Rhino-cerebral mucormycosis misdiagnosed as neuropsychiatric lupus in a 17-year-old diabetic ketoacidosis patient: a case report.

Rhino-cerebral mucormycosis misdiagnosed as neuropsychiatric lupus in a 17-year-old diabetic ketoacidosis patient: a case report. | 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 Rhino-cerebral mucormycosis misdiagnosed as neuropsychiatric lupus in a 17-year-old diabetic ketoacidosis patient: a case report. Hasan Hamdan, Tareq Muhammad, Zulfiqar Hamdan, Imad Almasri, Areej Alsabbagh, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4341140/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Two life-threatening fungal infections, zygomycosis and Aspergillosis, frequently occur in immunocompromised individuals. Because of the arterial vessel invasion, early and rapid diagnosis is crucial. Case presentation: A 17-year-old female with a history of photosensitivity presented to the emergency department with loss of consciousness due to diabetic ketoacidosis (DKA). Initial management included intravenous fluids, insulin, and electrolyte correction; further workup revealed juvenile systemic lupus erythematosus (JSLE) based on physical examination and laboratory tests. The patient initially improved with treatment for DKA and restored consciousness, but later developed right eye ptosis, vision problems, and facial numbness; with suspicion of cavernous sinus thrombosis. Due to limited diagnostic resources, a CT scan of the brain was performed which showed only mucosal thickening of the maxillary and ethmoid sinuses. Biopsy from a newly developed lesion on the palate confirmed a rare fungal infection (Aspergillus and Mucormycosis). Despite reduced-dose antifungal therapy due to kidney complications, the patient’s condition deteriorated and she passed away before surgical intervention. Conclusion: Early clinical recognition, prompt diagnosis of mucormycosis, and appropriate intervention are essential to avert the tragic outcome of this fatal disease Zygomycosis Diabetic ketoacidosis juvenile systemic lupus erythematosus Aspergillosis Mucormycosis. Figures Figure 1 Figure 2 Figure 3 Introduction Fungal infection of the paranasal sinuses is a recognized complication in both immunocompetent and immunocompromised individuals. Various fungi can cause paranasal mycosis, with Aspergillus and Zygomycetes being the most prevalent ( 1 ). Rhino-cerebral mucormycosis, also known as zygomycosis, is a rare disease first identified by Paltauf in 1885 ( 2 ), it is associated with an immunocompromised state, hemochromatosis, desferrioxamine therapy, malignancy, diabetes mellitus with or without organ transplantation, ketoacidosis, prolonged corticosteroid therapy, trauma and severe burns ( 3 ). Aspergillosis and Zygomycosis are the most common causes of central nervous system mycosis ( 4 ). Paranasal mycosis manifests in two unique forms: a benign or noninvasive infection and a more serious invasive infection. Invasive paranasal mycosis occurs primarily in immunocompromised individuals and is characterized by rapid onset, tissue invasion, and destruction. Early diagnosis is crucial because delayed treatment can be life-threatening due to the propensity of fungi to invade adjacent blood vessels and embolize to distant organs, including the brain ( 1 , 5 ). In rhino-cerebral mucormycosis, the infection originates in the nasal/sinus mucosa, located in the paranasal cavities behind the face, after inhalation of fungal spores. The disease progresses rapidly, extending to neighboring tissues such as the orbit and central nervous system ( 4 ). Rhino-cerebral mucormycosis has high morbidity and mortality due to the angioinvasive nature of the fungi, leading to vascular occlusion and extensive tissue necrosis. Impaired delivery of antifungal drugs due to vascular thrombosis and the limitations of aggressive surgery in the complex rhino-orbito-cerebral region highlight the importance of early diagnosis and aggressive management ( 5 , 6 ). This report describes an unusual case of rhino-cerebral zygomycosis with Aspergillosis in a 17-year-old female with undiagnosed type 1 diabetes and juvenile Systemic Lupus Erythematosus (JSLE). The patient's complex medical conditions contributed to a delayed diagnosis, which unfortunately resulted in her death. Case presentation A 17-year-old female presented to the emergency department of Deir ez-Zor hospital with loss of consciousness after 3 days of general asthenia, polyuria, anadipsia and vomiting. Initial workup in Deir ez-Zor Hospital: - Emergency laboratory tests revealed abnormalities as shown in (table 1). Table 1: abnormal findings in Deir ez-Zor hospital Glucose 600 mg/dl Normal range: 70 – 115 mg/dl Ketone bodies +++ Normal range: Negative Creatinine 2.9 mg/dl Normal range: 0.5 – 1.3 mg/dl CRP 21.9 mg/dl Normal range up to 5 mg/dl Hemoglobin 8.4 g/dl Normal range: 11.5 – 16.5 g/dl White blood cells 12100 Cells/µl Normal range: 4000 – 10000 Cells/µl 2 - Based on the findings, diabetic ketoacidosis (DKA) was diagnosed. Initial management: 1 - Intravenous (IV) fluids and Insulin therapy were initiated. 2 - Blood sugar levels Improved, but the patient's level of consciousness didn't. According to the situation, the patient was transferred to Yusuf al-Azma Hospital two days later for further management. Physical examination and vital signs upon arrival at Yusuf al-Azma Hospital: 1- Physical examination: Upon arrival to our hospital, she was unconscious and unresponsive with abdominal distention, a mild erythematous rash on the cheeks and nose, oral ulcers, swollen knees, pitting edema in the lower extremities, and diminished bilateral breath sounds on chest auscultation. 