We experienced the case of a patient who presented different clinical courses of lung lesions with cavitation due to IE-related SPE in the right lung and IPA in the left lung. Because the left lung nodule caused by IPA emerged 2 weeks after the diagnosis of IE, it was initially suspected to be a SPE caused by IE. After treatment with vancomycin, a blood culture test turned negative and the nodule in the right lung lobe was diminished. On the other hand, the nodule in the left lung lobe showed rapid growth, along with elevation of serum (1–3)-β-d-glucan and galactomannan antigen. Based on the different clinical courses of the nodules in the right and left lung, and the laboratory findings, we considered that the right lung lesion was associated with SPE and lung abscess secondary to IE and that the left lung nodule was caused by IPA. Indeed, autopsy revealed Groccott staining-positive aspergillus in the left lung, but not in the right lung. Although similar lung lesions with cavitation were observed in both the right and left lungs, the different transition of CT images helped us to estimate the etiology of the lung lesions; this was confirmed by autopsy. This case suggests that clinicians should consider the possibility that heterogeneous diseases may occur within the lungs, an assumption based on Hickam’s dictum .
When we see a nodule with cavitation, various differential diagnoses should be considered, including lung abscess, lung cancer, pulmonary tuberculosis, and IPA. IPA represents a critical condition, in which delayed treatment leads to increase mortality; however, it is difficult to diagnose at an early stage. The halo sign is a characteristic finding associated with IPA. Greene et al. reported that approximately 60% of IPA patients presented with a halo sign, although the majority of patients in that study had hematological immunosuppressive conditions, in contrast to our patient . The halo sign is pathophysiologically characterized as a nodule of angioinvasive aspergillosis with infarction and coagulative necrosis surrounded by alveolar hemorrhage, which are reported to be imaging features of IPA . Furthermore, the presence of the halo sign was reported to be associate with a significantly better response to antifungal treatment and survival . Other than the halo sign, micronodules, multiple nodules (> 10), and pleural effusion are other imaging features of IPA [3, 9, 10]. On the other hand, SPE contains pathogens that are embolized to the pulmonary artery and which cause focal lung abscess. Typical imaging features of SPE include multiple peripheral nodules in both lungs, cavitation, pleural effusion, and the halo sign [5, 6, 11, 12]. Notably, previous studies—with the exception of a study by Chou et al.—have not comprehensively described the association between SPE and the halo sign . In our case, the IPA in the left upper lobe showed the halo sign, whereas the SPE in the right lobe did not. Although it is not conclusive whether the halo sign is a useful finding for discriminating between IPA and SPE, these two diseases share a number of similar CT features.
IPA is a rare complication in patients with end-stage kidney disease (ESKD). IPA usually occurs in immunocompromised patients, such as those with hematologic malignancy, allogeneic bone marrow transplantation, solid organ transplantation, and late-stage HIV infection . Prolonged and high-dose corticosteroid therapy is an established risk factor for the development of IPA . Some previous cases of IPA with ESKD in patients other than kidney transplant recipients have been reported [15,16,17,18,19]. Most of these IPA cases with ESKD had classical risk factors, such as diabetes or hematologic malignancy [15,16,17]. Of note, a recent systematic review identified that the most frequently reported baseline clinical factor associated with poor outcomes was renal failure . Careful monitoring for IPA is needed when lung nodules are observed in patients with ESKD or kidney disease, especially those who have classical risk factors for IPA. It would also be important to assess whether the dose and duration of immunosuppressive therapy can be reduced.
The present patient’s serum was negative for (1–3)-β-d-glucan and galactomannan antigen at the time of the diagnosis with IE. These tests turned positive at the latter stage. As the diagnosis of IPA was delayed, the patient did not receive an adequate course of antifungal therapy in time before his death. For the diagnosis of patients at risk of IPA, a galactomannan antigen test shows higher sensitivity and specificity when applied to bronchoalveolar lavage samples than serum samples [21, 22]. Unfortunately, bronchoscopy could not be performed in this case due to the unfavorable status. The performance of a galactomannan antigen test using bronchoalveolar lavage samples would be useful for making a proper and earlier diagnosis and facilitate the initiation of antifungal therapy.
In conclusion, we experienced a case with concurrent IPA and IE-associated SPE, which both presented nodular lung lesions with cavitation, in a diabetic patient under hemodialysis with high-dose corticosteroid therapy. This case indicated that different causes may result in lung lesions with similar features. The different transition of the CT images of the lung lesions suggested that heterogeneous etiologies were involved. IPA is an infectious disease with a very poor prognosis and is associated with high mortality when it occurs in an immunocompromised host with or without classical risk factors. Thus, we should always consider the development of IPA and optimize immunosuppressive therapy of patients with risk factors for IPA.