Recurrent blastomycosis of the central nervous system: case report and review.

Although blastomycosis of the central nervous system (CNS) occurs in approximately 4% of patients with blastomycosis, recurrent CNS blastomycosis is very rare. We review the clinical features, treatment, and outcome of 4 previously reported cases. We also report a case of recurrent CNS blastomycosis successfully treated with surgery and liposomal amphotericin B after an inadequate response to amphotericin B therapy. This treatment may be an alternate approach for management of similar cases.     

Case report: treatment of blastomycosis with fluconazole.

The authors present two cases of systemic blastomycosis successfully treated with fluconazole. In one case, the disease involved the respiratory tract, and the central nervous system was presumed to be involved. The second case consisted only of pulmonary blastomycosis. Both patients were treated with oral fluconazole 200 mg twice per day for 9 and 6 months, respectively. Treatment with this new triazole antifungal agent resulted in the complete resolution of the disease in both patients. They have remained asymptomatic for more than 6 months after the completion of therapy.     

Blastomycosis in northwestern Ontario, 2004 to 2014

Blastomycosis is an invasive fungal disease caused by Blastomyces dermatitidis and the recently discovered Blastomyces gilchristii. The medical charts of 64 patients with confirmed cases of blastomycosis in northwestern Ontario during a 10-year period (2004 to 2014) were retrospectively reviewed. The number of patients diagnosed with blastomycosis in Ontario was observed to have increased substantially compared with before 1990, when blastomycosis was removed from the list of reportable diseases. Aboriginals were observed to be disproportionately represented in the patient population. Of the patients whose smoking status was known, 71.4% had a history of smoking. 59.4% of patients had underlying comorbidities and a higher comorbidity rate was observed among Aboriginal patients. The case-fatality rate from direct complications of blastomycosis disease was calculated to be 20.3%; this case-fatality rate is the highest ever to be reported in Canada and more than double that of previously published Canadian studies. The clinical characteristics of 64 patients diagnosed with blastomycosis are summarized.     

Blastomycosis acquired by three children in Toronto

Three paediatric cases of blastomycosis, apparently acquired in or near Toronto, Ontario, a region not known to be endemic for this disease, are described. Blastomycosis was not suspected clinically in any of the three cases, and the diagnosis was established only when the diagnostic net was broadened to include fungal and mycobacterial cultures. All three patients were diagnosed after significant delays, which is consistent with the rarity of the disease in children and its acquisition outside previously accepted geographical boundaries. Pulmonary involvement was present in all three children, while one also had multifocal osteomyelitis. Drug therapy was successful in all three cases, either with amphotericin B followed by itraconazole, or itraconazole alone. Blastomycosis should be included in the differential diagnosis of a patient from the Toronto area who presents with a compatible history despite a negative travel history to known endemic zones.Key Words: Blastomyces dermatitidis, Itraconazole, Musculoskeletal blastomycosis, Paediatric blastomycosis     

Blastomycosis in solid organ transplant recipients

BACKGROUND: Blastomyces dermatitidis, the etiologic agent of blastomycosis, causes severe disease and substantial mortality in those immunocompromised by acquired immunodeficiency syndrome or malignancy. In solid organ transplant recipients, the epidemiology, clinical features, and outcomes have not been fully described. METHODS: We conducted a retrospective case-series at the University of Wisconsin Hospital and Clinics. Case patients were solid organ transplant recipients with blastomycosis. RESULTS: From 1986 to 2004, we identified 11 cases of post-transplant blastomycosis with 64% occurring between 2000 and 2004. Onset of infection occurred a median of 26 months post transplantation with near equal distribution before and after the first year of transplantation. Rejection did not precede any case of post-transplant blastomycosis. Opportunistic co-infections were common, occurring in 36% of patients. Pneumonia was the most common clinical presentation and was frequently complicated by acute respiratory distress syndrome (ARDS). Extrapulmonary disease predominantly involved the skin and spared the central nervous system. The overall mortality rate was 36%; however, this increased to 67% in those with ARDS. None of the surviving patients relapsed or received routine secondary antifungal prophylaxis. CONCLUSION: Blastomycosis is an uncommon infection following solid organ transplantation that is frequently complicated by ARDS, dissemination, and opportunistic co-infection. After cure, post-transplant blastomycosis may not require lifelong antifungal suppression.     

Epidemiology of blastomycosis in a region of high endemicity in north central Wisconsin.

The clinical and epidemiologic features of 73 patients with laboratory-confirmed blastomycosis who were identified over an 11-year period in North Central Wisconsin are presented. Pulmonary disease was the sole manifestation in 77% of patients. More than one-half of all patients had symptoms that included fever, cough, weight loss, night sweats, and pleuritic chest pain. Virtually all were previously healthy, and most did not have an outdoor occupation. However, 82% of these patients lived or had visited within 500 m of rivers or associated waterways. The majority experienced the onset of symptoms between December and April. The estimated mean annual incidence rate of infection for Vilas County was 40.4 cases per 100,000 persons, and that for the largest city in the county was 101.3 cases per 100,000 persons. Several areas with an exceptionally high incidence of the infection were observed. We suggest that, in regions where blastomycosis is hyperendemic, clinical disease is most often pulmonary and occurs in immunocompetent individuals and that residence near an ecological focus may be a greater risk factor for acquisition of blastomycosis than is occupation.     

