systemic lupus erythematosus

systemic lupus erythematosus
Name	Systemic lupus erythematosus
Synonyms	Lupus, SLE
Caption	The classic malar or "butterfly" rash
Field	Rheumatology, Immunology
Symptoms	Variable, including rash, arthritis, fatigue, fever
Complications	Lupus nephritis, Neuropsychiatric lupus, Pleurisy, Pericarditis
Onset	Most common 15–45 years
Duration	Chronic
Causes	Complex interplay of genetic, hormonal, environmental factors
Risks	Female sex, family history, certain genetic markers
Diagnosis	Based on symptoms and blood tests (ANA, anti-dsDNA)
Differential	Rheumatoid arthritis, Sjögren syndrome, Fibromyalgia
Prevention	None known
Treatment	NSAIDs, Antimalarials, Corticosteroids, Immunosuppressants
Medication	Hydroxychloroquine, Azathioprine, Mycophenolate mofetil, Belimumab
Prognosis	Variable; improved with modern treatment
Frequency	~20–150 per 100,000

systemic lupus erythematosus is a chronic autoimmune disease characterized by multisystem inflammation and the production of autoantibodies. It can affect virtually any organ system, including the skin, joints, kidneys, and central nervous system. The clinical course is highly variable, ranging from mild episodic illness to severe, life-threatening disease. Its name derives from the Latin for "wolf," historically describing facial lesions, and "systemic" indicates its widespread nature.

Signs and symptoms

Constitutional symptoms like profound fatigue, fever, and weight loss are common. Cutaneous manifestations include the classic photosensitive malar "butterfly" rash, discoid lupus lesions, and oral or nasal ulcers. Musculoskeletal involvement often presents as a non-erosive polyarthritis or arthralgia. Serious internal organ disease may involve the kidneys, known as lupus nephritis, the pleura or pericardium causing pleurisy or pericarditis, and the brain leading to seizures or psychosis. Hematologic abnormalities like leukopenia, lymphopenia, and Coombs-positive hemolytic anemia are frequent.

Causes and pathophysiology

The etiology involves a complex interplay of genetic susceptibility, hormonal factors, and environmental triggers. Strong genetic associations exist with genes in the major histocompatibility complex, particularly HLA-DR2 and HLA-DR3, and other loci involved in immune regulation like IRF5 and STAT4. The female predominance suggests a role for estrogen. Environmental triggers include ultraviolet light, certain medications like procainamide, infections such as Epstein-Barr virus, and possibly silica exposure. Pathophysiologically, loss of immune tolerance leads to aberrant activation of B lymphocytes and T lymphocytes, production of autoantibodies like anti-double stranded DNA, and formation of immune complexes that drive inflammation and tissue damage.

Diagnosis

Diagnosis is clinical and serological, based on criteria established by organizations like the American College of Rheumatology and the European League Against Rheumatism. Key laboratory findings include a positive antinuclear antibody test, which is highly sensitive, and more specific antibodies such as anti-Smith and anti-double stranded DNA. Other supportive tests include assessment of complement levels (low C3 and C4), complete blood count, and urinalysis with sediment examination for active nephritis. Biopsy of affected tissue, particularly the kidney, is often crucial for classifying disease severity and guiding therapy.

Treatment

Treatment is tailored to disease severity and organ involvement. For mild disease, nonsteroidal anti-inflammatory drugs and antimalarials like hydroxychloroquine are cornerstone therapies. For major organ involvement, glucocorticoids such as prednisone and stronger immunosuppressive drugs are used, including azathioprine, mycophenolate mofetil, and cyclophosphamide. The monoclonal antibody belimumab, which inhibits B-lymphocyte stimulator, is approved for active autoantibody-positive disease. Other emerging therapies target specific pathways like the interferon signature. Management also emphasizes sun protection, cardiovascular risk reduction, and vaccinations.

Epidemiology

It disproportionately affects women of childbearing age, with a female-to-male ratio of about 9:1. Incidence and prevalence vary globally, being higher in people of African, Hispanic, Asian, and Native American ancestry compared to those of European descent. In the United States, prevalence estimates range from approximately 20 to 150 cases per 100,000 individuals. The reasons for these ethnic disparities are multifactorial, involving genetic, socioeconomic, and healthcare access factors. The disease can occur at any age, including childhood and older adulthood.

Prognosis

The prognosis has improved dramatically since the mid-20th century with earlier diagnosis and advanced immunosuppressive regimens, raising the 10-year survival rate to over 90%. However, mortality remains higher than the general population, often due to active disease, infections from immunosuppression, or accelerated atherosclerosis leading to myocardial infarction and stroke. Long-term damage accrual, as measured by tools like the Systemic Lupus International Collaborating Clinics Damage Index, significantly impacts quality of life. Factors associated with a poorer prognosis include major organ involvement, high disease activity, low socioeconomic status, and certain ethnic backgrounds.

Category:Autoimmune diseases Category:Rheumatology Category:Systemic connective tissue disorders