The carpal tunnel syndrome caused by Arthrinium phaeospermum infection: first case report and literature review

The carpal tunnel syndrome caused by Arthrinium phaeospermum infection: first case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report The carpal tunnel syndrome caused by Arthrinium phaeospermum infection: first case report and literature review Miaozhong Li, Yuning Li, Li Xueyuan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4139434/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Nov, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted 4 You are reading this latest preprint version Abstract Background: The carpal tunnel syndrome(CTS) caused by atypical infectious is a therapeutic and diagnostic challenge. Because non-specific clinical presentation often result in misdiagnosis and incorrect therapy, failing to elicit an accurate exposure. Case presentation: This article reports a case of deep infection leading to CTS manifestations. A male patient was admitted for numbness and pain of the left hand. Left carpal tunnel release, median nerve decompression, synovectomy of the carpal tunnel were performed. Inflamed synovium and effusion were submitted for bacterial culture and metagenomic next-generation sequencing(mNGS). The causing pathogen was identified as Arthrinium phaeospermum and the patient recovered after surgical debridement and 10 months of antimicrobial therapy. Conclusions: Diagnosis of fungi infection of the hand is challenging as the presentation mimics other conditions without much histological findings. NGS is proposed of great importance adjunctive diagnostic approach for identifying atypical infectious quickly. Arthrinium phaeospermum Next-generation sequencing Carpal tunnel syndrome Infectious Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Carpal tunnel syndrome(CTS) is the most common peripheral nerve compression disorder, caused by idiopathic carpal transverse ligament thickening, synovial hypertrophy, etc. 1 In addition, CTS caused by secondary infection of atypical bacteria such as mycobacterium tuberculosis, non-tuberculous mycobacteria and fungi, is a therapeutic and diagnostic challenge. Because the infection is rare and often fails to elicit a history of traumatic exposure. 2 Arthrinium phaeospermum is a globally distributed conditional pathogenic fungus with a wide host range, mainly in plants, and can also lead to skin lesions in humans and animals. 3 In 1990, Rai 4 reported the first case of human skin infection with this pathogen. Subsequently, four cases of human infection with A. phaeospermum were clinically reported, all of them were superficial skin infections occurring in mainland China. 5 – 8 This article reports a case of deep infection leading to CTS manifestations, the causing pathogen was identified as A. phaeospermum by Metagenomic next-generation sequencing(mNGS) and culture, and the patient recovered after surgical debridement and 10 months of antimicrobial therapy. The following report discussed the diagnosis and treatment process for this rare case of A. phaeospermum infection presented with acute CTS. Case Presentation A 64-year-old peasent, lives in coastal area. He was hospitalized for "numbness and pain in the 1–4 fingers of the left hand for 3 weeks". He had no obvious inducing factors, the pain radiated from finger to the palm, worsen at night, affecting his sleep. Antibacterial therapy was given in the local hospital without obvious effect. Medical history was unremarkable except a habit of alcohol consumption. Physical examination showed mild swelling of the left wrist, elevated skin temperature, mild atrophy of the thenar major muscles of the left palm, tenderness over the wrist and numbness over 1–4 fingers, along with positive Tinel's sign and Phalen's test. The finger flexion movement was restricted(figue 1). Pain score VAS: 6 points. Investigations The radiolographic imaging of the chest, hand and wrist were non-specific, as were the laboratory tests. EMG demonstrated slowed median nerve conduction velocity at the left wrist, abductor pollicis brevis motor unit potential amplitude 2.1mV, latency 4.5ms, which indicated CTS. Treatment The patient underwent left carpal tunnel release, and a synovectomy of carpal tunnel and forearm. About 1 ml of yellow exudate was observed in the carpal tunnel. The inflamed proliferative synovium was adherent to the flexor tendons. The median nerve was compressed and flattened, with congestive changes of the epineurium. The exudate and inflammatory synovial tissue were sent for routine bacterial culture, mycobacterial culture, pathology and mNGS, respectively. Then we performed thorough debridement of the inflamed synovium. Cefoperazone Sodium and Sulbactam Sodium 1.5g iv q12h was performed postoperatively. On the second day, mNGS reported A. phaeospermum infection. Fungal growth was reported in the culture, consistent with the characteristics of A. phaeospermum later.Histopathology showed chronic synovitis with non-caseating granulomas, inflammatory cell infiltrate with proliferating capillaries (Fig. 2).but there was no fungus was observed by special staining. The previous antibiotic was discontinued and Fluconazole 200mg twice daily was prescripted. At the 6-week postoperative follow-up, numbness and pain in the patient's left hand were significantly relieved. and the range of motion of fingers showed improvement compared to preoperative status. There was mild swelling of the wrist, and limited ability to make a fist with the fingers(figue 3). Two months after surgery, patient changed his medicine to Terbinafine in a local hospital. There was no significant relief of wrist redness and swelling and patient complained of gastrointestinal symptoms one month later. Thus Terbinafine was replaced with oral Fluconazole again (with a change in manufacturer). There was only occult swelling in the wrist and no signs of recurrence were observed at 6-months follow up. At the 10 month, the patient restored almost full range of motion of the hand activity without any symptom(figue 4). Discussion And Conclusions 1.Biological characteristics of A. phaeospermum A. phaeospermum belongs to the Ascomycota and can cause diseases in various plants. It is widely present in the environment. Khan et al. first confirmed it as a phytopathogenic fungus in 1980. 9 In 2009, Zhu et al. first proved that it could lead to withering disease of hybrid bamboo. 10 It is also one of the conditional pathogenic fungi causing cutaneous fungal diseases in humans and animals. Zhao Yaoming’s research confirmed that A. phaeospermum could infect rabbits, cavy and mice, damage hair follicles and sebaceous glands, and produce liposoluble toxins leading to skin damage. 11 In addition, Bloor 12 et al. found that A. phaeospermum could produce aromatic acids when infecting the human body, and Rai et al. 4 first isolated A. phaeospermum from the skin lesions of patients. In immunocompromised populations, fungi can occasionally cause deep hand tissue infections, which have been reported in individual cases, but not the A. phaeospermum . And this patient had no other evidence of immunodeficiency except a long history of alcohol drinking. In recent years, many studies have confirmed that it can produce various secondary metabolites and enzymatic proteins involved in pathogenesis. Li 13 et al. discovered that A. phaeospermum could produce a protein toxin that increases mitochondrial lipid peroxidation, inhibits respiration, and plays an important role in its pathogenicity. But the specific virulence-related genes and mechanisms of action need further in-depth study. 2. Characteristics of CTS caused by infection The carpal tunnel is a narrow anatomical canal. In addition to the median nerve, there are also nine flexor tendons inside the carpal tunnel cavity. Any inducing factor that alters the structures in the carpal tunnel can compress the median nerve, leading to characteristic symptoms with pain or paresthesias in radial 3 and a half fingers and weakness or muscle atrophy of the thenar major. Local inflammation is also involved in the occurrence of CTS. Acute or chronic local inflammation caused by infection may stimulate proliferation of the carpal tunnel contents, compressing the nerves indirectly. Infectious CTS is relatively rare, with most cases caused by Staphylococcus, which can lead to purulent tenosynovitis and cause CTS secondarily. Mascola JR 2 reviewed documented infectious causes of CTS, such as common bacteria, mycobacterium tuberculosis, atypical mycobacteria, and fungi. For those atypical infections, non-specific clinical presentation may lead to misdiagnosis and delayed therapy, even incorrect treatment 14 . Compared with mycobacterial infections, fungal infections such as Coccidioides immitis, Sporothrix schenckii. have a higher tendency of recurrence. Most patients begin to suspect infection when they see a large amount of inflamed proliferative synovium during surgery. Moreover, special cultures take 4-6 weeks or longer, causing more difficulties for treatment. After diagnosis, targeted antimicrobial treatment needs to last for months. This patient has been taking oral fluconazole for nearly one year and eventually recovered. Currently there is no sign of recurrence. We performed mNGS of the cultured strain, and the results showed that the fungal genome contains abundant gene clusters encoding carbohydrate active enzymes, effector proteins and secondary metabolism-related genes, some of which are related to pathogenicity. It indicates that A. phaeospermum may have been involved in the infection process of the lesion tissue through its metabolic products and effector proteins. Unlike pyogenic infections, fungal and mycobacterial infections are more likely to be overlooked in clinics. 