Disseminated Blastomycosis in an Immunocompetent Patient.

Blastomycoses dermatitidis is a dimorphic fungus that can cause disseminated blastomycosis with varying clinical manifestations and multiorgan involvement. While blastomycosis commonly causes pulmonary disease, extrapulmonary spread can result in skin, bone, and central nervous system involvement. Cutaneous blastomycosis can present as pustular lesions that evolve into ulcerative or verrucous plaques. We present a case of disseminated blastomycosis in an immunocompetent patient with both pulmonary and cutaneous features. The patient developed hypoxic respiratory failure and was subsequently diagnosed with disseminated blastomycosis after undergoing bronchoscopy with bronchial washing. He was found to have ulcerative nasal lesions as part of his disseminated disease. He was successfully treated with amphotericin B and ultimately discharged from the hospital.

Epistaxis and Facial Swelling Due to Nasal Blastomycosis in a Cat.

A 5 yr old castrated male domestic longhair was examined because of left-sided facial swelling and epistaxis. Head computed tomography with contrast identified a mass within the left nasal cavity and multifocal regions of nasal bone osteolysis. Histopathology of nasal mass biopsies and cytology of the facial swelling revealed pyogranulomatous inflammation due to Blastomyces dermatitidis. The cat experienced resolution of clinical signs following 8 mo of treatment with itraconazole. Although rare, clinicians should include blastomycosis on the differential diagnoses list of infectious causes for feline nasal disease if within an endemic area.

Diagnostic delay in pulmonary blastomycosis: a case series reflecting a referral center experience.

PURPOSE: The diagnosis of pulmonary blastomycosis is usually delayed because of its non-specific presentation. We aimed to assess the extent of diagnostic delay in hospitalized patients and detect the step in the diagnostic process that requires the most improvement. METHODS: Adult patients diagnosed with pulmonary blastomycosis during a hospital admission between January 2010 through November 2021 were eligible for inclusion. Patients who did not have pulmonary involvement and who were diagnosed before admission were excluded. Demographics and comorbid conditions, specifics of disease presentation, and interventions were evaluated. The timing of the diagnosis, antifungal treatment, and patient outcomes were noted. Descriptive analytical tests were performed. RESULTS: A total of 43 patients were diagnosed with pulmonary blastomycosis during their admissions. The median age was 47 years, with 13 (30%) females. Of all patients, 29 (67%) had isolated pulmonary infection, while 14 (33%) had disseminated disease, affecting mostly skin and musculoskeletal system. The median duration between the initial symptoms and health care encounters was 4 days, and the time to hospital admission was 9 days. The median duration from the initial symptoms to the diagnosis was 20 days. Forty patients (93%) were treated with empirical antibacterials before a definitive diagnosis was made. In addition, corticosteroid treatment was empirically administered to 15 patients (35%) before the diagnosis, with indications such as suspicion of inflammatory processes or symptom relief. In 38 patients (88%), the first performed fungal diagnostic test was positive. Nineteen patients (44%) required admission to the intensive care unit, and 11 patients (26%) died during their hospital stay. CONCLUSION: There was a delay in diagnosis of patients with pulmonary blastomycosis, largely attributable to the lack of consideration of the etiological agent. Novel approaches to assist providers in recognizing the illness earlier and trigger evaluation are needed.

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.

Does metabolite matter? Defining target itraconazole and hydroxy-itraconazole serum concentrations for blastomycosis.

BACKGROUND: Itraconazole is the recommended first-line treatment for mild-to-moderate blastomycosis and consolidation treatment of moderate-to-severe disease. Itraconazole is metabolised into three metabolites, including an active metabolite hydroxy-itraconazole. Literature provides little evidence indicating whether therapeutic drug monitoring targets should be based on itraconazole parent compound alone or a sum of itraconazole and hydroxy-itraconazole serum concentrations. OBJECTIVES: This study aims to compare clinical outcomes and adverse drug events (ADEs) of combined itraconazole and hydroxy-itraconazole concentrations versus itraconazole parent compound alone in patients with blastomycosis. PATIENTS/METHODS: This study was a retrospective cohort review of patients ≥18 years with probable or proven Blastomyces infection who received itraconazole with at least one documented serum itraconazole concentration. The primary outcome was rate of partial or complete treatment response across three patient groups: (1) Itraconazole parent compound >1.0 mcg/ml (parent), (2) parent compound <1.0 mcg/ml, but a combined itraconazole and hydroxy-itraconazole >1.0 mcg/ml (combined) and (3) failure to achieve a combined or parent concentration >1.0 mcg/ml (subtherapeutic) for >75% of the duration of itraconazole therapy. RESULTS: A total of 80 patients were included (parent = 32, combined = 36, subtherapeutic = 12). No statistically significant difference was observed for rate of partial or complete treatment response (97% parent vs 94% combined, p = .99). Significantly higher mortality due to blastomycosis was observed in patients in the subtherapeutic group (0% parent vs 3% combined vs 25% subtherapeutic, p = .01). CONCLUSIONS: This study supports an itraconazole therapeutic target combining itraconazole and hydroxy-itraconazole >1.0 mcg/ml for blastomycosis treatment.

