Erythema nodosum leprosum (ENL) (or type 2 reaction) is an immune-mediated complication of borderline lepromatous and lepromatous leprosy. It can appear before treatment, during multidrug therapy (MDT), and in some patients long after MDT has ended. In the dermatology outpatient clinic, a post-MDT patient with tender nodules and fever raises a real diagnostic problem. The differential includes relapse, reversal reaction, Lucio phenomenon, and unrelated panniculitides or neutrophilic dermatoses, while prior therapy may have altered both the bacillary and the histological picture. This narrative review summarizes published knowledge on the histopathological spectrum of ENL, the biopsy and staining practice needed to capture it, the way treatment history modifies the findings, and the features that separate ENL from its mimics. The central finding is neutrophilic infiltration of macrophage granulomas, usually with dermal edema, leukocytoclasia, and neutrophilic panniculitis. True vasculitis is inconsistent, and its prominence depends on the age of the lesion. After MDT, foamy histiocytes containing fragmented or granular acid-fast debris may persist. In at least one recent post-MDT series, about half of the biopsies still showed active disease or bacillary persistence, so a reaction after treatment should not be equated with bacteriological cure. We offer a comparison table of histological differentials and a clinicopathological checklist for reporting. We also identify gaps, notably the scarcity of studies that stratify ENL histology by time since MDT completion.
BT - Cureus DA - 10/2026 DO - 10.7759/cureus.118485 IS - 10 LA - ENG M3 - Article N2 -Erythema nodosum leprosum (ENL) (or type 2 reaction) is an immune-mediated complication of borderline lepromatous and lepromatous leprosy. It can appear before treatment, during multidrug therapy (MDT), and in some patients long after MDT has ended. In the dermatology outpatient clinic, a post-MDT patient with tender nodules and fever raises a real diagnostic problem. The differential includes relapse, reversal reaction, Lucio phenomenon, and unrelated panniculitides or neutrophilic dermatoses, while prior therapy may have altered both the bacillary and the histological picture. This narrative review summarizes published knowledge on the histopathological spectrum of ENL, the biopsy and staining practice needed to capture it, the way treatment history modifies the findings, and the features that separate ENL from its mimics. The central finding is neutrophilic infiltration of macrophage granulomas, usually with dermal edema, leukocytoclasia, and neutrophilic panniculitis. True vasculitis is inconsistent, and its prominence depends on the age of the lesion. After MDT, foamy histiocytes containing fragmented or granular acid-fast debris may persist. In at least one recent post-MDT series, about half of the biopsies still showed active disease or bacillary persistence, so a reaction after treatment should not be equated with bacteriological cure. We offer a comparison table of histological differentials and a clinicopathological checklist for reporting. We also identify gaps, notably the scarcity of studies that stratify ENL histology by time since MDT completion.
PB - Springer Science and Business Media LLC PY - 2026 SP - 1 EP - 9 T2 - Cureus TI - Histopathology of Erythema Nodosum Leprosum With Emphasis on Post-multidrug Therapy Considerations: A Narrative Review UR - https://assets.cureus.com/uploads/review_article/pdf/544645/20261024-1546164-pamv5i.pdf VL - 18 SN - 2168-8184 ER -