1Department of Ear, Nose & Throat, Suliaman Al Habib Hospital, Dubai, UAE; Departments of 2Microbiology and 3Ear, Nose & Throat, Al Zahra Hospital, Dubai, UAE; 4Center of Advanced Research in Medical Mycology, