Diagnosis of Mycobacterium marinum Infection Following Seroconversion of QuantiFERON ‐ TB Gold Assay

Despite seroconversion of the QuantiFERON-TB gold (QFT) assay in non-tuberculous mycobacteria (NTM) Mycobacterium (M.) marinum, M. kansasii, and M. szulgai infections being a well-known phenomenon, the clinical significance is seldom reported. We present a case of a 76-year-old male who had serial negative QFT assays and then seroconverted before the diagnosis of atypical M. marinum infection was confirmed on tissue culture. He had a 3-year history of erythematous papules and ulcerating nodules over his left fourth finger, forearm, and elbow. His past medical history was significant for rheumatoid arthritis, for which he was treated with golimumab. He was a Vietnam veteran and fished recreationally. Histopathology of the ulcer (Figure 1) revealed numerous non-necrotizing granulomas, occasional giant cells, and necrosis around the ulcer. Initial tissue cultures were negative for mycobacteria. A QFT assay was performed due to the histological findings of granulomas, and his previously negative assay was found to have seroconverted (Table 1). Active tuberculosis was excluded by history and negative findings on chest x-ray and sputum culture. Repeat biopsies were taken from a new erythematous nodule and this time his tissue cultures and panmycobacterial PCR were positive for M. marinum. After consultation with the Infectious Diseases service, he was commenced on and successfully completed rifampicin 600 mg daily and ethambutol 1200 mg daily for 12 weeks given his immunosuppression and drug–drug interactions between clarithromycin and his regular medications simvastatin/amitriptyline. There is an increasing incidence of NTM infection due to factors such as greater use of immunosuppressive medications and enhanced detection with PCR tests [1]. The diagnosis of M. marinum infection can be difficult because of nonspecific and sometimes subtle clinical presentations, coalesced with inadequate biopsy and culture techniques. To confirm a suspected diagnosis of M. marinum infection, lesional tissue samples should be sent for histopathological analysis, microbiological culture, and polymerase chain reaction (PCR). Although PCR cannot distinguish between M. marinum and M. ulcerans, it may be used in conjunction with microbiological culture to increase diagnostic yield [2]. Furthermore, as highlighted in our case, sufficient tissue for analysis is a critical feature in isolating the causative organism. The antigens used in QFT are early secretory antigenic target-6 (ESAT-6) and the 10-kDa culture filtrate protein (CFP-10), both present in MTB and select non-tuberculous mycobacterioses including M. marinum, M. kansasii, and M. szulgai [3]. Immunocompromised patients may yield indeterminate interferon gamma release assay (IGRA) results due to failure of the internal positive control [1]. Lu and colleagues conducted a single-centre retrospective study in Northern California and found that the overall specificity of QFT in 73 NTM patients without risk factors for latent MTB infection was 94.4% (67/71; 95% CI: 89.1, 99.7) [3]. The specificity of QFT in NTM infection decreased to 76.1% when including patients with risk factors for MTB (67/88; 95% CI: 67.2–85.0) [3]. Hermansen et al. reported a pooled positivity rate of 59% QFT in NTM infections (n = 58) sharing ESAT-6 and CFP-10 [4]. Emerging studies are evaluating the role of novel NTM-IGRA assays in paediatric patients presenting with cervicofacial lymphadenitis. Potentially, these tools could be adapted for broader application across a range of mycobacterial infections in the coming years [5]. Our case expands the existing literature, further emphasising the importance of repeat tissue cultures and consideration of QFT when clinical suspicion for atypical mycobacterial infection remains high. We would like to thank the Department of Dermatology and Department of Infectious Disease at the Sunshine Coast University Hospital for their contributions. No external funding was received for this case report. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.