AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Blastomycosis, which originally was described by Gilchrist and Stokes in 1894 and 1896, is an infection with a highly variable spectrum of clinical presentations. Disease can range from an asymptomatic, self-healing pulmonary infection to widely disseminated fatal disease.

Blastomyces dermatitidis is a dimorphic fungus. The mycelial form grows as a white mold. The conidia (spores) that convert to yeast are infectious to humans. The epidemiology is incompletely understood because of the lack of a sensitive and specific skin test and difficulties in establishing the ecologic niche of the organism in nature. In the United States, most infections are clustered in states adjacent to the Mississippi and Ohio rivers and the Great Lakes region. Although initial epidemiologic studies reported a higher incidence of infection in men, recent series have shown no predilection for any specific sex, age, race, or occupation or any seasonal variation. The disease is uncommon in children but is now recognized increasingly in immunocompromised hosts, particularly in patients with acquired immune deficiency syndrome (AIDS).

Infection is acquired via inhalation of the conidia. Once in the lungs, for infection to occur, the conidia need to mature into invasive yeast. In the immunocompetent host, there is a natural resistance to infection with Blastomyces because alveolar macrophages inhibit the transformation of conidia into yeast. Such natural resistance is supported by studies of blastomycosis epidemics, in which asymptomatic infection occurs in at least 50% of persons in whom Blastomyces has colonized. The factors that determine whether disease develops in infected persons are unclear. Cellular immune host resistance has been difficult to evaluate for its role in protection against infection but is probably an important factor for asymptomatic versus overt infection.

Pathophysiology

The term B dermatitidis refers to the imperfect (asexual) stage of Ajellomyces dermatitidis, which grows as a yeast at 37°C and mycelial form at room temperature. Two serotypes of B dermatitidis have been detected by exoantigen analysis. The perfect (ie, sexual form), A dermatitidis, is heterothallic and requires 2 compatible mating types for spore formation. The mycelial form, which bears conidiophores, produce single terminal conidia, which measure 2-10 µm in diameter and are round or oval.

Primary infection, which may be subclinical, occurs in the lung following inhalation of fungal conidia. Transition from the mold form to the yeast form occurs after deposition in the distal airways. The phase shift occurs as a result of heat-related stress, followed by uncoupling of oxidative phosphorylation. In the absence of nonspecific host defense mechanisms, cells increase in number in the lung parenchyma. Hilar lymph nodes may become involved, and, subsequently, lymphohematogenous spread to the other organs may occur. Incubation time averages 4-6 weeks and varies widely.

Subclinical cases of blastomycosis occur in at least 50% of infected individuals, thus supporting the hypothesis that some patients have natural resistance. Cellular immune response mediated by antigen-specific T lymphocytes and lymphokine-derived macrophage's cell-mediated immunity plays a critical role in aborting fungal growth.

Frequency

United States

The disease is endemic in midwestern, north central, and southeastern regions. Most clinical cases are reported in states surrounding the Mississippi and Ohio rivers and the Great Lakes region. Incidence of infection in individuals residing in endemic areas is unknown. Point-source epidemics of infection in endemic areas often have occurred with recreational and occupational activities in wooded areas along waterways and have implicated activities aerosolizing organically enriched soil.

International

Blastomycosis also has been reported in parts of Canada, India, Africa, and Central and South America. Because of the erroneous belief that the disease is limited only to the United States, blastomycosis often is referred by the term North American blastomycosis, which is an obsolete term. The term European blastomycosis is a confusing synonym of cryptococcosis, a systemic infection caused by the yeastlike fungus cryptococcus neoformans. Likewise, South American blastomycosis (ie, Brazilian blastomycosis) is an older name for paracoccidioidomycosis, a chronic often fatal mycosis caused by a large dimorphic fungus, Paracoccidioides brasiliensis.

Mortality/Morbidity

Before the advent of antifungal therapy, the mortality rate associated with blastomycosis exceeded 60%. The mortality rate in appropriately treated cases is 10% or less. In contrast, one third of immunocompromised patients do not respond to all therapy, and 30-40% die of the disease. Most deaths occur within the first few weeks of therapy.

