What is Systemic Lupus Erythematosus (SLE) and what are its signs and symptoms?

What is Systemic Lupus Erythematosus (SLE)?

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by immune complex deposition and vasculopathy that can affect any organ or tissue in the body. 1

Disease Definition and Epidemiology

• SLE is a prototypic autoimmune disease with clinical heterogeneity, predominantly affecting women (approximately 90% of cases) 1, 2
• Prevalence ranges from 20 to 150 cases per 100,000 population, with approximately 3.4 million people affected worldwide 1, 2
• The disease primarily affects women of reproductive age 1
• Pathogenesis involves a complex interplay between genetic susceptibility and environmental factors, with dysregulation of both innate and adaptive immune systems and type-1 interferon dysregulation as a common denominator 1

Signs and Symptoms

Constitutional and Early Manifestations

• Fatigue is one of the earliest and most common complaints 3
• Fever can be a presenting feature and is included in classification criteria 2

Mucocutaneous Manifestations

• Lupus-specific rash is a characteristic early symptom 3
• Mouth ulcers (oral or nasal ulcers) are common mucocutaneous features 3
• Alopecia (hair loss) frequently occurs 3
• Cutaneous involvement is a defining feature of the disease 1

Musculoskeletal Symptoms

• Joint pain (arthralgia) and arthritis are among the earliest complaints 3, 2
• Myalgia (muscle pain) is commonly reported 3
• Musculoskeletal manifestations affect most patients during disease course 1

Hematological Manifestations

• Cytopenia (low blood cell counts) including anemia, leukopenia, and thrombocytopenia 1, 2
• Hemolytic anemia can occur, particularly in advanced disease stages 1
• Autoimmune hemolytic anemia (AIHA) results from increased eryptosis (programmed red blood cell death) 1
• Lower hematocrit levels with higher percentages of phosphatidylserine-exposing erythrocytes 1

Renal Manifestations

• Lupus nephritis affects approximately 40% of SLE patients 2
• Proteinuria is a key indicator of kidney involvement 2
• Approximately 10% of lupus nephritis patients develop end-stage kidney disease after 10 years 2
• Renal involvement is a major cause of morbidity and mortality 1

Pulmonary Manifestations

• Between 20% and 90% of SLE patients develop respiratory involvement during disease course 1
• Pleural involvement is the most common pulmonary manifestation 1
• Dyspnea (shortness of breath) should prompt evaluation for lung disease 1
• Chest pain is a concerning respiratory symptom 1
• Reduced exercise tolerance may indicate pulmonary involvement 1
• Cough and hemoptysis warrant investigation for underlying lung disease 1
• Interstitial lung disease (ILD) occurs in 1% to 15% of SLE patients, though it is less severe than in other connective tissue diseases 1

Neurological Manifestations

• Neuropsychiatric symptoms can occur and affect the central nervous system 1, 3
• Neurologic involvement is part of the multisystem disease spectrum 1

Cardiovascular Manifestations

• Cardiovascular disease is a significant comorbidity requiring vigilant management 3
• Heart involvement can occur as part of multisystem disease 1

Gastrointestinal Manifestations

• Gastrointestinal symptoms may be present 1

Immunological Features

• Autoantibody production is a hallmark, with virtually all SLE patients having autoantibodies 1, 3, 2
• Anti-double-stranded DNA (anti-dsDNA) antibodies are highly specific for SLE 1, 2, 4
• Anti-Sm antibodies are highly specific for SLE and associated with hematological disorders 1, 2
• Anti-U1-RNP antibodies are associated with increased risk of interstitial lung disease 1
• Hypocomplementaemia (low complement levels) is characteristic 2
• Antiphospholipid antibodies may be present 2

Clinical Pitfalls and Important Considerations

• SLE has variable presentation, course, and prognosis, making early recognition challenging 1
• The disease can occasionally be limited to one or few organs initially, potentially delaying diagnosis 1
• Infections represent a paradoxical complication despite the autoimmune nature, accounting for 25-50% of overall mortality 1
• More than 20% of hospitalizations are due to infections, with Streptococcus pneumoniae being particularly common (13 times higher incidence than general population) 1
• Disease activity and immunosuppressive therapy both contribute to infection risk through aberrant immune responses, complement dysregulation, and medication effects 1
• Pulmonary manifestations follow a chronic course associated with significantly worse prognosis and higher mortality 1