2- Vital signs were as follow: - Blood pressure (BP): 110/60 mmHg. - Heart rate (HR): 100 beats per minute (bpm). - Temperature (Δ): 37 ̊C (axillary route). - Respiratory rate (RR): 30 breaths per minute. History from parents: - The parents reported photosensitivity as the only other significant medical history. Further workup: 1- Laboratory tests upon arrival showed the following abnormalities (table 2): Table 2: abnormal findings in Yusuf al-Azma Hospital upon arrival PH 6.846 Normal range: 7.35 – 7.45 pO2 56 mmHg Normal range: 75 – 100 mmHg pCO2 15.4 mmHg Normal range: 35 – 45 mmHg HCO3 3.4 mmol/l Normal range: 22 – 26 mmol/l Hemoglobin 8.4 g/dl Normal range: 11.5 – 16.5 g/dl Lympho count 600 Cells/µl Normal range: 1500 – 3500 Cells/µl Glucose 166.9 mg/dl Normal range: 70 – 115 mg/dl K 3.03 mmol/l Normal range: 3.6 – 5.2 mmol/l Creatinine 4.3 mg/dl Normal range: 0.5 – 1.3 mg/dl Urea 165.27 mg/dl Normal range: 10 – 45 mg/dl Protein in 24h urine 0.577 g Normal range: 0 – 0.15 g ESR 80 mm/h Normal range: up to 15 mm/h CRP 16 mg/dl Normal range: up to 5 mg/dl Antinuclear antibody (ANA) 1:160 Normal range: Negative (less or equal to 1:40) 2- Computed Tomography (CT) of the chest revealed pleural effusion (Figure 1). Initial management upon arrival: 1- The patient was unconscious so we put her on a ventilator. 2- Based on the findings in (table 2); Intravenous (IV) fluids (1 liter of saline solution every 6 hours at 125 ml/hr containing 40 ml of KCl), sodium bicarbonate (NaHCO3) (20 ml/hr), and Insulin therapy were initiated to manage the diabetic ketoacidosis (DKA). 3- Multidisciplinary consultation was performed for the patient, with regular assessment to adjust the treatment plan as needed. Multidisciplinary consultation result: 1- Renal consultation result: due to the diabetic ketoacidosis, high number of Creatinine and urea in the blood (table 2) they recommended performing daily hemodialysis sessions for the patient. 2- Rheumatology consultation result: according to the physical examination and laboratory tests the patient was diagnosed with juvenile systemic lupus erythematosus ((j)SLE) as she achieved 8 out of 11 of the 1997 American College of Rheumatology (ACR) criteria for classification of SLE (table 3); and they add Hydrocortisone 100mg 3 times daily and Hydroxychloroquine 200mg once at night to the treatment plan: Table 3: 1997 ACR criteria for the classification of SLE Criteria Findings in the patient 1- Malar (butterfly) rash. Mild erythematous rash on the cheeks and nose. 2- Discoid rash. 3- Photosensitivity The parents reported photosensitivity in her medical history. 4- Oral ulcers Physical examination revealed oral ulcers. 5- Arthritis Swollen knees. 6- Serositis Pleural effusion on the chest computed tomography (CT). 7- Renal disorder Protein in 24h urine = 0.577 g 8- Neurological disorders 9- Hematological disorders Laboratory tests showed lymphopenia 10- Immunological disorders 11- Antinuclear antibody (ANA) Laboratory tests showed ANA positivity. 3- Endocrinology consultation result: monitor blood sugar every 6 hours to adjust insulin dose as needed. 4- The cardiology and neurology consultation results were unremarkable. Initial management follow-up : The patient regained consciousness two days after hospital admission, with improvement in blood gas and glucose values, and was successfully weaned off the ventilator. However, the lymphocyte count continued to decrease; interpreted in the context of juvenile systemic lupus erythematosus, and there was slight improvement in renal function test numbers despite daily hemodialysis sessions. Table 4: patient follow-up after initial management Before After Notes PH 6.846 7.378 Normal range: 7.35 – 7.45 pO2 56 mmHg 75 mmHg Normal range: 75 – 100 mmHg pCO2 15.4 mmHg 18.6 mmHg Normal range: 35 – 45 mmHg HCO3 3.4 mmol/l 10.7 mmol/l Normal range: 22 – 26 mmol/l Lympho count 600 Cells/µl 200 Cells/µl Normal range: 1500 – 3500 Cells/µl Glucose 166.9 mg/dl 119.4 mg/dl Normal range: 70 – 115 mg/dl K 3.03 mmol/l 3.63 mmol/l Normal range: 3.6 – 5.2 mmol/l Creatinine 4.3 mg/dl 3.48 mg/dl Normal range: 0.5 – 1.3 mg/dl Urea 165.27 mg/dl 163.02 mg/dl Normal range: 17 – 43 mg/dl - On the fifth day, the patient developed right ptosis, blurred vision in the right eye, mydriasis with no light reflex, a feeling of heaviness followed by loss of movement in the right eye in all directions, during the patient's assessment, a painless white lesion was found on the roof of the palate with thick brown secretions and crusts in the nasal cavity, and a biopsy was taken from it. This was followed by respiratory failure and loss of consciousness, so the patient was re-intubated and connected to a ventilator. The multidisciplinary team suspected cavernous sinus thrombosis in the context of a lupus flare, and Magnetic Resonance Imaging (MRI) with contrast was requested. Unfortunately, MRI is not available in our hospital or any surrounding facilities, additionally, the patient has kidney failure; so a Computed tomography (CT) of the brain was performed, which only showed mucosal thickening of the maxillary and ethmoid sinuses (Figure 2). - On the sixth day, the biopsy showed that the patient had Aspergillus and Mucormycosis infection. There was bony exposure on the midline of the palatal vault and severe necrosis around it (Figure 3). - Due to the kidney failure, Amphotericin was given at a reduced dose of 50mg IV every 24h after hemodialysis sessions. The surgical team decided to perform a palatal vault resection with ethmoid curettage, but unfortunately, the patient passed away before any intervention could be performed. Discussion A rare but aggressive fungal infection, rhino-cerebral mucormycosis (also known as zygomycosis), targets the nose, paranasal sinuses, and brain. It thrives in individuals with compromised immune systems, often those undergoing immunosuppressive treatments or battling chronic illnesses. This rapid fungal growth can quickly become life-threatening. Early diagnosis and intervention are crucial to prevent permanent neurological damage and ensure patient survival. While typically presenting as an acute infection, chronic forms with slower progression over weeks have also been documented ( 7 , 8 ). Commonly associated medical conditions include diabetic ketoacidosis, prolonged corticosteroid therapy, severe burns, solid organ transplantation, hemochromatosis, steroid therapy, HIV-infected patients, neutropenia, malnutrition, and hematological malignancies ( 8 , 9 ). While systemic lupus erythematosus (SLE) is a risk factor for invasive mucormycosis due to immunosuppressive therapy ( 10 ), we believe in this case that diabetic ketoacidosis (DKA) is the stronger risk factor as the patient has not yet been treated with immunosuppressive