). When this occurs, immune complexes form. These complexes get lodged in small blood vessels throughout the body wreaking havoc on whatever organ system is involved.

The antibody-antigen complexes cause damage through several mechanisms. They can cause activation of the complement system. What is the complement system? It is a set of proteins involved in the immune response. So what happens? Well, one of these complement proteins binds to the antibody of the immune complex. This sets off the complement "cascade", which leads to inflammation and tissue damage. In addition, the immune complexes can bind to cellular proteins called "Fc receptors". When this happens that particular cell gets "marked" for destruction by the spleen.

Interestingly, individuals with certain human leukocyte antigen (HLA) genotypes have an increased risk of developing the disease. The HLA genotypes associated with this increased risk are the B8, DR2, and DR3 loci.

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Signs and Symptoms

SLE Butterfly Rash
Since systemic lupus erythematosus involves multiple organ systems the clinical presentation is highly variable.

Skin findings are common. About a fourth of patients present with the classic lupus "butterfly" rash on the face (see image to the left). In addition, a distinct facial rash known as "discoid lupus" can occur as an isolated rash, or as part of systemic lupus erythematosus. It can cause scarring and increased pigmentation of the skin. The ear canals are also commonly involved in discoid rashes. Finally, patients may have rashes on the neck, trunk, and limbs. The rashes of lupus are caused by deposition of immune complexes in the dermis and commonly occur on sun exposed skin.

Immune complex deposition can occur in the kidney causing "lupus nephritis". As a result, patients may present with swelling of the lower extremities, high blood pressure, and/or blood tinged urine. There are different grades of lupus nephritis depending on the clinical severity, and specific pathological process occurring in the kidney.

Organ Systems
Involved in SLE:
- Skin
- Kidneys
- Lungs
- Joints
- Heart
- CNS
- Blood

Joint involvement in lupus is extremely common. It can present in a variety of ways, and can affect a few joints or numerous joints. The arthritis can be symmetric or asymmetric, and both large and small joints can be affected. However, unlike rheumatoid arthritis it is not typically an erosive processes.

Both the lungs and heart can also be affected. Shortness of breath may occur if the lung tissue becomes inflamed. Inflammation of the heart muscle (myocarditis) or sac surrounding the heart (pericarditis) can cause arrhythmias (ie: abnormal heart rhythms) and possibly even heart failure.

The nervous system may be involved. Seizures and neuro-psychiatric symptoms (depression, hallucinations, etc.) can occur. Numbness and tingling secondary to inflammation in the blood vessels supplying the nerves is not uncommon.

Immune complexes can cause destruction of red blood cells, white blood cells, and platelets. As a result, anemia (decreased red blood cells), leukopenia (decreased white blood cells), and/or thrombocytopenia (decreased platelets) can occur. Roughly half of lupus sufferers develop antiphospholipid antibodies. These antibodies can increase the risk of blood clots; these antibodies can also cause recurrent abortions in women of childbearing years.

Ultimately, the clinical signs and symptoms are highly variable and depend on the specific organ system(s) affected. Lupus is considered a chronic, relapsing, and remitting disease.

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Diagnosis

Systemic lupus erythematosus is a diagnosis based on clinical findings and laboratory data. Like many rheumatological and autoimmune conditions there is no single test that can rule in, or rule out the disease. A patient is likely to have systemic lupus erythematosus if at least 4 of the following 11 criteria are met:

(1) Malar rash (see image below)
(2) Discoid rash
(3) Photosensitivity on exposed skin
(4) Oral ulcers
(5) Arthritis
     (a) Non-erosive, and
     (b) Involving 2 or more peripheral joints
(6) Serositis
     (a) Pleuritis, and/or
     (b) Pericarditis
(7) Kidney (renal) findings
     (a) Proteinuria (>500mg/d, 3+ on dipstick), and/or
     (b) Cellular casts on urinalysis
(8) Central nervous system findings
     (a) Seizures, and/or
     (b) Psychosis
(9) Blood (hematological) findings
     (a) Hemolytic anemia, and/or
     (b) Leukopenia, and/or
     (c) Lymphopenia, and/or
     (d) Thrombocytopenia
(10) Immunological findings
     (a) Antiphospholipid antibodies
         1. False positive test for syphilis, or
         2. Abnormal level of anticardiolipin antibodies, or
         3. Positive for lupus anticoagulant
     (b) Antibodies against native DNA (ie: anti-dsDNA)
     (c) Antibodies against Sm nuclear antigen (ie: anti-Sm)
(11) Antinuclear antibody (ANA) positive

If a patient has less than 4 of these criteria, a diagnosis of lupus is not excluded, but the likelihood is decreased.

Antinuclear antibodies (ANA) are very sensitive (ie: almost all patients with lupus have them), but are not specific (ie: there are other diseases that have elevated ANA levels). Anti-dsDNA antibodies are a relatively specific marker of the disease, but they are not very sensitive.

Monitoring of disease should be done using ESR ("sed rate") and complement levels. Complement levels usually show decreased C3 and C4; the degradation product C3d is elevated indicating activation of the complement cascade. Kidney disease can be followed with frequent urinalysis to evaluate for protein (proteinuria) and blood (hematuria) in the urine. Complete blood counts should also be done to assess for low levels of the various blood cell lines.

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Treatment

Treatment of lupus, like other autoimmune conditions, involves dampening the immune system with numerous medications.

Hydroxychloroquine is the drug of choice for patients with skin and joint involvement. It is also the drug of choice for maintaining disease remission, and should not be stopped even during asymptomatic periods.

Non-steroidal anti-inflammatories (NSAIDs) like ibuprofen can be used to treat pain associated with lupus.

In addition, for disease flairs corticosteroids like prednisone are commonly used to quickly and effectively dampen the immune system. In patients with severe disease long term steroid therapy is not an appropriate option because of numerous side effects. Because of this they are commonly replaced by "steroid sparing" agents like cyclophosphamide, mycophenolate mofetil, and azathioprine. Cyclophosphamide, in combination with corticosteroids, is especially useful for lupus nephritis.

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Overview

Systemic lupus erythematosus is an autoimmune disease characterized by antibodies directed against normal nuclear molecules. The disease presents with a variety of signs and symptoms and is multi-organ in nature. It is diagnosed based off of both clinical and laboratory data. Treatment is with medications that dampen the immune response. Steroid sparing medications are used if possible, but many patients require corticosteroids for disease control.

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Related Articles

- Rheumatoid arthritis

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References and Resources

(1) D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007 Feb 17;369(9561):587-96.

(2) Fine DM. Pharmacological therapy of lupus nephritis. JAMA. 2005 Jun 22;293(24):3053-60.

(3) Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh Edition. Philadelphia: Elsevier Saunders, 2004.

(4) Bickley LS, Szilagyi PG. Bates' Guide to Physical Examination and History Taking. Ninth Edition. New York: Lippincott Williams and Wilkins, 2007.

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An antibody is a protein released by specialized cells within the immune system. An antibodies' job is to bind to and "neutralize" a particular target. These targets are known as an "antigens". Antigens can be both self and non-self (ie: bacterial and viral proteins).