Leprosy Mailing List – November 12, 2017
Ref.: (LML) Methotrexate in ENL
From: Diana Lockwood and Steve Walker, London, UK
Dear Pieter,
We like to make a contribution to this ongoing and important discussion in LML about Steroid Dependency and the use of Methotrexate.
"Corticosteroid dependency" in ENL is a major problem. It is well recognised that patients require high and prolonged doses of oral corticosteroids to control their ENL. Patients with ENL experience a flare in their symptoms as the dose of corticosteroids is reduced which requires the dose to be increased. Tachyphylaxis also occurs with patients experiencing deterioration at progressively higher doses of corticosteroids.
We have demonstrated that ENL is associated with increased mortality in Ethiopia where thalidomide is not available. The majority of adverse outcomes were attributed to corticosteroids [1]. We have repeated this study with colleagues at Instituto Oswaldo Cruz - Fiocruz in Rio de Janeiro where thalidomide is available and corticosteroids did not appear to be a significant factor in mortality (Neves et al submitted Leprosy Review). We have several observations to make:
a) Thalidomide works well as an immunomodulatory agent in ENL. We need to push to make it more widely available in conjunction with safe prescribing practices. Thalidomide is not available in many leprosy endemic countries and where it is available cost often limits use. The lack of availability of thalidomide results in significant numbers of ENL patients being at risk of death and other severe adverse outcomes due to corticosteroids. It is also worth noting that adverse reactions to thalidomide sometimes limits its use. The neurotoxicity of Thalidomide also needs assessing with appropriate control lepromatous patients in a scientific design.
b) Methotrexate (MTX) is a cheap, widely available and potentially useful alternative. Currently there are only 13 published cases of the effect of MTX in ENL[2]. It would be very helpful for other clinicians to collect and publish data on their experience of using MTX in ENL. The recently published ENLIST ENL Severity Scale (EESS) would facilitate such reports and we recommend clinicians incorporate the EESS into their clinical practice [3].
c) The ENLIST Group are about to study the efficacy of MTX in a large, Leprosy Research Initiative-funded, multi-centre, randomised clinical trial - Methotrexate and Prednisolone studies (MaPS) in ENL.
d) It would be useful for other immunosuppressants, such as azathioprine [4], to be used in individual patients with steroid dependent ENL with careful prospective recording of outcomes.
e) We agree with our colleague Dr da Costa Nery that immunosuppression needs to be managed by physicians with experience in settings where ENL, its complications and adverse drug reactions can be monitored and managed. We believe this is the case not only for thalidomide, MTX and other second-line agents but also for oral corticosteroids whose adverse effect profile in ENL is often severe and under recognised.
f) The pilot study of minocycline in 10 patients with chronic ENL published by Dr Narang and colleagues is interesting. The acceptability of minocycline-induced dyspigmentation needs further assessment. The findings of the study require confirmation in a well-designed and adequately powered clinical trial. This is likely to require collaboration between centres. The ENLIST Group has the capacity to do this.
g) We encourage centres to join the ENLIST Group to facilitate doing other controlled ENL treatment studies. For further information email: enlist@lshtm.ac.uk
Best wishes
Diana Lockwood and Steve Walker
References
1. http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002690
2. https://www.lepra.org.uk/platforms/lepra/files/lr/Dec15/15-0041.pdf
3. http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005716
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620793/pdf/jcdr-11-FD01.pdf
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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