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Leprosy

Infectious Diseases | Part 5 – Infectious Diseases: Bacterial · Part 5 – Infectious Diseases: Bacterial · Chapter 184

Key Clinical Points

  1. Leprosy is caused by Mycobacterium leprae, an obligate intracellular acid-fast bacterium infecting macrophages and Schwann cells.
  2. Disease spectrum ranges from tuberculoid (TT) to lepromatous (LL) based on host cell-mediated immune response.
  3. Three cardinal signs for diagnosis: hypopigmented/erythematous skin lesions with sensory loss, peripheral nerve thickening with impairment, and positive AFB in smear/biopsy.
  4. WHO disability grading uses Eye-Hand-Foot (EHF) score: Grade 0 (no impairment), Grade 1 (anesthesia), Grade 2 (visible impairment).
  5. Type 1 reaction (T1R) is a delayed hypersensitivity causing acute nerve damage; Type 2 (T2R) is immune complex-mediated erythema nodosum leprosum.
  6. Slit-skin smear classifies disease: Paucibacillary (1–5 lesions) vs Multibacillary (6+ lesions).
  7. M. leprae cannot be cultured; diagnosis relies on smear, biopsy, or PGL-1 antibody testing.
  8. Early treatment prevents disability and social stigma associated with nerve damage.
  9. M. lepromatosis causes diffuse leprosy of Lucio and Latapí, found mainly in Mexico/Central America.
  10. Clofazimine causes skin staining; Dapsone can cause hemolysis in G6PD deficiency.

1. DEFINITION & OVERVIEW

• Overview: Chronic infectious disease caused by Mycobacterium leprae, primarily affecting the skin, peripheral nerves, eyes, and upper respiratory tract. • Immune Response: The host's cell-mediated immune (CMI) response determines the clinical spectrum from tuberculoid (TT) to lepromatous (LL). • Consequences: Immune-mediated reactions can cause nerve damage leading to disability and social stigma.

Definition (Harrison's 22e): Leprosy is a neglected disease and is often thought no longer to exist. However, 174,087 new cases from 182 countries were reported in 2022.

2. ETIOLOGY & PATHOPHYSIOLOGY

• M. leprae: ◦ Obligate intracellular, acid-fast rod-shaped bacterium (1–8 μm × 0.3 μm). ◦ Infects macrophages and Schwann cells. ◦ Growth: Cannot be cultured in artificial media; grows slowly in mouse footpads at 27–30°C. ◦ Structure: Contains cytoplasm, plasma membrane (protein antigens), cell wall (peptidoglycans/arabinogalactans/mycolic acids), and a capsule containing PGL-1 (a species-specific phenolic glycolipid).

• M. lepromatosis: ◦ Causes diffuse leprosy of Lucio and Latapí. ◦ Found mainly in Mexico and Central America. ◦ Microbiologically similar to M. leprae; both are acid-fast, noncultivable, and respond to same antimycobacterial regimens.

• Pathogenesis: ◦ Entry into peripheral nerves → immune response determines disease type. ◦ Strong CMI (TT) → Granuloma formation via macrophage-lymphocyte interaction. ◦ Weak/No CMI (LL) → Unrestricted bacillary proliferation within macrophages.

Ridley-Jopling Classification

• Tuberculoid (TT): Strong CMI, Stable, Single/few lesions, complete sensory loss, thickened nerves. • Borderline Tuberculoid (BT): Moderate CMI, Unstable, 3–9 asymmetric lesions, variable margins, susceptible to T1R. • Mid-Borderline (BB): Intermediate CMI, Unstable, Multiple bilateral plaques, moderate sensation loss. • Borderline Lepromatous (BL): Weak CMI, Unstable, Numerous bilateral lesions, minimal sensory loss, few bacilli. • Lepromatous (LL): No/weak CMI, Stable (polar)/unstable (subpolar), Innumerable bilateral lesions, no sensation loss, high bacillary load.

• WHO Simplified Clinical Classification: ◦ Paucibacillary (PB) → 1–5 lesions, negative smear. ◦ Multibacillary (MB) → ≥6 lesions, positive smear.

3. EPIDEMIOLOGY

• Global Status: ◦ 174,087 new cases in 2022. ◦ 80% of cases from three countries (India, Brazil, Indonesia). ◦ 8% of cases in children (<15 years) indicating ongoing transmission.

• Transmission & Reservoirs: ◦ Route: Droplets from untreated MB patients; skin contact. ◦ Zoonotic: Armadillos in southern U.S. ◦ Note: No evidence of transmission from monkeys or squirrels; environmental sources (water/soil) unlikely.

• Clinical Risk Factors: ◦ Incubation period: 2–10 years (longer for MB). ◦ Risk factors: Poverty, low education, and close contact with untreated patients.

• Disability Grading (Table 184-2): ◦ Grade 0: No anesthesia and no visible impairment. ◦ Grade 1: Anesthesia but no visible impairment. ◦ Grade 2: Visible impairment (e.g., vision <6/60, lagophthalmos, iridocyclitis, corneal opacities). ◦ Prevalence: Grade 2 disability reported in ≈5% of patients.

