What is leprosy, its aetiology, modes of transmission, clinical manifestations, subtypes, and treatment options?

Leprosy: Comprehensive Overview

Aetiology

Leprosy is a chronic bacterial infection caused by Mycobacterium leprae, an acid-fast bacillus with high infectivity but low pathogenicity and virulence. 1, 2

• The bacterium has a predilection for peripheral nerves, skin, and upper respiratory mucosa, with M. leprae primarily infecting Schwann cells in peripheral nerves leading to nerve damage and disabilities 1, 3
• The disease has a long incubation period ranging from two to six years 2, 4
• M. leprae can be found in nine-banded armadillos, which serve as a natural reservoir 5

Modes of Transmission

Transmission occurs through prolonged close contact via respiratory droplets from nasal secretions of untreated multibacillary patients. 1, 6

• Nasal droplet infection is considered the most likely route of transmission, though the exact mechanism remains incompletely understood 6
• Transmission can also occur through broken skin-to-skin contact 5
• Despite being highly infective, the disease demonstrates low pathogenicity and low virulence, meaning most exposed individuals do not develop clinical disease 1, 2

Clinical Manifestations

The cardinal clinical features include hypopigmented or erythematous skin lesions with definite sensory loss, thickened peripheral nerves, and acid-fast bacilli on skin smears or biopsy. 7, 3

• The disease primarily affects skin and peripheral nerves, NOT the central nervous system 7
• Upper respiratory mucosa involvement can lead to nasal symptoms including nasal congestion and epistaxis 8
• Advanced disease is characterized by disfiguring mutilations and irreversible disabilities if left untreated 6, 5
• Peripheral neuropathy develops progressively, causing weakness and sensory loss in affected body parts 5

Clinical Subtypes

The disease manifests as a spectrum based on the host's cellular immune response to M. leprae, ranging from tuberculoid (paucibacillary) with strong cell-mediated immunity to lepromatous (multibacillary) with weak cell-mediated immunity. 1, 8

Tuberculoid (Paucibacillary) Leprosy

• Characterized by one or a few well-demarcated, hypopigmented, and anesthetic skin lesions with active spreading edges and clearing centers 1, 8
• Peripheral nerve swelling may occur with few lesions 8, 2
• Represents strong cell-mediated immunity against the pathogen 1

Lepromatous (Multibacillary) Leprosy

• Presents with multiple erythematous papules and nodules or infiltration of the face, hands, and feet with bilateral and symmetrical distribution 1, 8
• Progresses to skin thickening and is the more contagious form 2, 4
• Oral manifestations occur in 20-60% of cases, presenting as multiple nodules (lepromas) that progress to necrosis and ulceration on the hard and soft palate, uvula, underside of tongue, lips, and gums 4

Borderline (Dimorphous) Forms

• Represent intermediate immune states along the spectrum between tuberculoid and lepromatous leprosy 7
• Display hybrid characteristics of both polar forms 4

Indeterminate Leprosy

• Frequently the initial form consisting of a few lesions that either evolve into other forms or resolve spontaneously 2

Treatment

The World Health Organization recommends multidrug therapy (MDT) with rifampin, clofazimine, and dapsone for multibacillary leprosy for at least 12 months, and rifampin and dapsone for paucibacillary leprosy for at least 6 months. 1, 6

Multibacillary Leprosy Treatment

• Rifampin + clofazimine + dapsone for at least 12 months 1, 6
• Baseline ECG is required before clofazimine due to risk of QT interval prolongation 1
• Clofazimine dosing in pediatrics: 1-2 mg/kg/day (maximum 100 mg) 1

Paucibacillary Leprosy Treatment

• Rifampin + dapsone for at least 6 months 1, 6
• Alternative single-dose regimen under evaluation: rifampin + ofloxacin + minocycline 2

Critical Pre-Treatment Requirements

• G6PD deficiency screening is mandatory before initiating dapsone due to risk of hemolytic anemia and methemoglobinemia 1
• Regular monitoring of complete blood count and liver function tests is necessary during dapsone therapy 1

Treatment Continuation Principles

• Treatment should NOT be interrupted due to skin complications, wound healing, or leprosy reactions 1
• Treatment should be continued during pregnancy as benefits outweigh risks, with close monitoring required 1

Management of Leprosy Reactions

• Leprosy reactions (Type 1 reversal reactions, Type 2 erythema nodosum leprosum) require anti-inflammatory management but continuation of MDT 1
• Type 1 reversal reactions should be treated with corticosteroids while continuing MDT 1
• Leprosy reactions during therapy may considerably aggravate the disease course 6

Common Pitfalls and Caveats

• Premature treatment discontinuation due to leprosy reactions worsens outcomes; reactions require anti-inflammatory therapy while continuing MDT 1
• Inadequate monitoring, such as failure to screen for G6PD deficiency before dapsone or monitor QT interval with clofazimine, can lead to serious adverse events 1
• Early detection and treatment are crucial to preventing irreversible nerve damage and disabilities 5, 2
• Delayed diagnosis allows progression to disfiguring mutilations that cannot be reversed even with appropriate treatment 6