Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus (SLE) is an auto-immune disorder in which antibodies against the body’s cells (nucleus and cytoplasm) are formed and affect different organs and organ systems. It has a relapsing and remitting course with multi-system involvement and varying clinical features.

The causes of SLE are multifactorial, with a mix of genetic, environmental, and host immune factors. The exact mechanism by which disease is caused is still not known. However following factors play an important role in causing SLE:

• Exaggerated immune response in which autoreactive cells produce pathogenic antibodies, the most common of which are anti-nuclear antibodies, leading to tissue injury.
• Environmental factors such as sunlight, smoking, exposure to chemicals, etc., can trigger lupus.
• Drugs such as hormone therapies and anti-hypertensives can also trigger lupus through an unknown mechanism.
• Genetics with a family history of autoimmune disorders

SLE belongs to a group of diseases called lupus. These are autoimmune diseases in which the body’s immune system attacks its tissues and causes various clinical manifestations. Following are the main types of lupus:

• Systemic lupus erythematosus (SLE)
• Drug-induced lupus erythematosus (DISLE)
• Discoid lupus erythematosus (DLE)
• Neonatal lupus erythematosus (NLE)

The worldwide prevalence of SLE varies. It remains undiagnosed for a considerable period. The highest prevalence is noted in the black population in European countries. It is primarily a disease of females. More than 90% of all diagnosed cases involve females. Males are rarely affected. The age range for affected females falls between 14 to 60 years. The high prevalence amongst females is not well-known but might have to do with estrogen effects.
Certain genetic conditions such as Klinefelter syndrome are also linked with a higher disease incidence. Risk factors for SLE include:

• Low birth weight
• Preterm birth
• Exposure to chemicals such as silica dust, pesticides, etc.
• Photosensitivity
• Estrogen therapy in postmenopausal women
• Pregnancy
• Vitamin D deficiency

The organs most affected by SLE include skin, joints, kidneys, blood cells, and nervous tissue. Signs and symptoms include:

• Malar rash-butterfly shaped reddish or purplish rash that covers cheeks and bridge of the nose. The rash can be flat or raised
• Mouth ulcers
• Renal involvement with blood, protein, and cellular casts in urine.
• Seizures
• Decreased white blood cell count and platelets
• Hemolytic anemia
• Fever – the classic triad of fever, joint pain, and rash in a woman of childbearing age should prompt investigations for a diagnosis of SLE
• Enlarged lymph nodes
• Weight changes
• Fatigue
• Photosensitivity
• Psychosis
• Plural effusion
• Pneumonia
• Nausea
• Abdominal pain
• Pericarditis

Diagnosis of SLE is based on clinical findings and lab investigations. Family history of auto-immune diseases with clinical features is highly suggestive of SLE. Lab studies used in the diagnosis of SLE include:

• CBC with differential counts
• Serum creatinine
• Urine analysis
• ESR and CRP levels
• Liver function tests
• Creatine kinase assay
• Auto-antibody tests
• Radiographs for joints, chest
• Chest CT scanning
• Echocardiography
• MRI for brain and heart involvement
• Synovial fluid aspiration
• Lumbar puncture
• Kidney biopsy

Differential diagnoses for SLE include:

• Discoid skin lesions
• Leukopenia
• Leukemia
• Interstitial lung disease
• Renal vasculitis
• Stroke
• Seizures
• Viral infections in which rash is common
• Vasculitis
• Thrombocytopenia
• Fibromyalgia
• Hepatitis C
• Rheumatoid arthritis
• Sarcoidosis
• Sjogren syndrome
• Connective tissue diseases

• Management of SLE depends upon disease severity and the extent of involvement of multiple organ systems. Skin manifestations are usually seen in milder diseases and can be controlled with NSAIDs and immunosuppressive therapy.
• Corticosteroids are used when vital organs such as the brain and kidneys are involved.
• Vitamin D supplementation can benefit patients with SLE by improving fatigue and decreasing disease activity such as cardiovascular disfunction.
• For photosensitivity sunscreen, protective clothing and avoiding sun exposure to prevent rash or disease flares are advised.
• Because of multisystem involvement multidisciplinary approach is taken with consultations from rheumatology, neurology, pulmonology, cardiology, etc.
• The mainstay of treatment is DMARD (Disease-modifying antirheumatic drugs) therapy with both biologic and non-biologic agents. It is self-administered by patients after decided intervals.
• Life-threatening conditions such as meningitis, vasculitis, and rapidly progressive glomerulonephritis require hospitalization. Fever in patients with SLE is also an indication for hospitalization as it is difficult to distinguish between fever due to acute flare from an infection.

Medications to treat SLE:

• Corticosteroids that include oral or IV prednisone.
• Antimalarials- hydroxychloroquine is very effective in patients with skin manifestations against SLE.
• DMARDS (Disease-modifying antirheumatic drugs) such as methotrexate, cyclosporin, cyclophosphamide, azathioprine, etc.
• Biologic DMARDs such as IV immunoglobulins
• NSAIDS such as ibuprofen for pain management.

SLE prognosis varies greatly depending upon several host factors such as immune response, age, gender, etc. It is a simple disease with minimal multisystem involvement and a good prognosis for some individuals. It might progress to severe complications that can cause morbidity and mortality in others.

Systemic Lupus Erythematosus is difficult to diagnose. Early diagnosis, prompt treatment, effective follow-up regimen, and lifestyle modifications are some ways to live with this remitting and recurring disease.

• When presenting clinically with multi-system involvement, at-risk individuals that include women aged 16 t0 60 years should always be considered for autoimmune disorders such as SLE.
• In most individuals, autoantibodies against the disease develop before any clinical signs or symptoms become apparent. So, people with a family history of autoimmune disorders should undergo screening early to detect the disease.
• After the disorder has been diagnosed, an effective multi-disciplinary approach should be taken for its management. Patients should be educated about the importance of treatment compliance.
• The diagnosed patient should be kept at follow-up at regular intervals to see the progress of the disease and determine the development of complications, if any. Clinical signs such as fever should not be ignored and prompt urgent clinical care or sometimes hospitalization.
• Because it is a lifetime disease, patient education regarding lifestyle modifications and their importance is essential. Lifestyle modifications include avoiding exposure to sunlight and harmful chemicals, maintaining a balanced diet, exercising regularly, avoiding harmful drugs that trigger SLE, avoiding smoking, adding vitamin D supplements to diet, etc.