194.1 🎓 醫孞生版

194.1.0.1 📌 䞀頁重點

  • 菌: Mycobacterium leprae + M. lepromatosis (Mexico, Caribbean) — acid-fast bacilli, intracellular, cannot culture in vitro (grow only in 9-banded armadillo + mouse footpad)
  • 流行病孞:
    • WHO 2024: ~ 175,000 new cases/yr globally
    • High burden: India (60%), Brazil (15%), Indonesia
    • Taiwan: very few; mostly imported
  • Transmission: prolonged close contact + droplet (less infectious than TB); ~ 95% humans innately resistant
  • Incubation: long (3-10 years average)
  • Reservoir (zoonotic component): armadillo (USA southern, Texas, Louisiana, Florida)
  • Spectrum (Ridley-Jopling):
    • Tuberculoid (TT): strong CMI, few well-defined hypopigmented anesthetic plaques, few bacilli, peripheral nerve thickening
    • Borderline (BT, BB, BL): intermediate
    • Lepromatous (LL): weak CMI, many bacilli, diffuse skin + multi-organ + leonine facies + saddle nose + glove-and-stocking neuropathy + ocular + nasal + bone changes
  • Clinical features:
    • Hypopigmented anesthetic skin plaques (loss of sensation key — distinguishes from other dermatoses)
    • Peripheral nerve thickening (ulnar, posterior auricular great, common peroneal, posterior tibial, supraorbital)
    • Neuropathic injury (Charcot foot, claw hand, lagophthalmos, foot drop)
  • Diagnosis:
    • Clinical (hypopigmented anesthetic patch + nerve thickening = suspect)
    • Slit-skin smear AFB (positive lepromatous, negative tuberculoid)
    • Skin biopsy histology + Fite stain
    • PCR (specialized labs)
  • Treatment (WHO MDT):
    • PB (paucibacillary, TT/BT): Rifampin 600 mg monthly + Dapsone 100 mg daily × 6 mo
    • MB (multibacillary, BB/BL/LL): Rifampin 600 mg monthly + Dapsone 100 mg daily + Clofazimine 300 mg monthly + 50 mg daily × 12 mo
    • Single skin lesion PB: ROM regimen — Rifampin + Ofloxacin + Minocycline × 1 dose alt
  • Reactions:
    • Type 1 (Reversal Reaction): T-cell mediated; pre-existing lesion inflamed; treat with steroid
    • Type 2 (ENL — Erythema Nodosum Leprosum): immune complex; new tender erythematous nodules + fever + neuritis; thalidomide + steroid
  • Prevention:
    • 2018 WHO PEP: single-dose rifampin 600 mg for household contacts (reduces incidence ~ 50%)
    • BCG vaccine — some efficacy
    • Active surveillance + early treatment

194.1.0.2 1⃣ 现菌孞

  • M. leprae — acid-fast bacillus, intracellular (macrophage, Schwann cell)
  • Cannot culture in vitro — only in armadillo or mouse footpad
  • 30-50% genome decay (degenerate metabolism; obligate parasite)
  • Optimal at 30-33°C (cooler body parts — skin, peripheral nerves, anterior chamber eye, nasal mucosa, ears)
  • M. lepromatosis — Mexico + Caribbean variant, often diffuse lepromatous form
194.1.0.2.1 Pathogenesis
  • Macrophage uptake → 慢 granuloma formation
  • Schwann cell tropism (cooler body parts) → demyelination → nerve thickening + neuropathic injury
  • Spectrum from cell-mediated (TT) to humoral (LL) immune response

194.1.0.3 2⃣ Spectrum (Ridley-Jopling)

