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.

Human Blastomycosis in South Africa Caused by Blastomyces percursus and Blastomyces emzantsi sp. nov., 1967 to 2014.

We reevaluated 20 cases of blastomycosis diagnosed in South Africa between 1967 and 2014, with Blastomyces dermatitidis considered to be the etiological agent, in light of newly described species and the use of more advanced technologies. In addition to histopathological and/or culture-based methods, all 20 isolates were phenotypically and genotypically characterized, including multilocus typing of five genes and whole-genome sequencing. Antifungal susceptibility testing was performed as outlined by Clinical and Laboratory Standards Institute documents M27-A3 and M38-A2. We merged laboratory and corresponding clinical case data, where available. Morphological characteristics and phylogenetic analyses of five-gene and whole-genome sequences revealed two groups, both of which were closely related to but distinct from B. dermatitidis, Blastomyces gilchristii, and Blastomyces parvus The first group (n = 12) corresponded to the recently described species Blastomyces percursus, and the other (n = 8) is described here as Blastomyces emzantsi sp. nov. Both species exhibited incomplete conversion to the yeast phase at 37°C and were heterothallic for mating types. All eight B. emzantsi isolates belonged to the α mating type. Whole-genome sequencing confirmed distinct species identities as well as the absence of a full orthologue of the BAD-1 gene. Extrapulmonary (skin or bone) disease, probably resulting from hematogenous spread from a primary lung infection, was more common than pulmonary disease alone. Voriconazole, posaconazole, itraconazole, amphotericin B, and micafungin had the most potent in vitro activity. Over the 5 decades, South African cases of blastomycosis were caused by species that are distinct from B. dermatitidis Increasing clinical awareness and access to simple rapid diagnostics may improve the diagnosis of blastomycosis in resource-limited countries.

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 peritonitis complicating peritoneal dialysis.

Fungal peritonitis is an uncommon complication in peritoneal dialysis patients. We report a case of blastomyces dermatitis peritonitis in a nonimmunocompromised peritoneal dialysis patient, who initially presented with symptoms of lower extremity weakness and altered mental status. Peritoneal blastomycosis is rare condition and not previously reported in end stage renal disease patients on peritoneal dialysis. Fungal peritonitis can present with subtle clinical findings so a high index of suspicion is needed as early detection and treatment may decrease mortality and morbidity.

A 45-Year-Old Woman With 3 Weeks of Cough and Night Sweats.

A 45-year-old woman who received a renal transplant 7 years prior presented with a 3-week history of low-grade fever, night sweats, and a dry cough with scant sputum production. Additionally, she reported generalized weakness and increased fatigability. She denied hemoptysis or weight loss, and there had been no change in medication or foreign travel. She had no history of latent tuberculosis or sick contacts. She had recently relocated to Baton Rouge, Louisiana. She was sexually active with her boyfriend who worked as a prison guard. She also reported that she was briefly incarcerated 7 years ago shortly after her renal transplantation. Her immunosuppression consisted of tacrolimus, mycophenolate, and prednisone.

Blastomycosis.

Blastomycosis is an endemic fungal infection due to Blastomyces dermatitidis that most commonly causes pneumonia; but the organism can disseminate to any organ system, most commonly the skin, bones/joints, and genitourinary tract. Both immunocompetent and immunocompromised persons can be infected, but more severe disease occurs in the immunocompromised. Blastomycosis can be diagnosed by culture, direct visualization of the yeast in affected tissue, and/or antigen testing. Treatment course and duration depend on severity of illness. For mild to moderate pulmonary disease the treatment is itraconazole. For severe blastomycosis, lipid formulation amphotericin B is given, followed by step-down therapy with itraconazole.

Risk Factors for Targeted Fungal and Mycobacterial Infections in Patients Taking Tumor Necrosis Factor Inhibitors.