15-16 Clinical reports of A. phaeospermum infection are rare. It is an opportunistic pathogen that tends to invade immunocompromised populations. This patient had nothing special but living in where suitable for bamboo and other agriculture. Given that A. phaeospermum can lead to withering disease of hybrid bamboo 8 , it reminds us that we should increase awareness of this pathogen and strengthen fungal culture and identification of surgical samples to avoid misdiagnosis. Regarding treatment, thorough removal of inflamed synovium combined with postoperative antifungal treatment is currently the consensus treatment plan. When selecting antifungal drugs, hand surgeons should consult opinions from infectious disease specialists to achieve adequate dosage and duration as much as possible. 14 3. Application of mNGS in the diagnosis of infectious diseases Traditional pathogen culture and morphological identification require a certain amount of time, and some pathogens are difficult to culture, causing some limitations. In recent years, the development of mNGS technology has brought new opportunities for the diagnosis of infectious diseases, and has been widely used in the detection of bacterial and viral infections. 17 Genomic sequencing can detect all pathogen information in body fluid and tissue samples by non-specific amplification and direct sequencing of all genomic DNA, enabling detection of unknown pathogens. This provides strong support for the diagnosis of infectious diseases. In this case, mNGS (Figue 5)quickly discovered the presence of A. phaeospermum in the patient's carpal tunnel synovial sample, providing important diagnostic evidence for the clinic. A. phaeospermum can cause multiple system infections in plants and animals, and its pathogenic mechanism is related to the secreted toxins and enzymes. This case suggests that A. phaeospermum can also stimulate synovial hyperplasia in the carpal tunnel, leading to the rare fungal CTS. Its clinical manifestations are similar to mycobacterial infections, and are very easily overlooked clinically. For abnormal inflammatory hyperplastic synovial changes found during surgery, timely bacteriological testing should be performed. The current mNGS technology technique allows rapid detection of pathogens, avoiding misdiagnosis and mistreatment. Abbreviations CTS carpal tunnel syndrome mNGS metagenomic next-generation sequencing Declarations Ethics approval and consent to participate The study was conducted in accordance with the local legislation and institutional requirements which was approved by the Ethics Committee of Ningbo No. 6 Hospital. The patient provided his written informed consent to participate in this study. Consent for publication: Written informed consent was obtained from the patient for publication of this case and any accompanying images report. A copy of the written consent is available for review by the Editor of this journal. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that the research was conducted in the absence of any commercial or fifinancial relationships that could be construed as a potential conflflict of interest. Funding: This study was supported by grants form the Ningbo Top Medical and Health Research Program (No.2022020506), Ningbo Key Research and Development Program (No. 2022Z146). Authors' contributions: Conception and design of the study, Operation: Xueyuan Li and Miaozhong Li. Acquisition of data: Yuning Li. Analysis and interpretation of the data: Miaozhong Li. Writing of the manuscript: Miaozhong Li. Critical revision of the manuscript for intellectual content: Xueyuan Li. All authors contributed to the article and approved the submitted version. Acknowledgements: The authors thank the workmates for their efforts in the clinical management of this patient. References Pai GM, Bhat AK, Acharya AM, Reddy SP, et al. Unusual presentation of carpal tunnel syndrome due to Mycobacterium marinum infection of hand. BMJ Case Rep. 2022;15(12):e251692. https://doi.org/10.1136/bcr-2022-251692 . Mascola JR, Rickman LS. Infectious causes of carpal tunnel syndrome: case report and review. Rev Infect Dis. 1991;13(5):911–7. https://doi.org/10.1093/clinids/13.5.911 . Li SJ, Tang YW, Fang XM, Qiao TM, Han S, Zhu TH. Whole-genome sequence of Arthrinium phaeospermum, a globally distributed pathogenic fungus. Genomics. 2020;112(1):919–29. https://doi.org/10.1016/j.ygeno.2019.06.007 . Rai MK. Mycosis in man due to Arthrinium phaeospermum var. indicum. First case report. Mycoses. 1989;32(9):472–5. https://doi.org/10.1111/j.1439-0507.1989.tb02285.x . Zhao YM, Deng CR, Chen X, Liu ML, Chen SP, Wang Z, Sun HL. Arthrinium phaeospermum causing dermatomycosis, a new record of China. Acta Mycologica Sinica. 