Clinical features of pulmonary mucormycosis in patients with different immune status

Abstract

Background: Pulmonary mucormycosis (PM) is a relatively rare but often fatal and rapidly progressive disease. Most studies of PM are case reports or case series with limited numbers of patients, and focus on immunocompromised patients. We investigated the clinical manifestations, imaging features, treatment, and outcomes of patients with PM with a focus on the difference in clinical manifestations between patients with different immune status.

Methods: Clinical records, laboratory results, and computed tomography scans of 24 patients with proven or probable PM from January 2005 to December 2018 in Peking Union Medical College Hospital were retrospectively analyzed.

Results: Ten female and 14 male patients were included (median age, 43.5 years; range, 13-64 years). Common presenting symptoms were fever (70.8%), cough (70.8%), sputum production (54.2%), and hemoptysis (41.7%). Radiological findings included consolidation (83.3%), ground-glass opacities (58.3%), nodules (50.0%), masses (37.5%), cavities (33.3%), mediastinal lymphadenopathy (29.2%), and halo sign (12.5%); one patient had a reversed halo sign. Seven patients (29.2%) had no obvious predisposing risk factors, and 17 (70.8%) had underlying diseases including diabetes, hematological malignancy, and use of immunosuppressants. Compared with immunocompromised patients, immunocompetent patients with PM were younger {23 [13-46] vs. 48 [17-64] years, P=0.023}, comprised a higher proportion of men (100.0% vs. 41.2%, P=0.019), had a longer disease course {34 [8-47] vs. 9 [2-102] weeks, P=0.033}, had a higher eosinophil count [0.66 (0.07-2.00) ×10⁹/L vs. 0.04 (0.00-0.23) ×10⁹/L, P=0.001], and had a lower erythrocyte sedimentation rate {12 [1-88] vs. 74 [9-140] mm/h, P=0.032}.

Conclusions: PM can occur in heterogeneous patients with different immune status, and the clinical phenotype differs between immunocompetent and immunocompromised patients. Because of the lack of specific clinic and imaging manifestations, aggressive performance of invasive procedures to obtain histopathological and microbial evidence is crucial for a definitive diagnosis.

Keywords: Mucormycosis; fungal; lung diseases; zygomycosis.

Figure 1

A 24-year-old man with disseminated mucormycosis. (A) Chest computed tomography (lung window) shows consolidation in the left lower lobe; (B) chest computed tomography (mediastinal window) shows consolidation with central necrosis, mediastinal lymphadenopathy, and invasion of the chest wall; (C) microscopic examination of lung biopsy showing necrosis in the lung tissue accompanied by an epithelioid cell response and Mucor hyphae with a width of 6–10 µm [hematoxylin and eosin (HE), 200×]; (D) microscopic examination of lung biopsy indicates eosinophilic infiltration (HE, 200×); (E) microscopic examination of abdominal subcutaneous nodule biopsy shows necrosis, eosinophilic infiltration, and Mucor hyphae with a width of 8–12 µm (HE, 200×); (F) after 14 months of treatment, the pulmonary opacity and mediastinal lymphadenopathy improved.

Figure 2

A 20-year-old man with pulmonary mucormycosis. (A) Chest computed tomography reveals a perimediastinal mass and subpleural consolidation in the right lung; (B) chest computed tomography (mediastinal window) shows a mass invading the mediastinum and compressing the left atrium and right lower pulmonary vein; (C,D) chest computed tomography indicates that the lesions have been significantly absorbed after 9 months of treatment.

Figure 3

A 44-year-old man with pulmonary mucormycosis that manifested as massive hemoptysis. (A,B) Chest computed tomography reveals small nodules with varying sizes, randomly distributed in the bilateral lungs and superimposed on ground-glass opacities.

Figure 4

A 61-year-old woman with pulmonary mucormycosis and acute myeloid leukemia. (A) Chest computed tomography shows ground-glass opacity in the upper right lung, surrounded by consolidation shadow (reversed halo sign); (B) microscopic examination of a lung biopsy reveals chronic inflammation accompanied by necrosis [hematoxylin and eosin (HE), 40×]; (C) Mucor hyphae with a width of 6–8 µm could be observed in the lung tissue (HE, 200×); (D) chest computed tomography illustrates a clearer reversed halo sign after 2 weeks; (E) chest computed tomography illustrates a cavity in the right upper lung at month 5; (F) the lesion in the right upper lung had significantly resolved and left a thin-walled cavity after 9 months.

Figure 5

A 63-year-old woman with aplastic anemia and pulmonary mucormycosis. (A) Chest computed tomography shows consolidation neighboring the left heart margin as well as multiple ground glass opacities and nodules in the bilateral lungs; (B) chest computed tomography (mediastinal window) shows a lung lesion involving the pericardium.

Figure 6

A 45-year-old man with acute myelogenous leukemia and pulmonary mucormycosis. (A) Chest computed tomography show a mass in the left upper lobe surrounded by a ground-glass opacity shadow (halo sign). A small nodule is also present in the right upper lobe; (B) chest computed tomography (mediastinal window) shows a mass with central necrosis in the left upper lobe; (C) direct microscopy of bronchoalveolar lavage fluid reveals non-septate, ribbon-like, right-angle branching Mucor hyphae with a width of ~10 µm (Gram stain, 1,000×); (D) after 4 months of treatment, chest computed tomography indicates absorption of both the mass in the left upper lung and the small nodule in the right upper lung.