Armando Hasudungan
Biology and Medicine videos

Systemic Lupus Erythematosus

Overview

Overview Systemic lupus erythematosus (SLE) is an autoimmune disease. SLE is a chronic multi-system disorder that most commonly affects women during their reproductive years.  The pathophysiology of SLE involve many vital organs and tissues such as the brain, blood, and the kidney, the vast majority affecting women of childbearing age. Immune-system aberrations, as well as heritable, hormonal, and environmental factors, contribute to the expression of organ damage. Immune complexes, autoantibodies, autoreactive lymphocytes, dendritic cells, and local factors are all involved in clinical manifestations of SLE. Earlier diagnosis and better management have resulted in a lower prevalence of life-threatening disease.

Definition
Systemic lupus erythematosus (SLE): Complex clinical syndrome characterized by autoimmune-mediated, systemic inflammation that can affect multiple organs.

Epidemiology

  • The prevalence ranges from 20 to 150 cases per 100,000 population
  • SLE occurs most frequently between the ages of 15 and 45 years, when it is 12 times more common in females than in males.

Risk Factors

  • Female sex
  • 15-45 years of age
  • African/Asian decent in Europe and US
  • Drugs

Precipitating factors

  • Sun exposure (UV-B)
  • Infections
  • Stress
  • Surgery
  • Pregnancy
Side note Precipitating factors are factors that exacerbate and cause acute SLE reactions

Sign and Symptoms

SLE is 10–20 times more common in women than men, and most likely to develop between the ages of 15–40 years.

Constitutional symptoms

  • Fatigue
  • Myalgia
  • Weight Loss
  • Fever

Specific Organ involvement

  • Arthritis
    • Morning stiffness and polyarticular, symmetrical arthralgia or arthritis occur in 90% of cases
  • Rash
    • Butterfly rash – 50% (following sun exposure lasts a few days and is reocurring)
    • Discoid rash (Erythematous raised patches with adherent keratotic scaling and follicular plugging.)
  • Photosensitivity
  • Raynaud phenomenon
  • Hypertension
  • Renal Involvement (50% of cases) – 9 Classes of lupus nephritis according to WHO
  • Gastrointestinal Involvement
    • Abdominal pain
    • Nausea, vomiting
    • Ulceration [also medication side effects]
  • Pulmonary Involvement
    • Pleurisy
    • Pleural effusion
    • Pneumonitis
    • Interstitial lung disease
    • Pulmonary hypertension
    • Alveolar hemorrhage
  • Neurological Involvement
    • Cognitive defects
    • Delirium
    • Psychosis
    • Seizures
    • Headache
    • Peripheral neuropathies
  • Cardiavascular involvement
    • Pericardial disease such as percardial effusion
  • Keratoconjunctivitis sicca
  • Lymphadenopathy
Keratoconjunctivitis sicca also known as dry eye is a disorder of the tear film which occurs due to tear deficiency or excessive tear evaporation; it causes damage to the interpalpebral ocular surface and is associated with a variety of symptoms reflecting ocular discomfort

Differential Diagnosis

Non-inflammatory Arthritis

Inflammatory Arthritis

  • Crystal arthropathy
  • Infectious
  • Seronegative arthritis (spondylarthropathies)
    • Ankylosing spondylitis
    • Psoriatic arthritis
    • Reactive arthritis
    • IBD arthritis
  • Seropositive arthritis
    • Rheumatoid Arthritis
    • Scleroderma
    • Vasculitis
    • Sjögren syndrome
Side note Antiphospholipid antibodies are present in up to one-third of patients with SLE (antiphospholipid syndrome)
Sjögren syndrome is a systemic autoimmune disease characterized by dry eyes and dry mouth. Other organ systems are affected in many patients. Sjögren syndrome is classified as primary or secondary. In primary disease, Sjögren syndrome is a solitary process, whereas secondary disease accompanies another autoimmune disease—often rheumatoid arthritis

Investigations

  • FBC
  • Coagulation screen
  • Inflammtory markers – ESR/CRP
  • EUC
  • LFT
  • Urinalysis
  • Immunological tests
    • Antinuclear antibodies (90% of cases)
    • dsDNA antibodies (60% of cases)
    • Smith antobodies
    • Rheumatoid Factor
    • Anti CCP
Remember check renal function in SLE as nephritis is a common complication

Diagnosis a SLE flare

  • C3/C4 decreased
  • dsDNA antibodies elevated

Pathophysiology

Production of autoantibodies causing multi-organ in ammation. Multi-factorial aetiology:

  • Genetics – common association with HLA-B8/DR3; ~10% have positive family history
  • Environment – UV radiation, cigarette smoking, infection, vitamin D deficiency
  • Oestrogen
  • Infection
  • Drug-induced

Management

General

  • Rest when appropriate
  • Avoid overexposure to sunlight
  • Sunblock
  • Control cardiovascular risk factors
    • Smoking cessation
    • Alcohol cessation
    • Aspirin – if antiphospholipid syndrome present
    • Statins for cholesterol problems
    • Control Diabetes
    • Control Hypertension
  • Calcium and Vitamin D supplements
    • Bisphosphonates (women on long term glucocorticoids)
  • Vaccinations
  • Avoid high oestrogen contraceptive pills

Medical Treatment

  • NSAIDs (caution renal disease)
  • Corticosteroid cream for rashes
  • Hydroxychloroquine – for arthralgia/myalgia/lethargy
  • Prednisolone + azathiopurine – for rash, inflammatory changes, renal and CNS involvement
  • Rituximab – Anti-CD20 monoclonal antibody
  • Anti-TNFα

Acute SLE Characterised by haemolytic anaemia, nephritis, severe pericarditis or central nervous system involvement

  • IV cyclophosphamide
  • High dose prednisolon

Complications and Prognosis

Complications

  • Chronic Kidney Disease
  • Cardiovascular disease
  • Osteoporosis
  • Miscarriages – associated with antiphospholipid syndrome
    • Screen for anti-Ro antibodies

Prognosis

  • ~80% survival at 15 years

Antiphospholipid Syndrome

The antiphospholipid syndrome (APS) was first described in the 1980s and comprises arterial and venous thrombosis with or without pregnancy morbidity in the presence of anticardiolipin (ACL) antibodies or the lupus anticoagulant (LAC). It can be primary, or secondary to other autoimmune diseases, most commonly systemic lupus erythematosus (SLE).

  • Associated with 30% of SLE cases

Clinical features – CLOTS

  • Coagulation defect
  • Livedo reticularis
  • Obstetrics (recurrent miscarriage)
  • Thrombocytopaenia (↓platelets)
  • SLE (found 30%)