Rhino-orbital-cerebral mucormycosis in acute myeloid leukemia patients: A case series from Sri Lanka

Rhino-orbital-cerebral mucormycosis in acute myeloid leukemia patients: A case series from Sri Lanka | 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-orbital-cerebral mucormycosis in acute myeloid leukemia patients: A case series from Sri Lanka Pradeep Siriwardena, Ushani Wariyapperuma, Pasindu Nanayakkara, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4805516/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Dec, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted 16 You are reading this latest preprint version Abstract Background: Rhino-cerebral mucormycosis varies widely in incidence across Europe, from 0.2 to 3 cases per million(1), and is underreported and underdiagnosed in the Indian subcontinent(2). Nonetheless, it is a medical emergency. This infection often arises in patients with hematological malignancies, particularly in patients with neutropenia, leading to multi-organ failure requiring ICU management. Despite intensive care, invasive fungal infections in hematological malignancies often result in poor outcomes(3). This case series details the presentations and unique challenges faced during management in patients with acute myeloid leukemia who developed rhino-cerebral mucormycosis. Case presentation: We present three cases of rhino-cerebral mucormycosis occurring in patients with acute myeloid leukemia: two females aged 35 and 29, and one male aged 42. Symptoms manifested during chemotherapy induction, with all patients experiencing symptoms suggestive of rhino, orbital or cerebral infection in a background of severe neutropenia (ANC < 0.5). Nasal endoscopy revealed necrotic tissue in all cases, with contrast-enhanced CT confirming invasive fungal infection. Rhizopus species were isolated in cultures from the two female patients, and histopathological evidence of fungal invasion was noted in one. Treatment with Amphotericin B combined with debridement with functional endoscopic sinus surgery (FESS) resulted in survival of two patients, though one succumbed during treatment. Conclusions: This case series highlights the importance of clinical vigilance and initiation of early multidisciplinary team management for better clinical outcome in patients with hematological malignancies. Endoscopic procedures are crucial not only for surgical debridement but also for obtaining vital tissue samples for diagnosis. Early, multidisciplinary involvement will significantly improve the outcome of these patients. Rhino-cerebral mucormycosis Hematological malignancies Neutropenia immunocompromised patients Functional Endoscopic Sinus Surgery Figures Figure 1 Figure 2 Background Mucormycosis, is a rare yet potentially life-threatening fungal infection which, in humans is caused by the filamentous fungi of genera in the order Mucorales( 4 ). Fungal spores are found in the in the environment and although humans are frequently exposed, human infection is rare as it is effectively eliminated by the intact immune system( 5 ). Multiple studies have identified diabetes mellitus and hematological malignancies to be the leading factors predisposing to this infection.( 5 )( 6 )( 7 )( 8 ). Mucormycosis demonstrates a spectrum of clinical manifestations, ranging from commonest presentations of rhino-orbital-cerebral involvement and pulmonary infections to less common gastrointestinal, cutaneous and isolated central nervous system (CNS) infections. The cardinal feature is the vascular invasion by the fungal hyphae leading to infarction and necrosis of host tissues( 9 ). The patients frequently present with fever, headache, sinusitis, visual impairment and periorbital and facial swelling in the case of rhino-orbital involvement and pneumonia in the case of pulmonary infection( 9 ). An escalation of mucormycosis cases has been observed in patients with hematological malignancies over the last decade. This has shown to be associated with exposure to prophylactic antifungal treatment with voriconazole in these patients( 10 )( 11 ). The diagnosis requires detection of organisms in tissue by histopathology followed by culture confirmation. However, often the culture reveals no growth and histopathological identification of an organism with a structure typical of Mucorales is the only evidence of infection. Endoscopic evaluation of sinuses may aid in identifying tissue necrosis and obtaining specimens. Both computed tomography (CT) and Magnetic Resonance Imaging (MRI) are useful to detect the fungal invasion of the vasculature and involvement other tissues( 12 ). Treatment involves a combination of surgical debridement and antifungal treatment( 13 )( 14 ). Despite early diagnosis and combined aggressive medical and surgical treatment, the prognosis is often poor( 3 ). The National Cancer Institute of Sri Lanka (NCISL), currently known as Apeksha Hospital, is the tertiary referral center for cancer care in Sri Lanka. This case series from the hemato-oncolgy units of Apeksha hospital, highlights the importance of clinical vigilance and initiation of early multidisciplinary team management for mucormycosis to achieve a better clinical outcome in patients with hematological malignancies. Case Presentation Case 1 A 35-year-old female diagnosed with acute myeloid leukemia (AML), undergoing the fludarabine, cytarabine and filgrastim (FLAG) chemotherapy regimen for residual disease, presented with severe right-sided headache and pain in her right ear. Autoscore examination of the right ear was normal. Although there was mild right eye proptosis, there was no