Disseminated Blastomycosis in an African American immunocompetent pediatric patient: Lessons learned.

Disseminated blastomycosis can be challenging to diagnose given possible involvement of nearly any extrapulmonary organ system and the limitations of fungal diagnostic testing. Certain racial groups are at increased risk of disseminated fungal infections, even in immunocompetent patients. We describe a case of disseminated blastomycosis with cutaneous involvement in an African American adolescent with delayed diagnosis. Dermatologists can play an important role in the timely diagnosis of this disease entity by performing appropriate cutaneous biopsy techniques and should be involved early in these cases.

Negative Antigenuria in a Dog with Suspected Central Nervous System Localized Blastomycosis.

A 7 yr old female spayed mixed-breed dog was presented for a 1 wk history of neck pain and pelvic limb weakness. Examination revealed nonambulatory paraparesis and thoracolumbar hyperesthesia. MRI revealed extensive intramedullary T2-weighted/short tau inversion recovery hyperintensity and diffuse severe T1-post contrast meningeal enhancement of the thoracolumbar spinal cord. An L5-L6 cerebrospinal fluid sample revealed a suppurative pleocytosis (81% neutrophils, total protein 4362.5 mg/dL and nucleated cell count 352,000/µL). While awaiting the results of infectious disease testing, the dog was treated for suspected meningoencephalitis of unknown etiology with corticosteroids, cyclosporine, and a cytarabine arabinoside infusion. The dog neurologically declined and was started on broad-spectrum antibiotics. The dog continued to decline despite antibiotics, and infectious disease titers subsequently revealed serum antibody positivity for blastomycosis. The dog was then referred to a multispecialty referral hospital and was treated with amphotericin B followed by fluconazole. Prednisone was continued at anti-inflammatory doses. Urine blastomycosis antigen testing was submitted for subsequent disease monitoring but was negative. Five months after presentation the dog was clinically doing well with no identifiable neurologic deficits. This case demonstrates that neurologic blastomycosis may have negative urine antigen concentrations in some dogs and that other diagnostic modalities should be pursued when central nervous system fungal disease is suspected.

Disseminated blastomycosis with cutaneous involvement in a 57-year-old woman: a case report and review of management.

Blastomycosis is an infectious disease produced by the fungal organisms, Blastomyces dermatiditis and Blastomyces gilchristi. We present a 57-year-old woman with pulmonary blastomycosis and secondary cutaneous involvement. Her diagnosis was facilitated by dermatology consultation after approximately one year of delay. In endemic areas including Canada and the USA, individuals are at risk for blastomycosis when non-motile fungal spores are inhaled, thus producing pulmonary disease. The organism may disseminate over time, affecting a variety of extrapulmonary organ systems including the skin. In endemic regions of blastomycosis, this important cutaneous manifestation of disease should be considered with a high index of suspicion as to avoid delayed resolution and adverse outcomes.

A rare presentation of blastomycosis as a multi-focal infection involving the spine, pleura, lungs, and psoas muscles in a Saudi male patient: a case report.

