Systemic Lupus Erythematosus

Systemic lupus erythematosus is a chronic autoimmune disorder primarily affecting young to middle-aged females, characterised by ANA autoantibodies, leading to immune complex deposition and multi-organ damage.

Description

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterised by multi-system involvement and chronic inflammation. It has a broad range of clinical manifestations and falls under the umbrella of rheumatic diseases. SLE primarily affects females, with a 9:1 female to male ratio, and typically presents during young adulthood.

Pathogenesis

The precise pathogenesis of SLE is complex and multifactorial, involving genetic predisposition, hormonal influences, and environmental triggers that result in abnormal immune responses. The production of autoantibodies, formation of immune complexes, and deposition in tissues lead to inflammation and eventual organ damage.

Subtype

SLE does not have distinct subtypes but the clinical presentation and organ involvement vary significantly amongst patients.

Epidemiology, Risk Factors & Associations

• Predominantly affects females of childbearing age (9:1 female to male ratio)
• More common in young adulthood
• Higher prevalence in individuals of African, Hispanic, and Asian descent
• Familial predisposition or family history of autoimmune disease
• Environmental factors including UV exposure, certain drugs, and viral infections
• Klinefelter syndrome (47, XXY) – 14 times higher risk

Clinical Features

The clinical manifestations of SLE are diverse, affecting almost any organ system.

• Constitutional symptoms (vatigue, malaise, fever, anorexia, and weight loss) are seen in >90%
• Lupus nephritis – New-onset hypertension, hematuria, proteinuria, lower extremity edema, and elevation in creatinine
• Intractable headaches are the most common CNS manifestation
• Anaemia of chronic disease is the most common haemotological manifestation
• Pleuritis is the most common pulmonary manifestation and may not always be associated with pleural effusion
• Pericarditis associated with exudative pericardial effusions is the most common cardiac manifestation
• Keratoconjunctivitis sicca is frequently seen in SLE in the presence or absence of secondary Sjogren syndrome
• Lupus arthritis is typically a non-erosive, symmetrical inflammatory polyarthritis affecting predominantly the small joints of the hands, knees, and wrists, although any joint can be involved.
• Jaccoud arthropathy results from the joint capsule and ligament laxity, leading to non-erosive deformities of the hands, including ulnar deviation and subluxation of the metacarpophalangeal joints that may mimic rheumatoid arthritis
• MDSOAPBRAIN: Malar rash, Discoid rash, Serositis, Oral ulcers, Arthritis, Photosensitivity, Blood disorders, Renal involvement, ANA positivity, Immunologic disorders, and Neurologic disorders are typical features.

Complications

Complications vary based on the organ systems involved and may include:

• Renal disease, specifically lupus nephritis, which may manifest as proteinuria, hematuria, or renal insufficiency
• Cardiovascular disease, including premature atherosclerosis, which can lead to myocardial infarction and stroke, myocarditis and pericarditis (with fibrinous exudate) which may present as chest pain and pericardial effusion
• Libman-Sacks endocarditis, also named as nonbacterial thrombotic endocarditis (NBTE) or marantic endocarditis – large vegetations on previously normal heart valves (most often mitral and aortic, on the forward flow side of the valve)
• Infections resulting from immune suppression due to the disease itself or the treatments. These infections can involve the skin, respiratory system, urinary tract, or may be systemic
• Neuropsychiatric SLE manifesting as cognitive dysfunction, mood disorders, seizures, or psychosis

Pathological Features

Histopathology

• Macroscopic: No specific macroscopic features
• Microscopic: Non-caseating granulomas, vasculitis, interface dermatitis, “wire loop” lesions in the kidneys indicating glomerular basement membrane thickening, and Libman-Sacks endocarditis in the heart. LE body or hematoxylin body is a hallmark of SLE pathology (globular mass of nuclear material that stains bluish-purple with hematoxylin)

Serology

• Antinuclear antibodies (ANA) are the hallmark of the disease
• Anti-dsDNA antibodies, Anti-Sm antibodies

Biochemistry

• Decreased complement levels (C3, C4)

Grading and Staging

No specific grading or staging system is available for SLE. Disease activity is typically monitored using clinical and laboratory markers.

Diagnosis

The diagnosis of SLE is based on a combination of clinical and laboratory criteria, outlined by the American College of Rheumatology (ACR) or the Systemic Lupus International Collaborating Clinics (SLICC) criteria.

Differential Diagnosis

• Other connective tissue diseases, e.g., Rheumatoid Arthritis, Sjögren’s Syndrome, Systemic Sclerosis
• Infectious diseases, e.g., HIV, Hepatitis C
• Drug-induced lupus

Management

The management of SLE often involves a multidisciplinary team including rheumatologists, nephrologists, and others depending on the organ involvement. Management often involves immunosuppressive therapy, with the specific regimen tailored to the individual’s disease activity and organ involvement.