Title: Clinical and Cytokine Profile in Type-2 Reaction in Leprosy in Response to Thalidomide: A Randomized Control 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 control trial 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. The two study-groups comprised of leprosy cases and the age, sex and area of residence matched healthy controls respectively. Blood samples and skin biopsy were taken at baseline and on 14th day after Thalidomide therapy in the treated patients and were 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 in 1-2 weeks.
Results: Our study found that 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 and there was significant correlation of increased CD-64 expression with the severity of reaction.
Conclusion: TNF-alpha and IFN-gamma are sensitive markers of type-2 reaction, however, did not correlate with treatment response to Thalidomide and hence may be used as screening biomarkers for reaction. CD-64 expression on neutrophils may be an early biomarker for diagnosis, prognosis and clinical response to Thalidomide and it is not time-consuming as well. We also propose that anti-CD 64 antibodies may become one of the treatment modalities in type-2 reactions in future where Thalidomide is contraindicated or is less favored especially in childhood leprosy cases <12 years where safety data of Thalidomide is limited and in pregnant females.
Dr. Rohit Kothari, presently working as Senior Resident at Dept. Of Dermatology, Command Hospital, Bengaluru, India. Earlier he worked as post-graduate resident at Command Hospital and Armed Forces Medical college (AFMC), Pune, India. He received MD degree in the year 2021 from AFMC, Pune, India. His research prime objective is to spread awareness and reduce stigma associated with leprosy in the community. To his credit, he has published 16 articles in various international peer reviewed journals.