BACKGROUND: Blastomycosis is a disease caused by the fungus Blastomyces-a thermally dimorphic fungus that can cause granulomatous and/or purulent infection. CASE PRESENTATION: We report here a case of chronic blastomycosis infection in a 24-year-old male patient from Saudi Arabia who presented with recurrent skin abscesses associated with deep-seated and multilevel paraspinal (dorsal and lumbar) collections and bilateral empyema with pulmonary involvement and bilateral psoas abscesses. The diagnosis was made after a CT-guided pleural biopsy revealed the characteristic histopathological findings of blastomycosis. The patient underwent several drainage procedures and was successfully treated with a long-term course of oral itraconazole. CONCLUSIONS: Chronic blastomycosis may have clinical and radiologic features similar to thoracic tuberculosis or malignant disease. There is no definite clinical symptom of blastomycosis, and thus a high degree of suspicion is required for early diagnosis. This case is a rare form of blastomycosis with chronic multifocal purulent infection and is the second case of blastomycosis reported in Saudi Arabia.

Disseminated blastomycosis in a 1-year-old, male golden retriever-poodle crossbred dog.

A 1-year-old male golden retriever-poodle crossbred dog was brought to a veterinary clinic with a 1-month travel history to Muskoka, Ontario and a 1-week history of left eye irritation and ocular discharge. Ophthalmic examination and blood analysis revealed bilateral uveitis with a normal complete blood (cell) count and biochemistry panel. Symptomatic treatment was administered with no improvement observed and the dog returned 2 weeks later for assessment of a draining swelling of the left hind 4th digit. Clinical examination of thoracic radiographs and abdominal ultrasound showed evidence of disseminated blastomycosis characterized by pulmonary lesions, and multifocal lymphadenopathy. Biopsy of the draining lesion and cytological examination of an enlarged lymph node established diagnosis. The dog was started on a standard antifungal treatment protocol (itraconazole) but returned after 11 d of treatment with neurological signs including ataxia, paraparesis, left head tilt, and compulsive turning. Humane euthanasia was chosen and the diagnosis was confirmed at postmortem examination.

Blastomycose disséminée chez un chien croisé golden retriever-caniche mâle de 1 an. Un chien croisé golden retriever-caniche mâle âgé d'un an a été amené à une clinique vétérinaire avec un historique de voyage d'un mois à Muskoka, en Ontario et une histoire d'irritation de l'oeil gauche et d'écoulement oculaire d'une semaine. L'examen ophtalmologique et l'analyse sanguine ont révélé une uvéite bilatérale avec une numération globulaire complète et un bilan biochimique normaux. Un traitement symptomatique a été administré sans amélioration observée et le chien est revenu 2 semaines plus tard pour l'évaluation d'une enflure drainante du 4e doigt postérieur gauche. L'examen clinique des radiographies thoraciques et de l'échographie abdominale a montré des signes de blastomycose disséminée caractérisée par des lésions pulmonaires et une lymphadénopathie multifocale. Une biopsie de la lésion drainante et un examen cytologique d'un noeud lymphatique augmenté de volume ont permis d'établir le diagnostic. Le chien a débuté un protocole de traitement antifongique standard (itraconazole) mais est revenu après 11 jours de traitement avec des signes neurologiques, notamment ataxie, paraparésie, inclinaison de la tête à gauche et tournis compulsif. L'euthanasie sans cruauté a été choisie et le diagnostic a été confirmé lors de l'autopsie.(Traduit par Dr Serge Messier).

Reconstruction of full width, full thickness cicatricial eyelid defect after eyelid blastomycosis using a modified tarsoconjunctival flap advancement.

Following effective treatment with systemic antifungal therapy, eyelid lesions from blastomycosis infection may be replaced by disfiguring fibrosis and scarring, which may be surgically challenging to correct. A 68-year-old man with biopsy-proven eyelid blastomycosis was treated with 6 months of oral voriconazole, but resolution of the lesion was complicated by cicatricial changes causing complete lower eyelid defect, epicanthal web, cicatricial mechanical ptosis, and skin plaques. Although repair adhered to the fundamentals of eyelid reconstruction, cicatricial changes associated with blastomycosis infection necessitated a modified approach and attachment sites. A tarsoconjunctival flap (Hughes flap) with modified flap connections utilizing cicatrix and remaining viable tissue was employed to reconstruct the lower eyelid defect and combined with tissue advancement using a Mustardé four-flap epicanthoplasty and post-auricular full-thickness skin graft. Satisfactory cosmetic outcome was achieved at last follow-up of 3.5 months postoperatively. This case demonstrates a feasible technique for reconstruction of significant eyelid defects following robust cicatricial changes such as those after blastomycosis. This report also presents the first description of reconstruction of lower eyelid defect and of posterior lamellar loss after blastomycosis infection.