ophthalmoplegia or visual impairment. Blood investigations reveled absolute neutrophil count (ANC) of 0.32 x 10 9 /L. X-ray sinus view revealed bilateral haziness in maxillary sinus. Contrast enhanced computer tomography (CECT) brain showed enlarged lacrimal gland due to extra medullary deposit of known AML with right proptosis. Mucosal disease involving bilateral sphenoid and maxillary sinuses was also noted without definitive evidence of fungal sinusitis. The patient underwent functional endoscopic sinus surgery (FESS) and samples were sent for bacterial culture, fungal studies and histopathology. Subsequently, the patient developed right eye blindness with restriction of medial eye movement. A blood-stained discharge was also noted from right side nose. Rigid nasal endoscopy revealed necrotic debris. At this point, the patient was started on intravenous Amphotericin B 5mg/kg/day. Further examination revealed necrosis of the nasal septum & inferior turbinate. Biopsy taken from inferior turbinate suggested appearance consistent with a fungal infection of the paranasal sinuses, morphology favoring mucor organisms. Magnetic resonance imaging of Brain revealed bilateral pan sinusitis indicating residual para nasal sinus mucormycosis (Fig. 1 ). There was right side intra orbital extension of the disease with compression of R/optic nerve and R/medial rectus muscle at the orbital apex. Repeat FESS under general anesthesia revealed necrotic tissue seen in bilateral inferior turbinate, maxillary sinus and ethmoid sinuses. Direct smear became positive for mucormycosis and Rhizopus spp. were isolated in fungal culture. She received IV Amphotericin for a duration of 3 months which successfully eliminated the fungal infection and led to the resolution of proptosis and ophthalmoplegia. However, blindness still persists as a result of significant damage to the right optic nerve as revealed by visual evoked potential. She is currently under regular review by the (Ear, Nose and Throat) ENT and Oncology teams. Case 2 A 42-year-old male with acute myeloid leukemia undergoing induction chemotherapy with daunorubicin and cytarabine (Ara-C) 7 + 3 therapy developed right-sided headache, facial swelling, and paresthesia. There was right eye proptosis. Blood investigations revealed an absolute neutrophil count (ANC) 0.27 x 10^9/L. Contrast enhanced computer tomography (CECT) brain revealed sinusitis of right side maxillary and right side ethmoid sinus with involvement of inferior part of orbital fossa through eroded orbital floor causing proptosis. Patient was started on IV Amphotericin B 5mg/kg/day suspecting rhino-orbital-mucormycosis. Patient underwent functional endoscopic sinus surgery (FESS) and samples were sent for histology and culture While on antifungal treatment, the patient developed worsening right periorbital swelling and repeat CECT brain revealed acute invasive fungal infection of R/maxillary sinus and mass extending to inferior temporal facial orbit. During this period, the patient developed neutropenic sepsis and antibiotics were added to the treatment regimen. Patient underwent the second FESS where necrotic debris in right side maxillary sinus & inferior orbital sinus were removed and samples were negative by fungal culture. After receiving IV amphotericin for three months, patient clinically improved with resolution of headache. There was no visual impairment or ophthalmoplegia. FESS done prior to discharge was clear of necrotic debris. Chemotherapy for AML was successfully resumed after resolution of fungal sinusitis and neutropenic sepsis. Case 3 A 29-year -old female patient with AML receiving induction chemotherapy with daunorubicin cytarabine (Ara-C) 7 + 3 therapy developed fever and right jaw pain. Absolute neutrophil count (ANC) was 0.21 x 10^9/L and patient was started on antibiotics for neutropenic sepsis. However, she developed worsening jaw pain, swelling & difficulty in opening the mouth. She further developed severe thrombocytopenia and anemia. Nasal endoscopy revealed necrotic areas in left side hard palate & retro molar region clinically suggestive of mucormycosis. Rhizopus species was isolated in culture and fungal hyphae was noted in direct smear(Fig. 2 ). Patient was started on IV Amphotericin B 5mg/kg/day promptly. CECT revealed evidence of local infection in maxillary region including left side oropharynx with early abscess formation at left side retro alveolar region of maxilla. While undergoing sinus debridement under general anesthesia, the patient developed uncontrolled bleeding due to disseminated intravascular coagulation and succumbed to death. Discussion This case series brings out some of the cardinal features of mucormycosis in immune compromised patients. Mucormycosis has been identified as a cause of fungal infections among leukemia patients. This is largely attributed to increased use of chemotherapy and steroids( 15 ). In all three of the above cases, the patients developed symptoms while undergoing induction phase of the chemotherapy with severe neutropenia (ANC < 0.5). None of them had diabetes or other immunodeficiency conditions apart from their malignancy. All three patients developed rhino-cerebral form of mucormycosis. However, the literature suggests the pulmonary infection is more common in patients with hematological malignancies( 16 ). The presentation of these patients which included headache, facial pain and swelling, proptosis, and fever are consistent with the commonest presentations of rhino-cerebral mucormycosis. The diagnosis is mainly by histopathological identification of the organism in tissue samples as the