What are the skin manifestations of Systemic Lupus Erythematosus (SLE) in dermatology?

From the Guidelines

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies against nuclear antigens, leading to immune complex formation, complement activation, and subsequent tissue damage, with skin manifestations being a common and significant aspect of the disease. The pathophysiology of SLE involves a complex interplay of genetic predisposition, environmental triggers, and hormonal factors that result in dysregulation of both innate and adaptive immune responses. In SLE, there is impaired clearance of apoptotic cells, leading to exposure of nuclear antigens to the immune system. This triggers B-cell activation and production of autoantibodies, particularly antinuclear antibodies (ANAs), which form immune complexes that deposit in various tissues, causing inflammation and organ damage through complement activation and recruitment of inflammatory cells.

Skin Manifestations of SLE

Skin manifestations are present in approximately 70-80% of SLE patients and are collectively referred to as "cutaneous lupus erythematosus" (CLE) in dermatology. The classic skin manifestation is the malar or "butterfly" rash, a photosensitive erythematous rash across the cheeks and nose that spares the nasolabial folds, classified as acute cutaneous lupus erythematosus (ACLE) 1.

• Subacute cutaneous lupus erythematosus (SCLE) presents as photosensitive, non-scarring, papulosquamous or annular lesions on sun-exposed areas.
• Chronic cutaneous lupus erythematosus (CCLE), most commonly discoid lupus erythematosus (DLE), features well-defined, erythematous, scaly plaques that can lead to scarring and atrophy.
• Other cutaneous manifestations include lupus panniculitis (inflammation of subcutaneous fat), bullous lupus (vesiculobullous lesions), and non-specific findings like livedo reticularis, Raynaud's phenomenon, and vasculitic lesions. These skin manifestations not only serve as diagnostic markers but also significantly impact patients' quality of life and can precede systemic involvement by years.

Diagnosis and Treatment of Skin Manifestations

The diagnosis of CLE may be difficult, as many conditions may mimic LE, and therefore may require evaluation by an experienced dermatologist and a skin biopsy for histological analysis 1.

• The use of Cutaneous Lupus Disease Area and Severity index (CLASI) in clinical practice might be considered, at least in patients with SLE with prevalent cutaneous manifestations 1.
• First-line treatment of skin disease in SLE includes topical agents (GC, calcineurin inhibitors), antimalarials (HCQ, quinacrine), and/or systemic GC 1.
• In non-responsive cases or cases requiring high-dose GC, methotrexate, retinoids, dapsone, or mycophenolate can be added 1.

From the Research

Pathophysiology of SLE

• Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by an immune response against nuclear components 2.
• The abnormal activation of the innate immunity is central to SLE physiopathology, with dendritic cells activation and unabated secretion of IFN-alpha being key features of the disease 2.
• Autoantibodies play a crucial role in the pathogenesis of SLE, with many complement structures and additional factors implicated in the complex pathogenesis of the disease 3.
• The formation of antigen-antibody complexes triggers an immune response, leading to tissue damage and clinical manifestations of SLE 4.

Skin Manifestations of SLE

• SLE patients can experience a wide array of clinical manifestations, including skin and mucosal manifestations, which can range from mild to severe 5.
• The skin manifestations of SLE can include discoid skin lesions and the butterfly or malar rash, which have been documented in cases of SLE for nearly two centuries 5.
• Autoantibodies, such as antinucleosome and anti-dsDNA antibodies, have been associated with certain clinical manifestations of SLE, including nephritis and leukopenia 4.
• The presence of certain autoantibodies can also be associated with disease activity and damage accrual in SLE patients 4.

Dermatological Aspects of SLE

• The skin manifestations of SLE are an important aspect of the disease, with many patients experiencing skin symptoms such as rashes and lesions 5.
• The dermatological aspects of SLE can be complex, with many different factors contributing to the development of skin symptoms, including autoantibodies and immune system dysregulation 2.
• A greater understanding of the autoantibodies and immune system dysregulation involved in SLE can lead to the development of new approaches to more accurate assessments and treatments of the disease 4.