Association between erythema nodosum/erythema induratum of Bazin and Mycobacterium tuberculosis infection in Koreans

Background: Erythema nodosum and erythema induratum of Bazin are similar inflammatory diseases of the lower extremities. These are clinically distinguishable entities, though overlap can occur. Both diseases are reported to be related to Mycobacterium tuberculosis infection, but it is very difficult to identify Mycobacterium tuberculosis in skin lesions. Aim: This study aimed to develop a new nested polymerase chain reaction targeting the IS6110 insertion sequence of M. tuberculosis to improve the M. tuberculosis detection rate in skin lesions of erythema nodosum or erythema induratum of Bazin. Methods: From May 2016 to Jan 2018, 14 patients with clinically suspicious erythema nodosum or erythema induratum were enrolled in the study. Two cases were classified as erythema nodosum and 12 as erythema induratum. Individual patients were subjected to a 4-mm punch biopsy, and their venous whole blood was sampled immediately after diagnosis. Results: Eight patients were tested for M. tuberculosis using QuantiFERON, of which seven (87.5%) were positive. IS6110-nested polymerase chain reaction on all 14 patients identified 11(78.6%) positive cases. Four of the eight (50%) individuals tested with QuantiFERON were also positive in the IS6110 nested polymerase chain reaction. The difference between the outcomes of the QuantiFERON and the IS6110-nested polymerase chain reaction tests was not statistically significant. There was also no significant agreement between the results of both assays. Sequencing the IS6110-nested polymerase chain reaction products showed a 97%-100% nucleotide sequence identity with the H37Rv genome. Conclusion: It is important to test for tuberculosis in patients with multiple tender subcutaneous nodules on their lower extremities in high-burden tuberculosis countries like Korea. Limitations: We need to register more suspicious patients to verify the association between erythema nodosum/erythema induratum of Bazin and M. tuberculosis. Furthermore, it is necessary to improve the more sensitive polymerase chain reaction technique to identify M. tuberculosis directly in cutaneous lesions.