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Internal Medicine

Systemic lupus erythematosus (SLE)

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and is characterized by the presence of autoantibodies directed against nuclear antigens.

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and is characterized by the presence of autoantibodies directed against nuclear antigens.


Classification

Lupus

Lupus is a chronic inflammatory autoimmune disease with a wide range of clinical presentations resulting from its effect on multiple organ systems.

There are 4 main types of lupus:

  • Neonatal/pediatric lupus erythematosus (NLE) (rare)
    • Result from maternal autoantibodies passing through the placenta.
  • Discoid lupus erythematosus (DLE)
    • Chronic scarring and atrophic photosensitive dermatosis, which may progress to SLE or may occur in patients with SLE.
  • Drug-induced lupus (DIL)
    • Occurs after exposure to a medication, causing an autoimmune response.
  • Systemic lupus erythematosus (SLE) (M/C type)
    • Differentiated from other types by its multi-organ system effects

Etiopathogenesis

  • (90% cases)
  • Environmental factorsSunlight (UV light)
  • Genetic factors
  • Sex hormones (Oestrogen)
    • Reproductive age: ♀ >> ♂
    • Non-reproductive age: ♀ >> ♂
  • Lifestyle factors (smoking)
  • Drug-induced lupus (DIL):
    • Sulphonamides/sulfasalazine, hydralazine, isoniazid, procainamide, para-aminosalicylic acid, methyldopa, chlorpromazine, quinidine

Type III hypersensitivity reaction (mainly) > Type II hypersensitivity reaction (lesser extent)

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Histopathology:

  • Blood vessels: Acute necrotizing vasculitis with fibrinoid necrosis
  • Kidney:
    • “Wire-loop” lesions
    • Tubulointerstitial lesions
  • Skin:
    • Vacuolar degeneration of the basal layer of the epidermis
    • Vasculitis with fibrinoid necrosis
  • Joints: Non-erosive arthritis
  • Cardiovascular system:
    • Fibrinous pericarditis
    • Libman–Sacks endocarditis
  • Spleen:
    • Splenomegaly
    • Capsular thickening
    • Follicular hyperplasia
    • Onion-skin lesions of arteries (concentric intimal and smooth muscle cell hyperplasia)
  • Lungs:
    • Pleuritis, pleural effusion, chronic interstitial fibrosis and secondary pulmonary hypertension
  • Bone marrow:
    • Hematoxylin bodies
  • Lymph nodes:
    • Lymphadenopathy with hyperplastic follicles
    • Necrotizing lymphadenitis

Presentation

The Great Imitator: Produces symptoms resembling a large number of pathologies.

Constitutional symptoms (90%):

  • Fatigue (M/C), weight loss, and fever
  • Other symptoms:
    • Malar rash (31%)
    • Photosensitivity (23%)
    • Pleuritic chest pain (16%)
    • New-onset Raynaud phenomenon (16%)
    • Mouth sores (12.5%)

Musculoskeletal manifestations (>90%):

  • Arthralgia > arthritis (70%): Migratory, symmetrical
  • Jaccoud’s arthropathy (JA) (5%): ‘Reversible’ joint deformities such as swan neck, thumb subluxation, ulnar deviation, ’boutonniere’ and hallux valgus, along with an absence of articular erosions on a plain radiograph.
    • Also seen in RA
RA: Hand deformities, including swan neck deformity, Z deformity of the thumb, and ulnar deviation of the fifth digit
A 58-year-old man presented with a 15-year history of systemic lupus erythematosus (SLE) that was characterized by polyarthritis, photosensitivity, malar rash, and pleuritis. Hand deformities, including swan neck deformity, Z deformity of the thumb, and ulnar deviation of the fifth digit, developed over a 10-year period (Panel A ). These deformities were reducible and are characteristic of Jaccoud’s arthropathy. MRI showed no erosions (Panel B). Although classically described in rheumatic fever, Jaccoud’s arthropathy has also been described in SLE and other diffuse connective-tissue diseases. In Jaccoud’s arthropathy, the deformities result mainly from soft-tissue abnormalities, such as laxity of ligaments, fibrosis of the capsule, and muscular imbalance, rather than from destruction of the bone of joints, as occurs in rheumatoid arthritis. The mainstay of the management of Jaccoud’s arthropathy includes physical therapy and the use of orthotic devices. | Santiago, M., & Machicado, V. (2015). Jaccoud’s Arthropathy. New England Journal of Medicine, 373(1), e1. https://doi.org/10.1056/NEJMicm1410743
SLE musculoskeletal manifestations
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Mucocutaneous lupus (70-80%):

  • Specific lesions:
    • Malar rash: Butterfly rash on the cheeks and nose
    • Discoid rash: Red, raised, disk-shaped rash
    • Photosensitivity
  • Non-specific lesions:
    • Subacute cutaneous lupus
    • Alopecia
    • Livedo reticularis, purpura, vasculitis, urticaria
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Haematological manifestations (> 90%):

  • Anaemia, thrombocytopenia, leucopenia
  • Lymphadenopathy (50% cases)
  • Splenomegaly (esp during active disease)

Renal symptoms (50%) (M/C cause of death):

  • Glomerulonephritis: Lupus nephritis (LN) (M/C cause of death)
  • Proteinuria, haematuria, uraemia

Cardiac manifestations (28-40%):

  • Verrucous (Libman-Sacks) endocarditis
  • Pericarditis (common)
  • Myocarditis (rare)
  • Accelerated atherosclerosis with coronary heart disease (CHD) (major cause of mortality)

Respiratory manifestations (16%)

  • Pleurisy, pleural effusions, interstitial lung disease, pulmonary hypertension, pulmonary haemorrhage, pulmonary fibrosis

Gastrointestinal (GI) symptoms and hepatic features (39–67%):

Mostly d/t medication side effects than from active SLE.

