What to do for a patient with a lichenoid drug rash during Anti-Tuberculosis (ATT) treatment?

Management of Lichenoid Drug Rash During Anti-Tuberculosis Treatment

For lichenoid drug rash during anti-tuberculosis treatment, immediately discontinue all potentially responsible drugs (rifampicin, isoniazid, and pyrazinamide), provide symptomatic relief with topical steroids and antihistamines, and then sequentially reintroduce each drug to identify the culprit medication.

Initial Management

Step 1: Recognition and Immediate Action

• Lichenoid drug rash presents as violaceous (dark red/purple) papules and plaques without scale over the trunk and extremities, often with significant pruritus 1
• Immediately discontinue all potentially responsible anti-TB drugs when lichenoid drug eruption is suspected 2
• Provide symptomatic relief:
  • High-potency topical steroids (e.g., clobetasol 0.05% or fluocinonide 0.05% cream/ointment) 1
  • Tacrolimus 0.1% ointment for affected areas 1
  • Oral antihistamines for pruritus relief 1, 2

Step 2: Supportive Care

• For mild-moderate reactions:
  • Continue topical corticosteroids and oral antihistamines 2
  • Consider gel formulations for mucosal involvement, solution for scalp involvement, and cream/ointment for other areas 1
• For severe reactions:
  • Consider oral prednisone (starting at 0.5-2 mg/kg/day) 2
  • Taper over 3-4 weeks once symptoms improve to Grade 1 1
  • Consider dermatology consultation 1

Identification of Culprit Drug

Step 3: Sequential Reintroduction

After symptoms resolve (typically 2-3 weeks), sequentially reintroduce each anti-TB drug to identify the offending agent 2, 3:

1. Start with isoniazid at 50 mg/day, gradually increasing to 300 mg/day over 3 days 2
2. If no reaction, add rifampicin at 75 mg/day, gradually increasing to weight-appropriate dose over 3 days 2
3. If no reaction, add pyrazinamide at 250 mg/day, gradually increasing to weight-appropriate dose over 3 days 2
4. If no reaction, add ethambutol at low dose, gradually increasing to weight-appropriate dose over 3 days 2

• Monitor daily for recurrence of rash during reintroduction 2
• Allow 3 days between introduction of each drug to clearly identify the culprit 3

Alternative Regimen Development

Step 4: Modify Treatment Based on Identified Culprit

• If pyrazinamide is the offending drug:

  • Continue rifampicin and isoniazid for 9 months (instead of 6)
  • Add ethambutol for the initial 2 months 2

• If isoniazid or rifampicin is the offending drug:

  • Consult with TB specialist to develop an alternative regimen 2
  • Consider using fluoroquinolones (levofloxacin 500-1000 mg daily) as replacement 1
  • For isoniazid replacement, consider ethambutol plus a fluoroquinolone 1
  • For rifampicin replacement, extend treatment duration to 12-18 months 1

Step 5: Additional Therapeutic Options

For persistent lichenoid reactions despite drug modification:

• Consider narrow-band UVB phototherapy if available 1
• For severe cases resistant to conventional therapy, consider:
  • Acitretin (if no childbearing potential) 1
  • Doxycycline in combination with nicotinamide 1
  • Other steroid-sparing immunosuppressants such as azathioprine, cyclosporine, hydroxychloroquine, methotrexate, or mycophenolate mofetil 1

Monitoring and Follow-up

• Daily clinical assessment for recurrence of rash during drug reintroduction 2
• Monitor liver function tests if hepatotoxicity was part of the initial reaction 2
• Continue treatment until completion of the modified regimen based on drug susceptibility 1
• Ensure DOT (Directly Observed Therapy) to improve adherence to the modified regimen 1

Important Considerations

• Lichenoid drug eruptions from anti-TB drugs are characterized by type IV hypersensitivity reactions 3
• Rechallenge is important to ensure safer treatment since the risk of disseminated and multi-drug-resistant tuberculosis increases with cessation of anti-TB therapy 3
• Case reports have identified isoniazid, rifampicin, pyrazinamide, and cycloserine as potential causes of lichenoid drug eruptions 3, 4, 5
• In rare cases, lichenoid drug reactions can progress to erythroderma (exfoliative dermatitis) 6, 7

By following this algorithmic approach, you can effectively manage lichenoid drug rash during anti-tuberculosis treatment while ensuring continued effective therapy for tuberculosis.