Voriconazole-induced periostitis in a child with finger pain and nodules: case report and literature review

Voriconazole-induced periostitis in a child with finger pain and nodules: 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 Voriconazole-induced periostitis in a child with finger pain and nodules: case report and literature review Hiroshi Urakawa, Kunihiro Ikuta, Tomohisa Sakai, Hiroshi Koike, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4518669/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Aug, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted 4 You are reading this latest preprint version Abstract Background Voriconazole-induced periostitis is predominantly reported in adults, with pediatric cases being exceedingly rare. Case presentation: This report describes an 8-year-old boy with voriconazole-induced periostitis presenting with finger pain and nodules, initially suspected to be bone tumors. The patient had been on voriconazole for three years to treat Aspergillus pneumonia and had been hospitalized for six months due to chronic graft-versus-host disease following hematopoietic stem cell transplantation and total body irradiation for severe congenital neutropenia. The patient presented with a five-month history of pain and a one-month history of a mass in the middle finger of his right hand. Radiographs revealed bone formation outside the cortical bone in the proximal phalanx of the right middle finger and the distal ulna. Differential diagnoses included benign bone-forming tumors, such as osteochondroma post-total body irradiation, and bizarre parosteal osteochondromatous proliferation. The diagnosis of voriconazole-induced periostitis was confirmed as multiple bone lesions and new bone formation became apparent during the disease course. Conclusions Voriconazole-induced periostitis should be considered, even in pediatric patients, when multiple nodular periosteal reactions are observed in immunosuppressed patients undergoing long-term voriconazole therapy. Voriconazole-induced periostitis Diagnosis Case report Literature review Figures Figure 1 Figure 2 Figure 3 Background Voriconazole (VRC) is extensively used to prevent and treat fungal infections in immunosuppressed patients with hematologic malignancies, autoimmune diseases, and those who have undergone solid organ or hematopoietic stem cell transplantation. The Food and Drug Administration (FDA) approved VRC in 2002, and the first case series of VRC-induced periostitis was published in 2009 [ 1 ]. Lie et al. reviewed case reports and case series of VRC-induced periostitis published between 2009 and 2021, encompassing 44 patients with a median age of 58 years (range 29–74 years) [ 2 ]. VRC-induced periostitis is rare in children. An analysis of data from the FDA Adverse Event Reporting System found that the proportion of patients younger than 18 years with VRC-induced periostitis was 4 out of 143 (2.8%) [ 3 ]. Tarlock et al. reported a case of a 7.5-month-old girl who developed VRC-induced periostitis after 4.5 months of treatment for disseminated aspergillus [ 4 ]. She had undergone hematopoietic cell transplantation at five and seven months of age. Here, we report an extremely rare case of VRC-induced periostitis in an 8-year-old boy that required differentiation from a bone tumor. Case presentation An 8-year-old boy presented to our hospital with a five-month history of pain and a mass in his right middle finger persisting for one month. Four years earlier, he had been treated for severe congenital neutropenia with total-body irradiation and hematopoietic stem cell transplantation. He had been on voriconazole (VRC) for three years to treat Aspergillus pneumonia and had been hospitalized for six months for chronic graft-versus-host disease. Radiographs revealed bone formation outside the cortical bone in the proximal phalanx of the right middle finger and the right distal ulna (Fig. 1 A, B). Magnetic resonance imaging (MRI) indicated that the bone formation in the proximal phalanx was hypointense on T1-weighted, T2-weighted, and fat-suppressed short tau inversion recovery (STIR) images and was well enhanced (Fig. 1 C-E). Computed tomography (CT) demonstrated dense cortical bone formation in the proximal phalanx of the right middle finger (Fig. 1 F, G) and the right distal ulna (Fig. 1 H). Serum alkaline phosphatase levels were slightly elevated at 341 U/L (normal < 322 U/L). Differential diagnoses included benign bone-forming tumors such as osteochondroma (Fig. 2 A) following total body irradiation and bizarre parosteal osteochondromatous proliferation (BPOP) (Fig. 2 B). As multiple bone lesions and new bone formation appeared, the patient was diagnosed with VRC-induced periostitis. Radiographs taken one month after his initial visit showed new bone formation on the cortical bone of the left distal ulna (Fig. 3 A) and the right distal radius two months after the initial visit (Fig. 3 B). CT scans performed two months after the initial visit revealed dense cortical bone formation in the right clavicle (Fig. 3 C), bilateral scapulae, left rib (Fig. 3 D), and right femur (Fig. 3 E). VRC was discontinued two months post-diagnosis and replaced with posaconazole, which alleviated his pain. However, the bone lesions did not shrink or disappear during follow-up, and the patient died three months after the initial diagnosis due to the progression of the underlying disease. Discussion and Conclusions VRC-induced periostitis is a recognized side effect of VRC, characterized by multiple bone pains. It predominantly occurs in patients with hematologic malignancies, autoimmune diseases, and following solid organ or hematopoietic stem cell transplantation [ 2 , 5 ]. Case reports and series of VRC-induced periostitis published in the past decade are summarized in Table 1 . Among 32 published cases, the median age was 63 years (range 0.6–74 years), and 17 cases (53%) involved female patients. The distribution included 20 cases (63%) of solid organ transplantation, seven (22%) of hematopoietic stem cell transplantation, two (6%) of hematologic malignancies, two (6%) with no underlying disease, and one (3%) of acute granulomatosis and polyangiitis. The median treatment duration was seven months (range 2–96 months), although data were missing for five patients. The VRC dosage varied, and all patients exhibited multiple lesions. Table 1 Case reports or series of voriconazole-induced periostitis published in the last 10 years Authors Year of publication Age Sex Transplantation/Disease Reasons for voriconazole medication Dose Administration period Site Rheinboldt M et al.