First Japanese case of disseminated blastomycosis imported from North America: A case report.

Blastomycosis is a fungal infectious disease that can occur in both immunocompromised and immunocompetent populations endemic in North America, with no previous reports in Japan. A 26-year-old Japanese female patient with no relevant medical history presented intermittent left back pain and an abnormal shadow in the left upper lung field eight months ago at a local clinic. She was referred to our hospital for further evaluation and treatment. The patient currently lives in Japan, but until two years ago had spent several years in New York, Vermont and California. Chest computed tomography revealed a 30 mm mass with a cavity in the left pulmonary apex. The specimens obtained by transbronchial biopsy showed periodic acid-Schiff stain (PAS)-positive and Grocott-positive yeast-like fungi scattered among the granulomas, with no malignant findings, and the initial pathology did not lead to a definitive diagnosis. She was empirically started on fluconazole because of onset of multiple subcutaneous abscesses and was referred to the Medical Mycology Research Center. Although antibody tests could not diagnose the disease, blastomycosis was suspected based on the pathology of the skin and lung tissue at the Medical Mycology Research Center, and Blastomyces dermatitidis was identified by ITS analysis of the rRNA region. Her symptoms and CT findings gradually improved with fluconazole. We reported the first Japanese case of blastomycosis with pulmonary and cutaneous involvement in Japan. As the number of overseas travelers is expected to continue increasing, we would like to emphasize the importance of travel history interviews and information of blastomycosis.

Direct Tissue PCR and Genotyping for Species Identification in a Case of Laryngeal Blastomycosis.

Otolaryngologic manifestations of infection with Blastomyces species are extremely rare and restricted geographically to recognized endemic regions. Here, we describe a case of laryngeal blastomycosis that presented as slowly progressive dysphonia. While a preliminary diagnosis was made using routine histopathology, a species identification of Blastomyces dermatitidis was made using polymerase chain reaction amplification and rapid genotyping without the need for fungal culture. All symptoms resolved following 1 month of antifungal therapy. Rapid molecular differentiation of B dermatitidis from Blastomyces gilchristii provides important insights into pathogenesis given recent recognition of differences in clinical spectra.

Blastomyces Induced Otomastoiditis With Local Soft Tissue Invasion: A Case Report.

The aim of this report is to document a very rare case of Blastomycosis dermatitidis mastoiditis with extension into the retromastoid soft tissue and surrounding muscle. Blastomycosis dermatitidis is a dimorphic fungus of endemic areas which classically infiltrates the lungs; however, dissemination presenting as otomastoiditis is exceedingly rare. The patient was an immunocompetent 27-year-old male with no significant preexisting health conditions. He had significant work exposure to dust and soil and was referred to our department for evaluation of otalgia with headaches, hearing loss, and intermittent facial paralysis. Initially, the extent of the infection was unknown. Based on extensive disease on magnetic resonance imaging, the patient was scheduled for urgent tympanoplasty and mastoidectomy. Postoperative treatment with itraconazole resolved any further manifestations and halted further soft tissue invasion. It is important to consider uncommon fungal infections in the workup of persistent otalgia, especially when presenting with facial paralysis and a history of environmental exposure to soil and dust. This type of infection should be considered regardless of immunodeficiency status. Early detection may prevent hearing loss and local invasion into surrounding structures.

Laryngeal Blastomycosis, an Unexpected Diagnosis: A Case Report.

Isolated laryngeal blastomycosis is an extremely rare entity with few cases described in the medical literature. Nonspecific and chronic presenting symptoms such as dysphonia, dyspnea, dysphagia, and/or cough are described, with isolated reports requiring urgent management related to respiratory distress. We present a case report of a 63-year-old immunocompetent female diagnosed with isolated laryngeal blastomycosis, document the treatment regimen and subsequent clinical course. In view of the rarity of this diagnosis, isolated laryngeal blastomycosis has the potential for clinical and pathologic misdiagnosis. Without an accurate diagnosis, blastomycosis remains untreated and the risk for airway disease progression increases.