Blastomycosis in Africa: a new case from Tunisia.

Although blastomycosis is prevalent in the North American continent, it occurs only sporadically in Africa. We describe a 42 yr old patient who complained of intermittent cough and haemoptysis. Clinical findings were strongly suggestive of lung cancer. The diagnosis of pulmonary blastomycosis was made at thoracotomy. This rather unusual disease in our areas caused a considerable delay in securing the diagnosis and we suggest that this infection may be found elsewhere in Africa and the distribution may be wider than has previously been suspected.     

Pulmonary blastomycosis

Blastomyces dermatitidis is acquired in almost all cases via inhalation, and pulmonary disease is the most frequent clinical manifestation of blastomycosis. Pulmonary disease can range from asymptomatic infection to rapidly severe and fatal disease. Most cases will present as pneumonia, either acute or chronic, or as a lung mass. In rare cases pulmonary blastomycosis is associated with the acute respiratory distress syndrome. Blastomycosis can present as isolated pulmonary disease or along with coexisting extrapulmonary disease that usually will involve the skin, bony structures, genitourinary tract, or central nervous system. Diagnosis is largely based on isolation of the organism via culture or visualization of the organism in clinical specimens. Detection of urinary Blastomyces antigen is a recent addition to diagnostic options. Itraconazole is the drug of choice for most forms of the disease; amphotericin B is reserved for the more severe forms. Newer azoles such as voriconazole and posaconazole have a limited role in the treatment of pulmonary blastomycosis.     

Blastomycosis acquired by three children in Toronto.

Three paediatric cases of blastomycosis, apparently acquired in or near Toronto, Ontario, a region not known to be endemic for this disease, are described. Blastomycosis was not suspected clinically in any of the three cases, and the diagnosis was established only when the diagnostic net was broadened to include fungal and mycobacterial cultures. All three patients were diagnosed after significant delays, which is consistent with the rarity of the disease in children and its acquisition outside previously accepted geographical boundaries. Pulmonary involvement was present in all three children, while one also had multifocal osteomyelitis. Drug therapy was successful in all three cases, either with amphotericin B followed by itraconazole, or itraconazole alone. Blastomycosis should be included in the differential diagnosis of a patient from the Toronto area who presents with a compatible history despite a negative travel history to known endemic zones.     

Human and canine blastomycosis: A common source infection

In fall 1993 a man and a dog developed blastomycosis after visiting an island off Bayfield Inlet, Georgian Bay, located near Parry Sound, Ontario. The man recovered but the dog died of blastomycosis. It was hypothesized that the common source of exposure was the island since the permanent residences of the two cases were in different cities. One further case of human infection, based on positive serology, and four additional cases of probable canine blastomycosis were identified. All cases had travelled to Bayfield Inlet during summer and early fall 1993. To the authors' knowledge this is the first Canadian report of a common source of infection of human and canine blastomycosis. This report also provides evidence for a new endemic area of blastomycosis infection.     

Intracranial blastomycoma

Although meningitis is the most common form of central nervous system (CNS) blastomycosis, solitary mass lesions are not an infrequent presentation. Four of our patients presented with focal neurological deficits as a result of single intracranial mass lesions. Only 1 had clearcut evidence of extraneural blastomycosis. One was a coal miner, another worked with soil samples, and one was an engineer for a wood pulp company. All were previously healthy and 2 had diabetes. Complement fixation and immunodiffusion tests were negative in all 4 patients, and white blood cell counts and erythrocyte sedimentation rates were normal. Wet mount of tissue obtained intraoperatively by aspiration demonstrated the organism in 2 cases, culture from a lung lesion made the diagnosis in 1 case, and stain and culture of ventricular fluid revealed the organisms in the fourth case. Multiple cultures of cerebrospinal fluid from lumbar puncture were negative. All 4 patients survived. Amphotericin B alone was curative in 2 cases; surgical removal alone was curative in 1. All 4 computerized tomographic scans revealed isodense or slightly hyperdense single mass lesions with homogeneous contrast enhancement and surrounding edema, and tumor was the preoperative diagnosis in 2 cases. Such scans should suggest CNS blastomycoma in patients from the endemic area, despite the lack of other systemic manifestations. Diagnosis nevertheless rests on the characteristic histopathologic appearance in tissues and/or culture. Solitary intracranial blastomycomas may be less rare than previously thought; at our institution, we observed 4 cases in 4 years.     

Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America.