agents. The ocular and neurological symptoms and the rapid progression led us to suspect cavernous sinus thrombosis, a complication of SLE, according to our knowledge it is uncommon for diabetic patients in this age group to develop invasive mucormycosis, so it was not on the differential diagnosis list for the multidisciplinary team ( 11 ). After reviewing hospital data and files and communicating with specialists in some nearby hospitals, cases of invasive mucormycosis associated with diabetes only as a risk factor were very few and all patients were over 60 years old with type 2 diabetes; which already reported in medical literature around the world at this old age ( 12 , 13 ). It is important to note that the patient's Renal Function Tests (RFT) have deteriorated again after administration of Amphotericin due to its nephrotoxicity ( 14 ). A review by Saegeman et all, showed that Rhizopus is the leading suspect for this fungal infection. Mortality is high (55%), with co-infection by Aspergillus. Confirmed or likely in 44% of cases. Combining surgery with antifungal medication offers the best chance of survival ( 15 ). Conclusion This case highlights the unusual occurrence of invasive rhinocerebral mucormycosis in a 17-year-old diabetic patient with juvenile Systemic Lupus Erythematosus, emphasizing the importance of early diagnosis and treatment for this fatal fungal infection. Declarations - Ethics approval and consent to participate: No ethical approval was needed. - Consent for publication: Written informed consent was obtained from the patient parents for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor-in-chief of this journal on request. - Availability of data and materials: Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. - Competing of interests: There were no conflicts of interest. - Funding: There was no source of funding for this study. - Author's contributions: Dr.Hasan Hamdan: provided medical treatment, wrote and supervise the scientific aspects of the manuscript . Dr. Tareq Muhammad: provided medical treatment, wrote and supervise the scientific aspects of the manuscript. Dr. Zulfiqar Hamdan: reviewed the literature, wrote and revised the manuscript, supervise the academic and scientific aspects of the manuscript, and made grammar and spelling language editing. Dr. Imad Almasri : provided medical treatment, and wrote the manuscript. Dr. Areej Alsabbagh: Participated in writing. Dr.Maher Mohamad : provided medical treatment, and Participated in writing. - Acknowledgements: We would like to thank Dr. Akram Alabbas, director of Yusuf al-Azma Military Hospital for his assistance and dedication towards making this study possible. We also express our appreciation to Dr. William Alsheikh, intensive care specialist at Yusuf al-Azma Military Hospital. We also thanks the doctors from ENT, Endocrinology, Histology, Cardiology, and Neurologic departments in Yusuf al-Azma Military Hospital (MDT team) who provided essential data and expertise that led to completing this work. References Alam A, Chander BN, Sabhikhi GS, Bhatia M. Sinonasal Mucormycosis: Diagnosis Using Computed Tomography. Med J Armed Forces India. 2003;59(3):243-5. doi:10.1016/s0377-1237(03)80018-7 Paltauf A. Mycosis mucorina. Virchows Archiv. 1885;102(3):543-64. Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect. 2004;10 Suppl 1:31-47. doi:10.1111/j.1470-9465.2004.00843.x Eucker J, Sezer O, Graf B, Possinger K. Mucormycoses. Mycoses. 2001;44(7-8):253-60. Vaidya D, Shah P. Coinfection by Aspergillus and zygomycetes species in a case of acute rhinosinusitis. Case Rep Otolaryngol. 2011;2011:382473. doi:10.1155/2011/382473 Hussain S, Salahuddin N, Ahmad I, Salahuddin I, Jooma R. Rhinocerebral invasive mycosis: occurrence in immunocompetent individuals. Eur J Radiol. 1995;20(2):151-5. doi:10.1016/0720-048x(95)00644-6 Harrill WC, Stewart MG, Lee AG, Cernoch P. Chronic rhinocerebral mucormycosis. Laryngoscope. 1996;106(10):1292-7. doi:10.1097/00005537-199610000-00024 Bhandari J, Thada PK, Nagalli S. Rhinocerebral Mucormycosis. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC.; 2024. Gonzalez CE, Couriel DR, Walsh TJ. Disseminated zygomycosis in a neutropenic patient: successful treatment with amphotericin B lipid complex and granulocyte colony-stimulating factor. Clin Infect Dis. 1997;24(2):192-6. doi:10.1093/clinids/24.2.192 Mok CC, Que TL, Tsui EY, Lam WY. Mucormycosis in systemic lupus erythematosus. Semin Arthritis Rheum. 2003;33(2):115-24. doi:10.1016/s0049-0172(03)00081-7 El-Shereef RR, Mohamed AS, Hamdy L. Ocular manifestation of systemic lupus erythematosus. Rheumatol Int. 2013;33(6):1637-42. doi:10.1007/s00296-011-2296-x Malhothra S, Mandal S, Meena R, Patel P, Bhatia NK, Duggal N. A treated case of rhinocerebral zygomycosis with aspergillosis: a case report from India. Access Microbiol. 2020;2(8):acmi000139. doi:10.1099/acmi.0.000139 Sweet R, Hovenden M, Harvey CE, Peterson W, Lott I. Rhino-Orbital Cerebral Mucormycosis in a Diabetic Patient: An Emergency Medicine Case Report. J Emerg Med. 2023;64(3):385-7. doi:10.1016/j.jemermed.2022.12.007 Hamill RJ. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs. 2013;73(9):919-34. doi:10.1007/s40265-013-0069-4 Saegeman V, Maertens J, Ectors N, Meersseman W, Lagrou K. Epidemiology of mucormycosis: review of 18 cases in a tertiary care hospital. Med Mycol. 2010;48(2):245-54. doi:10.1080/13693780903059477 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-4341140","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":298568407,"identity":"6040c92d-d260-4369-9676-6dd53f9f3583","order_by":0,"name":"Hasan Hamdan","email":"","orcid":"","institution":"Yusuf Al-Azma Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hasan","middleName":"","lastName":"Hamdan","suffix":""},{"id":298568409,"identity":"70417d0c-533b-43df-af93-9aad5421b382","order_by":1,"name":"Tareq Muhammad","email":"","orcid":"","institution":"Tishreen Military 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07:55:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4341140/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4341140/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56396042,"identity":"30d7b472-3bee-4d19-9a82-7368c4d04cb9","added_by":"auto","created_at":"2024-05-13 15:42:50","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":59176,"visible":true,"origin":"","legend":"\u003cp\u003eCT of the chest with pleural effusion\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4341140/v1/e622e215086ddb58232c3a27.jpg"},{"id":56396043,"identity":"089b28d5-3285-49ab-b5fb-5c0c5b8eb673","added_by":"auto","created_at":"2024-05-13 15:42:50","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":77667,"visible":true,"origin":"","legend":"\u003cp\u003eCT of the brain. \u003cstrong\u003eFigure 2-A.