The clinical course of blastomycosis is more severe in the immunocompromised host, including patients with late stages of AIDS, transplant recipients, and those receiving immunosuppressive or cytotoxic therapy. Severe pulmonary disease complicated by adult respiratory distress syndrome occurs in approximately 20% of compromised hosts. Central nervous system disease appears to be 3-5 times more common in immunocompromised patients than in normal hosts.

Sex

Although initial epidemiologic studies reported a higher incidence of infection in men, recent series have shown no predilection for any specific sex, age, race, or occupation or any seasonal variation. In children, as in adults, both sexes are equally susceptible.

Age

Men aged 30-50 years are affected most commonly. The disease is rare in children and adolescents. In 1983-1995, a retrospective study at a children's hospital identified only 10 patients with the disease. However, in past reviews, about 2-10% of patients reported were younger than 15 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The clinical spectrum of blastomycosis is highly variable, including asymptomatic infection (in nearly one half of patients infected), acute or chronic pneumonia, and extrapulmonary disease.

• Most cases of blastomycosis are sporadic. Nearly one half of patients infected may be asymptomatic. In one study involving 46 children and 2 adults, symptoms began 21-106 days (median 45 d) after exposure to the pathogen in a beaver pond. Patients may complain of an influenzalike illness with the following nonspecific constitutional symptoms:
• • Fever
  • Chills
  • Night sweats
  • Weight loss
  • Malaise
  • Myalgia
• Acute pulmonary infection is the most frequent presentation of blastomycosis in children. Symptoms include the following:
• • Productive cough
  • Dyspnea
  • Wheezing
  • Chest pain
  • Hemoptysis (rarely)
• Symptoms of chronic pneumonia may last for 2-6 months and include weight loss, night sweats, fever, cough, and chest pain. Most adult patients diagnosed with blastomycosis have an indolent onset of chronic pneumonia.

Physical

• Signs of acute or chronic pneumonia may be noted. Life-threatening progressive lung disease and disseminated infection can occur in 10% of reported cases.
• Disseminated blastomycosis usually begins with pulmonary infection followed by cutaneous, osseous, genitourinary, or CNS involvement.
• Less commonly, primary cutaneous blastomycosis may follow after traumatic inoculation of the fungus into the skin.
• Extrapulmonary disease in blastomycosis includes the following:
• • Skin, most commonly (25%)
  • Bone (25%)
  • Prostatitis or epididymitis (17%), a common manifestation in adults but has not been reported in prepubescent children
  • Neurologic involvement (occurs in 3-5% of extrapulmonary infections and is manifested as intracranial or epidural abscesses and rarely meningitis)
• Skin lesions are the most common manifestation of extrapulmonary disease. Cutaneous lesions favor exposed areas and enlarge over many weeks—from pimples that are minimally tender to well-circumscribed verrucous or ulcerative lesions, often with little inflammation. Verrucous lesions demonstrate raised irregular borders with crusting and purulent drainage, while ulcerative lesions are characterized by sharp and heaped-up borders with centrally located granulation tissue and exudate.
• Osteolytic lesions may occur in nearly any bone and present as a cold abscess or draining sinus.
• Extension to a contiguous joint may result in indolent swelling, pain, and restriction of movement. The vertebra, skull, ribs, and long bones are affected most commonly.
• Intrauterine or congenital infections are unusual.
• Other unusual metastatic sites of infection include larynx, reticuloendothelial system (liver, spleen, lymph nodes, bone marrow), oropharynx, nose, and thyroid.

Causes

B dermatitidis is a thermal dimorphic fungus that exists in mycelial form in nature and as yeast in infected tissue.

