Comorbidity of sarcoidosis and non-tuberculosis mycobacteria: a case description

Introduction

Nontuberculous mycobacteria (NTM) is a general term for a large mycobacterial group other than Mycobacterium tuberculosis and Mycobacterium leprae (1). NTM-induced lung lesions are referred to as NTM-pulmonary disease (NTM-PD) (2). Sarcoidosis is a noncaseating necrotizing epithelial cell granulomatous inflammatory disease that primarily invades the lung parenchyma and involves multiple body organs, such as the lymph nodes and skin (3). NTM-PD and pulmonary sarcoidosis rarely occur together, and thus far, no clinical reports of NTM-PD combined with pulmonary sarcoidosis have been reported. We treated a patient diagnosed with NTM-PD complicated with pulmonary sarcoidosis. To improve clinicians’ understanding of the disease, we report the diagnosis and treatment of the condition and its efficacy.

Case description

A 45-year-old woman was admitted to a local hospital for persistent cough and sputum lasting over 1 year that had aggravated 1 month prior to her hospital visit. She underwent chest plain and contrast-enhanced computed tomography (CT) (Figure 1). On chest CT, nodular exudate shadows were noted in both upper lungs, and multiple lymph node enlargement was evident in the mediastinum. Tuberculosis could not be ruled out. Therefore, the patient was admitted to The Second Hospital of Nanjing. Following admission, no abnormalities were noted in the blood routine, urine routine, stool routine, C-reactive protein level, coagulation function, or biochemical examination. The serum angiotensin-converting enzyme (SACE) level was 75.5 U/L (normal reference value: 5–52 U/L). The interferon-gamma release assay was negative. Electrocardiography showed a sinus rhythm, and echocardiography was normal. Electronic bronchoscopy revealed no obvious abnormalities in the trachea, bronchi, or lobe bronchi. Lavage was performed in the posterior segment of the upper lobe of the right lung. The lavage solution Gene Xpert MTB/RIF (Xpert) was negative for the tuberculosis smear. Metagenomic next-generation sequencing (mNGS) of the lavage fluid revealed Mycobacterium abscessus with sequence number 1,699. NTM were noted in the lavage fluid used for the tuberculosis culture. B-ultrasound indicated bilateral cervical lymphadenopathy, and right cervical lymph node biopsy demonstrated non-necrotizing epithelioid granulomatous inflammation (Figure 2). Both acid-fast staining and periodic acid-Schiff staining were negative. To treated M. abscessus complicated with stage II pulmonary sarcoidosis, the patient was administered 0.5 g of clarithromycin (once a day) plus 0.6 g of linezolid (once a day) orally, 0.4 g of amikacin (once a day) intramuscularly, and 30 mg of prednisone (once a day) orally. After 2 months of treatment, chest CT (Figure 3) revealed that the mediastinal lymph nodes were significantly reduced. The lung lesions were obviously absorbed, and the efficacy was significant. Anti-NTM-PD therapy was continued, and the prednisone dose was gradually reduced.

Figure 1 Chest computed tomography imaging examination on December 21, 2023. (A,B) Nodular exudate shadows on both upper lungs. (C) Multiple lymph node enlargement in the mediastinum.

Figure 2 Pathological examination of lymph node biopsy in the right neck. Image of a nonnecrotic epithelioid granulomatous inflammation (hematoxylin and eosin staining, ×200). The black arrows indicate the nonnecrotic epithelioid granulomatous inflammation.

Figure 3 Chest computed tomography imaging examination on January 28, 2024. (A,B) Clearly absorbed nodular exudate shadows in both upper lungs. (C) Mediastinal lymph node reduction.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of the article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Globally, 2–160 per 100,000 people are affected by sarcoidosis (4). In China, detailed epidemiological data on sarcoidosis are lacking. The incidence of NTM is increasing worldwide. The annual incidence of NTM-PD in the United States increased from 3.13 to 4.73 per 100,000 persons from 2008 to 2015 (5). According to a 2021 survey of acid-fast smear-positive patients in 17 designated tuberculosis hospitals across China, NTM-PD accounted for 6.8% of the total patients surveyed (6). The increase in the NTM isolation rate in previous epidemiological surveys of tuberculosis also suggests an upward trend in NTM disease (7).

The etiology of sarcoidosis is unknown, but it is speculated that pathogen infection may be closely related to sarcoidosis occurrence. According to recent studies (8,9), the persistence of pathogens or their associated antigens in genetically susceptible patients, for reasons unknown, trigger a sustained adaptive immune response stimulated by certain environmental factors. This may be the cause of the formation of sarcoidosis granulomas. In one study, NTM were isolated from patients with sarcoidosis (10). Another study reported an association between sarcoidosis and mycobacteria, including both Mycobacterium tuberculosis and NTM (11). Additionally, the reverse blot hybridization test was used in one study to detect six cases of mycobacteria isolated from the tissues of nine patients with cutaneous sarcoidosis, two of whom had NTM-PD. No crossover was noted between the different mycobacteria (12), which also indicates that NTM may play a role in sarcoidosis. NTM is categorized as fast-growing and slow-growing types, among which M. abscessus is the most common strain of fast-growing mycobacteria and the second most common pathogen of NTM-PD (13).