[ 9 ] 2015 59 years Male Lung transplantation Fungal superinfection 200 mg BID 2 years Multiple (sternum, rib, spine) 66 years Male Hematopoietic stem cell transplantation Fungal pneumonia 200 mg BID 6 months Multiple (rib) 65 years Female Liver transplantation Fungal pneumonia 200 mg BID 3.5 months Multiple (rib) Tailor TD et al.[ 10 ] 2015 74 years Female Lung transplantation Pulmonary aspergillosis Unknown Unknown Multiple (extremity, rib, clavicle) Tarlock K et al.[ 4 ] 2015 7.5 months Female Hematopoietic stem cell transplantation Disseminated aspergillus Unknown 4.5 months Multiple (lower extremity) Paudyal S et al.[ 11 ] 2015 67 years Female Heart transplantation Unknown 200 mg BID Unknown Multiple (upper extremity) Baird JH et al.[ 12 ] 2015 64 years Male Hematopoietic stem cell transplantation Fungal pneumonia 400 mg daily 4 months Multiple (rib, extremity) Glushko T et al.[ 13 ] 2015 66 years Female T-cell prolymphocytic leukemia Invasive neurohistoplasmosis 300 mg BID 10 months Multiple (extremity) Davis DL[ 14 ] 2015 39 years Female Lung transplantation Abnormal bronchoalveolar lavage 200 mg BID 5 months Multiple (lower extremity) Reber JD et al.[ 15 ] 2016 62 years Male None Multiorganism abdominal aortic stent-graft infection Unknown 3 years Multiple (extremity, rib) Sircar M et al.[ 16 ] 2016 56 years Male Liver transplantation Cerebral infection by Scedosporium apiospermum 400 mg BID 2 months Multiple (extremity, rib, scapula) 71 years Male Heart transplantation Cerebral infection by Scedosporium Unknown 7 months Multiple (extremity, clavicle, ribs, scapula, spine) Sweiss K et al.[ 17 ] 2016 58 years Female Hematopoietic stem cell transplantation Invasive fungal infection Unknown Unknown Multiple (hand) Ladak K et al.[ 18 ] 2017 30 years Male Lung transplantation Pulmonary aspergillosis 200 mg BID 4 years Multiple (extremities, pelvis) Metayer B et al.[ 19 ] 2017 49 years Male Lung transplantation Unknown 400 mg BID 3 months Multiple (extremities, rib) Poinen K et al.[ 20 ] 2018 64 years Male Kidney transplantation Pulmonary aspergillosis 350 mg BID 3 months Multiple (lower extremity) Cormican S et al.[ 21 ] 2018 61 years Male Acute granulomatosis and polyangiitis Pulmonary aspergillosis 300 mg BID 7 months Multiple (extremity, scapula) Haemels M et al.[ 22 ] 2019 34 years Male Hematopoietic stem cell transplantation Pulmonary aspergillosis 600 mg BID 4 months Multiple (skull, extremity, ribs, pelvis) Hedrick J et al.[ 23 ] 2019 65 years Female Lung transplantation Prevention of infections Unknown 8 years Multiple (extremity, spine) Elmore S et al.[ 24 ] 2019 55 years Female Lung transplantation Prevention of infections with immunosuppressive therapy 300 mg BID 3 months Multiple (extremity) 29 years Male Lung transplantation Detection of Mycelia sterilia in culture of bronchoscopy specimens 300 mg BID 17 months Multiple (extremity) Malek AE et al.[ 25 ] 2020 66 years Female Hematopoietic stem cell transplantation Pulmonary aspergillosis 200 mg BID 4 years Multiple (ankle) Guarascio AJ et al.[ 8 ] 2021 19 years Male Heart transplantation Pulmonary aspergillosis 550 mg BID 11 months Multiple (extremity, clavicle) Fernández Ávila DC et al[ 26 ] 2021 44 years Female Hematopoietic stem cell transplantation Cutaneous, cerebral, and pulmonary infection by Scedosporium apiospermum 300 mg BID 9 months Multiple (extremity, scapula) Bennett MJ et al.[ 27 ] 2022 68 years Female Lung transplantation Mycetoma formation in the right lung by Lomentospora prolificans 400 mg TID 18 months Multiple (extremity, rib) 68 years Male Acute myeloid leukemia Pulmonary aspergillosis 400 mg BID 7 months Unknown Stefan S et al.[ 28 ] 2022 66 years Female Lung transplantation Pulmonary aspergillosis 200 mg BID 7 years Multiple (extremity) Valor-Méndez L et al.[ 29 ] 2022 30 years Female None Pulmonary and cerebral aspergillosis Unknown 3 months Multiple (hand) Murray OM et al.[ 30 ] 2022 71 years Female Lung transplantation Sepsis by Scedosporium apiospermum Unknown Unknown Multiple (extremity, rib) Al Waragli N et al.[ 31 ] 2023 65 years Female Kidney transplantation Pulmonary aspergillosis 200 mg BID 16 months Multiple (extremity, rib) Suthar PP et al.[ 32 ] 2024 43 years Female Liver transplantation Unknown Unknown Unknown Multiple (extremity, rib) Shetty AN et al.[ 33 ] 2024 65 years Male Liver transplantation Pulmonary aspergillosis 300 mg BID 3 months Multiple (clavicle, rib, scapula) This case 8 years Male Hematopoietic stem cell transplantation Pulmonary aspergillosis 100 mg BID 3 years Multiple (extremity, clavicle, rib, scapula) BID: twice a day, TID: three times a day As of April 21, 2024, a PubMed search ( https://pubmed.ncbi.nlm.nih.gov/ ) using the keywords "voriconazole," "periostitis," and "child" identified only three articles [ 3 – 5 ]. These included two non-review articles: one case series and one study based on the FDA Adverse Event Reporting System data. Tarlock et al. reported a case of a 7.5-month-old girl with VRC-induced periostitis after 4.5 months of VRC treatment for disseminated aspergillus [ 4 ]. Her medical history included two hematopoietic stem cell transplantations, with increased serum fluoride and alkaline phosphatase levels observed three months after initiating VRC. Li et al. found that the proportion of patients under 18 years old with VRC-induced periostitis was 4 out of 143 (2.8%), based on FDA Adverse Event Reporting System data [ 3 ]. Reports of VRC-induced periostitis in children are scarce, and this is the first documented case in a non-infant child. Similar to the case reported by Tarlock et al., this case also involved a history of hematopoietic stem cell transplantation. The differential diagnoses for this