Systemic Lupus Erythematosus (SLE)

• Systemic Lupus Erythematosus (SLE) is a chronic multisystem autoimmune disease.
• The disease is characterized by periods of remission and exacerbation.
• SLE has a higher prevalence in women, with a female-to-male ratio of 9:1.
• The frequency of SLE is approximately 1 in 700 among women of childbearing age (20s-30s).
• The prevalence of SLE is 1 in 2500 in certain populations.
• SLE is 2-3 times more prevalent in blacks and Hispanics compared to whites.
• Any organ of the body can be affected by SLE.

Etiology and Pathogenesis of SLE

• The exact cause of SLE is unknown.
• A fundamental defect in SLE is the loss of self-tolerance.
• Genetic, environmental, and immunological factors contribute to the development of SLE.

Genetic Factors

• Family members of individuals with SLE have an increased risk of developing the disease.

Environmental Factors

• Exposure to UV light can induce apoptosis in cells, altering DNA and making it immunogenic and stimulates keratinocytes to produce IL-1, which promotes inflammation.
• Women are 10 times more likely to develop SLE than men during reproductive years.
• Exacerbations of SLE can occur during normal menses and pregnancy.
• Certain drugs such as Hydralazine, Procainamide, Isoniazid, and D-penicillamine can induce SLE symptoms.
  • These symptoms arise months to years after exposure to the drugs.
  • Symptoms typically resolve within days to months after the drug is withdrawn.
• Infections may trigger SLE via molecular mimicry and nonspecific activation of T or B cells.
  • Epstein-Barr virus and Cytomegalovirus have been a recent area of interest in SLE etiology.

Immunological Factors

• Loss of self-tolerance in B cells is an immunological factor of SLE.
• Loss of self-tolerance in CD4+ helper T cells is an immunological factor of SLE.
• Unregulated B-cell activation is an immunological factor of SLE.
• Self nucleic acids mimic microbial antigens, releasing type I interferons.
  • This activates dendritic cells and B cells, promoting T helper-1 (TH1) responses, and leads to the production of autoantibodies.
• Nuclear DNA and RNA in immune complexes activate B lymphocytes, leading to the production of antinuclear autoantibodies.

Summary of SLE Development

• SLE is a complex disorder of multifactorial origin which results from interactions among genetic, immunological, and environmental factors.
• Activation of helper T cells and B cells contribute to SLE.
• Production of autoantibodies drives SLE.

Spectrum of Autoantibodies in SLE

• A hallmark of SLE is the production of autoantibodies.
• Types of autoantibodies include:
  • Nuclear.
  • Cytoplasmic components.
  • Targets Against cell surface antigens of blood cells.
  • Antiphopholipid.

Antinuclear Antibodies (ANAs)

• ANAs are directed against nuclear antigens.
• ANAs are grouped into four categories:
  • Antibodies to DNA.
  • Antibodies to histones.
  • Antibodies to non-histone proteins bound to RNA.
  • Antibodies to nucleolar antigens.
• Indirect immunofluorescence is a common method for detecting ANAs.
• Antibodies diagnostic of SLE include Anti ds-DNA and Anti-Sm.

Mechanism of Tissue Injury

• Immune complexes (DNA-anti-DNA complexes) deposit in tissues.
• A type III hypersensitivity reaction is triggered.
• Inflammation is induced.
• Neutrophils and monocytes release lysosomal enzymes and toxic free radicals.
• This leads to tissue injury and visceral lesions.
• LE bodies or hematoxylin bodies occur in tissues when nuclei of damaged cells react with ANAs, lose their chromatin pattern, and become homogenoeus.

Clinical Manifestations of SLE

• Common sites affected by SLE include:
  • Dermatological involvement
  • Mucosal involvement
  • Renal disorder
  • Neurological disorder
  • Musculoskeletal disorder
  • Hematological abnormalities
  • Cardiovascular manifestations
  • Pulmonary manifestations
  • Gastrointestinal, hepatic, and pancreatic manifestations
  • Secondary Sjogren's syndrome

General Symptoms

• Fatigue.
• Fever.
• Weight changes.

Dermatological Involvement

• Includes 3 important features:
  • Malar rash (Butterfly rash): Fixed erythema, flat or raised, over the malar eminences affecting up to 50% of SLE patients.
  • Discoid rash: Erythematous raised patches with scaling.
  • Photosensitivity.

Mucosal Involvement

• Causes Painless oral or nasopharyngeal ulcerations.

Renal Disorder (Lupus Nephritis)

• Persistent proteinuria (>0.5g protein/day or 3+).
• Cellular casts in urine (RBC, Hb, Granular).
• Hematuria.

Musculoskeletal System

• Arthralgia.
• Myalgia.
• Arthritis: Non-erosive arthritis with no deformity affecting small joints of the hands, wrists and knees.

Neurological Disorder

• Antibodies against synaptic membrane protein.
• Manifestations include:
  • Seizures: Generalized or partial.
  • Psychosis: Paranoia or hallucinations.

Hematological Abnormalities

• Hemolytic anemia
• Leukopenia
• Lymphopenia
• Thrombocytopenia.

Pulmonary Manifestations

• Two most common manifestations (50% patients):
  • Pleuritis.
  • Pleural effusion.

Cardiovascular Manifestations

• Pericarditis is the most common cardiac manifestation.
• Myocarditis.
• Endocarditis (Libman-Sacks endocarditis).
• Valvular abnormalities: stenosis and/or regurgitation
• Accelerated coronary atherosclerosis: angina, MI.
• Vasculitis: Deep vein thrombosis (DVT).

Gastrointestinal, Pancreatic, Splenic and Hepatic Manifestation

• Nausea, dyspepsia and peptic ulcer disease (drug related in most cases).
• Mesenteric vasculitis.
• Bowel infarction.
• Peritonitis.
• Pancreatitis.
• Lupus hepatitis.
• Splenomegaly.

Secondary Sjogren's Syndrome

• Includes:
  • Dry eyes (keratoconjunctivitis sicca)
  • Dry mouth (xerostomia)
• Immunologically mediated destruction of lacrimal and salivary glands.

Diagnostic Criteria for SLE

• In order to diagnose SLE, the patients must meet 4 of the 11 the criteria.
• Malar rash includes Fixed erythema, flat or raised, sparing the nasolabial folds.
• Discoid Rash includes Erythematous raised patches with adherent karatotic scaling and follicular plugging and atrophic scarring occurs in older lesions.
• Photosensitivity presents as Unusual reaction to sunlight.
• Oral Ulcers include Painless oral ulcertation or nasopharyngeal ulcerations, usually painless,.
• Arthritis is Nonerosive arthritis involving two or more peripheral joints.
• Serositis includes Pleuritis or Pericarditis.
• Renal disorder presents as Persistent proteinuria >0.5 gm/dL or >3 if quantitation cannot be performed or Cellular casts.
• Neurologic Disorder presents as Seizures or Psychosis.
• Hematologic Disorder presents as Hemolytic anemia, Leukopenia, Lymphopenia or Thrombocytopenia.
• Immunological disorder presents as Anti-DNA antibody to native DNA in abnormal titer, or Anti-Sm-presence of antibody to Sm nuclear antigen and Positive finding of antiphospholipid antibodies.
• Antinuclear Antibody is an abnormal titer of antinuclear antibody by immunofluorescence.

Prognosis

• With good management, the ten years survival in SLE is over 90%.
• Major cause of death is Renal Failure and Infections.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. It's more common in women and certain ethnic groups. Genetic and environmental factors play a role in its development.