Reverse Halo Sign in Pulmonary Mucormyosis
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1 QJM Advance Access published February 6, 2014 Reverse Halo Sign in Pulmonary Mucormyosis Yu-Hsiang Juan MD 1,2, Sachin S Saboo, MD FRCR 1, Yu-Ching Lin MD 2, James R. Conner MD, Ph.D 3, Francine L. Jacobson MD, Ph.D 1, Ashish Khandelwal, MD 1 1 Department of Radiology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA 2 Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan 3 Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA Short title: Reverse Halo Sign in Mucormycosis List of Acronyms: Pulmonary Mucormycosis (PM); Computerized Tomography (CT); Reverse Halo Sign (RHS); Acute Myeloid Leukemia (AML) Word Count: 576 words Correspondence: Ashish Khandelwal, MD Brigham and Women s Hospital 75 Francis Street Boston, MA-02115, The Author Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please journals.permissions@oup.com 1
2 Phone: Fax
3 Learning Point for Clinicians Invasive pulmonary mucormycosis (PM) is dreadful complication in immunosuppressed patients. Pulmonary mucormycosis is difficult to diagnose clinically and potential delay can occur while waiting for biopsy results. Computerized tomography (CT) is helpful in detecting the presence of PM with the help of typical radiological appearance resulting in early diagnosis and treatment. Introduction: Reverse Halo Sign (RHS), also called the atoll sign, was described as a rim of consolidation surrounding a center of ground-glass opacity on computed tomography (CT). 1,2 Although RHS was previously considered as non-specific sign for various disorders, recent study showed that it is a strong indicator of pulmonary mucormycosis (PM). 2,3 We present a case of PM with typical imaging presentation on CT which highlights the importance of RHS in predicting PM, especially in patients with acute leukemia and immunocompromised status. 2 Case presentation A 59-year-old man with history of acute myeloid leukemia (AML) in complete remission following chemotherapy presented with fever and cough. His physical examination was unremarkable except for scattered rhonchi in the right lung. CT scan revealed multiple nodular and consolidative opacities in the superior segment of the lower lobe of right lung, with central ground-glass opacity surrounded by peripheral consolidation, known as "reverse halo sign" (Fig. 1). In addition, reticulation is seen in 3
4 the center of the lesion (Fig. 1), and the wall measures 1.3 cm in maximum thickness with no evidence of associated pleural effusion or lymphadenopathy was seen. CT guided fine needle aspiration cytology revealed ribbon like broad hyphae with 90 degrees angle on Grocott's methenamine silver stain (400X) consistent with PM. After confirming the diagnosis, patient initially started on 5 mg/kg liposomal amphotericin B following which his creatinine raised to 1.58 milligrm per deciliter from a baseline of 0.7 milligram per deciliter. He was then started on oral posaconazole 400 mg after discontinuing amphotericin following which creatinine improved. On follow up, he was asymptomatic with reduction in size of consolidation on CT. Patient is currently awaiting bone marrow transplant for AML. Discussion Mucormycosis is an opportunistic fungal infection with the lung as the most common infectious site, and PM is increasingly identified among patients with acute leukemia and immunocompromised status. 2,4,5 RHS on CT may represent different disease entities depending on the immune condition of the patient; while cryptogenic organizing pneumonia is most common in immunocompetent patients, RHS is highly suggestive sign for PM in immunocompromised hosts. 1,3 PM is nearly 100% fatal if undiagnosed, and treatment is often delayed due to non-specific clinical symptoms and the time taken for pathologic proof. 2 Since both cryptogenic organizing pneumonia and PM can occur in immunocompromised host, early and accurate diagnosis of PM is important. 2 Marchiori et al. demonstrated that three signs can support the diagnosis of PM over crytogenic organizing pneumonia, including 4
5 the presence of reticulation in the center, thickness of the consolidated rim > 1 cm and the presence of pleural effusion. 3 Although pleural effusion is not present, our patient satisfied two of the criteria (wall thickness 1.3 cm and presence of reticulation), thus PM should be considered over cryptogenic organizing pneumonia. RHS is most commonly seen in the right upper lobe of lung, 1,6 and our patient exhibits similar location of PM in the superior segment of the right lower lobe. PM can be treated by medication alone or with combination of surgery, and Amphotericin B is the most effective regimen, followed by posaconazole and itraconazole. 1 Our patient started with Amphotericin B but later changed to posaconazole owing to deterioration of renal function. He successfully recovers uneventfully with reduction in size of consolidation on follow-up CT. Conclusion While pulmonary mucormycosis is difficult to diagnose clinically with potential delay while waiting for biopsy result, CT is beneficial in detecting the presence of PM and thus supporting early diagnosis and treatment of pulmonary mucormycosis. Funding source or Conflict of Interest: None Acknowledgement: None 5
6 References 1. Stewart JI, D'Alonzo GE, Ciccolella DE, Patel NB, Durra H, Clauss HE. Reverse halo sign on chest imaging in a renal transplant recipient. Transpl Infect Dis doi: /tid (Epub ahead of print). 2. Legouge C, Caillot D, Chretien ML, Lafon I, Ferrant E, Audia S, et al. The Reversed Halo Sign: Pathognomonic Pattern of Pulmonary Mucormycosis in Leukemic Patients With Neutropenia? Clin Infect Dis 2014 (Epub ahead of print). 3. Marchiori E, Marom EM, Zanetti G, Hochhegger B, Irion KL, Godoy MC. Reversed halo sign in invasive fungal infections: criteria for differentiation from organizing pneumonia. Chest 2012;142: Khandelwal A, Gupta P, Gupta A, Virmani V. Renal mucormycosis in aplastic anemia: a novel presentation. Int Urol Nephrol 2013;45: Carbone KM, Pennington LR, Gimenez LF, Burrow CR, Watson AJ. Mucormycosis in renal transplant patients--a report of two cases and review of the literature. Q J Med 1985;57: Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis: the last 30 years. Arch Intern Med 1999;159:
7 Figure Legend Figure 1. Computed tomography of the chest with axial CT image in lung window shows central ground-glass opacity and reticulations surrounded by peripheral rimconsolidation, giving reverse halo appearance with maximum wall thickness of 1.3 cm. 7
8 70x63mm (300 x 300 DPI)
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