Systemic Lupus Erythematosus (SLE):How does SLE affect the body?
Describe The Etiology , Clinical Features or Symptoms , Diagnostic Criteria and Treatment of Systemic Lupus Erythematosus (SLE)?
What is systemic lupus erythematosus(SLE)?
Systemic Lupus Erythematosus is a multisystem Connective tissue Disease Characterised by the presence of numerous Antibodies in the Blood , Circulating Immune Complexes widespread Immune-mediate tissue Damage.
Systemic Lupus Erythematosus (SLE) is the classical example of Systemic Autoimmune or Collagen Diseases. The Disease derives its name “Lupus“ from the Latin Word meaning “Wolf” since initially this disease was believed to affect skin only and eat away skin like a wolf.
Two Forms/Types of Lupus Erythematosus(SLE) are described:
Systemic or Disseminated Type:
is Characterized by Acute and Chronic Inflammatory lesions widely scattered in the body and there is presence of various nuclear and cytoplasmic autoimmune in the plasma.
is characterized by chronic and localized skin lesions involving the bridge of Nose and Adjacent cheeks without any Systemic manifestations . Rarely , Discoid form may develop into Disseminated form.
The onset of Systemic Lupus Erythematosus (SLE) is most Commonly in the 2rd and 3rd decades with a female/mail Ratio of 9:1.
Etiology/Causes of Systemic Erythematosus(SLE):
The Exact Etiology of Systemic Lupus Erythematosus (SLE) is not Known.However,Auto-antibodies against Nuclear and Cytoplasmic Components of the cells are demonstable in plasma by immune-fluorescence tests in almost all cases of SLE. Some of the important Antinuclear Antibodies(ANAs) or Antinuclear Factors (ANFs) against different antigens are as Under:
- Antinuclear Antibodies (ANA) are the Antibodies against common nuclear antigen that includes DNA as well as RNA.
- Antibodies to double-stranded (anti-dsDNA) or single-stranded DNA (anti-ssDNA) is the most specific , present in half the cases of SLE.
- Anti-Smith antigen antibodies (anti-SmAg), in which antibodies appear against Smith antigen which is part of Ribonucleoproteins.
- Anti-Ribonucleroproteins (anti-RNP) are not Specific for SLE but are seen more often in Sjogren’s syndrome.
- Anti-histone antibodies to Nucleolar Antigens.
- Anti-phospholipid antibodies or lupus Anticoagulant are quite specific for SLE and are responsible for thrombotic Complications in cases of SLE.
The Source of these Auto-antibodies as well as Hypergammaglobulinaemia in SLE is the Polyclonal Activation of B cells brought about by following derangements:
- Immunological Factors :
- An Inherited defect in B cells
- Stimulation of B cells by Micro-Organisms
- T-helper cell Hyperactivity
- T-Suppressor cell Defect.
- Genetic Factors:
- Genetic predisposition to develop auto-antibodies to nuclear and Cytoplasmic antigens in SLE is due to the immune-regulatory functions of class 2nd HLA genes implicated in the pathogenesis of SLE.
- Other Factors:
Various other Factors express the genetic susceptibility of an individual to develop clinical disease.
- Certain Drugs example Penicillamine D
- Viral Infections example EBV infection
- Certain Hormones example Oestrogen
Pathogenesis or Pathophysiology of Sytemic Lupus Erythematosus (SLE):
The Auto-antibodies Formed by any of the Mechanisms explained above are the mediators of tissue injury in SLE
Two types of immunologic Tissue injury can occur in SLE:
Type 2nd Hypersensitivity:
is characterized by Formation of Auto-antibodies against blood cells (Red Blood Cells, Platelets, Leucocytes) and results in Haematologic Derangement in SLE.
Type 3nd Hypersensitivity:
is Characterized by Antigen-Antibody Complex (Commonly DNA-anti-DNA antibody; Sometimes Ig-anti-Ig Antibody Complex ) which is deposited at sites such as Renal Glomeruli, Walls of Small Blood Vessels etc.
Common Features/Symptoms of Systemic Lupus Erythematosus (SLE):
Systemic Symptoms of Systemic Lupus Erythematosus (SLE)
- Weight Loss
Musculoskeletal Symptoms of Systemic Lupus Erythematosus (SLE)
- Non-Erosive Polyarthritis
- Jaccoud’s Arthropathy
Musculocutaneous Symptoms of Systemic Lupus Erythematosus (SLE)
- Malar Rash or Butterfly Rash
- Discoid Rash
- Oral Ulcers
- Dryness of Mouth or Sjogren’s Syndrome.
Haematological Symptoms of Systemic Lupus Erythematosus (SLE)
- Normocytic Normochromic Anaemia
- Coombs-Positive Haemolytic Anaemia
Neurological or Neuropsychiatric Symptoms of Systemic Lupus Erythematosus (SLE)
- Organic Brain Syndromes
- Renal Failure
- Cellular Casts
- Peripheral Nervous System involvement causing Neuropathy.
