Leprosy

Detailed Overview

Leprosy exhibits a clinical spectrum depending on the hosts cellular immune response. Tuberculoid leprosy (paucibacillary) involves a strong cellular immune response, presenting with few skin lesions and localized nerve involvement. Lepromatous leprosy (multibacillary) is characterized by a weak cellular response, leading to widespread skin lesions, leonine facies, and symmetric nerve damage. Though largely eliminated globally as a public health problem, it remains endemic in regions like India, Brazil, and Indonesia. Treatment requires prolonged multi-drug therapy (MDT).

Epidemiology & Demographics

Global prevalence is around 200,000 cases annually, primarily in India (accounts for >60%), Brazil, and Indonesia. In the US, 150-250 cases are reported annually, often associated with exposure to armadillos in southern states. Affects all ages, but peak incidence is between 20-30 years.

Etiological Mechanism

Infection by Mycobacterium leprae, a slow-growing, acid-fast bacillus that prefers cooler body temperatures (27-30C). Transmission is likely via respiratory droplets during prolonged close contact.

Primary Causes

Infection primarily through respiratory droplets from untreated multibacillary patients. Zoonotic transmission from nine-banded armadillos is recognized in the Americas.

• Prolonged close contact: Living with an untreated household contact with multibacillary leprosy.
• Armadillo exposure: Handling or consuming nine-banded armadillos in the southern US/Americas.
• Immunosuppression: Conditions or drugs that impair T-cell mediated immunity.

M. leprae invades Schwann cells of the peripheral nervous system and macrophages in the skin. The bacilli bind to laminin-2 on Schwann cells, causing demyelination and axonal dysfunction (loss of sensation, weakness). The clinical manifestation is dictated by the Th1 vs Th2 immune response. A Th1 response (IL-2, IFN-gamma) forms granulomas that contain the infection (Tuberculoid leprosy). A Th2 response (IL-4, IL-10) fails to control bacterial replication, allowing massive bacillary dissemination (Lepromatous leprosy).

Characteristic Clinical Presentation

• Hypopigmented Macules: Skin patches that are lighter than the surrounding skin, with associated loss of sensation.
• Numbness: Loss of temperature and touch sensation, typically starting in the extremities.
• Muscle Weakness: Weakness in the hands or feet (e.g., foot drop) due to peripheral nerve damage.
• Nasal Congestion: Chronic stuffiness and epistaxis in lepromatous forms.

Physical Examination Signs

• Enlarged, thickened peripheral nerves (e.g., ulnar, common peroneal, greater auricular).
• Anesthetic skin lesions (loss of pinprick and light touch).
• Leonine facies (thickened facial skin and nodule formation in lepromatous leprosy).
• Madarosis (loss of the lateral third of the eyebrows).

• Neuropathy: Irreversible sensory and motor loss leading to painless trauma, ulcers, and amputations.
• Type 1 Reversal Reaction: Delayed hypersensitivity reaction causing acute inflammation of skin lesions and nerves.
• Erythema Nodosum Leprosum (Type 2): Immune complex mediated reaction presenting as painful subcutaneous nodules and fever.
• Blindness: Due to corneal anesthesia, exposure keratitis (lagophthalmos), and iridocyclitis.

Diagnostic Criteria & Guidelines

Diagnosis requires at least one of the cardinal signs: 1) Hypopigmented/reddish patch with definite loss of sensation; 2) Thickened peripheral nerve with loss of sensation/weakness; 3) Positive slit-skin smears for acid-fast bacilli.

Differential Diagnosis

• Vitiligo (lesions are depigmented, not hypopigmented, and have normal sensation)
• Pityriasis versicolor
• Sarcoidosis
• Diabetic neuropathy

Laboratory Tests & Biomarkers

• Slit-Skin Smear: Demonstrates acid-fast bacilli (Fite stain positive) in multibacillary disease. Often negative in paucibacillary.
• Skin Biopsy: Shows non-caseating granulomas (tuberculoid) or foamy macrophages filled with bacilli (lepromatous).

Imaging Modalities & Findings

• Ultrasound of Peripheral Nerves:

• Paucibacillary (PB)
  1-5 skin lesions, asymmetrical nerve involvement, strong immune response, negative skin smears.
• Multibacillary (MB)
  >5 skin lesions, symmetrical nerve involvement, weak immune response, positive skin smears.

Second-Line & Adjunctive Therapy

For MDT resistance or severe toxicity: Ofloxacin 400 mg daily + Minocycline 100 mg daily + Clarithromycin 500 mg daily for 6-12 months.

Surgical & Procedural Management

Nerve decompression for acute neuritis unresponsive to steroids. Tendon transfers to correct foot drop or claw hands. Amputation of non-healing, osteomyelitis-infected digits.

Recommended Lifestyle Changes

• Daily visual inspection of hands and feet to detect painless injuries.
• Use of protective footwear and gloves.
• Regular soaking and oiling of dry, anhidrotic skin.

Patient Counseling & Advice

Inform the patient that they are non-infectious within 72 hours of starting MDT, hence no isolation is needed. Warn about Clofazimine causing reversible red/brown skin discoloration. Emphasize that treatment cures the infection but may not reverse existing nerve damage.

Follow-Up & Monitoring Schedule

Monthly clinical check for first 6 months, monitoring for lepra reactions (Type 1 and 2). Routine neurologic exam mapping sensory loss via monofilament testing.

Preventive Strategies

Contact tracing and screening of household contacts. Single-dose Rifampicin (SDR) prophylaxis for close contacts is recommended by WHO.

Excellent for curing the infection with MDT (cure rate >95%). However, morbidity remains high due to irreversible neuropathy if treated late.