\u003c/strong\u003e mucosal thickening of the ethmoid sinus. \u003cstrong\u003eFigure 2-B.\u003c/strong\u003e mucosal thickening of the maxillary sinus.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4341140/v1/aa27768fb60d97b866dd4c9b.jpg"},{"id":56396044,"identity":"aa5e7b6c-4d46-4f9e-8429-874de496f589","added_by":"auto","created_at":"2024-05-13 15:42:50","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":83515,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA.\u003c/strong\u003e Tissue biopsy of the ulcer. \u003cstrong\u003eBlue circles:\u003c/strong\u003e Aspergillus, the \u003cstrong\u003eblack arrow:\u003c/strong\u003e Mucormycosis.\u0026nbsp;\u003cstrong\u003eB.\u0026nbsp;\u003c/strong\u003eBony exposure on the midline of the palatal vault and severe necrosis around it.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4341140/v1/bc58ca15576b1b8e07cea7f6.jpg"},{"id":56398924,"identity":"9758d7ed-513c-485d-a49d-8a72e183b48f","added_by":"auto","created_at":"2024-05-13 15:58:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":746975,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4341140/v1/bc853417-18a2-4df6-a6e1-3a82417307ea.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Rhino-cerebral mucormycosis misdiagnosed as neuropsychiatric lupus in a 17-year-old diabetic ketoacidosis patient: a case report.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFungal infection of the paranasal sinuses is a recognized complication in both immunocompetent and immunocompromised individuals. Various fungi can cause paranasal mycosis, with Aspergillus and Zygomycetes being the most prevalent (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRhino-cerebral mucormycosis, also known as zygomycosis, is a rare disease first identified by Paltauf in 1885 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), it is associated with an immunocompromised state, hemochromatosis, desferrioxamine therapy, malignancy, diabetes mellitus with or without organ transplantation, ketoacidosis, prolonged corticosteroid therapy, trauma and severe burns (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Aspergillosis and Zygomycosis are the most common causes of central nervous system mycosis (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Paranasal mycosis manifests in two unique forms: a benign or noninvasive infection and a more serious invasive infection. Invasive paranasal mycosis occurs primarily in immunocompromised individuals and is characterized by rapid onset, tissue invasion, and destruction. Early diagnosis is crucial because delayed treatment can be life-threatening due to the propensity of fungi to invade adjacent blood vessels and embolize to distant organs, including the brain (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In rhino-cerebral mucormycosis, the infection originates in the nasal/sinus mucosa, located in the paranasal cavities behind the face, after inhalation of fungal spores. The disease progresses rapidly, extending to neighboring tissues such as the orbit and central nervous system (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Rhino-cerebral mucormycosis has high morbidity and mortality due to the angioinvasive nature of the fungi, leading to vascular occlusion and extensive tissue necrosis. Impaired delivery of antifungal drugs due to vascular thrombosis and the limitations of aggressive surgery in the complex rhino-orbito-cerebral region highlight the importance of early diagnosis and aggressive management (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This report describes an unusual case of rhino-cerebral zygomycosis with Aspergillosis in a 17-year-old female with undiagnosed type 1 diabetes and juvenile Systemic Lupus Erythematosus (JSLE). The patient's complex medical conditions contributed to a delayed diagnosis, which unfortunately resulted in her death.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 17-year-old female presented to the emergency department of Deir ez-Zor hospital with loss of consciousness after 3 days of general asthenia, polyuria, anadipsia and vomiting.\u003c/p\u003e\n\u003cul class=\"decimal_type\"\u003e\n \u003cli\u003e\u003cstrong\u003eInitial workup in Deir ez-Zor Hospital:\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u0026nbsp; - Emergency laboratory tests revealed abnormalities as shown in (table 1).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"3\"\u003e\u003cstrong\u003eTable 1: abnormal findings in Deir ez-Zor hospital\u003c/strong\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.239202657807308%\"\u003e\n \u003cp\u003eGlucose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.588039867109636%\"\u003e\n \u003cp\u003e600 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.17275747508306%\"\u003e\n \u003cp\u003eNormal range: 70 \u0026ndash; 115 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.239202657807308%\"\u003e\n \u003cp\u003eKetone bodies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.588039867109636%\"\u003e\n \u003cp\u003e+++\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.17275747508306%\"\u003e\n \u003cp\u003eNormal range: Negative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.239202657807308%\"\u003e\n \u003cp\u003eCreatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.588039867109636%\"\u003e\n \u003cp\u003e2.9 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.17275747508306%\"\u003e\n \u003cp\u003eNormal range: 0.5 \u0026ndash; 1.3 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.239202657807308%\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.588039867109636%\"\u003e\n \u003cp\u003e21.9 