Systemic lupus erythematosus (SLE)- USMLE1

Systemic lupus erythematosus (SLE):

·         SLE is a chronic autoimmune connective tissue disease that can affect any part of the body.

·         In SLE the immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage.

·         SLE affects the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system.

• The course of the disease is unpredictable, with periods of illness (called flares) alternating with remissions.
• The disease occurs nine times more often in women than in men, especially between the ages of 15 and 50, and is more common in those of non-European descent
• Survival for patients with SLE in the United States, Canada, and Europe is approximately 95% at five years, 90% at 10 years, and 78% at 20 years.

Causes:

·         There is no one specific cause of SLE. There are however a number of environmental triggers and a number of genetic susceptibilities.

Genetics

·         SLE may have a genetic link. SLE does run in families.

·         The most important genes are located in the HLA region on chromosome 6, where mutations may occur randomly or may be inherited.

Environmental triggers

·         They include extreme stress, exposure to sunlight, hormones, and infections. UV radiation has been shown to trigger the photosensitive lupus rash and some evidence suggests that UV light might be capable of altering the structure of the DNA, leading to the creation of autoantibodies. Sex hormones such as estrogen play an important role in the occurrence of SLE and it is observed that during reproductive years, the frequency of SLE is 10 times greater in females than in males.

Drug reactions

·         Symptoms of drug-induced lupus generally disappear once the medication that triggered the episode is stopped.

·         There are about 400 medications that can cause this condition, the most common of which are INH, procainamide, hydralazine, quinidine, d-penicillamine and phenytoin

·         These drugs are known to stimulate the immune system (by drugs with slow acetylation reactions) and cause SLE.

Signs and Symptoms:

Common initial and chronic complaints include :fever, malaise, joint pains, myalgias, fatigue.

·         Dermatological manifestations : Most common is the skin rash: malar rash (or butterfly rash)

·         Some may exhibit thick, red scaly patches on the skin (referred to as discoid lupus)

·         Anemia

·         mouth, nasal, and vaginal ulcers

·         Cardiac manifestation: pericarditis, myocarditis, and endocarditis. The endocarditis of SLE is characteristically noninfective (Libman-Sacks endocarditis) and involves either the mitral valve or the tricuspid valve.

·         Pulmonary manifestations: Lung and pleura inflammation can cause pleuritis,  pleural effusion, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli,  pulmonary hemorrhage.

·         Renal involvement : Painless hematuria or proteinuria

·         A histological hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities. This finding  is due to immune complex deposition along the glomerular  basement membrane, leading to a typical granular appearance  in immunofluorescence testing.

·         CNS manifestations of SLE include:  headache, cognitive dysfunction, mood disorder, cerebrovascular disease, seizures, polyneuropathy, anxiety disorder, and psychosis.

·         Patients with SLE may have an association with antiphospholipid antibody syndrome (a thrombotic disorder), wherein autoantibodies to phospholipids are present in their serum.

·         Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged PTT and a positive test for antiphospholipid antibodies.

·         Another autoantibody finding in SLE is the anticardiolipin antibody, which can cause a false positive test for syphilis.

How is lupus diagnosed?

CBC: anaemia, sedimentation rate and C-reactive protein

For autoimmune SLE:

·         anti-dsDNA antibodies

·         anti-Sm [Smith] antibody

·         antinuclear antibody

For drug induced SLE:

·         Anti-histone antibody

·         Low level of C3, C4 and high level of anti-dsDNA 

·         antibody associated with relapse(flare up) and poor prognosis.

Treatment:

·         There is no cure for SLE. Treatment is aimed at controlling symptoms

·         NSAIDs (Nonsteroidal anti-inflammatory medications) are used to treat arthritis and pleurisy.

·         An anti-malaria drug (hydroxychloroquine) and low dose corticosteroids are sometimes used for skin and arthritis symptoms

·         Immunosuppressive : azathioprine and cyclophosphamide for renal and cerebral involvement

·         For drug induced SLE: withdrawal of medication

·         Patients should wear protective clothing, sunglasses, and sunscreen when in the sun