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.

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.

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.

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.

Heterogeneity of blastomycosis-like pyoderma: A selection of cases from the last 35 years.

Blastomycosis-like pyoderma is a form of pyoderma with variable clinical findings and histopathological features. We present a case series of 39 patients collected over a 35-year period to demonstrate its clinical features and histological findings. The most common clinical presentations found were solitary plaques, solitary nodules, sinuses, crypts, verrucous plaques and discharge, usually on sun-exposed skin. The most common histopathological findings were chronic granulomatous inflammation, suppurative inflammation, sinus and abscess formation, pseudoepitheliomatous hyperplasia, transepidermal elimination and scarring. We discuss its treatment and the recent literature that has focused on its response to acitretin.

Cutaneous blastomycosis masquerading as pyoderma gangrenosum.

Cutaneous blastomycosis (CB) is associated with a variety of skin manifestations. Among other entities, CB may be mistaken for pyoderma gangrenosum due to overlap of findings on histopathologic examination. We report a case of CB, initially diagnosed as pyoderma gangrenosum and treated with steroids, leading to disseminated blastomycosis and acute respiratory distress syndrome (ARDS).

Unexpected Blastomyces dermatitidis etiology of fungal sinusitis and erosive palatal infection in a diabetic patient.

We present what is believed to be the initial report of hard-palate infection caused by Blastomyces dermatitidis. The organism was cultivated from biopsy material obtained from a diabetic patient presenting with complaints of headache and malaise. Radiologic findings revealed a malignant-appearing soft-tissue mass with paranasal sinus base destruction.

Variation in clinical phenotype of human infection among genetic groups of Blastomyces dermatitidis.

BACKGROUND: Blastomyces dermatitidis, the etiologic agent of blastomycosis, has 2 genetic groups and shows varied clinical presentation, ranging from silent infections to fulminant respiratory disease and dissemination. The objective of this study was to determine whether clinical phenotype and outcomes vary based on the infecting organism's genetic group. METHODS: We used microsatellites to genotype 227 clinical isolates of B. dermatitidis from Wisconsin patients. For each isolate, corresponding clinical disease characteristics and patient demographic information were abstracted from electronic health records and Wisconsin Division of Health reportable disease forms and questionnaires. RESULTS: In univariate analysis, group 1 isolates were more likely to be associated with pulmonary-only infections (P < .0001) and constitutional symptoms such as fever (P < .0001). In contrast, group 2 isolates were more likely to be associated with disseminated disease (P < .0001), older patient age (P < .0001), and comorbidities (P = .0019). In multivariate analysis, disease onset to diagnosis of >1 month (P < .0001), older age at diagnosis (P < .0001), and current smoking status (P = .0001) remained predictors for group 2 infections. CONCLUSIONS: This study identified previously unknown associations between clinical phenotype of human infection and genetic groups of B. dermatitidis and provides a framework for further investigations of the genetic basis for virulence in B. dermatitidis.

Blastomycosis in India: report of an imported case and current status.

We report a case of disseminated blastomycosis in a female resident of Delhi, who acquired the infection during travel to the USA, which was successfully treated with oral itraconazole. In addition, we present a critical literature review, indicating that blastomycosis is endemic in India but its areas of endemicity, prevalence, and the natural habitat of the etiologic agent, remain undetermined. The diagnosis of blastomycosis was made by examination of Gomori's methenamine silver stained sections of tissue obtained from a biopsy of a subcutaneous, abdominal nodular. These studies revealed thick-walled, broad-based budding yeast cells compatible with Blastomyces dermatitidis, and consistent with the isolation of the fungus in cultures inoculated with posterior auricular lymph node aspirate. Microscopically, the isolate had thin, septate hyphae and characteristic spherical to pyriform, smooth-walled microconidia. Its identity was confirmed by conversion to its typical yeast form on pea seed agar at 37°C and by DNA sequencing of ITS and BAD 1 promoter regions.

Clinical and molecular epidemiology of veterinary blastomycosis in Wisconsin.

