Leprosy¶

Chapter 184 | Part 5: Infectious Diseases

KEY CLINICAL POINTS¶

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, characterized by skin lesions, peripheral nerve damage, and systemic complications.
The Ridley-Jopling classification divides leprosy into five categories: tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), and lepromatous (LL).
Multidrug therapy (MDT) is the cornerstone of treatment, with rifampin, dapsone, and clofazimine forming the standard regimen for multibacillary leprosy.

1. DEFINITION & OVERVIEW¶

Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae. It primarily affects the skin, peripheral nerves, eyes, and upper respiratory tract. The immune response to M. leprae determines the clinical spectrum, ranging from tuberculoid to lepromatous leprosy.

WHO-Recommended Multidrug Treatment for Leprosy¶

DRUG, AGE GROUP	PAUCIBACILLARY LEPROSYa	MULTIBACILLARY LEPROSYb
Dapsone	100 mg/d	100 mg/d
Rifampin	600 mg monthly	600 mg monthly
Clofaziminec	50 mg/d plus 300 mg monthly	50 mg/d plus 300 mg monthly

1.1 Pathogenesis¶

M. leprae infects macrophages and Schwann cells, leading to granuloma formation. The immune response, particularly cell-mediated immunity (CMI), dictates the disease progression. The bacterium's slow growth and resistance to culture in vitro contribute to its pathogenicity.

1.2 Genome and Culture¶

M. leprae has a genome of 2.2 × 10^9 Da with 3,268,203 base pairs. Its genome has undergone reductive evolution, resulting in a smaller genome with many deleted genes. Cultivation is challenging, requiring animal models like armadillos and mice.

2. EPIDEMIOLOGY¶

Leprosy is a neglected disease with 174,087 new cases reported in 2022. It is more prevalent in regions with poor healthcare access, poverty, and low socioeconomic development. The disease is rare in children under 5 years old, with a global incidence of 0.001–0.002 per 1,000 population.

2.1 Incidence and Prevalence¶

Global incidence has declined since 2000, but elimination remains challenging. India, Brazil, and Indonesia account for ~80% of new cases. The WHO defines elimination as <1 case per 10,000 population.

2.2 Risk Factors¶

Risk factors include close contact with untreated multibacillary cases, genetic susceptibility, and immunosuppression. Poverty, poor hygiene, and lack of awareness contribute to delayed diagnosis.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

M. leprae is an obligate intracellular bacterium with a unique genome. Its pathogenesis involves immune evasion, granuloma formation, and nerve damage. The species-specific phenolic glycolipid PGL-1 and other antigens play a role in immune responses.

3.1 Immune Response¶

M. leprae induces both humoral and cell-mediated immunity. The lepromin test assesses CMI status, with negative results indicating lepromatous disease.

3.2 Transmission¶

Transmission occurs via respiratory droplets from untreated multibacillary cases. Zoonotic transmission via armadillos and rodents is possible, though human-to-human spread is the primary route.

4. CLINICAL FEATURES¶

Clinical manifestations vary by leprosy type. Tuberculoid leprosy presents with hypopigmented macules and sensory loss, while lepromatous leprosy involves diffuse skin lesions and nerve damage. Complications include blindness, deformities, and disabilities.

4.1 Ridley-Jopling Classification¶

The classification system divides leprosy into five categories based on immune response and clinical features. TT and LL are stable, while BT, BB, and BL are unstable and prone to progression.

4.2 Leprosy Reactions¶

Type 1 reactions (T1R) are immune-mediated and associated with CMI reversal, while Type 2 reactions (T2R) involve immune complex-mediated inflammation (ENL).

5. DIFFERENTIAL DIAGNOSIS¶

Leprosy must be differentiated from conditions like vitiligo, pityriasis versicolor, sarcoidosis, and leishmaniasis. Skin lesions, nerve involvement, and immunologic tests help distinguish leprosy from other dermatological conditions.

5.1 Skin Lesions¶

Hypopigmented macules, plaques, and nodules are characteristic. Differentiation from pityriasis alba, vitiligo, and post-inflammatory hypopigmentation is critical.

5.2 Nerve Involvement¶

Peripheral neuropathy, sensory loss, and motor deficits are key features. Conditions like diabetes, amyloidosis, and Guillain-Barré syndrome must be considered.

6. INVESTIGATIONS & DIAGNOSIS¶

Diagnosis combines clinical findings, slit-skin smears, PCR, and immunologic tests. The lepromin test and PGL-1 antibody test aid in classification and monitoring.

6.1 Diagnostic Tests¶

Slit-skin smears detect acid-fast bacilli (AFB). PCR identifies M. leprae DNA. The lepromin test assesses CMI status, while PGL-1 antibody testing is useful for serologic diagnosis.

6.2 Nerve Function Assessment¶

Sensory testing (Semmes-Weinstein monofilament), nerve conduction studies, and ultrasound imaging evaluate neuropathy. Touch and temperature sensation are critical for early detection.

7. MANAGEMENT & TREATMENT¶

Multidrug therapy (MDT) is the standard treatment. Glucocorticoids and thalidomide manage leprosy reactions. Rehabilitation and psychosocial support are essential for long-term outcomes.

7.1 Multidrug Therapy¶

MDT regimens include rifampin, dapsone, and clofazimine. Paucibacillary leprosy requires two drugs (rifampin + dapsone), while multibacillary leprosy requires three (rifampin + dapsone + clofazimine).

7.2 Treatment of Reactions¶

T1R is managed with glucocorticoids, while T2R (ENL) may require thalidomide or clofazimine. Supervised therapy ensures adherence and prevents relapse.

8. PROGNOSIS & COMPLICATIONS¶

Early treatment prevents irreversible nerve damage and disabilities. Complications include blindness, deformities, and social stigma. Relapse rates are low with MDT but higher in patients with high bacillary load.

8.1 Long-Term Outcomes¶

Nerve damage is irreversible after 6 months of symptoms. Patients with multibacillary leprosy have a 65% risk of additional damage. Rehabilitation and psychosocial support are critical.

Leprosy stigma leads to social exclusion, affecting employment and mental health. Public health initiatives and education are vital to reduce discrimination.

9. SPECIAL CONSIDERATIONS¶

Pregnancy, pediatric, and elderly patients require tailored management. Clofazimine-induced skin discoloration and drug interactions must be monitored. Multidisciplinary care is essential for complex cases.

9.1 Pregnancy and Pediatrics¶

Dapsone is contraindicated in pregnancy. Children receive adjusted dosages. Early treatment prevents long-term disabilities in pediatric cases.

9.2 Elderly Patients¶

Elderly patients may have comorbidities requiring careful drug selection. Clofazimine-induced skin discoloration is more pronounced in older adults.

10. KEY POINTS & CLINICAL PEARLS¶

Leprosy is a curable disease requiring early diagnosis and MDT. The Ridley-Jopling classification guides treatment. Regular follow-up and rehabilitation are essential to prevent disabilities. Public health education reduces stigma and improves outcomes.