culture often provides no growth( 17 ). One of the above patients revealed histopathological evidence of mucormycosis, cultures were positive in two patients. Further evaluation with CT/MRI imaging is recommended for evaluation of extent of infection. CT is preferred over MRI as it can detect bony erosions. CT or MRI evaluation was done in all three patients which revealed evidence of extent of sinus involvement and spread to adjacent structures like orbits, mandibular region. Polymerase chain reaction (PCR) test, although has shown to be useful in several studies, their utility in clinical practice is not established( 18 ). IV Amphotericin B is the drug of choice for initial treatment. However, early surgical debridement of necrotic tissue has shown to improve survival. Use of endoscopic procedure for debridement and obtaining specimens is particularly noteworthy in the above cases and it has shown to greater accuracy and less operative morbidity( 19 ). Delay in diagnosis is a key factor contributing to poor prognosis. Outcome of two of the three patients were remarkable due to early suspicion and initiation of appropriate treatment. Mucormycosis in patients with hematological malignancies presents a severe and often fatal complication, with mortality rates approaching nearly 100%. The primary challenge in managing this infection lies in correcting neutropenia, as the immunocompromised state of these patients significantly impairs their ability to fight off the fungal invasion. Additionally, obtaining adequate diagnostic samples is complicated by the presence of multiple co-morbidities, which can limit invasive procedures and delay timely diagnosis and treatment. Addressing these issues is critical for improving outcomes in this vulnerable population, necessitating a multidisciplinary approach to manage both the underlying malignancy and the opportunistic infection effectively. Conclusion The above case series highlights the importance of clinical vigilance and prompt initiation of treatment for mucormycosis upon suspicion in patients with hematological malignancies, particularly those who have severe neutropenia. Endoscopic procedures are useful not only for surgical debridement but also for obtaining tissue samples. Abbreviations ICU Intensive care unit AML Acute myeloid leukemia CNS Central nervous system ANC Absolute neutrophil count FLAG fludarabine, cytarabine and filgrastim ENT Ear, nose and throat GA General anesthesia DIC Disseminated intravascular coagulation FESS functional endoscopic sinus surgery MRI Magnetic resonance imaging CECT Contrast enhanced computed tomography PCR Polymerase chain reaction. Declarations Ethics approval and consent to participate The study protocol conformed to the ethical guidelines of the 1975 Helsinki Declaration. In relation to ethical considerations patient’s informed written consent was taken to participate and report these cases in an international journal. Consent to publication Written informed consent was obtained from the patients’ and/or their relations to publish these case reports and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Competing interests The authors declare that they have no competing interests. Funding No particular funding source used for this work. Author Contribution PS (Corresponding Author): Diagnosed and managed patients, and facilitated overall communication among team members at the National Cancer Institute, Maharagama, Sri Lanka. UM (Co-author): Led the team according to the timeline, conducted the literature review, and drafted the manuscript. PN (Co-author): Managed communication with authors and patients, gathered investigation results and contributed to writing the manuscript. NJ, DM, MB, and BS (Co-authors): Specialist team at the National Cancer Institute, Maharagama, Sri Lanka, who contributed to investigating the disease and managing patient care. All authors have read and approved the final manuscript. Acknowledgement Staff of the Hemato-oncology Unit, Department of Histopathology and Department of Microbiology of National Cancer Hospital, Sri Lanka for their dedicated patient care and support given for the authors. Availability of data and material Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. References Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi. 2019;5(1). Yago MR et al. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-. Ann Oncol. 2020;(January):19–21. Jestin M, Azoulay E, Pène F, Bruneel F, Mayaux J, Murgier M et al. Poor outcome associated with mucormycosis in critically ill hematological patients: results of a multicenter study. Ann Intensive Care [Internet]. 2021;11(1). https://doi.org/10.1186/s13613-021-00818-4 Kauffman CA, Malani AN. Zygomycosis: an emerging fungal infection with new options for management. Curr Infect Dis Rep [Internet]. 2007;9(6):435–40. http://www.ncbi.nlm.nih.gov/pubmed/17999877 Sharma A, Goel A. Mucormycosis: risk factors, diagnosis, treatments, and challenges during COVID-19 pandemic. Folia Microbiol (Praha) [Internet]. 2022;67(3):363–87. http://www.ncbi.nlm.nih.gov/pubmed/35220559 Kumar D, Ahmad F, Kumar A, Bishnoi M, Grover A, Rewri P. Risk Factors, Clinical Manifestations, and Outcomes of COVID-19-Associated Mucormycosis and Other Opportunistic Fungal Infections. Cureus. 2023;15(9). Patade Y. G R. Risk Factors of Rhino Orbital Mucormycosis. Cureus [Internet]. 2022; https://www.cureus.com/articles/129143-risk-factors-of-rhino-orbital-mucormycosis Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis [Internet]. 2005;41(5):634–53. http://www.ncbi.nlm.nih.gov/pubmed/16080086 Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis [Internet]. 