활액에서 분리된 Coccidioides posadasii의 분자생물학적 동정
Molecular Identification of Coccidioides posadasii in Synovial Fluid in Korea
서울대학교 의과대학 검사의학교실1, 서울대학교병원 진단검사의학과2, 서울특별시보라매병원 진단검사의학과3, 서울대학교병원 호흡기내과4, 보훈공단 중앙보훈병원 호흡기내과5
Department of Laboratory Medicine1, Seoul National University College of Medicine; Department of Laboratory Medicine2, Seoul National University Hospital; Department of Laboratory Medicine3, SMG-SNU Boramae Medical Center; Department of Internal Medicine4, Seoul National University Hospital; Department of Internal Medicine5, Veterans Health Service Medical Center, Seoul, KoreaCorrespondence to:
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lab Med Online 2021; 11(1): 60-63
Published January 1, 2021
Copyright © The Korean Society for Laboratory Medicine.
Coccidioidomycosis is a fungal infection caused by the
An 80-year-old Korean man with a medical history of early gastric cancer and subtotal gastrectomy in 1993 visited the outpatient department of Boramae Medical Center from 2012 to 2018. He complained of chronic cough, recurrent pneumonia, and left knee pain and swelling. No evidence of mycosis was detected during the six-year outpatient visits. In June 2018, he opted to have total knee replacement surgery and underwent a preoperative evaluation. Chest radiographs and computed tomography images revealed multiple solid and cavitary nodules of variable size in both lungs. We suspected, that he had either pulmonary metastasis of a malignant tumor or a mycobacterial infection. At the time, he refused further diagnosis and treatment. Subsequently, in November 2019, he reported increased sputum production and aggravated dyspnea. A complete blood count (CBC) test indicated mild eosinophilia (592/μL) with normal leukocyte count (8,710/μL). A transbronchoscopic lung biopsy and pathological examination revealed granulomatous inflammation and necrosis of bronchial tissue, indicative of coccidioidomycosis. Both Gomori Methenamine Silver and periodic acid-Schiff staining of bronchial tissue were positive, while acid-fast bacillus staining was negative. However, no organism growth was detected in the culture of bronchial washings. Meanwhile, the patient complained of severe arthralgia of the left knee, and therefore underwent an ultrasound-guided joint fluid aspiration for diagnosis. The fluid had a yellow jelly-like consistency with debris. After 3 weeks of incubation on Sabouraud dextrose agar at 30°C, there was white cottony mold on the plate, that grew into white fluffy circles (Fig. 1A). Microscopic examination revealed branched hyphae with alternating barrel-shaped arthroconidia that suggested
Figure 1. Microbiological findings in culture of synovial fluid: (A) Colony of white cottony mold on Sabouraud dextrose agar after 3 weeks at 30°C, (B) Arthroconidia of
Coccidioides posadasii(lactophenol cotton blue stain, 1,000× magnification).
We extracted the DNA from the isolated colony by boiling at 100°C for 10 min. PCR amplification and sequencing of the internal transcribed spacer (ITS) region was then conducted using the ITS1 (5′-TCCGTAGGTGAACCTGCGG-3′) and ITS4 (5′-TCCTCCGCTTATTGATATGC-3′) primers. We thus obtained a 628 bp consensus sequence (GenBank accession number MH862946.1) which was found to share 100% similarity with
He was administered fluconazole 400 mg/d IV for 2 weeks, 200 mg/d IV for 1 week, and 200 mg/d PO for 10 days. Following that, he was administered amphotericin B 200 mg/d IV for 4 weeks and fluconazole 300 mg/d for 4 weeks. He was discharged with improvement of symptoms.
Although coccidioidomycosis is common in America, it is rarely recognized or diagnosed in non-endemic regions . In our case, it was only after his diagnosis, that the patient informed us of having visited Phoenix, Arizona, USA several times from 2010 to 2012. This lack of information delayed accurate diagnosis. Therefore, while taking patients’ medical history it is necessary to include travel history, to facilitate accurate diagnosis. In addition, pneumonia of unknown etiology should be eliminated as a possible cause of coccidioidomycosis, which accounts for 30% of cases of community-acquired pneumonia in endemic regions . Since it was first reported in 1976 in Korea, 17 previous cases of coccidioidomycosis, have been confirmed by histopathology or culture with microscopic identification . Of these, 8 were of disseminated coccidioidomycosis (Table 1). Including our case, this number accounts for half of the total cases. Most cases (87.5%) involved the skin, while only our case involved the joint. Further, a review of coccidioidomycosis in China, has reported 30 total cases, of which 12 (40%) were that of disseminated infection . Although extrapulmonary involvement of coccidioidomycosis accounts for less than 1% of total infections , disseminated infection is more common in Asian patients than in patients from endemic regions [7, 8]. It is also more common in men, pregnant women, infants, non-Caucasians, and immunocompromised individuals . In Korea, 66.7% cases of disseminated infection were male and 55.6% (including our case) were immunosuppressed patients (Table 1).
Our patient showed chronic pulmonary pneumonia and disseminated infection. As it happened in our case, pulmonary coccidioidomycosis is often mistaken for pulmonary malignancies due to morphological similarities. It presents as a nodular or cavitary lesion, cavitary pulmonary disease with fibrosis, or military pulmonary dissemination . Therefore, laboratory confirmation by histological or microbiological testing is important. Although, culture is the gold standard in diagnosis, it is slow . Moreover, since Korea is a non-endemic region, the serological test that is commonly used in America, is not easily available here. Therefore, in addition to the serologic test, we analyzed the synovial fluid by culture, followed by ITS sequencing of the fungal isolate. Disseminated infection requires lifelong treatment with anti-fungal agents. The Infectious Diseases Society of America (IDSA) recommends fluconazole or itraconazole for chronic pneumonia, azole therapy for bone and joint coccidioidomycosis, and amphotericin B as initial therapy in severe cases . In our case, we started with fluconazole, but later changed to amphotericin B after diagnosis of joint infection. Further,
In summary, we identified
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