Clinical Manifestations and Outcomes in Immunocompetent and Immunocompromised Patients With Blastomycosis.

BACKGROUND: Blastomyces is a dimorphic fungus that infects persons with or without underlying immunocompromise. To date, no study has compared the clinical features and outcomes of blastomycosis between immunocompromised and immunocompetent persons. METHODS: A retrospective study of adult patients with proven blastomycosis from 2004-2016 was conducted at the University of Wisconsin. Epidemiology, clinical features, and outcomes were analyzed among solid-organ transplantation (SOT) recipients, persons with non-SOT immunocompromise (non-SOT IC), and persons with no immunocompromise (NIC). RESULTS: A total of 106 cases met the inclusion criteria including 74 NIC, 19 SOT, and 13 non-SOT IC (malignancy, HIV/AIDS, idiopathic CD4+ lymphopenia). The majority of patients (61.3%) had at least 1 epidemiologic risk factor for acquisition of Blastomyces. Pneumonia was the most common manifestation in all groups; however, immunocompromised patients had higher rates of acute pulmonary disease (P = .03), more severe infection (P = .007), respiratory failure (P = .010), and increased mortality (P = .02). Receipt of SOT primarily accounted for increased severity, respiratory failure, and mortality in immunosuppressed patients. SOT recipients had an 18-fold higher annual incidence of blastomycosis than the general population. The rate of disseminated blastomycosis was similar among NIC, SOT, and non-SOT IC. Relapse rates were low (5.3-7.7%). CONCLUSIONS: Immunosuppression had implications regarding the acuity, severity, and respiratory failure. The rate of dissemination was similar across the immunologic spectrum, which is in sharp contrast to other endemic fungi. This suggests that pathogen-related factors have a greater influence on dissemination for blastomycosis than immune defense.

Symptoms in Blastomycosis, Coccidioidomycosis, and Histoplasmosis Versus Other Respiratory Illnesses in Commercially Insured Adult Outpatients-United States, 2016-2017.

BACKGROUND: Blastomycosis, coccidioidomycosis, and histoplasmosis cause various symptoms and syndromes, which may present similarly to other infections such as bacterial or viral community-acquired pneumonia, influenza, and tuberculosis. METHODS: We used the IBM MarketScan Research Databases to identify adult outpatients with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), diagnosis codes during 2016-2017 for blastomycosis, coccidioidomycosis, histoplasmosis, pneumonia (viral, bacterial, Streptococcus pneumoniae, and unspecified pneumonia), influenza; tuberculosis, and other lower and upper respiratory infections. We compared symptoms on and in the 90 days before diagnosis between patients with these diagnosis codes. RESULTS: Fever was less common in blastomycosis (2.6%), histoplasmosis (5.3%), and coccidioidomycosis (9.4%) than in patients with influenza (18.5%) or pneumonia (12.6-16.3%). Fungal diseases resembled bacterial, viral, and unspecified pneumonias for many pulmonary symptoms. However, cough was more common with coccidioidomycosis (31.4%) and less common with histoplasmosis (14.0%) and blastomycosis (13.1%) versus influenza (20.2%). Although less frequent, solitary pulmonary nodule (5.2-14.4%), enlarged lymph nodes (3.7-9.0%), hyperhidrosis (<2%), and erythema nodosum (<2%) were particularly suggestive of fungal diseases. CONCLUSIONS: Despite limitations inherent in administrative coding, this analysis of symptom codes across disease types suggests that fungal diseases may be difficult to clinically distinguish from other causes of pneumonia except when certain uncommon symptoms are present. Healthcare providers caring for patients with pneumonia, especially if nonresponsive to conventional treatment, should consider fungal diseases as possible etiologies.

Central nervous system blastomycosis clinical characteristics and outcomes.

