What is the recommended treatment for leprosy (Hansen's disease)?

Leprosy Diagnosis and Treatment

Diagnostic Approach

Leprosy diagnosis requires clinical assessment of skin lesions with sensory loss, thickened peripheral nerves, and acid-fast bacilli on skin smears or biopsy, followed by classification into paucibacillary (PB) or multibacillary (MB) disease to guide multidrug therapy selection. 1

Classification Criteria

• Paucibacillary leprosy: 1-5 skin lesions with no bacilli on skin smears 2
• Multibacillary leprosy: >5 skin lesions or any number with positive skin smears 2
• Classification determines treatment duration and drug combinations 1

Treatment Regimens

Multibacillary Leprosy (Standard WHO Regimen)

The WHO-recommended regimen consists of rifampin 600 mg monthly (supervised), dapsone 100 mg daily, and clofazimine 300 mg monthly (supervised) plus 50 mg daily for 12 months. 1, 3

• Treatment duration is fixed at 12 months regardless of bacteriological status 1, 2
• Rifampin provides powerful bactericidal activity 4
• Clofazimine dosing: 50-100 mg daily with meals or milk to maximize absorption 1
• Dapsone maintained at full 100 mg daily dose without interruption 3

Paucibacillary Leprosy

The WHO regimen for paucibacillary disease consists of rifampin 600 mg monthly (supervised) plus dapsone 100 mg daily for 6 months. 1, 2

• Fixed 6-month duration regardless of clinical response 2
• Single-lesion paucibacillary leprosy can be treated with single-dose rifampin 600 mg, ofloxacin 400 mg, and minocycline 100 mg 2

Alternative Regimen (RMM)

Monthly rifampin 600 mg, moxifloxacin 400 mg, and minocycline 100 mg for 12-24 months represents an effective alternative with superior tolerability and no skin hyperpigmentation. 5

• All 10 patients in recent US case series completed treatment without interruptions 5
• No significant adverse effects or skin hyperpigmentation occurred 5
• Particularly useful when clofazimine is contraindicated or poorly tolerated 5
• The US National Hansen's Disease Program increasingly considers this as first-line therapy 5

Pre-Treatment Screening

Essential Laboratory Tests

• Screen for G6PD deficiency before initiating dapsone due to hemolytic anemia risk 1
• Baseline complete blood count and liver function tests 1
• Baseline ECG when using clofazimine to assess QT interval 1

Monitoring During Treatment

Drug Toxicity Surveillance

• Complete blood count and liver function tests regularly to monitor for dapsone-induced hemolytic anemia, methemoglobinemia, and hepatotoxicity 1
• ECG monitoring at 2 weeks after clofazimine initiation and when adding QT-prolonging medications 1
• Monitor for clofazimine adverse effects: skin pigmentation (75-100% within 1-4 weeks), ichthyosis, gastrointestinal intolerance 1

Clinical Response Assessment

• Lesion flattening expected by 4-6 weeks after treatment initiation 1
• Bacteriological index decreases approximately 1.1+ during first year, 0.9+ second year, then <0.5+ per year in multibacillary disease 6
• Post-treatment surveillance to monitor for relapse signs 1

Management of Leprosy Reactions

Leprosy reactions (Type 1 reversal reactions and Type 2 erythema nodosum leprosum) require anti-inflammatory management but continuation of multidrug therapy—these are NOT treatment failures. 1

Type 1 Reversal Reactions

• Occur in 13% of paucibacillary and 17-43% of multibacillary patients during treatment 6
• Accelerate bacteriological index decrease 6
• Continue MDT while adding corticosteroids for inflammation 1

Type 2 Reactions (Erythema Nodosum Leprosum)

• Occur in 41% of multibacillary patients during treatment 6
• Delay bacteriological index decrease 6
• Continue MDT while managing with anti-inflammatory agents 1

Special Populations

Pregnancy

Treatment should be continued during pregnancy as benefits outweigh risks, with close monitoring required. 1

Pediatric Patients

• Clofazimine: 1-2 mg/kg/day (maximum 100 mg) 1
• Dapsone and rifampin: correspondingly smaller doses than adults 3
• Well-tolerated in pediatric leprosy trials 1

Critical Pitfalls to Avoid

Distinguishing Reactions from Treatment Failure

• Do not stop MDT when reactions occur—this is the most common error 1
• Reactions reflect immune response, not drug resistance 6
• Add anti-inflammatory therapy while continuing antimicrobials 1

Suspected Dapsone Resistance

• Suspect when lepromatous/borderline lepromatous patients relapse clinically and bacteriologically with solid-staining bacilli in new lesions 3
• Confirm with mouse footpad drug sensitivity testing (available through US National Hansen's Disease Program: 1-800-642-2477) 3
• Switch to alternative drugs if resistance confirmed 3

Clofazimine-Specific Warnings

• Warn patients about pink to brownish-black skin discoloration occurring in 75-100% within 1-4 weeks, resolving 6-12 months after stopping 1
• Cannot split 100 mg capsules—adjust dosing accordingly 1
• Avoid combining with other QT-prolonging medications without ECG monitoring 1

Inadequate Treatment Duration

• Approximately 20% of paucibacillary patients on 6-month WHO-MDT continue to have active disease at discharge 7
• Some tuberculoid patients require 6-24 months for clinical cure (mean 19.5 months) 6
• Multibacillary patients require average 66.5 months to achieve bacteriological negativity with daily regimens 6