Systemic lupus erythematosus

SLE is a chronic autoimmune disease with a heterogeneous clinical course and progressive involvement of multiple organs.

SLE is a multifactorial autoimmune disease characterized by loss of self-tolerance, leading to autoantibody production, immune complex formation, and widespread inflammation. The pathophysiology involves a combination of genetic, epigenetic, hormonal, immunologic, and environmental factors. Genetic susceptibility includes specific HLA haplotypes, single nucleotide polymorphisms in immune-related genes, and deficiencies in complement components C1q and C4. Epigenetic mechanisms, including DNA hypomethylation, alter immune cell function and gene expression. Hormonal influences, particularly estrogen and the presence of two X chromosomes, contribute to the female predominance observed in SLE. Defective clearance of apoptotic cells exposes nuclear antigens, triggering abnormal activation of dendritic cells and B and T lymphocytes. This leads to the production of pathogenic autoantibodies, most notably anti-dsDNA and anti-Sm, and the formation of circulating immune complexes. These complexes deposit in tissues, activate complement, and drive local inflammation and organ damage. Dysregulated type I interferon signaling, aberrant B-cell hyperactivity, and impaired regulatory T-cell function contribute to disease propagation and chronicity. The multisystem involvement reflects the systemic distribution of immune complex deposition and inflammatory mediators.

In the US, the estimated incidence of SLE ranges from 4.9 to 7.4 cases per 100,000 person-years, while the estimated prevalence ranges from 72.8 to 178 persons per 100,000 population.

Risk factors for SLE include female sex, particularly during reproductive years, and non-White ethnicity, with higher prevalence and severity reported in individuals of African, Asian, Hispanic, and Indigenous descent. Genetic predisposition plays a key role, with increased risk among first-degree relatives and associations with specific HLA haplotypes. Environmental triggers such as UV light exposure, infections (such as EBV), and cigarette smoking may contribute to disease onset or flares. Certain drugs (such as hydralazine, minocycline, lithium, D-penicillamine, TNF-α blockers) can induce lupus-like syndromes. Hormonal factors, including estrogen exposure, are also implicated in disease susceptibility.

SLE is a chronic, relapsing-remitting autoimmune disease with a highly variable presentation. Disease activity can range from mild symptoms such as fatigue, arthralgia, and mucocutaneous lesions to severe organ involvement. Flares may occur intermittently, often triggered by environmental or physiological stressors, and are followed by periods of partial or complete remission. Lupus nephritis develops in up to 50% of patients and may present with proteinuria, hematuria, nephrotic syndrome, or progressive renal dysfunction. Neurologic involvement is reported in up to 56% of patients and can affect both the central and PNSs. Central manifestations include cognitive dysfunction, psychosis, seizures, headache, and cerebrovascular events. Peripheral neuropathies are reported in up to 28% of patients and may be sensory, motor, or mixed, including small fiber neuropathy, distal symmetric polyneuropathy, mononeuritis multiplex, and cranial neuropathies. Additional systemic involvement may include hematologic abnormalities (anemia, leukopenia, thrombocytopenia), antiphospholipid syndrome, serositis, ILD, and premature CVD.

The 10-year survival rate of patients with SLE is approximately 70%. The all-cause standard mortality rate is increased 2.6 fold in patients with SLE, and the risk of mortality is increased by 4.98, 4.67, and 2.25 fold for infections, renal disease, and CVD, respectively.