  • NSAIDs ± glucocorticoids → Gastritis, peptic ulcers
  • SLE vasculitis → Pancreatitis, peritonitis, and colitis
  • Lupoid hepatitis (rare)
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Neurological manifestations (12-23%):

  • Common: Cognitive defects, organic brain syndromes, delirium, psychosis, seizures, headache, and/or peripheral neuropathies
  • Less common: Movement disorders, cranial neuropathies, myelitis, and meningitis.

Vascular manifestations:

  • Raynaud’s phenomenon, vasculitis, thrombosis
Raynaud’s phenomenon

Ophthalmologic manifestations:

  • Keratoconjunctivitis sicca (M/C): Dryness of the conjunctiva and cornea
    • Some have Sjögren’s syndrome
  • Uncommon: Cotton wool exudates (due to retinal vasculitis), episcleritis/scleritis, and anterior uveitis (iritis, iridocyclitis)

Obstetric complications:

  • Miscarriages, intrauterine growth restriction (IUGR), and preterm birth

Diagnosis

 American College of Rheumatology (ACR) criteria (1982):

  • SOAP BRAIN MD≥ 4 have to be met
    • Serositis (pleurisy or pericarditis)
    • Oral ulcers (oral or nasopharyngeal ulcers)
    • Arthritis (non-erosive arthritis of ≥ 2 peripheral joints, with tenderness, swelling, or effusion)
    • Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups)
    • Blood disorders (hemolytic anaemia, leukopenia, lymphopenia, or thrombocytopenia in the absence of offending drug, hypocomplementemia or to congenitally complement deficiency)
    • Renal abnormalities (> 0.5 g/day proteinuria or cellular casts)
    • ANA+
    • Immunologic phenomenon (anti-Smith, anti-ds DNA, antiphospholipid antibody, or false positive serological test for syphilis)
    • Neurologic symptoms (seizures or psychosis; not explained otherwise)
    • Malar rash (rash on cheeks)
    • Discoid rash (red, scaly patches on skin that cause scarring)

Urinalysis:

  • Proteinuria (100%)
  • Microscopic hematuria (80%), invariably associated with proteinuria
  • Macroscopic hematuria (rare, < 5%)
  • Urinary RBC casts (30%)
  • Other urinary cellular casts (30%)
  • ↓ Glomerular filtration rate (GFR) (50%)

Systemic Lupus International Collaborating Clinics (SLICC) criteria:

Diagnostic criteria for SLE
Lam, N. C., Ghetu, M. V., & Bieniek, M. L. (2016). Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management. American family physician, 94(4), 284–294.

Serology:

  • Serum biomarkers:
    • Antinuclear antibody (ANA) (94%): Best initial test: High sensitivity, low specificity
      • Most patients with SLE are ANA(+), but most ANA (+) cases do not have SLE
    • More specific tests:
      • Anti–double-stranded DNA (anti-dsDNA)
      • Anti-Smith (anti-Sm)
      • Antiphospholipid antibodies (APLA)
      • Anti-RNP
      • Anticardiolipin
      • Beta-2 glycoprotein antibodies
      • Lupus anticoagulant
  • Renal involvement: Anti-Smith antibodies, anti-C1q antibodies, low complement, and anti-dsDNA are associated with renal involvement
  • Acute phase reactants:
    • ↑ Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
  • Other tests:
    • ↓ Complements C3 and C4
    • Urinalysis
    • Comprehensive metabolic panel
    • Complete blood count (CBC)
    • Direct Coombs test

Enzyme-linked immunosorbent assay (ELISA):

  • Antinuclear antibody (ANA) (CONFIRMATORY)

Differential diagnosis:

Differential diagnosis of SLE
Lam, N. C., Ghetu, M. V., & Bieniek, M. L. (2016). Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management. American family physician, 94(4), 284–294.

Management

Management of SLE | Lam, N. C., Ghetu, M. V., & Bieniek, M. L. (2016). Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management. American family physician, 94(4), 284–294.

Disease-modifying anti-rheumatic drugs (DMARDs):

Biologic and nonbiologic disease modifying antirheumatic drugs (DMARDs)
Biologic and nonbiologic disease modifying antirheumatic drugs (DMARDs) | Wasserman A. M. (2011). Diagnosis and management of rheumatoid arthritis. American family physician, 84(11), 1245–1252.

Summary

SLE
Kaul, A., Gordon, C., Crow, M. K., Touma, Z., Urowitz, M. B., van Vollenhoven, R., … Hughes, G. (2016). Systemic lupus erythematosus. Nature Reviews Disease Primers, 2(1), 16039. https://doi.org/10.1038/nrdp.2016.39

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