What is the recommended management of erythema nodosum leprosum (ENL)?

Management of Erythema Nodosum Leprosum (ENL)

Corticosteroids are the first-line anti-inflammatory treatment for ENL, with thalidomide reserved for steroid-dependent or refractory cases due to its teratogenicity and neurotoxicity risks. 1

First-Line Treatment: Corticosteroids

• Prednisone is the anti-inflammatory of choice for acute ENL episodes, though optimal dosing regimens remain unstandardized due to lack of formal guidelines 1, 2
• High-dose oral corticosteroids control acute inflammation and neuritis, but carry significant risk of dependence, particularly in chronic or recurrent ENL 1, 3
• Corticosteroids may not be universally effective and pose serious adverse effects with prolonged use 3

Second-Line Treatment: Thalidomide

• Thalidomide has rapid action and is highly effective for short-term treatment of ENL skin manifestations, as well as post-remission maintenance therapy to prevent recurrence 2
• Dosing and duration should be carefully monitored; early institution of thalidomide induces faster remission and prevents ENL recurrence 3
• Thalidomide is absolutely contraindicated in pregnant women, women of childbearing age, and sexually active men not using contraception due to devastating teratogenic effects 2
• Common adverse effects include somnolence, constipation, rash, and pedal edema (73.5% of patients), but thalidomide-induced peripheral neuropathy is a critical cause for drug discontinuation 3, 2
• Thalidomide can be administered in outpatient settings with rigorous contraception counseling and monitoring 3

Thalidomide Efficacy Data

• Among compliant patients, 66.7% improved with thalidomide treatment, though ENL recurrence occurred in 16.2% 3
• Patients with bacillary index ≤4.0 had 37% higher recovery rates 3
• Acute ENL patients were twice as likely to recover compared to chronic ENL patients 3
• Recovery was 2.5 times greater among patients who completed multidrug therapy (MDT) versus those still on MDT 3

Third-Line and Adjunctive Therapies

• Clofazimine is reserved for patients who do not respond to first-line treatment, but has slow action and important adverse effects 1, 4
• Pentoxifylline has slow action and significant adverse effects, limiting its utility 1
• Combination therapy with thalidomide and corticosteroids is effective and allows steroid-sparing in chronic cases 2

Refractory Disease Management

• TNF-α inhibitors (etanercept) can achieve full resolution in severe refractory ENL that fails conventional therapy over years, though evidence is limited to case reports 4, 5
• Other emerging options for refractory cases include thalidomide analogs, tenidap, cyclosporine A, plasma exchange, and intravenous immunoglobulin (IVIG), though these lack robust evidence 5

Treatment Goals and Monitoring

• The primary goals are to control acute inflammation and neuritis, prevent onset of new episodes, and minimize disability 1
• ENL is frequently recurrent and/or chronic, requiring long-term management strategies 1, 3

Critical Pitfalls to Avoid

• Do not use thalidomide without rigorous contraception counseling and monitoring—teratogenicity risk is absolute 3, 2
• Do not continue corticosteroids indefinitely—steroid dependence is common and adverse effects accumulate, particularly in chronic ENL 1
• Do not delay thalidomide in appropriate candidates—early institution prevents recurrence and reduces steroid burden 3
• Monitor for peripheral neuropathy with thalidomide use, as this is a critical reason for discontinuation 2
• Recognize that no standardized treatment guidelines exist—management must be adapted based on disease severity, chronicity, and individual patient factors 1