Methotrexate in erythema nodosum leprosum: Pitfalls to avoid

Sir,

We read with interest the short report by Rani et al. entitled “An uncommon variant of erythema nodosum leprosum responding well to methotrexate: Report of two cases.” ¹ The authors describe two cases of erythema nodosum leprosum (ENL) with ‘atypical features’ and good response to low dose methotrexate. A closer examination of the report reveals several treatment concerns that hamper the prospect of drawing meaningful conclusions from this report.

First case is a 40-year-old male with Hansen disease of unspecified spectrum presenting with severe ENL. Prednisolone was started at an initial dose of 20 mg, which was later increased to 50 mg, in combination with clofazimine 100 mg thrice a day. No justification has been provided for this dosage schedule instead of the WHO recommended dose of prednisolone for ENL (40 mg in field setting and up to 1 mg/kg in referral centres, tapered in two weeks), nor for the co-administration of clofazimine. ²

ENL recurred as the steroids were tapered, at which point methotrexate was also instituted at a dose of 15 mg per week. Methotrexate was tapered after two months, in view of favorable clinical response. Since onset of action of methotrexate at low-moderate dose requires around 8–12 weeks, the response must have been due to continued prednisolone, leading one to question the logic of introduction and utility of methotrexate and its tapering without waiting for the appropriate pharmacological response. ³ Continued clofazimine administration must have contributed to the reaction control as well, hence giving the sole credit to methotrexate can not be justified. Further, instead of tapering corticosteroids, methotrexate was tapered. Traditional clinical dictum is to combine tapering doses of a rapidly acting agent such as prednisolone for acute disease control, along with a slower acting steroid sparing agent for long-term maintenance. ⁴ Remission was maintained in this case with prednisolone 15 mg, hence the “steroid-dependent ENL” seems to have been managed with continued steroid use, claimed advantage with methotrexate in controlling the reaction and its steroid sparing effects notwithstanding. The prolonged period required to obtain full impact of drugs like clofazimine and methotrexate should be heeded in assessing treatment response.

Second case had severe acute ENL and was managed with oral prednisolone 50 mg and clofazimine 100 mg thrice a day along with standard multidrug therapy. Standard guidelines do not recommend the use of clofazimine in acute ENL, ² as these cases respond well to corticosteroids alone. ⁵ The patient developed anemia, hepatomegaly and deranged liver functions within a few weeks of therapy. While some of these features may be explained by severe ENL, the possibility of dapsone hypersensitivity syndrome cannot be ruled out from the provided information. The authors again chose methotrexate as the therapy for ENL, which may not be a sagacious alternative in a patient with hemoglobin of 71 g/l, ³ and further, methotrexate may take 8–12 weeks for noticeable therapeutic effect in acute ENL.^3,4

We are for the use of methotrexate in ENL, however we do oppose the inappropriate use of this agent and then crediting it for the action it did not produce in the first case. Methotrexate was tapered off as soon the onset of action was expected. In the second case methotrexate was prescribed despite clear contraindications. ⁶ The ‘unusual’ clinical feature in first case, i.e., collarette of scales, may very well be merely superficial desquamation due to ENL-related cutaneous inflammation. In the second case described as ‘novel’ variant of ENL (granuloma annulare-like), the morphology of lesions bears striking resemblance to previously reported cases of erythema multiforme-like ENL.^7,8 The authors’ suggestion that methotrexate is effective especially in unusual variants of ENL appears unsubstantiated. Further, to extrapolate the effectiveness of methotrexate to other ‘unusual’ variants of ENL based on these two cases seems neither justifiable nor scientifically fair. Methotrexate appears to be a valuable addition for chronic or recurrent ENL, but not for acute ENL.^9,10 The authors in their personal capacity may manage the patients as they deem proper, however a publication in which various established protocols have not been followed sends a wrong message to the readers and may affect the rational management of ENL.

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