1. Multiple hypoesthetic, mildly erythematous large plaques with elevated margins - this points away from pure tuberculoid (which has very few, well-defined lesions) and away from lepromatous (which has many small, poorly defined, symmetric lesions)
2. Bilateral enlarged peripheral nerves (ulnar + lateral popliteal) - nerve enlargement is prominent in the tuberculoid spectrum
3. Hypoesthesia - indicates significant immune-mediated nerve damage, typical of the tuberculoid end of the spectrum

• Few to several plaques (more than pure TT, but not numerous)
• Large plaques with raised, well-defined outer edges and sloping inner edges
• Marked hypoesthesia
• Peripheral nerve thickening (classically ulnar and lateral popliteal nerves)
• Paucibacillary on slit-skin smear

---

Leprosy (Hansen's Disease) - Complete Guide

---

PART 1: SIMPLE EXPLANATION (Beginner Level)

What is leprosy?

The One Big Concept: It's a SPECTRUM

STRONG IMMUNITY ←————————————————————→ WEAK IMMUNITY
  
      TT ——— BT ——— BB ——— BL ——— LL
  
   Few lesions,            Many lesions,
   few bacteria,           many bacteria,
   lots of nerve damage    less nerve damage early

• Left side (TT): Your immune system fights hard. It kills most bacteria. But in doing so, it destroys the nerves too. Few skin lesions, lots of nerve damage.
• Right side (LL): Your immune system barely responds. Bacteria multiply everywhere. Many skin lesions all over, but nerve damage comes later.
• Middle (Borderline types): Mix of both features.

Simple Memory Trick

---

PART 2: DETAILED GUIDE (Final Year MBBS Level)

---

The Organism

• Cannot be cultured in vitro (grown in labs)
• Grows best at 27-33°C (prefers cool body areas: skin, peripheral nerves, testes, nasal mucosa, ear lobes)
• Its virulence is partly due to PGL-1 (phenolic glycolipid-1), which helps it invade host cells
• Primarily infects Schwann cells and dermal macrophages
• A newer species, M. lepromatosis (discovered 2008), causes diffuse lepromatous leprosy mainly in Mexico/Central America

---

Transmission

• Primarily via respiratory secretions (nasal droplets) from untreated multibacillary patients
• Rare zoonotic transmission from armadillos
• Prolonged close contact required; the disease is NOT highly contagious
• Incubation period: 2-12 years (average ~5 years)

---

Immunology - The Key to Understanding the Spectrum

• HLA-DR2 and HLA-DR3 → tuberculoid form
• HLA-DQ1 → lepromatous form

---

Classifications of Leprosy

1. Ridley-Jopling Classification (Most important for exams)

2. WHO Classification (Used in field/control programs)

3. Indian Classification (Used in India)

• Indeterminate, Tuberculoid, Borderline, Lepromatous, Pure Neuritic (no skin lesions - unique to Indian classification)

---

Cardinal Features of Leprosy (Diagnose if ANY ONE present)

1. Hypopigmented/erythematous skin patch with loss of sensation
2. Thickened peripheral nerve trunk
3. AFB positive on slit-skin smear or biopsy

---

Each Type in Detail

1. Indeterminate Leprosy (IL)

• Earliest stage - may be the only manifestation
• 1-2 ill-defined hypopigmented or faintly erythematous macules, 1-5 cm
• Occurs on limbs, buttocks, face
• Mild to moderate loss of touch/thermal sensation
• No nerve thickening
• Either self-heals or progresses to any determinate type depending on immunity
• Biopsy shows only lymphocytic infiltration (no granuloma yet)

---

2. Tuberculoid Leprosy (TT)

• Single or very few (up to 3) well-defined lesions
• Raised, erythematous/copper-colored plaque with clearly defined outer edge sloping inward to a hypopigmented, depressed center (central healing)
• Can be of any size; surface is dry, hairless, anhidrotic, and completely anesthetic
• Complete loss of fine touch and temperature sensation over the lesion

• One peripheral nerve near the lesion may be thickened
• Asymmetric nerve involvement
• Nerve thickening with sensory loss and possible motor deficit

---

3. Borderline Tuberculoid (BT) Leprosy

• 3 to 9+ lesions, asymmetrically distributed
• Plaques with edges sloping outward (opposite to TT)
• Smaller "satellite" lesions around the main lesion
• Variable loss of sensation (less than TT)
• Several peripheral nerves enlarged asymmetrically (ulnar, lateral popliteal commonly)
• Highly prone to Type 1 (reversal) reactions
• Bacteriologic Index (BI): 0 to 1+
• Lepromin test: Positive (weakly)
• If untreated, may downgrade toward BB or BL

