{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T18:34:28Z","timestamp":1786473268143,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014410","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000}}],"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Hospital Homes of St. Giles","award":["ITCRZM25"],"award-info":[{"award-number":["ITCRZM25"]}]},{"DOI":"10.13039\/501100021734","name":"Leprosy Research Initiative","doi-asserted-by":"publisher","award":["704.16.71"],"award-info":[{"award-number":["704.16.71"]}],"id":[{"id":"10.13039\/501100021734","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Erythema nodosum leprosum (ENL) is a severe inflammatory complication of lepromatous leprosy characterised by recurrent inflammatory episodes often requiring prolonged immunosuppression. The severity of ENL can be quantified using the validated and reliable ENLIST ENL Severity Scale (EESS). The longitudinal course of ENL and how it is captured using standardised severity measures has not been well described. We prospectively evaluated the changes in ENL severity over time using the EESS in a randomised clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:bold>Ethics statement.<\/jats:bold>\n                      The trial was performed according to the Helsinki Declaration as revised in 2024 and ethical approval was obtained from the London School of Hygiene &amp; Tropical Medicine Research Ethics Committee (15762). Approval was obtained from Dr. Soetomo Hospital Ethics Committee, Indonesian Food and Drug Authority, Ethiopian Ministry of Education Ethics Committee, Ethiopian Food and Drug Authority, AHRI\/ALERT Ethics Review Committee, Bombay Leprosy Project Committee, the Leprosy Mission Trust India Ethics Committee, Nepal Health Research Council and Department of Drug Administration, Nepal Government. All participants provided written informed consent before enrolment. MaPs in ENL was registered at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\" xlink:type=\"simple\">www.clinicaltrials.gov<\/jats:ext-link>\n                      (NCT03775460) and the Clinical Trials Registry India (CTRI\/2020\/11\/029074). We conducted a prespecified secondary analysis of participants enrolled in the Methotrexate and Prednisolone Study in ENL, an international multicentre randomised controlled trial conducted in Ethiopia, India, Indonesia, and Nepal. Adults with severe ENL (EESS score \u22659) were followed for 60 weeks with repeated EESS assessments. Longitudinal trajectories were analysed using mixed-effects regression models. Item-level analyses characterised the clinical phenotype captured by the scale. Associations between EESS score, prednisolone exposure, and dermatology-specific health-related quality of life measured using the Dermatology Life Quality Index (DLQI) were examined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>A total of 135 participants contributed 1,958 EESS assessments. Mean EESS declined rapidly during the first four weeks of treatment (\u22122.10 points\/week; 95% CI \u22122.36 to \u22121.84; p\u2009&lt;\u20090.001), increased modestly during reduction in corticosteroid dose (weeks 4\u201320), and gradually declined thereafter. Severe ENL (EESS score \u22659) occurred in 20.6% of visits and was characterised primarily by pain and cutaneous inflammatory manifestations. Participants who required additional prednisolone had persistently higher EESS scores and showed limited improvement compared with those who did not receive additional prednisolone. Longitudinal EESS scores were strongly correlated with the DLQI score (Spearman\u2019s \u03c1\u2009=\u20090.75; p\u2009&lt;\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The EESS captures clinically meaningful changes in ENL severity, aligns with treatment decisions, and reflects patient-reported severity over time. These findings support the use of the EESS as a robust tool for monitoring ENL severity in both clinical research and routine care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014410","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:38:35Z","timestamp":1785778715000},"page":"e0014410","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal performance of the ENLIST ENL severity scale in individuals with severe erythema nodosum leprosum: Responsiveness, trajectories and clinical features \u2013 a secondary analysis of the Methotrexate and Prednisolone study - MaPs in ENL"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-8165","authenticated-orcid":true,"given":"Barbara","family":"de Barros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulnaser","family":"Hamza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alemtsehay","family":"Getachew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medhi Denisa","family":"Alinda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farha","family":"Sultana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishwanath","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek V.","family":"Pai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Wakade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagyashree","family":"Bhame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna A.","family":"Hagge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra","family":"Napit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeta","family":"Maximus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joydeepa","family":"Darlong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Yulianto","family":"Listiawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimelis N.","family":"Doni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nicholls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Genser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba M.","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana N. J.","family":"Lockwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Erythema Nodosum Leprosum International Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"issue":"1","key":"pntd.0014410.ref001","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s41572-024-00575-1","article-title":"Leprosy","volume":"10","author":"ML Grijsen","year":"2024","journal-title":"Nat Rev Dis Primer"},{"issue":"10530","key":"pntd.0014410.ref002","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/S0140-6736(25)01963-4","article-title":"Leprosy.","author":"H