Drug-induced Lupus

Background

• Drug-induced lupus (DIL) is caused by specific drugs (most notably hydralazine, procainamide, isoniazid, sulfadiazine, and quinidine) that trigger an autoimmune response resulting in either systemic DIL, subacute cutaneous DIL, or chronic cutaneous DIL (rare).
• In about 10% of patients initially diagnosed with idiopathic systemic lupus erythematosus (SLE), DIL is ultimately diagnosed, which occurs more frequently in older patients.
• Incidence of DIL varies by drug, with longer drug duration and higher cumulative dose increasing the risk.

Evaluation

• No universal criteria exist for the diagnosis of DIL; however, suspect DIL in patients with exposure to drugs suspected of inducing DIL for ≥ 1 month, in addition to the following:
  • no preexisting SLE or other autoimmune disease
  • common signs and symptoms, including:
    • arthralgia
    • myalgia
    • fever
    • serositis
    • rash for those with cutaneous DIL
  • blood tests that typically show positive antinuclear antibodies (ANA) and antihistone antibodies, but usually without evidence of:
    • anti-Smith antibodies
    • anti-double-stranded DNA (anti-dsDNA) antibodies
    • antiextractable nuclear antigens (ENAs)
  • symptom resolution within days, weeks, or months of stopping offending drug
• Blood tests to consider for DIL include:
  • complete blood count (leukopenia, thrombocytopenia, and anemia commonly seen in idiopathic SLE are less frequently found in DIL)
  • basic metabolic panel (renal abnormalities are more common in idiopathic SLE than in DIL)
  • erythrocyte sedimentation rate (usually elevated)
  • C-reactive protein
  • complement
  • liver enzymes
  • serologies such as:
    • ANA (very commonly elevated)
    • ENAs (uncommon in DIL)
    • antihistone antibodies (present in most patients, as in idiopathic SLE)
    • antichromatin (antinucleosome) antibodies (present in DIL and in idiopathic SLE)
    • anti-Smith antibodies (almost exclusive of idiopathic SLE, but rare in DIL)
    • anticitrullinated protein antibodies (markers for rheumatoid arthritis)
    • anticardiolipin antibodies (reported in some cases to be associated with procainamide, hydralazine, or minocycline)
    • anti-dsDNA antibodies (rare, but common in patients taking tumor necrosis factor-alpha inhibitors)
    • anti-Ro/SSA antibodies ; positive in:
      • > 80% of patients with drug-induced subacute cutaneous lupus erythematosus (SCLE)
      • < 5% of patients with systemic DIL
    • anti-La/SSB antibodies (reported to be positive in > 45% of patients with drug-induced SCLE)
    • perinuclear antineutrophil cytoplasmic antibody
      • 50% of propylthiouracil-associated cases
      • 67%-100% of minocycline-associated cases (with myeloperoxidase as autoantigen)
    • rheumatoid factor autoantibodies (reported in 20%-50% of patients)

Management

• Discontinue treatment with the presumed offending drug.
• Treatment is supportive, as symptoms typically resolve before the disappearance of autoantibodies, and therefore autoantibody testing should not guide management.
• Consider a preexisting occult form of SLE if drug discontinuance does not clear the condition.
• Treatment options beyond drug discontinuance generally vary based on the type and severity of symptoms.
  • In patients with cutaneous forms of DIL:
    • Consider topical drugs such as corticosteroids or tacrolimus or systemic drugs such as corticosteroids or hydroxychloroquine.
    • For resistant cases, consider immunosuppressants such as thalidomide, azathioprine, cyclophosphamide, or mycophenolate.
    • Consider sun protection for photosensitivities.
  • In patients with systemic DIL:
    • Consider high-dose corticosteroids (especially for serositis), nonsteroidal anti-inflammatory drugs (especially for arthritis), hydroxychloroquine, and immunosuppressants.
    • In patients with major organ involvement, such as glomerulonephritis, central nervous system disease, and severe hematologic conditions (anemia, leukopenia, and thrombocytopenia), administer systemic immunosuppressive therapy. Regimens are typically derived from idiopathic SLE protocols.