What is the diagnosis and treatment approach for a patient suspected of having leprosy, regardless of age or demographic?

Leprosy (Hansen Disease): Comprehensive Clinical Overview

Definition and Epidemiology

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, primarily affecting the skin and peripheral nerves, with approximately 210,000-250,000 new cases detected annually worldwide, predominantly in India, Brazil, and Indonesia. 1, 2, 3

• The disease has low pathogenicity and virulence with an incubation period of 8-20 weeks to several years 1
• Transmission likely occurs through nasal droplet infection, though the exact route remains incompletely understood 2
• The disease course is determined by the host's T-cell-mediated immune response 4

Clinical Classification and Presentation

Major Clinical Forms

The disease presents along a spectrum based on cellular immune response to M. leprae 5:

Tuberculoid Leprosy (Paucibacillary):

• One or few well-demarcated, hypopigmented, anesthetic skin lesions 5
• Frequently with active, spreading edges and clearing center 5
• Peripheral nerve swelling or thickening may occur 5
• Few bacilli present 1

Lepromatous Leprosy (Multibacillary):

• Multiple erythematous papules and nodules or facial, hand, and foot infiltration 5
• Bilateral and symmetrical distribution with progressive skin thickening 5
• More contagious form with higher bacillary load 1
• May involve thickened peripheral nerves 1

Borderline (Dimorphous) Leprosy:

• Skin lesions characteristic of both tuberculoid and lepromatous forms 5
• Intermediate immune response 2

Indeterminate Leprosy:

• Early lesions, usually hypopigmented macules 5
• Without developed tuberculoid or lepromatous features 5
• May evolve into other forms or resolve spontaneously 1

Neurological Manifestations

Peripheral nerve damage is the hallmark complication, causing the disability and stigma associated with leprosy. 4

• Nerves are often functionally impaired before developing obvious symptoms ("silent neuropathy") 4
• Advanced disease characterized by disfiguring mutilations 2
• Propensity to cause nerve damage with resulting disability 4

Diagnostic Approach

Clinical Diagnosis

The diagnosis of leprosy is made from three cardinal criteria: 4

1. Characteristic skin lesions in association with thickened nerves 4
2. Demonstration of acid-fast bacilli in slit skin smears 4
3. Histopathology of skin biopsies 4

Laboratory Confirmation

Confirmed case definition requires demonstration of acid-fast bacilli in skin or dermal nerve obtained from full-thickness skin biopsy of a lepromatous lesion. 5

• Skin bacilloscopy complements clinical diagnosis 1
• Nerve biopsy is necessary to establish diagnosis of pure "neural leprosy" 4
• Some patients may have multibacillary leprosy in nerves and paucibacillary leprosy in skin, emphasizing the usefulness of nerve biopsy 4

Critical Diagnostic Considerations

• Biopsy the nasal mucosa if it appears macroscopically abnormal (91% positive yield) 5
• If nasal mucosa appears normal, biopsy will usually be negative (92%) 5
• Special stains are mandatory on all biopsy specimens to exclude mycobacteria and fungi before diagnosing non-infectious causes 6

Differential Diagnosis

The differential diagnosis includes other granulomatous diseases: 5

• Syphilis, tuberculosis, rhinoscleroma 5
• Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) 5
• Berylliosis, fungal disease, cat scratch fever 5
• Lymphomas and diffuse granulomatous disease 5
• Sarcoidosis 5

Treatment

WHO Multidrug Therapy (MDT)

All patients with leprosy should receive WHO-recommended multidrug therapy combining rifampicin, clofazimine, and dapsone to prevent resistance and achieve cure. 7, 2, 3

Paucibacillary Leprosy Treatment

For paucibacillary (tuberculoid and indeterminate) disease, treat with rifampicin 600 mg daily plus dapsone 100 mg daily for 6 months. 7, 2

• Under WHO guidelines, daily rifampicin may be replaced by 600 mg rifampicin monthly if supervised 7
• Continue dapsone until all signs of clinical activity are controlled, usually an additional 6 months 7
• Then continue dapsone for an additional 3 years for tuberculoid and indeterminate patients, and 5 years for borderline tuberculoid patients 7

Multibacillary Leprosy Treatment

For multibacillary (lepromatous and borderline lepromatous) disease, treat with rifampicin 600 mg daily, dapsone 100 mg daily, and clofazimine 50-100 mg daily for 12 months. 7, 2

• Under WHO guidelines, daily rifampicin may be replaced by 600 mg rifampicin monthly if supervised 7
• May elect concurrent administration of a third anti-leprosy drug, usually ethionamide 250-500 mg daily 7
• Continue dapsone 100 mg daily for 3-10 years until all signs of clinical activity are controlled with skin scrapings and biopsies negative for one year 7
• Then continue dapsone for an additional 10 years for borderline patients and for life for lepromatous patients 7

Pediatric Dosing

• Dosage should be individually titrated starting with 50 mg dapsone daily in adults and correspondingly smaller doses in children 7
• If full control is not achieved within the range of 50-300 mg daily, higher doses may be tried 7

Alternative Single-Dose Regimen

The combination of rifampicin, ofloxacin, and minocycline given as a single dose has been recommended for treatment of paucibacillary leprosy. 1

Management of Leprosy Reactions

Immune-mediated "reactions" can rapidly lead to further nerve damage and require prompt recognition and treatment. 4

Types of Reactions

• Reversal reaction: Requires early recognition and prompt treatment with corticosteroids 4
• Erythema nodosum leprosum: Requires early recognition and prompt treatment with corticosteroids 4
• Silent neuropathy: Nerves are functionally impaired before developing obvious symptoms; requires early recognition and prompt corticosteroid treatment to prevent disability 4

Drug Resistance

Secondary dapsone resistance should be suspected whenever a lepromatous or borderline lepromatous patient receiving dapsone treatment relapses clinically and bacteriologically, with solid staining bacilli found in smears from new active lesions. 7

• If no response to regular and supervised dapsone therapy within 3-6 months, or good compliance for the past 3-6 months can be assured, dapsone resistance should be considered confirmed clinically 7
• Determination of drug sensitivity using the mouse footpad method is recommended and available from USPHS, Carville, LA 7
• Patients with proven dapsone resistance should be treated with other drugs 7
• Resistant strains are emerging despite multidrug therapy; identifying and monitoring resistance remains necessary 8

Prevention and Control Strategies

To reduce secondary dapsone resistance, dapsone should be commenced in combination with one or more anti-leprosy drugs, maintaining dapsone at full dosage of 100 mg daily without interruption. 7

• Early diagnosis and therapy is the most important strategy for disease control 1
• Intervention at early stage will avoid onset of more serious signs and symptoms 1
• WHO-supported preventive measures and strategies play a key role in endemic areas 2
• Global implementation of multidrug therapy resulted in a 90% decrease in registered patients from 1985 to 2000 3

Critical Clinical Pitfalls

• Never diagnose sarcoidosis or other non-infectious granulomatous disease without excluding leprosy through special stains and cultures in patients from endemic areas 6
• Early recognition of silent neuropathy is critical—nerves are often functionally impaired before developing obvious symptoms 4
• Prompt treatment with corticosteroids of leprous reactions and silent neuropathies is essential to prevent disability 4
• Some patients may have multibacillary leprosy in nerves despite paucibacillary skin findings, emphasizing the importance of nerve biopsy when diagnosis is uncertain 4