Systemic Lupus Erythematosus

Snapshot

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  • A 26-year-old woman presents to the dermatology clinic for fatigue, weakness, and fevers for the past month. She reports significant weight loss despite eating a normal diet. She reports that she sunburns very easily and has a facial rash that is hard to cover with makeup. On physical exam, she has a butterfly rash with nasolabial sparing on her face, several discoid lesions on her fingers, and a erythematous rash on her chest in a V-neck distribution. On laboratory exam, she has a highly positive antinuclear antibody and positive anti-double-stranded DNA antibody.

Introduction

  • Clinical definition
    • systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by acute flares, commonly presenting with rash, joint pain, and fever
      • multiple organ systems are involved, including renal, neurologic, dermatologic, cardiovascular, and hematologic
  • Epidemiology
    • demographics
      • more common in female patients of reproductive age
      • African American, Asian, or Hispanic descent
    • risk factors
      • family history
      • oral contraceptive use
      • hormone replacement therapy
      • other autoimmune diseases
  • Pathogenesis
    • unknown but thought to be an interaction among immune dysfunction, genetic factors, and environmental factors
      • autoantibodies precipitate immune complexes in multiple organs, including kidneys, skin, and brain
        • form of type 3 hypersensitivity reaction 
      • polyclonal activation of B-cells with the production of autoantibodies against DNA
      • complement factors and cytokines also play a key role
      • environmental triggers include sunlight (photosensitive rash), infection, and drugs (HIP)
        • Hydralazine
        • Isoniazid
        • Procainamide
  • Associated conditions
    • antiphospholipid syndrome
      • increased risk of thrombosis
      • increased risk of atherosclerosis
    • lupus nephritis
      • anti-DNA immune complexes deposition in glomeruli
      • nephritic or nephrotic syndrome
        • diffuse proliferative is the most common and most severe type
    • drug-induced lupus
      • typically positive for antinuclear antibody and antihistone antibody
      • typically without renal or neurologic involvement
      • complement level is typically normally
    • Libman-Sacks endocarditis (LSE)
      • noninfectious endocarditis characterized by thrombi on the mitral or aortic valves (LSE in SLE)
    • Raynaud phenomenon
  • Prognosis
  • often have recurrent flares

Presentation

  • Symptoms 
    • constitutional symptoms
      • fatigue, fever, or weight loss
    • arthralgias
    • serositis 
      • pericarditis, pleural effusion, or myocarditis
  • Physical exam
    • cutaneous findings
      • malar rash (raised or flat erythematous butterfly rash on cheeks/nose and spares nasolabial fold)
      • discoid lesions (erythematous raised plaques with keratotic scale and follicular plugging) 
      • photosensitive rash
      • oral ulcers
    • neurologic findings
      • behavioral changes
      • stroke
      • seizures
      • headaches
      • chance in psychiatric status
    • renal findings 
      • hematuria
      • proteinuria
    • hematologic findings 
      • anemia of chronic disease
      • leukopenia
  • thrombocytopenia

Studies

  • Labs
    • antibodies
      • antinuclear antibody (ANA) 
        • best initial test
        • high sensitivity but low specificity
      • anti-double-stranded DNA (dsDNA) antibody 
        • often rises during flares
        • high specificity but low sensitivity
        • poor prognostic factor
        • often indicates renal disease
      • anti-Smith antibody (antibody to snRNPs)
        • high specificity (more than anti-dsDNA) but low sensitivity
      • antihistone antibody
        • high sensitivity for drug-induced lupus
    • ↓ complement levels during a flare
      • ↓C3, C4, and CH50
    • ↑ erythrocyte sedimentation rate
    • pancytopenia
      • leukopenia, thrombocytopenia, or hemolytic anemia
    • elevated partial thromboplastin time (PTT) 
      • lupus anticoagulant increases the risk for thrombi and miscarriages 
      • associated with antiphospholipid syndrome
  • Urinalysis
    • proteinuria or hematuria may indicate renal disease
  • Making the diagnosis
    • based on clinical presentation and laboratory studies
    • diagnosis confirmed with 4 or more criteria from RASHNIA4
      • Renal disease
      • Arthralgias
      • Serositis
      • Hematologic abnormalities
      • Neurologic abnormalities
      • Immunologic derangements
      • Antinuclear antibodies
      • 4 types of rashes
        • malar
        • discoid
        • photosensitive
  • oral ulcers

Differential

  • Acne rosacea 
    • distinguishing factors
      • erythematous papules and pustules on face without nasolabial sparing
      • no other systemic findings
  • Sarcoidosis 
    • distinguishing factors
      • adenopathy
      • restrictive lung disease
  • skin findings of lupus pernio, rather than malar rash, discoid lesions, or ulcers

Treatment

  • Management approach
    • antimalarials are often used alongside steroids for acute flares
    • management is often dictated by specific organ involvement
  • Conservative
    • use sunscreen and avoid sun exposure
      • indication
        • for all patients
  • Medical
    • non-steroidal anti-inflammatory drugs (NSAIDs)
      • indication
        • arthralgias
    • antimalarials
      • indications
        • dermatologic findings and joint pain
        • often used in conjunction with other medications, including steroids
      • drugs
        • hydroxychloroquine
        • chloroquine
      • side effects
        • risk of retinopathy
    • steroids
      • indication
        • acute flares
      • drugs
        • prednisone
    • immunosuppressants
      • indications
        • patients not responsive to steroids
        • patients unable to tolerate steroid taper
        • lupus nephritis
      • drugs
        • azathioprine
        • methotrexate
        • mycophenolate
          • for patients with lupus nephritis
        • cyclophosphamide
          • for patients with lupus nephritis
    • belimumab
      • indication
        • patients not responsive to steroids or other immunosuppressants
      • mechanism
  • inhibits B-cells

Complications

  • Causes of death in SLE
    • infections
    • renal disease
    • cardiovascular disease
  • Lupus nephropathy
    • can be fatal
  • Cardiovascular disease
    • leading cause of death in patients with SLE
    • includes Libman-Sacks endocarditis, hypertension, and cardiac tamponade
  • Thrombosis