1990;9(3):232–5. https://doi.org/10.13346/j.mycosystema.1990.02.011 . Lu GX, Shen YN, Chen W, Hu SQ, Li HZ, Liu WD. Cutaneous Mycosis Caused by Arthrinium phaeospermum: A Case Report. Chin J Dermatol. 2005;38(4):232–4. https://doi.org/10.3760/j.issn:0412-4030.2005.04.012 . Hu SQ, Zhan P, Lu GX, Mei H, Zeng XS, Liu WD. A case of cutaneous Arthrinium phaeospermum infection after lower limb amputation. Chin J Dermatol. 2016;49(10):726–8. https://doi.org/10.3760/cma.j.issn.0412-4030.2016.10.012 . Chen XW, Zhu HM, Wen H. A case of cutaneous mycosis caused by Arthrinium phaeospermum. Chin J Mycol. 2016;11(6):357–60. ,365. Khan KR, Sullia SB. Arthrinium phaeospermum var. indicum var. nov. a new market pathogen of cowpea, garden pea and French bean. Acta Bot Ind. 1980;8:103–4. https://doi.org/10.1007/BF00121015 . Zhao YM, Wen ST, Liu ML, Jiang YB, Zhang SS. Mycosis caused by Arthrinium phaeospermum, its animal toxicity and pathological analysis. Mycosystema. 1997;5:112–6. https://doi.org/10.1007/s00376-997-0061-6 . Bloor S. Arthrinic acid, a novel antifungal polyhydroxyacid from Arthrinium phaeospermum. J Antibiot (Tokyo). 2008;61(8):515–7. https://doi.org/10.1038/ja.2008.69 . Li SJ, Liang M, Zhu TH. Selection of an antagonistic bacterium against Arthrinium phaeospermumand its antibacterial protein analysis. J Nanjing Forestry Univ. 2013;13(37):27–32. https://doi.org/10.3969/j.issn.1000-2006.2013.06.006 . King V, Crouser N, Speeckaert A, Bhatt R. Infection Management for the Hand Surgeon. Hand Clin. 2023;39(3):465–73. https://doi.org/10.1016/j.hcl.2023.04.003 . Hassanpour SE, Gousheh J. Mycobacterium tuberculosis-induced carpal tunnel syndrome: management and follow-up evaluation. J Hand Surg Am. 2006;31(4):575–9. .https://doi.org/10.1016/j.jhsa.2005.01.018 . Fox MP, Jacoby SM. Fungal Infections of the Hand. Hand Clin. 2020;36(3):355–60. https://doi.org/10.1016/j.hcl.2020.03.009 . Zhang KY, Yu C, Li YX, Wang Y. Next-generation sequencing technology for detecting pulmonary fungal infection in bronchoalveolar lavage fluid of a patient with dermatomyositis: a case report and literature review. BMC Infect Dis. 2020;20(1):608. 10.1186/s12879-020-05341-8 . Fang X, Yan P, Luo F, Han S, Lin T, Li S, et al. Functional Identification of Arthrinium phaeospermum Effectors Related to Bambusa pervariabilis × Dendrocalamopsis grandis Shoot Blight. Biomolecules. 2022;12(9):1264. https://doi.org/10.3390/biom12091264 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Nov, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 05 Apr, 2024 Submission checks completed at journal 01 Apr, 2024 Editor assigned by journal 01 Apr, 2024 First submitted to journal 20 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4139434","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":286379632,"identity":"11e65b04-4d63-4526-b542-b7caff510e48","order_by":0,"name":"Miaozhong Li","email":"","orcid":"","institution":"Ningbo No.6 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Miaozhong","middleName":"","lastName":"Li","suffix":""},{"id":286379633,"identity":"2c3a3170-3b81-4477-a91e-1d45327c31b6","order_by":1,"name":"Yuning Li","email":"","orcid":"","institution":"Ningbo No.6 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuning","middleName":"","lastName":"Li","suffix":""},{"id":286379634,"identity":"2be59633-8fd8-4e04-82c0-f4f92f9c21a8","order_by":2,"name":"Li Xueyuan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYBACPmYYi72x4UBChYScPCEtbHAtPIcPPvhwxsLYsIGQFjhLIi3ZcGZbRSLDAUJa2HnMJD62HZY3Z8gxk+adJ5HA2MD88NENvA5jS5Oc2XbYcGfDGaCWbRJ57AxsxsY5eLUwH5PmbTvMuOFgD1hLMWMDD5s0fi2MbdJ/2w7bbzjMA9QyRyKx4QBBLUBbGNsOJ244xgb0fgNRWtiSLXvOpSdvOMMMDORjEsaGzQT8ws9/xvDGjzJr2w33HwKjsqZOTp69+eFjfFrAgJENmceMSxkK+EOUqlEwCkbBKBipAAAYE0ih6TIZRwAAAABJRU5ErkJggg==","orcid":"","institution":"Ningbo No.6 Hospital","correspondingAuthor":true,"prefix":"","firstName":"Li","middleName":"","lastName":"Xueyuan","suffix":""}],"badges":[],"createdAt":"2024-03-20 20:44:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4139434/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4139434/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-024-10232-3","type":"published","date":"2024-11-21T15:57:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54178293,"identity":"82248386-9db0-4266-9d77-18dd599357d7","added_by":"auto","created_at":"2024-04-05 16:13:31","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29617,"visible":true,"origin":"","legend":"\u003cp\u003eBefore surgery, the finger flexion movement was restricted.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4139434/v1/7c9e8b6f73b61f2cef1a7d3a.jpg"},{"id":54178292,"identity":"af9a4e12-6fd4-4143-b175-dfdca7ab7b63","added_by":"auto","created_at":"2024-04-05 16:13:31","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55206,"visible":true,"origin":"","legend":"\u003cp\u003eThere is prominent synovial hyperplasia characterized by the development of nodular structures, with a notable infiltrate comprising lymphocytes, plasma cells, and foam cells evident upon microscopic examination. The presence of these cellular constituents suggests an active inflammatory process within the synovium.