BACKGROUND: Erythema nodosum leprosum is an immune-mediated complication of leprosy whose underlying mechanism has not yet been fully elucidated, making management difficult.

OBJECTIVES: To determine the serum cytokine profile of ENL compared to non-reactional leprosy states.

METHODS: An open literature search was performed using MEDLINE, Cochrane Library, TRIP and HERDIN electronic databases using the keywords ("cytokines" or "inflammatory mediators") and ("erythema nodosum leprosum" or "ENL") and ("leprosy" or "lepra"). Studies were selected by two independent review authors. Risk of bias was assessed using the Newcastle-Ottawa Scale and statistical analysis was performed using RevMan 5.3 software.

RESULTS: Eight cross-sectional studies with 197 participants were included. Meta-analysis showed that both serum IL-17 and serum IFN-? were significantly decreased (Z 2.39, p = 0.02 and Z 2.74, p = 0.01, respectively) in ENL compared to non-reactional states. However, for IL-1?, IL-6, IL-10, IL-22, TNF-? and TGF-?, no significant differences were found between the two groups.

CONCLUSION: ENL appears to be an exacerbation of the Th2 cytokine response seen in the lepromatous pole of leprosy. However, despite pooling of data, sample sizes remain small resulting in significant heterogeneity. Future studies involving large sample sizes and investigating a wider range of cytokines are encouraged.