case included benign bone-forming tumors such as osteochondroma and BPOP (Fig. 2 ) after total body irradiation. Osteochondroma is a known complication following total body irradiation and subsequent hematopoietic stem cell transplantation, with a mean latent period of 7.5 years (range: 5.7–9.4 years) to clinical presentation [ 6 ]. This patient developed finger pain four years after total body irradiation, and there are few reports of osteochondromas in the fingers following such treatment. Additionally, the typical features of osteochondroma, such as continuity with the bone marrow or the presence of a cartilage cap, were not observed. In contrast, BPOP commonly occurs in the hands and fingers [ 7 ] and remained a differential diagnosis in this case. As multiple bone lesions and new bone formation were identified during the disease course, the patient was diagnosed with VRC-induced periostitis. A thorough review of his medications and knowledge of this disease was crucial for the diagnosis. VRC-induced periostitis is attributed to the fluoride present in VRC. Unlike nonfluorinated itraconazole, VRC contains three fluoride atoms, whereas fluconazole, isavuconazole, and posaconazole each contain two fluoride atoms [ 8 ]. Some fluoride from VRC is released into the serum, leading to elevated serum fluoride levels. This increase has been documented in five patients under 19 years of age who were treated with VRC for more than three months [ 4 ]. Elevated fluoride levels result in high fluorapatite deposits, which cause disorganized osteoblastic reactions. This leads to periosteal thickening or ossification, exostosis, and osteosclerosis, collectively known as skeletal fluorosis [ 8 ]. Symptoms typically resolve in approximately 60% of cases within two weeks after discontinuing the drug [ 2 ]. In the present case, pain improvement was noted after switching to posaconazole. There are some limitations in this study. First, due to the deterioration of the underlying disease, it was not possible to perform an appropriate follow-up with imaging after discontinuation of VRC, and we were only able to follow up symptoms. Second, we presented case reports and series of VRC-induced periostitis published in the past decade in Table 1 , but journals that charged a fee for institute access or were not written in English were excluded. Although VRC-induced periostitis is rare, it should be considered in pediatric patients when multiple nodular periosteal reactions are observed in immunosuppressed individuals undergoing long-term VRC therapy. Abbreviations VRC: voriconazole FDA: Food and Drug Administration MRI: magnetic resonance imaging STIR: short tau inversion recovery CT: computed tomography BPOP: bizarre parosteal osteochondromatous proliferation Declarations Acknowledgements We thank the patient and his family for their time, effort, and consent to participate in this study. Authors’ contributions HU designed and drafted the manuscript and came up with the concept. HU and SI revised the manuscript and provided supervision. KI, TS, HK, TF, and YN provided treatment for the voriconazole-induced periostitis. All the authors have read and approved the final version of the manuscript. Funding One author (HU) received research funding from the Ministry of Education, Culture, Sports, Science and Technology of Japan [Grant-in-Aid 23K08696 for Scientific Research (C)]. Availability of data and materials This is the case report of a single patient. To protect the privacy and to respect confidentiality, no raw data are available in any public repository. Original operation reports, intraoperative photographs, imaging studies, and outpatient clinic records were retained as per normal procedures within the medical records of our institution. Declarations Competing interests The authors declare that they have no competing interests. Ethics approval and consent to participate As this is a case report, ethics approval is not applicable. Consent for publication Written informed consent was obtained from the patient’s family for the publication of this case report and any accompanying images. Author details 1 Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan 2 Department of Orthopedic Surgery, Nagoya University Hospital, Nagoya, Japan 3 Department of Rehabilitation Medicine, Nagoya University Hospital, Nagoya, Japan References Wang TF, Wang T, Altman R, Eshaghian P, Lynch JP, 3rd, Ross DJ, Belperio JA, Weigt SS, Saggar R, Gregson A, et al. Periostitis secondary to prolonged voriconazole therapy in lung transplant recipients. Am J Transplant. 2009;9(12):2845-50. Li Z, Wu C, Wang C, Deng Z. Spectrum of voriconazole-associated periostitis in clinical characteristics, diagnosis and management. Infection. 2022;50(5):1217-24. Li H, Zhang M, Jiao X, Zhu Y, Liu Y, Zeng L, Wang H, Zhang L, Zhang W, Zhang L. Using disproportionality analysis to explore the association between periostitis and triazole antifungals in the FDA Adverse Event Reporting System Database. Sci Rep. 2023;13(1):4475. 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Reumatismo. 2021;73(1):44-47. Bennett MJ, Balcerek MI, Lewis EA, Zhang RL, Bachmeier C, Tey S, Faux S, Girgis L, Greenfield JR, Lazarus S. Voriconazole-Associated Periostitis: New Insights into Pathophysiology and Management. JBMR Plus. 2022;6(2):e10557. Stefan S, Altork N, Alzedaneen Y, Whitlatch H, Munir KM. Voriconazole-Induced Diffuse Periostitis. AACE Clin Case Rep. 2022;8(5):191-93. Valor-Mendez L, Wacker J, Schett G, Manger B, Furst J, Strauss R, Kleyer A. Clinical Images: Voriconazole-induced synovitis, enthesitis, and periostitis. Arthritis Rheumatol. 2022;74(7):1183. Murray OM, Hynes JP, Murray MA, Kavanagh EC. Voriconazole-induced periostitis post lung transplantation. Radiol Case Rep. 2022;17(5):1587-90. Al Waragli N, Bachmeyer C, Ouali N, Sabater AM, Kerrou K. 18F-NaF positron emission tomography/computed tomography in voriconazole-induced periostitis. Clin Rheumatol. 2023;42(7):1987-89. Suthar PP, Virmani S. Voriconazole-Induced Periostitis in a Patient after Orthotopic Liver Transplantation. Radiology. 