• Clinical science

Systemic lupus erythematosus (SLE…)

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that particularly affects women of childbearing age. The exact cause is still unknown, but a genetic predisposition, as well as hormonal and immunological influences, are considered likely etiological factors. The presentation of the disease is variable and may range from mild localized symptoms to life-threatening systemic disease. Typical findings include fever and fatigue, a malar rash (facial "butterfly rash"), myalgia, and arthritis. Any organ may be affected; however, damage to the kidneys (lupus nephritis) or the nervous system is especially associated with a poor prognosis. The diagnosis of SLE is based on clinical findings and is further supported by antibody tests, particularly for ANA and anti-dsDNA. Management consists of supportive measures, such as avoiding sun exposure, and medication adapted to disease severity. Hydroxychloroquine is administered in the majority of cases to maintain disease remission. For acute flares, glucocorticoids are given as induction therapy, with dose and treatment duration adapted to the severity of the flare. In severe cases, additional immunosuppressants (e.g., mycophenolate, azathioprine) may be given.

Epidemiology

  • Sex: >> (10:1); more than 90% of cases reported in women
  • Peak incidence: women aged 20–40 years; no particular age of manifestation in men
  • US prevalence: highest in African-American, Hispanic, and Asian populations

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Genetic predisposition: HLA-DR2 and HLA-DR3 commonly found in patients with SLE
  • Hormonal factors: suspected modulatory effect of hormones on immune system
  • Immunological findings: ANA and anti-dsDNA autoantibodies
  • Environmental factors: e.g., stimulation of immune cells through bacteria and viruses (disease flares following infection)

References:[1]

Clinical features

The severity varies from case to case, with some patients only experiencing mild symptoms, while others suffer from severe symptoms and rapid disease progression. Additionally, SLE is usually characterized by a relapsing and remitting disease course and can affect any organ.

Most common presenting symptoms

  • Skin (> 70% of cases)
    • Malar rash (“butterfly rash”) with sparing of the nasolabial folds
    • Photosensitivity
    • Discoid rash
    • Oral ulcers
  • Joints
    • Arthritis and arthralgia (> 90% of cases)
    • Mostly nonerosive polyarthritis (normal x-ray)
  • Fever; (> 50% of cases), fatigue (> 80% of cases), weight loss

Other symptoms

Damage to the kidneys or nervous system is associated with a poor prognosis!

References:[2]

Subtypes and variants

Cutaneous lupus erythematosus

Discoid lupus erythematosus (DLE)

  • Accounts for 50–85% of cases of cutaneous lupus erythematosus
  • Clinical features
    • Usually seen on face, neck, and head (triggered by sunlight exposure)
    • Begins as raised erythematous, scaling plaques with active inflammation
    • Heals and leaves scar tissue with central atrophy
  • Rare form: chilblain lupus
    • Violaceous plaques on acral areas from exposure to cold
  • Diagnosis
  • Prognosis: Patients with DLE have approx. a 10–15% risk of developing SLE.

Subacute cutaneous lupus erythematosus (SCLE)

  • About 10% of SLE patients have SCLE.
  • Clinical features
    • Usually affects the neck, shoulders, and forearms, but spares the face
    • Small erythematous lesions that develop into either annular or psoriasiform lesions

Drug-induced lupus erythematosus (DILE)

Drug-induced lupus erythematosus can have many of the features of idiopathic SLE such as fever, arthritis, malar rash, and serositis. However, unlike idiopathic SLE, DILE typically does not affect the oral mucosa, brain, or kidneys!

References:[3][4][5][6][7][8]

Diagnostics

Diagnostic criteria (according to the American college of rheumatology (ACR))

Requirements: at least 4 of the 11 criteria must be met (specificity: 95%, sensitivity: 85%):

ACR criteria for SLE
Dermatological
  1. Malar rash ("butterfly rash") with sparing of the nasolabial folds
  2. Discoid rash
  3. Photosensitivity
  4. Oral or nasopharyngeal ulcers
Internal organs
  1. Nonerosive arthritis: involving at least two peripheral joints; rarely deforming (normal x-ray)
  2. Pleuritis or pericarditis (possibly with effusion)
  3. Renal disorder: lupus nephritis with proteinuria ; cellular casts (red cells, hemoglobin, granular or tubular)
  4. Neurologic disorder: seizures, psychosis, and/or personality changes
Laboratory tests
  1. Hematologic disorders: autoimmune hemolytic anemia, thrombocytopenia, leukopenia, lymphopenia
  2. Immunological findings: anti-dsDNA, anti-Sm, or antiphospholipid antibodies
  3. Antinuclear antibodies (ANA)

Laboratory tests

Antibodies Characteristics

Anti-nuclear antibody (ANA)

Anti-dsDNA antibody
  • Positive in 70% of patients and highly specific
  • Correlates with disease activity
  • Associated with lupus nephritis
Anti-C1q antibody
  • Correlates with disease activity
Anti-Sm antibody
  • Positive in only 30% of patients, but highly specific
Anti-Ro/SSA antibody
Anti-La/SSB antibody
Anti-U1 RNP
  • Positive in ∼ 25% of patients, low sensitivity
→ see also antibody diagnosis of autoimmune diseases

Further diagnostics


References:[9][1][10][11]

Treatment

General management

  • Avoid exposure to sun
  • Stop smoking
  • Immunize patients before initiating immunosuppressants

Medical therapy

Mild symptoms, no vital organs affected Severe symptoms, no vital organs affected Organ damage
Basic therapy
Induction therapy

UV phototherapy as well as UV photochemotherapy (PUVA) are contraindicated!

References:[12]

Complications

Lupus nephritis (LN)

Comorbid conditions

References:[9][12][13][14]

We list the most important complications. The selection is not exhaustive.

Prognosis

  • Mortality:
    • 10-year survival rate > 90%
    • 15-year survival rate approx. 80%
    • Approx. 35% of deaths occur in people < 45 years
  • Causes of death:
    • In early disease
    • In late disease: cardiovascular complications, end-stage renal disease (most common), adverse effects of long-term medication

References:[1]

Special patient groups

SLE and pregnancy

References:[15][16]