Blastomycosis is a local or systemic infection, caused by Blastomyces dermatitidis (B. dermatitidis) or B. gilchristii. Blastomycosis has been described as "the great pretender," alluding to the fact that it manifests in a wide range of symptoms and disease severity. Central nervous system (CNS) involvement, although rare, carries significant mortality. Due to the limited published reports of CNS blastomycosis, we present an updated cohort with eight cases of proven or probable CNS blastomycosis describing presentation, diagnosis, treatment and outcomes. Headache was the most common presenting symptom. Magnetic resonance imaging (MRI) proved to be the superior imaging study. All patients in our cohort were diagnosed by histopathological staining or cultures of tissue or fluid obtained from CNS or extra-CNS lesions. All patients that received treatment with Liposomal amphrotericin B for at least 10 days followed by a prolonged azole therapy did not have relapse. Two patients with late diagnoses died during hospitalization. Our findings confirm the importance of timely diagnosis and treatment of CNS blastomycosis to improve outcomes especially with an azole that have a high CNS penetration and a good intrinsic activity for B. dermatitidis such as voriconazole.

Disseminated blastomycosis in a kidney transplant recipient.

Disseminated blastomycosis in solid organ transplant is uncommon. The diagnosis is usually challenging due to vague clinical presentations, which could lead to a devastating outcome. We reported a unique case of disseminated blastomycosis with laryngeal involvement in a kidney transplant recipient who presented with hoarseness. The diagnosis was made by histopathology and culture of laryngeal mass.

Blastomycosis in solid organ transplant recipients-A retrospective series from southeastern Wisconsin.

Blastomycosis is a fungal infection caused primarily by Blastomyces dermatitis. The fungus is endemic to the Ohio, Mississippi, and St. Lawrence River areas of the United States. Organ transplant recipients are at risk of blastomycosis due to pharmacologic immunosuppression. Over a 20-year period, 30 cases of blastomycosis post-solid organ transplantation were identified at our center. The cumulative incidence of blastomycosis among SOT recipients was 0.99%. There was a male predominance (70% male) and a median age of 59 at the time of diagnosis. Regarding transplant type, 23 patients received kidney transplants, 4 received liver transplants, 2 received pancreas transplants and 1 received a heart transplant. Median time to blastomycosis identification post-transplant was 67.8 months (range: 1-188 months). Amphotericin B was used as initiation therapy in most cases, followed by itraconazole, voriconazole, or in select cases fluconazole or posaconazole maintenance therapy. Regarding comorbid conditions, 87% of patients had diabetes, 50% had congestive heart failure, and 20% had chronic pulmonary disease. Nine patients (30%) developed blastomycosis-related acute respiratory distress syndrome, 33% of these died with a median time to death of 22 days (range 20 days to 2 months); these were the only deaths attributable to blastomycosis.

Reconstruction Following Talectomy Due to Disseminated Blastomycosis in Immunocompetent Adult Utilizing Total Talus Prosthesis: A Case Report.

Blastomycosis is a rare condition affecting specific endemic areas in North America. Blastomycosis is characterized primarily as a pulmonary disease but can disseminate to affect other organ systems. Osteomyelitis due to disseminated blastomycosis is a rare condition with limited functional reconstructive options in a young adult. We present a rare case with prolonged antifungal therapy and staged reconstruction with a total talus prosthesis.

Blastomycosis in Minnesota, USA, 1999-2018.

Blastomycosis is a systemic disease caused by Blastomyces spp. fungi. To determine its epidemiology in blastomycosis-endemic Minnesota, USA, we evaluated all cases reported to public health officials during 1999-2018. We focused on time to diagnosis, exposure activities, and exposure location. A total of 671 cases and a median of 34 cases/year were reported. Median time to diagnosis was 31 days; 61% of patients were not tested for blastomycosis until they were hospitalized. The case-fatality rate was 10%, and patients who died were 5.3 times more likely to have a concurrent medical condition. Outdoor activities and soil exposure were reported by many patients, but no specific activity or exposure was common to most. Almost one third of patients were probably exposed in geographic areas other than their home county. Providers should consider alternative etiologies for patients with pneumonia not responding to antibacterial treatment, and public health officials should increase awareness in blastomycosis-endemic areas.

Spiromastigoides asexualis: Phylogenetic Analysis and Evaluation as a Cause of False-Positive Blastomyces DNA Probe Test Results.

This is the first case of Spiromastigoides asexualis human infection, and it notably gave a false-positive Blastomyces DNA probe laboratory result. We further investigated other Spiromastigoides isolates as a cause of false-positive testing results, their phylogenetic relationship, and their susceptibility profiles to clinically available antifungal agents. Other S. asexualis isolates also resulted in positive Blastomyces DNA probe results, while Spiromastigoides species other than S. asexualis did not.