Clinical Analysis of Non-AIDS Patients with Pulmonary Cryptococcosis and the Change in Their Clinical Features over 30 Years in a Tertiary Hospital in Beijing, China.

Over the past few decades, the clinical features of pulmonary cryptococcosis (PC) have progressed; however, there is a lack of data on the manifestations of PC over time. To investigate the differences in the clinical characteristics of PC across different time periods, we retrospectively reviewed 130 non-acquired immunodeficiency syndrome (AIDS) patients diagnosed with pathologically or microbiologically confirmed PC from 1990-2020. Among the 130 patients with PC, 24 (18.5%) exhibited immunosuppression, and 44 (33.8%) had underlying diseases. In radiology, 118 (90.8%) presented with subpleural lesions, and 68 (53.1%) presented with nodules with diameters ranging from 1-5 cm. Seventy-five (57.7%) patients underwent surgery alone. The clinical features of PC at different time periods showed that hospitalization days decreased (P = 0.009), and the number of patients with symptoms decreased over time. The number of patients exhibiting isolated lesions decreased (P = 0.022), and the number of patients exhibiting subpleural lesions increased (P = 0.020). In addition, the number of patients with lesions presenting 3-10 mm nodules increased (P = 0.028). In conclusion, an increasing number of patients have been diagnosed with PC over the last 30 years. The timing of PC diagnosis has shifted to the early stages of disease progression. Pulmonary lesions caused by cryptococcosis are easily misdiagnosed and may require unnecessary surgical treatment. Further research is needed to identify the lung lesions caused by cryptococcosis.

An unusual case of reactivated latent pulmonary cryptococcal infection in a patient after short-term steroid and azathioprine therapy: a case report.

BACKGROUND: Cryptococcus is one of the major fungal pathogens infecting the lungs. Pulmonary cryptococcal infection is generally considered a community-acquired condition caused by inhalation of dust contaminated with fungal cells from the environment. Here, we report a case developing pulmonary cryptococcosis 3 months after hospital admission, which has rarely been reported before. CASE PRESENTATION: A 73-year-old female patient who was previously immunocompetent experienced persistent dry cough for 2 weeks, 3 months after admission. Chest computed tomography (CT) showed a new solitary pulmonary nodule developed in the upper lobe of the left lung. Staining and culture of expectorated sputum smears were negative for bacteria, acid-fast bacilli, or fungus. The patient then underwent biopsy of the lesion. Histopathology findings and a positive serum cryptococcal antigen titer (1:8) indicated pulmonary cryptococcosis. Daily intravenous 400 mg fluconazole was administered initially followed by oral fluconazole therapy. Follow-up chest CT after 3 months of antifungal therapy showed complete disappearance of the pulmonary nodule. Respiratory symptoms of the patient also resolved. A complete investigation excluded the possibility of a patient-to-patient transmission or primarily acquiring the infection from the hospital environment. Based on the patient's history of exposure to pigeons before admission and recent steroid and azathioprine use after admission for the treatment of myasthenic crisis, reactivation of a latent pulmonary cryptococcal infection acquired before admission, in this case, is impressed. CONCLUSIONS: Although rarely reported, pulmonary cryptococcal infection should be included in the differential diagnosis of hospitalized patients with respiratory symptoms, especially in those with predisposing risk factors. Chest image studies and further surgical biopsy are needed for confirmation.

Crazy-paving patterns as rare radiological manifestations of pulmonary cryptococcosis: a case report.

BACKGROUND: Crazy-paving patterns are rarely reported as radiological manifestations of pulmonary cryptococcosis. CASE PRESENTATION: Herein, we presented a very rare case of a crazy-paving pattern as a radiological manifestation of pulmonary cryptococcosis in a patient with primary ciliary dyskinesia. The diagnosis of pulmonary cryptococcosis and primary ciliary dyskinesia was ultimately confirmed by bronchoscopic biopsy, fungus culture, whole exome sequencing of blood, etc. The patient received flucytosine (PO, 5 g per day) and amphotericin B (IV, 70 mg per day) during hospitalization and sequential therapy with voriconazole (PO, 200 mg twice a day) after discharge. He recovered during follow-up. CONCLUSIONS: We concluded that pulmonary cryptococcosis should be considered a possible cause of crazy-paving patterns in chest CT scans.