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.17275747508306%\"\u003e\n \u003cp\u003eNormal range up to 5 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.239202657807308%\"\u003e\n \u003cp\u003eHemoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.588039867109636%\"\u003e\n \u003cp\u003e8.4 g/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.17275747508306%\"\u003e\n \u003cp\u003eNormal range: 11.5 \u0026ndash; 16.5 g/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.239202657807308%\"\u003e\n \u003cp\u003eWhite blood cells\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.588039867109636%\"\u003e\n \u003cp\u003e12100 Cells/\u0026micro;l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.17275747508306%\"\u003e\n \u003cp\u003eNormal range: 4000 \u0026ndash; 10000 \u0026nbsp; \u0026nbsp; Cells/\u0026micro;l\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2 - Based on the findings, diabetic ketoacidosis (DKA) was diagnosed.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eInitial management:\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e1 - Intravenous (IV) fluids and Insulin therapy were initiated.\u003c/p\u003e\n\u003cp\u003e2 - Blood sugar levels Improved, but the patient\u0026apos;s level of consciousness didn\u0026apos;t.\u003c/p\u003e\n\u003cp\u003eAccording to the situation, the patient was transferred to Yusuf al-Azma Hospital two days later for further management.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003ePhysical examination and vital signs upon arrival at Yusuf al-Azma Hospital:\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e1- Physical examination:\u003c/p\u003e\n\u003cp\u003eUpon arrival to our hospital, she was unconscious and unresponsive with abdominal distention, a mild erythematous rash on the cheeks and nose, oral ulcers, swollen knees, pitting edema in the lower extremities, and diminished bilateral breath sounds on chest auscultation.\u003c/p\u003e\n\u003cp\u003e2- Vital signs were as follow:\u003c/p\u003e\n\u003cp\u003e- Blood pressure (BP): 110/60 mmHg.\u003c/p\u003e\n\u003cp\u003e- Heart rate (HR): 100 beats per minute (bpm).\u003c/p\u003e\n\u003cp\u003e- Temperature (\u0026Delta;): 37 ̊C (axillary route).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;- Respiratory rate (RR): 30 breaths per minute.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eHistory from parents:\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; - The parents reported photosensitivity as the only other significant medical history.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eFurther workup:\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e1- Laboratory tests upon arrival showed the following abnormalities (table 2):\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2: abnormal findings in Yusuf al-Azma Hospital upon arrival\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003ePH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e6.846\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 7.35 \u0026ndash; 7.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003epO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e56 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 75 \u0026ndash; 100 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003epCO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e15.4 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 35 \u0026ndash; 45 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eHCO3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e3.4 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 22 \u0026ndash; 26 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eHemoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e8.4 g/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 11.5 \u0026ndash; 16.5\u0026nbsp;g/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eLympho count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e600 Cells/\u0026micro;l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 1500 \u0026ndash; 3500 Cells/\u0026micro;l\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eGlucose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e166.9 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 70 \u0026ndash; 115 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e3.03 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 3.6 \u0026ndash; 5.2 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eCreatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e4.3 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 0.5 \u0026ndash; 1.3 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eUrea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e165.27 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 10 \u0026ndash; 45 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eProtein in 24h urine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e0.577 g\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: 0 \u0026ndash; 0.15 g\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eESR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e80 mm/h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: up to 15 mm/h\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e16 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: up to 5 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.945091514143094%\"\u003e\n \u003cp\u003eAntinuclear antibody (ANA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.465890183028286%\"\u003e\n \u003cp\u003e1:160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"46.58901830282862%\"\u003e\n \u003cp\u003eNormal range: Negative (less or equal to 1:40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2- Computed Tomography (CT) of the chest revealed pleural effusion (Figure 1).\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eInitial management upon arrival:\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e1- The patient was unconscious so we put her on a ventilator.\u003c/p\u003e\n\u003cp\u003e2- Based on the findings in (table 2); Intravenous (IV) fluids (1 liter of saline solution every 6 hours at 125 ml/hr containing 40 ml of KCl), sodium bicarbonate (NaHCO3) (20 ml/hr), and Insulin therapy were initiated to manage the diabetic ketoacidosis (DKA).