Blastomycosis is an endemic dimorphic fungus most commonly found in southeastern and south central states, especially those bordering the Mississippi and Ohio river basins [1, 2]. Recent reports have shown an increase in the incidence of blastomycosis in some regions with the highest incidence reported in Wisconsin. The yearly incidence rates of blastomycosis are 1 to 2 cases per 100,000. The initial causative mechanism of pulmonary infection is thought to be the inhalation of the conidia of B. dermatitidis. In nature, the organism exists in the mycelial form but converts to the yeast phase in the alveoli. The organism is typically found in soil that is warm and moist and rich in organic debris; thus, the major risk for infection is exposure to soil near waterways or in wooded areas. However, there is some evidence that some cases may arise in the home, especially in basements and attics [3]. While general preventive measures are difficult, individuals with weakened immune systems are at higher risk of blastomycosis.
Clinical manifestations of blastomycosis are quite variable and require a high degree of suspicion. The lungs serve as the portal of entry. Pulmonary infection can manifest as acute or chronic pneumonia, the latter being more common [1]. Acute pneumonia can present with fevers, fatigue, chills, and cough and may be difficult to differentiate from other infectious pneumonia [2]. Spontaneous resolution of acute infections have been reported although the frequency is unknown [4]. Diagnosis during the acute infection can be delayed for weeks to months, leading to the development of chronic pulmonary blastomycosis. During this period, patients typically receive multiple courses of antibiotics before a diagnosis is established. Symptoms during chronic pulmonary blastomycosis may include malaise, weight loss, night sweats, chills, fever, and possible hemoptysis2. These symptoms can be difficult to differentiate from other diseases. Indeed, a differential diagnosis during this time may include malignancy, tuberculosis, sarcoidosis, and other pulmonary infections or fungal diseases such as histoplasmosis.
Blastomycosis can present with a myriad of radiographic features including air-space consolidation, mass-like lesion, intermediate-sized nodules, interstitial disease, miliary disease, or cavitary lesions5. Air-space like consolidation is the most common radiographic finding and is often mistaken for a bacterial pneumonia. Masses on chest imaging are the second most common radiographic finding. They may be found in up to 31% of cases; typically in patients with a chronic presentation of the disease [5, 6]. These masses are often mistaken for lung malignancy, and in one case series from the Mayo Clinic, 55% of such masses were resected for suggestive bronchogenic carcinoma [6]. Similar to other fungal pneumonias, false positive PET-CT scan results can occur because of the recruitment of inflammatory cells, which have a high metabolic rate and thus increased uptake of FDG [7, 8]. In endemic areas, the differential for a lesion suspicious for lung cancer should include fungal pneumonias.
The most common site of extra-pulmonary manifestations of blastomycosis is the skin [1, 2]. Cutaneous lesions may be present in 40–80% of cases of blastomycosis and typically present as verrucous or ulcerative lesions [9,10,11,12,13,14,15]. Verrucous lesions have an irregular, raised border with possible exudate from an associated abscess in the subcutaneous tissue. These lesions can often be mistaken for squamous cell carcinoma. Ulcers have a more uniform and regular appearance1. Both lesions can be seen in the same patient.
In patients with pulmonary blastomycosis, there is a high positive yield with sputum cultures (86%) and an even higher yield with specimens obtained via bronchoscopy (92%) [16]. Although the diagnostic yield of wet preparations of sputum or pus is low, it should be considered given the low cost and simplicity. Serologic tests are available but have varying degrees of sensitivity and specificity and a significant amount of cross reactivity with other endemic mycoses [17]. Given these problems, serology is not thought to be the primary test for the diagnosis of blastomycosis. On histopathologic examination, the presence of pyogranulomas should prompt the possibility of blastomycosis. It may be difficult to visualize yeast forms with routine hematoxylin and eosin stain, thus specials stains are usually required.
Although culture and cytopathology remain the gold standards for diagnosing Blastomycosis, the detection of B. dermatitidis antigens may be a useful adjunct. The sensitivity of B. dermatitidis antigen assays for detecting antigenuria is between 85 to 93% and 57% for antigenemia [18,19,20]. The specificity is high, 99–100%, among healthy subjects or those without a known fungal infection. However, significant cross reactivity has been reported in patients with histoplasmosis as well as other fungal infection [19, 20]. Thus, a positive B. dermatitidis antigen assay should be interpreted with caution given the knowledge of known cross-reactivities. The utility of antigen detection assays for monitoring response to therapy remains an open question. A steady decline in detectable antigenuria and antigenemia has been shown in dogs treated with itraconazole for blastomycosis [21]. In humans, patients who responded to antifungal therapy have been shown to clear antigens, and the persistence of antigens may indicate treatment failure or non-adherance [22, 23]. A recent study has shown promising results with an antibody enzyme immunoassay using the B. dermatitidis surface protein Bad-1 [24].
Current treatment for blastomycosis includes azole antifungals such as itraconazole and flucanazole for mild to moderate infection with a lipid-based formulation of amphotericin reserved for severe life-threatening cases of the disease. With recent approval in the past decade of newer antifungals such as voriconazole and posaconazole, the number of available azole antifungals has expanded. Early studies of posaconazole compared it with amphotericin B, itraconazole, and flucanazole in mice infected with B. dermatitidis, and showed potent posaconazole activity with an MIC at which 90% of the isolates were inhibited of 0.06 mg/mL [25]. While larger trials are lacking, posaconazole has since been successfully used in treating patients with Blastomycosis [26]. We have had similar success at our center in treating blastomycosis with posaconazole. It is well tolerated, the oral tablet formulation is adequately absorbed, and the drug levels can be measured as well.
In conclusion, chronic blastomycosis, like other fungal infections, can occasionally present with clinical and radiographic features indistinguishable from thoracic malignancies. There is no clinical syndrome specific for blastomycosis, thus a high degree of suspicion is required for early diagnosis. Definitive diagnosis requires visualizing the organism by histopathologic examination or obtaining a positive culture. Given the vastly different approach to treatment between fungal infections and malignancy, fungal infections, particularly in endemic areas, should be considered in the patient with a suspicious lesion negative for malignancy or failure to respond to treatment for a typical lung infection.
