Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that primarily affects the skin but can also involve multiple organ systems. Since its initial description in the 19th century, understanding of SLE has significantly evolved. Characterized by periods of flare-ups and remissions, SLE often presents a diagnostic challenge due to its wide range of nonspecific symptoms. While SLE is more common in women, particularly in those of reproductive age, its prevalence is higher in individuals of African descent compared to Caucasians. Although the exact cause of SLE remains unclear, it is generally considered to result from a complex interaction of genetic susceptibility and environmental factors, leading to an autoimmune attack. 

Epidemiology

SLE predominantly affects women, with a male-to-female ratio of approximately 1:9. The disease often manifests in individuals during their 30s or 40s. The prevalence of SLE is higher in people of African descent, with African American women demonstrating a fourfold higher incidence when compared with Caucasian individuals. Ethnic disparities in disease severity and clinical outcomes have been observed, with African-American and Hispanic populations often experiencing more severe manifestations and complications. Furthermore, SLE occurs more frequently in individuals with a family history of autoimmune diseases, suggesting a genetic predisposition to the condition.

Pathophysiology

The pathogenesis of SLE involves the dysregulation of the immune system, resulting in the production of autoantibodies that attack the body’s own tissues. Genetic factors, such as the presence of certain human leukocyte antigen (HLA) alleles, combined with environmental triggers (e.g., ultraviolet (UV) light, infections, and certain medications), contribute to disease development. Immune complexes form when these autoantibodies bind to antigens, leading to tissue inflammation and damage through complement activation and the recruitment of inflammatory cells, particularly neutrophils.

Clinical Manifestations

The clinical presentation of SLE is diverse. The most common organ systems affected include the skin, joints, renal system, pulmonary system, heart, and neurological system. The most common dermatologic manifestation is the characteristic “butterfly rash,” which is a malar erythema that spans the cheeks and nose. This rash is often aggravated by sunlight, a phenomenon known as photosensitivity, which is a hallmark of SLE.

Other cutaneous manifestations include:

• Discoid rash: Red, scaly plaques that may cause scarring, typically seen on sun-exposed areas such as the face, scalp, and neck.
• Oral and nasal ulcers: Painless, shallow lesions often present on mucosal surfaces, which may persist for weeks.
• Subacute cutaneous lupus erythematosus (SCLE): Characterized by red, raised, annular lesions with an outer rim of scaling, commonly found on the chest, shoulders, and upper arms.

Systemic involvement is common in SLE and includes:

• Musculoskeletal symptoms: Joint pain and arthritis are frequent, often affecting small joints such as those in the hands, wrists, and knees. It is commonly an early finding. 
• Renal involvement: Lupus nephritis occurs in up to 60% of patients, manifesting as protein and blood in the urine, and impaired kidney function.
• Neurological manifestations: SLE can cause seizures, strokes, cognitive dysfunction, and peripheral neuropathy, known collectively as neuropsychiatric lupus.
• Cardiovascular involvement: The disease increases the risk of atherosclerosis, myocardial infarction, and pericarditis.
• Hematologic abnormalities: Anemia, leukopenia, thrombocytopenia, and the presence of antiphospholipid antibodies can lead to an increased risk of thrombosis.

Diagnosis

Diagnosing SLE is often a process of exclusion, with other diseases needing to be ruled out before SLE can be confirmed. The American College of Rheumatology established classification criteria in 1982, which were later revised in 1997 and 2012. A diagnosis is typically made when four or more of the following criteria are met at any point during the disease course:

• Malar rash (butterfly-shaped rash)
• Discoid rash
• Photosensitivity
• Oral or nasal ulcers
• Arthritis (non-erosive)
• Serositis (pleuritis or pericarditis)
• Renal disorder (proteinuria, cellular casts)
• Neurological disorder (seizures, psychosis)
• Hematologic disorder (anemia, leukopenia, thrombocytopenia)
• Immunologic disorder (positive antinuclear antibody or antiphospholipid antibodies)
• Antinuclear antibody (ANA) positivity

Blood tests, particularly for ANA, anti-double-stranded DNA, and anti-Smith antibodies, are instrumental in confirming the diagnosis. Kidney biopsy may also be required to assess the extent of renal involvement, especially in cases of lupus nephritis. Finally, skin biopsy can be diagnostic for lupus. 

Treatment

The treatment of SLE aims to control symptoms, prevent flare-ups, minimize organ damage, and improve quality of life. Management is typically multidisciplinary, involving rheumatologists, dermatologists, nephrologists, and neurologists, depending on the organs involved.

• Nonpharmacological management:

• • • Sun protection: Strict sun avoidance and use of sunscreens with a high SPF are crucial to preventing photosensitivity-related flare-ups.
    • Lifestyle modifications: Smoking cessation and regular physical activity can help reduce disease activity and improve overall health.

• Pharmacological treatment:

• • • Corticosteroids: Prednisone is commonly used to manage inflammation and acute flare-ups. Dosing varies based on disease severity and organ involvement.
    • Immunosuppressive agents: Drugs like azathioprine, methotrexate, and mycophenolate mofetil are used to control inflammation and prevent organ damage, especially in severe disease or when corticosteroid use needs to be minimized.
    • Antimalarial drugs: Hydroxychloroquine has been a cornerstone in the treatment of SLE for decades, particularly for managing skin and joint symptoms, as well as reducing flare-ups.
    • Biologics: Newer biologic therapies such as belimumab, a monoclonal antibody targeting B-lymphocyte stimulator, and rituximab, which depletes B-cells, have shown promise in managing refractory SLE. These therapies are particularly useful in patients with severe organ involvement, such as lupus nephritis.
    • NSAIDs: Arthritis, joint pain, and muscle pain can be managed with anti-inflammatory medication. 

• Targeted therapies:

• • Janus kinase (JAK) inhibitors: Medications like tofacitinib have been studied in SLE with encouraging results, offering another option for patients with moderate to severe disease who are unresponsive to traditional therapies.

Prognosis

The prognosis of SLE varies significantly based on the extent of organ involvement and the timeliness of treatment. With proper management, the 5-year survival rate is approximately 93%, and many patients achieve long-term remission. However, organ damage, particularly to the kidneys and cardiovascular system, remains a significant cause of morbidity and mortality.

Conclusion

Systemic lupus erythematosus is a multifaceted autoimmune disease that can affect various organ systems, with dermatologic manifestations often being among the first signs. Early diagnosis and individualized treatment are crucial for preventing irreversible organ damage and improving patient outcomes. Ongoing research into targeted therapies, including biologics and JAK inhibitors, offers hope for more effective treatments in the future.

References

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