2024;310(3):e232902. Shetty AN, Cummings KW, Gotway MB, Jensen EA, Jokerst CE, Panse PM, Rojas CA. Thoracic periosteal reaction secondary to voriconazole use in an adult transplant patient. Radiol Case Rep. 2024;19(1):346-48. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Aug, 2025 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted Editor invited by journal 14 Jun, 2024 Editor assigned by journal 12 Jun, 2024 Submission checks completed at journal 11 Jun, 2024 First submitted to journal 02 Jun, 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. 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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-4518669","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":315104229,"identity":"2a41daa6-c1c1-4cfc-99e5-bac8829773b6","order_by":0,"name":"Hiroshi Urakawa","email":"data:image/png;base64,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","orcid":"","institution":"Nagoya University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Urakawa","suffix":""},{"id":315104232,"identity":"663f8245-6ac4-4d59-9d14-73207aa8eaf6","order_by":1,"name":"Kunihiro Ikuta","email":"","orcid":"","institution":"Nagoya University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kunihiro","middleName":"","lastName":"Ikuta","suffix":""},{"id":315104235,"identity":"7aed0625-e410-4e6d-a4f0-ebe28a2ab89d","order_by":2,"name":"Tomohisa Sakai","email":"","orcid":"","institution":"Nagoya University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomohisa","middleName":"","lastName":"Sakai","suffix":""},{"id":315104240,"identity":"7326c708-a1ac-4580-ac8c-e1b77cbb29d4","order_by":3,"name":"Hiroshi Koike","email":"","orcid":"","institution":"Nagoya University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Koike","suffix":""},{"id":315104242,"identity":"257e2214-94d1-41ba-8be5-4336e8561fe5","order_by":4,"name":"Takeo Fujito","email":"","orcid":"","institution":"Nagoya University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takeo","middleName":"","lastName":"Fujito","suffix":""},{"id":315104243,"identity":"c42f462e-11e3-4f81-a9ab-87f38b738ba6","order_by":5,"name":"Yoshihiro Nishida","email":"","orcid":"","institution":"Nagoya University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yoshihiro","middleName":"","lastName":"Nishida","suffix":""},{"id":315104245,"identity":"359ef0e1-265a-40e1-98e3-1051c6d14de5","order_by":6,"name":"Shiro Imagama","email":"","orcid":"","institution":"Nagoya University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shiro","middleName":"","lastName":"Imagama","suffix":""}],"badges":[],"createdAt":"2024-06-03 01:46:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4518669/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4518669/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12891-025-09059-z","type":"published","date":"2025-08-12T15:57:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":59606689,"identity":"7cd19d63-2369-47f1-a00f-fb5e1c29a48b","added_by":"auto","created_at":"2024-07-03 18:53:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":6383978,"visible":true,"origin":"","legend":"\u003cp\u003eImages from the first visit to the orthopedic department. Radiographs of the anteroposterior (A) and lateral (B) views. Coronal views of the magnetic resonance T1-weighted image (C), T2-weighted image (D), and fat-suppressed STIR (E). Coronal view of CT in the proximal phalanx of the right middle finger (F), and axial views of CT in the proximal phalanx of the right middle finger (G) and the distal ulna (H). Arrowheads indicate bone formation.\u003c/p\u003e\n\u003cp\u003eSTIR: short tau inversion recovery, CT: computed tomography\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4518669/v1/1dc602a0c10f2921b5a4002d.png"},{"id":59606686,"identity":"7dd3ca92-c23f-4b42-b958-6322f5092072","added_by":"auto","created_at":"2024-07-03 18:53:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":952342,"visible":true,"origin":"","legend":"\u003cp\u003eRadiographs of osteochondroma (not after total body irradiation) in the proximal phalanx of the left ring finger (A) and BPOP in the proximal phalanx of the left middle finger (B).\u003c/p\u003e\n\u003cp\u003eBPOP: bizarre parosteal osteochondromatous proliferation\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4518669/v1/4a7ee959489ada29c4e65044.png"},{"id":59606688,"identity":"d733bf82-1ecf-4e5b-a717-0f371ea35667","added_by":"auto","created_at":"2024-07-03 18:53:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2995941,"visible":true,"origin":"","legend":"\u003cp\u003eRadiographs of anteroposterior views 1 month (A) and 2 months (B) after the patient's first visit. Arrowheads indicate new bone formation. Axial views of CT 2 months after the first visit (C-E). Arrowheads indicate bone formation.\u003c/p\u003e\n\u003cp\u003eCT: computed tomography\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4518669/v1/f8ecce822bb3e47e72e413f2.png"},{"id":89310579,"identity":"3d5366b6-353f-4dd8-bea3-0f95da5bfe60","added_by":"auto","created_at":"2025-08-18 16:08:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":15670522,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4518669/v1/441842b8-18a6-4bb1-b7be-6e71ce5d9720.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Voriconazole-induced periostitis in a child with finger pain and nodules: case report and literature review","fulltext":[{"header":"Background","content":"\u003cp\u003eVoriconazole (VRC) is extensively used to prevent and treat fungal infections in immunosuppressed patients with hematologic malignancies, autoimmune diseases, and those who have undergone solid organ or hematopoietic stem cell transplantation. The Food and Drug Administration (FDA) approved VRC in 2002, and the first case series of VRC-induced periostitis was published in 2009 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Lie et al. reviewed case reports and case series of VRC-induced periostitis published between 2009 and 2021, encompassing 44 patients with a median age of 58 years (range 29\u0026ndash;74 years) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVRC-induced periostitis is rare in children. An analysis of data from the FDA Adverse Event Reporting System found that the proportion of patients younger than 18 years with VRC-induced periostitis was 4 out of 143 (2.8%) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Tarlock et al. reported a case of a 7.5-month-old girl who developed VRC-induced periostitis after 4.5 months of treatment for disseminated aspergillus [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. She had undergone hematopoietic cell transplantation at five and seven months of age.