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Descriptions of the natural history of erythema nodosum leprosum to inform clinical classification – A semi-systematic review
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Descriptions of the natural history of erythema nodosum leprosum to inform clinical classification – A semi-systematic review
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Journal Article
Descriptions of the natural history of erythema nodosum leprosum to inform clinical classification – A semi-systematic review
2026
Overview
Erythema nodosum leprosum (ENL) is a severe immunological complication of leprosy, characterised by painful nodules, fever, arthralgia, oedema, and systemic symptoms. Temporal classifications-acute, recurrent, and chronic-are inconsistently applied, complicating data comparisons. Standardised and agreed definitions are essential to ensure consistency in diagnosis, research, and clinical management.
To examine how temporal classifications of ENL are used in modern literature and compare them to descriptions from the pre-corticosteroid era.
We conducted a semi-systematic review of historical and contemporary literature. Historical texts published before 1940, prior to the introduction of sulfone antibiotics and corticosteroids, were purposively selected to capture descriptions of the natural history of ENL. For modern studies, we systematically searched PubMed, EMBASE, LILACS, SciELO, Scopus, African Index Medicus, Cochrane, and ClinicalTrials.gov from May 2024 to March 2025. The systematic review identified 572 articles after de-duplication, and 41 met inclusion criteria for providing definitions of ENL subtypes.
Five historical treatises were selected. Their clinical observations of nodular skin lesions with systemic symptoms-ranging in duration from weeks to months or even years-align with contemporary understandings of ENL. 41 studies included, at least one of the three temporal classifications (acute, recurrent, or chronic). The six-month criterion distinguishing acute and chronic ENL is used in all current definitions. However, definitions for recurrent and chronic ENL frequently overlapped, both referring to prolonged or multiple episodes after initial treatment, underscoring a lack of conceptual clarity.
The absence of standardised ENL terminology impedes data comparison, meta-analysis, and clinical guideline development. A Delphi consensus process and longitudinal observational studies are recommended to refine, standardise agreed ENL classifications.
Publisher
Public Library of Science,PLOS,Public Library of Science (PLoS)
Subject
/ Erythema Nodosum - classification
/ Erythema Nodosum - diagnosis
/ Erythema Nodosum - drug therapy
/ Erythema Nodosum - pathology
/ History
/ Humans
/ Leprosy, Lepromatous - classification
/ Leprosy, Lepromatous - diagnosis
/ Leprosy, Lepromatous - history
/ Leprosy, Lepromatous - pathology