4. CLINICAL FEATURES

• Tuberculoid (TT): Few well-defined hypopigmented/erythematous lesions with complete sensory loss, thickened nerves. • Borderline Tuberculoid (BT): 3–9 asymmetric lesions, variable margins, susceptible to T1R. • Mid-Borderline (BB): Multiple bilateral plaques, moderate sensation loss, asymmetrical nerve thickening. • Borderline Lepromatous (BL): Numerous bilateral macular lesions, minimal sensory loss, negative lepromin test. • Lepromatous (LL): Innumerable symmetric erythema/copper-colored patches, no sensation loss, 'lion face' appearance, earlobe thickening, and madarosis (eyebrow loss).

• Indeterminate Leprosy (IL): ◦ 1–5 hypopigmented/erythematous macules on limbs/buttocks/faces. ◦ Mild sensory impairment, no nerve thickening. ◦ May resolve spontaneously or progress to TT/BT/LL.

• Primary Neuritic Leprosy: ◦ 2–10% of cases in India/Nepal. ◦ Peripheral nerve involvement without skin lesions → progresses to papules/nodules with sensory/motor deficits.

5. DIFFERENTIAL DIAGNOSIS

• Tuberculoid (TT): Differentiated from psoriasis, vitiligo, and other hypopigmented dermatoses by presence of sensory loss and nerve thickening. • Lepromatous (LL): Distinguished from syphilis, leishmaniasis, and sarcoidosis by characteristic skin distribution and high bacillary load.

• Diagnostic Clues: ◦ TT: Sensory loss > nerve thickening. ◦ LL: Symmetric erythema; 'lion face' appearance. ◦ T1R vs T2R: Acute swelling (T1R) vs fever/nodules (T2R).

6. DIAGNOSTIC APPROACH

  1. Clinical Evaluation: Assess skin lesions, nerve thickening, and sensory loss.
  2. Slit-skin Smear: Determine Bacteriological Index (0–6+) and morphologic index (viable bacilli percentage).
  3. Biopsy: Perform for histopathology (e.g., globi in LL) and AFB detection.
  4. Serology: Perform PGL-1 antibody testing if smear is negative (useful for paucibacillary cases).

7. MANAGEMENT & TREATMENT

  1. Determine Classification:
  2. Paucibacillary (PB) → 1–5 lesions, negative smear.
  3. Multibacillary (MB) → ≥6 lesions, positive smear.
  4. Initiate Multidrug Therapy (MDT):
  5. Paucibacillary (PB):
  6. Rifampin: 600 mg monthly.
  7. Dapsone: 100 mg daily.
  8. Duration: 6 months.
  9. Multibacillary (MB):
  10. Rifampin: 600 mg monthly.
  11. Clofazimine: 50 mg daily + 300 mg monthly.
  12. Dapsone: 100 mg daily.
  13. Duration: 12 months.
  14. Manage Reactional Episodes:
  15. T1R/T2R → Corticosteroids.
  16. ENL (T2R) → Thalidomide.
  17. Monitoring & Prevention:
  18. Early treatment to prevent disability.
  19. Monitor nerves for signs of damage.
  20. Note: Clofazimine causes skin staining; Dapsone requires caution in G6PD deficiency (risk of hemolysis).

Table 184-1 Summary (Dosages): - Dapsone: Adult 100 mg/d; Child <10 years (weight adjusted). - Rifampin: Adult 600 mg monthly; Child 10–14 years 450 mg monthly; Child <10 years (weight adjusted). - Clofazimine: Adult 50 mg/d + 300 mg monthly; Child <10 years (weight adjusted).

8. COMPLICATIONS & PROGNOSIS

• Prognosis: ◦ TT: Excellent with MDT; minimal disability. ◦ LL: High risk of irreversible nerve damage, facial disfigurement, and blindness if untreated.

• Complications: ◦ Grade 2 disability (visible impairment) in ≈5% of patients. ◦ Social stigma. ◦ Secondary infections.

9. SPECIAL CONSIDERATIONS

• M. lepromatosis: Treated similarly to M. leprae; no distinct management required. • Histoid Leprosy: Rare LL variant with waxy nodules; managed with standard MDT. • Pregnancy: Safe to treat with MDT; avoid thalidomide due to teratogenicity.

10. KEY PEARLS & HIGH-YIELD POINTS

• Pearls: ◦ Early treatment is the primary defense against permanent disability. ◦ T1R/T2R are medical emergencies requiring corticosteroids or thalidomide. ◦ PGL-1 serology is a critical tool for diagnosing paucibacillary cases.

• Traps: ◦ Do not mistake TT for psoriasis or vitiligo (check sensation!). ◦ Do not assume LL has no risk of disability due to lack of initial sensory loss. ◦ Be aware of gender-based underdiagnosis in women due to socioeconomic barriers.

Reference Tables

Harrison's 22e, p.1411

DRUG, AGE GROUP PAUCIBACILLARY
LEPROSYa		 MULTIBACILLARY
LEPROSYb
Dapsone
Adult 100 mg/d 100 mg/d
50 mg/d
Child <10 years Dose adjusted to body
weight		 Dose adjusted to body
weight
Rifampin
600 mg monthly
Child 10–14 years 450 mg monthly 450 mg monthly
Dose adjusted to body
weight
Clofaziminec
Adult — 50 mg/d plus 300 mg
monthly
—
Child <10 years — Dose adjusted to body
weight