\u003c/p\u003e \u003cp\u003eHere, we report an extremely rare case of VRC-induced periostitis in an 8-year-old boy that required differentiation from a bone tumor.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eAn 8-year-old boy presented to our hospital with a five-month history of pain and a mass in his right middle finger persisting for one month. Four years earlier, he had been treated for severe congenital neutropenia with total-body irradiation and hematopoietic stem cell transplantation. He had been on voriconazole (VRC) for three years to treat Aspergillus pneumonia and had been hospitalized for six months for chronic graft-versus-host disease. Radiographs revealed bone formation outside the cortical bone in the proximal phalanx of the right middle finger and the right distal ulna (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, B). Magnetic resonance imaging (MRI) indicated that the bone formation in the proximal phalanx was hypointense on T1-weighted, T2-weighted, and fat-suppressed short tau inversion recovery (STIR) images and was well enhanced (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC-E). Computed tomography (CT) demonstrated dense cortical bone formation in the proximal phalanx of the right middle finger (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF, G) and the right distal ulna (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eH). Serum alkaline phosphatase levels were slightly elevated at 341 U/L (normal\u0026thinsp;\u0026lt;\u0026thinsp;322 U/L). Differential diagnoses included benign bone-forming tumors such as osteochondroma (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA) following total body irradiation and bizarre parosteal osteochondromatous proliferation (BPOP) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). As multiple bone lesions and new bone formation appeared, the patient was diagnosed with VRC-induced periostitis. Radiographs taken one month after his initial visit showed new bone formation on the cortical bone of the left distal ulna (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA) and the right distal radius two months after the initial visit (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). CT scans performed two months after the initial visit revealed dense cortical bone formation in the right clavicle (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC), bilateral scapulae, left rib (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD), and right femur (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE). VRC was discontinued two months post-diagnosis and replaced with posaconazole, which alleviated his pain. However, the bone lesions did not shrink or disappear during follow-up, and the patient died three months after the initial diagnosis due to the progression of the underlying disease.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eVRC-induced periostitis is a recognized side effect of VRC, characterized by multiple bone pains. It predominantly occurs in patients with hematologic malignancies, autoimmune diseases, and following solid organ or hematopoietic stem cell transplantation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Case reports and series of VRC-induced periostitis published in the past decade are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among 32 published cases, the median age was 63 years (range 0.6\u0026ndash;74 years), and 17 cases (53%) involved female patients. The distribution included 20 cases (63%) of solid organ transplantation, seven (22%) of hematopoietic stem cell transplantation, two (6%) of hematologic malignancies, two (6%) with no underlying disease, and one (3%) of acute granulomatosis and polyangiitis. The median treatment duration was seven months (range 2\u0026ndash;96 months), although data were missing for five patients. The VRC dosage varied, and all patients exhibited multiple lesions.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCase reports or series of voriconazole-induced periostitis published in the last 10 years\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYear of publication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTransplantation/Disease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReasons for voriconazole medication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDose\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAdministration period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSite\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eRheinboldt M et al.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFungal superinfection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (sternum, rib, spine)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFungal pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (rib)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiver transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFungal pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.5 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (rib)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTailor TD et al.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, rib, clavicle)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTarlock K et al.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.5 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDisseminated aspergillus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.5 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (lower extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaudyal S et al.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHeart transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (upper extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaird JH et al.