Oral posaconazole and bronchoscopy as a treatment for pulmonary mucormycosis in pediatric acute lymphoblastic leukemia patient: A case report.

RATIONALE: Mucormycosis is a rare fungal infection that typically occurs in immunosuppressed patients following chemotherapy or hematopoietic stem cell transplantation. PATIENT CONCERNS: An 11-year-old child with newly developed acute lymphoblastic leukemia suffered from the paroxysmal left chest pain, fever, and hemoptysis. DIAGNOSES: We made a histopathologic diagnosis aided by bronchoscopy techniques, which indicated invasive fungal hyphae that are characteristic of mucormycosis. INTERVENTIONS: The patient was treated with oral posaconazole and repeated bronchoscopy interventions for 4 months. OUTCOMES: The patient's clinical signs and symptoms and signs were no longer present. The prior lung lesions were also no longer observable using radiologic methods, and a 3-month follow-up with the patient showed no signs of mucormycosis recurrence. Finally, the patient was cured, when the cancer chemotherapy was stopped. Close follow-up for another 2 years showed no evidence of recurrence. LESSONS: Mucormycosis diagnosis is difficult as clinical and imaging findings vary. This case demonstrates that posaconazole monotherapy combined with bronchoscopy interventions may be a safe and effective treatment option for pediatric pulmonary mucormycosis.

[The spectrum of pathogens in 187 cases of pulmonary fungal disease diagnosed by histopathology-a retrospective analysis].

Objective: To investigate the spectrum of pathogens causing lung fungal disease diagnosed by histopathology through histochemical special staining, compared to the fungal culture results, and to further evaluate the diagnostic value of histochemical special staining in pulmonary fungal disease. Methods: We performed a retrospective analysis of 187 cases of pulmonary fungal disease diagnosed by histopathology in Peking Union Medical College Hospital from 2001 to 2015 (including 92 cases with pulmonary resection or open lung biopsy, 33 with percutaneous lung biopsy and 62 ones with fiberoptic bronchoscopic lung biopsy). All cases were treated with hexamine silver, PAS, mucus carmine and acid-fast staining in addition to conventional HE staining. The clinical records and the fungal culture results were reviewed. Results: There were 103 male and 84 female patients, aged from 12 to 70 years [average (48±14) years]. There were 85 cases(45.5%) of pulmonary aspergillosis(including 60 cases of invasive infection and 25 cases of aspergilloma), 51 cases(27.3%) of pulmonary cryptococosis, 6 cases (3.2%)of pulmonary mucormycosis, 3 cases(1.6%) of pulmonary histoplasmosis, 3 cases (1.6%)of pulmonary candidiasis, and 2 cases (1.1%) of pneumocystosis, while in the remaining 37 cases (19.8%) the pathogens could not be clearly classified by microscopy due to limited tissue or degeneration. Among the 88 patients with pulmonary fungal disease diagnosed by histopathology from 2011 to 2015, 35 ones (39.9%) were detected by fungal culture (including lung biopsy, intraoperative swab, blood, bronchoalveolar lavage fluid and sputum, etc.). The diagnostic results of 18 cases were completely consistent between histopathological examination and fungal culture (18/35, 51.4%), while 13 cases (13/35, 37.1%) were diagnosed by histopathology but no fungi were cultured, and in 3 cases (3/35,8.6%) the culture was positive for fungi which could not be classified clearly by histopathology. In another case the pathogen was found to be Cryptococcus histopathologically but the lavage culture grew"candida", but the patient's blood cryptococcal antigen was positive. Conclusions: Among patients with histopathological diagnosis of pulmonary fungal disease, pulmonary aspergillosis was the most common, followed by pulmonary cryptococcosis, pulmonary mucormycosis, pulmonary histoplasmosis, pulmonary candidiasis and pneumocystosis. A small number of cases could not be classified by histopathology through histochemical special staining. There was a high consistency in discovering fungal pathogens between pathological histochemical special staining and culture method, but 37% pulmonary fungal disease diagnosed by histopathology were culture negative. In practice, the role of histochemical special staining in diagnosing pulmonary fungal disease should be paid more attention.

