Importance of the reversed halo sign for diagnosis of mucormycosis

We read with interest the Clinical Picture by Timothy Sullivan and Meenakshi Rona,1Sullivan T Rana M The reversed halo sign and mucormycosis.Lancet Infect Dis. 2019; 191379Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar who reported the case of a 62-year-old immunocompromised patient presenting on CT a pulmonary lesion with an appearance compatible with the reversed halo sign. A transbronchial biopsy was done, and the final diagnosis was mucormycosis. The authors reported that the reversed halo sign is a non-specific finding, and that given the broad range of diagnoses associated with it, biopsy is necessary to establish the correct diagnosis. By contrast, other authors2Caillot D Valot S Lafon I et al.Is it time to include CT "reverse halo sign" and qPCR targeting mucorales in serum to EORTC-MSG criteria for the diagnosis of pulmonary mucormycosis in leukemia patients?.Open Forum Infect Dis. 2016; 3ofw190Crossref PubMed Scopus (19) Google Scholar, 3Legouge C Caillot D Chrétien ML et al.The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia?.Clin Infect Dis. 2014; 58: 672-678Crossref PubMed Scopus (97) Google Scholar, 4Marchiori E Marom EM Zanetti G Hochhegger B Irion KL Godoy MCB Reversed halo sign in invasive fungal infections: criteria for differentiation from organizing pneumonia.Chest. 2012; 142: 1469-1473Summary Full Text Full Text PDF PubMed Scopus (37) Google Scholar have concluded that the reversed halo sign in immunocompromised patients is strongly suggestive of mucormycosis, and have even speculated about whether it is pathognomonic of this disease, especially in leukaemic patients with neutropenia.3Legouge C Caillot D Chrétien ML et al.The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia?.Clin Infect Dis. 2014; 58: 672-678Crossref PubMed Scopus (97) Google Scholar We do not believe that the reversed halo sign is a pathognomonic sign of mucormycosis; although this disease is the most common cause of the reversed halo sign in immunocompromised patients, we would like to emphasise that other pulmonary diseases, such as invasive aspergillosis, organising pneumonia, and tuberculosis, also need to be considered as possible causes of the reversed halo sign in this population. Publications in the past decade have shown the usefulness of some morphological characteristics of the reversed halo sign for differential diagnosis. For example, the presence of nodular walls or nodules inside the reversed halo sign were found to strongly favour the diagnosis of active pulmonary tuberculosis over organising pneumonia. Another study, which aimed to identify CT findings that differentiate the reversed halo sign caused by invasive fungal infections from that caused by organising pneumonia, showed that the presence of reticulation inside the reversed halo sign, with an outer consolidation rim greater than 1 cm thick, is strongly suggestive of invasive fungal infections, particularly mucormycosis.4Marchiori E Marom EM Zanetti G Hochhegger B Irion KL Godoy MCB Reversed halo sign in invasive fungal infections: criteria for differentiation from organizing pneumonia.Chest. 2012; 142: 1469-1473Summary Full Text Full Text PDF PubMed Scopus (37) Google Scholar This concept has been widely accepted and confirmed in the medical literature.5Bourcier J Heudes PM Morio F et al.Prevalence of the reversed halo sign in neutropenic patients compared with non-neutropenic patients: data from a single-centre study involving 27 patients with pulmonary mucormycosis (2003–2016).Mycoses. 2017; 60: 526-533Crossref PubMed Scopus (19) Google Scholar In conclusion, although the reversed halo sign is not pathognomonic of mucormycosis, careful analysis of its morphological characteristics might narrow differential diagnosis. Reticulation inside the reversed halo sign and a thick outer rim in an immunocompromised patient are strongly suggestive of mucormycosis. This conclusion is important because although definitive diagnosis should be biopsy based, the time from symptom onset to microbiological or histopathological assessment can be long. Thus, the presence of the reversed halo sign with these morphological characteristics should be sufficient for the early initiation of appropriate therapy, thereby improving outcome. We declare no competing interests. The reversed halo sign and mucormycosisA 62-year-old man with a history of uncomplicated kidney transplantation and diabetes mellitus presented 2 months after transplantation with 1 week of cough, right-sided chest pain, and shortness of breath. He denied sputum production, haemoptysis, or fevers. Immunosuppression consisted of oral tacrolimus 8 mg twice daily and oral mycophenolate mofetil 500 mg twice daily. Full-Text PDF