Title : Clinical and Cytokine Profile in Type-2 Reaction in Leprosy in Response to Thalidomide: A Randomized Controlled Trial
Background: Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae (M. Lepra). Reactions may interrupt its usual chronic course. Type-2 leprosy reaction or erythema nodosum leprosum (ENL) is an acute event which is type-III hypersensitivity response and manifests clinically as tender evanescent skin-colored or erythematous nodules and systemic features. Various cytokines like TNF-alpha and IFN-gamma may be increased in ENL along with CD-64 which may be overexpressed due to massive influx of neutrophils during this reaction. Thalidomide is considered the drug of choice for type-2 lepra reaction. We tried to extrapolate these facts in the treatment of Leprosy reactions in the form of reduction of these molecules following Thalidomide use and therefore predicting response and prognosis.
Objective: To find a correlation between TNF-alpha, IFN-gamma and CD-64 expression on circulating neutrophils following Thalidomide treatment and predicting response and prognosis in cases of Type-2 lepra reaction.
Methodology: This randomized controlled trial consisted of fifty confirmed cases of type-2 leprosy reaction and fifty age, sex and area of residence matched healthy controls. It was conducted in a tertiary care hospital in Bengaluru, India. The diagnosis of leprosy was made by the presence of cardinal features in the form of pale or red skin patch with definite loss of sensation, thickened or enlarged peripheral nerves with sensory and/or motor deficit, and positive slit skin smear for M. Lepra bacillus. Type-2 reaction was diagnosed in case the leprosy patient developed tender evanescent skin-colored or red nodules with systemic symptoms and neutrophil leukocytosis. Blood samples and skin biopsy were taken at baseline and on 14th day after Thalidomide therapy in the treated patients and subjected to histopathology, immunohistochemistry, immunofluorescence, Reverse Transcriptase-Polymerase Chain reaction (RT-PCR Quantitative) and flow cytometry. All patients with ENL responded well to Thalidomide and the lesions resolved within 1-2 weeks.
Results: TNF-alpha and IFN-gamma are increased in almost all cases of type-2 reaction. CD-64 expression is also upregulated in type-2 reaction and downregulated in patients who received Thalidomide and showed favorable clinical response. There was significant correlation of increased CD-64 expression with the severity of reaction.