A Unique Case of Coexisting Anaplasmosis and Blastomycosis.

INTRODUCTION: In presenting this case of tick-borne illness in a patient with known disseminated blastomycosis, we aim to discuss the clinical reasoning and decision-making process when treating a septic presentation in a complex patient with multiple exposures and risk factors, from identifying and addressing the most devastating differentials to selecting appropriate empiric anti-infective regimens. CASE PRESENTATION: We present the case of a 60-year-old male with a medical history of diastolic heart failure, cirrhosis, sarcoidosis, hypertension, splenectomy, and recently diagnosed disseminated blastomycosis, who developed sepsis following a recent tick exposure. DISCUSSION: While a review of the literature revealed a paucity of cases of coexisting fungal and tick-borne illness, each is independently well-studied. Several reported commonalities exist between Blastomyces and Anaplasma, including endemic regions and at-risk populations.

Beware of the Acute Respiratory Distress Syndrome in a Pulmonary Blastomycosis!

Blastomyces dermatitidis is a dimorphic fungus that can range from mild to severe disease presentation, including the acute respiratory distress syndrome (ARDS) based on the individual's immunity. Acute respiratory distress syndrome is an uncommon presentation having an incidence of about 10% to 15% but has a high mortality exceeding 90%. This is a case of a 50-year-old female with past medical history of asthma and type 2 diabetes mellitus who presented to the pulmonology clinic with worsening dyspnea for the last 2 months. She also had a lesion in the left lower back, which was draining purulent fluid. Chest radiographs showed bilateral infiltrates and was started empirically on vancomycin and piperacillin-tazobactam. Bronchoalveolar lavage was done and the cultures grew B dermatitidis. The patient was moved to a higher level of care and given amphotericin B. Unfortunately, the patient experienced septic shock, which later deteriorated into cardiac arrest, ultimately leading to their passing. The importance of early diagnosis of blastomycosis and timely treatment has been emphasized in this case report.

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.

Intensive Care Unit and Hospital Outcomes of Patients Admitted with Blastomycosis: A 14-Year Retrospective Study.

INTRODUCTION: Blastomycosis is an uncommon; potentially life-threatening granulomatous fungal infection. The aim of this study is to report hospital and intensive care unit (ICU) outcomes of patients admitted with blastomycosis. METHODS: All patients admitted for treatment of blastomycosis at the Mayo Clinic-Rochester, Minnesota between 01/01/2006 and 09/30/2019 were included. Demographics, comorbidities, clinical presentation, ICU admission, and outcomes were reviewed. RESULTS: A total of 84 Patients were identified with 90 unique hospitalizations primarily for blastomycosis. The median age at diagnosis was 49 (IQR 28.1-65, range: 6-85) years and 56 (66.7%) were male. The most frequent comorbidities included hypertension (n = 28, 33.3%); immunosuppressed state (n = 25, 29.8%), and diabetes mellitus (n = 21, 25%). The lungs were the only organ involved in 56 (66.7%) cases and the infection was disseminated in 19 (22.6%) cases. A total of 29 patients (34.5%) underwent ICU admission due to complications of blastomycosis. ICU related events included mechanical ventilation (n = 20, 23.8%), acute respiratory distress syndrome (ARDS) (n = 13, 15.5%), tracheostomy (n = 9, 10.7%), renal replacement therapy (n = 8, 9.5%), and extracorporeal membrane oxygenation (ECMO) (n = 4, 4.8%). A total of 12 patients (14.3%) died in the hospital; all of whom had undergone ICU admission. In-hospital mortality was associated with renal replacement therapy (RRT) (P = 0.0255). CONCLUSION: Blastomycosis is a serious, potentially life-threatening infection that results in significant morbidity and mortality with a 34.5% ICU admission rate. RRT was associated with in-hospital mortality.

Pulmonary Blastomycosis: A Rare Cause of Acute Chest Syndrome and Prolonged Fevers in a Pediatric Patient With Sickle Cell Disease.