OBJECTIVE: To identify predictors of the receipt of medical care, including the receipt of pre-drug screening, for diagnostically targeted fungal or mycobacterial infections among patients prescribed a tumor necrosis factor inhibitor (TNFi). METHODS: We conducted a case-control study using deidentified patient health claims information from a data set representing a commercially insured US population of 15 million patients annually from January 1, 2007 to December 31, 2009. Descriptive statistics as well as a 2-sample t-test, chi-square test of association, Fisher's exact test, and multivariate logistic regression were used for data analysis. RESULTS: A total of 30,772 patients received a TNFi during the study period. Of these, 158 patients (0.51%) developed targeted fungal and/or mycobacterial infections (cases). The median number of infections per case was 1.0 (interquartile range 1.0-2.0). Tuberculosis was diagnosed in 61% of cases, followed by histoplasmosis in 60%, nontuberculous mycobacterial infections in 11%, coccidioidomycosis in 10%, unspecified fungal infection in 8%, blastomycosis in 4%, cryptococcal infection in 3%, and pneumocystosis in 2%. Compared to controls (n = 474), a higher proportion of cases were prescribed prednisone (55% versus 37%; P < 0.001). Patients who were prescribed prednisone during the study period were twice as likely as those not taking prednisone to seek medical care attributable to a targeted fungal or mycobacterial infection (odds ratio 2.03; P < 0.001). CONCLUSION: Development of a targeted fungal or mycobacterial infection among patients taking a TNFi is rare. Concomitant use of prednisone predicted development of such infections.

Blastomycosis infection of the knee treated with staged total knee arthroplasty.

Blastomycosis is a rare fungal disease that can cause intraarticular infection and joint destruction requiring surgical reconstruction. We describe a patient who presented with destruction of the knee joint of unknown etiology. The patient was initially treated with debridement and spacer placement followed by antifungal therapy after cultures grew blastomycosis. Following adequate treatment of the infection, the patient was taken back to the operating room for reconstruction with a total knee arthroplasty. The patient had a successful outcome with no evidence of infection at two years following surgery. To our knowledge, this case report represents the first documented case in which a blastomycotic infection of a native knee was successfully treated with a two-stage total knee arthroplasty.

A rare opportunistic infection in a woman with systemic lupus erythematosus and multiple skin lesions.

Cutaneous lesions in patients with systemic lupus erythematosus (SLE) represent diagnostic challenges. Opportunistic infections should be considered when lupus patients are on immunosuppressive therapy and other causes, such as disease activity, are less likely to explain the skin lesions. Within the spectrum of skin opportunistic infections that might occur in SLE patients, Blastomyces dermatitidis should be suspected when acid-fast positive material with no bacilliform organisms is seen on Ziehl-Nielsen skin biopsy preparations. In this study, we describe one patient with SLE on immunosuppressive therapy, who developed cutaneous blastomycosis despite living in a non-endemic area. Because of lack of awareness about this association and misinterpretation of the skin biopsy results, the diagnosis of atypical mycobacterial infection was initially considered. Subsequent proper tissue staining and interpretation revealed the correct diagnosis of disseminated cutaneous blastomycosis. This description represents the first report of this rare opportunistic skin infection in SLE, illustrating the importance of performing correct preparation and elucidation of the skin biopsy to avoid misdiagnosis and treatment delay.

Fungal infections in solid organ transplantation.

Fungal infections in solid organ transplant recipients continue to be a significant cause of morbidity and mortality. Candida spp. and Aspergillus spp. account for most invasive fungal infections. The incidence of fungal infection varies with type of solid organ transplant. Liver transplant recipients have highest reported incidence of candida infections while lung transplant recipients have highest rate of Aspergillus infections. Recent epidemiological studies suggest the emergence of resistant strains of candida as well as mycelial fungi other than Aspergillus in these patients. The current review incorporates the recent changes in the epidemiology of fungal infections in solid organ transplant recipients and highlights the newer data on the diagnosis, prophylaxis and treatment of fungal infections in these patients.