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFungal pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e400 mg daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (rib, extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlushko T et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT-cell prolymphocytic leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInvasive neurohistoplasmosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDavis DL[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbnormal bronchoalveolar lavage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (lower extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReber JD et al.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMultiorganism abdominal aortic stent-graft infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, rib)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSircar M et al.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiver transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCerebral infection by \u003cem\u003eScedosporium apiospermum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e400 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, rib, scapula)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHeart transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCerebral infection by \u003cem\u003eScedosporium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, clavicle, ribs, scapula, spine)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSweiss K et al.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInvasive fungal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (hand)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLadak K et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremities, pelvis)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetayer B et al.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e400 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremities, rib)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoinen K et al.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eKidney transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e350 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (lower extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCormican S et al.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAcute granulomatosis and polyangiitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, scapula)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemels M et al.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e600 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (skull, extremity, ribs, pelvis)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHedrick J et al.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePrevention of infections\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, spine)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eElmore S et al.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePrevention of infections with immunosuppressive therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDetection of \u003cem\u003eMycelia sterilia\u003c/em\u003e in culture of bronchoscopy specimens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalek AE et al.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (ankle)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGuarascio AJ et al.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHeart transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e550 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, clavicle)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFern\u0026aacute;ndez \u0026Aacute;vila DC et al[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCutaneous, cerebral, and pulmonary infection by \u003cem\u003eScedosporium apiospermum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, scapula)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBennett MJ et al.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMycetoma formation in the right lung by \u003cem\u003eLomentospora prolificans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e400 mg TID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, rib)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAcute myeloid leukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e400 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStefan S et al.[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eValor-M\u0026eacute;ndez L et al.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary and cerebral aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (hand)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMurray OM et al.[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSepsis by \u003cem\u003eScedosporium apiospermum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, rib)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAl Waragli N et al.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eKidney transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, rib)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuthar PP et al.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiver transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, rib)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShetty AN et al.