Blastomyces is a fungus found in the soil of regions of North America including the Mississippi and Ohio River Valleys. It can be inhaled into the lungs and cause pneumonia and disseminated disease. Although blastomycosis is not widely reported in the sickle cell literature, sickle cell patients may be at increased risk of complications from blastomycosis pneumonia due to their immune compromise and risk of developing acute chest syndrome. We describe the case of a 13-year-old female with homozygous sickle cell disease who presented with pneumonia and acute chest syndrome and was found to have pulmonary blastomycosis.

Unremitting Pain and Fever in a 15-Year-Old Boy With Osteomyelitis.

A previously healthy 15-year-old boy from a rural county in the southeastern United States was evaluated in the emergency department with fever and worsening toe pain in the absence of trauma. He initially presented to his primary care physician 4 weeks before with upper respiratory symptoms and was treated with corticosteroids for presumed reactive airway disease. His respiratory symptoms resolved. One week after this presentation, he developed fever and right great toe pain and presented to an outside hospital. Inflammatory markers were elevated. MRI confirmed a diagnosis of osteomyelitis with associated periosteal abscess. He was treated with intravenous antibiotics and drainage of the abscess. Ten days after his discharge from the outside hospital, he developed fever and had increasing drainage of the toe and pain refractory to oral pain medications. He presented to our facility for further evaluation. Repeat MRI and inflammatory markers corroborated his worsening disease, and he was admitted to the hospital for intravenous antibiotics and underwent serial surgical debridement. He developed painful subcutaneous nodules on his lower extremities and was found to have lung abnormalities on chest radiograph. A multispecialty team collaborated in the management of this patient and unveiled a surprising diagnosis.

Upper Airway Obstruction Due to Primary Laryngeal Blastomycosis in a Dog.

A 9 yr old female spayed Labrador retriever presented for progressive dyspnea. Inspiratory stridor and inspiratory and expiratory dyspnea were present, consistent with an upper airway obstruction. A laryngeal exam revealed severe thickening of the arytenoid cartilages and masses associated with the arytenoids. A tracheostomy tube was placed, and the masses were biopsied. Histopathology showed pyogranulomatous inflammation secondary to Blastomyces dermatitidis. The dog was initially treated with amphotericin B and terbinafine in the hospital until the airway obstruction resolved and the tracheostomy tube could be removed. The dog experienced complete recovery after long-term treatment with itraconazole and terbinafine. This is the first report of laryngeal obstruction secondary to primary laryngeal blastomycosis in a dog. Blastomycosis should be considered for cases of obstructive laryngeal disease, and a good outcome can be achieved with antifungal treatment.

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.

Altered Pharmacokinetics and Dosing of Liposomal Amphotericin B and Isavuconazole during Extracorporeal Membrane Oxygenation.

Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2-fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.

Pleural Effusion in Pulmonary and Extrapulmonary Blastomycosis.

OBJECTIVE: Pleural effusion secondary to blastomycosis infection is an uncommon clinical manifestation of the disease. We undertook a retrospective study to assess the incidence and involvement of pleural effusion in patients with blastomycosis infection. STUDY DESIGN: Institutional cytology and surgical pathology records were searched from December 1995 to October 2017 for cases of blastomycosis. The cytologic, surgical pathology, and clinical pertinent information was reviewed in detail. RESULTS: A total of 77 cases of blastomycosis infection were recorded, with a male-to-female ratio of 1.7:1.0. Forty-eight cases of blastomycosis were pulmonary (62.3%), while 29 cases of blastomycosis were found in extrapulmonary sites (37.7%). The diagnosis of pulmonary blastomycosis was established by 24 lung biopsies/wedge resections, 22 bronchial alveolar lavages, and 2 lung fine needle aspirations. The 29 cases of extrapulmonary blastomycosis included 13 cases of bone (44.8%), 8 cases of skin (27.6%), 6 cases of soft tissue (20.7%), and 2 cases of brain infections (6.8%). Twenty-eight of 48 pulmonary cases were complicated by unilateral or bilateral pleural effusion (58.3%) detected by imaging studies. Four of the 28 pleural effusions were aspirated and examined by cytology. Two of the 4 pleural fluid cytologies showed involvement by blastomycosis (50%). In the extrapulmonary blastomycosis group, 9 of 29 patients showed unilateral or bilateral pleural effusions (31.0%), including 4 cases of bone, 4 cases of skin, and 1 case of brain involvement. Only 2 of the 9 pleural effusions were aspirated for cytology study. One of the 2 pleural fluid cytologies showed blastomycosis (50%). CONCLUSION: Pleural effusion detected by imaging is common in blastomycosis patients. Blastomycosis can involve pleural fluid in both pulmonary and extrapulmonary diseases. A broad infectious differential that includes blastomycosis should be considered to make a timely diagnosis and initiate antifungal therapy to prevent systemic infection and further dissemination of the disease.

