Blastomycosis

• Sajeev Handa, M.D.

 Basic Information

Definition

Blastomycosis is a systemic pyogranulomatous disease caused by a dimorphic fungus, Blastomyces dermatitidis. Since 2013, another variant, Blastomyces gilchristii, has been described in the literature.

ICD-10CM CODES
B40.9	Blastomycosis, unspecified
B40.0	Acute pulmonary blastomycosis
B40.1	Chronic pulmonary blastomycosis
B40.2	Pulmonary blastomycosis, unspecified
B40.3	Cutaneous blastomycosis
B40.7	Disseminated blastomycosis
B40.89	Other forms of blastomycosis

Epidemiology & Demographics

Incidence & Prevalence

1. •

   Most patients reside primarily in North America in the southeastern and south central states, especially those bordering the Mississippi and Ohio River valleys, the Midwestern states, and Canadian provinces bordering the Great Lakes.

2. •

   Point source outbreaks usually occur.

3. •

   Rare cases reported outside the U.S.

Risk Factors

1. •

   Widely disseminated disease is most common in immunocompromised hosts, especially those with acquired immunodeficiency syndrome (AIDS).

2. •

   Initial infections result from inhalation of conidia into the lungs, although primary cutaneous blastomycosis has been reported after dog bites.

Physical Findings & Clinical Presentation

1. •

   Acute infection: <50% symptomatic, median incubation 30 to 45 days. Symptoms are nonspecific: mimic influenza or bacterial infection with abrupt onset of myalgias, arthralgias, chills, and fever; transient pleuritic pain, cough that is initially nonproductive. Resolution within 4 wk is usual.

2. •

   Chronic or recurrent infection: indolent, progressive; includes pulmonary or extrapulmonary disease.

Pulmonary Manifestations

Symptoms and signs of chronic pneumonia: productive cough, hemoptysis, pleuritic chest pain, weight loss, low-grade pyrexia.

1. •

   B. gilchristii infection has been linked to fatal acute respiratory distress syndrome in adults.

Extrapulmonary Manifestations

1. 1.

   Cutaneous: most common; may occur with or without pulmonary disease (Fig. E1). Two different lesions:

   1. ○

      Verrucous: beginning as a small papulopustular lesion on exposed body areas that may develop into an eschar with peripheral microabscesses (Fig. E2).

   2. ○

      Ulcerative: Subcutaneous nodules (cold abscesses) and rarely cutaneous inoculation blastomycosis may occur.

      

      

2. 2.

   Bone and joint: 10% to 50% have osteolytic lesions (Fig. E3); affects long bones, vertebrae, and ribs; lesions may present with contiguous soft tissue abscess or draining sinus that spreads to a joint, resulting in pyarthrosis

   

3. 3.

   Genitourinary: 10% to 30%; prostatic involvement is most common and may present as obstruction; epididymis and testes may also be affected

4. 4.

   Central nervous system: 5% normal host; 40% AIDS patients; meningitis and abscess formation

Etiology

B. dermatitidis exists in warm, moist soil that is rich in organic material. When these microfoci are disturbed, the aerosolized spores or conidia are inhaled into the lungs. Disease at other sites is a result of dissemination from the initial pulmonary infection; the latter may be acute or chronic.

Diagnosis

Differential Diagnosis

Pulmonary Infection

1. •

   Bacterial pneumonia

2. •

   Histoplasmosis

3. •

   Coccidioidomycosis

4. •

   Tuberculosis

5. •

   Bronchogenic carcinoma

Cutaneous Infection

1. •

   Bromoderma

2. •

   Pyoderma gangrenosum

3. •

   Mycobacterium marinum infection

4. •

   Squamous cell carcinoma

5. •

   Giant keratoacanthoma

Workup

1. •

   Physical examination and laboratory data

2. •

   Definitive diagnosis established by culture or by visualization of organisms by fungal stains.

3. •

   Antibody tests lack sensitivity.

