How to manage pruritus (itching) induced by anti-tubercular (anti-tuberculosis) therapy?

Management of Anti-Tubercular Induced Pruritus

For anti-tubercular therapy (ATT)-induced pruritus, immediately start topical moderate-to-high potency corticosteroids (mometasone furoate 0.1% or betamethasone valerate 0.1% ointment) applied 3-4 times daily to affected areas, combined with non-sedating antihistamines during the day (loratadine 10 mg daily) and sedating antihistamines at night (hydroxyzine 25-50 mg or diphenhydramine 25-50 mg) if sleep is disrupted. 1, 2, 3

Initial Assessment and Severity Grading

When a patient on ATT develops pruritus, document the following specific details:

• Timing: Onset relative to ATT initiation (typically occurs within days to 8 weeks of starting therapy) 4, 5
• Distribution: Localized facial/truncal versus generalized body involvement 4, 6
• Associated skin changes: Presence of maculopapular rash, erythema, scaling, or bullae formation 4, 5
• Severity: Impact on sleep, daily activities, and presence of excoriations from scratching 1
• Specific ATT drugs: Isoniazid and pyrazinamide are the most common culprits 4, 6

Stepwise Treatment Algorithm

Mild Pruritus (Grade 1)

Localized itching without significant skin changes:

• Apply topical corticosteroids (hydrocortisone 1% or mometasone 0.1%) to affected areas 3-4 times daily 1, 3
• Use emollients liberally to prevent xerosis, which exacerbates itching 1, 2
• Continue ATT without interruption 1
• Reassess after 2 weeks 1

Moderate Pruritus (Grade 2)

Widespread or intense itching, intermittent, limiting instrumental activities:

• Continue topical corticosteroids (upgrade to high-potency if needed: betamethasone valerate 0.1%) 1
• Add oral antihistamines:
  • Daytime: Non-sedating agents (loratadine 10 mg daily or fexofenadine 180 mg daily) 1
  • Nighttime: Sedating agents if sleep disrupted (hydroxyzine 25-50 mg or diphenhydramine 25-50 mg) 1, 2
• Consider adding menthol 0.5% topical preparations for additional symptomatic relief 1
• Continue ATT but monitor closely 1
• Reassess after 2 weeks 1

Severe Pruritus (Grade 3) or Progressive Skin Changes

Constant widespread itching limiting self-care, or development of erythroderma/bullae:

• Immediately discontinue all ATT drugs 4, 5, 6
• Initiate systemic corticosteroids: Oral prednisone 0.5-1 mg/kg daily 4, 5
• Continue antihistamines and topical corticosteroids 4, 5
• Provide intravenous fluid and electrolyte support if extensive skin involvement 5
• Hospitalize if signs of Stevens-Johnson syndrome, toxic epidermal necrolysis, or AGEP develop 6

Alternative Antipruritic Agents (Second-Line)

If antihistamines fail to control symptoms adequately:

• Gabapentin 900-3600 mg daily (divided doses) or pregabalin 25-150 mg daily may provide relief through modulation of peripheral and central itch pathways 1
• Avoid gabapentin in hepatic dysfunction, which may coexist with ATT-induced liver injury 1

Critical Pitfall: Rifampicin Paradox

Do NOT use rifampicin as an antipruritic agent in ATT-induced pruritus, despite its effectiveness for cholestatic pruritus in primary biliary cholangitis. 1, 7 Rifampicin itself is an ATT drug and can cause significant hepatotoxicity (7.3% incidence of hepatitis, with potential for liver synthetic dysfunction requiring transplantation). 7

Rechallenge Protocol After Resolution

Once pruritus and skin changes completely resolve (typically 3 weeks after ATT discontinuation):

1. Reintroduce ATT drugs sequentially, one at a time, starting with the least likely culprit 4
2. Start with rifampicin alone for 3-7 days, monitor for recurrence 4
3. Add isoniazid next (most common culprit after pyrazinamide) 4, 6
4. Add ethambutol, then finally pyrazinamide (highest risk drug) 4, 6
5. If pruritus recurs with a specific drug, permanently avoid that agent and substitute with second-line ATT (moxifloxacin, bedaquiline, or fluoroquinolones) 5, 8

Alternative ATT Regimens

When first-line ATT cannot be reintroduced due to recurrent severe cutaneous reactions:

• Substitute with second-line agents: Moxifloxacin plus bedaquiline, avoiding the culprit drug 5, 8
• Consult infectious disease or TB specialist for individualized regimen design 5, 8
• Ensure adequate treatment duration (typically 18-24 months for second-line regimens versus 6 months for first-line) 8

Monitoring During Treatment

• Reassess every 2 weeks during active pruritus management 1
• Monitor liver function tests weekly during ATT rechallenge, as hepatotoxicity often accompanies cutaneous reactions 4, 7, 6
• Document all reactions thoroughly for future prescribing decisions 2
• Refer to dermatology if pruritus persists beyond 4 weeks despite appropriate management or if diagnostic uncertainty exists 1