194.1.0.3.1 Tuberculoid (TT)
  • Strong CMI, granulomatous response
  • Few well-defined hypopigmented anesthetic plaques (1-3 lesions)
  • Peripheral nerve thickening
  • Few bacilli on slit-skin smear (paucibacillary)
  • Less infectious
194.1.0.3.2 Borderline Tuberculoid (BT)
  • More lesions
  • Variable bacterial load
194.1.0.3.3 Borderline Borderline (BB)
  • Intermediate, unstable
194.1.0.3.4 Borderline Lepromatous (BL)
  • Many lesions, increasing bacilli
194.1.0.3.5 Lepromatous (LL)
  • Weak CMI, Th2 humoral response
  • Many bacilli (multibacillary, high infectivity)
  • Diffuse skin involvement, infiltration
  • Leonine facies (loss of eyebrows, infiltration of forehead + cheeks)
  • Saddle nose (nasal cartilage destruction)
  • Madarosis (eyebrow loss)
  • Glove-and-stocking neuropathy (symmetric)
  • Hands + feet: clawing, ulceration, autoamputation
  • Eye: lagophthalmos, corneal anesthesia, iritis, cataracts
  • Nasal: chronic rhinitis, congestion, perforation
  • Bone: osteo destruction
  • Genital: orchitis (infertility in men)
194.1.0.3.6 Diffuse Lepromatous
  • Variant — diffuse infiltration without discrete lesions
  • M. lepromatosis often
  • Lucio’s phenomenon (vasculitis necrosis)

194.1.0.4 3⃣ Clinical Features

194.1.0.4.1 Skin
  • Hypopigmented or erythematous plaques with loss of sensation (KEY distinguishing feature)
  • Borders well-defined (TT) or ill-defined (LL)
  • Anhidrosis (loss of sweating in lesion)
  • Hair loss in lesion
  • Distribution: cooler body parts (face, ears, extensor surfaces; usually spare axilla, groin, perineum)
194.1.0.4.2 Peripheral Nerve
  • Nerve thickening (palpable):
    • Ulnar at elbow
    • Posterior auricular great in neck
    • Common peroneal at fibular neck
    • Posterior tibial at medial malleolus
    • Supraorbital, infraorbital, mandibular in face
    • Radial cutaneous at wrist
    • Sural in lower leg
  • Sensory deficits: glove-and-stocking (LL) or focal in lesion (TT)
  • Motor deficits:
    • Claw hand (ulnar + median palsy → MCP hyperextended, IP flexed)
    • Foot drop (common peroneal)
    • Lagophthalmos (CN VII facial — orbicularis oculi)
    • Lateral popliteal: foot drop
  • Charcot joint: neuropathic destruction
  • Plantar ulcers: unfelt repetitive trauma
194.1.0.4.3 Eye
  • Lagophthalmos + corneal anesthesia + dry eye → corneal damage
  • Iritis, scleritis, uveitis (LL)
  • Cataracts
  • Blindness in advanced
194.1.0.4.4 Nasal + Upper Airway
  • Chronic rhinitis
  • Septum perforation
  • Saddle nose (chronic LL)
194.1.0.4.5 Bone
  • Cortical thinning, resorption
  • Osteoperiostitis
194.1.0.4.6 Other
  • Orchitis (LL, men) → infertility
  • Lymphadenopathy
  • Hepatomegaly (LL)

194.1.0.5 4⃣ Diagnosis

194.1.0.5.1 Clinical Criteria (WHO)
  • ≥ 1 of:
    • Hypopigmented or erythematous skin lesion with definite sensory loss
    • Thickened peripheral nerve(s)
    • Positive slit-skin smear (AFB)
194.1.0.5.2 Slit-Skin Smear
  • AFB stain (acid-fast bacilli)
  • Sites: earlobes, elbow, knee, suspected lesions
  • Positive in LL/BL (multibacillary)
  • Negative in TT/BT (paucibacillary)
194.1.0.5.3 Skin Biopsy
  • Histology: granulomas (TT) vs foam cells (LL)
  • Fite stain (modified AFB) for M. leprae
  • “Globi” — clusters of bacilli (LL)
194.1.0.5.4 Other
  • PCR (specialty labs)
  • Phenolic glycolipid I (PGL-I) antibody (rare clinical)
  • Nerve biopsy (rare)
  • Imaging: nerve thickening on US

194.1.0.6 5⃣ Treatment (WHO MDT)