Laboratory Tests

1. •

   Presumptive diagnosis can be made by visualizing the distinctive yeast forms in clinical specimens.

2. •

   Culture: on Sabouraud medium or more enriched media.

   1. 1.

      Aspirated material from abscesses

   2. 2.

      Skin scrapings

   3. 3.

      Prostatic secretions (urine culture with prostatic massage)

3. •

   Direct examination of specimens.

   1. 1.

      Wet preparation with 10% KOH (Fig. E4)

      

   2. 2.

      Histopathology: typically demonstrates pyogranulomas; yeast identification requires special stains

1. •

   A commercial test for Blastomyces antigen in specimens of urine, blood, and other fluids is available.

2. •

   Serologic tests: A negative test result cannot exclude blastomycosis, and a positive titer should not be an indication to start treatment; therefore, current serologic assays serve no role.

Imaging Studies

In chronic disease, chest radiographic findings are nonspecific, but lobar or segmental alveolar infiltrates, especially of the upper lobes, are most common and may progress to cavitation.

Treatment

1. •

   Treatment remains controversial for acute pulmonary blastomycosis. Generally, all immunocompromised patients and patients with moderate to severe pneumonia or disseminated infection require therapy.

2. •

   Because the acute form may be benign and self-limited, some patients may be closely observed.

3. •

   Resolution of chronic blastomycosis without antifungal therapy is uncommon, and untreated blastomycosis has been associated with mortality rates approaching 60%.

Non–Central Nervous System Blastomycosis

Moderately severe to severe

1. •

   Liposomal amphotericin B (L-AmB) 3 to 5 mg/kg/day or L-AmB 0.7 to 1 mg/kg/day × 1 to 2 wk or until clinical response, then itraconazole oral solution 2.5 mg/kg po tid for 3 days, then once daily or bid for 6 to 12 months

Mild to moderate

1. •

   Itraconazole 200 mg PO tid for 3 days and then once or bid for 6 to 12 months

Alternative regimens

1. •

   Posaconazole delayed-release tabs 300 mg PO bid for 2 doses and then 300 mg PO daily; suspension 200 mg qid and then 400 mg po bid after stabilization of disease or 300 mg IV over 90 min bid for 1 day and then 300 mg IV daily

2. •

   Voriconazole 4 mg/kg po bid

3. •

   Fluconazole 400 to 800 mg PO once a day for those intolerant to itraconazole

Central Nervous System Blastomycosis

Liposomal amphotericin B at a dosage of 5 mg/kg/day over 4 to 6 wk, followed by either fluconazole 800 mg/day or voriconazole 6 mg/kg bid for two doses and then 4 mg/kg bid for at least 12 months and until resolution of cerebrospinal fluid abnormalities

Note:

1. •

   Lifelong suppressive therapy with oral itraconazole 200 mg/day may be required, especially in immunocompromised individuals.

2. •

   Serum itraconazole levels should be determined in all patients after they have received treatment with this agent for 2 wk.

3. •

   Surgery may be indicated for drainage of large abscesses.

Disposition

1. •

   Before antifungal therapy, the disease had a progressive course with eventual extrapulmonary disease and a mortality rate approaching 60%.

2. •

   Relapse rate for patients treated with AmB is 5%; relapse is more common in AIDS patients.

Pearls & Considerations

1. •

   Blastomyces dermatitidis may mimic other diseases.

2. •

   Colonization does not occur as with Candida and Aspergillus species.

Suggested Readings

• J.R. Bariola, et al.: Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infec Dis. 50:797–804 2010

• D. Dalcin, et al.: Blastomyces gilchristii as cause of fatal acute respiratory distress syndrome. Emerg Infect Dis. 22 (2):306–308 2016 https://dx.doi.org/10.3201/eid2202.151183 26812599

• M. Roy, et al.: A large community outbreak of blastomycosis in Wisconsin with geographic and ethnic clustering. Clin Infec Dis. 57:655–662 2013