BACKGROUND: Several studies have shown that Blastomyces dermatitidis, the etiologic agent of blastomycosis, is a genetically diverse pathogen. Blastomycosis is a significant health issue in humans and other mammals. Veterinary and human isolates matched with epidemiological case data from the same geographic area and time period were used to determine: (i) if differences in genetic diversity and structure exist between clinical veterinary and human isolates of B. dermatitidis and (ii) if comparable epidemiologic features differ among veterinary and human blastomycosis cases. RESULTS: Genetic typing of 301 clinical B. dermatitidis isolates produced 196 haplotypes (59 unique to veterinary isolates, 134 unique to human isolates, and 3 shared between canine and human isolates). Private allelic richness was higher in veterinary (median 2.27) compared to human isolates (median 1.14) (p = 0.005). Concordant with previous studies, two distinct genetic groups were identified among all isolates. Genetic group assignment was different between human and veterinary isolates (p < 0.001), with more veterinary isolates assigned to Group 2. The mean age of dogs diagnosed with blastomycosis was 6 years. Thirty cases were in male dogs (52%) and 24 were females (41%). The breed of dog was able to be retrieved in 38 of 58 cases with 19 (50%) being sporting breeds. Three of four felines infected with blastomycosis were domestic shorthair males between ages 6-12, and presented with disseminated disease. The other was a lynx with pulmonary disease. The equine isolate was from an 11-year-old male Halflinger with disseminated disease. Disseminated disease was reported more often in veterinary (62%) than human cases (19%) (p < 0.001). CONCLUSIONS: Isolates from all hosts clustered largely into previously identified genetic groups, with 3 haplotypes being shared between human and canine isolates confirming that B. dermatitidis isolates capable of infecting both species occur in nature. Allelic diversity measures trended higher in veterinary samples, with a higher number of total alleles and private alleles. Veterinary isolates of B. dermatitidis contributed a substantial amount of diversity to the overall population genetic structure demonstrating the importance of including veterinary isolates in genetic studies of evolution and virulence in this organism.

Oronasal blastomycosis in a golden retriever.

Blastomycosis is one of the most common systemic fungal infections in dogs in North America Pulmonary manifestations are most common; localized disease is rare. A case of localized oronasal blastomycosis mimicking oral neoplasia is described. Long-term therapy with itraconazole resulted in clinical cure.

Blastomycose oronasale chez un golden retriever. La blastomycose est l'une des infections fongiques systémiques les plus courantes chez les chiens en Amérique du Nord. Les manifestations pulmonaires sont les plus fréquentes; une maladie localisée est rare. Un cas de blastomycose orale imitant la néoplasie orale est décrit. Un traitement à long terme avec l'itraconazole a produit une guérison clinique.(Traduit par Isabelle Vallières).

Carpal intra-articular blastomycosis in a Labrador retriever.

A 6-month-old male castrated Labrador retriever was presented for coughing and forelimb lameness. Blastomyces dermatitidis was identified in cytology of sputum and synovial fluid. Repeat arthrocentesis 7 months later revealed resolution of septic arthritis. Fungal septic arthritis should be considered for cases of monoarthritis and may respond to oral itraconazole treatment.

Blastomycose carpienne intra-articulaire chez un Labrador retriever. Un Labrador retriever mâle castré âgé de 6 mois a été présenté pour une toux et une boiterie du membre antérieur. Blastomyces dermatitidis a été identifié lors d'une cytologie de l'expectoration et du liquide synovial. Une nouvelle arthrocentèse 7 mois plus tard a révélé la résolution de l'arthrite septique. L'arthrite septique fongique devrait être considérée pour les cas de mono-arthrite et elle peut réagir au traitement à l'itraconazole oral.(Traduit par Isabelle Vallières).

Pulmonary blastomycosis during pregnancy: case report and review of the literature.

Blastomycosis rarely presents in pregnancy. Pregnancy is a state of partial immunodeficiency that predisposes to blastomyces infection, especially in endemic areas. Blastomycosis in pregnancy has been reported in a few female patients and their offspring. We are reporting a 32-year-old pregnant patient at 34 weeks of gestation who presented with a lung mass. The cytopathological exam of the biopsy taken by fine needle aspiration showed evidence of Blastomyces organisms. She received Liposomal Amphotericin B and was followed closely until delivery. The placenta was examined and did not show evidence of infection in the fetus. Healthcare professionals in endemic areas such as Tennessee should be aware of blastomycosis in pregnancy.

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.