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Pulmonary Mucormycosis,History,A 64-year-old woman with a history of mantle cell lymphoma and stem cell transplantation 2.5 years earlier presented with cough and chest pain. She had received voriconazole prophylaxis, and she had cytopenia, recurrent graft-versus-host disease, and diabetes mellitus. Chest computed tomography (CT) was performed to assess the patients cough and chest pain.,The initial CT examination (Figs 1, 2) revealed a rounded consolidation with surrounding ground-glass opacity (GGO) (halo sign) in the anterior segment of the right upper lobe. The second CT examination (Figs 3, 4) revealed that the pulmonary opacity had increased in size and changed in morphology from a halo configuration to a reversed halo configuration (central GGO with surrounding irregular rim of consolidation). In addition, the consolidation and GGO extended to the pleura, resulting in pleural thickening (Figs 3, 4).,1,Initial axial noncontrast chest CT image of the right upper lobe. There is a focal area of consolidation in the anterior segment of the right upper lobe with surrounding GGO.,2,Initial coronal noncontrast chest CT image of the right upper lobe. There is a focal area of consolidation in the anterior segment of the right upper lobe with surrounding GGO.,3,Axial noncontrast chest CT image of the right upper lobe obtained 1 week after Figure 1. The previously demonstrated consolidation has increased in size. There is also new central GGO with a surrounding irregular rim of consolidation (reversed halo sign). In addition, the conglomerate consolidation and GGO have extended to the visceral pleura, resulting in pleural thickening.,4,Coronal noncontrast chest CT image of the right upper lobe obtained 1 week after Figure 2. The previously demonstrated consolidation has increased in size. There is also new central GGO with a surrounding irregular rim of consolidation (reversed halo sign). In addition, the conglomerate consolidation and GGO have extended to the visceral pleura, resulting in pleural thickening.,Partial opacification of the maxillary and ethmoid sinuses was visible on contrast materialenhanced CT images of the head obtained 5 days after the initial chest CT examination was performed 。 Frothy material in the sphenoid sinus was also seen (Fig 6). Subtle contrast enhancement was present along the left medial orbital wall and associated with destruction of the lamina papyracea and extraconal extension of inflammation (Fig 5).,5、6,Discussion,The reversed halo sign was first described in the setting of cryptogenic organizing pneumonia but is not specific to this disease . It also occurs in the setting of paracoccidioidomycosis, lymphomatoid granulomatosis, Wegener granulomatosis, and mucormycosis (25). In this patient, cryptogenic organizing pneumonia was unlikely, given the focality, dramatic growth, and location of the consolidation and GGO. Paracoccidioidomycosis was not considered, as the patient had not traveled to any endemic area (2). Also, lymphomatoid granulomatosis was unlikely because of the absence of the typical radiographic findings of multiple pulmonary nodules along the bronchovas-cular tree (3). Although this patient had upper airway inflammation and pulmonary disease consistent with Wegener granulomatosis, the typical radiographic findings of multiple pulmonary nodules with potential cavitation were not present. Furthermore, this patient did not have nephritis, which is present in over 80% of patients with Wegener granulomatosis (6).,Invasive aspergillosis was the initial consideration in this patient, given the halo sign on the initial CT images. However, the following factors favored a diagnosis of mucormycosis: diabetes, recent prophylaxis with voriconazole, concomitant sinusitis, and the reversed halo sign at follow-up CT,Mucormyocosis is infection by fungi in the class Zygomycetes, most commonly in the order Mucorales. Infection is usually caused by inhalation of spores; therefore, the paranasal sinuses and lungs are most commonly affected (9). Risk factors for infection include diabetes (especially in the setting of diabetic ketoacidosis), hematologic malignancy, stem cell or solid organ transplantation, immunosuppression, graft-versus-host disease, and desferoxamine therapy (10). The majority of these risk factors act by imparing neutrophil function (7).,A high index of suspicion is necessary to diagnose mucormycosis. The clinical presentation varies depending on the site affected. Pulmonary infection causes fever, cough, hemoptysis, and pleuritic chest pain, as in this patient. Sinus infection causes facial pain, anosmia, congestion, epistaxis, or headache (11). On histopathologic examination, Zygomycetes hyphae are broad and irregular with right-angled branching, as opposed to Aspergillus hyphae, which are thinner with more acute-angled branching. There may be pulmonary angioinvasion, vascular thrombosis, or necrosis,Imaging findings are mostly nonspecific and include consolidation, nodules, masses, cavities, lymphadenopathy, and pleural effusion . Findings suggestive of invasive fungal infection include the air crescent sign (a thin rim of air between the necrotic lung and the surrounding parenchyma) and the halo sign (consolidation with a rim of surrounding GGO).,It is important to distinguish mucormycosis from aspergillosis because the treatments can differ and because appropriate early treatment of mucormycosis may improve the outcome (13). Given the high suspicion for mucormycosis, this patient was treated with a broad antifungal agent instead of voriconazole, which is ineffective against mucormycosis. In the appropriate clinical setting (as in this patient), the reversed halo sign is suggestive of mucormycosis (5,14). In eight patients with invasive fungal infection and the reversed halo sign, seven had mucormycosis and one had aspergillosis (5). Multiple pulmonary nodules (10 or more), pleural effusion, development of infection despite voriconazole prophylaxis, and sinusitis favor mucormycosis over aspergillosis (8).,Treament,Treatment for mucormycosis depends on antifungal agents, surgery, and control of predisposing conditions. Amphotericin B and, more recently, posaconazole are efficacious in the treatment of mucormycosis
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