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.

Unique Oral Presentations of Deep Fungal Infections: A Report of Four Cases.

Deep fungal infections rarely involve the oral cavity and most commonly affect immunocompromised patients. Oral deep fungal infections typically manifest as chronic mucosal ulcerations or granular soft tissue overgrowths. Since these lesions are non-specific and can mimic malignancy, it is crucial to obtain a thorough clinical history and an adequate biopsy to render the appropriate diagnosis. We report four new cases of deep fungal infections, diagnosed as histoplasmosis, blastomycosis and chromoblastomycosis, exhibiting unique oral and perioral presentations. Awareness of these unusual entities can help dental and medical practitioners expedite proper multidisciplinary care and minimize morbidity and mortality.

A young male with chronic nonproductive cough diagnosed with blastomycosis in China: a case report.

BACKGROUND: Blastomycosis is a fungal infectious disease prevalent in North America and rarely reported in Asia. Misdiagnosis of malignancy and other infectious diseases were reported. CASE PRESENTATION: A 24-years-old male patient presented with chronic non-productive cough of 4 months duration. He had been diagnosed with Mycobacterium tuberculosis infection and lung malignancy elsewhere and presented to us as the symptoms persisted. We offered him the biopsy under endobronchial ultrasound-guide sheath-transbronchial lung biopsy and sample specimen were sent for next generation sequencing analysis, returned as Blastomyces Dermatitidis infection. The patient was treated by itraconazole for 6 months, his symptoms decreased significantly and the CT scan showed resolution of the lesion. CONCLUSION: We shared a case of blastomycosis with delayed and difficult diagnosis and reviewed the knowledge regarding differential diagnosis and next generation sequencing technologies.

Bronchoscopy in the diagnosis of pulmonary blastomycosis.

OBJECTIVES: Diagnosing pulmonary blastomycosis (PB) requires the detection of Blastomyces dermatitidis in pulmonary secretions or tissue, which can be achieved via bronchoscopic procedures like bronchoalveolar lavage (BAL) or brush and transbronchial biopsy (TBBx). This descriptive study retrieved the data of PB that was diagnosed by bronchoscopy to define which bronchoscopic procedure produced the highest yield. METHODS: Retrospectively, all patients diagnosed with PB via bronchoscopic approach were identified. Non-invasive BAL was referred to when performed first in the order of bronchoscopic procedures, and invasive BAL was used when it was performed after other bronchoscopic procedures. RESULTS: A total of 111 patients were included in the study. BAL produced the highest yield of all bronchoscopic procedures (>87%), regardless if it was performed first in order (non-invasive, 87.3%) or not (invasive BAL, 89.6%) (p = 0.43). Performing bronchoscopy and BAL earlier in the course of the disease resulted in a significantly better diagnostic yield. CONCLUSIONS: BAL is probably enough to diagnose PB. Also, it had the best yield when performed earlier, regardless of whether it was performed first in order or not. BAL culture had a better yield in detecting Blastomyces dermatitidis over fungal stain and cytology.

Atypical Laryngeal Infections: Localized Lesions from Unusual Organisms May Simulate Malignancy.

