What is the recommended treatment for an adult or child with leprosy (Hansen's disease), with no prior medical history, living in an endemic area?

Treatment of Leprosy (Hansen's Disease)

For adults and children with leprosy in endemic areas, the World Health Organization-recommended multidrug therapy (MDT) consisting of rifampin, dapsone, and clofazimine for multibacillary disease, or rifampin and dapsone for paucibacillary disease, remains the standard treatment, with duration of 12-24 months for multibacillary and 6 months for paucibacillary forms. 1, 2

Classification and Treatment Selection

The treatment regimen depends on disease classification based on the number of skin lesions and bacterial load:

Paucibacillary Leprosy (Tuberculoid/Indeterminate):

• Characterized by one to five hypopigmented, well-demarcated, anesthetic skin lesions with active spreading edges 1, 3
• Treatment: Rifampin 600 mg monthly (supervised) plus dapsone 100 mg daily for 6 months 1, 2
• After completing initial therapy, continue dapsone for an additional 3 years for tuberculoid/indeterminate patients and 5 years for borderline tuberculoid patients 4

Multibacillary Leprosy (Lepromatous/Borderline Lepromatous):

• Characterized by multiple erythematous papules, nodules, or facial infiltration with bilateral symmetrical distribution 1, 5
• Treatment: Rifampin 600 mg monthly (supervised), clofazimine 300 mg monthly (supervised) plus 50 mg daily, and dapsone 100 mg daily for 12-24 months 1, 2, 4
• Continue dapsone for 10 additional years for borderline patients and lifelong for lepromatous patients after completing initial MDT 4

Pediatric Dosing Adjustments

• Dapsone: 1-2 mg/kg daily (used safely in children for leprosy without adverse effects on growth and development) 6
• Clofazimine: 1-2 mg/kg daily (maximum 100 mg), well-tolerated in pediatric leprosy trials 6, 1
• Rifampin: Dose proportionally reduced based on weight 1

Mandatory Pre-Treatment Screening

Before initiating therapy, the following assessments are critical to prevent serious adverse events:

• G6PD deficiency screening is mandatory before dapsone due to risk of dose-related hemolysis (occurs even in patients without G6PD deficiency when daily doses exceed 200 mg) 6, 1, 2
• Baseline ECG is required before clofazimine due to QT interval prolongation risk, with monthly ECG monitoring when multiple QT-prolonging agents are used 6, 1, 2
• Baseline complete blood count and liver function tests with regular monitoring during dapsone therapy 1, 2

Management of Leprosy Reactions

A critical pitfall is interrupting MDT when leprosy reactions occur—this worsens outcomes and must be avoided:

Type 1 Reversal Reactions:

• Present as acute inflammation of existing skin lesions with new nerve involvement 7, 8
• Continue MDT without interruption and add corticosteroids for anti-inflammatory management 1, 2, 7

Type 2 Reactions (Erythema Nodosum Leprosum):

• Present as painful subcutaneous nodules with systemic symptoms 7, 8
• Continue MDT and add corticosteroids, thalidomide (where available), or pentoxifylline 7
• Treatment should not be interrupted due to skin complications or wound healing 1, 2

Alternative Regimen for Improved Tolerability

Monthly rifampin 600 mg, moxifloxacin 400 mg, and minocycline 100 mg (RMM) for 12-24 months represents an emerging alternative with superior tolerability:

• A 2022 US case series demonstrated 100% treatment completion without interruptions, no skin hyperpigmentation, and rapid improvement of skin lesions 9
• This regimen avoids clofazimine-related skin discoloration (which can take years to resolve) and dapsone-related hemolysis 6, 9
• Consider as first-line therapy when patient adherence concerns exist or when avoiding cosmetic side effects is prioritized 9, 7

Monitoring During Treatment

• Clinical assessment every 1-3 months for skin lesion improvement (expect flattening by 4-6 weeks) and nerve function 2
• Complete blood count and liver function tests every 3-6 months during dapsone therapy 1, 2
• ECG monitoring when using clofazimine, especially with concurrent QT-prolonging medications 6, 1, 2
• Skin smears and biopsies to assess bacterial clearance in multibacillary disease 4

Special Populations

Pregnancy:

• Continue MDT during pregnancy as benefits outweigh risks 1
• Close monitoring required but treatment should not be interrupted 1

Suspected Dapsone Resistance:

• Consider when lepromatous/borderline lepromatous patients relapse clinically and bacteriologically with solid-staining bacilli in new lesions despite 3-6 months of supervised therapy 4
• Switch to alternative regimens containing moxifloxacin, ofloxacin, minocycline, or clarithromycin 4, 7

Common Pitfalls to Avoid

• Never discontinue MDT during leprosy reactions—reactions require anti-inflammatory therapy while continuing antibacterial treatment 1, 2, 7
• Never skip G6PD screening before dapsone—hemolysis can be severe and life-threatening 6, 1, 2
• Never ignore QT interval monitoring with clofazimine—cardiac arrhythmias are preventable with proper surveillance 6, 1, 2
• Never delay treatment while awaiting biopsy confirmation—clinical diagnosis with characteristic hypopigmented anesthetic lesions and thickened nerves is sufficient to initiate therapy 1, 5