---

4. Mid-Borderline (BB) Leprosy

• Most immunologically unstable form - can upgrade or downgrade
• Multiple lesions of varying sizes and shapes
• Characteristic "Swiss cheese" (punched-out) lesions - central clearing with a sharp inner edge but sloping outer edge
• Lesions may look like annular plaques with a "punched-out" pale center
• Sensation impaired but not totally lost
• Nerves involved but less severely than BT
• BI: 2+ to 3+
• Lepromin test: Negative or weakly positive
• Most likely to undergo lepra reactions

---

5. Borderline Lepromatous (BL) Leprosy

• Many lesions (more numerous and smaller than BB)
• Less-defined margins, more symmetric distribution than BT/BB
• Macules, papules, plaques, nodules
• Reduced sensation but not absent
• Nerve involvement: multiple nerves, more symmetric than BT
• BI: 3+ to 5+
• Lepromin test: Negative
• Can undergo Type 2 reactions (ENL - Erythema Nodosum Leprosum)

---

6. Lepromatous Leprosy (LL)

• Many (dozens to hundreds) of lesions, symmetric distribution
• Early: poorly defined hypopigmented macules
• Late: papules, nodules, and plaques - especially on face, ears, wrists, elbows, knees
• Leonine facies = thickened, corrugated skin of face due to nodule coalescence
• Madarosis = loss of lateral eyebrows (pathognomonic)
• Saddle-nose deformity (nasal collapse from septal destruction)
• Ear lobes thickened and infiltrated
• Sensation relatively preserved early

• Symmetric peripheral nerve involvement
• Nerves invaded with bacteria but minimal inflammation
• Commonly affected: ulnar, median, lateral popliteal, posterior tibial, radial cutaneous, facial, greater auricular
• "Glove and stocking" sensory loss pattern

• Orchitis → testicular atrophy → sterility and gynaecomastia
• Eye involvement: iridocyclitis, corneal anesthesia, lagophthalmos
• Laryngeal involvement → hoarseness
• Lymphadenopathy
• Hepatosplenomegaly
• In advanced disease: bacilli in blood and sputum

• "Globi" = clumps of AFB in macrophages
• Virchow cells (lepra cells) = lipid-laden macrophages packed with AFB

---

Histology at a Glance

---

Nerves Commonly Affected (Must Know)

---

Leprosy Reactions (Acute Episodes)

Type 1 Reaction (Reversal Reaction)

• Who: BT, BB, BL patients (borderline types only)
• Mechanism: Sudden increase in CMI (delayed hypersensitivity) - upgrade reaction
• Features: Existing lesions become acutely inflamed (red, hot, edematous, tender); new lesions; acute nerve palsies (very important!)
• Treatment: Prednisolone 40-60 mg/day, tapered over months

Type 2 Reaction - Erythema Nodosum Leprosum (ENL)

• Who: BL and LL patients only (multibacillary end)
• Mechanism: Immune complex deposition (Type III hypersensitivity) - NOT a change in CMI
• Features: Painful, tender, erythematous nodules on skin; fever, malaise; can have uveitis, orchitis, neuritis, arthritis, lymphadenopathy
• Treatment: Thalidomide (drug of choice), or clofazimine, or prednisolone

Lucio's Phenomenon

• Only in diffuse lepromatous leprosy (M. lepromatosis)
• Necrotizing vasculitis → skin necrosis and ulceration

---

Diagnosis

---

WHO MDT Treatment (Current Regimen)

Paucibacillary (PB) - 6 months

Multibacillary (MB) - 12 months

• Rifampicin: hepatotoxicity, orange urine
• Dapsone: hemolytic anemia (especially in G6PD deficiency), methemoglobinemia, dapsone hypersensitivity syndrome
• Clofazimine: skin pigmentation (orange-brown discoloration), ichthyosis, GI symptoms

---

High-Yield Points for Exams

1. Most common nerve affected in leprosy overall: Ulnar nerve
2. Most common cause of foot drop in leprosy: Lateral popliteal (common peroneal) nerve
3. Pathognomonic skin finding: Madarosis (loss of lateral eyebrow)
4. Only nerve visible AND palpable: Greater auricular nerve
5. Lepromin test = test of immunity, NOT a diagnostic test
6. Most unstable type: BB (mid-borderline)
7. Type 1 reaction only in borderline; Type 2 (ENL) only in BL and LL
8. Drug of choice for ENL: Thalidomide (contraindicated in pregnancy - teratogenic)
9. BCG vaccination gives partial protection (~50%) against leprosy
10. Deformity of nose in LL = Saddle nose deformity (not "button nose")
11. "Leonine facies" = LL leprosy
12. Most common cause of blindness in leprosy = Lagophthalmos (facial nerve palsy → corneal exposure)
13. Pure neuritic leprosy (no skin lesions) - recognized in Indian classification only
14. Armadillos are the only non-human animal reservoir

---

Sources

• Harrison's Principles of Internal Medicine, 22nd Edition, 2025 - Chapter 184
• Robbins, Cotran & Kumar - Pathologic Basis of Disease - Chapter 8
• Park's Textbook of Preventive and Social Medicine - Chapter on Leprosy