OBJECTIVE: The identification of rare sources of laryngeal infection in immunocompetent patients. Recovered organisms were Mycobacterium tuberculosis (laryngeal tuberculosis [LTB]), Mycobacterium fortuitum (laryngeal Mycobacterium fortuitum [LMF]), and Blastomyces dermatiditis (laryngeal blastomycosis [LB]). METHOD: Single institution retrospective case series of three patients over a 2.5-year period and review of the literature on laryngeal infections by three atypical organisms. RESULTS: Three patients presented with hoarseness and cough; one additionally had throat pain (LTB). Indirect laryngoscopy demonstrated diffuse laryngeal ulceration (LTB, LMF) and an exophytic, contiguous glottic mass (LB). Direct microlaryngoscopic biopsies and cultures established the diagnoses, including a frozen section in one case (LB), which prevented a simultaneously planned surgical resection. Appropriate antimicrobial therapy yielded dramatic laryngeal and corresponding vocal improvement, for which we provide unique photo and audio documentation. In the last 10 years, fewer than 500 cases of LTB have been reported in the English language medical literature, principally outside the United States. To date, there have been reports of only 34 LB and no cases of LMF. CONCLUSION: Atypical infections of the larynx may be localized and mimic laryngeal cancer on endoscopy. Tissue examination as well as microbiologic samples are diagnostic and complementary.

Primary Laryngeal Blastomycosis: Diagnostic Challenges and Advances in a Rare Cause of Laryngitis.

Blastomyces dermatitidis is a fungal organism endemic to the central and southern United States and capable of causing numerous diseases. Primary blastomycosis of the larynx is a rare clinical entity with a limited number of reported cases in the literature. Diagnosis is challenging as a result of nonspecific physical exam findings, difficulty of histopathologic detection and culture, and need for operative laryngeal biopsy for definitive identification. Molecular and serologic testing is not widely available. The authors present a case of laryngeal blastomycosis, the diagnosis of which was facilitated by in-office biopsy, and discuss diagnostic challenges. Laryngoscope, 129:2531-2533, 2019.

Blastomycosis in Southern Saskatchewan 2000-2015: Unique presentations and disease characteristics.

In the literature, cases of blastomycosis in Canada have been documented in provinces bordering the Great Lakes, including Ontario and Quebec, as well as Manitoba. This is the first study to our knowledge reporting cases of mycosis seen in southern Saskatchewan suggesting a broader area of endemicity. We searched the Regina Qu'Appelle Health Region (RQHR) Microbiology Laboratory for all culture-confirmed cases of Blastomyces from January 2000 to December 2015 and identified 15 cases. Thirteen cases were reviewed, identifying common presenting symptoms, misdiagnosis, comorbidities, travel history, time from presentation to diagnosis, diagnostic specimen, treatment, and clinical outcome. Nine patients had no travel to areas known to be endemic to environmental blastomycosis. Eight patients presented with respiratory symptoms, four with skin lesions, four with constitutional symptoms, and one presented with chest pain after a fall. Initial misdiagnosis occurred in nine (69%) of the 13 cases, and all six patients that died of the disease were misdiagnosed. These six patients (46%) were acutely ill with refractory disseminated disease, leading to respiratory failure. It is probable that Blastomyces is present as an endemic fungus in the soil of southern Saskatchewan. Possibly due to a lack of awareness of this pathogen in the area, initial misdiagnoses were common and likely contributed to significant morbidity and mortality.

Disseminated blastomycosis in a transplant patient.

A 51-year-old woman from Wisconsin with past medical history of kidney transplantation from her sibling 8 weeks prior, presented with symptoms of shortness of breath, cough, and a new skin rash over a 2-week period.

Blastomyces dermatitidis pneumonia in a llama.

A 20-y-old female llama ( Lama glama) was euthanized after a history of chronic dyspnea and osteoarthritis. At autopsy, the lungs were covered by clear gelatinous material and expanded by firm, variably discrete, tan-white nodules up to 8 cm diameter containing tan-white, viscous material. The tracheobronchial lymph nodes were firm and enlarged up to 6 × 4 × 3 cm; the thoracic aorta and carotid arteries were lined by hard, tan-white, mineralized intimal plaques. Histologic examination of lung revealed numerous 10-20 µm diameter yeasts with clear 1-2 µm thick double-contoured walls, central basophilic nuclei, and frequent broad-based budding, consistent with Blastomyces dermatitidis. DNA sequencing confirmed the diagnosis. B. dermatitidis should be considered in the differential diagnosis of pulmonary disease in llamas.