Leprosy reactions: New knowledge on pathophysiology, diagnosis, treatment and prevention

Leprosy, or Hansen’s disease, caused by Mycobacterium leprae and Mycobacterium lepromatosis, is a chronic granulomatous infectious disease. Leprosy reactions, characterised by neurocutaneous inflammation, complicate the disease’s indolent course, leading to significant morbidity. However, limited knowledge of reaction pathophysiology stems from a lack of experimental models and the abrupt onset of reactional episodes, posing challenges in delineating initial pathogenic steps. In type 1 reactions, ongoing studies explore the roles of interferon-gamma which results in increased interleukin (IL)-15 and autophagy. Leprosy reactions also exhibit an increase in T helper 17 (Th17) and a decrease in T-regulatory cell (Treg) populations, resulting in diminished tumour growth factor-beta and heightened IL-6 and IL-21 production. Exploring the pathogenesis of erythema nodosum leprosum (ENL) reveals insights into neutrophils, Toll-like receptor 9, B-cells, myeloid-derived suppressor cells, IL-10 pathway and neurotrophins. Noteworthy therapeutic targets include increased expression of cyclooxygenase 2 and vascular endothelial growth factor. Early reaction diagnosis is crucial to limit neural damage, with high-resolution ultrasonography showing promise in detecting minimal nerve involvement. Therapies for ENL management, such as thalidomide, methotrexate, apremilast, minocycline and tumour necrosis factor-alpha inhibitors, hold potential. This review addresses recent advances in leprosy reaction pathogenesis and diagnostics, offering therapeutic insights and preventive strategies to mitigate their onset.