• The fungus grows on Sabouraud agar at room temperature (250°C) as a white fluffy mold. Alternatively, at body temperature (37°C) and on blood agar, the fungus forms a brown wrinkled colony.
• The mycelial form of B dermatitidis has been isolated from soil, although its ecologic niche is not characterized as well as other endemic fungi.
• Inhalation of the microconidia from the mold form of B dermatitidis into the lungs leads to infection.
• In infected tissue specimens, B dermatitidis appears as a characteristic thick-walled yeast cell (8- to 15-mcg diameter) with broad-based daughter cells.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Bacterial pneumonia
Tuberculosis
Other endemic mycoses
Sarcoidosis
Cancer

The typical verrucous or ulcerative cutaneous lesions of blastomycosis may mimic skin cancers, such as basal cell carcinoma and squamous cell carcinoma. Other disorders, such as pyoderma gangrenosum or keratoacanthoma, also may be confused with blastomycosis.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Sputum examination: In general, sputum specimens processed with 10% potassium hydroxide or a fungal stain are examined first in adolescent and adult patients because specimens have a high overall yield (approximately 80%). In addition, cytologic specimens can be examined for a dependable diagnosis.
• Culture
• • The diagnosis of blastomycosis can be made by growth of the fungus in a culture of sputum, tracheal aspirates, bronchoalveolar lavage fluid, tissue biopsy specimens, cerebrospinal fluid, or urine. Because colonization with B dermatitidis does not occur, detection of the fungus from any sterile site is diagnostic. The organism can be cultured on brain-heart infusion and Sabouraud dextrose agar at room temperature. In experienced hands, diagnosis of blastomycosis by visualization of the characteristic budding yeast formed in wet smear or histopathologic section is adequate.
  • Because primary cutaneous blastomycosis has been reported by accidental autoinoculation, clinical laboratory personnel and pathologists should be notified about the possibility of blastomycosis in the differential diagnosis when handling potential infected tissue or body fluid specimens.
• Skin tests and serodiagnosis
• • Skin testing and serodiagnosis of blastomycosis using complement fixation (CF) antibodies and immunodiffusion (ID) precipitin bands currently have very limited roles in diagnosis because of poor sensitivity and specificity, with cross-reactivity of other fungi.
  • Recently developed enzyme immunoassay with the A-antigen of B dermatitidis has been shown to be more sensitive than CF and ID tests; however, this test has limited clinical use because it is not available in most commercial laboratories.
• Chemiluminescent DNA probes are available for identification of B dermatitidis.

Imaging Studies

• Chest radiography: The chest radiograph is abnormal in two thirds of cases and may reveal alveolar or masslike infiltrates, reticulonodular pattern, pleural effusion, and, rarely, cavitation.
• Bone scanning: A radionuclide bone scan and other imaging modalities, such as computed tomography scans or even the more sensitive, magnetic resonance imaging, may help detect skeletal involvement in some cases of extrapulmonary blastomycosis.

Other Tests

• Skin biopsy: Blastomycosis can present with cutaneous lesions. In these situations, histology and culture on skin biopsy specimens may reveal the organism.
• Immune deficiency workup: In recent years, serious infection with blastomycosis is recognized increasingly in immunocompromised hosts, especially AIDS patients. However, other fungal infections, such as progressive disseminated histoplasmosis or cryptococcal meningitis, are more likely to be opportunistic. Blastomycosis is not an AIDS-defining illness and no official recommendations exist regarding screening for HIV-1 infection in patients diagnosed with blastomycosis.
• Lumbar puncture: Neurologic manifestations of blastomycosis include meningitis and even more commonly, epidural or cranial abscesses. Diagnosis is difficult, and evaluation of lumbar spinal fluid is rarely definitive. Ventricular fluid has been associated with higher rates of culture positivity.

Procedures

• The diagnosis of blastomycosis is more difficult in children. Children with pulmonary disease who are unable to produce sputum may require invasive procedures, such as bronchoscopy with bronchoalveolar lavage, percutaneous needle biopsy of lung, open lung biopsy, for diagnostic confirmation.

Histologic Findings

The definitive diagnosis of blastomycosis is based on identification of the characteristic thick-walled broad-based budding yeast cells in tissue specimens or growth of the fungus in culture. Pathologically, a pyogranulomatous tissue response including lymphocytes, giant cells, and neutrophils is observed with associated necrosis and fibrosis. Pseudoepitheliomatous hyperplasia may be striking and may lead to an erroneous diagnosis of squamous cell carcinoma. Typically, the granuloma of blastomycosis does not caseate or calcify as in tuberculosis.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Treatment of blastomycosis in the pediatric age group is based largely on experience with adult patients.
• Therapeutic approaches have evolved in recent years with the advent of oral azoles, primarily itraconazole, which has replaced amphotericin B for most indications in adult patients.
• Close observation alone may be an option in cases of mild pulmonary blastomycosis because they can resolve spontaneously; however, reactivation of the disease may occur, and, with the availability of new oral azoles, there is now a tendency to treat all symptomatic cases.
• All immunocompromised patients and patients with progressive pulmonary disease or extrapulmonary disease should be treated.

