What is the treatment approach for a patient with Erythema Nodosum Leprosum (ENL) in the context of leprosy?

Treatment and Diagnostic Approach of Erythema Nodosum Leprosum (ENL) in Leprosy

Immediate Treatment Strategy

For acute ENL, initiate oral prednisolone at 0.5-1 mg/kg/day as first-line therapy, with thalidomide (200-400 mg/day) as the preferred alternative when available and appropriate, providing superior long-term control and avoiding prolonged steroid complications. 1

First-Line Treatment Options

Corticosteroids:

• Start prednisolone at 0.5-1 mg/kg/day orally for acute ENL 2
• If inadequate response to once-daily dosing, consider split-dose regimen (dividing the same total daily dose) rather than escalating the dose—this provides better control with less HPA axis suppression and lower relapse rates 2
• Taper gradually once inflammation is controlled; avoid abrupt discontinuation 1
• Critical pitfall: High-dose prolonged steroids cause severe morbidity including infections, steroid dependence, and mortality—one case series documented death from intracranial infection after 15 months of high-dose therapy 3

Thalidomide (when available and appropriate):

• Dose: 200-400 mg/day provides rapid control of ENL 1, 4
• Controlled trials demonstrate superiority over aspirin and pentoxifylline 1
• Provides better long-term control than steroids and avoids steroid-related adverse effects 1
• Absolute contraindication: Women of childbearing potential without reliable contraception due to severe teratogenicity 1
• Monitor for peripheral neuropathy, which can be irreversible 1
• Unavailable in many leprosy-endemic countries 1

Adjunctive Therapy

Clofazimine:

• Add clofazimine 300 mg/day for 6 months, then 100 mg/day for maintenance 5
• Useful as steroid-sparing agent in chronic/recurrent ENL 5
• Takes several weeks to months for full effect 1

Diagnostic Approach

Clinical Recognition:

• Tender, erythematous, evanescent subcutaneous nodules in patients with lepromatous or borderline lepromatous leprosy 2
• Systemic symptoms: fever, malaise, arthralgias, neuritis 1
• Typically occurs within 2 years of starting multi-drug therapy 1
• Affects approximately 30% of lepromatous leprosy patients even with WHO MDT 1

Key Assessment Points:

• Document organ involvement (eyes, nerves, joints, kidneys, testes) as ENL can cause irreversible damage 1
• Assess for neuritis—requires urgent treatment to prevent permanent nerve damage 1
• Distinguish from Type 1 (reversal) reactions, which require different management 1

Management of Chronic/Recurrent ENL

When ENL persists or recurs despite initial therapy:

1. Azathioprine (steroid-sparing agent):

   • Start 100 mg/day (approximately 1.5-2 mg/kg) 5
   • Expect symptom resolution within 1 week, no recurrences by 10 weeks 5
   • Continue for 8-12 months, then taper to 50 mg/day for 4 months before discontinuation 5
   • Allows complete withdrawal of prednisolone after gradual tapering 5

2. For refractory cases failing conventional therapy:

   • Consider TNF-α inhibitors (etanercept) when ENL fails to respond to steroids, thalidomide, and clofazimine over prolonged periods 4
   • Case report demonstrates full resolution with etanercept in severe 6-year refractory ENL 4
   • Reserve for severe cases with significant morbidity from disease or treatment side effects 4

Critical Clinical Pitfalls to Avoid

• Never escalate steroid doses indefinitely—this leads to steroid dependence, severe immunosuppression, and potentially fatal infections 3
• Do not prescribe thalidomide without rigorous contraception counseling and pregnancy testing in women of childbearing age 1
• Monitor for thalidomide-induced peripheral neuropathy, which may be irreversible and requires drug discontinuation 1, 5
• Recognize that ENL can run a chronic/recurrent course for years—plan for long-term management strategy from the outset rather than repeated short courses 1
• Assess and treat neuritis urgently as part of ENL to prevent permanent nerve damage and disability 1

Treatment Algorithm Summary

1. Acute ENL: Prednisolone 0.5-1 mg/kg/day OR thalidomide 200-400 mg/day (if available and appropriate) 1, 2
2. Inadequate response: Switch to split-dose prednisolone regimen before escalating total dose 2
3. Chronic/recurrent ENL: Add clofazimine 300 mg/day, then add azathioprine 100 mg/day as steroid-sparing agent 5
4. Refractory ENL (>6 months of failed conventional therapy): Consider TNF-α inhibitor (etanercept) 4
5. Throughout treatment: Continue WHO multi-drug therapy for leprosy; ENL treatment does not replace antimicrobial therapy 1