Basics
Description
- Systemic infection caused by the dimorphic soil fungus Blastomyces dermatitidis
- Dimorphism is characterized by a mold phase (mycelial form) that grows at room temperature and a yeast form that grows at body temperature.
- Incubation period estimated at 30-45 days
Epidemiology
- Similar to other dimorphic fungi, B. dermatitidis is a soil saprophyte (mycelial form).
- Congenital infections occur rarely.
- Infection is endemic in the upper Midwest and Southern United States, particularly in the wooded Mississippi and Ohio River valleys and the Great Lakes. The highest incidence in the United States is in Wisconsin, Mississippi, and Tennessee followed by Minnesota, Illinois, North Dakota, Alabama, and Louisiana.
- Substantial disease occurs in the Canadian provinces of Manitoba and northwestern Ontario. Other reported areas of infection include Africa, India, and South America.
- Children account for 3-11% of all cases of blastomycosis.
- Blastomycosis is a very uncommon diagnosis even in endemic regions.
Risk Factors
- Blastomycosis is more common in males. This is thought to be due to occupational or recreational activities that increase risk of exposure.
- Underlying immunodeficiency is rarely observed among children with blastomycosis.
General Prevention
- No special precautions for hospitalized patients are indicated.
- The natural reservoir is undetermined.
Pathophysiology
- Inhalation of the fungus into the lung is followed by an inflammatory response with neutrophils and macrophages.
- Blastomycosis most commonly presents as subacute pulmonary disease, but the clinical spectrum of the disease extends from asymptomatic to disseminated disease that can involve lung, skin, bone, and central nervous system (CNS).
- As many as 50% of infections are asymptomatic.
Etiology
- Infection is almost always caused by inhalation of spores from B. dermatitidis.
- Rarely, blastomycosis has occurred through accidental inoculation, dog bites, conjugal transmission, and intrauterine transmission.
- Point-source outbreaks have occurred with occupational and recreational activities that occur in areas with moist soil and decaying vegetation, such as along streams and rivers.
- Natural infection occurs in humans and dogs.
Commonly Associated Conditions
- Pulmonary blastomycosis
- Most common form of infection by Blastomyces in children
- Can be acute, subacute, or chronic
- Illness severity can vary greatly, from asymptomatic to upper respiratory tract infection, bronchitis, pleuritis, pneumonia, or severe respiratory distress.
- Cutaneous blastomycosis
- Skin manifestations are variable and include nodules, verrucous lesions, subcutaneous abscesses, or ulcerations.
- Cutaneous disease usually occurs after pulmonary infection with dissemination to the skin, rarely by direction inoculation.
- Bone blastomycosis
- Bone disease usually occurs after pulmonary infection with dissemination to the bone resulting in osteomyelitis and bone destruction.
- Disseminated blastomycosis
- Recent series suggest that this occurs in less than 1/2 of children
- Usually begins as pulmonary infection, with subsequent spread to involve skin, bone, genitourinary tract, and/or CNS.
- Can disseminate to virtually any organ
- The classic triad of lung, bone, and skin disease occurs in ≤15% of children.
Diagnosis
History
- History of residence or travel to an endemic area is very important.
- For children with acute pulmonary blastomycosis, the most common presenting symptoms are the following:
- Cough (may be productive)
- Fever
- Chest pain
- Malaise
- Children with chronic pulmonary disease present with the following:
- Chronic (>2 weeks) nonproductive cough
- Pleuritic chest pain
- Poor appetite
- May also be a history of fever, chills, weight loss, fatigue, night sweats, or, rarely, hemoptysis
Physical Exam
- Initial pulmonary infection may present with physical exam findings similar to those of bacterial pneumonia.
- Respiratory signs and symptoms often have resolved by the time cutaneous manifestations are apparent.
- Skin involvement appears as nodules, nodules with ulceration, or granulomatous lesions.
- Bone involvement usually presents with progressive focal pain and point tenderness.
Diagnostic Tests & Interpretation
Diagnostic Procedures/Other
- Definitive diagnosis requires the growth of B. dermatitidis from a clinical specimen. In the cooler temperature at which fungal culture is performed in the laboratory, B. dermatitidis usually switches back to the mold form.
- Direct visualization of the yeast form may be performed on samples of sputum, urine, cerebrospinal fluid, bronchoalveolar lavage sample, or tissue biopsy.
- Although the most accurate serologic test is the enzyme immunoassay, all serologic tests have poor sensitivity and specificity.
- An assay to detect Blastomyces antigen in urine is available and is about 93% sensitive. Cross-reactivity occurs in patients with histoplasmosis, paracoccidioidomycosis, and Penicillium marneffei infections.
- Chest radiography commonly reveals lobar consolidation. Cavitation, fibronodular patterns, mass, and mass effect may also be seen.
Differential Diagnosis
- Acute bacterial infection
- Neoplasm
- Tuberculosis
- Sarcoidosis
- Other fungal infections causing pneumonia (e.g., histoplasmosis)
Treatment
Medication
- Although acute pulmonary infections may resolve without treatment, the high rate of progression to extrapulmonary disease leads many experts to recommend treatment for all cases of blastomycosis.
- Mild or moderate pulmonary or extrapulmonary disease
- Oral itraconazole
- Alternative agents include fluconazole or voriconazole.