Agudelo","year":"2026","journal-title":"Lancet"},{"issue":"37","key":"pntd.0014410.ref003","first-page":"365","article-title":"Global leprosy (Hansen disease) update, 2024: Beyond zero cases - what elimination of leprosy really means","volume":"100","author":"World Health Organization","year":"2025","journal-title":"Wkly Epidemiol Rec"},{"issue":"5","key":"pntd.0014410.ref004","doi-asserted-by":"crossref","first-page":"868","DOI":"10.4269\/ajtmh.2006.74.868","article-title":"Clinical course of erythema nodosum leprosum: an 11-year cohort study in Hyderabad, India","volume":"74","author":"L Pocaterra","year":"2006","journal-title":"Am J Trop Med Hyg"},{"issue":"2","key":"pntd.0014410.ref005","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1489\/1544-581X(2004)072<0125:ECOLRY>2.0.CO;2","article-title":"Epidemiological characteristics of leprosy reactions: 15 years experience from North India","volume":"72","author":"B Kumar","year":"2004","journal-title":"Int J Lepr Other Mycobact Dis"},{"key":"pntd.0014410.ref006","doi-asserted-by":"crossref","first-page":"321","DOI":"10.47276\/lr.89.3.321","article-title":"The incidence of erythema nodosum leprosum in India: a retrospective follow-up of the INFIR cohort","volume":"89","author":"SL Walker","year":"2018","journal-title":"Lepr Rev"},{"issue":"9","key":"pntd.0014410.ref007","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004065","article-title":"ENLIST 1: an international multi-centre cross-sectional study of the clinical features of erythema nodosum leprosum","volume":"9","author":"SL Walker","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"pntd.0014410.ref008","doi-asserted-by":"crossref","first-page":"211","DOI":"10.47276\/lr.87.2.211","article-title":"Experiences with thalidomide for erythema nodosum leprosum\u2013 a retrospective study","volume":"87","author":"J Darlong","year":"2016","journal-title":"Lepr Rev"},{"issue":"1","key":"pntd.0014410.ref009","doi-asserted-by":"crossref","first-page":"100","DOI":"10.47276\/lr.91.1.100","article-title":"Health-related quality of life associated with erythema nodosum leprosum in Purulia, West Bengal, India","volume":"91","author":"J Darlong","year":"2020","journal-title":"Lepr Rev"},{"issue":"3","key":"pntd.0014410.ref010","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0002690","article-title":"The mortality associated with erythema nodosum leprosum in Ethiopia: a retrospective hospital-based study","volume":"8","author":"SL Walker","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pntd.0014410.ref011","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003431","article-title":"Household costs of leprosy reactions (ENL) in rural India","volume":"9","author":"DJ Chandler","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014410.ref012","doi-asserted-by":"crossref","first-page":"68","DOI":"10.47276\/lr.90.1.68","article-title":"Retrospective study of the morbidity associated with Erythema Nodosum Leprosum in Brazilian leprosy patients","author":"D Neves","year":"2019","journal-title":"Lepr Rev"},{"issue":"3","key":"pntd.0014410.ref013","article-title":"A systematic review of adverse effects associated with systemic corticosteroids in the management of leprosy. Fastenau A, editor","volume":"20","author":"AI Lun","year":"2026","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0014410.ref014","doi-asserted-by":"crossref","first-page":"332","DOI":"10.47276\/lr.87.3.332","article-title":"The development of a severity scale for Erythema Nodosum Leprosum\u2013the ENLIST ENL severity scale","volume":"87","author":"SL Walker","year":"2016","journal-title":"Lepr Rev"},{"issue":"7","key":"pntd.0014410.ref015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0005716","article-title":"A leprosy clinical severity scale for erythema nodosum leprosum: an international, multicentre validation study of the ENLIST ENL Severity Scale","volume":"11","author":"SL Walker","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"pntd.0014410.ref016","doi-asserted-by":"crossref","DOI":"10.1111\/jdv.17585","article-title":"Apremilast in multibacillary leprosy patients with chronic and recurrent erythema nodosum leprosum: a prospective single-centre pilot study","volume":"35","author":"T Narang","year":"2021","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"1","key":"pntd.0014410.ref017","doi-asserted-by":"crossref","first-page":"373","DOI":"10.15562\/bmj.v13i1.5001","article-title":"Correlation between serum interleukin-6 levels and the severity of Enlist ENL Severity Scale (EESS) in Erythema Nodosum Leprosum (ENL) patients","volume":"13","author":"Nahrisyah","year":"2024","journal-title":"Bali Med J"},{"issue":"11","key":"pntd.0014410.ref018","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2020-037700","article-title":"Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial","volume":"10","author":"B de Barros","year":"2020","journal-title":"BMJ Open"},{"key":"pntd.0014410.ref019","unstructured":"Regional Office for South-East Asia. Leprosy\/Hansen Disease: Management of reactions and prevention of disabilities. 2017. http:\/\/apps.who.int\/bookorders"},{"issue":"4","key":"pntd.0014410.ref020","doi-asserted-by":"crossref","first-page":"731","DOI":"10.4269\/ajtmh.24-0871","article-title":"Utility of the erythema nodosum leprosum international study severity scale for erythema nodosum leprosum: a clinically supported critical appraisal","volume":"113","author":"HM Zimmerman","year":"2025","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0014410.ref021","article-title":"Dermatology Life Quality Index (DLQI)\u2014a simple practical measure for routine clinical use","author":"AY Finlay","year":"1994","journal-title":"Clin Exp Dermatol"},{"issue":"2","key":"pntd.0014410.ref022","doi-asserted-by":"crossref","first-page":"190","DOI":"10.25259\/IJDVL_143_20","article-title":"Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker","volume":"87","author":"FR Vilani-Moreno","year":"2021","journal-title":"Indian J Dermatol Venereol Leprol"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0014410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:45:25Z","timestamp":1786470325000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0014410"}},"subtitle":[],"editor":[{"given":"Anil","family":"Fastenau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":22,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0014410","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}