194.1.0.6.1 PB (Paucibacillary): TT, BT, Single Lesion
  • Rifampin 600 mg PO once monthly (supervised)
  • Dapsone 100 mg PO daily (self-administered)
  • Duration: 6 months
  • Cure rate > 95%
194.1.0.6.2 MB (Multibacillary): BB, BL, LL
  • Rifampin 600 mg PO once monthly (supervised)
  • Dapsone 100 mg PO daily
  • Clofazimine 300 mg PO once monthly + 50 mg PO daily
  • Duration: 12 months (2018 WHO update — previously 24 mo)
194.1.0.6.3 Single Skin Lesion (ROM)
  • Rifampin 600 mg + Ofloxacin 400 mg + Minocycline 100 mg
  • Single dose (alt to 6-mo PB regimen)
  • Logistic advantage for remote / single-lesion cases
194.1.0.6.4 Pediatric Dosing
  • Weight-based
  • Same drugs
  • Rifampin caution if hepatic issues
194.1.0.6.5 Pregnancy + Lactation
  • Standard MDT OK
  • Dapsone safe; rifampin safe; clofazimine — neonatal skin discoloration (resolves)
194.1.0.6.6 G6PD Deficiency + Dapsone
  • Dapsone causes hemolysis in G6PD def
  • Screen G6PD before starting
  • Substitute clofazimine + minocycline if G6PD positive
194.1.0.6.7 Resistance
  • Emerging in some regions (~ 5% MB cases)
  • Resistance testing — specialized labs
  • Alternative drugs: ofloxacin, minocycline, clarithromycin
194.1.0.6.8 Free MDT
  • WHO provides MDT free of charge globally through Novartis donation
  • Available in all endemic countries

194.1.0.7 6⃣ Leprosy Reactions

194.1.0.7.1 Type 1: Reversal Reaction
  • Cell-mediated, sudden inflammation of pre-existing lesions
  • Skin: erythema, swelling, ulceration of existing patches
  • Nerve: acute neuritis with pain + functional loss
  • Onset: during or after MDT, especially BT/BB/BL
  • Treatment: prednisolone 40-60 mg PO qd taper × 12-24 weeks
  • Continue MDT
  • Surgical decompression if severe nerve
194.1.0.7.2 Type 2: Erythema Nodosum Leprosum (ENL)
  • Immune complex deposition (LL/BL)
  • New tender erythematous nodules + fever + arthralgia + neuritis + iritis + lymphadenitis
  • Glomerulonephritis, orchitis, vasculitis
  • Recurrent episodes
  • Treatment:
    • Mild: NSAID
    • Moderate-severe: prednisolone + thalidomide (highly effective for ENL)
    • Thalidomide 100-400 mg PO qd — pregnancy contraindicated (teratogenic — STEPS program in US)
    • Clofazimine (anti-inflammatory) adjunct
    • Continue MDT
194.1.0.7.3 Lucio’s Phenomenon
  • M. lepromatosis diffuse LL
  • Vasculitis with skin necrosis
  • High mortality
  • Treatment: MDT + steroid

194.1.0.8 7⃣ Prevention + Public Health

194.1.0.8.1 2018 WHO Post-Exposure Prophylaxis (PEP)
  • Single dose rifampin 600 mg PO for household + close contacts of new cases
  • Reduces incidence in contacts ~ 50% (LPEP trial)
  • Cost-effective
  • Integrating in many endemic programs
194.1.0.8.2 BCG Vaccine
  • Some efficacy against leprosy (~ 50% — variable)
  • Routine in some endemic
  • BCG revaccination — some evidence
194.1.0.8.3 Active Surveillance
  • Contact screening (3-5 years post case)
  • Self-skin checks in endemic
  • Early diagnosis + treatment
194.1.0.8.4 Stigma Reduction
  • Lifelong impact of disability + stigma
  • Counseling, vocational rehabilitation
  • Term “Hansen’s disease” (after Gerhard Hansen who identified M. leprae 1873) preferred over “leprosy” in many contexts
194.1.0.8.5 WHO Roadmap
  • Global leprosy strategy 2021-2030: end leprosy as public health problem
  • Zero new pediatric cases with disability
  • Zero new transmission