Blastomycosis: The great pretender can also be an opportunist. Initial clinical diagnosis and underlying diseases in 123 patients.

Lemos LB, Baliga M, Guo M. Department of Pathology, University of Texas, Houston; and the Department of Pathology, University of Mississippi, Jackson. Ann Diagn Pathol 2002 Jun;6(3):194-203 

Clinically, blastomycosis can be difficult to recognize even in the endemic areas where clinicians are aware of this problem. In only 18% of 123 patients from the University of Mississippi Medical Center (Jackson, MS) blastomycosis was correctly suspected at the initial patient evaluation. Pneumonia (40%), malignant tumors (16%), and tuberculosis (14%) were the most common misdiagnoses. The false first impression frequently resulted in unnecessary surgeries or treatment delays, with patients receiving inefficient antibiotic therapy for months. The presence of cutaneous involvement by the disease makes its' recognition easier for the clinician, raising the percentage of correct initial diagnosis to 64%. To evaluate the association with immunodepression, the presence of other diseases was also searched among the 123 patients. An immunodepressive condition preceded the fungal disease in 25% of patients. Another associated disease commonly found in blastomycotic patients was diabetes mellitus (22%).

Blastomycosis is correctly suspected at the first clinical evaluation in only a small percentage of patients; pneumonia, cancer, and tuberculosis are the most common clinical considerations. Cutaneous involvement leads the clinician to the correct diagnosis in the majority of cases. One fourth of the patients with blastomycosis had underlying immunodepressive conditions, and underlying diabetes mellitus is present in 22% of patients.

The Epidemiology of Blastomycosis in Illinois and Factors Associated with Death.

Author(s) Mark S. Dworkin, Amy N. Duckro, Laurie Proia, Jeffery D. Semel, and Greg Huhn. Clinical Infectious Diseases, volume 41 (2005), pages e107–e111

Abstract  Background.  Blastomycosis is a systemic fungal disease that may be asymptomatic or progressive and may lead to death. Methods.  In response to a reported increase in the number of cases of blastomycosis in Illinois, surveillance data reported to the Illinois Department of Public Health from January 1993 to August 2003 were analyzed and the medical records of 4 patients who died were reviewed. Results.  Among the 500 cases reported, the median age of the patients was 43 years (range, 487 years), and 34 patients (7%) died. Higher rates of mortality were observed among persons who were black, who were 65 years of age and older, and who were male. Death was associated with a time from onset of illness to diagnosis of 128 days (OR, 2.1; 95% CI, 1.04.8). During the period from 1993 through 2002, the number of cases reported per year increased from 24 to 87 (P<.05)Conclusions:  The incidence of blastomycosis has been increasing in Illinois. To reduce mortality related to delay in diagnosis and treatment, medical providers need to be educated about blastomycosis, with an emphasis on symptom recognition, methods of diagnosis, and appropriate antifungal treatment.

N Engl J Med. 1986 Feb 27;314(9):529-34.    
Klein BS et al. Isolation of Blastomyces dermatitidis in soil associated with a large outbreak of blastomycosis in Wisconsin.

In investigating six cases of blastomycosis in two school groups that had separately visited an environmental camp in northern Wisconsin in June 1984, we identified a large outbreak of the disease and isolated Blastomyces dermatitidis from soil at a beaver pond near the camp. Of 89 elementary-school children and 10 adults from the two groups, 48 (51 percent) of the 95 evaluated in September had blastomycosis. Of the cases, 26 (54 percent) were symptomatic (the median incubation period was 45 days; range, 21 to 106 days). No cases were identified in 10 groups that visited the camp two weeks before or after these two groups. A review of camp itineraries, a questionnaire survey, and environmental investigation showed that blastomycosis occurred in two of four groups that visited a beaver pond and in none of eight groups that did not. Walking on the beaver lodge and picking up items from its soil were associated with illness. Cultures of soil from the beaver lodge and decomposed wood near the beaver dam yielded B. dermatitidis. We conclude that B. dermatitidis in the soil can be a reservoir for human infection.

Pulmonary blastomycosis: an appraisal of diagnostic techniques.

Martynowicz MA, Prakash UB. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Medical School and Mayo Medical Center, Rochester, MN 55905-0001, USA.  Chest 2002 Mar;121(3):768-73 Abstract quote

OBJECTIVES: Pulmonary blastomycosis often mimics bacterial pneumonia or bronchogenic carcinoma, which may result in delayed therapy or the performance of unnecessary diagnostic procedures. We have reviewed the utilization of diagnostic techniques in the workup of patients with pulmonary blastomycosis, defined their diagnostic yields, and proposed an optimal diagnostic approach for the patient in whom pulmonary blastomycosis is considered. DESIGN: Retrospective chart review of all patients with the diagnosis of blastomycosis at a major academic medical center.