[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiver transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (clavicle, rib, scapula)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThis case\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematopoietic stem cell transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary aspergillosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e100 mg BID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMultiple (extremity, clavicle, rib, scapula)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eBID: twice a day, TID: three times a day\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs of April 21, 2024, a PubMed search (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) using the keywords \"voriconazole,\" \"periostitis,\" and \"child\" identified only three articles [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These included two non-review articles: one case series and one study based on the FDA Adverse Event Reporting System data. Tarlock et al. reported a case of a 7.5-month-old girl with VRC-induced periostitis after 4.5 months of VRC treatment for disseminated aspergillus [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Her medical history included two hematopoietic stem cell transplantations, with increased serum fluoride and alkaline phosphatase levels observed three months after initiating VRC. Li et al. found that the proportion of patients under 18 years old with VRC-induced periostitis was 4 out of 143 (2.8%), based on FDA Adverse Event Reporting System data [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Reports of VRC-induced periostitis in children are scarce, and this is the first documented case in a non-infant child. Similar to the case reported by Tarlock et al., this case also involved a history of hematopoietic stem cell transplantation.\u003c/p\u003e \u003cp\u003eThe differential diagnoses for this case included benign bone-forming tumors such as osteochondroma and BPOP (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) after total body irradiation. Osteochondroma is a known complication following total body irradiation and subsequent hematopoietic stem cell transplantation, with a mean latent period of 7.5 years (range: 5.7\u0026ndash;9.4 years) to clinical presentation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This patient developed finger pain four years after total body irradiation, and there are few reports of osteochondromas in the fingers following such treatment. Additionally, the typical features of osteochondroma, such as continuity with the bone marrow or the presence of a cartilage cap, were not observed. In contrast, BPOP commonly occurs in the hands and fingers [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and remained a differential diagnosis in this case. As multiple bone lesions and new bone formation were identified during the disease course, the patient was diagnosed with VRC-induced periostitis. A thorough review of his medications and knowledge of this disease was crucial for the diagnosis.\u003c/p\u003e \u003cp\u003eVRC-induced periostitis is attributed to the fluoride present in VRC. Unlike nonfluorinated itraconazole, VRC contains three fluoride atoms, whereas fluconazole, isavuconazole, and posaconazole each contain two fluoride atoms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Some fluoride from VRC is released into the serum, leading to elevated serum fluoride levels. This increase has been documented in five patients under 19 years of age who were treated with VRC for more than three months [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Elevated fluoride levels result in high fluorapatite deposits, which cause disorganized osteoblastic reactions. This leads to periosteal thickening or ossification, exostosis, and osteosclerosis, collectively known as skeletal fluorosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Symptoms typically resolve in approximately 60% of cases within two weeks after discontinuing the drug [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In the present case, pain improvement was noted after switching to posaconazole.\u003c/p\u003e \u003cp\u003eThere are some limitations in this study. First, due to the deterioration of the underlying disease, it was not possible to perform an appropriate follow-up with imaging after discontinuation of VRC, and we were only able to follow up symptoms. Second, we presented case reports and series of VRC-induced periostitis published in the past decade in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, but journals that charged a fee for institute access or were not written in English were excluded.\u003c/p\u003e \u003cp\u003eAlthough VRC-induced periostitis is rare, it should be considered in pediatric patients when multiple nodular periosteal reactions are observed in immunosuppressed individuals undergoing long-term VRC therapy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eVRC: voriconazole\u003c/p\u003e\n\u003cp\u003eFDA: Food and Drug Administration\u003c/p\u003e\n\u003cp\u003eMRI: magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eSTIR: short tau inversion recovery\u003c/p\u003e\n\u003cp\u003eCT: computed tomography\u003c/p\u003e\n\u003cp\u003eBPOP: bizarre parosteal osteochondromatous proliferation\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the patient and his family for their time, effort, and consent to participate in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHU designed and drafted the manuscript and came up with the concept. HU and SI revised the manuscript and provided supervision. KI, TS, HK, TF, and YN provided treatment for the voriconazole-induced periostitis. All\u0026nbsp;the authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne author (HU) received research funding from the Ministry of Education, Culture, Sports, Science and Technology of Japan [Grant-in-Aid 23K08696 for Scientific Research (C)].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is the case report of a single patient. To protect the privacy and to respect confidentiality, no raw data are available in any public repository. Original operation reports, intraoperative photographs, imaging studies, and outpatient clinic records were retained as per normal procedures within the medical records of our institution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs this is a case report, ethics approval is not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient\u0026rsquo;s family for\u0026nbsp;the publication of\u0026nbsp;this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Orthopedic Surgery, Nagoya University Hospital, Nagoya, Japan\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003eDepartment of Rehabilitation Medicine, Nagoya University Hospital, Nagoya, Japan\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWang TF, Wang T, Altman R, Eshaghian P, Lynch JP, 3rd, Ross DJ, Belperio JA, Weigt SS, Saggar R, Gregson A, et al. 