- Severe pulmonary disease, other severe infection, or immunosuppression
- IV amphotericin B: Many experts prefer a lipid formulation of amphotericin B over amphotericin B deoxycholate.
- Therapy may be switched to oral itraconazole after clinical stabilization with amphotericin B.
- CNS blastomycosis
- Lipid formulation of amphotericin B at 5 mg/kg/day over 4-6 weeks, followed by an oral azole
- During pregnancy
- IV amphotericin B
- Azoles should be avoided owing to potential teratogenicity.
- Length of therapy is site dependent:
- ≥6 months or longer for pulmonary disease
- ≥12 months or longer for bone or CNS disease
- Lifelong suppressive therapy with oral itraconazole may be required for immunosuppressed patients and in patients who experience relapse despite appropriate therapy.
- Voriconazole, a newer azole, has in vitro activity against B. dermatitidis and penetrates the CSF better than itraconazole. Anecdotal reports support its use as an option for step-down therapy for CNS infection.
Surgery/Other Procedures
Occasionally, drainage of abscesses and debridement of bone are necessary. �
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- All azoles can cause hepatitis. Thus, hepatic enzymes should be measured before starting therapy, 2-4 weeks after therapy has begun, and every 3 months during therapy.
- All azoles interact with P450 enzymes. Consider drug-drug interactions when the patient is taking other medications.
- Itraconazole capsules are poorly absorbed; the oral solution is poorly tolerated due to taste. Monitoring adherence to therapy is important and many recommend following itraconazole levels.
- Amphotericin B commonly causes acute kidney injury and electrolyte wasting (particularly potassium and magnesium). Infusion-related toxicity is also common. Lipid formulations are typically better tolerated than the deoxycholate.
Prognosis
- Before antifungal medications were available, the mortality associated with blastomycosis was up to 90%.
- Appropriate treatment with antifungal medications results in excellent cure rates and mortality rates of <10%.
- Worse outcomes tend to occur in association with a delay between onset of symptoms and establishment of a diagnosis.
Complications
- Dissemination is the main complication of the infection, occurring in less than 50% of children with blastomycosis.
- Residual orthopedic issues can persist in children with bone involvement.
- Systemic infection may be well advanced before symptoms are noted, requiring long-term therapy and follow-up.
Additional Reading
- Anderson �EJ, Ahn �PB, Yogev �R, et al. Blastomycosis in children: a study of 14 cases. J Ped Infect Dis Soc. 2014;2:386-390.
- Baddley �JW, Winthrop �KL, Patkar �NM, et al. Geographic distribution of endemic fungal infections among older persons, United States. Emerg Infect Dis. 2011;17:1664-1669. �[View Abstract]
- Chapman �SW, Dismukes �WE, Proia �LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1801-1812. �[View Abstract]
- Chu �JH, Feudtner �C, Heydon �KH, et al. Hospitalizations for endemic mycoses: a population based national sample. Clin Infect Dis. 2006;42(6):822-825. �[View Abstract]
- Durkin �M, Witt �J, LeMonte �A, et al. Antigen assay with the potential to aid in diagnosis of blastomycosis. J Clin Micro. 2004;42:4873-4875. �[View Abstract]
- Fanella �S, Skinner �S, Trepman �E, et al. Blastomycosis in children and adolescents: a 30 year experience from Manitoba. Med Mycol. 2011;49(6):627-632. �[View Abstract]
- Montenegro �BL, Arnold �JC. North American dimorphic fungal infections in children. Pediatr Rev. 2010;31(6):e40-e48. �[View Abstract]
Codes
ICD09
ICD10
- B40.9 Blastomycosis, unspecified
- B40.2 Pulmonary blastomycosis, unspecified
- B40.7 Disseminated blastomycosis
- B40.3 Cutaneous blastomycosis
- B40.8 Other forms of blastomycosis
- B40.81 Blastomycotic meningoencephalitis
- B40.0 Acute pulmonary blastomycosis
- B40.89 Other forms of blastomycosis
- B40.1 Chronic pulmonary blastomycosis
SNOMED
- 69996000 Blastomycosis (disorder)
- 233616001 Pulmonary blastomycosis (disorder)
- 187067000 Disseminated blastomycosis (disorder)
- 187065008 Cutaneous blastomycosis
- 406562008 Blastomyces infection of central nervous system
FAQ
- Q: When should I suspect blastomycosis?
- A: Consider blastomycosis in a child with exposure to an endemic blastomycosis area that is presenting with subacute to chronic pneumonia. Oftentimes, these children will have been treated with multiple prior antibiotics and have ongoing or progressive pneumonia or develop skin or bone lesions.
- Q: Blastomycosis is on my differential; how can I best test for it?
- A: The urine antigen test is the most sensitive test for the detection of blastomycosis but can be falsely positive. Usually, a clinical specimen is ultimately needed to establish a diagnosis.
- Q: I have a child hospitalized with blastomycosis; should I start with itraconazole or amphotericin B?
- A: If the child is not in the ICU, is not acutely worsening, and is able to take itraconazole by mouth, then it is reasonable to start with itraconazole. Itraconazole is generally much better tolerated than are amphotericin B formulations.