Failure of First-Generation GeneXpert MTB/RIF to Detect Rifampicin Resistance in Cutaneous Tuberculosis: A Case Report

Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis. The diagnosis remains challenging because of its clinical polymorphism and low bacillary load. We report the case of a 19-year-old Moroccan woman receiving methotrexate for recently diagnosed rheumatoid arthritis who developed cutaneous tuberculosis in the deltoid region. Initial GeneXpert MTB/RIF analysis detected Mycobacterium tuberculosis without identifying rifampicin resistance, leading to first-line anti-tuberculosis treatment. Despite excellent adherence and multidisciplinary follow-up, the lesion progressively worsened. Repeat molecular testing with GeneXpert MTB/RIF Ultra and GeneXpert MTB/XDR revealed rifampicin monoresistance, subsequently confirmed by phenotypic drug susceptibility testing. Adjustment of the treatment regimen according to the resistance profile resulted in rapid clinical improvement and progressive lesion regression. This case highlights the diagnostic limitations of the first-generation GeneXpert MTB/RIF assay in paucibacillary cutaneous tuberculosis and emphasizes the value of next-generation molecular techniques for the early detection of anti-tuberculosis drug resistance, particularly in immunocompromised patients.