RESULTS: Of the 119 patients with blastomycosis, 56 (47%) had pulmonary involvement. A total of 92 specimens were obtained by noninvasive means (sputa, 72 specimens; tracheal secretions, 5 specimens; and gastric washings, 15 specimens) in 35 patients. KOH smears were prepared from 22 of those specimens (24%). The diagnostic yield from these culture specimens obtained by noninvasive means was 86% per patient, and 75% per single sample. The diagnostic yields from KOH smears were 46% and 36%, respectively. Flexible bronchoscopy was performed in 24 patients and yielded a diagnosis in 22 (92%). Cultures of bronchial secretions (19 patients) and BAL fluid (6 patients) were positive in 100% and 67% of patients, respectively. The corresponding yields of KOH preparations were 17% (1 of 6 preparations) and 50% (3 of 6 preparations), respectively. Pathology specimens including those from bronchoscopic lung biopsies (nine patients), bronchial brushings (two patients), and bronchoscopic needle aspiration (one patient) were positive in 22%, 50%, and 0% of cases, respectively. Cytology was usually performed to exclude malignancy and was positive for Blastomyces dermatitidis in five patients (sputum, three patients; bronchial washings, two patients). Thoracotomy was performed in 11 cases, and in all patients the procedure yielded a diagnosis. Serology results were available in 25 patients. Immunodiffusion was positive in 10 patients (40%), and complement fixation in 4 patients (16%).

CONCLUSIONS: In patients with pulmonary blastomycosis, the positive yield from respiratory specimen cultures is high, but the confirmation of a diagnosis may take up to 5 weeks. Wet smears and cytology examinations of respiratory specimens provide quicker diagnoses but are underutilized. Their routine use is recommended in endemic areas. Commonly used serologic assays are insensitive and are not useful for diagnostic screening.

Culture   Sabouraud glucose agar, brain heart infusion agar, yeast-extract-phosphate agar, and a medium with cycloheximide, and then incubate at 30C.  Grows best on the yeast extract agar or agar containing yeast extract such as Mould Inhibitory Agar (IMA) Mould form to yeast form conversion is necessary to ensure that the fungus suspected to be B. dermatitidis is not a similar fungus-accomplished by inoculating Kelley's agar or blood agar supplemented with glutamine and then incubating the inoculated tubes at 37C. Exoantigen technique and a DNA culture confirmation kit.

Practice Guidelines for the Management of Patients with Blastomycosis Stanley W. Chapman et al

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 non–life-threatening non-CNS blastomycosis.

April 2000. This guideline is part of a series of updated or new guidelines from the IDSA. Clinical Infectious Diseases 2000;30:679–83 q 2000 by the Infectious Diseases Society of America.    

Blastomycosis: organ involvement and etiologic diagnosis. A review of 123 patients from Mississippi.

Lemos LB, Guo M, Baliga M. Cytopathology Service, Pathology Department, University of Mississippi Medical Center, Jackson, MS, USA.  Ann Diagn Pathol 2000 Dec;4(6):391-406 Abstract quote

Blastomycosis can only be diagnosed through the identification of the yeasts of Blastomyces dermatitidis in body fluids, tissues, or cultured material.  The charts from 123 patients treated for blastomycosis at the University of Mississippi Medical Center from January 1980 through May 2000 were reviewed to determine the role of wet preparation, cytology, histology, and culture in diagnosing this fungal disease. Cytology uncovered the etiologic agent in 56.1% of all cases and in 71.8% of pulmonary cases. Cytology also was the first method to disclose the fungus in 57.7% of pulmonary cases. Sputum was the cytology specimen examined in 51% of the patients. In 69 patients with lung involvement, pulmonary cytology was positive in 97% of cases. Wet preparation was the second method to most commonly uncover the fungus in 37.4% of all cases. Histology was the third method with 32.5% of positive cases. Cultures were positive in 64.2% of all cases but they were the first to detect the fungus in only 3.2% of all patients. There was pulmonary involvement in 87% of patients, cutaneous involvement in 20%, osseous involvement in 15%, and central nervous involvement in 3%. In the medical literature the relative proportion of pulmonary versus disseminated disease clearly increased in series reported after 1959.

Proportionally to the pattern of patients admitted to the University of Mississippi Medical Center, there is a clear predominance of black males among patients with blastomycosis followed by black females. White females constitute the sex/ethnic group least affected by this fungal disease.

Michael J.G. Harrison, DM, FRCP, Justin C. McArthur, MBBS, MPHInfect Med 15(7):474-478, 1998.