2012;54 Suppl 1:S23-34. http://www.ncbi.nlm.nih.gov/pubmed/22247442 Sharifpour A, Gholinejad-Ghadi N, Ghasemian R, Seifi Z, Aghili SR, Zaboli E et al. Voriconazole associated mucormycosis in a patient with relapsed acute lymphoblastic leukemia and hematopoietic stem cell transplant failure: A case report. J Mycol Med [Internet]. 2018;28(3):527–30. http://www.ncbi.nlm.nih.gov/pubmed/29807852 Trifilio SM, Bennett CL, Yarnold PR, McKoy JM, Parada J, Mehta J et al. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant [Internet]. 2007;39(7):425–9. http://www.ncbi.nlm.nih.gov/pubmed/17310132 Wali U, Balkhair A, Al-Mujaini A. Cerebro-rhino orbital mucormycosis: an update. J Infect Public Health [Internet]. 2012;5(2):116–26. http://www.ncbi.nlm.nih.gov/pubmed/22541257 Wolthers MS, Schmidt G, Gjørup CA, Helweg-Larsen J, Rubek N, Jensen LT. Surgical management of rhinocerebral mucormycosis: A case series. JPRAS open [Internet]. 2021;30:33–7. http://www.ncbi.nlm.nih.gov/pubmed/34401438 Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards J, Ibrahim AS. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis [Internet]. 2009;48(12):1743–51. http://www.ncbi.nlm.nih.gov/pubmed/19435437 Pagano L, Offidani M, Fianchi L, Nosari A, Candoni A, Picardi M et al. Mucormycosis in hematologic patients. Haematologica [Internet]. 2004;89(2):207–14. http://www.ncbi.nlm.nih.gov/pubmed/15003897 Pak J, Tucci VT, Vincent AL, Sandin RL, Greene JN. Mucormycosis in immunochallenged patients. J Emerg Trauma Shock [Internet]. 2008;1(2):106–13. http://www.ncbi.nlm.nih.gov/pubmed/19561989 Goel A, Kini U, Shetty S. Role of histopathology as an aid to prognosis in rhino-orbito-cerebral zygomycosis. Indian J Pathol Microbiol [Internet]. 2010;53(2):253–7. http://www.ncbi.nlm.nih.gov/pubmed/20551527 Millon L, Larosa F, Lepiller Q, Legrand F, Rocchi S, Daguindau E et al. Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin Infect Dis [Internet]. 2013;56(10):e95-101. http://www.ncbi.nlm.nih.gov/pubmed/23420816 Jiang RS, Hsu CY. Endoscopic sinus surgery for rhinocerebral mucormycosis. Am J Rhinol [Internet]. 1999;13(2):105–9. http://www.ncbi.nlm.nih.gov/pubmed/10219438 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 26 Dec, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 25 Sep, 2024 Reviews received at journal 24 Sep, 2024 Reviews received at journal 19 Sep, 2024 Reviewers agreed at journal 18 Sep, 2024 Reviews received at journal 15 Sep, 2024 Reviewers agreed at journal 14 Sep, 2024 Reviewers agreed at journal 14 Sep, 2024 Reviewers agreed at journal 12 Sep, 2024 Reviews received at journal 17 Aug, 2024 Reviewers agreed at journal 12 Aug, 2024 Reviewers agreed at journal 10 Aug, 2024 Reviewers invited by journal 08 Aug, 2024 Editor invited by journal 07 Aug, 2024 Editor assigned by journal 06 Aug, 2024 Submission checks completed at journal 06 Aug, 2024 First submitted to journal 26 Jul, 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-4805516","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":341768781,"identity":"b8c3e08e-df57-4fd4-89cc-ed9e8399b8d7","order_by":0,"name":"Pradeep Siriwardena","email":"data:image/png;base64,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","orcid":"","institution":"National Cancer Institute","correspondingAuthor":true,"prefix":"","firstName":"Pradeep","middleName":"","lastName":"Siriwardena","suffix":""},{"id":341768783,"identity":"6d27bb38-366e-47c0-a1a1-3e02b6dcd9b5","order_by":1,"name":"Ushani Wariyapperuma","email":"","orcid":"","institution":"Faculty of Medicine, University of Moratuwa","correspondingAuthor":false,"prefix":"","firstName":"Ushani","middleName":"","lastName":"Wariyapperuma","suffix":""},{"id":341768784,"identity":"49b0d2fa-4927-4dff-a804-7adfb86b7b12","order_by":2,"name":"Pasindu Nanayakkara","email":"","orcid":"","institution":"Postgraduate Institute of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Pasindu","middleName":"","lastName":"Nanayakkara","suffix":""},{"id":341768785,"identity":"e75de369-5e39-4218-a4de-eddc2d547999","order_by":3,"name":"Naamal Jayawardena","email":"","orcid":"","institution":"National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Naamal","middleName":"","lastName":"Jayawardena","suffix":""},{"id":341768786,"identity":"ff9bd59e-3652-4d64-b66f-b2094921f76c","order_by":4,"name":"Dhanushka Mendis","email":"","orcid":"","institution":"National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Dhanushka","middleName":"","lastName":"Mendis","suffix":""},{"id":341768787,"identity":"cf84c58a-9c63-4ebe-a090-26a235b1cb18","order_by":5,"name":"Milhan Bahar","email":"","orcid":"","institution":"National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Milhan","middleName":"","lastName":"Bahar","suffix":""},{"id":341768788,"identity":"911f3c73-6ab0-426e-9d0e-9f542d79214e","order_by":6,"name":"Buddhika Somawardana","email":"","orcid":"","institution":"National Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Buddhika","middleName":"","lastName":"Somawardana","suffix":""}],"badges":[],"createdAt":"2024-07-26 05:33:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4805516/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4805516/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-024-10334-y","type":"published","date":"2024-12-26T15:57:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":64570632,"identity":"0d898134-89d3-4a95-a289-242990490602","added_by":"auto","created_at":"2024-09-16 01:03:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":4078444,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea-d \u003c/strong\u003eHistopathological