\u003c/p\u003e","description":"","filename":"Picture1Copy.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4139434/v1/313c8db9ed2fd4333c877026.jpg"},{"id":54178295,"identity":"1649d494-6abf-4760-833b-5d40f29a8f95","added_by":"auto","created_at":"2024-04-05 16:13:31","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":43943,"visible":true,"origin":"","legend":"\u003cp\u003eThere was mild swelling of the wrist, and limited ability to make a fist with the fingers at the 6 weeks follow-up.\u003c/p\u003e","description":"","filename":"Picture1Copy2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4139434/v1/75738a55279010f99bf05589.jpg"},{"id":54178294,"identity":"7b6dd5e3-3e79-4b6b-9439-7ef75f3ac07a","added_by":"auto","created_at":"2024-04-05 16:13:31","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":33984,"visible":true,"origin":"","legend":"\u003cp\u003eAt the 10 month, the patient made almost full recovery of the motion rage without any symptom.\u003c/p\u003e","description":"","filename":"Picture1Copy3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4139434/v1/dc9ac5ac69ae2ef1d1f9b133.jpg"},{"id":54178297,"identity":"1e0051a9-dca1-4881-a386-1106bc8f7665","added_by":"auto","created_at":"2024-04-05 16:13:31","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":42353,"visible":true,"origin":"","legend":"\u003cp\u003emNGS result of the patient’s synovium tissue. Mapping of Arthrinium phaeospermum \u0026nbsp;reads to the genome community in synovium tissue sample.\u003c/p\u003e","description":"","filename":"Picture1Copy4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4139434/v1/3804f7ee5e71f34ca219f1c9.jpg"},{"id":69835771,"identity":"3fbd016b-47c6-4a1f-835e-368403864445","added_by":"auto","created_at":"2024-11-25 16:14:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":435624,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4139434/v1/58fda53f-8529-4be7-8fdd-9d55bf08eef5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The carpal tunnel syndrome caused by Arthrinium phaeospermum infection: first case report and literature review","fulltext":[{"header":"Background","content":"\u003cp\u003eCarpal tunnel syndrome(CTS) is the most common peripheral nerve compression disorder, caused by idiopathic carpal transverse ligament thickening, synovial hypertrophy, etc.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e In addition, CTS caused by secondary infection of atypical bacteria such as mycobacterium tuberculosis, non-tuberculous mycobacteria and fungi, is a therapeutic and diagnostic challenge. Because the infection is rare and often fails to elicit a history of traumatic exposure.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cem\u003eArthrinium phaeospermum\u003c/em\u003e is a globally distributed conditional pathogenic fungus with a wide host range, mainly in plants, and can also lead to skin lesions in humans and animals.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e In 1990, Rai\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e reported the first case of human skin infection with this pathogen. Subsequently, four cases of human infection with \u003cem\u003eA. phaeospermum\u003c/em\u003e were clinically reported, all of them were superficial skin infections occurring in mainland China.\u003csup\u003e\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e This article reports a case of deep infection leading to CTS manifestations, the causing pathogen was identified as \u003cem\u003eA. phaeospermum\u003c/em\u003e by Metagenomic next-generation sequencing(mNGS) and culture, and the patient recovered after surgical debridement and 10 months of antimicrobial therapy. The following report discussed the diagnosis and treatment process for this rare case of \u003cem\u003eA. phaeospermum\u003c/em\u003e infection presented with acute CTS.\u003c/p\u003e "},{"header":"Case Presentation","content":"\u003cp\u003eA 64-year-old peasent, lives in coastal area. He was hospitalized for \"numbness and pain in the 1\u0026ndash;4 fingers of the left hand for 3 weeks\". He had no obvious inducing factors, the pain radiated from finger to the palm, worsen at night, affecting his sleep. Antibacterial therapy was given in the local hospital without obvious effect. Medical history was unremarkable except a habit of alcohol consumption.\u003c/p\u003e \u003cp\u003ePhysical examination showed mild swelling of the left wrist, elevated skin temperature, mild atrophy of the thenar major muscles of the left palm, tenderness over the wrist and numbness over 1\u0026ndash;4 fingers, along with positive Tinel's sign and Phalen's test. The finger flexion movement was restricted(figue 1). Pain score VAS: 6 points.