A Systematic Review on the Epidemiological Data of Erythema Nodosum Leprosum, a Type 2 Leprosy Reaction

Background: Erythema Nodosum Leprosum (ENL) is a humoral immunological response in leprosy that leads to inflammatory skin nodules which may result in nerve and organ damage, and may occur years after antibiotic treatment. Multiple episodes are frequent and suppression requires high doses of immunosuppressive drugs. Global occurrence is unknown. Methodology/Principal Findings: Systematic review of evidence on ENL incidence resulted in 65 papers, predominantly from India (24) and Brazil (9), and inclusive of four reviews. Average incidences are based on cumulative incidence and size of study populations (n>100). In field-based studies 653/54,737 (1.2%) of all leprosy cases, 194/4,279 (4.5%) of MB cases, and 86/560 (15.4%) of LL cases develop ENL. Some studies found a range of 1–8 per 100 person-years-at-risk (PYAR) amongst MB cases. Hospital samples indicate that 2,393/17,513 (13.7%) of MB cases develop ENL. Regional differences could not be confirmed. Multiple ENL episodes occurred in 39 to 77% of ENL patients, with an average of 2.6. Some studies find a peak in ENL incidence in the first year of treatment, others during the second and third year after starting MDT. The main risk factor for ENL is a high bacteriological index. Conclusions/Significance: Few studies reported on ENL as a primary outcome, and definitions of ENL differed between studies. Although, in this review averages are presented, accurate data on global and regional ENL incidence is lacking. Large prospective studies or accurate surveillance data would be required to clarify this. Health staff needs to be aware of late reactions, as new ENL may develop as late as five years after MDT completion, and reoccurrences up to 8 years afterwards. Author Summary: This systematic review addresses an underpublicized and yet highly significant leprosy topic. Erythema Nodosum Leprosum (ENL) is a serious complication in multi-bacillary (MB) leprosy that may lead to severe disability. Inflammatory skin nodules may result in nerve and organ damage and require high doses of immunosuppressive drugs. ENL can occur long after patients are released from antibiotic treatment. Frequency and severity of ENL is unknown; this review confirms the lack of accurate data at global, regional, and national levels. Available data indicates that ENL incidence ranges between 0.7–4.6% of all MB cases and late reoccurrence up to 8 years after release from treatment. ENL episodes often reoccur, with an average of 2.6 times. The main risk factor for ENL is a high bacteriological index. Additionally, data indicate a wide variation of ENL occurrence between and within countries. The conclusions demonstrate the need for increased awareness about ENL, in research, patient surveillance, and in programme management.