Leprosy Mailing List – April 22, 2021
Ref.: (LML) ENL Prevention is better than cure
From: Diana Lockwood and Steve Walker, London, UK
Dear Pieter,
We thank Joel Almeida for highlighting the severe impact that erythema nodosum leprosum (ENL) has on individuals with borderline lepromatous (BL) leprosy and lepromatous leprosy (LL) in his posting on "ENL, prevention is better than cure" [LML April 12, 2021]. The ENLIST Group demonstrated pain is a major determining factor of ENL severity[1] and the ENLIST ENL Severity Scale incorporates an assessment of pain along with nine other clinical features of ENL[2].
ENL is an antigen driven immune-mediated complication of leprosy which occurs before, during and after completion of multi-drug therapy (MDT). We do not agree that there is good evidence that extending the duration of MDT will prevent ENL but it will increase the risk of severe adverse effects associated with MDT.
The retrospective study of Balagon and colleagues cited by Almeida describes reactions (including ENL) occurring in the two years following completion of 12 or 24 months of multibacillary (MB) MDT[3]. The higher rate of ENL in the 12-month treated group (7.6%) compared to the 24-month group (3%) were not significant and likely reflect the natural history of ENL with incident cases of ENL being counted 12 months "earlier" in the 12-month MB MDT treated cohort.
Balagon and colleagues did not report the incidence of ENL during MDT in their two cohorts. However, most individuals present with ENL at diagnosis or during MDT even when taken for 24 months [4, 5]. In the INFIR Cohort Study (ICS) individuals with a bacterial index of 3 or more received 24 months of MB MDT[6]. A retrospective review of the 105 individuals with BL leprosy or LL in the ICS showed that six individuals presented with ENL at the time of leprosy diagnosis, 14 developed ENL during the 24 months whilst on MDT and only one individual developed ENL after completing MDT[7].
It would be better to focus on improving the diagnosis and management of ENL including safe access to thalidomide in countries where it is not permitted than to expose patients to unnecessary prolonged MDT which is not supported by the current evidence.
Steve Walker
Associate Professor
Diana Lockwood
Emeritus professor of Tropical Medicine
London School of Hygiene & Tropical Medicine
London
References
1. Walker, S.L., et al., ENLIST 1: An International Multi-centre Cross-sectional Study of the Clinical Features of Erythema Nodosum Leprosum. PLoS Negl Trop Dis, 2015. 9(9): p. e0004065.
2. Walker, S.L., et al., A leprosy clinical severity scale for erythema nodosum leprosum: An international, multicentre validation study of the ENLIST ENL Severity Scale. PLoS Negl Trop Dis, 2017. 11(7): p. e0005716.
3. Balagon, M.V., et al., Reactions following completion of 1 and 2 year multidrug therapy (MDT). Am J Trop Med Hyg, 2010. 83(3): p. 637-44.
4. Kumar, B., S. Dogra, and I. Kaur, Epidemiological characteristics of leprosy reactions: 15 years experience from north India. Int J Lepr Other Mycobact Dis, 2004. 72(2): p. 125-33.
5. Voorend, C.G. and E.B. Post, A Systematic Review on the Epidemiological Data of Erythema Nodosum Leprosum, a Type 2 Leprosy Reaction. PLoS Negl Trop Dis, 2013. 7(10): p. e2440.
6. van Brakel, W.H., et al., The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in north India. Lepr Rev, 2005. 76(1): p. 14-34.
7. Walker, S.L., et al., The Incidence of Erythema Nodosum Leprosum in India: A Retrospective Follow-up of the INFIR Cohort. Leprosy Review, 2018. 89(3): p. 321-324
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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