Cardio-pulmonary Symptoms of Systemic Lupus Erythematosus (SLE)
- Pleural Effusions
- Artherlosclerosis and Vasculitis
- Vanishing Lung Syndrome
- Pulmonary Haemorrhage
- Pulmonary Artery Hypertension
Renal Symptoms of Systemic Lupus Erythematosus (SLE)
- Nephrotic Syndrome
- Renal Failure
- Cellular Casts
Gastrointestinal Symptoms of Systemic Lupus Erythematosus (SLE)
- Bleeding and Perforation
- Abnormal Liver Enzymes
- Non- Specific Abdominal Pain
- Mesenteric Vasculities
Ocular Symptoms of Systemic Lupus Erythematosus (SLE)
- Retinal Vasculitis
- Sicca Syndrome
Other Symptoms of Systemic Lupus Erythematosus (SLE):
- Weight Loss
Above symptoms not Life- Threatening, they have a Significant impact on quality of Life.
Systemic Lupus Erythematous Medical Diagnostic Criteria:
Le Cell Phenomenon:
- This was the First Diagnostic Laboratory Test Described For Systemic Lupus Erythematosus (SLE).
- The test is Based on the Principle that ANAs cannot penetrate the Intact cells and thus cell Nuclei should be Exposed to bind them with the ANAs.
- The Binding of Exposed Nucleus with ANAs results in Homogeneous Mass of Nuclear chromatin material which is called LE body or Haemotoxylin body.
LE cell is a Phagocytic Leucocyte,Commonly Polymorphonuclear neutrophil, and sometimes a monocyte, which engulfs the Homogeneous nuclear material of the injured cell.For Demonstration of LE cell phenomenon in Vitro,the blood sample is Traumatised to Expose the Nuclei of Blood Leucocytes to ANAs. This results in Binding of Denatured and damaged Nucleus with ANAs.
The ANA-coated denatured nucleus is chemotactic for Phagocytic Cells.
- If this mass is Engulfed by a Neutrophil , Displacing the Nucleus of Neutrophil to the rim of the cell, it is Called LE Cell.
- If the mass, more often an intact lymphocyte , is phagocytosed by a monocyte , it is Called Tart cell.
LE cell test is Positive in 70% cases of SLE while newer and more sensitive immunofluorescence test for Auto-Antibodies are positive in Almost 100% cases of SLE .A Few Other conditions may also Slow Positive LE test Example: Rheumatoid Arthritis, Lupoid Hepatitis , Penicillin Sensitivity etc.
Auto-Antibodies in Patients with Systemic Lupus Erythematosus (SLE) are:
- Anti-Nuclear Antibodies ( ANA)
- Anti-DNA ( Anti-dsDNA & Anti-ssDNA)
- Anti-RO (SSA)
- Anti-La (SSB)
- Anti-Nuclear Antibody (ANA) are the best Screeening Test. More than 90% of the Patients have a test.
- A positive test is not specific for SLE , as it can occur in a Variety of other situations like in some Normal People ( Especially Elderly/Old age), Other Autoimmune Disease, Acute Viral Infections, Chronic Inflammatory Processes and with Certain Drugs.
- Anti-ds DNA and Anti-Sm are Relatively specific for Systemic Lupus Erythematosus (SLE)
- Rising Levels of Anti-dsDNA and loe levels of Complement ( C3 and C4) usually Reflect Disease Activity.
Other Abnormalities Associated with SLE
- The Erythrocyte Sedimentation Rate( ESR) is Raised in Some Patient.
- The C-Reactive Protein (CRP), Unlike the ESR , Does not Usually Rise with disease activity unless there is Arthritis or Serositis. Infection Should be Excluded if a Raised CRP is Found in a Patient with SLE.
- Anaemia, Leucopaenia, Lymphopaenia and Thrombocytopaenia may be Present.
- With Active Nephritis , Urinalysis shows Proteinuria, Haematuria, and Cellular or Granular Casts.
- Blood Urea and Serum Creatinine are Elevated.
- Renal Biopsy Confirms Renal Involvement.
- Other Non-Specific Abnormalities Include False-Positive Tests for Syphilis,prolonged partial Thromboplastin time and positive Test for Rheumatoid Factor.
- CNS disease usually Warrants Magnetic Resonance Imaging (MRI) of Brain or Spinal Cord and Examination of the Cerebrospinal Fluid where appropriate.
Hey,how is lupus treated ?
Treatment of Systemic Lupus Erythematosus (SLE)
- Patient with Mild Features ( Arthralgias, Arthritis, Myalgias, Fever and mild Serositis) Should be Managed with NSAIDS.
- Hydrochloroquine may be added if Required.
- Skin Lesions and Arthritis also Respond to Hydroxychloroquine.
- Photosensitive Skin Lesions Require Application of Sun-Screen Lotions.
- Patient with Severe Symptoms or Life-Threatening Features should Receive Corticosteroids.
- Actually ill patient with patient with proliferative Glomerulo-nephritis may be treated with “Pulses” of Methylprednisolone for 3 days (1 gram/day) followed by Oral Steroids.
- Immuno-suppressants likr Azathioprine, Methotrexate,Cyclophosphamide,Mycophenolate Mofetil are also useful in Controlling Severe Disease. These agents are Particularly useful in patient with Renal Invovlement. In this Regard a Combination of Intravenous Cyclophosphamide and Steroids in the Effective Redimen.