Strengths and Limitations of Imaging for Diagnosis of IFI

Dr Tan Ban Hock
Senior Consultant
Department of Infectious Diseases
Singapore General Hospital
Singapore

In the most recent iteration of the European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus, the clinical criteria for defining probable lower respiratory tract fungal disease are all radiologic.¹ They are based on the presence of 1 or more of the following signs on computed tomography (CT)¹:

• Dense, well-circumscribed lesions(s) with or without a halo sign;
• Air-crescent sign; or
• Cavity.

These criteria were developed more for research use rather than usual clinical practice, but they nonetheless provide potentially valuable guidance.

Halo sign

The CT halo sign indicates ground glass attenuation surrounding a pulmonary nodule.² It is caused by angioinvasion and tissue infarction, with surrounding hemorrhage.

The halo sign is not unique to invasive fungal infections (IFI), and can be caused by other pathologies, such as Wegener’s granulomatosis and Kaposi’s sarcoma.² However, in an autopsy-based study of neutropenic patients with hematologic malignancy, with or without invasive pulmonary aspergillosis (IPA), the halo sign appeared to be the most specific for IPA: it was evident in 13/17 IPA versus 0/31 non-IPA patients (p<0.0001).³

However, the halo sign is transient and therefore will not be visible on CT in all patients with IPA.⁴ Thus, early CT is valuable. Furthermore, the halo sign is prognostic: initiation of antifungal treatment based on identification of a halo is associated with significantly improved treatment response and survival.⁵

Air-crescent and reversed halo sign

In the context of IPA, an air-crescent sign requires no pre-existing cavity, and is caused by parenchymal cavitation.⁶ It typically occurs about 2 weeks after detection of the initial radiographic abnormality, and often coincides with white blood cell recovery.⁶

Meanwhile, a reversed halo sign may be an indicator of pulmonary mucormycosis, and detection may allow the early initiation of appropriate therapy. 

Overall, used appropriately and in context, lung CT remains a key pillar of the diagnostic process for IFI, particularly in neutropenic patients.

Highlights of the Medical Mycology Training Network Conference, August 5–6, 2017, Kuala Lumpur, Malaysia.

References

1. De Pauw B, et al. Clin Infect Dis 2008;46:1813-1821.
2. Lee YR, et al. Br J Radiol 2005;78:862-865.
3. Kami M, et al. Mycoses 2002;45:287-294.
4. Caillot D, et al. J Clin Oncol 2001;19:253-259.
5. Greene RE, et al. Clin Infect Dis 2007;44:373-379.
6. Walker CM, et al. AJR Am J Roentgenol 2014;202:479-492.
7. Legouge C, et al. Clin Infect Dis 2014;58:672-678.