A Novel Case of Disseminated Blastomycosis in China
Blastomycosis is a fungal infection caused by Blastomyces dermatitidis, a dimorphic fungus that thrives in soil and decaying organic matter, particularly in regions near lakes and rivers. This disease is endemic to certain areas of North America, notably the regions surrounding the St. Lawrence-Great Lakes and the Mississippi River systems. However, sporadic cases have also been reported in Africa and India. The infection typically begins in the lungs after inhalation of fungal spores, but it can disseminate to other parts of the body, including the skin, bones, genitourinary tract, and central nervous system. Blastomycosis can affect both immunocompromised and immunocompetent individuals, and its clinical manifestations can vary widely, making it a challenging condition to diagnose, especially in non-endemic regions.
This article presents a detailed account of a 25-year-old male patient who was diagnosed with disseminated blastomycosis in China. The patient had recently returned from the United States, where he had lived in Vermont for four years without traveling outside the state. Vermont is located in the northeastern United States, an area known to be endemic for blastomycosis. The patient initially presented with symptoms of fever, cough, and knee pain, which were initially misdiagnosed as a common cold. He was treated with non-steroidal anti-inflammatory analgesics and oral antibiotics, but his symptoms did not improve. Over time, the swelling and pain in his left knee worsened, and a red rash with mild pain appeared on his lower limbs.
Upon admission to a municipal hospital in Hangzhou, China, a chest computed tomography (CT) scan revealed high-density areas in the left lower lobe and left hilum. Laboratory tests indicated an elevated white blood cell (WBC) count of 11.6 × 10^9/L, with neutrophils accounting for 88.2% of the WBCs, and a C-reactive protein (CRP) level of 70.3 mg/dL. The patient was initially diagnosed with community-acquired pneumonia and treated with moxifloxacin injections (400 mg per day) for one week. However, his condition did not improve, and his liver enzymes became elevated, with alanine transaminase (ALT) reaching 191 U/L and aspartic transaminase (AST) at 121 U/L. Additionally, his WBC count increased to 16.6 × 10^9/L, and his CRP level rose to 213 mg/dL.
The patient’s left knee joint swelling and pain continued to progress, and a magnetic resonance imaging (MRI) scan revealed bone marrow edema in the distal femur and joint effusion. Meanwhile, the skin lesions on his lower limbs increased in number and size, with some lesions rupturing and discharging pus. Bronchoscopy revealed a neoplasm in the left lingular bronchus (B4 + B5), and a tissue biopsy identified suspicious spore-like substances. Due to the complexity of the case, the patient was transferred to the Respiratory Department of the First Affiliated Hospital, School of Medicine, Zhejiang University, on May 28th, 2018.
Upon admission to the hospital, a thorough review of the patient’s medical history revealed that he had lived in Vermont for four years, a region endemic for blastomycosis. Physical examination findings included a low-grade fever of 37.8°C, a positive floating patella test in the left knee joint, and clusters of skin lesions on the lower limbs. Laboratory tests showed a WBC count of 17.2 × 10^9/L, neutrophils at 89.9%, CRP at 218.5 mg/dL, ALT at 214 U/L, and AST at 93 U/L. Tests for tuberculosis (T-SPOT.TB assay), fungal infections ((1,3)-β-D-glucan assay, galactomannan assay), and Cryptococcus (capsular polysaccharide antigen latex agglutination test) were all negative. Ultrasonography revealed no organic lesions in the liver and gallbladder.
Given the patient’s clinical presentation and history, the initial diagnosis considered the hematogenous spread of a gram-positive bacterium, such as methicillin-resistant Staphylococcus aureus (MRSA). Linezolid injections (600 mg every 12 hours) were prescribed. Histologic examination of the bronchus mucous membrane biopsy revealed yeast spores with thick, doubly refractile cell walls. An articular puncture was performed, and approximately 25 mL of light brown bloody fluid was obtained from the left knee joint. The joint effusion and skin pus were sent for culture and smear examination. Fluorescence-stained microscopic examination revealed round spores in both the joint effusion and skin pus.
Based on the clinical characteristics and the patient’s history of living in an endemic area, the diagnosis of disseminated blastomycosis was considered. To confirm this, the skin pus was sent for pathogen detection using next-generation sequencing (NGS) technology (PMseq™, BGI, Shenzhen, China). The NGS analysis identified 57 sequences uniquely corresponding to Blastomyces dermatitidis. Additionally, fungal colonies with a white and glabrous appearance were cultured from the skin pus on a Sabouraud medium, further confirming the diagnosis of blastomycosis.
On the third day after admission, the patient was started on empirical antifungal treatment with oral posaconazole suspension (400 mg twice per day for 12 days, followed by 200 mg three times per day due to elevated liver enzymes). A follow-up chest CT scan after 10 days of antifungal therapy showed significant radiographic resolution. The patient’s clinical symptoms, including cough and knee joint pain, improved, and the skin lesions on his lower limbs began to shrink and crust. He was discharged after three weeks of hospitalization with a continued prescription for posaconazole. Monthly follow-up visits showed improved physical ability, further absorption of pulmonary effusions, and slightly elevated liver enzymes. The patient continued taking posaconazole for approximately nine months.
Blastomycosis is often referred to as “the great pretender” because it can mimic a wide range of diseases, including pneumonia, tuberculosis, and malignancy. This lack of specificity makes it difficult to diagnose promptly, leading to the overuse of antibiotics, particularly in non-endemic regions. In China, nine cases of blastomycosis have been reported previously, most of which were in male patients with a median age of 29 years. The majority of these patients had a history of living or traveling in endemic areas, although two cases had no such history, suggesting that blastomycosis may be sporadically present in China. The median delay in diagnosis was 2.5 months, with most cases initially misdiagnosed as common respiratory infections and treated with antibiotics for extended periods. Three patients were subsequently treated for suspected tuberculosis, and two cases were misdiagnosed as malignancy.
The definitive diagnosis of blastomycosis is typically made through the culture of Blastomyces dermatitidis, although this method is time-consuming. Direct histopathological or cytopathological examinations can facilitate a more prompt diagnosis. In this case, the use of NGS-based pathogen detection allowed for early diagnosis and timely antifungal therapy. Treatment recommendations for blastomycosis depend on the severity of the disease, the site of infection, the patient’s immune status, and pregnancy. For mild to moderate disseminated blastomycosis, oral itraconazole is the first-line treatment, while amphotericin B is recommended for moderate to severe cases. Posaconazole has been reported as a successful treatment option in some cases, and in this patient, it proved to be effective and well-tolerated.
In conclusion, this case highlights the importance of considering blastomycosis in patients with a history of travel or residence in endemic areas, even in non-endemic regions like China. The use of advanced diagnostic techniques, such as NGS, can facilitate early diagnosis and appropriate treatment, reducing the risk of complications and improving patient outcomes. Posaconazole may be a viable alternative treatment option for disseminated blastomycosis, particularly in patients with elevated liver enzymes.
doi.org/10.1097/CM9.0000000000000566
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