Symptoms of pulmonary blastomycosis: northern Wisconsin, United States.

OBJECTIVE: Pulmonary disease is the most common manifestation of the systemic fungal infection, blastomycosis. This study examines symptoms of pulmonary blastomycosis and possible age and gender differences in a 22-year case series. METHODS: Laboratory-confirmed cases of blastomycosis were identified from mandatory reports to the Vilas County Health Department (1984--2001) and from hospital records and case contacts before mandated reports (November 1979--1983). Symptoms were ascertained by interviews of respondent cases (or next of kin) by using a standard form. Proportions were compared with the chi-square test or Fisher exact test. RESULTS: One hundred seventy cases of blastomycosis (mean age 44, 56% male) were identified and pulmonary manifestations were present in 154 (91%). Of the 118 interviewed cases, the following symptoms were common: cough (90%), fever (75%), night sweats (68%), weight loss (66%), chest pain (63%), dyspnea (54%), and aches (50%). Hemoptysis occurred in 18%, and nearly all queried patients had fatigue. The dyad of cough and fever occurred in 73%, and triads of fever-cough-night sweats, fever-cough-weight loss, and fever-cough-chest pain occurred in 58%, 57%, and 51%, respectively. Among men, fever (P = .03), cough and fever (P = .03), fever-cough-weight loss (P = .03), and fever-cough-night sweats (P = .03) were less common in those 50 years of age and older. Symptoms did not vary by duration of illness. CONCLUSIONS: Cough, fever, night sweats, weight loss, chest pain, dyspnea, and aches are common symptoms of pulmonary blastomycosis. Symptom constellations that included fever were less common in men 50 years of age and older. There was no apparent difference in symptoms between acute and chronic blastomycosis.

Cutaneous blastomycosis presenting as non-healing ulcer and responding to oral ketoconazole.

Primary cutaneous blastomycosis is a rare infection of the skin that usually follows trauma and presents as a papule or nodule that ulcerates. Although this infection often heals spontaneously, we present a case of a nonhealing ulcer following surgical drainage of cellulitis. Blastomycosis was diagnosed by histopathological examination and the infection responded well to oral ketoconazole therapy.

Cluster of pulmonary blastomycosis in a rural community: evidence for multiple high-risk environmental foci following a sustained period of diminished precipitation.

Much of our understanding of the epidemiologic features of infection with Blastomyces dermatitidis has come from cluster and outbreak investigations which have established the association of human disease with recreational pursuits and the presence of infectious microfoci in areas of moist soil with high organic content. This report describes the clustering of eight cases of pulmonary blastomycosis without an apparent common source exposure which occurred during a 90 day period in a 96 square mile area (population 4,450) within Oconto County, Wisconsin. We conclude that multiple high-risk environmental foci may have existed following a sustained five-year period of diminished precipitation in the cluster area. A case-control study which included family and community controls concluded that multiple earth-disturbing activities engaged in by case-patients was statistically associated with illness. Lymphocyte-proliferation assays of whole blood samples detected previously unrecognized infection with B. dermatititidis among five of 32 family controls.

Using new genetic tools to study the pathogenesis of Blastomyces dermatitidis.

Fungal pathogens have emerged as a public health menace owing to the expanding population of vulnerable patients and a heightened exposure to fungi in our environment, particularly for the systemic dimorphic fungi that inhabit soil worldwide. A better understanding of these invaders and their pathogenic mechanisms is badly needed to further research into therapeutic options. Advances in the molecular tools available for genetic manipulation of Blastomyces dermatitidis have enhanced our ability to study this poorly understood dimorphic fungal pathogen. Recent refinements in gene-transfer techniques, new selection markers, reliable reporter fusions and successes in gene targeting have shed light upon the importance of the mycelium-to-yeast transition and the crucial and complex role the BAD1 adhesin plays in pathogenesis.