Pulmonary Mycosis Drives Forkhead Box Protein A2 Degradation and Mucus Hypersecretion through Activation of the Spleen Tyrosine Kinase-Epidermal Growth Factor Receptor-AKT/Extracellular Signal-Regulated Kinase 1/2 Signaling.

Pulmonary mycoses are difficult to treat and detrimental to patients. Fungal infections modulate the lung immune response, induce goblet cell hyperplasia and metaplasia, and mucus hypersecretion in the airways. Excessive mucus clogs small airways and reduces pulmonary function by decreasing oxygen exchange, leading to respiratory distress. The forkhead box protein A2 (FOXA2) is a transcription factor that regulates mucus homeostasis in the airways. However, little is known whether pulmonary mycosis modulates FOXA2 function. Herein, we investigated whether Blastomyces dermatitidis and Histoplasma capsulatum-infected canine and feline lungs and airway epithelial cells could serve as higher animal models to examine the relationships between fungal pneumonia and FOXA2-regulated airway mucus homeostasis. The results indicate that fungal infection down-regulated FOXA2 expression in airway epithelial cells, with concomitant overexpression of mucin 5AC (MUC5AC) and mucin 5B (MUC5B) mucins. Mechanistic studies reveal that B. dermatitidis infection, as well as ß-glucan exposure, activated the Dectin-1-SYK-epidermal growth factor receptor-AKT/extracellular signal-regulated kinase 1/2 signaling pathway that inhibits the expression of FOXA2, resulting in overexpression of MUC5AC and MUC5B in canine airway cells. Further understanding of the role of FOXA2 in mucus hypersecretion may lead to novel therapeutics against excessive mucus in both human and veterinary patients with pulmonary mycosis.

Chronic granulomatous 'Aspergillus lung mass'.

The diverse clinicopathological spectrum of pulmonary aspergillosis is a consequence of varying levels of invasiveness of this ubiquitous fungus, which largely depends on the host immune response and pre-existing lung disease. The clinical presentation of pulmonary aspergillosis spans a wide spectrum from hypersensitivity to life threatening angio-invasive and disseminated disease. We report the case of a young immunocompetent male with no underlying lung disease, who presented with an incidentally detected 'infective mass' lesion in the lung associated with minimal respiratory symptoms. The diagnostic challenges posed by the unusual clinical, radiological and histological picture as well as the therapeutic dilemmas faced are discussed in this report.

Pulmonary mucormycosis following autologous hematopoietic stem cell transplantation for rapidly progressive diffuse cutaneous systemic sclerosis: A case report.

RATIONALE: The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc). PATIENT CONCERNS: A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT. DIAGNOSES: The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample. INTERVENTIONS AND OUTCOMES: Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up. LESSONS: With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.

Conidiobolus pachyzygosporus invasive pulmonary infection in a patient with acute myeloid leukemia: case report and review of the literature.

BACKGROUND: Conidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy. CASE PRESENTATION: A 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions. CONCLUSIONS: This is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country.

Pulmonary Mucormycosis: Risk Factors, Radiologic Findings, and Pathologic Correlation.

