Mycobacterium shinjukuense pulmonary disease in a young woman: a case report and literature review

Abstract

Background

Mycobacterium shinjukuense is a rare type of non-tuberculous mycobacterium (NTM) first reported in Japan. Reported cases of Mycobacterium shinjukuense pulmonary diseases are rare where hosts exhibited apparent risk factors for NTM infection. No consensus has been made on its treatment regimen.

Case presentation

We report a case of Mycobacterium shinjukuense pulmonary disease in a previously healthy young woman presented as focal bronchiectasis and nodules. The diagnosis was established with 16S rRNA sequencing on bronchoalveolar lavage fluid mycobacterium culture. The patient was successfully treated with a thrice-a-week regimen of azithromycin, isoniazid and rifampicin. Whole-exome sequencing revealed mutations in TNFRSF13B and TLR2.

Conclusion

The presence of Mycobacterium shinjukuense pulmonary disease was confirmed in China. Macrolide, rifampicin and isoniazid was effective in treatment of Mycobacterium shinjukuense pulmonary disease. Genetic susceptibility to NTM should be considered in young patients without apparent risk factors

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-026-13446-9.

Introduction

Non-tuberculous mycobacterium (NTM) represents a group of opportunistic pathogens that causes various infections. The most frequent form of NTM infection is NTM pulmonary disease (NTM-PD). Although Mycobacterium avium complex (MAC) is the main species causing NTM-PD, many rare NTM species are also occasionally reported [1]. Mycobacterium shinjukuense (M. shinjukuense) was firstly identified in Japan in 2011 [2]. 20 cases were reported since then, most of which were identified in Japan (18/20) and complicated with advanced age, structural lung disease or compromised immunity. No consensus on treatment of M. shinjukuense has been made. Standard regimen for MAC (macrolide, rifampicin, and ethambutol) was effective in several cases including cavitating lesion [3]. Here, we report a case of M. shinjukuense pulmonary disease in a previously healthy young woman and conduct a comprehensive review on related literature.

Presentation

A 33-year-old woman with abnormal lung opacities presented to the department of pulmonary and critical care medicine in October 2023. She reported no history of chronic pulmonary disease, diabetes, autoimmunological disorder, immunosuppressive medications or travelling abroad. She underwent auricle reconstruction with intercostal cartilage at the age of 5. Computed tomography (CT) of chest revealed bronchiectasis and nodules in right middle lobe (Fig. 1A-B). She was asymptomatic with normal vital signs. Laboratory analyses including blood cell count, C-reactive protein (CRP), coagulation, erythrocyte sedimentation rate (ESR) and liver function and kidney function were within normal range. Blood interferon-gamma release assay (IGRA) (QuantiFERON-TB Gold Plus, QIAGEN, Venlo, Netherlands) was negative. She subsequently underwent bronchoscopy and bronchoalveolar lavage (BAL). As acid-fast smear (AFS), GeneXpert MTB/RIF (Cephid, CA, USA) (GeneXpert), 1-3-𝛽-G-glucan and galactomannan tests, and bacterial culture on bronchoalveolar lavage fluid (BALF) all returned negative, the patient was discharged without further medical intervention. However, mycobacterium culture (BACTEC MGIT 960, BD, MD, USA) detected NTM with a time to positivity (TTP) of 42 days. The NTM strain was identified as M. shinjukuense with 16S rRNA sequencing. Although the patient fulfilled the diagnosis criteria for NTM pulmonary disease in ATS/ERS/ESCMID/IDSA 2020 guidelines, due to the asymptomatic status of the disease, no medical treatment was initiated, and the patient was followed up closely. In December 2024, progressive bronchiectasis and infiltration were identified with chest CT scan (Fig. 1C-D). Her laboratory analysis remained normal. As we did not find any apparent risk factors for NTM infection, a whole exome sequencing (WES) was conducted with peripheral blood. Mutations in TNFRSF13B [NM_012452.2:c.306 C > A (p.Tyr102*)] [PVS1 + PM2 according to American College of Medical Genetics (ACMG) guidelines] and TLR2 [NM_003264.3:c.1318T > C(p.Tyr440His)] (PM2 according to ACMG guidelines) were detected with whole exome sequencing [4]. Although TNFRSF13B mutation is potentially associated with common variable immunodeficiency (OMIM: 240500) and immunoglobulin A deficiency (OMIM: 609529), her immunoglobulin concentrations were normal. TLR2 mutation is related with susceptibility to mycobacterium infection (OMIM: 607948). As drug susceptibility test for slow-growing NTM was not implemented in our center, we referred to regimen in previous reports, and designed a thrice-weekly oral regimen consisted of azithromycin 500 mg, rifampicin 450 mg, and ethambutol 1500 mg with a duration of 15 months³. However, as the patient expressed concern for retrobulbar neuritis, we substituted ethambutol with isoniazid 300 mg thrice a week. The patient was followed-up monthly and no treatment-associated liver injury was detected. Subsequent CT scan at the end of month 10 of treatment showed resolution of nodules and right middle lobe infiltrate (Fig. 1E-F). The patient was unable to produce spontaneous or induced sputum throughout the course of treatment and refused a repeat bronchoalveolar lavage to evaluate for microbiological status.