Guidelines for the treatment of blastomycosis are presented; these guidelines are the consensus opinion of an expert panel representing the National Institute of Allergy and Infectious Diseases Mycoses Study Group and the Infectious Diseases Society of America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and extrapulmonary disease. Most patients with blastomycosis will require therapy. Spontaneous cures may occur in some immunocompetent individuals with acute pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure may have occurred before the diagnosis is made and without treatment; such a patient should be followed up closely for evidence of disease progression or dissemination. In contrast, all patients who are immunocompromised, have progressive pulmonary disease, or have extrapulmonary disease must be treated. Treatment options include amphotericin B, ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment of choice for patients who are immunocompromised, have life-threatening or central nervous system (CNS) disease, or for whom azole treatment has failed. In addition, amphotericin B is the only drug approved for treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic alternative to amphotericin B for treating immunocompetent patients with mild to moderate pulmonary or extrapulmonary disease, excluding CNS disease. Although there are no comparative trials, itraconazole appears more efficacious than either ketoconazole or fluconazole. Thus, itraconazole is the initial treatment of choice for nonlife-threatening non-CNS blastomycosis.     

Pulmonary blastomycosis.

Pulmonary blastomycosis has a number of chest radiographic manifestations that may closely resemble those of tuberculosis, histoplasmosis, and other fungal diseases. Radiographic presentations of disease include airspace consolidation, nodular opacities, air bronchograms, masslike lesions, and military disease. Because the geographic distribution of blastomycosis overlaps that of histoplasmosis, distinguishing one from the other on the basis of the radiographic features may be difficult. In blastomycosis, the paucity of calcifications, lymphadenopathy, and cavitation is striking. The article reviews the clinical and radiologic features of blastomycosis and provides illustrative cases to enhance understanding of this disease.     

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.     

Chronic blastomycotic meningitis

Three cases of blastomycosis which presented as chronic meningitis are reported. Blastomycotic meningitis is an uncommon form of chronic fungal meningitis and is difficult to diagnose during life unless the patient has obvious systemic blastomycosis elsewhere. Evaluation of cerebrospinal fluid obtained by lumbar tap is usually not diagnostic. Obstructive hydrocephalus developed in all three patients during the course of their fungal meningitis. Culture of ventricular fluid yielded the fungus in all three patients (although only after death in one case). One patient received only minimal therapy before death whereas the third patient received a full course of amphotericin B with restoration to his premorbid state. Blastomycosis should be included in the differential diagnosis of chronic meningitis and, when suspected, the cisternal or ventricular fluid should be sampled.     

Asymptomatic blastomycosis of the central nervous system with progression in patients given ketoconazole therapy: a report of two cases

Ketoconazole (KTZ) has largely replaced amphotericin B as first-line therapy for blastomycosis. However, KTZ penetrates poorly into the central nervous system (CNS), and therapeutic failure may be caused by initially unrecognized CNS infection. Two patients (22% [2/9] of all culture-proven cases of blastomycosis at Grady Memorial Hospital, Atlanta, over 15 years) developed CNS blastomycosis while receiving KTZ. Neither initially had CNS symptoms; both had cutaneous and pulmonary disease that responded to KTZ. If KTZ or other fungistatic imidazoles are to continue as primary therapy for blastomycosis, studies are needed to improve the ability to identify patients likely to experience treatment failure or develop CNS disease. Possibly all patients with disseminated blastomycosis, even those without CNS symptoms, should have lumbar puncture and computed tomography of the head before therapy. Critical evaluation of their immune function also may be required before making a therapeutic decision to use KTZ or amphotericin B.     

Blastomycosis presenting as multiple splenic masses

Blastomyces dermatitidis is a fungus that causes a wide spectrum of disease in humans. The clinical and pathological entity of splenic abscess due to blastomycosis is extremely rare. A case of splenic blastomycosis is reported, and its cytopathological and radiological features are described.     

Otitis media due to blastomycosis: report of two cases.

Blastomycosis as a causative agent in cases of otitis media has not previously been reported. Two patients recently presented with otitis media and head and neck masses due to Blastomyces dermatitidis. Initial evaluation suggested neoplastic disease, but biopsy confirmed a fungal etiology for the masses in both patients. Relapse after administration of ketoconazole was noted in one patient, who was an adult; the other patient was a child. Otitis media and masses of the head and neck are unusual features of blastomycosis. Blastomycosis should be considered in the differential diagnosis for patients with such mass lesions and for patients with otitis media.     

结肠占位合并肝右叶占位的罕见病例多学科讨论及文献回顾

胆管癌是一种罕见的胆管上皮癌,仅占胃肠道恶性肿瘤的3%,是一种具有高度侵袭性、预后极差的恶性肿瘤。肝内胆管癌常转移到肝、腹膜、肺,转移到结肠的病例极为罕见,本文描述了1例结肠占位合并肝右叶占位初诊为结肠癌肝转移而术后病理诊断为肝内胆管细胞癌肠转移病例的诊疗过程,是国内外文献报道的第9例个案报道。这类罕见病例给临床的诊断和治疗带来了挑战,我们报道这个病例,一方面是给同行提供借鉴,提高罕见病的诊疗;另一方面是想引起共鸣,希望更多类似的病例能被报道,以寻找其共性,探究其机制。