What is the modified anti-tuberculosis treatment (ATT) regimen for a patient with a lichenoid drug rash adverse drug reaction (ADR)?

Modified ATT Regimen for Lichenoid Drug Rash ADR

In cases of lichenoid drug rash adverse drug reaction (ADR) to anti-tuberculosis treatment (ATT), the modified regimen should exclude the offending drug and substitute with alternative effective anti-TB medications while ensuring the regimen contains at least four effective drugs.

Identification of the Offending Drug

When a lichenoid drug rash develops during ATT, the following approach should be taken:

1. Temporarily discontinue all ATT drugs when lichenoid drug eruption is identified 1
2. Monitor the patient clinically until the skin reaction resolves
3. Sequential drug reintroduction to identify the causative agent:
   • Begin with isoniazid at 50 mg/day, increasing to 300 mg/day after 2-3 days if no reaction occurs
   • After 2-3 days without reaction, add rifampicin at 75 mg/day, increasing to 300 mg after 2-3 days, then to full dose (450-600 mg based on weight) after another 2-3 days
   • Finally, add pyrazinamide at 250 mg/day, increasing to full dose over 2-3 days
   • Monitor for recurrence of skin reaction during each drug reintroduction 1

Alternative Regimens Based on Identified Offending Drug

If Ethambutol is the Offending Drug:

• Continue with isoniazid, rifampicin, and pyrazinamide for the standard 6-month regimen 2
• No need to replace ethambutol if the patient has drug-susceptible TB

If Pyrazinamide is the Offending Drug:

• Treatment should be extended to 9 months with:
  • Isoniazid and rifampicin for 9 months
  • Ethambutol for the initial 2 months 1

If Isoniazid is the Offending Drug:

• Rifampicin, pyrazinamide, and ethambutol for 6 months
• Consider adding a fluoroquinolone (levofloxacin or moxifloxacin) 1

If Rifampicin is the Offending Drug:

• Treatment duration should be extended to 18 months
• Regimen should include isoniazid, ethambutol, pyrazinamide, and a fluoroquinolone 1

Special Considerations

1. For severe or extensive disease: If the patient is unwell or has sputum-positive TB within two weeks of starting treatment, temporary alternative therapy is needed while awaiting resolution of the skin reaction:

   • Use streptomycin and ethambutol (with appropriate monitoring) until liver function normalizes 1
   • Avoid drugs with known hepatotoxicity

2. For drug-resistant TB: Consult with TB specialists to design an individualized regimen with at least 5 effective drugs 1

3. For HIV co-infected patients: These patients have higher risk of drug reactions (27.7% of CADR cases) 3, so careful monitoring is essential

Management of Lichenoid Drug Rash

While modifying the ATT regimen:

1. Treat the lichenoid reaction with:

   • Antihistamines for symptomatic relief
   • Topical corticosteroids for localized lesions
   • Systemic corticosteroids for severe reactions (short course)
   • Consider tacrolimus for persistent lesions 2, 4

2. Monitor for resolution of the rash before reintroduction of ATT drugs

Important Caveats

• Lichenoid drug eruptions are characterized by type IV hypersensitivity reactions 2
• The risk of developing multidrug-resistant TB increases with treatment interruption, so prompt identification of the offending drug and reestablishment of effective therapy is critical 2
• Pyrazinamide appears to be the most common cause of cutaneous ADRs among first-line ATT drugs (2.38%), followed by streptomycin (1.45%), ethambutol (1.44%), rifampicin (1.23%), and isoniazid (0.98%) 3
• Most cutaneous ADRs occur within the first two months of treatment (97%) 3

By following this approach, effective TB treatment can be maintained while avoiding recurrence of the lichenoid drug reaction, ensuring optimal outcomes for patients with tuberculosis.