림프절변연부 B세포림프종 환자에서 Mucor circinelloides에 의한 복막염 및 파종성 털곰팡이증 증례
A Case of Peritonitis and Disseminated Mucormycosis Caused by Mucor circinelloides in a Patient with Nodal Marginal Zone B-cell Lymphoma
2성균관대학교 의과대학 삼성서울병원 진단검사의학과
1Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea
2Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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 2020; 10(3): 250-254
Published July 1, 2020
Copyright © The Korean Society for Laboratory Medicine.
Mucormycosis is one of the most common fungal infections caused by species belonging to the order Mucorales such as
A 59-year-old man who was diagnosed with nodal marginal zone B-cell lymphoma and received scheduled chemotherapy was hospitalized for one day for high fever (39.5°C) and general weakness. His complete blood counts were as follows: hemoglobin 86 g/L, white blood cells (WBC) 0.11×109/L, platelets 36× 109/L. He also had a neutropenic fever. After two days, he showed abnormal results of liver function test (LFT), and his other blood tests reports were as follows: aspartate aminotransferase 13,476 IU/L, alanine aminotransferase 4,591 IU/L, total bilirubin 3.37 mg/dL, γ-glutamyl transferase 51 IU/L, and high-sensitivity C-reactive protein 18.80 mg/dL.
Figure 1. Computed tomography (CT) scan and identified
Mucor circinelloidesfrom the patient. (A) Ascites in abdominal CT. (B) Macroscopic feature on Sabouraud dextrose agar plate. (C) Microscopic features (×200) after lactophenol cotton blue staining.
A specimen of ascites in a blood culture bottle was transferred to laboratory, and cultured on a blood agar plate at 37°C and 5% CO2 atmosphere for 15 hours. Mold grown on blood agar plate was inoculated on a Sabouraud dextrose agar and incubated at 30°C. A uffy, white, cottony growth was observed on Sabouraud dextrose agar at 48 hours (Fig. 1B). The color turned greyish brown with time, though the part visible from the bottom of the plate remained pale white. Staining with lactophenol cotton blue showed irregular aseptate hyphae branched at obtuse angles without rhizoids. Globose sporangia were filled with round spores and located at the end of long sporangiophores (Fig. 1C). The macroscopic and microscopic morphologies were consistent with
For accurate identification of the species, the pure culture isolated on Sabouraud dextrose agar was analyzed by using polymerase chain reaction and direct sequencing analysis targeting the internal transcribed spacer (ITS) and the D1/D2 regions. DNA extraction was performed on a MagNA Pure 96 system (Roche Diagnostics, Mannheim, Germany) according to the procedure recommended by the manufacturer. BigDye Terminator Cycle Sequencing Ready Reaction Kit (Applied Biosystems, Foster City, CA, USA) and ABI Prism 3730 Genetic Analyzer (Applied Biosystems) were used for sequencing of the extracted and amplified DNA products. According to the Clinical and Laboratory Standards Institute guidelines (MM18-A) , primer sets of ITS-1/ITS-4 and ITS-5/ITS-4 were used for amplifying ITS, and a primer set of NL-1/NL-4 was used for amplifying the D1/D2 region of ribosomal DNA. For identification, the BLAST search was performed in the GenBank database available at the NCBI website (http://www.ncbi.nlm.nih.gov). Targeted DNA sequencing confirmed the isolate as
Mucormycosis is a fatal infection caused by fungi of the order Mucorales. The most common genera that cause mucormycosis are
Unlike other fungal infections, mucormycosis shows rapid progression and angioinvasion, and causes tissue necrosis and dissemination. Mucorales cause invasive infection at various levels including cutaneous, rhinocerebral, pulmonary, GI, and disseminated. In rare cases, mucormycosis can also cause peritonitis, endocarditis, and osteomyelitis [2, 3].
Several cases of mucormycosis peritonitis were reported, and most of them were related with peritoneal dialysis related mucormycosis [10-14]. Only a few cases of peritonitis were preceded by GI mucormycosis, three such reported cases are listed in Table 1 [5-7]: two were related to perforation of sigmoid colon or small intestine caused by
GI mucormycosis is uncommon, accounting for 0% to 9% of mucormycosis depending on the host conditions, notably 3% in patients with malignancy . GI mucormycosis can occur after ingestion of foods contaminated with mold, and can proceed to perforation, peritonitis, and sepsis caused by fungal invasion to bowel walls and blood vessels . In addition, an outbreak of GI mucormycosis has also been reported, which occurred after ingesting yogurts contaminated with mold that were later identified as
So far, there are no available serological biomarkers for diagnosing mucormycosis, such as (1,3)-β-D-glucan and galactomannan, which are used for diagnosing other invasive fungal infection . The traditional culture method is still important, however, it takes time to isolate and identify a fungus as compared to the rapid progression of Mucorales . Amphotericin B has been recommended as first-line treatment for mucormycosis [16, 17]. Posa-conazole and voriconazole are more effective against some Mucorales . Various Mucorales and even the individual species show variable response to anti-fungal agents . Therefore, mucormycosis is difficult to diagnose early and to be treated successfully, which results into higher mortality that exceeds 50% despite anti-fungal treatment . Disseminated mucormycosis especially shows fatal outcome . In this case, the patient died four days after receiving amphotericin B. He had several risk factors that were prone to fungal infection and its fast dissemination, including hematology malignancy, neutropenic status, and use of antibiotics. Five days after identifying
Yang et al.  have reported the identification of Mucorales using molecular methods. But there have been some discrepancies cases between microscopic morphological and molecular identification. Some species of Mucorales cannot be easily identified solely based on the morphology. Therefore, molecular methods are considered to be more reliable and need to be performed for accurate identification of Mucorales . This case showed concordance between morphological and molecular identification.
In conclusion, we report a rare case of peritonitis and disseminated mucormycosis probably preceded by GI mucormycosis caused by
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