Blastomycosis Meningitis

Blastomyces dermatitidis is a dimorphic yeast that is endemic in the south and south central US and in the Great Lakes area. Seeding of the CNS can occur after dissemination from a respiratory focus. Meningitis occurs in about 5% of cases, and mass lesions or blastomycomas can develop occasionally. CSF culture is rarely positive. An EIA using purified antigen A has a high sensitivity for blastomycosis and good specificity, and distinguishes blastomycosis from coccidioidomycosis. Experience is limited, but the recommended treatment at this time is intravenous amphotericin B, at least 2g.

Laryngeal blastomycosis: a commonly missed diagnosis.

Hanson JM, Spector G, El-Mofty SK. Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, USA. Ann Otol Rhinol Laryngol 2000 Mar;109(3):281-6

Blastomycosis is a relatively uncommon fungal disease that most commonly affects the lungs. Other organs may be involved, usually secondary to dissemination of the organism. Laryngeal blastomycosis may occur in isolation from active pulmonary disease. The signs, symptoms, clinical features, and pathological findings of laryngeal blastomycosis mimic those of squamous cell carcinoma. Misdiagnosis may result in inappropriate treatment with potential morbidity. Proper understanding of the clinical presentation and familiarity with the histopathologic features of this disease are therefore imperative. In this paper, we report 2 cases of laryngeal blastomycosis, 1 of which was misdiagnosed as squamous cell carcinoma, clinically and microscopically, with consequent radiotherapy and laryngectomy. In the other case, a clinical diagnosis of glottic squamous cell carcinoma was rendered. However, blastomycosis was identified in a biopsy specimen. We also review cases of isolated laryngeal blastomycosis that have been reported in the English-language literature during the last 80 years. A number of those cases were misdiagnosed clinically and microscopically as squamous cell carcinoma.

Peritoneal blastomycosis.

Perez-Lasala G, Nolan RL, Chapman SW, Achord JL. Division of Infectious Diseases, University of Mississippi Medical Center, Jackson. Am J Gastroenterol 1991 Mar;86(3):357-9 Abstract quote

Blastomycosis is a systemic fungal infection caused by Blastomyces dermatitidis. Involvement of the peritoneum is unusual, with only two previously reported cases that occurred in association with disseminated disease. A single case of histopathologically proven blastomycosis involving the peritoneum is presented, as well as a short overview of previously published cases on gastrointestinal and peritoneal blastomycosis. The case is unique in that chronic peritonitis was the only manifestation of disease. The diagnosis was made by laparoscopy.

Blastomycosis of the lumbar spine: case report and review of the literature, with emphasis on diagnostic laboratory tools and management. Eur Spine J. 1998;7(5):416-21
Hadjipavlou AG et al University of Texas Medical Branch, Department of Orthopaedics and Rehabilitation, Galveston 77555-0792, USA.

We report on the conservative and surgical management of a patient with blastomycosis of the lumbar spine, causing severe and crippling deformity. The diagnosis was made through biopsy. Curative removal, reconstruction and realignment of the spine were achieved. Imaging modalities were highlighted, with a detailed discussion of the histology and conservative and surgical management. We emphasize the importance of early, aggressive treatment of blastomycosis to prevent deformity and disability, and to enable identification of the best management of a destructive lesion with deformity. This case demonstrates that empirical treatment should not be used in cases of unusual sinus and abscess locations. Specific diagnosis and early treatment are indicated to prevent dreadful complications and spinal deformity resulting from blastomycosis. Aggressive antifungal therapy can cure the disease but does not control complications related to deformity. The latter can only be addressed by surgical reconstruction. We review the literature of surgical treatment, focusing on abscess drainage, bone fusion and posterior instrumentation in the absence of addressing the deformity component.

Giant forms of Blastomyces dermatitidis in the pulmonary lesions of blastomycosis.Potential confusion with Coccidioides immitis.

Watts JC, Chandler FW, Mihalov ML, Kammeyer PL, Armin AR.Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Michigan 48072.  Am J Clin Pathol 1990 Apr;93(4):575-8 Abstract quote

Typical yeast-phase cells of Blastomyces dermatitidis have a characteristic appearance in tissue sections. Fungal morphologic variation occurs infrequently in the lesions of blastomycosis, yet it can complicate the differential diagnosis, particularly if fresh tissue is not available for microbiologic culture. The authors report a case of pulmonary blastomycosis, confirmed by culture and direct immunofluorescence, in which some of the yeast-like cells were abnormally large. These giant yeast-like cells exceeded the size range accepted for the tissue forms of B. dermatitidis; therefore, coccidioidomycosis was considered initially in the differential diagnosis. Otherwise characteristic morphologic features of these cells, in particular multinucleation and the production of broad-based blastoconidia, helped resolve the differential diagnosis. The diagnosis can be confirmed by direct immunofluorescence or microbiologic culture.

