NTM represents over 190 species and subspecies, some of which are conditional pathogens. M. Colombiense is a novel recognized member of Mycobacterium Avium Complex (MAC), the most common slow-growing NTM . Infection with M. colombiense is very rare and has been only reported in a few cases. However, in view of the inability of prior molecular methods to discriminate the species diversity comprising MAC, the real prevalence of M. Colombiense may have been underestimated [12, 13]. According to prior studies, M. colombiense is prone to cause pulmonary disease and lymphadenopathy, rarely affecting skin and bone [12, 13]. To our knowledge, this is the first report of disseminated M. colombiense infection presented with pulmonary mass, pathological fracture and dermapostasis.
Pulmonary MAC infection is typically insidious, with chronic cough usually productive of purulent sputum and occasional hemoptysis. Besides typical upper-lobe fibrocavitary or nodular bronchiectatic presentation on pulmonary CT, mass or mass-like consolidation mimicking cancer, as illustrated in this case, can also be encountered. As previously reported, the incidence of NTM pulmonary disease mimicking malignancy is 3.6%, which represents a small but meaningful ratio because the consequences of misdiagnosis can be lethal . Microbiological evidence is critical for definitive diagnosis of NTM infection. However, conventional acid-fast staining cannot distinguish NTM from M. tuberculosis while culture is time-consuming and sometimes shows false-negative results. Recently, mNGS has been increasingly applied in detecting microorganisms due to its advantages of accurate and rapid species-level pathogen identification . It also provided important clue for considering NTM disease in our case, suggesting its potential value in NTM diagnosis.
Skin involvement is common in disseminated MAC infection. The presentation of cutaneous lesions may vary greatly from patient to patient, including panniculitis, papules, nodules, granulomas, pustules and ulcerations. Lesions in multiple stages of development may co-exist. Morphological features are usually non-specific and skin biopsy is the gold standard for diagnosis . Data regarding cutaneous disease in M. Colombiense infection is scarce and only one case has been reported before. The patient presented with an impetiginous rash with hard exfoliation on his cranial-facial region, different from the morphology and distribution of cutaneous lesions in our patient . Further investigation is needed to identify the pattern of dermopathy in patients with M. Colombiense infection.
NTM infection of bone leading to osteolytic lesions is a rare condition and can be easily misdiagnosed as M. tuberculosis infection. Different from M. tuberculosis which primarily affects load-bearing joints such as the thoracolumbar spine, hips, and knees, NTM can affect any bone of the body, often presenting as multiple bone involvement. The most frequently involved sites include the vertebrae, sternum, clavicle, and ribs, followed by the femur and ilium. Pathological fracture has been previously reported in several dNTM cases, mainly related to M. abscessus and M. intracellulare, which is also a member of MAC [18, 19]. Furthermore, IFN-γ is important in the maintenance of the balance between osteoclasts and osteoblasts . Therefore, the defective IFN-γ signaling may also contribute to the pathogenesis of osteolytic lesions in our patient.
As a typical opportunistic pathogen, NTM usually invades immunocompromised hosts. Identifying these underlying reasons of NTM infections is always crucial as many of them are modifiable and neglecting them can lead to unfavorable outcomes . AOID in patients with neutralizing anti-IFN-γ autoantibodies is an important risk factor of NTM infection. This syndrome appeared for the first time in 2004 and has become an emerging medical issue recently, particularly in Southeast Asia . The exact etiology of AOID remains elusive. Nearly all the patients to date are of Asian descent, implicating the involvement of a common genetic factor . According to a previous study, unexpectedly high frequencies of two HLA alleles, DRB1*16:02 and DQB1*05:02, were found in AOID patients, suggesting a potential association between HLA polymorphism and the development of anti-IFN-γ autoantibodies . Patients with AOID are susceptible to severe and refractory infections caused by opportunistic pathogens, especially NTM . As presented in this case, reactivation of varicella-zoster virus infection is also common in AOID hosts. Based on a prior report, 71% AOID patients suffered from herpes zoster . The diagnosis of this syndrome can be established in patients with infections caused by unusual intracellular pathogens and positive for the anti-IFN-γ autoantibody. According to prior reports in Taiwan and Thailand, the prevalence of AOID can be extremely high in otherwise healthy patients with dNTM . However, as a rare immunodeficiency disorder primarily affecting elderly patients with an insidious onset and indolent clinical course, AOID can be easily missed. Additionally, the lack of distinctive clinical manifestations and involvement of specific testing not routinely available make its early recognition even more challenging. An average diagnostic delay of 1.6 years has been reported recently . AOID should thus be routinely screened when patients get the first episode of NTM infection, particularly when other risk factors are excluded [5, 20].
Frequent recurrences of infection are common in AOID patients despite prolonged anti-infective therapy and good patient compliance . Therefore, treatment targeting the underlying condition is necessary to achieve long-term control of infections, but currently no standardized approach has been widely accepted. While immunosuppressive therapy seems counterintuitive in patients with disseminated infections, B-cell-depleting therapy with rituximab has shown promising results in several small studies [10, 21]. Consistent to these prior reports, a favorable response to rituximab was observed in our case. Future studies with a large sample size and longer follow-up period are warranted to further investigate the effectiveness and safety of rituximab in treatment of dNTM associated with AOID.
In conclusion, we present an intriguing case of dNTM infection manifested with pulmonary mass, pathological fracture and skin abscesses mimicking metastatic malignancy in a patient with AOID caused by abnormal formation of anti-IFN-γ autoantibodies. Considering the substantial challenge in early diagnosis of AOID, it is crucial to increase awareness of this syndrome among clinicians. Additional studies are warranted to provide a better understanding of the pathogenesis, clinical course and treatment strategies of this disease.