features of tissue from right side sphenoid and ethmoid sinuses (Hematoxylin and eosin stain, 100x magnification)sections \u003cstrong\u003e(a to c)\u003c/strong\u003e show fragments of viable and necrotic mucosal fragments with a moderate infiltrate of acute and chronic inflammatory cells. The necrotic fragments contain a dense growth of filamentous fungus with show separation. The underline bone fragments appeared unremarkable. Vascular invasion is evident in the section \u003cstrong\u003ed\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4805516/v1/817b8c02dcef6fe69e7abbe2.jpg"},{"id":64570631,"identity":"b500932a-a1ef-4010-a25f-9efa2549ac1f","added_by":"auto","created_at":"2024-09-16 01:03:23","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1225711,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u0026amp; b \u003c/strong\u003eMacroscopic morphology \u003cstrong\u003e(a)\u003c/strong\u003e of the isolate in Saboraud Dextrose Agar incubated at 37\u003csup\u003eo\u003c/sup\u003eC for 48 hours and microscopic morphology \u003cstrong\u003e(b)\u003c/strong\u003e in Lacto phenol Cotton Blue x40 magnification showing Rhizopus species.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4805516/v1/6d83b77eb86df9e99e0e7bc2.jpg"},{"id":72640779,"identity":"655241b5-7121-4916-8d7a-a9ce1959eff4","added_by":"auto","created_at":"2024-12-30 16:09:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5639271,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4805516/v1/25b41188-5be9-4a0b-8267-f7b6953d4b74.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Rhino-orbital-cerebral mucormycosis in acute myeloid leukemia patients: A case series from Sri Lanka","fulltext":[{"header":"Background","content":"\u003cp\u003eMucormycosis, is a rare yet potentially life-threatening fungal infection which, in humans is caused by the filamentous fungi of genera in the order Mucorales(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Fungal spores are found in the in the environment and although humans are frequently exposed, human infection is rare as it is effectively eliminated by the intact immune system(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Multiple studies have identified diabetes mellitus and hematological malignancies to be the leading factors predisposing to this infection.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMucormycosis demonstrates a spectrum of clinical manifestations, ranging from commonest presentations of rhino-orbital-cerebral involvement and pulmonary infections to less common gastrointestinal, cutaneous and isolated central nervous system (CNS) infections. The cardinal feature is the vascular invasion by the fungal hyphae leading to infarction and necrosis of host tissues(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The patients frequently present with fever, headache, sinusitis, visual impairment and periorbital and facial swelling in the case of rhino-orbital involvement and pneumonia in the case of pulmonary infection(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAn escalation of mucormycosis cases has been observed in patients with hematological malignancies over the last decade. This has shown to be associated with exposure to prophylactic antifungal treatment with voriconazole in these patients(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe diagnosis requires detection of organisms in tissue by histopathology followed by culture confirmation. However, often the culture reveals no growth and histopathological identification of an organism with a structure typical of Mucorales is the only evidence of infection. Endoscopic evaluation of sinuses may aid in identifying tissue necrosis and obtaining specimens. Both computed tomography (CT) and Magnetic Resonance Imaging (MRI) are useful to detect the fungal invasion of the vasculature and involvement other tissues(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Treatment involves a combination of surgical debridement and antifungal treatment(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Despite early diagnosis and combined aggressive medical and surgical treatment, the prognosis is often poor(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe National Cancer Institute of Sri Lanka (NCISL), currently known as Apeksha Hospital, is the tertiary referral center for cancer care in Sri Lanka. This case series from the hemato-oncolgy units of Apeksha hospital, highlights the importance of clinical vigilance and initiation of early multidisciplinary team management for mucormycosis to achieve a better clinical outcome in patients with hematological malignancies.\u003c/p\u003e"},{"header":"Case Presentation","content":" \u003cp\u003e \u003cstrong\u003eCase 1\u003c/strong\u003e \u003cp\u003eA 35-year-old female diagnosed with acute myeloid leukemia (AML), undergoing the fludarabine, cytarabine and filgrastim (FLAG) chemotherapy regimen for residual disease, presented with severe right-sided headache and pain in her right ear. Autoscore examination of the right ear was normal. Although there was mild right eye proptosis, there was no ophthalmoplegia or visual impairment. Blood investigations reveled absolute neutrophil count (ANC) of 0.32 x 10\u003csup\u003e9\u003c/sup\u003e/L. X-ray sinus view revealed bilateral haziness in maxillary sinus. Contrast enhanced computer tomography (CECT) brain showed enlarged lacrimal gland due to extra medullary deposit of known AML with right proptosis. Mucosal disease involving bilateral sphenoid and maxillary sinuses was also noted without definitive evidence of fungal sinusitis.