NTM infection is caused by generally free-living organisms that are ubiquitous in the environment . With the development of new microbiological methods, NTM infection in human diseases has become increasingly recognized and reported . M. avium complex and M. kansasii are believed to be the most common species , which is in accordance with our literature review results. On the one hand, NTM infection, especially disseminated NTM infection, is usually observed in patients with immunosuppressive conditions ; on the other hand, NTM infection can trigger HPS, a strong and uncontrolled immune response. Our literature review found 11 cases (including ours) in total indicating that the correlation is still rarely reported, and all cases were reported after 2010. However, secondary HPS is often associated with intracellular bacteria that induce classical Th1 immune responses, which, in animal models, are needed for the control of tuberculosis infection . This might also be the reason why NTM infection can cause HPS.
Most of the reported patients, including ours, had disseminated NTM infection. All patients except ours had known underlying immune-compromised conditions. Our initial evaluation of the patient’s immune state showed that the counts of B cells, T cells and NK cells were all decreased, while serum immunoglobulin levels were within normal ranges. After treatment, the patient’s B cell, T cell and NK cell counts gradually rose. Thus, we doubt the decreases in the patient’s lymphocytes and NK cells might be the result, rather than the cause, of her NTM infection. However, we cannot rule out the possibility that our patient might have undiscovered immunosuppressive conditions. Interestingly, case 2 was found to have advanced femoral sarcoma 5 months after being diagnosed with NTM infection and HPS. However, our patient was lost to follow-up 6 months later, and a more thorough investigation of possible underlying diseases, for example, malignancy, was not performed. As mentioned before, serum testing for interferon-γ autoantibody was not available in our hospital until recently. Thus, we were not able to verify our suspicions before the patient was discharged and then lost to follow-up. Therefore, it is recommended that patients who are diagnosed with NTM infection complicated by HPS are carefully investigated to determine possible concomitant immune-compromised conditions.
M. intracellulare was grown from both the blood and cervical lymph node biopsy tissue cultures of our patient. Her chest CT scan also revealed bilateral nodules and right pleural effusion, indicating possible pulmonary involvement, even though no pathogens were successfully grown from the patient’s sputum. No other focus of NTM involvement was found. M. intracellulare is reported to exist naturally in the environment, and the lung is the most common organ involved in M. intracellulare infection. Thus, we suspect that the port of entry of the mycobacteraemia might be from the respiratory tract, as is usually seen in patients with disseminated M. intracellulare infection. All patients reported constitutional symptoms as major complaints, which was in accordance with the fact that most cases were disseminated and lacked specific localized symptoms. In the majority of patients, HPS was suspected and diagnosed before NTM infection was detected and speciated. Interestingly, nearly half of the patients were found to have granuloma from bone marrow biopsy, which Is usually a routine examination when HPS is suspected. This biopsy finding could often be revealed earlier than the culture result, making it a promising positive predictor of disseminated mycobacterial (TB  or NTM) infection as the cause of HPS. In immunocompromised patients, HPS plus granuloma from bone marrow biopsy might justify a more thorough investigation and suspicion of possible mycobacterial infection.
Although treatment varied considerably, especially for HPS, the overall prognoses of NTM infection complicated with HPS seemed promising. Eight out of 11 patients recovered after treatment, and the correct diagnosis of NTM infection as the cause of HPS instead of ALL relapse even prevented haematopoietic stem cell transplantation in 1 patient, further indicating the importance of timely diagnosis of NTM infection complicated with HPS and starting treatment as soon as possible.
In conclusion, NTM infection is a rare cause of secondary HPS. Here, we report a 21-year-old female with disseminated M. intracellulare infection complicated by HPS who was successfully treated with antibiotics and corticosteroid. We reviewed relevant publications of NTM infection with HPS. Most reported NTM-related cases were caused by disseminated infection. Lack of localized symptoms might add to the difficulty involved in making the right diagnosis. While it usually takes time to obtain tissue or blood culture results, granuloma in a bone marrow biopsy might be an early indicator of possible mycobacterial infection. Although treatments varied, when patients were treated in a timely manner with antibiotics and anti-inflammation therapy, the overall prognosis of NTM-related HPS was promising.