What type of vasculitis is associated with methimazole?

Methimazole-Associated Vasculitis

Methimazole causes ANCA-positive vasculitis, which can manifest as leukocytoclastic cutaneous vasculitis, glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis, and neuropathy. 1

Clinical Manifestations

• Methimazole-induced vasculitis is typically associated with anti-neutrophilic cytoplasmic antibodies (ANCA), particularly perinuclear-ANCA (p-ANCA) with antimyeloperoxidase specificity 2
• The vasculitis can manifest with various clinical presentations:
  • Leukocytoclastic cutaneous vasculitis with hemorrhagic and necrotic bullous lesions 3
  • Acute kidney injury and glomerulonephritis 1
  • Alveolar/pulmonary hemorrhage 1, 2
  • CNS vasculitis 1
  • Peripheral neuropathy 1

Severity and Prognosis

• While many cases resolve with drug discontinuation, severe presentations can occur with potentially fatal outcomes 2
• The vasculitis can range from mild cutaneous manifestations to life-threatening systemic involvement with multi-organ failure 3, 2
• Severe cases may require aggressive treatment beyond simply stopping the medication 1

Diagnostic Features

• Positive ANCA serology, particularly p-ANCA with antimyeloperoxidase specificity 2
• Histopathologic findings may include:
  • Leukocytoclastic vasculitis in skin biopsies 3
  • Crescentic glomerulonephritis in kidney biopsies 2
  • Transmural necrotizing vasculitis in affected vessels 2

Management

• Immediate discontinuation of methimazole is the first and most critical step in management 1, 3
• More severe cases may require additional therapeutic measures:
  • Corticosteroids 1
  • Immunosuppressant therapy 1
  • Plasmapheresis in severe cases 1, 2
• Careful monitoring for progression of organ involvement is essential 3

Comparison with Other Antithyroid Drugs

• While both methimazole and propylthiouracil (PTU) can cause ANCA-associated vasculitis, it is more commonly reported with PTU 3, 4
• The FDA label specifically notes that vasculitis resulting in severe complications has been reported in patients receiving methimazole therapy 1

Prevention and Monitoring

• Patients on methimazole should be monitored for symptoms that may indicate vasculitis 1
• Healthcare providers should instruct patients to promptly report:
  • New rash or skin lesions 1
  • Hematuria or decreased urine output 1
  • Dyspnea or hemoptysis 1
  • Fever, joint pain, or general malaise 1

Historical Context

• The first reported case of ANCA-associated vasculitis caused by methimazole was documented in 1995 5
• Since then, multiple case reports have confirmed this rare but serious adverse effect 3, 2

Methimazole-induced vasculitis represents a rare but potentially life-threatening complication that requires prompt recognition and management to prevent significant morbidity and mortality.