Clinical diagnosis
Case 253
【Discussion】
Non tuberculous mycobacteria (NTM) is termed for not causing tuberculosis and leprosy. NTM is present at everywhere in the daily life including soils and water pipes, which indicates that everyone contacts or inhales NTM. The healthy person can drive NTM invasion away by immune potency. When immune potency becomes weak, NTM can infect to human. NTM occurs in females after menopause probably because their immune potency changes or becomes weak (1-4)). Our two patients were female aged 77 and 89. The progress of this disease gradually advances and the prognosis is not so poor as tuberculosis. However, there are some patients with NTM with progressive and poor prognosis.
On chest CT, NTM occurs often at right middle lobe and left lingular segment. Middle lobe lingular syndrome once termed might be caused by NTM. It largely categorizes into nodular-bronchiectasis type, fibro-cavitary type and mixed type (1). Nodules appear at the center in lobules.
The mechanism of forming nodule is as follows (5): The inhaled NTM reaches to peripheral pulmonary parenchyma, macrophages and killer cells phagocyte NTM, they can phagocyte NTM but cannot digest or kill NTM, followed by viable NTM appears after phagocytes die. Then, another healthy macrophages phagocyte bodies fragments and NTM. However, NTM survives and proliferate. Then, the more macrophages and lymphocytes for antibody production accumulate surrounding NTM (5). Necrotic fragments enlarge because of macrophages being unable to dispose of, inducing caseous necrosis. NTM can survive and proliferate in the caseous necrosis apart from macrophages attack. When caseous necrosis with NTM was excreted via bronchial trees, remaining formation of cavity (1, 5). NTM survives in the surrounding of cavity. Then, NTM can move other pulmonary area via bronchial tract draining cavity. The cavity formation implies the advancement of the disease, which indicates triumph of NTM, inducing poor prognosis.
For drug sensitivity test, clarithromycin CAM is only positive for NTM. Rifampin RFP and ethambutol EB are not positive but exert an effect as companion drugs with CAM (1). The problems of companion drugs are side effects. RFP side effects most often appear: interstitial pneumonia, liver disorder, renal disorder and leukopenia, while EB causes optic nerve disorder, narrow visible field. Then, to avoid side effects of the companion drugs, CAM alone is prescribed for the first week, CAM and EB are done for the second week followed by CAM, EB and RFP for the third week (1).
On July 8 2020, Japan NTM guideline reported Azithromycin (AZM) is recommended to be replaced in taking place of CAM as the first selective macrolide antibiotics that be effective on inhibition of intracellular protein production of bacillus. It is because that AZM is the same potency of effectiveness as CAM on NTM with the less volume, inducing less side effects and easily taking of one time per day.
【Summary】
We presented two patients with nontuberculous mycobacterium. Chest CT depict bronchiectasis and nodules mainly in the right middle lobe and left lingular segment. It was borne in mind that minute nodules are formed of NTM surrounded by macrophages and lymphocytes, while large nodules are formed of caseous necrosis implying dead macrophages, viable NTM, macrophages and lymphocytes. Macrophages can phagocyte NTM but they cannot kill NTM probably due to lowering immunity potency. When caseous necrosis. When it is excreted via bronchus, it forms cavity. NTM can survive in the caseous necrosis because immune cells are difficult to enter the caseous necrosis and NTM move to the other pulmonary area. Cavity formation implies the victory of NTM because NTM gets a chance move to other pulmonary area. As treatment medicines, clarithromycin CAM plays a leading role and Rifampin RFP and ethambutol EB are companion drugs which enhance the effect of CAM on NTM. Three medicines of CAM, RFP and EB are standard combination to be prescribed for treating NTM. Azithromycin (AZM) is recommended to be replaced in taking place of CAM as the first selective macrolide antibiotics because of less side effects and ease taking once per day.
【References】
1.Sasaki Y “Kekkaku, hikekkaku kousannkinnsyouwo nitijousinnryoudemiru” Youdosya in Japanese. https://www.kinokuniya.co.jp/f/dsg-01-9784758118026
2.Ryu YJ, et al. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives. Tuberc Respir Dis (Seoul). 2016 Apr; 79(2): 74–84
3.Kendall BA, Winthrop KL. Update on the epidemiology of pulmonary nontuberculous mycobacterial infections. Semin Respir Crit Care Med. 2013;34:87–94.
4.Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med. 2015;36:13–34.
5.Prasla Z, et al. Macrophage Signaling Pathways in Pulmonary Nontuberculous Mycobacteria Infections.American Journal of Respiratory Cell and Molecular Biology, 01 Aug 2020, 63(2):144-151
2021.12.21