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eThe patient underwent functional endoscopic sinus surgery (FESS) and samples were sent for bacterial culture, fungal studies and histopathology. Subsequently, the patient developed right eye blindness with restriction of medial eye movement. A blood-stained discharge was also noted from right side nose. Rigid nasal endoscopy revealed necrotic debris. At this point, the patient was started on intravenous Amphotericin B 5mg/kg/day. Further examination revealed necrosis of the nasal septum \u0026amp; inferior turbinate. Biopsy taken from inferior turbinate suggested appearance consistent with a fungal infection of the paranasal sinuses, morphology favoring mucor organisms. Magnetic resonance imaging of Brain revealed bilateral pan sinusitis indicating residual para nasal sinus mucormycosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere was right side intra orbital extension of the disease with compression of R/optic nerve and R/medial rectus muscle at the orbital apex. Repeat FESS under general anesthesia revealed necrotic tissue seen in bilateral inferior turbinate, maxillary sinus and ethmoid sinuses. Direct smear became positive for mucormycosis and \u003cem\u003eRhizopus\u003c/em\u003e spp. were isolated in fungal culture. She received IV Amphotericin for a duration of 3 months which successfully eliminated the fungal infection and led to the resolution of proptosis and ophthalmoplegia. However, blindness still persists as a result of significant damage to the right optic nerve as revealed by visual evoked potential. She is currently under regular review by the (Ear, Nose and Throat) ENT and Oncology teams.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 2\u003c/strong\u003e \u003cp\u003eA 42-year-old male with acute myeloid leukemia undergoing induction chemotherapy with daunorubicin and cytarabine (Ara-C) 7\u0026thinsp;+\u0026thinsp;3 therapy developed right-sided headache, facial swelling, and paresthesia. There was right eye proptosis. Blood investigations revealed an absolute neutrophil count (ANC) 0.27 x 10^9/L. Contrast enhanced computer tomography (CECT) brain revealed sinusitis of right side maxillary and right side ethmoid sinus with involvement of inferior part of orbital fossa through eroded orbital floor causing proptosis. Patient was started on IV Amphotericin B 5mg/kg/day suspecting rhino-orbital-mucormycosis. Patient underwent functional endoscopic sinus surgery (FESS) and samples were sent for histology and culture While on antifungal treatment, the patient developed worsening right periorbital swelling and repeat CECT brain revealed acute invasive fungal infection of R/maxillary sinus and mass extending to inferior temporal facial orbit. During this period, the patient developed neutropenic sepsis and antibiotics were added to the treatment regimen. Patient underwent the second FESS where necrotic debris in right side maxillary sinus \u0026amp; inferior orbital sinus were removed and samples were negative by fungal culture. After receiving IV amphotericin for three months, patient clinically improved with resolution of headache. There was no visual impairment or ophthalmoplegia. FESS done prior to discharge was clear of necrotic debris. Chemotherapy for AML was successfully resumed after resolution of fungal sinusitis and neutropenic sepsis.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase 3\u003c/strong\u003e \u003cp\u003eA 29-year -old female patient with AML receiving induction chemotherapy with daunorubicin cytarabine (Ara-C) 7\u0026thinsp;+\u0026thinsp;3 therapy developed fever and right jaw pain. Absolute neutrophil count (ANC) was 0.21 x 10^9/L and patient was started on antibiotics for neutropenic sepsis. However, she developed worsening jaw pain, swelling \u0026amp; difficulty in opening the mouth. She further developed severe thrombocytopenia and anemia. Nasal endoscopy revealed necrotic areas in left side hard palate \u0026amp; retro molar region clinically suggestive of mucormycosis. \u003cem\u003eRhizopus\u003c/em\u003e species was isolated in culture and fungal hyphae was noted in direct smear(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Patient was started on IV Amphotericin B 5mg/kg/day promptly. CECT revealed evidence of local infection in maxillary region including left side oropharynx with early abscess formation at left side retro alveolar region of maxilla. While undergoing sinus debridement under general anesthesia, the patient developed uncontrolled bleeding due to disseminated intravascular coagulation and succumbed to death.\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eThis case series brings out some of the cardinal features of mucormycosis in immune compromised patients. Mucormycosis has been identified as a cause of fungal infections among leukemia patients. This is largely attributed to increased use of chemotherapy and steroids(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In all three of the above cases, the patients developed symptoms while undergoing induction phase of the chemotherapy with severe neutropenia (ANC\u0026thinsp;\u0026lt;\u0026thinsp;0.5). None of them had diabetes or other immunodeficiency conditions apart from their malignancy. All three patients developed rhino-cerebral form of mucormycosis. However, the literature suggests the pulmonary infection is more common in patients with hematological malignancies(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The presentation of these patients which included headache, facial pain and swelling, proptosis, and fever are consistent with the commonest