Surgical Care

Surgery has only a limited role in the treatment of blastomycosis.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Amphotericin B remains the antifungal agent with the most success against B dermatitidis. Cumulative doses less than 1 g have resulted in cure without relapse in 70-91% of adult cases of blastomycosis. A recent retrospective study of blastomycosis cases in Mississippi reported a cure rate of 86.5% and a relapse rate of only 3.9% for patients treated with amphotericin.

Toxicity often necessitates interruption of therapy. Cutaneous and noncavitary lung disease should be treated for approximately 8-10 weeks. Cavitary lung disease or infection extending beyond the lung and skin should be treated for about 10-12 weeks with a cumulative dose of 2.5 g or more of amphotericin B.

Amphotericin B is the drug of choice for treating children with life-threatening and central nervous system infections caused by blastomycosis. Most experts recommend a total cumulative dose of 30 mg/kg or higher of amphotericin B. Human trials of lipid formulations of amphotericin B in the treatment of blastomycosis have not been performed. However, limited clinical data suggest that these preparations may be used for selected patients intolerant to standard amphotericin B therapy.

The azoles are an equally effective and less toxic alternative to amphotericin B for treating adult immunocompetent patients with mild-to-moderate pulmonary or extrapulmonary disease, excluding CNS disease. In a multicenter clinical trial involving adult patients, itraconazole was found to be more effective and associated with fewer adverse effects than ketoconazole.

Most experts recommend a minimum of 6 months of oral azole therapy for mild-to-moderate pulmonary or nonmeningeal disseminated blastomycosis. Safety and efficacy data using oral azole therapy in children are limited. Itraconazole has been used successfully as treatment in a small number of pediatric patients with non–life-threatening non-CNS disease. Short courses of amphotericin B (5-10 mg/kg total dose) followed by oral itraconazole for 6 months may be used to treat extrapulmonary blastomycosis.

The oral azoles are not beneficial in treating central nervous system blastomycosis. If oral azole antifungal agents are used for non–life-threatening cases, patients should be monitored closely. Amphotericin B should be substituted for the oral azole agent if clinical deterioration is noted or serum levels of medications are not adequate.

Acute pneumonia complicated by ARDS and extrapulmonary disease may need treatment with moderate doses of amphotericin B (>1.5 g total dose) or short courses of amphotericin B (500 mg total dose) followed by 6 months of oral itraconazole. In pregnant women with blastomycosis, amphotericin B is the drug of choice because the oral azoles are contraindicated due to their embryotoxic and teratogenic effects.

Although unusual, in recent years, an increased number of cases of blastomycosis have been reported in compromised hosts, including patients with AIDS, bone marrow and solid organ transplant recipients, and patients receiving cytotoxic or long-term immunosuppressive therapy. Early and aggressive therapy with amphotericin B therapy is warranted because multiple organ and central nervous system involvement with resultant mortality is relatively common in this population. Furthermore, response to antifungal therapy may be suboptimal, and relapses are common.

Most experts recommend treating blastomycosis in children with AIDS with 30 mg/kg of amphotericin B over a 4- to 6-week period, followed by itraconazole for at least 6 months in those who have responded to a primary course of amphotericin B. Until more data are available, primary therapy with itraconazole should be used with caution in compromised patients with blastomycosis and considered only in mild illness without CNS infection and stable or improving disease.

Long-term suppressive therapy may be needed in immunocompromised patients. Some experts recommend itraconazole as probably the best secondary prophylaxis for AIDS patients with blastomycosis.

