Leprosy: Clinical Determinants, Reactions, and Treatment
Question 1: Disease Determinants
The patient's symptoms and disease type in leprosy are primarily determined by the strength of their cellular immune response (Answer B). 1
The clinical spectrum of leprosy reflects the host's cell-mediated immunity against Mycobacterium leprae:
- Tuberculoid leprosy develops in patients with strong Th1-mediated cellular immunity, characterized by well-demarcated granulomas with CD4+ T lymphocytes, epithelioid cells, and multinucleated giant cells producing IFN-γ and IL-2 2
- Lepromatous leprosy occurs when cellular immunity is weak, with Th2 response (IL-4, IL-5, IL-10) predominating, resulting in unstructured accumulation of ineffective macrophages filled with bacilli 2, 3
- Borderline forms represent intermediate immune states along this spectrum 1, 4
The age at infection (A), specific Mycobacterium species (C - only M. leprae causes leprosy), and geographic region (D) do not determine the disease phenotype 5, 4.
Question 2: Leprosy Reactions
Painful, red, tender subcutaneous nodules are characteristic of Type 2 reaction (Erythema Nodosum Leprosum - ENL) (Answer C). 6
Distinguishing Features:
Type 2 (ENL):
- Occurs mainly in lepromatous and some borderline patients (approximately 50% in first year of treatment) 6
- Presents with fever and tender erythematous nodules that may become pustular or ulcerate 6
- Associated with malaise, neuritis, orchitis, albuminuria, joint swelling, iritis, epistaxis, or depression 6
- Histologically shows vasculitis with intense polymorphonuclear infiltrate 6
Type 1 (Reversal reaction):
- Occurs in borderline or tuberculoid patients, often soon after chemotherapy starts 6
- Manifests as swelling of existing skin and nerve lesions due to enhanced delayed hypersensitivity 6
- Does not typically present as new tender nodules 6
Question 3: ENL Pathophysiology
Erythema Nodosum Leprosum is caused by immune complex deposition (Answer B). 6
ENL is mediated by elevated circulating immune complexes, resulting in vasculitis with polymorphonuclear infiltrate 6. This contrasts with Type 1 reactions, which are caused by delayed hypersensitivity mechanisms 6.
Question 4: Cardinal Features
Central nervous system involvement is NOT a cardinal feature of leprosy (Answer D). 1, 4
The Three Cardinal Clinical Features (WHO criteria):
- Hypopigmented or erythematous skin lesions with sensory loss 1, 4
- Thickened peripheral nerves 1, 4
- Acid-fast bacilli in skin smears or biopsy 1, 4
Leprosy primarily affects skin and peripheral nerves, not the central nervous system 1, 5, 4, 7. Diagnosis requires at least one of these cardinal signs 4.
Question 5: Drug-Related Hemolysis
Dapsone can cause hemolysis in patients with G6PD deficiency (Answer C). 6
Treatment Regimen Context:
Multibacillary leprosy (12 months minimum): 6, 7
- Rifampicin 600 mg daily (or monthly if supervised)
- Dapsone 100 mg daily
- Clofazimine 50-100 mg daily
Paucibacillary leprosy (6 months minimum): 6, 7
- Rifampicin 600 mg daily (or monthly if supervised)
- Dapsone 100 mg daily
Critical Dapsone Considerations:
- Dosing must account for acetylation rates, which influence drug levels 6
- For dermatitis herpetiformis, start at 50 mg daily in adults with individual titration 6
- Monitor for hemolysis in G6PD-deficient patients 6
Common pitfall: Rifampicin (A), clofazimine (B), and ofloxacin (D) do not cause G6PD-related hemolysis, though rifampicin has other significant adverse effects 6, 5.