Pulmonary mucormycosis (PM) is an uncommon fungal infection most often seen in immunocompromised patients. The fungus grows on decaying food, soil, and animal excrement. Patients usually become infected by inhalation of spores. The most common risk factors include diabetes mellitus, hematologic malignancy, and solid organ or stem cell transplant. PM can have a nonspecific appearance at imaging. For example, early imaging may show peribronchial ground-glass opacity. Later, the disease progresses to consolidation, nodules, or masses. Because patients are usually immunocompromised, the differential diagnosis often includes invasive pulmonary aspergillosis (IPA). Various radiologic findings suggestive of PM have been identified to help differentiate it from IPA. For example, the reverse halo sign is more closely associated with PM than with IPA. The reverse halo sign is an area of ground-glass opacity surrounded by a rim of consolidation. In addition, the presence of pleural effusions and more than 10 nodules is more suggestive of PM than it is of IPA. PM can progress rapidly in neutropenic patients. Identification of the hyphae in tissue by using endobronchial or percutaneous sampling can allow differentiation from IPA and help confirm the diagnosis of mucormycosis. Because of the high mortality rate associated with PM, early identification of the disease is critical for an improved likelihood of survival. A multimodality treatment approach with antifungal agents and surgical débridement has been shown to improve outcomes. The authors review the risk factors for PM, describe its imaging appearance and disease process, and describe the treatment of the disease. ©RSNA, 2020.

Non-HIV talaromycosis: Radiological and clinical analysis.

To investigate the characteristics of spiral computed tomography (CT), positron emission tomography-computed tomography (PET/CT) and clinical manifestations of talaromycosis to improve the diagnostic level and deepen its recognition in radiology.Radiological, clinical, and pathological manifestations of 15 patients of non-HIV talaromycosis confirmed by bronchofiberscope lung biopsy and/or abscess puncture fluid culture and/or blood culture and/or sputum culture were analyzed retrospectively. All patients underwent chest CT, among them, six had a brain MRI, and six had a PET/CT scan before treatment.On plain CT scan, there were multiple patches and massive consolidation in 6 patients, multiple patchy consolidations and patchy ground-glass opacities in 3 patients, solitary or multiple nodules and masses in 3 patients, multiple cavities and small nodules in 3 patients. Multiple lymphadenectasis appeared in bilateral hila, mediastinum, and neck in 10 patients. In contrast CT scan, the parenchyma of the lesions had a slight enhancement in 10 patients, moderate enhancement in 3 patients, obvious enhancement in 2 patients. Seven cases had bone destruction and hyperplasia, cranial involvement in 1 patient and liver involvement in 3 patients, respectively. On PET/CT, five patients showed elevated standard uptake value (SUV).The radiological manifestations of non-HIV talaromycosis show multiple consolidations, ground-glass opacities, multiple nodules or masses in bilateral lungs, deep-seated enlarged lymph nodes and bone destruction in multiple systems. The final diagnosis should be based on the culture of talaromycosis.

How could hypoglycemia-inducing glycogen storage disease lead to hyperglycemia-induced mucormycosis?

Mucormycosis is an increasingly frequent, difficult to diagnose, difficult to treat, often fatal infection, especially in patients with hyperglycemia from uncontrolled diabetes. Type I (von Gierke) glycogen storage disease is due to inherited deficiency of enzymes in glycogen metabolism, which causes hypoglycemia. This report is the case of a patient with von Gierke disease and a missed diagnosis of pulmonary mucormycosis. This report illustrates the importance of having a high index of suspicion for mucormycosis in the appropriate clinical context.

[Pulmonary Metastase of a Knee Mycetoma in Senegal]. / Métastase pulmonaire d'un mycétome du genou au Sénégal.

Mycetoma is transmitted by thorns infected. The commonest site for mycetoma is the foot. The primary pulmonary are rare and usually secondary to other primary site. We report a case of pulmonary fungal mycetoma secondary to primary site in the knee. We do a review of the literature and we discuss the way of dissemination.

Le mycétome se transmet principalement par piqures d'épines d'arbustes infectés. Les localisations primitives au niveau du pied sont les plus fréquentes. Les localisations pulmonaires sont exceptionnelles et secondaires à des localisations périphériques primitives. Nous rapportons un cas de localisation pulmonaire d'un mycétome fongique secondaire à une localisation au niveau du genou, puis nous faisons une revue de la littérature et nous discutons de la voie de dissémination.