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Skeletal Radiol. 2016;45(6):839-42.\u003c/li\u003e\n\u003cli\u003eSircar M, Kotton C, Wojciechowski D, Safa K, Gilligan H, Heher E, Williams W, Thadhani R, Tolkoff-Rubin N. Voriconazole-Induced Periostitis \u0026amp; Enthesopathy in Solid Organ Transplant Patients: Case Reports. J Biosci Med (Irvine). 2016;4(11):8-17.\u003c/li\u003e\n\u003cli\u003eSweiss K, Oh A, Rondelli D, Patel P. Voriconazole-Induced Periostitis Mimicking Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation. Case Rep Infect Dis. 2016;2016:3242196.\u003c/li\u003e\n\u003cli\u003eLadak K, Rubin L. Voriconazole-Induced Periostitis Deformans: A Mimicker of Hypertrophic Pulmonary Osteoarthropathy. Clin Med Res. 2017;15(1-2):19-20.\u003c/li\u003e\n\u003cli\u003eMetayer B, Bode-Milin C, Ansquer C, Haloun A, Maugars Y, Berthelot JM. Painful and swollen hands 3 months after lungs graft: Suracute voriconazole-induced periostitis and exostosis. 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Voriconazole-associated periostitis presenting as hypertrophic osteoarthropathy following lung transplantation report of two cases and review of the literature. Semin Arthritis Rheum. 2019;49(2):319-23.\u003c/li\u003e\n\u003cli\u003eMalek AE, Skaff Y, Mulanovich VE. Voriconazole-induced periostitis in stem cell transplant patient. Infection. 2020;48(5):809-10.\u003c/li\u003e\n\u003cli\u003eFernandez Avila DC, Diehl M, Degrave AM, Buttazzoni M, Pereira T, Aguirre MA, Basquiera AL, Scolnik M. Voriconazole-induced periostitis. Reumatismo. 2021;73(1):44-47.\u003c/li\u003e\n\u003cli\u003eBennett MJ, Balcerek MI, Lewis EA, Zhang RL, Bachmeier C, Tey S, Faux S, Girgis L, Greenfield JR, Lazarus S. Voriconazole-Associated Periostitis: New Insights into Pathophysiology and Management. JBMR Plus. 2022;6(2):e10557.\u003c/li\u003e\n\u003cli\u003eStefan S, Altork N, Alzedaneen Y, Whitlatch H, Munir KM. Voriconazole-Induced Diffuse Periostitis. AACE Clin Case Rep. 2022;8(5):191-93.\u003c/li\u003e\n\u003cli\u003eValor-Mendez L, Wacker J, Schett G, Manger B, Furst J, Strauss R, Kleyer A. Clinical Images: Voriconazole-induced synovitis, enthesitis, and periostitis. Arthritis Rheumatol. 2022;74(7):1183.\u003c/li\u003e\n\u003cli\u003eMurray OM, Hynes JP, Murray MA, Kavanagh EC. Voriconazole-induced periostitis post lung transplantation. Radiol Case Rep. 2022;17(5):1587-90.\u003c/li\u003e\n\u003cli\u003eAl Waragli N, Bachmeyer C, Ouali N, Sabater AM, Kerrou K. 18F-NaF positron emission tomography/computed tomography in voriconazole-induced periostitis. Clin Rheumatol. 2023;42(7):1987-89.\u003c/li\u003e\n\u003cli\u003eSuthar PP, Virmani S. Voriconazole-Induced Periostitis in a Patient after Orthotopic Liver Transplantation. Radiology. 2024;310(3):e232902.\u003c/li\u003e\n\u003cli\u003eShetty AN, Cummings KW, Gotway MB, Jensen EA, Jokerst CE, Panse PM, Rojas CA. Thoracic periosteal reaction secondary to voriconazole use in an adult transplant patient. Radiol Case Rep. 2024;19(1):346-48.\u003c/li\u003e\n\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-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Voriconazole-induced periostitis, Diagnosis, Case report, Literature review","lastPublishedDoi":"10.21203/rs.3.rs-4518669/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4518669/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eVoriconazole-induced periostitis is predominantly reported in adults, with pediatric cases being exceedingly rare.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eThis report describes an 8-year-old boy with voriconazole-induced periostitis presenting with finger pain and nodules, initially suspected to be bone tumors. The patient had been on voriconazole for three years to treat Aspergillus pneumonia and had been hospitalized for six months due to chronic graft-versus-host disease following hematopoietic stem cell transplantation and total body irradiation for severe congenital neutropenia. The patient presented with a five-month history of pain and a one-month history of a mass in the middle finger of his right hand. Radiographs revealed bone formation outside the cortical bone in the proximal phalanx of the right middle finger and the distal ulna. Differential diagnoses included benign bone-forming tumors, such as osteochondroma post-total body irradiation, and bizarre parosteal osteochondromatous proliferation. The diagnosis of voriconazole-induced periostitis was confirmed as multiple bone lesions and new bone formation became apparent during the disease course.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eVoriconazole-induced periostitis should be considered, even in pediatric patients, when multiple nodular periosteal reactions are observed in immunosuppressed patients undergoing long-term voriconazole therapy.\u003c/p\u003e","manuscriptTitle":"Voriconazole-induced periostitis in a child with finger pain and nodules: case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-03 18:53:49","doi":"10.21203/rs.3.rs-4518669/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvited","content":"","date":"2024-06-14T20:36:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-12T04:00:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-12T03:58:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Musculoskeletal Disorders","date":"2024-06-03T01:44:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6e00732c-72bf-42a1-b5bb-9edc740f2248","owner":[],"postedDate":"July 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-18T16:02:20+00:00","versionOfRecord":{"articleIdentity":"rs-4518669","link":"https://doi.org/10.1186/s12891-025-09059-z","journal":{"identity":"bmc-musculoskeletal-disorders","isVorOnly":false,"title":"BMC Musculoskeletal Disorders"},"publishedOn":"2025-08-12 15:57:50","publishedOnDateReadable":"August 12th, 2025"},"versionCreatedAt":"2024-07-03 18:53:49","video":"","vorDoi":"10.1186/s12891-025-09059-z","vorDoiUrl":"https://doi.org/10.1186/s12891-025-09059-z","workflowStages":[]},"version":"v1","identity":"rs-4518669","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4518669","identity":"rs-4518669","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}