What is the role of steroids, such as prednisolone, in the management of leprosy reactions?

Role of Steroids in the Management of Leprosy Reactions

Prednisolone is the cornerstone treatment for leprosy reactions, with a recommended starting dose of 0.5-1 mg/kg daily for Type 1 reactions and nerve function impairment, tapered over 3-6 months depending on clinical response.

Types of Leprosy Reactions

• Type 1 (Reversal) Reactions are characterized by a strong Th1 immune profile with cells in cutaneous and neural lesions expressing interferon-γ and interleukin-12 1
• Erythema Nodosum Leprosum (ENL) is a systemic inflammatory complication occurring mainly in patients with lepromatous leprosy and borderline lepromatous leprosy 2

Mechanism of Action of Steroids in Leprosy Reactions

• Steroids modulate pro-inflammatory cytokines (TNF, IFN-γ, IL-1β, IL-6, IL-17A) either directly or through suppression of immune cells producing these inflammatory cytokines 2
• By day 28 of prednisolone treatment, significant decreases in IFN-gamma, IL-12, and inducible nitric oxide synthase (iNOS) are observed in most patients with Type 1 reactions 1, 3
• Prednisolone increases regulatory cytokines (IL-10, TGF-β) in both blood and skin lesions after treatment 2

Treatment Regimen

Dosing for Type 1 Reactions

• Initial treatment: Prednisolone 0.5-1 mg/kg/day (typically 30-40 mg daily) 1, 4
• Duration: Minimum 16 weeks with gradual tapering 5
• For severe cases: Consider high-dose intravenous methylprednisolone (1g daily for 3 days) followed by oral prednisolone, although evidence shows limited additional benefit over oral prednisolone alone 5

Dosing for ENL Reactions

• Initial treatment: Prednisolone 0.5-1 mg/kg/day 2
• Duration: Variable depending on clinical response, often requiring longer treatment courses

Monitoring and Response Assessment

• Clinical improvement should be assessed by:

  • Reduction in inflammation of skin lesions 1
  • Improvement in nerve function (sensory and motor) 5
  • Resolution of systemic symptoms 2

• Regular monitoring is essential as approximately 50% of individuals with Type 1 reactions and/or nerve function impairment require additional prednisolone despite treatment with 16 weeks of corticosteroids 5

Treatment Effectiveness and Limitations

• Effectiveness of steroid treatment is variable, with only about 60% of patients regaining nerve function 1
• Some patients maintain cytokine production even at day 180, indicating ongoing inflammatory activity despite prolonged steroid treatment 1, 3
• Silent nerve damage may occur when prednisolone is discontinued too early 4

Important Considerations and Precautions

• Gastric protection with proton pump inhibitors should be considered for patients on prolonged steroid therapy 6
• For patients at risk of bone density loss (postmenopausal women, men over 50 years), calcium and vitamin D supplementation and possibly bisphosphonates are recommended 6
• Monitor for common steroid-related adverse effects including:
  • Hyperglycemia/diabetes
  • Hypertension
  • Increased susceptibility to infections
  • Mood changes
  • Weight gain

Duration of Treatment

• The WHO recommendation of 12 weeks of prednisolone treatment may be insufficient for many patients with Type 1 reactions 4
• Longer courses (16 weeks or more) with gradual tapering are often necessary to prevent recurrence of reactions and nerve damage 5, 4
• Treatment should be tailored based on clinical response, with close monitoring for signs of reaction recurrence during tapering 1

Future Directions

• Additional studies of different glucocorticoids and non-steroidal immunosuppressants for the treatment of leprosy reactions are needed 1
• Research into risk factors for recurrent reactions and nerve function impairment during and after corticosteroid treatment would help optimize management strategies 5