Fig. 1.

Chest computed tomography before and after treatment. A-B Baseline computed tomography showing nodules and bronchiectasis in the right S4 in September 2023. C-D Computed tomography showing progressive nodules and bronchiectasis in the right S4 in December 2024. E-F High-resolution computed tomography showing resolution of nodules after 10 months of treatment

Discussion and conclusion

Since the discovery of M. shinjukuense, cases of clinical isolation were mostly reported in Japan (Supplementary Table 1). Only one case of M. shinjukuense pulmonary disease was previously reported in China whose identification method was unclear [5]. The earliest isolation of M. shinjukuense of our center was in 2022 from sputum mycobacterium culture, however, the patient only completed one sputum culture before being lost to follow-up, hence we could not make an exact diagnosis of NTM-PD.

M. shinjukuense is one of the NTM strains genetically closest to Mycobacterium tuberculosis [6]. In previous reports, M. tuberculosis identification kit (TRCRapid M.TB rRNA identification kit, Tosoh Bioscience, Tokyo, Japan) failed to distinguish between M. shinjukuense and M. tuberculosis [7]. GeneXpert identifies M. tuberculosis based on the sequence of rpoB, which has higher specificity than 16S rRNA for TRCRapid kits [8, 9]. In this case, a negative GeneXpert MTB/RIF on BALF sample along with a negative IGRA effectively ruled out pulmonary tuberculosis. The diagnosis was eventually established through 16S rRNA sequencing on mycobacterium culture, which is also the primary identification method in other cases (10/20). However, culture-based identification exhibits a significantly long time-to-positive. Next-generation sequencing (NGS) enables rapid detection of rare pathogens and has been reported to successfully identify rare NTM infection [10]. But the consistency between NGS and culture-based identification methods like 16S rRNA, rpoB, or hsp65 sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) requires further comparison [11].

As an opportunistic environmental pathogen, the pathogenesis of NTM-PD depends largely on host factors including advanced age, previous NTM infection, malnutrition, tuberculosis cavity, diabetes and other immunocompromised conditions or immunodeficiency diseases. In this case, surgical alteration of costal cartilage could induce deficiency of airway clearance. Also, as the patient was relatively young without other underlying general risk factors, latent immunodeficient conditions should be considered. Variants in TNFRSF13B and TLR2 were detected through WES, although the patient did not fulfill the criteria for common variable immunodeficiency disease, those mutations could still have impact on anti-mycobacterium immunity [12, 13]. It is prompted that mutations in anti-NTM immunity pathway, even without manifestations of immunodeficiency, could still increase the risk for NTM infection.

The prognosis for M. shinjukuense pulmonary disease is generally favorable in previous reports. It usually presents a mild or even asymptomatic course with a low probability of recurrence (1/21). Oral regimen was effective even in patients with fibrocavitary disease, unlike most NTM species that require intravenous application or inhalation of antibiotics [14, 15]. M. shinjukuense is usually susceptible to common anti-tuberculosis drugs like isoniazid, ethambutol and rifampicin as well as macrolides. Macrolide-based treatment regimen was adapted in 9 out of 21 cases treated successfully. There were 9 cases where anti-tuberculosis regimen was used either according to drug susceptibility or continuing previous therapy after being misdiagnosed as PTB. However, the patient experienced recurrence in one case treated with a single macrolide [7]. This distinctive drug susceptibility profile could be attributed to its genetic similarity with M. tuberculosis [6]. However, it should be noted that strains with potentially induced macrolide resistance have been reported [16].

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Xiaojing Cui supervised the study and was responsible for patient follow-up, acquisition of funding and manuscript writing. Siwei Gu conducted clinical information collection, patient follow-up and manuscript writing. Chunlei Wang and Binghuai Lu was responsible for microorganism culture, isolation and identification and manuscript writing. All authors read and approved the manuscript.

Funding

This work received funding from Noncommunicable Chronic Diseases-National Science and Technology Major Project (Grant number 2024ZD0523003).

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Consent to participate

This case report was approved by the Ethics Committee of China-Japan Friendship Hospital. All procedures were conducted in accordance with institutional guidelines and relevant local regulations.

Consent for publication

Written informed consent for publication of clinical details and images was obtained from the patient. No identifiable personal information is included in this report.

Competing interests

The authors declare no competing interests.