Drug Category: Antifungal agents

Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Drug Name	Itraconazole (Sporanox)
Description	Oral itraconazole (at a dosage of 200-400 mg/d) is now the azole of choice in adult patients with indolent nonmeningeal blastomycosis of mild-to-moderate severity, whether given as primary therapy to stable patients or following a course of amphotericin B. Compared to other oral azoles, itraconazole is better absorbed and has enhanced antimycotic activity with fewer adverse effects. In a prospective phase 2 clinical trial involving adult patients, itraconazole was effective in 90% of cases receiving 200-400 mg/d. In a cohort study of 42 patients, similar success rates were noted for patients treated with 200 mg of itraconazole.
Adult Dose	200-400 mg/d PO with food (to enhance absorption); 200 mg/d initially; if poor response, increase dose in 100 mg increments; not to exceed 400 mg/d in 2 divided doses
Pediatric Dose	5-7 mg/kg/d PO qd or divided q12h
Contraindications	Documented hypersensitivity; coadministration with cisapride may cause adverse cardiovascular effects (possibly death)
Interactions	Decreased effect of itraconazole with carbamazepine, isoniazid, rifampin, phenytoin, phenobarbital (increased metabolism); H2-antagonists, omeprazole, antacids, didanosine (decreased absorption); inhibits CYP450 3A4 isoenzyme, thus increases effect of cyclosporine, tacrolimus (interferes with clearance); digoxin, warfarin and hypoglycemic agents (decreased metabolism); increased toxicity of terfenadine (recalled from US market), astemizole (recalled from US market), and cisapride (cardiotoxicity)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Rare cases of serious cardiovascular adverse event, including death, ventricular tachycardia, and torsade de pointes have been observed because of increased terfenadine, astemizole, and cisapride concentrations induced by itraconazole; itraconazole solution and capsules should not be used interchangeably; oral solution is administered on an empty stomach and capsules are taken with food

Drug Name	Ketoconazole (Nizoral)
Description	An effective alternative agent in the treatment of immunocompetent patients with mild-to-moderate blastomycosis. In prospective randomized clinical trials conducted by the Mycoses Study Group , cure rates of 70-85% have been documented in patients treated with 400-800 mg/d. Relapse rates of 10-14% have been reported, and close follow-up monitoring is warranted for 1-2 years after therapy with ketoconazole.
Adult Dose	400-800 mg/d PO; divide 800 mg/d in 2 doses
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; concomitant administration with terfenadine, astemizole, or cisapride
Interactions	Drugs that decrease absorption (raise gastric pH), such as antacids, H2-receptor blockers; drugs that decrease serum concentrations of ketoconazole (rifampin, isoniazid) Potent inhibitor of CYP450 3A4, drug concentrations that are increased by ketoconazole (phenytoin, cyclosporine, cisapride, astemizole (recalled from US market), digoxin, theophylline, terfenadine (recalled from US market), warfarin); drugs that cause hepatotoxicity; alcohol may cause disulfiramlike reactions
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Administration has been associated with hepatotoxicity, including some fatalities; high doses may depress adrenocortical function; risk of serious cardiac arrhythmias in patients receiving concomitant terfenadine, astemizole, or cisapride

Drug Name	Fluconazole (Diflucan)
Description	The role of fluconazole therapy in blastomycosis is limited. In a small pilot study involving 23 patients, a successful outcome was noted in only 15 (65%) of cases. Better results were reported recently using higher dosages of fluconazole (400-800 mg/d). A successful outcome was noted for 34 (87%) of 39 patients treated for a mean duration of 8.9 mo. Although fluconazole demonstrates excellent CNS penetration, its role in the treatment of blastomycotic meningitis and cerebral abscesses is anecdotal.
Adult Dose	400-800 mg/d PO
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; coadministration with cisapride
Interactions	Levels may increase with hydrochlorothiazides; fluconazole levels may decrease with long-term coadministration of rifampin; coadministration of fluconazole may decrease phenytoin clearance; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration; increases in cyclosporine concentrations may occur when administered concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use with caution in patients with renal and hepatic dysfunction (decrease dose); discontinue if hepatic injury is suspected

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention

• Although immunocompromised patients (including those with HIV/AIDS) living in or visiting blastomycosis-endemic areas cannot completely avoid exposure to B dermatitidis, they should be counseled about reducing the risk of acquiring blastomycosis by avoidance of occupational and recreational activities known to be associated with increased risk (eg, wooded areas along waterways). Although no specific data are available regarding blastomycosis in children with HIV, it is reasonable to administer lifelong suppressive therapy with itraconazole after an acute episode of the disease.