presentations of rhino-cerebral mucormycosis. The diagnosis is mainly by histopathological identification of the organism in tissue samples as the culture often provides no growth(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). One of the above patients revealed histopathological evidence of mucormycosis, cultures were positive in two patients. Further evaluation with CT/MRI imaging is recommended for evaluation of extent of infection. CT is preferred over MRI as it can detect bony erosions. CT or MRI evaluation was done in all three patients which revealed evidence of extent of sinus involvement and spread to adjacent structures like orbits, mandibular region. Polymerase chain reaction (PCR) test, although has shown to be useful in several studies, their utility in clinical practice is not established(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). IV Amphotericin B is the drug of choice for initial treatment. However, early surgical debridement of necrotic tissue has shown to improve survival. Use of endoscopic procedure for debridement and obtaining specimens is particularly noteworthy in the above cases and it has shown to greater accuracy and less operative morbidity(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Delay in diagnosis is a key factor contributing to poor prognosis. Outcome of two of the three patients were remarkable due to early suspicion and initiation of appropriate treatment.\u003c/p\u003e \u003cp\u003eMucormycosis in patients with hematological malignancies presents a severe and often fatal complication, with mortality rates approaching nearly 100%. The primary challenge in managing this infection lies in correcting neutropenia, as the immunocompromised state of these patients significantly impairs their ability to fight off the fungal invasion. Additionally, obtaining adequate diagnostic samples is complicated by the presence of multiple co-morbidities, which can limit invasive procedures and delay timely diagnosis and treatment. Addressing these issues is critical for improving outcomes in this vulnerable population, necessitating a multidisciplinary approach to manage both the underlying malignancy and the opportunistic infection effectively.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe above case series highlights the importance of clinical vigilance and prompt initiation of treatment for mucormycosis upon suspicion in patients with hematological malignancies, particularly those who have severe neutropenia. Endoscopic procedures are useful not only for surgical debridement but also for obtaining tissue samples.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAML\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute myeloid leukemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCentral nervous system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAbsolute neutrophil count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFLAG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efludarabine, cytarabine and filgrastim\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eENT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEar, nose and throat\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGeneral anesthesia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDIC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDisseminated intravascular coagulation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFESS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efunctional endoscopic sinus surgery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCECT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eContrast enhanced computed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolymerase chain reaction.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThe study protocol conformed to the ethical guidelines of the 1975 Helsinki Declaration. In relation to ethical considerations patient\u0026rsquo;s informed written consent was taken to participate and report these cases in an international journal.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to publication\u003c/strong\u003e \u003cp\u003eWritten informed consent was obtained from the patients\u0026rsquo; and/or their relations to publish these case reports and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo particular funding source used for this work.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003ePS (Corresponding Author): Diagnosed and managed patients, and facilitated overall communication among team members at the National Cancer Institute, Maharagama, Sri Lanka. UM (Co-author): Led the team according to the timeline, conducted the literature review, and drafted the manuscript. PN (Co-author): Managed communication with authors and patients, gathered investigation results and contributed to writing the manuscript. NJ, DM, MB, and BS (Co-authors): Specialist team at the National Cancer Institute, Maharagama, Sri Lanka, who contributed to investigating the disease and managing patient care. All authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eStaff of the Hemato-oncology Unit, Department of Histopathology and Department of Microbiology of National Cancer Hospital, Sri Lanka for their dedicated patient care and support given for the authors.\u003c/p\u003e\u003ch2\u003eAvailability of data and material\u003c/h2\u003e \u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analyzed during the current study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePrakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi. 2019;5(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYago MR et al. 