Can etanercept be an option in management of recurrent steroid-dependent erythema nodosum leprosum? A retrospective study of six patients

Sir,

Erythema nodosum leprosum is an immune complex-mediated reaction seen in leprosy patients in lepromatous spectrum of disease.¹ Systemic corticosteroids are the mainstay of treatment but are not safe for long-term use in cases of recurrent episodes. Thalidomide, an effective steroid sparing agent is beyond the reach of most of the patients due to its cost. Other immunosuppressants such as methotrexate, cyclosporine and azathioprine have been found to have variable efficacy.^2-4 As tumour necrosis factor (TNF) is one of the main mediators of erythema nodosum leprosum, biologicals with tumour necrosis factor inhibition as target have a potential role. We share our experience with six cases of recurrent erythema nodosum leprosum treated with etanercept.

We retrospectively analysed the data from patients of erythema nodosum leprosum, who received injection etanercept during the years 2018–2019 in the Department of Dermatology, All India Institute of Medical Sciences, Bhopal. Patients with steroid dependent erythema nodosum leprosum of greater than six months duration who had poor control with conventional immunosuppressants for at least three months, received etanercept. The diagnosis of erythema nodosum leprosum was based on classical clinical presentation, histopathology and slit skin smear. Other medical treatments taken by patients were either continued or tapered/escalated in follow-up according to standard guidelines by NLEP. Pre treatment evaluation included complete blood count, liver function test, hepatitis B, C and HIV screening, chest X-ray and Mantoux test. Etanercept was administered every week as 50 mg subcutaneous injection one hour after premedication. Treatment response was categorised in terms of change in frequency of erythema nodosum leprosum, number of lesions in each episode, appearance of necrotic lesions and total cumulative steroid doses received six months before and after receiving treatment with etanercept. The parameters were compared using paired t-test.

A total of six male patients (age: 13–43 years) of erythema nodosum leprosum (mean BI: 3) received etanercept over a one-year period. Two patients were continuing MB-MDT (multibacillary multi drug therapy) while four others had completed the regimen prior. The duration of erythema nodosum leprosum ranged from 6 to 18 months (10 ± 4.6 months). All patients were on prednisolone 20–40 mg/day, while two patients each were additionally on methotrexate 15 mg/wk and thalidomide 100 mg/day respectively while one patient was on clofazimine 100 mg three times a day. The frequency of erythema nodosum leprosum episodes ranged from 1 to 5 (mean = 3) in the past six months and cumulative prednisolone dose ranged from 625 to 2180 mg (mean: 1489.83 mg). All the patients had necrotic lesions of erythema nodosum leprosum as well [Figure 1]. The number of lesions varied from 15 to 50 lesions/episode (mean: 37). Patients received between one to nine doses of etanercept (1–9) depending on the availability of the medicine in hospital supply and treatment response [Figure 2].

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Figure 1:

Necrotic erythema nodosum leprosum lesions over arm in a patient

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Figure 2:

Temporal graph of erythema nodosum leprosum episodes, etanercept doses, systemic steroid and steroid sparing immunosuppressant in the six months after starting etanercept

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All patients showed improvement in erythema nodosum leprosum after treatment. One patient did not develop any further erythema nodosum leprosum episodes after the first dose itself, three out of the remaining five had remission while on treatment but relapsed on stopping etanercept. Another two patients continued to develop erythema nodosum leprosum episodes but with lesser severity during treatment period. The frequency of erythema nodosum leprosum (number of episodes in every six months) decreased from mean of 2.67 to 2 during next six months (P = 0.174). There was 42.8% decrease in cumulative prednisolone dose from a mean of 1489.8mg before etanercept to 851.5mg after receiving etanercept (P = 0.03). The average number of erythema nodosum leprosum lesions at each episode decreased significantly, from a mean of 37 to 16 (P = 0.019) [Table 1] [Figure 3]. None of the patients developed necrotic lesions post-treatment. In three patients steroids could be stopped completely within six months, while in the remaining three tapering of the prednisolone dose was possible.

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Figure 3:

Change in frequency of erythema nodosum leprosum: (a) average number of lesions per episode (b), cumulative steroid dose and (c) before and after treatment with etanercept

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All the patients experienced minor side effects in the form weight gain (6), dyspepsia (1) and pyodermas (2). However, none of the patients experienced injection site reactions or any serious adverse event.

Erythema nodosum leprosum is an immune complex mediated reaction where tumour necrosis factor is considered as the main mediator.^5,6 Tumour necrosis factor inhibitor biologicals have been reported to be effective in management of erythema nodosum leprosum in few reports.^7-11 Faber et al. showed good and sustained response in one patient of erythema nodosum leprosum following three doses of infliximab.⁸ We chose etanercept due to its easy availability in our hospital low treatment cost. Etanercept has been used previously in steroid dependent erythema nodosum leprosum in isolated case reports showing beneficial role allowing tapering and discontinuation of systemic steroids. However, duration of treatment varied from six weeks to 12 months. In contrast, we found significant reduction in frequency and severity of erythema nodosum leprosum episodes along with decrease in total cumulative steroid doses of steroid with much fewer doses [Figure 3]. The limitation of our study was its retrospective study design and variability in dosing. No standard protocol was followed for treatment. Based on this study alone, it cannot be said with certainty that etanercept is a treatment option for erythema nodosum leprosum. However, it reflects that etanercept can be considered for future randomised controlled trials in erythema nodosum leprosum to prove its actual efficacy as a steroid sparing agent in this condition.