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Systemic Lupus Erythematosus (SLE)

Updated : January 5, 2024





Background

  • Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by systemic inflammation and immune dysregulation. SLE can affect multiple organ systems, including the skin, joints, kidneys, heart, lungs, and central nervous system. It is a rare condition, with an estimated prevalence of 20-150 cases per 100,000 people worldwide.
  • Women are affected more commonly than men, and onset typically occurs in the reproductive years, with a peak incidence in the third decade of life. The etiology of SLE is thought to be multifactorial, with genetic, environmental, and hormonal factors all believed to play a role. Treatment for SLE typically involves the use of immunosuppressive agents and corticosteroids to manage inflammation and prevent organ damage. With proper management, many patients with SLE can lead full and productive lives. 

Epidemiology

Anatomy

Pathophysiology

The pathophysiology of Systemic Lupus Erythematosus (SLE) involves immune system dysregulation resulting in autoantibodies against self-antigens. Below are the details:  

  • Genetics: SLE has a strong genetic component, with multiple genes involved in the development of the disease. Mutations in genes encoding complement components, interferon receptors, and toll-like receptors have been linked to the disease. 
  • Environmental factors: Environmental factors, including UV radiation, infections, and medications, have been implicated in the pathogenesis of SLE. 
  • Immune system dysregulation: Dysregulation of both the innate and adaptive immune systems in SLE leads to the production of autoantibodies against self-antigens, such as dsDNA, histones, and ribonucleoproteins. Immune complexes formed by these autoantibodies and their targets can then deposit in tissues and organs, leading to inflammation and tissue damage. 
  • Type I interferon pathway activation: Activation of the type I interferon pathway is a hallmark of SLE, and it is thought to be driven by immune complex deposition and the recognition of self-DNA by toll-like receptors. 
  • B cell hyperactivity: Abnormalities in B cell activation, differentiation, and survival also contribute to the pathogenesis of SLE. B cells in SLE patients produce autoantibodies and are resistant to apoptosis, which contributes to the persistence of autoantibodies. 
  • T cell abnormalities: T cells in SLE patients are also dysregulated, with a shift towards Th2 and Th17 responses, as well as abnormal activation of T follicular helper cells, which are important for B cell activation and differentiation. 
  • Inflammatory cytokines: Inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha, are also elevated in SLE patients and contribute to the chronic inflammation and tissue damage seen in the disease. 
  • Complement system activation: Dysregulation of the complement system, both in terms of deficiency and overactivation, is also implicated in the pathogenesis of SLE. 

Etiology

  • Genetics: There are multiple genes implicated in its pathogenesis with strong genetic component to SLE. Studies have shown that relatives of individuals with SLE have a higher risk of developing the disease. 
  • Environmental factors: Several environmental factors have been linked to the development of SLE, including exposure to sunlight, infections, and certain medications. Exposure to UV light is thought to trigger disease in genetically susceptible individuals. Infections with certain viruses, such as Epstein-Barr virus, have also been associated with the development of SLE. Certain medications, such as hydralazine and procainamide, have been shown to induce SLE-like symptoms in some patients. 
  • Hormonal factors: Hormonal factors, particularly estrogen, are thought to play a role in the development of SLE. The disease is less common in men when compared to women, and symptoms may worsen during pregnancy or with the use of hormonal contraceptives. 
  • Immune dysregulation: SLE is characterized by dysregulation of the immune system, with an imbalance between T cells, B cells, and other immune cells. The production of autoantibodies, which attack the body’s own tissues, is a hallmark of the disease. 
  • Other factors: SLE include smoking, stress, and exposure to certain chemicals may contribute to the development of disease. 

