What is the best approach to managing a patient with Erythema Nodosum Leprosum (ENL)?

Management of Erythema Nodosum Leprosum (ENL)

Oral prednisolone is the first-line treatment for ENL, starting at 0.5-1 mg/kg/day, with thalidomide reserved as a steroid-sparing agent for chronic or recurrent cases, though its use requires strict contraception counseling due to teratogenicity. 1, 2

Initial Assessment and Diagnosis

ENL presents as painful, tender erythematous nodules occurring in multibacillary leprosy patients, accompanied by systemic symptoms including fever, malaise, and extreme fatigue that may persist for weeks to months. 1, 3 Key distinguishing features include:

• Systemic involvement: Fever, arthralgias (typically symmetrical, affecting distal lower extremities without effusions), and constitutional symptoms 4
• Nodule characteristics: Unlike erythema nodosum (which affects anterior tibial areas bilaterally), ENL nodules can occur more diffusely and may become necrotic or ulcerative 1, 5
• Chronicity pattern: ENL is frequently recurrent and/or chronic, causing significant disability 1

First-Line Treatment: Corticosteroids

Prednisolone dosing strategy:

• Start with 0.5-1 mg/kg/day orally for acute ENL 1, 3
• For cases not responding to once-daily dosing, consider split-dose regimen (dividing the same total daily dose) rather than escalating the dose, which provides better control with less HPA axis suppression 5
• Taper gradually over weeks to months based on clinical response 1

Critical caveat: Corticosteroids may cause dependence, especially in chronic ENL patients, and prolonged use carries risks of infections, metabolic complications, and immunosuppression. 1, 3 Monitor closely for steroid-related adverse effects during tapering, as many patients experience recurrence. 1

Second-Line and Steroid-Sparing Agents

Thalidomide (Preferred Steroid-Sparing Agent)

Thalidomide is highly effective for chronic/recurrent ENL with rapid action, but requires mandatory contraception counseling and monitoring. 1, 2

• Dosing: Typically 100-400 mg/day (specific dosing varies by severity) 1
• Efficacy: 66.7% compliance and improvement rate in outpatient settings, with only 16.2% recurrence among compliant patients 2
• Timing: Early institution induces faster remission and prevents ENL recurrence 2
• Key advantages: Steroid-sparing effect, rapid control of inflammation 1, 2
• Absolute requirements:
  • Strict contraception counseling for all women of childbearing potential 2
  • Monitor for neurotoxicity (peripheral neuropathy) 1
  • Most common side effect is pedal edema (73.5% of patients) 2

Prognostic factors for better thalidomide response:

• Bacillary index ≤4.0 (37% increase in recovery incidence) 2
• Acute ENL presentation (twice as likely to recover vs. chronic ENL) 2
• Completed multidrug therapy (2.5 times greater improvement vs. those still on MDT) 2

Alternative Steroid-Sparing Agents

Minocycline (for chronic/recurrent ENL):

• Dosing: 100 mg once daily for 12 weeks 6
• Efficacy: Achieves initial control faster than clofazimine (2.97 vs. 4 weeks, p=0.048) and maintains longer remission after initial control (p=0.001) 6
• Advantages: Fewer adverse events than clofazimine (p=0.047), superior efficacy profile 6

Clofazimine:

• Dosing: 100 mg three times daily 6
• Limitations: Slower action, more adverse effects, and skin discoloration 1, 6
• Comparable recurrence rates to minocycline (71.4% vs. 55.2%) but shorter remission duration 6

Pentoxifylline:

• Has slow action and significant adverse effects, making it less preferred 1

Treatment Algorithm by ENL Presentation

Acute ENL (First Episode)

1. Start prednisolone 0.5-1 mg/kg/day orally 1, 3
2. Monitor inflammatory markers (TNF, IFN-γ, IL-1β, IL-6, IL-17A decrease with treatment; IL-10 and TGF-β increase) 3
3. Taper gradually based on clinical response 1
4. If inadequate response after 1-2 weeks, consider split-dose regimen before escalating total dose 5

Chronic/Recurrent ENL

1. Prednisolone plus thalidomide (if no contraindications and adequate contraception) 1, 2
2. Alternative: Prednisolone plus minocycline 100 mg daily if thalidomide contraindicated 6
3. Second alternative: Prednisolone plus clofazimine 100 mg three times daily 6

Steroid-Dependent ENL

1. Transition to thalidomide as primary steroid-sparing agent 1, 2
2. If thalidomide contraindicated or not tolerated, use minocycline 6
3. Taper prednisolone gradually while maintaining steroid-sparing agent 1

Monitoring and Follow-Up

• Clinical response: Assess nodule resolution, systemic symptoms, and neuritis control 1
• Recurrence surveillance: ENL commonly recurs; maintain vigilance during and after steroid taper 1, 2
• Adverse effects:
  • Corticosteroids: Cushingoid features, hyperglycemia, infections, HPA suppression 1, 5
  • Thalidomide: Peripheral neuropathy, pedal edema, teratogenicity 1, 2
  • Minocycline: Generally well-tolerated with fewer side effects than clofazimine 6

Common Pitfalls to Avoid

• Escalating prednisolone dose prematurely: Try split-dose regimen first to avoid excessive immunosuppression and long-term complications 5
• Delaying thalidomide in chronic cases: Early institution prevents recurrence and reduces steroid burden 2
• Inadequate contraception counseling: Thalidomide is highly teratogenic; pregnancy prevention is mandatory 2
• Treating ENL like standard erythema nodosum: ENL requires immunosuppression, not just NSAIDs, and has different pathophysiology 4, 1
• Abrupt steroid withdrawal: Taper gradually to prevent rebound and HPA axis complications 1, 5