The histopathology of sarcoidosis and NTM-PD involves granulomatous lesions. Granulomatous lung disease (GLD) is a heterogeneous group of diseases broadly classified as noninfectious and infectious. Sarcoidosis is the most common noninfectious granulomatous disease, with granulomatosis with polyangiitis, chronic beryllium disease, hypersensitivity pneumonitis, and drug- or tumor-induced sarcoid-like reactions being the other less common causes. M. tuberculosis is the most common cause of infectious GLD, especially in areas with high tuberculosis endemicity, and is followed by fungi, parasites, etc. (14). The potential link between M. abscessus and sarcoidosis cannot be ignored. The infection and invasion of M. abscessus may trigger the abnormal response of the human immune system through some mechanism and then promote the formation of granuloma (15). The possible pathogenesis may include an abnormal immune response or cytokine regulation imbalance. (I) In abnormal immune response, infection with M. abscessus may trigger an overreaction of the body’s immune system, resulting in the accumulation of immune cells in the lungs and other organs, forming granulomatous structures. (II) Studies have shown that certain cytokines play a key role in the pathogenesis of sarcoidosis. Infection with M. abscessus may affect the formation and progression of granuloma by regulating the expression of these cytokines. Because pathological changes associated with NTM-PD are similar to those associated with tuberculosis, the two diseases are pathologically indistinguishable (16). Therefore, to diagnose granulomatous lesions with pathological manifestations, details regarding the medical history, occupational history, and drug and allergen contact history must be queried, and culture and polymerase chain reaction detection of M. tuberculosis must be improved. If necessary, mNGS should be conducted to determine the basis for pathogenic infection.

In our case, the patient’s respiratory symptoms were predominantly cough and sputum. The clinical manifestations were nonspecific, and the elevated SACE level was suggestive of sarcoidosis. Chest CT revealed multiple nodular and cord-like, patchy hyperdense shadows along the bronchi, thickened bronchial vascular bundles in the lesion area, positive interface signs, and several enlarged mediastinal lymph nodes, consistent with the imaging characteristics of sarcoidosis (17). mNGS of the lavage fluid showed M. abscessus, and the subsequent culture results confirmed the presence of NTM. Cervical lymph node biopsy was performed, and the pathology indicated non-necrotizing epithelioid granulomas, consistent with the pathological features of sarcoidosis. The coexistence of NTM-PD (M. abscessus) with sarcoidosis was diagnosed on the basis of the patient’s clinical features presence of non-necrotizing granulomas on chest imaging, etiology, and tissue biopsy. Evidence of other causes of granulomas was lacking. Sarcoidosis involves a certain degree of self-healing, and the spontaneous remission rate of stage II pulmonary sarcoidosis can be 40–70% (18). Anti-sarcoidosis therapy can be initiated in patients with significant respiratory or systemic symptoms and progressive worsening of pulmonary lesions on chest CT. Oral corticosteroids are the core drugs used for sarcoidosis treatment (19). For patients with concomitant NTM-PD, anti-NTM-PD therapy can be initiated simultaneously. In this case, the patient’s symptoms of cough and sputum progressively worsened, and the imaging manifestations revealed multiple nodular, cord-like, patchy hyperdense shadows with lymphadenopathy, which fulfilled the indications for glucocorticoid therapy. Therefore, oral prednisone was administered on the basis of anti-NTM-PD therapy, and the clinical symptoms significantly improved in the subsequent follow-up. The chest CT revealed that the mediastinal lymph nodes were significantly reduced. The lung lesions were obviously absorbed, and the efficacy of treatment was deemed significant.

M. abscessus is considered the most pathogenic rapid-growing mycobacterium in humans, is not sensitive to many drugs, involves difficult-to-treat infection, and is associated with a poor prognosis (20). The pulmonary lesions of the patient in this case were mainly of lymphatic interstitial distribution and improved significantly in a short time, in similar fashion to sarcoidosis. However, there remained a number of lung lesions distributed along the airway, which is a manifestation similar to that of early M. abscessus infection, and the lung shadow also significantly improved after anti-M. abscessus treatment in a short time.

In summary, we encountered a rare case NTM-PD concurrent with pulmonary sarcoidosis. The patient exhibited good results after the administration of anti-NTM-PD therapy combined with glucocorticoids. We also analyzed the diagnosis and treatment of NTM-PD complicated with pulmonary sarcoidosis so as to improve the clinicians’ understanding of these coexisting conditions and offer experience and reference for clinical treatment.

Acknowledgments

Funding: This study was funded by the Jiangsu Commission of Health (No. M2021073).

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1207/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the patient for publication of the article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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