Dacryoadenitis Caused by Blastomycosis: A Case Report.

This is the first case of histopathologically proven blastomycosis involving the lacrimal gland. A 51-year-old woman with a history of disseminated blastomycosis involving her lungs and skin, on oral itraconazole, presented with 3 days of right upper eyelid swelling, erythema, and pain concerning for recurrent dacryoadenitis. MRI showed enlargement of the right lacrimal gland with a cystic lesion at the anterior aspect of the gland with a radiographic differential diagnosis of abscess versus cyst. After no improvement with intravenous antibiotics, orbitotomy with lacrimal gland biopsy and incision and drainage of the cystic lesion were performed. Culture and pathology of the drained fluid demonstrated an abscess with both viable and nonviable broad-based budding yeast consistent with partially treated blastomycosis. The patient's symptoms improved after the surgery and continued itraconazole therapy.

Treatment of pulmonary blastomycosis with high-dose liposomal amphotericin B in a patient receiving extracorporeal membrane oxygenation.

Blastomycosis-associated acute respiratory distress syndrome (ARDS) has a rare incidence. We report the case of a 29-year-old man with blastomycosis-associated ARDS receiving extracorporeal membrane oxygenation and managed with high-dose liposomal amphotericin B. This case illustrates the importance of timely diagnosis of pulmonary blastomycosis and appropriate dosing of antifungal therapy.

Apparent interference with extracorporeal membrane oxygenation by liposomal amphotericin B in a patient with disseminated blastomycosis receiving continuous renal replacement therapy.

PURPOSE: We describe the use of liposomal amphotericin B and amphotericin B deoxycholate in a critically ill patient with pulmonary blastomycosis receiving both venovenous extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). SUMMARY: A 50-year-old African American man presented for dyspnea and cough and was noted to have blastomycosis on bronchoscopy. He developed respiratory failure and acute kidney injury, requiring mechanical ventilation, ECMO, and CRRT. After 4 days of liposomal amphotericin, the transmembrane pressure gradient on the membrane oxygenator increased dramatically without visualization of a clot, requiring a circuit exchange. A trough amphotericin B level taken the day before the exchange was undetectable for amphotericin B. After the circuit exchange, the patient was switched to amphotericin B deoxycholate. A subsequent trough level was 3.8 µg/mL. The patient improved and was able to be decannulated. However, he did require tracheostomy and long-term hemodialysis. CONCLUSION: In our case we believe that liposomal amphotericin B was significantly removed by ECMO and was responsible for the failure of the ECMO circuit. We would suggest amphotericin B deoxycholate be used in such patients preferentially and that serum levels of the drug be assessed when possible.

Veno-venous extracorporeal life support for blastomycosis-associated acute respiratory distress syndrome.

BACKGROUND: Blastomyces is a dimorphic fungus endemic to regions of North America, which can lead to pneumonia and fatal severe acute respiratory diseases syndrome in up to 89% of patients. Extracorporeal life support can provide adequate oxygenation while allowing the lungs to rest and heal, which might be an ideal therapy in this patient group, although long-term clinical and radiological outcomes are not known. CLINICAL FEATURES: We report on five consecutive patients admitted to Toronto General Hospital intensive care unit between January 2012 and September 2016, with progressive respiratory failure requiring veno-venous extracorporeal life support within 24-96 hours following mechanical ventilation. Ultra-lung protective mechanical ventilation was achieved within 24 hours. Recovery was the initial goal in all patients. Extracorporeal life support was provided for a prolonged period (up to 49 days), and four patients were successfully discharged from the intensive care unit. Long-term radiological assessment in three patients showed major improvement within 2 years of follow-up with some persistent disease-related changes (bronchiectasis, fibrosis, and cystic changes). In two patients, long-term functional and neuropsychological outcomes showed similar limitations to what is seen in acute respiratory distress syndrome patients who are not supported with extracorporeal life support and in acute respiratory distress syndrome patients without blastomycosis, but worse pulmonary function outcomes in the form of obstructive and restrictive changes that correlated with the radiological imaging. CONCLUSION: Veno-venous extracorporeal life support can effectively provide prolonged support for patients with blastomycosis-associated acute respiratory distress syndrome that is safe and associated with favorable long-term outcomes.

