What is lupus?

Systemic Lupus Erythematosus (SLE): A Comprehensive Overview

Systemic lupus erythematosus is a complex multisystemic autoimmune disease that causes inflammation and immune-mediated damage to multiple organ systems, resulting in irreversible damage, diminished quality of life, and reduced life expectancy if not properly managed. 1

Definition and Pathophysiology

SLE is characterized by:

• Autoantibody production, particularly against nuclear antigens
• Immune complex formation and deposition in tissues
• Chronic inflammation affecting multiple organ systems
• Loss of self-tolerance and abnormal immunological function 2

Genetic and environmental factors play important roles in its pathogenesis, with disease manifestations and severity varying according to patients' racial/ethnic background and socioeconomic status 1.

Epidemiology

• Affects approximately 3.4 million people worldwide
• Predominantly affects women (~90% of cases)
• More common and severe in certain ethnic groups:
  • Latin American and North American Mestizo patients
  • African descendants
  • Native Americans 1, 3

These populations tend to develop lupus earlier, experience more severe disease, have higher disease activity levels, accrue more organ damage, and have higher mortality rates 1.

Clinical Manifestations

SLE can affect virtually any organ system:

Common Early Presentations

• Constitutional symptoms: fatigue, fever
• Mucocutaneous: lupus-specific rashes, photosensitivity, mouth ulcers, alopecia
• Musculoskeletal: joint pain, arthritis, myalgia 2

Other System Involvement

• Renal: lupus nephritis (affects ~40% of patients)
• Neuropsychiatric: seizures, psychosis, peripheral neuropathy, cognitive dysfunction
• Cardiovascular: pericarditis, myocarditis, accelerated atherosclerosis
• Pulmonary: pleural effusions, interstitial lung disease (rare, 1-15%)
• Hematologic: anemia, leukopenia, thrombocytopenia
• Gastrointestinal: various manifestations 1, 3

Diagnosis

While there are no universally accepted diagnostic criteria, the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria are widely used (96.1% sensitivity, 93.4% specificity) 3.

Key diagnostic elements include:

• Clinical manifestations: fever, cytopenia, rash, arthritis, proteinuria
• Immunologic measures: SLE-specific autoantibodies (anti-dsDNA, anti-Sm)
• Low complement levels (C3, C4)

Anti-dsDNA antibodies are particularly important for diagnosis and monitoring disease activity, though they require proper standardization as they can be found in other disorders 1.

Treatment Approach

Overarching Principles

1. Treatment must be individualized based on disease manifestations and severity
2. The therapeutic goal is to achieve remission or low disease activity as quickly as possible
3. Treatment should include preventive measures (photo-protection, osteoporosis, cardiovascular, infection prevention)
4. All patients with lupus should receive antimalarials unless contraindicated
5. Glucocorticoids should be used at the lowest possible dose for the shortest period 1

Pharmacologic Management

First-Line Therapy

• Hydroxychloroquine (HCQ): Cornerstone of SLE treatment that should be prescribed to all patients unless contraindicated
  • Reduces disease activity, prevents flares, improves long-term survival 4, 3

Additional Therapies Based on Disease Severity

• Mild disease: NSAIDs, low-dose glucocorticoids
• Moderate to severe disease: Immunosuppressive agents
  • Azathioprine
  • Mycophenolate mofetil
  • Cyclophosphamide (for severe manifestations)
• Newer FDA-approved medications:
  • Belimumab (for active SLE and lupus nephritis)
  • Voclosporin (for lupus nephritis)
  • Anifrolumab (for active SLE) 4, 3

Specific Organ System Management

Lupus Nephritis:

• Class III/IV: Methylprednisolone pulses followed by oral prednisone with mycophenolate mofetil or cyclophosphamide
• Class V: Prednisone with mycophenolate mofetil
• High-risk: High-dose intravenous cyclophosphamide 4

Neuropsychiatric Lupus:

• Inflammatory manifestations: High-dose glucocorticoids plus cyclophosphamide for severe cases
• Thrombotic/ischemic manifestations: Anticoagulation when antiphospholipid antibodies are present 4

Antiphospholipid Syndrome:

• Venous thrombosis: Warfarin with INR target 2.0-3.0
• Arterial or recurrent thrombosis: Higher intensity anticoagulation (INR 3.0-4.0) 1, 4

Monitoring and Follow-up

Regular assessment should include:

• Disease activity using validated indices (SLEDAI, BILAG)
• Annual damage assessment using SLICC/ACR Damage Index
• Laboratory monitoring (more frequent during active disease)
• Screening for comorbidities
• Drug toxicity monitoring 4

Pregnancy Considerations

• Pregnancy may increase lupus disease activity and cause mild-to-moderate flares
• Lupus nephritis and antiphospholipid antibodies are risk factors for hypertensive complications and pre-eclampsia
• Medications to avoid during pregnancy: mycophenolate mofetil, cyclophosphamide, methotrexate
• Safe medications: hydroxychloroquine, azathioprine, low-dose aspirin 1, 4

Preventive Measures

• Sun protection
• Vaccination (inactivated vaccines recommended; live vaccines avoided during immunosuppression)
• Cardiovascular risk factor control
• Osteoporosis prevention
• Lifestyle modifications: regular exercise, smoking cessation, weight control, stress management 4

Prognosis

Despite advances in treatment, SLE patients have an almost 5-fold increased risk of death compared to the general population. Common causes of morbidity and mortality include infections, cardiovascular disease, and end-organ damage 1, 3.

With proper treatment, the primary goal is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while on maintenance doses of immunomodulatory or immunosuppressive medications 3.