\u003c/p\u003e\n\u003cp\u003e3- Multidisciplinary consultation was performed for the patient, with regular assessment to adjust the treatment plan as needed.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eMultidisciplinary consultation result:\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e1- Renal consultation result: due to the diabetic ketoacidosis, high number of Creatinine and urea in the blood (table 2) they recommended performing daily hemodialysis sessions for the patient.\u003c/p\u003e\n\u003cp\u003e2- Rheumatology consultation result: according to the physical examination and laboratory tests the patient was diagnosed with juvenile systemic lupus erythematosus ((j)SLE) as she achieved 8 out of 11 of the 1997 American College of Rheumatology (ACR) criteria for classification of SLE (table 3); and they add Hydrocortisone 100mg 3 times daily and Hydroxychloroquine 200mg once at night to the treatment plan:\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3: 1997 ACR criteria for the classification of SLE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCriteria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFindings in the patient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e1- Malar (butterfly) rash.\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003eMild erythematous rash on the cheeks and nose.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e2- Discoid rash.\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e3- Photosensitivity\u0026nbsp;\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003eThe parents reported photosensitivity in her medical history.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e4- Oral ulcers\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003ePhysical examination revealed oral ulcers.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e5- Arthritis\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003eSwollen knees.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e6- Serositis\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003ePleural effusion on the chest computed tomography (CT).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e7- Renal disorder\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003eProtein in 24h urine = 0.577 g\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e8- Neurological disorders\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e9- Hematological disorders\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003eLaboratory tests showed lymphopenia\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e10- Immunological disorders\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\"\u003e11- Antinuclear antibody (ANA)\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"50%\"\u003e\n \u003cp\u003eLaboratory tests showed ANA positivity.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e3- Endocrinology consultation result: monitor blood sugar every 6 hours to adjust insulin dose as needed.\u003c/p\u003e\n\u003cp\u003e4- The cardiology and neurology consultation results were unremarkable.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eInitial management follow-up\u003c/strong\u003e:\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe patient regained consciousness two days after hospital admission, with improvement in blood gas and glucose values, and was successfully weaned off the ventilator. However, the lymphocyte count continued to decrease; interpreted in the context of juvenile systemic lupus erythematosus, and there was slight improvement in renal function test numbers despite daily hemodialysis sessions.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"671\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4: patient follow-up after initial management\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNotes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003ePH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e6.846\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e7.378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 7.35 \u0026ndash; 7.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003epO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e56 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e75 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 75 \u0026ndash; 100 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003epCO2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e15.4 mmHg\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e18.6 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 35 \u0026ndash; 45 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003eHCO3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e3.4 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e10.7 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 22 \u0026ndash; 26 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003eLympho count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e600\u0026nbsp;Cells/\u0026micro;l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e200\u0026nbsp;Cells/\u0026micro;l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 1500 \u0026ndash; 3500 Cells/\u0026micro;l\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003eGlucose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e166.9 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e119.4 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 70 \u0026ndash; 115 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003eK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e3.03 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e3.63 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 3.6 \u0026ndash; 5.2 mmol/l\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003eCreatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e4.3 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e3.48 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 0.5 \u0026ndash; 1.3 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003eUrea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\"\u003e\n \u003cp\u003e165.27 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.330849478390462%\"\u003e\n \u003cp\u003e163.02 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.666169895678095%\"\u003e\n \u003cp\u003eNormal range: 17 \u0026ndash; 43 mg/dl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e- On the fifth day, the patient developed right ptosis, blurred vision in the right eye, mydriasis with no light reflex, a feeling of heaviness followed by loss of movement in the right eye in all directions, during the patient\u0026apos;s assessment, a painless white lesion was found on the roof of the palate with thick brown secretions and crusts in the nasal cavity, and a biopsy was taken from it. This was followed by respiratory failure and loss of consciousness, so the patient was re-intubated and connected to a ventilator. The multidisciplinary team suspected cavernous sinus thrombosis in the context of a lupus flare, and Magnetic Resonance Imaging (MRI) with contrast was requested. Unfortunately, MRI is not available in our hospital or any surrounding facilities, additionally, the patient has kidney failure; so a Computed tomography (CT) of the brain was performed, which only showed mucosal thickening of the maxillary and ethmoid sinuses (Figure 2).\u003c/p\u003e\n\u003cp\u003e- On the sixth day, the biopsy showed that the patient had Aspergillus and Mucormycosis infection. There was bony exposure on the midline of the palatal vault and severe necrosis around it (Figure 3).\u003c/p\u003e\n\u003cp\u003e- Due to the kidney failure, Amphotericin was given at a reduced dose of 50mg IV every 24h after hemodialysis sessions. The surgical team decided to perform a palatal vault resection with ethmoid curettage, but unfortunately, the patient passed away before any intervention could be performed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eA rare but aggressive fungal infection, rhino-cerebral mucormycosis (also known as zygomycosis), targets the nose, paranasal sinuses, and brain. It thrives in individuals with compromised immune systems, often those undergoing immunosuppressive treatments or battling chronic illnesses. This rapid fungal growth can quickly become life-threatening. Early diagnosis and intervention are crucial to prevent permanent neurological damage and ensure patient survival. While typically presenting as an acute infection, chronic forms with slower progression over weeks have also been documented (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Commonly associated medical conditions include diabetic ketoacidosis, prolonged corticosteroid therapy, severe burns, solid organ transplantation, hemochromatosis, steroid therapy, HIV-infected patients, neutropenia, malnutrition, and hematological malignancies (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). While systemic lupus erythematosus (SLE) is a risk factor for invasive mucormycosis due to immunosuppressive therapy (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), we believe in this case that diabetic ketoacidosis (DKA) is the stronger risk factor as the patient has not yet been treated with immunosuppressive agents. The ocular and neurological symptoms and the rapid progression led us to suspect cavernous sinus thrombosis, a complication of SLE, according to our knowledge it is uncommon for diabetic patients in this age group to develop invasive mucormycosis, so it was not on the differential diagnosis list for the multidisciplinary team (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). After reviewing hospital data and files and communicating with specialists in some nearby hospitals, cases of invasive mucormycosis associated with diabetes only as a risk factor were very few and all patients were over 60 years old with type 2 diabetes; which already reported in medical literature around the world at this old age (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). It is important to note that the patient's Renal Function Tests (RFT) have deteriorated again after administration of Amphotericin due to its nephrotoxicity (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). A review by Saegeman et all, showed that Rhizopus is the leading suspect for this fungal infection. Mortality is high (55%), with co-infection by Aspergillus. Confirmed or likely in 44% of cases. Combining surgery with antifungal medication offers the best chance of survival (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights the unusual occurrence of invasive rhinocerebral mucormycosis in a 17-year-old diabetic patient with juvenile Systemic Lupus Erythematosus, emphasizing the importance of early diagnosis and treatment for this fatal fungal infection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e- Ethics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo ethical approval was needed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Consent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient parents for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor-in-chief of this journal on request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Availability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Competing of interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Funding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no source of funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Author\u0026apos;s contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr.Hasan Hamdan:\u003c/strong\u003e provided medical treatment,\u0026nbsp;wrote and supervise the scientific aspects of the manuscript\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr.\u003c/strong\u003e\u003cstrong\u003eTareq Muhammad:\u0026nbsp;\u003c/strong\u003eprovided medical treatment, wrote and supervise the scientific aspects of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr.\u003c/strong\u003e\u003cstrong\u003eZulfiqar Hamdan:\u0026nbsp;\u003c/strong\u003ereviewed the literature, wrote and revised the manuscript, supervise the academic and scientific aspects of the manuscript, and made grammar and spelling language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Imad Almasri\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eprovided medical treatment,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eand\u0026nbsp;wrote\u0026nbsp;the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Areej Alsabbagh:\u0026nbsp;\u003c/strong\u003eParticipated in writing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr.Maher Mohamad\u003c/strong\u003e:\u0026nbsp;provided medical treatment,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eand Participated in writing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Acknowledgements:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Dr. Akram Alabbas, director of Yusuf al-Azma Military Hospital for his assistance and dedication towards making this study possible. We also express our appreciation to Dr. William Alsheikh, intensive care specialist at Yusuf al-Azma Military Hospital. We also thanks the doctors from ENT, Endocrinology, Histology, Cardiology, and Neurologic departments in Yusuf al-Azma Military Hospital (MDT team) who provided essential data and expertise that led to completing this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlam A, Chander BN, Sabhikhi GS, Bhatia M. Sinonasal Mucormycosis: Diagnosis Using Computed Tomography. Med J Armed Forces India. 2003;59(3):243-5. doi:10.1016/s0377-1237(03)80018-7\u003c/li\u003e\n\u003cli\u003ePaltauf A. Mycosis mucorina. Virchows Archiv. 1885;102(3):543-64.\u003c/li\u003e\n\u003cli\u003ePrabhu RM, Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect. 2004;10 Suppl 1:31-47. doi:10.1111/j.1470-9465.2004.00843.x\u003c/li\u003e\n\u003cli\u003eEucker J, Sezer O, Graf B, Possinger K. Mucormycoses. Mycoses. 2001;44(7-8):253-60.\u003c/li\u003e\n\u003cli\u003eVaidya D, Shah P. Coinfection by Aspergillus and zygomycetes species in a case of acute rhinosinusitis. Case Rep Otolaryngol. 2011;2011:382473. doi:10.1155/2011/382473\u003c/li\u003e\n\u003cli\u003eHussain S, Salahuddin N, Ahmad I, Salahuddin I, Jooma R. Rhinocerebral invasive mycosis: occurrence in immunocompetent individuals. Eur J Radiol. 1995;20(2):151-5. doi:10.1016/0720-048x(95)00644-6\u003c/li\u003e\n\u003cli\u003eHarrill WC, Stewart MG, Lee AG, Cernoch P. Chronic rhinocerebral mucormycosis. Laryngoscope. 1996;106(10):1292-7. doi:10.1097/00005537-199610000-00024\u003c/li\u003e\n\u003cli\u003eBhandari J, Thada PK, Nagalli S. Rhinocerebral Mucormycosis. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright \u0026copy; 2024, StatPearls Publishing LLC.; 2024.\u003c/li\u003e\n\u003cli\u003eGonzalez CE, Couriel DR, Walsh TJ. Disseminated zygomycosis in a neutropenic patient: successful treatment with amphotericin B lipid complex and granulocyte colony-stimulating factor. Clin Infect Dis. 1997;24(2):192-6. doi:10.1093/clinids/24.2.192\u003c/li\u003e\n\u003cli\u003eMok CC, Que TL, Tsui EY, Lam WY. Mucormycosis in systemic lupus erythematosus. Semin Arthritis Rheum. 2003;33(2):115-24. doi:10.1016/s0049-0172(03)00081-7\u003c/li\u003e\n\u003cli\u003eEl-Shereef RR, Mohamed AS, Hamdy L. Ocular manifestation of systemic lupus erythematosus. Rheumatol Int. 2013;33(6):1637-42. doi:10.1007/s00296-011-2296-x\u003c/li\u003e\n\u003cli\u003eMalhothra S, Mandal S, Meena R, Patel P, Bhatia NK, Duggal N. A treated case of rhinocerebral zygomycosis with aspergillosis: a case report from India. Access Microbiol. 2020;2(8):acmi000139. doi:10.1099/acmi.0.000139\u003c/li\u003e\n\u003cli\u003eSweet R, Hovenden M, Harvey CE, Peterson W, Lott I. Rhino-Orbital Cerebral Mucormycosis in a Diabetic Patient: An Emergency Medicine Case Report. J Emerg Med. 2023;64(3):385-7. doi:10.1016/j.jemermed.2022.12.007\u003c/li\u003e\n\u003cli\u003eHamill RJ. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs. 2013;73(9):919-34. doi:10.1007/s40265-013-0069-4\u003c/li\u003e\n\u003cli\u003eSaegeman V, Maertens J, Ectors N, Meersseman W, Lagrou K. Epidemiology of mucormycosis: review of 18 cases in a tertiary care hospital. Med Mycol. 2010;48(2):245-54. doi:10.1080/13693780903059477\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Zygomycosis, Diabetic ketoacidosis, juvenile systemic lupus erythematosus, Aspergillosis, Mucormycosis.","lastPublishedDoi":"10.21203/rs.3.rs-4341140/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4341140/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eTwo life-threatening fungal infections, zygomycosis and Aspergillosis, frequently occur in immunocompromised individuals. Because of the arterial vessel invasion, early and rapid diagnosis is crucial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation: \u003c/strong\u003eA 17-year-old female with a history of photosensitivity presented to the emergency department with loss of consciousness due to diabetic ketoacidosis (DKA). Initial management included intravenous fluids, insulin, and electrolyte correction; further workup revealed juvenile systemic lupus erythematosus (JSLE) based on physical examination and laboratory tests. The patient initially improved with treatment for DKA and restored consciousness, but later developed right eye ptosis, vision problems, and facial numbness; with suspicion of cavernous sinus thrombosis. Due to limited diagnostic resources, a CT scan of the brain was performed which showed only mucosal thickening of the maxillary and ethmoid sinuses. Biopsy from a newly developed lesion on the palate confirmed a rare fungal infection (Aspergillus and Mucormycosis). Despite reduced-dose antifungal therapy due to kidney complications, the patient’s condition deteriorated and she passed away before surgical intervention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eEarly clinical recognition, prompt diagnosis of mucormycosis, and appropriate intervention are essential to avert the tragic outcome of this fatal disease\u003c/p\u003e","manuscriptTitle":"Rhino-cerebral mucormycosis misdiagnosed as neuropsychiatric lupus in a 17-year-old diabetic ketoacidosis patient: a case report.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-13 15:42:45","doi":"10.21203/rs.3.rs-4341140/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0b426fbd-45a8-4418-b558-5806b8b00909","owner":[],"postedDate":"May 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-13T15:42:47+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-13 15:42:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4341140","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4341140","identity":"rs-4341140","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}