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Indian J Pathol Microbiol [Internet]. 2010;53(2):253\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/pubmed/20551527\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/pubmed/20551527\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMillon L, Larosa F, Lepiller Q, Legrand F, Rocchi S, Daguindau E et al. Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin Infect Dis [Internet]. 2013;56(10):e95-101. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/pubmed/23420816\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/pubmed/23420816\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang RS, Hsu CY. Endoscopic sinus surgery for rhinocerebral mucormycosis. Am J Rhinol [Internet]. 1999;13(2):105\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/pubmed/10219438\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/pubmed/10219438\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Rhino-cerebral mucormycosis, Hematological malignancies, Neutropenia, immunocompromised patients, Functional Endoscopic Sinus Surgery","lastPublishedDoi":"10.21203/rs.3.rs-4805516/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4805516/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eRhino-cerebral mucormycosis varies widely in incidence across Europe, from 0.2 to 3 cases per million(1), and is underreported and underdiagnosed in the Indian subcontinent(2). Nonetheless, it is a medical emergency. This infection often arises in patients with hematological malignancies, particularly in patients with neutropenia, leading to multi-organ failure requiring ICU management. Despite intensive care, invasive fungal infections in hematological malignancies often result in poor outcomes(3). This case series details the presentations and unique challenges faced during management in patients with acute myeloid leukemia who developed rhino-cerebral mucormycosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation: \u003c/strong\u003eWe present three cases of rhino-cerebral mucormycosis occurring in patients with acute myeloid leukemia: two females aged 35 and 29, and one male aged 42. Symptoms manifested during chemotherapy induction, with all patients experiencing symptoms suggestive of rhino, orbital or cerebral infection in a background of severe neutropenia (ANC \u0026lt; 0.5). Nasal endoscopy revealed necrotic tissue in all cases, with contrast-enhanced CT confirming invasive fungal infection. Rhizopus species were isolated in cultures from the two female patients, and histopathological evidence of fungal invasion was noted in one. Treatment with Amphotericin B combined with debridement with functional endoscopic sinus surgery (FESS) resulted in survival of two patients, though one succumbed during treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThis case series highlights the importance of clinical vigilance and initiation of early multidisciplinary team management for better clinical outcome in patients with hematological malignancies.\u003c/p\u003e\n\u003cp\u003eEndoscopic procedures are crucial not only for surgical debridement but also for obtaining vital tissue samples for diagnosis. Early, multidisciplinary involvement will significantly improve the outcome of these patients.\u003c/p\u003e","manuscriptTitle":"Rhino-orbital-cerebral mucormycosis in acute myeloid leukemia patients: A case series from Sri Lanka","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-16 01:03:18","doi":"10.21203/rs.3.rs-4805516/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-25T06:48:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-24T14:50:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-19T07:40:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160295797685665557848669520147055030998","date":"2024-09-18T09:55:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-15T08:45:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"251572200667361336566163813880084166960","date":"2024-09-14T07:38:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139223564454266287692913816916744166408","date":"2024-09-14T06:34:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"32806379570479685975657294962364436221","date":"2024-09-13T03:09:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-17T19:59:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"188142197385699493370723873597073185242","date":"2024-08-12T05:55:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"340128299901666185985499823245038521563","date":"2024-08-10T18:22:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-08T18:19:47+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-07T05:28:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-07T01:31:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-07T01:31:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-07-26T05:32:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6394faed-13a2-47ed-825d-ae50a41f76a8","owner":[],"postedDate":"September 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-30T16:05:24+00:00","versionOfRecord":{"articleIdentity":"rs-4805516","link":"https://doi.org/10.1186/s12879-024-10334-y","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2024-12-26 15:57:47","publishedOnDateReadable":"December 26th, 2024"},"versionCreatedAt":"2024-09-16 01:03:18","video":"","vorDoi":"10.1186/s12879-024-10334-y","vorDoiUrl":"https://doi.org/10.1186/s12879-024-10334-y","workflowStages":[]},"version":"v1","identity":"rs-4805516","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4805516","identity":"rs-4805516","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}