\u003c/p\u003e \u003cp\u003eInvestigations\u003c/p\u003e \u003cp\u003eThe radiolographic imaging of the chest, hand and wrist were non-specific, as were the laboratory tests. EMG demonstrated slowed median nerve conduction velocity at the left wrist, abductor pollicis brevis motor unit potential amplitude 2.1mV, latency 4.5ms, which indicated CTS.\u003c/p\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003cp\u003eThe patient underwent left carpal tunnel release, and a synovectomy of carpal tunnel and forearm. About 1 ml of yellow exudate was observed in the carpal tunnel. The inflamed proliferative synovium was adherent to the flexor tendons. The median nerve was compressed and flattened, with congestive changes of the epineurium. The exudate and inflammatory synovial tissue were sent for routine bacterial culture, mycobacterial culture, pathology and mNGS, respectively. Then we performed thorough debridement of the inflamed synovium. Cefoperazone Sodium and Sulbactam Sodium 1.5g iv q12h was performed postoperatively.\u003c/p\u003e \u003cp\u003eOn the second day, mNGS reported \u003cem\u003eA. phaeospermum\u003c/em\u003e infection. Fungal growth was reported in the culture, consistent with the characteristics of \u003cem\u003eA. phaeospermum\u003c/em\u003e later.Histopathology showed chronic synovitis with non-caseating granulomas, inflammatory cell infiltrate with proliferating capillaries (Fig.\u0026nbsp;2).but there was no fungus was observed by special staining.\u003c/p\u003e \u003cp\u003eThe previous antibiotic was discontinued and Fluconazole 200mg twice daily was prescripted. At the 6-week postoperative follow-up, numbness and pain in the patient's left hand were significantly relieved. and the range of motion of fingers showed improvement compared to preoperative status. There was mild swelling of the wrist, and limited ability to make a fist with the fingers(figue 3). Two months after surgery, patient changed his medicine to Terbinafine in a local hospital. There was no significant relief of wrist redness and swelling and patient complained of gastrointestinal symptoms one month later. Thus Terbinafine was replaced with oral Fluconazole again (with a change in manufacturer). There was only occult swelling in the wrist and no signs of recurrence were observed at 6-months follow up. At the 10 month, the patient restored almost full range of motion of the hand activity without any symptom(figue 4).\u003c/p\u003e"},{"header":"Discussion And Conclusions","content":"\u003cp\u003e1.Biological characteristics of \u003cem\u003eA. phaeospermum\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eA. phaeospermum\u003c/em\u003e belongs to the Ascomycota and can cause diseases in various plants. It is widely present in the environment. Khan et al. first confirmed it as a phytopathogenic fungus in 1980.\u003csup\u003e9\u003c/sup\u003e In 2009, Zhu et al. first proved that it could lead to withering disease of hybrid bamboo.\u003csup\u003e10\u003c/sup\u003e It is also one of the conditional pathogenic fungi causing cutaneous fungal diseases in humans and animals. Zhao Yaoming\u0026rsquo;s research confirmed that \u003cem\u003eA. phaeospermum\u003c/em\u003e could infect rabbits, cavy and mice, damage hair follicles and sebaceous glands, and produce liposoluble toxins leading to skin damage.\u003csup\u003e11\u003c/sup\u003e In addition, Bloor\u003csup\u003e12\u003c/sup\u003e et al. found that \u003cem\u003eA. phaeospermum\u003c/em\u003e could produce aromatic acids when infecting the human body, and Rai et al.\u003csup\u003e4\u003c/sup\u003e first isolated \u003cem\u003eA. phaeospermum\u003c/em\u003e from the skin lesions of patients. In immunocompromised populations, fungi can occasionally cause deep hand tissue infections, which have been reported in individual cases, but not the \u003cem\u003eA. phaeospermum\u003c/em\u003e. And this patient had no other evidence of immunodeficiency except a long history of alcohol drinking.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn recent years, many studies have confirmed that it can produce various secondary metabolites and enzymatic proteins involved in pathogenesis. Li\u003csup\u003e13\u003c/sup\u003e et al. discovered that \u003cem\u003eA. phaeospermum\u003c/em\u003e could produce a protein toxin that increases mitochondrial lipid peroxidation, inhibits respiration, and plays an important role in its pathogenicity. But the specific virulence-related genes and mechanisms of action need further in-depth study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. Characteristics of CTS caused by infection\u003c/p\u003e\n\u003cp\u003eThe carpal tunnel is a narrow anatomical canal. In addition to the median nerve, there are also nine flexor tendons inside the carpal tunnel cavity. Any inducing factor that alters the structures in the carpal tunnel can compress the median nerve, leading to characteristic symptoms with pain or paresthesias in radial\u003csup\u003e3\u003c/sup\u003e and a half fingers and weakness or muscle atrophy of the thenar major.