Management of Anti-Tuberculosis Treatment (ATT) Induced Drug Rash
When a patient develops a drug rash during anti-tuberculosis treatment, all potentially responsible drugs (rifampicin, isoniazid, and pyrazinamide) should be stopped immediately, followed by sequential reintroduction once symptoms resolve to identify the culprit drug.
Initial Management of ATT-Induced Drug Rash
Immediate Steps
- Stop all potentially hepatotoxic anti-TB drugs (isoniazid, rifampicin, pyrazinamide) 1
- Assess severity of the reaction and patient's clinical status
- If patient is not clinically unwell and TB is non-infectious, no treatment is needed until symptoms resolve 1
- If patient is unwell or has smear-positive TB within two weeks of starting treatment, alternative drugs (streptomycin and ethambutol) should be used until symptoms resolve 1
Supportive Care
- Administer antihistamines for symptomatic relief of mild reactions 1
- For severe reactions (Stevens-Johnson syndrome, exfoliative dermatitis), provide appropriate supportive care including corticosteroids 1, 2
- Monitor for systemic involvement (hepatitis, eosinophilia, organ dysfunction) which may indicate DRESS syndrome 3, 4
Sequential Reintroduction Protocol
Once the rash has resolved completely, reintroduce drugs sequentially with careful monitoring:
1. Isoniazid Reintroduction
- Start with isoniazid at 50 mg/day 1
- Increase to 300 mg/day after 2-3 days if no reaction 1
- Continue isoniazid if no adverse reaction
2. Rifampicin Reintroduction (after 2-3 days of full-dose isoniazid)
- Start rifampicin at 75 mg/day 1
- Increase to 300 mg after 2-3 days if no reaction 1
- Further increase to weight-appropriate dose (450 mg for <50 kg or 600 mg for >50 kg) after another 2-3 days 1
3. Pyrazinamide Reintroduction (after full-dose rifampicin is tolerated)
- Start pyrazinamide at 250 mg/day 1
- Increase to 1.0 g after 2-3 days 1
- Further increase to weight-appropriate dose (1.5 g for <50 kg or 2.0 g for >50 kg) 1
Management Based on Rechallenge Results
If No Further Reaction
- Continue standard chemotherapy with all drugs 1
- Withdraw any temporary alternative drugs
If Reaction Recurs
- Permanently exclude the offending drug from the regimen 1
- Develop an alternative regimen based on the excluded drug:
- If pyrazinamide is the offending drug: Continue rifampicin and isoniazid for 9 months, with ethambutol for the initial 2 months 1, 5
- If isoniazid cannot be used: Consider regimen of rifampicin, ethambutol, and a fluoroquinolone for 12-18 months 5
- If rifampicin is the culprit: Consult with TB specialist for alternative regimen, which may include levofloxacin, ethambutol, streptomycin, and cycloserine 3
Special Considerations
Monitoring During Rechallenge
- Perform daily clinical assessment for recurrence of rash
- Monitor liver function tests if hepatotoxicity was part of initial reaction 5
- Be vigilant for DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), which can occur with anti-TB drugs, particularly rifampicin 3, 6, 4
Risk Factors for Severe Reactions
- Female sex (2.5× higher risk) 7
- Age over 60 years (2.9× higher risk) 7
- Birth in Asia (2.5× higher risk) 7
- HIV-positive status (3.8× higher risk) 7
Drug-Specific Considerations
- Pyrazinamide has the highest incidence of major adverse effects (1.48 per 100 person-months) compared to isoniazid (0.49) and rifampicin (0.43) 7
- Rifampicin-associated adverse events are particularly increased in HIV-positive patients (8× higher risk) 7
Prevention and Patient Education
- Educate patients about symptoms requiring immediate medical attention (rash, fever, jaundice) 5
- Avoid concurrent use of other medications that may increase risk of reactions 5
- Consider more frequent monitoring in high-risk patients 5
Remember that desensitization and reintroduction of the offending drug may be necessary in cases where drug options are limited due to resistance patterns, but this should always be done under close supervision with coverage of at least two other anti-TB drugs to prevent resistance development 1.