Genetics

Prognostic Factors

  • Age of onset: SLE that begins at a younger age is associated with a more severe disease course and worse outcomes. 
  • Ethnicity: People of African, Hispanic, and Asian descent tend to have worse outcomes than people of European descent. 
  • Disease severity: The severity of SLE symptoms at the time of diagnosis can predict future disease activity and organ damage. 
  • Organ involvement: SLE can affect various organs, and the involvement of certain organs, such as the kidneys or central nervous system, can indicate a worse prognosis. 
  • Autoantibodies: The presence of certain autoantibodies, such as anti-dsDNA and anti-Ro/SSA, can indicate a more severe disease course and worse outcomes. 
  • Treatment response: Response to treatment is an important prognostic factor, as those who respond poorly to standard treatments may have a worse prognosis. 

Clinical History

Systemic Lupus Erythematosus (SLE) can present with a variety of symptoms, and the clinical presentation can vary widely depending on the patient’s age, sex, race, and other factors. 

  • Age group: SLE can affect individuals of all ages, but it is mostly diagnosed in women of childbearing age (15-45 years). However, it can also affect children, adolescents, and older adults. 

Physical Examination

  • Skin: The presence of a butterfly rash across the cheeks and nose is a classic sign of SLE. Other skin findings may include discoid lesions, photosensitivity, and skin ulcerations. 
  • Joints: Joint pain, stiffness, and swelling may be present, with tenderness and limited range of motion. This can be symmetrical or asymmetrical. 
  • Cardiovascular system: Heart murmurs, pericardial rubs, or irregular rhythms may indicate inflammation or damage to the heart. 
  • Respiratory system: Pleuritic chest pain, shortness of breath, and coughing may indicate lung involvement in SLE. 
  • Renal system: Proteinuria and hematuria may be present, which could indicate kidney involvement. 
  • Neurological system: Cranial nerve abnormalities, seizures, cognitive dysfunction, and mood disorders may indicate nervous system involvement. 
  • Gastrointestinal system: Abdominal pain, diarrhoea, and nausea may indicate gastrointestinal involvement. 

Age group

Associated comorbidity

  • SLE is often associated with other autoimmune diseases such as rheumatoid arthritis, Sjogren’s syndrome, and systemic sclerosis. In addition, SLE can be triggered by certain medications, infections, and environmental factors. 

Associated activity

Acuity of presentation

  • SLE can have an acute or insidious onset, and the symptoms can develop over weeks, months, or years. Some patients may present with a sudden onset of symptoms such as fever, rash, and joint pain, while others may have a more gradual onset of fatigue, malaise, and arthralgia. The severity of disease can range from mild to life-threatening, and patients may experience flares and remissions throughout the course of the disease. 

Differential Diagnoses

  • Rheumatoid arthritis 
  • Sjögren’s syndrome 
  • Systemic sclerosis (scleroderma) 
  • Dermatomyositis 
  • Polymyositis 
  • Mixed connective tissue disease 
  • Vasculitis 
  • Drug-induced lupus erythematous 
  • Infectious diseases such as viral hepatitis, Lyme disease, and HIV/AIDS. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

  • Patients with SLE are advised to avoid exposure to direct sunlight, to wear protective clothing, and to use sunscreen. They should avoid smoking and limit alcohol intake. 

  • a. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids: NSAIDs may be used to relieve pain and inflammation, while corticosteroids may be used to reduce inflammation in moderate to severe cases. 
  • b. Disease-modifying antirheumatic drugs (DMARDs): DMARDs may be used to control the underlying disease and prevent organ damage. Examples of DMARDs include hydroxychloroquine, methotrexate, and azathioprine. 
  • c. Immunosuppressive agents: Immunosuppressive agents may be used to suppress the immune system and prevent damage to organs. Examples include cyclophosphamide and mycophenolate mofetil. 
  • d. Biologic agents: Biologic agents may be used in severe cases of SLE to target specific cells or proteins in the immune system. Examples include rituximab and belimumab. 

  • a. Plasmapheresis: Plasmapheresis is a procedure in which the liquid portion of the blood (plasma) is removed and replaced with a fluid such as saline or albumin. It may be used in severe cases of SLE to remove antibodies that are attacking the body’s own tissues. 
  • b. Kidney transplantation: In cases where SLE has caused kidney failure, kidney transplantation may be necessary. 