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLocal inflammation is also involved in the occurrence of CTS. Acute or chronic local inflammation caused by infection may stimulate proliferation of the carpal tunnel contents, compressing the nerves indirectly. Infectious CTS is relatively rare, with most cases caused by Staphylococcus, which can lead to purulent tenosynovitis and cause CTS secondarily. Mascola JR\u003csup\u003e2\u003c/sup\u003e reviewed documented infectious causes of CTS, such as common bacteria, mycobacterium tuberculosis, atypical mycobacteria, and fungi. For those atypical infections, non-specific clinical presentation may lead to misdiagnosis and delayed therapy, even incorrect treatment\u003csup\u003e14\u003c/sup\u003e. Compared with mycobacterial infections, fungal infections such as Coccidioides immitis, Sporothrix schenckii. have a higher tendency of recurrence. Most patients begin to suspect infection when they see a large amount of inflamed proliferative synovium during surgery. Moreover, special cultures take 4-6 weeks or longer, causing more difficulties for treatment. After diagnosis, targeted antimicrobial treatment needs to last for months.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis patient has been taking oral fluconazole for nearly one year and eventually recovered. Currently there is no sign of recurrence. We performed mNGS of the cultured strain, and the results showed that the fungal genome contains abundant gene clusters encoding carbohydrate active enzymes, effector proteins and secondary metabolism-related genes, some of which are related to pathogenicity. It indicates that \u003cem\u003eA. phaeospermum\u003c/em\u003e may have been involved in the infection process of the lesion tissue through its metabolic products and effector proteins.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnlike pyogenic infections, fungal and mycobacterial infections are more likely to be overlooked in clinics.\u003csup\u003e15-16\u003c/sup\u003e Clinical reports of \u003cem\u003eA. phaeospermum\u003c/em\u003e infection are rare. It is an opportunistic pathogen that tends to invade immunocompromised populations. This patient had nothing special but living in where suitable for bamboo and other agriculture. Given that \u003cem\u003eA. phaeospermum\u003c/em\u003e can lead to withering disease of hybrid bamboo\u003csup\u003e8\u003c/sup\u003e, it reminds us that we should increase awareness of this pathogen and strengthen fungal culture and identification of surgical samples to avoid misdiagnosis. Regarding treatment, thorough removal of inflamed synovium combined with postoperative antifungal treatment is currently the consensus treatment plan. When selecting antifungal drugs, hand surgeons should consult opinions from infectious disease specialists to achieve adequate dosage and duration as much as possible.\u003csup\u003e14\u003c/sup\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3. Application of mNGS in the diagnosis of infectious diseases \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTraditional pathogen culture and morphological identification require a certain amount of time, and some pathogens are difficult to culture, causing some limitations. In recent years, the development of mNGS technology has brought new opportunities for the diagnosis of infectious diseases, and has been widely used in the detection of bacterial and viral infections.\u003csup\u003e17\u003c/sup\u003e Genomic sequencing can detect all pathogen information in body fluid and tissue samples by non-specific amplification and direct sequencing of all genomic DNA, enabling detection of unknown pathogens. This provides strong support for the diagnosis of infectious diseases. In this case, mNGS (Figue 5)quickly discovered the presence of \u003cem\u003eA. phaeospermum\u003c/em\u003e in the patient\u0026apos;s carpal tunnel synovial sample, providing important diagnostic evidence for the clinic.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eA. phaeospermum\u003c/em\u003e can cause multiple system infections in plants and animals, and its pathogenic mechanism is related to the secreted toxins and enzymes. This case suggests that \u003cem\u003eA. phaeospermum\u003c/em\u003e can also stimulate synovial hyperplasia in the carpal tunnel, leading to the rare fungal CTS. Its clinical manifestations are similar to mycobacterial infections, and are very easily overlooked clinically. For abnormal inflammatory hyperplastic synovial changes found during surgery, timely bacteriological testing should be performed. The current mNGS technology technique allows rapid detection of pathogens, avoiding misdiagnosis and mistreatment.