What is the recommended treatment for leprosy?

Leprosy Treatment

Leprosy requires multidrug therapy (MDT) with rifampin, dapsone, and clofazimine, with treatment duration of 6 months for paucibacillary disease and 12 months for multibacillary disease, as recommended by the World Health Organization. 1, 2

Classification-Based Treatment Regimens

Paucibacillary Leprosy (Tuberculoid and Indeterminate Forms)

• Administer rifampin 600 mg monthly (supervised) plus dapsone 100 mg daily for 6 months 1, 2
• The combination effectively eliminates Mycobacterium leprae while preventing drug resistance 3
• Continue dapsone for an additional 6 months after completing rifampin, then maintain for 3 years in tuberculoid cases and 5 years in borderline tuberculoid cases 2

Multibacillary Leprosy (Lepromatous and Borderline Lepromatous Forms)

• Use triple therapy: rifampin 600 mg monthly (supervised), dapsone 100 mg daily, and clofazimine 50-100 mg daily for 12 months 1, 2
• The WHO regimen allows monthly supervised rifampin 600 mg to replace daily dosing, improving adherence 4
• After completing 12 months of triple therapy, continue dapsone for 10 additional years in borderline cases and lifelong in lepromatous cases 2
• Consider adding a third anti-leprosy drug (ethionamide 250-500 mg daily) in severe cases 2

Medication-Specific Guidance

Dapsone Dosing and Monitoring

• Start adults at 50 mg daily and titrate up to 100 mg daily; use correspondingly smaller doses in children 2
• Screen for G6PD deficiency before initiating treatment due to hemolytic anemia risk 1
• Monitor complete blood count and liver function tests regularly for hemolysis, methemoglobinemia, and hepatotoxicity 1, 2
• Dapsone levels are influenced by acetylation rates; patients with high acetylation may require dose adjustment 2

Clofazimine Administration

• Dose at 50-100 mg daily with meals or milk to maximize absorption and reduce gastrointestinal effects 5, 1
• Warn patients about pink to brownish-black skin discoloration occurring in 75-100% within 1-4 weeks, which resolves 6-12 months after stopping 5
• Perform baseline ECG and monitor QT interval at 2 weeks and after adding any QT-prolonging medications 5, 1
• Available as 100 mg capsules that cannot be split 5

Rifampin Considerations

• Rifampin induces hepatic cytochrome P450 enzymes (especially CYP3A4), decreasing dapsone half-life and its own metabolism 6
• This drug interaction is clinically managed within the standard MDT regimen without dose adjustment 6
• Monthly supervised dosing of 600 mg (or 1200 mg in some protocols) is therapeutically equivalent to daily dosing and costs one-tenth as much 4

Special Populations

Pregnancy and Lactation

• Continue treatment during pregnancy as benefits outweigh risks, with close monitoring required 1
• All three standard MDT drugs can be used, though careful surveillance is essential 1

Pediatric Patients

• Use weight-based dosing: clofazimine 1-2 mg/kg/day (maximum 100 mg), with proportionally reduced doses of other agents 1
• Clofazimine has been well-tolerated in pediatric leprosy trials 1

Monitoring and Follow-Up

Treatment Response Assessment

• Expect lesion flattening by 4-6 weeks after treatment initiation 1
• Perform clinical evaluation with bacterial index (BI) and morphological index (MI) at baseline, every 4 weeks during initial treatment, then every 8 weeks 7
• MI should reach 100% reduction by 8 weeks in responsive patients 7
• Skin biopsies at 0,12, and 48 weeks help assess histopathological improvement 7

Toxicity Monitoring

• Perform routine complete blood count, renal function, and liver function tests intermittently throughout treatment 5, 1
• Baseline and symptomatic audiometry for clofazimine-associated hearing loss 5
• ECG monitoring for QT prolongation with clofazimine, especially when combined with other QT-prolonging drugs 5, 1

Post-Treatment Surveillance

• Monitor for signs of relapse indefinitely, as clinical and bacteriological relapses can occur 1, 2
• Suspect secondary dapsone resistance if lepromatous patients relapse with solid-staining bacilli in new active lesions despite regular supervised therapy 2
• Confirmed resistance requires switching to alternative drugs and consideration of mouse footpad sensitivity testing (available through specialized centers) 2

Alternative Regimens

Single-Dose ROM for Paucibacillary Disease

• Rifampin 600 mg, ofloxacin 400 mg, and minocycline 100 mg as a single supervised dose has been recommended for single-lesion paucibacillary leprosy 1, 3

Shorter Duration Intensive Regimen

• A 12-week regimen of daily rifampin 600 mg, sparfloxacin 200 mg, clarithromycin 500 mg, and minocycline 100 mg showed 73.92% clinical improvement and comparable BI reduction to standard 12-month WHO/MDT 7
• This regimen caused minocycline-induced hyperpigmentation in most patients and mild gastrointestinal effects 7
• Consider for operational settings where monthly supervision is impractical, though this is not yet standard of care 7

Common Pitfalls

• Never use dapsone monotherapy, as this leads to drug resistance 3, 8
• Do not discontinue treatment prematurely; the full duration is essential even if clinical improvement occurs early 2
• Distinguish leprosy reactions (type 1 reversal reactions, type 2 erythema nodosum leprosum) from treatment failure—reactions require anti-inflammatory management but continuation of MDT 5, 7
• Ensure supervised monthly rifampin doses are actually observed, as adherence is critical for preventing resistance 4