  • The management of SLE involves distinct phases, including acute, subacute, and chronic phases. During the acute phase, treatment is focused on relieving symptoms and preventing organ damage.
  • In the subacute phase, treatment is focused on controlling the underlying disease and preventing organ damage. In the chronic phase, treatment is focused on preventing flares and maintaining remission. Regular monitoring and follow-up are also important during all phases of management. 

Medication

 

aspirin

3 g orally in divided doses as needed



hydroxychloroquine sulfate 

200 - 400

mg

Tablet

Orally 

once a day



belimumab 

Indicated for the above condition in people who are already receiving a therapy
Intravenous
10 mg/kg intravenously every 2 weeks multiplied by 3 doses
Maintenance dose- 10 mg/kg intravenously every month
Subcutaneous
200 mg subcutaneously every week
If changing from intravenous to subcutaneous dose, administer the 1st subcutaneous dose 7-28 days later and the last intravenous dose



amiselimod phosphate (investigational drug) 

0.2 - 0.4

mg

Orally 

Off-label as per clinical study



resomelagon 

It is currently in the developmental stages for treating various systemic inflammatory diseases including lupus erythematosus and psoriatic arthritis



 

azathioprine 

For >5 years old:
Take a dose of 2 to 3 mg/kg orally daily



 

Media Gallary

Systemic Lupus Erythematosus (SLE)

Updated : January 5, 2024




  • Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by systemic inflammation and immune dysregulation. SLE can affect multiple organ systems, including the skin, joints, kidneys, heart, lungs, and central nervous system. It is a rare condition, with an estimated prevalence of 20-150 cases per 100,000 people worldwide.
  • Women are affected more commonly than men, and onset typically occurs in the reproductive years, with a peak incidence in the third decade of life. The etiology of SLE is thought to be multifactorial, with genetic, environmental, and hormonal factors all believed to play a role. Treatment for SLE typically involves the use of immunosuppressive agents and corticosteroids to manage inflammation and prevent organ damage. With proper management, many patients with SLE can lead full and productive lives. 

The pathophysiology of Systemic Lupus Erythematosus (SLE) involves immune system dysregulation resulting in autoantibodies against self-antigens. Below are the details:  

  • Genetics: SLE has a strong genetic component, with multiple genes involved in the development of the disease. Mutations in genes encoding complement components, interferon receptors, and toll-like receptors have been linked to the disease. 
  • Environmental factors: Environmental factors, including UV radiation, infections, and medications, have been implicated in the pathogenesis of SLE. 
  • Immune system dysregulation: Dysregulation of both the innate and adaptive immune systems in SLE leads to the production of autoantibodies against self-antigens, such as dsDNA, histones, and ribonucleoproteins. Immune complexes formed by these autoantibodies and their targets can then deposit in tissues and organs, leading to inflammation and tissue damage. 
  • Type I interferon pathway activation: Activation of the type I interferon pathway is a hallmark of SLE, and it is thought to be driven by immune complex deposition and the recognition of self-DNA by toll-like receptors. 
  • B cell hyperactivity: Abnormalities in B cell activation, differentiation, and survival also contribute to the pathogenesis of SLE. B cells in SLE patients produce autoantibodies and are resistant to apoptosis, which contributes to the persistence of autoantibodies. 
  • T cell abnormalities: T cells in SLE patients are also dysregulated, with a shift towards Th2 and Th17 responses, as well as abnormal activation of T follicular helper cells, which are important for B cell activation and differentiation. 
  • Inflammatory cytokines: Inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha, are also elevated in SLE patients and contribute to the chronic inflammation and tissue damage seen in the disease. 
  • Complement system activation: Dysregulation of the complement system, both in terms of deficiency and overactivation, is also implicated in the pathogenesis of SLE. 
  • Genetics: There are multiple genes implicated in its pathogenesis with strong genetic component to SLE. Studies have shown that relatives of individuals with SLE have a higher risk of developing the disease. 
  • Environmental factors: Several environmental factors have been linked to the development of SLE, including exposure to sunlight, infections, and certain medications. Exposure to UV light is thought to trigger disease in genetically susceptible individuals. Infections with certain viruses, such as Epstein-Barr virus, have also been associated with the development of SLE. Certain medications, such as hydralazine and procainamide, have been shown to induce SLE-like symptoms in some patients. 
  • Hormonal factors: Hormonal factors, particularly estrogen, are thought to play a role in the development of SLE. The disease is less common in men when compared to women, and symptoms may worsen during pregnancy or with the use of hormonal contraceptives. 
  • Immune dysregulation: SLE is characterized by dysregulation of the immune system, with an imbalance between T cells, B cells, and other immune cells. The production of autoantibodies, which attack the body’s own tissues, is a hallmark of the disease. 
  • Other factors: SLE include smoking, stress, and exposure to certain chemicals may contribute to the development of disease. 
  • Age of onset: SLE that begins at a younger age is associated with a more severe disease course and worse outcomes. 
  • Ethnicity: People of African, Hispanic, and Asian descent tend to have worse outcomes than people of European descent. 
  • Disease severity: The severity of SLE symptoms at the time of diagnosis can predict future disease activity and organ damage. 
  • Organ involvement: SLE can affect various organs, and the involvement of certain organs, such as the kidneys or central nervous system, can indicate a worse prognosis. 
  • Autoantibodies: The presence of certain autoantibodies, such as anti-dsDNA and anti-Ro/SSA, can indicate a more severe disease course and worse outcomes. 
  • Treatment response: Response to treatment is an important prognostic factor, as those who respond poorly to standard treatments may have a worse prognosis. 

