Patients with GPA are typically treated with initial immunosuppressive therapy (commonly cyclophosphamide and glucocorticoids) followed by maintenance therapy with azathioprine or methotrexate, typically for 12–18 months. However, relapses are common, occurring on average 8–9 months after ceasing immunosuppressive therapy.
Infections have been hypothesized to trigger some disease flares by inducing expression of the ANCA antigens (PR3 and MPO) on the surface of circulating neutrophils. This can, in the presence of ANCA, lead to neutrophil degranulation, the release of oxygen radicals, and vascular injury .
A recent study comparing cyclophosphamide with rituximab for induction therapy concluded that the rate of remission induction at six months was significantly higher with rituximab (67 versus 42%). There is however no conclusive evidence that rituximab is superior to cyclophosphamide although subgroup analysis raises the possibility that rituximab may be optimal therapy for patients with relapsing disease .
Pulmonary fibrosis has been rarely reported in patients with vasculitis and typically with active disease rather than after remission . Additionally, substantial tissue fibrosis has been reported from kidney biopsies of patients with other ANCA associated disease . ANCA antigens have a number of bioeffects and are potent activators of latent TGF-β  which is known to promote fibrogenesis . The binding of circulating ANCA results in neutrophil degranulation and the release of reactive oxygen species which have been suggested may lead to subsequent injury and consequent fibrosis .
Although pulmonary fibrosis is a well-recognised complication of M. tuberculosis infections, we could find no case reports of this complicating M. abscessus lung disease. The isolation of M. abscessus may represent infection or colonization. However this gentleman had a short history or progressive respiratory symptoms and repeated isolation of mycobacteria from cultures which raises the likelihood of indolent disease . Histological evidence to prove invasive disease may be helpful but was not done. Additionally, he was seen by our infectious diseases specialist team who felt that he likely had true infection warranting treatment.
Pulmonary fibrosis has been occasionally reported to be associated with cyclophosphamide therapy . Hadjinicolau et al.,  recently conducted a literature review to identify non-infectious pulmonary complications associated with the newer biologic agents (rituximab, certolizumab, golimumab, tocilizumab and abatacept) used for the treatment of rheumatic conditions. Interstitial lung disease, idiopathic pulmonary fibrosis, allergic pneumonitis, and culture-negative pneumonia have been reported.
Our patient developed progressive dyspnea shortly after completing induction therapy with cyclophosphamide followed by rituximab, towards the end of the treatment of his M. abscessus infection. Although a chest x-ray and computed tomography scans showed an improvement in the radiological appearances of his lungs, there was a marked deterioration in his FEVI, PEF and FVC suggesting both obstructive and restrictive lung disease. Bronchoscopic evaluation showed pulmonary fibrosis with arrears of significant narrowing.
Ototoxicity was an unfortunate consequence of both his GPA and prolonged treatment with amikacin. Fortunately, cochlear implants may be used in this instance and have been gaining popularity since they were first used 50 years ago for treating sensorineural hearing loss. They are surgically implanted prostheses that use electrical stimulation to provide hearing. Concerns about the ototoxicity of amikacin have led to small but successful trials of aerosolized amikacin in M. avium intracellulare pulmonary infections . Unfortunately, the efficacy of this mode of administration in M. abscessus infections remains unknown.
The presence of Aspergillus spp. in sputum has been shown to be associated with the isolation of non-tuberculous mycobacteria in a study in involving patients with cystic fibrosis (66.7% vs. 21.5% of controls) in sputum samples . Interestingly our patient had Aspergillus sp isolated from his sputum on two occasions during the treatment of his M. abscessus infection. It has been suggested that the strong association between infection with NTM and Aspergillus spp. may reflect the severity of the pulmonary disease or that these organisms may create favorable conditions for the co-colonization such as by altering mucociliary clearance .