Complications

• Potential complications include progressive pulmonary disease and extrapulmonary dissemination.
• • Diffuse pulmonary infiltrates complicated by acute respiratory distress syndrome (ARDS) have been reported.
  • Extrapulmonary disease, frequently to the skin, bones, and genitourinary system, can occur in 25-40% of patients with blastomycosis.
• Extensive cutaneous lesions may undergo central healing with scarring and contracture.
• In compromised individuals, disseminated blastomycosis occurs more frequently.
• CNS involvement manifesting as either meningitis or mass lesions has been reported to occur in approximately 40% of adult patients with AIDS.

Prognosis

• Prognosis is poor for immunocompromised patients with blastomycosis.
• Mortality rates of 30-40% have been reported in AIDS patients. Most deaths tend to occur within the first few weeks of therapy.
• Pulmonary disease complicated by respiratory failure and ARDS has a high mortality rate.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose blastomycosis in a timely fashion

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Chapman SW, Bradsher RW JR, Campbell GD Jr, et al. Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America. Clin Infect Dis. Apr 2000;30(4):679-83. [Medline].
• Dismukes WE, Bradsher RW Jr, Cloud GC, et al. Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group. Am J Med. Nov 1992;93(5):489-97. [Medline].
• Dismukes WE, Cloud G, Bowles C. Treatment of blastomycosis and histoplasmosis with ketoconazole. Results of a prospective randomized clinical trial. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Ann Intern Med. Dec 1985;103(6 ( Pt 1)):861-72. [Medline].
• Klein BS, Vergeront JM, Weeks RJ, et al. Isolation of Blastomyces dermatitidis in soil associated with a large outbreak of blastomycosis in Wisconsin. N Engl J Med. Feb 27 1986;314(9):529-34. [Medline].
• Meyer KC, McManus EJ, Maki DG. Overwhelming pulmonary blastomycosis associated with the adult respiratory distress syndrome. N Engl J Med. Oct 21 1993;329(17):1231-6. [Medline].
• Panicker J, Walsh T, Kamani N. Recurrent central nervous system blastomycosis in an immunocompetent child treated successfully with sequential liposomal amphotericin B and voriconazole. Pediatr Infect Dis J. Apr 2006;25(4):377-9. [Medline].
• Pappas PG, Threlkeld MG, Bedsole GD, et al. Blastomycosis in immunocompromised patients. Medicine (Baltimore). Sep 1993;72(5):311-25. [Medline].
• Pappas PG, Bradsher RW, Chapman SW, et al. Treatment of blastomycosis with fluconazole: a pilot study. The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis. Feb 1995;20(2):267-71. [Medline].
• Pappas PG, Pottage JC, Powderly WG, et al. Blastomycosis in patients with the acquired immunodeficiency syndrome. Ann Intern Med. May 15 1992;116(10):847-53. [Medline].
• Sarosi GA, Hammerman KJ, Tosh FE, Kronenberg RS. Clinical features of acute pulmonary blastomycosis. N Engl J Med. Mar 7 1974;290(10):540-3. [Medline].
• Schutze GE, Hickerson SL, Fortin EM, et al. Blastomycosis in children. Clin Infect Dis. Mar 1996;22(3):496-502. [Medline].
• Shetty AK, Quinonez JM, Steele RW. Fever, hemoptysis and pneumonia in a twelve-year-old girl. Pediatr Infect Dis J. Sep 1998;17(9):849; 852-3. [Medline].
• Steele RW, Abernathy RS. Systemic blastomycosis in children. Pediatr Infect Dis. Jul-Aug 1983;2(4):304-7. [Medline].
• Sugar AM, Picard M. Macrophage- and oxidant-mediated inhibition of the ability of live Blastomyces dermatitidis conidia to transform to the pathogenic yeast phase: implications for the pathogenesis of dimorphic fungal infections. J Infect Dis. Feb 1991;163(2):371-5. [Medline].

Article Last Updated: Jun 20, 2006