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCTS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecarpal tunnel syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emNGS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emetagenomic next-generation sequencing\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the local legislation and institutional requirements which was approved by the Ethics Committee of Ningbo No. 6 Hospital. The patient provided his written informed consent to participate in this study.\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case and any accompanying images report. A copy of the written consent is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or fifinancial relationships that could be construed as a potential conflflict of interest.\u003c/p\u003e\n\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants form the Ningbo Top Medical and Health Research Program (No.2022020506), Ningbo Key Research and Development Program (No. 2022Z146).\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions:\u003c/p\u003e\n\u003cp\u003eConception and design of the study, Operation: Xueyuan Li and Miaozhong Li. Acquisition of data: Yuning Li. Analysis and interpretation of the data: Miaozhong Li. Writing of the manuscript: Miaozhong Li. Critical revision of the manuscript for intellectual content: Xueyuan Li. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003eAcknowledgements:\u003c/p\u003e\n\u003cp\u003eThe authors thank the workmates for their efforts in the clinical management of this patient.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePai GM, Bhat AK, Acharya AM, Reddy SP, et al. Unusual presentation of carpal tunnel syndrome due to Mycobacterium marinum infection of hand. 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Functional Identification of Arthrinium phaeospermum Effectors Related to Bambusa pervariabilis \u0026times; Dendrocalamopsis grandis Shoot Blight. Biomolecules. 2022;12(9):1264. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/biom12091264\u003c/span\u003e\u003cspan address=\"10.3390/biom12091264\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Arthrinium phaeospermum, Next-generation sequencing, Carpal tunnel syndrome, Infectious","lastPublishedDoi":"10.21203/rs.3.rs-4139434/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4139434/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: The carpal tunnel syndrome(CTS) caused by atypical infectious is a therapeutic and diagnostic challenge. Because non-specific clinical presentation often result in misdiagnosis and incorrect therapy, failing to elicit an accurate exposure.\u003c/p\u003e\n\u003cp\u003eCase presentation: This article reports a case of deep infection leading to CTS manifestations. A male patient was admitted for numbness and pain of the left hand. Left carpal tunnel release, median nerve decompression, synovectomy of the carpal tunnel were performed. Inflamed synovium and effusion were submitted for bacterial culture and metagenomic next-generation sequencing(mNGS). The causing pathogen was identified as \u003cem\u003eArthrinium phaeospermum\u003c/em\u003e and the patient recovered after surgical debridement and 10 months of antimicrobial therapy.\u003c/p\u003e\n\u003cp\u003eConclusions: Diagnosis of fungi infection of the hand is challenging as the presentation mimics other conditions without much histological findings. NGS is proposed of great importance adjunctive diagnostic approach for identifying atypical infectious quickly.\u003c/p\u003e","manuscriptTitle":"The carpal tunnel syndrome caused by Arthrinium phaeospermum infection: first case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-05 16:13:26","doi":"10.21203/rs.3.rs-4139434/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-05T12:54:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-02T02:43:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-02T02:43:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-03-20T20:36:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"05cd0135-ef03-4513-a71d-60aef948927c","owner":[],"postedDate":"April 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-25T16:10:34+00:00","versionOfRecord":{"articleIdentity":"rs-4139434","link":"https://doi.org/10.1186/s12879-024-10232-3","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2024-11-21 15:57:45","publishedOnDateReadable":"November 21st, 2024"},"versionCreatedAt":"2024-04-05 16:13:26","video":"","vorDoi":"10.1186/s12879-024-10232-3","vorDoiUrl":"https://doi.org/10.1186/s12879-024-10232-3","workflowStages":[]},"version":"v1","identity":"rs-4139434","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4139434","identity":"rs-4139434","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}