Delayed diagnosis of osseous blastomycosis in two patients following environmental exposure in nonendemic areas.

Veligandla SR, Hinrichs SH, Rupp ME, Lien EA, Neff JR, Iwen PC.Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-6495, USA Am J Clin Pathol 2002 Oct;118(4):536-41 Abstract quote

Blastomycosis generally results from inhalation of Blastomyces dermatitidis conidia following exposure to contaminated soil in an endemic area. Primary infections commonly involve the lungs, although secondary dissemination to other body sites may occur. We describe 2 cases of osseous blastomycosis in people living outside the endemic areas. Both patients reported exposure to soil following injury to the knee from occupational activities. Mold isolated from each case was identified as B dermatitidis by micromorphologic characteristics including yeast conversion testing and by a positive AccuProbe Blastomyces dermatitidis test (GenProbe, San Diego, CA). Retrospective review of histologic slides, initially reported as negative, identified rare poorly staining, broad-based budding yeast forms in each case. Both patients were treated successfully with itraconazole with no evidence of recurrent infection after 1 year. These cases illustrate the importance of considering blastomycosis in the differential diagnosis of bony lesions, even though the patient may live outside an endemic area for B dermatitidis.

Blastomycosis: report of three cases from Alberta with a review of Canadian cases. Mycopathologia. 1979 Aug 31;68(1):53-63

Sekhon AS, Bogorus MS, Sims HV.

Approximately 120 cases of blastomycosis have been reported from Canada to-date. The great majority of these occurred in the Eastern provinces. Since 1970, three cases of blastomycosis have been seen in Alberta. The first case, with meningeal and pulmonary involvements, was diagnosed at post-mortem. The second case was that of a 75-year-old male with a history of pancytopenia, aortic arteriosclerosis, exposure to mercury, and fever. KOH and periodic-acid schiff (PAS) stained smears of the lung tissue, received after autopsy, showed numerous budding yeast cells of Blastomyces dermatitidis along with some hyphal filaments. Similarly, budding cells of B. dermatitidis and hyphal segments were observed in large numbers in the PAS and Gomori's methenamine-silver (GMS) stained sections made from adrenals, lung, kidney, and spleen tissues. Attempts to culture the fungus on a variety of selective and non-selective media were unsuccessful, due to heavy bacterial contamination. The indirect fluoroscent antibody results were 2+ with the B. dermatitidis conjugate. The third case was that of a 31-year-old male, who was admitted to the hospital with the chief complaint of chest pain. Biopsy tissue sections, stained with the GMS procedure revealed a few foci with B. dermatitidis yeast cells. The immunodiffusion and complement fixation (CF) tests gave positive results against B. dermatitidis antigen (titre, 1:16). The CF titre declined following treatment with amphotericin B and the immunodiffusion test became negative after the institution of antifungal therapy. Except for the last patient, the other two patients had no history of travel in any known endemic areas. In addition to these cases, a survey of blastomycosis occurring in this country has been presented along with on the disease in dogs and a cat.

Blastomycosis in the Immunocompromised Host

Recent reports indicate that B. dermatitidis may infrequently act as an opportunistic pathogen, notably in patients who are in the late stages of AIDS, transplant recipients, and patients treated with immunosuppressive or cytotoxic chemotherapy [11, 20]. Disease in these patients is more aggressive and more often fatal than disease in the normal host. Pulmonary disease is more likely to present with diffuse pulmonary infiltrates and respiratory failure. Dissemination to multiple organs, including the CNS, also occurs more frequently. Mortality rates of 30%–40% have been reported, and most deaths attributed to blastomycosis occur during the first few weeks of therapy. Thus, early and aggressive treatment with amphotericin B (0.7–1 mg/ kg/d) is indicated for blastomycosis in the immunocompromised patient (AII). Most experts recommend a total dose of 1.5–2.5 g, although treatment for selected patients without CNS infection may be switched to itraconazole after clinical stabilization with amphotericin B (usually a minimum dose of 1 g)(BIII). Despite amphotericin B treatment, frequent relapses occur in patients with AIDS and in those patients who continue immunosuppressive therapy [11, 20]. Some authorities therefore recommend chronic suppressive therapy with an azole, preferably itraconazole, for those patients who respond to a primary course of amphotericin B treatment. Treatment with ketoconazole is discouraged because relapse rates are  higher (DIII). Fluconazole treatment may be given special consideration  for selected patients who have had CNS disease or patients unable to tolerate itraconazole owing to toxicity or drug interactions.