What is leprosy and how is it treated?

Leprosy (Hansen's Disease): Essential Clinical Knowledge

What is Leprosy?

Leprosy is a chronic bacterial infection caused by Mycobacterium leprae that primarily affects the skin, peripheral nerves, and upper respiratory mucosa, with clinical presentation determined by the host's immune response to the pathogen. 1, 2, 3

• The disease has a long incubation period of 2-6 years and is transmitted person-to-person via aerosol droplets and broken skin contact 4, 5
• M. leprae specifically targets Schwann cells in peripheral nerves, leading to nerve damage and potential disabilities 3
• Despite being highly infective, it has low pathogenicity and low virulence 6

Clinical Forms and Presentations

The Four Major Clinical Forms

The clinical spectrum of leprosy reflects the patient's cell-mediated immune response, ranging from tuberculoid (strong immunity) to lepromatous (weak immunity). 1, 2, 7

Tuberculoid (Paucibacillary) Form

• One or few well-demarcated, hypopigmented, and anesthetic skin lesions 1, 2
• Active spreading edges with clearing centers 1, 2
• Peripheral nerve swelling or thickening may occur 1, 2
• Results from vigorous cellular immune response with limited humoral response 7

Lepromatous (Multibacillary) Form

• Multiple erythematous papules and nodules 1, 2
• Infiltration of face, hands, and feet with bilateral and symmetrical distribution 1, 2
• Progressive skin thickening 1, 2
• Oral manifestations occur in 20-60% of cases, including nodules (lepromas) on hard/soft palate, uvula, tongue, lips, and gums 4
• Most contagious form due to inability to mount effective cellular-mediated response 6, 7

Borderline (Dimorphous) Form

• Skin lesions characteristic of both tuberculoid and lepromatous forms 1, 2
• Intermediate immune response 1, 2

Indeterminate Form

• Early lesions, usually hypopigmented macules 1, 2
• Occurs in individuals who have not yet developed cell-mediated immunity against M. leprae 7
• May evolve into other forms or resolve spontaneously 6, 7

Diagnosis

Clinical Diagnosis

Diagnosis requires identification of one or more of three cardinal signs: hypopigmented or erythematous skin patches with definite loss of sensation, thickened peripheral nerves, and acid-fast bacilli on skin smears or biopsy. 3

Laboratory Confirmation

Laboratory confirmation is established by demonstrating acid-fast bacilli in skin or dermal nerve obtained from full-thickness skin biopsy of a lepromatous lesion. 1, 2

• Skin bacilloscopy and histopathology complement the clinical picture 6
• Lepromin test (intradermal reaction) is negative in lepromatous form and positive in tuberculoid form 4

Treatment

Multidrug Therapy (MDT) Regimens

The World Health Organization recommends fixed-dose multidrug therapy combining rifampin, dapsone, and clofazimine to effectively eliminate M. leprae and prevent resistance. 8, 4, 6

Medication Details

Rifampin (Rifampicin):

• Core component of all MDT regimens 4, 6, 5

Dapsone:

• Requires screening for G6PD deficiency before initiation due to risk of hemolytic anemia and methemoglobinemia 8, 9
• Monitor complete blood count and liver function tests regularly 8, 9
• Side effects include hemolysis, methemoglobinemia, nausea, and vomiting 8

Clofazimine:

• Dosage: 50-100 mg daily with meals or milk to maximize absorption 8
• Available as 50 and 100 mg gelcaps that cannot be split 8
• Pink to brownish-black skin discoloration occurs in 75-100% of patients within 1-4 weeks, resolving 6-12 months after stopping 8
• Adverse effects include skin pigmentation, ichthyosis, gastrointestinal intolerance, and QT interval prolongation 8
• Requires baseline ECG and QT interval monitoring at 2 weeks and after adding any QT-prolonging medications 8

Alternative Agents

• Quinolones (ofloxacin, pefloxacin) and macrolides (clarithromycin) are effective alternatives 4, 6
• Single-dose combination of rifampin, ofloxacin, and minocycline has been recommended for paucibacillary leprosy 6

Treatment Duration

• Duration was reduced from 24 to 12 months for multibacillary leprosy 6
• Treatment should be continued during pregnancy as benefits outweigh risks, with close monitoring required 8

Pediatric Dosing

• Clofazimine: 1-2 mg/kg/day (maximum 100 mg) 8
• Well-tolerated in pediatric leprosy trials 8

Monitoring and Follow-up

Clinical monitoring should assess for treatment response, with lesion flattening expected by 4-6 weeks after treatment initiation. 8

• Monitor for drug toxicity with regular liver function tests and complete blood count 8
• Post-treatment surveillance to monitor for signs of relapse 8
• ECG monitoring necessary when using clofazimine, especially with other QT-prolonging medications 8

Leprosy Reactional States (Critical Complication)

Abrupt changes in clinical activity occur with any effective treatment and represent immunological reactions, not treatment failure—MDT must be continued while managing the reaction. 8, 9

Type 1 Reaction (Reversal Reaction)

• Occurs in borderline or tuberculoid patients, often soon after chemotherapy starts 9
• Results from enhanced delayed hypersensitivity response to residual infection 9
• Swelling of existing skin and nerve lesions 9
• If severe or neuritis present, large doses of steroids should always be used 9
• Severe cases require hospitalization 9
• Continue anti-leprosy treatment while adding analgesics, steroids, or surgical decompression of swollen nerve trunks 9

Type 2 Reaction (Erythema Nodosum Leprosum - ENL)

• Occurs mainly in lepromatous patients and small numbers of borderline patients 9
• Approximately 50% of treated patients show this reaction in the first year 9
• Clinical features: fever, tender erythematous skin nodules, malaise, neuritis, orchitis, albuminuria, joint swelling, iritis, epistaxis, or depression 9
• Skin lesions can become pustular and/or ulcerate 9
• Mechanism: vasculitis with intense polymorphonuclear infiltrate and elevated circulating immune complexes 9
• Severe cases require hospitalization 9
• Continue anti-leprosy treatment while adding analgesics, steroids, and other suppressive agents 9

Critical Pitfalls and Caveats

Distinguish leprosy reactions from treatment failure—reactions require anti-inflammatory management but continuation of MDT. 8

• Early diagnosis and treatment are crucial to preventing irreversible nerve damage and disabilities 6, 5
• Without treatment, tuberculoid forms may progress and lepromatous forms lead to widespread disease 6, 7
• Oral lesions in lepromatous leprosy can cause destruction of anterior maxilla and tooth loss 4
• The disease remains endemic in tropical and subtropical regions such as India and Brazil 6
• New case detection rates remain high despite reduced prevalence, indicating active transmission 3

Differential Diagnosis

Consider systemic lupus erythematosus, sarcoidosis, cutaneous leishmaniasis, tertiary syphilis, lymphomas, systemic mycosis, traumatic lesions, and malignant neoplasias when evaluating suspected leprosy. 4