Systemic Lupus Erythematosus (SLE) can present with a variety of symptoms, and the clinical presentation can vary widely depending on the patient’s age, sex, race, and other factors. 

  • Age group: SLE can affect individuals of all ages, but it is mostly diagnosed in women of childbearing age (15-45 years). However, it can also affect children, adolescents, and older adults. 
  • Skin: The presence of a butterfly rash across the cheeks and nose is a classic sign of SLE. Other skin findings may include discoid lesions, photosensitivity, and skin ulcerations. 
  • Joints: Joint pain, stiffness, and swelling may be present, with tenderness and limited range of motion. This can be symmetrical or asymmetrical. 
  • Cardiovascular system: Heart murmurs, pericardial rubs, or irregular rhythms may indicate inflammation or damage to the heart. 
  • Respiratory system: Pleuritic chest pain, shortness of breath, and coughing may indicate lung involvement in SLE. 
  • Renal system: Proteinuria and hematuria may be present, which could indicate kidney involvement. 
  • Neurological system: Cranial nerve abnormalities, seizures, cognitive dysfunction, and mood disorders may indicate nervous system involvement. 
  • Gastrointestinal system: Abdominal pain, diarrhoea, and nausea may indicate gastrointestinal involvement. 
  • SLE is often associated with other autoimmune diseases such as rheumatoid arthritis, Sjogren’s syndrome, and systemic sclerosis. In addition, SLE can be triggered by certain medications, infections, and environmental factors. 
  • SLE can have an acute or insidious onset, and the symptoms can develop over weeks, months, or years. Some patients may present with a sudden onset of symptoms such as fever, rash, and joint pain, while others may have a more gradual onset of fatigue, malaise, and arthralgia. The severity of disease can range from mild to life-threatening, and patients may experience flares and remissions throughout the course of the disease. 
  • Rheumatoid arthritis 
  • Sjögren’s syndrome 
  • Systemic sclerosis (scleroderma) 
  • Dermatomyositis 
  • Polymyositis 
  • Mixed connective tissue disease 
  • Vasculitis 
  • Drug-induced lupus erythematous 
  • Infectious diseases such as viral hepatitis, Lyme disease, and HIV/AIDS. 

  • Patients with SLE are advised to avoid exposure to direct sunlight, to wear protective clothing, and to use sunscreen. They should avoid smoking and limit alcohol intake. 

  • a. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids: NSAIDs may be used to relieve pain and inflammation, while corticosteroids may be used to reduce inflammation in moderate to severe cases.