Disseminated Blastomycosis in a Teenager Presenting with Pleural Effusion and Splenomegaly.

BACKGROUND: Blastomycosis is caused by a fungus endemic to states and providences bordering the Lawrence Rivers and the Great Lakes. It can lead to significant pathology in both immunocompetent and immunocompromised hosts. This case report describes disseminated blastomycosis in an otherwise healthy 16-year-old patient. CASE REPORT: A 16-year-old male presented with a chief complaint of flank pain. In the Emergency Department he described additional symptoms of emesis, cough, and weight loss. His vitals were appropriate; however, he had absent lung sounds in the left lower lung field, splenomegaly, a left thigh abscess, and lower-extremity edema. Imaging studies showed a left pleural effusion, mediastinal shift to the right, splenomegaly, a left psoas abscess, and undifferentiated bony involvement of L1 transverse process and the left 12th rib. Abscess cultures grew Blastomyces dermatitides. He was treated with amphotericin B, demonstrated clinical improvement, and was discharged on itraconazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The case fatality rate of blastomycosis is estimated at between 4.3% and 6.4%. Patients with solid organ transplant and associated immune suppression had a mortality of 33-38%. Given the nonspecific nature of this condition, a high level of suspicion is required for diagnosis, and early diagnosis is essential, as end organ damage in disseminated disease can include high-severity illness, including acute respiratory distress syndrome and central nervous system dysfunction. If any patient presents with symptomatology involving both skin and pulmonary systems, blastomycosis must be entertained as a possible diagnosis. Prompt diagnosis and treatment will significantly improve morbidity and mortality.

The feared five fungal infections in kidney transplant recipients: A single-center 20-year experience.

Invasive fungal infections are a feared complication in kidney transplant recipients (KTRs). Here we present the University of Wisconsin experience with 5 invasive fungal infections-aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis-in KTRs transplanted between 01/01/1994 and 06/30/2014. During this period, there were 128 cases of fungal infections; aspergillosis was the most common (72), followed by cryptococcosis (29), histoplasmosis (14), blastomycosis (10), and coccidioidomycosis (3). The mean interval from transplant to fungal infection was 3.19 ± 3.58 years (range 5 days-15.8 years). By 6 months postinfection, there were 53 (41%) graft failures and 24 (19%) deaths. Graft failure occurred in 46%, 38%, 21%, 40%, and 67% of patients with aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis, respectively. Anti-thymocyte globulin (ATG) induction (HR, 1.49; 95% CI, 1.03-2.16; P = .04), diabetes (HR, 1.53; 95% CI, 1.05-2.21; P = .03), and age (HR, 1.47; 95% CI, 1.27-1.70; P ≤ .001) were associated with an increased risk for infection in univariate analysis. Multivariate adjustment retained ATG induction and older age. A large proportion of kidney transplant recipients with invasive fungal infections suffer graft failure within 3 years. Preventive, therapeutic, and monitoring strategies are needed to improve graft and patient outcomes.

Blastomycosis-like Pyoderma Arising in Lichen Planus.

Blastomycosis-like pyoderma (BLP) is a rare reactive skin disease that is most commonly caused by bacterial infection. Herein we present a case of BLP arising in lichen planus, a chronic inflammatory disease. We propose Wolf's isotopic response, or the appearance of a new skin disease at the site of an existing and unrelated disease, as the underlying molecular mechanism responsible for this unusual physical presentation. It is important that clinicians recognize atypical morphologies such as BLP, which mimics squamous cell carcinoma both clinically and pathologically. These similarities highlight the need for a tissue diagnosis to identify infectious etiologies and rule out malignancy when BLP is suspected. J Drugs Dermatol. 2018;17(2):233-235.