What medications are associated with vasculitis?

From the Guidelines

Medications such as hydralazine, propylthiouracil, minocycline, and levamisole-adulterated cocaine are associated with vasculitis, and discontinuation of the offending agent is critical to control the disease and prevent relapses. According to the 2023 study by Beck Jr et al 1, these therapeutic agents are linked to ANCA-associated vasculitis (AAV), characterized by high-titre MPO ANCA positivity, dual MPO and PR3 ANCA positivity, and discordance of ANCA type by immunofluorescence and ELISA. Some key points to consider when evaluating medication-associated vasculitis include:

• The presence of a clinical presentation compatible with small vessel vasculitis and a positive MPO/PR3 ANCA serology is sufficient to begin immunosuppressive therapy while awaiting kidney biopsy to be performed or reported 1
• Testing for ANCA directed to either PR3 or MPO is recommended to screen for AAV, as it is present in 90% of patients with GPA and MPA 1
• Drug-induced AAVs are often associated with positivity for ANA and antihistone antibodies, and in the case of levamisole-induced AAV, neutropenia and retiform purpuric rash are often present 1
• Discontinuation of the offending agent is critical to control AAV and to prevent relapses, and immunosuppressive therapy may be necessary in some cases 1

From the FDA Drug Label

Inform patients that cases of vasculitis resulting in severe complications and death have occurred with propylthiouracil. Inform patients to promptly report symptoms that may be associated with vasculitis including new rash, hematuria or decreased urine output, dyspnea or hemoptysis

• Propylthiouracil is associated with vasculitis, which can result in severe complications and death.
• Patients should be instructed to report any symptoms that may be associated with vasculitis, such as:
  • New rash
  • Hematuria
  • Decreased urine output
  • Dyspnea
  • Hemoptysis 2

From the Research

Medications Associated with Vasculitis

The following medications have been associated with vasculitis:

• Propylthiouracil 3, 4, 5, 6
• Hydralazine 3, 4, 5, 6, 7
• Colony-stimulating factors 3
• Allopurinol 3, 6
• Cefaclor 3
• Minocycline 3, 4, 5, 6
• D-penicillamine 3, 5
• Phenytoin 3
• Isotretinoin 3
• Methotrexate 3
• Levamisole-adulterated cocaine 4

Clinical Features and Treatment

These medications can cause a range of clinical features, including:

• Cutaneous manifestations, such as purpuric rash 6, 7
• Systemic manifestations, such as renal disease 6, 7 and interstitial lung disease 7
• ANCA-associated vasculitis, which can be life-threatening 4, 6 Treatment typically involves discontinuing the offending medication and, in some cases, immunosuppression, plasma exchange, or dialysis 3, 4, 6.

Diagnosis and Testing

Diagnosis of drug-induced vasculitis can be challenging, and clinicians should be aware of the potential for certain medications to cause vasculitis 3, 5. Testing for ANCA and other autoantibodies can be helpful in diagnosis 4, 7. In cases where cocaine use is suspected, urine testing for levamisole should also be performed 4.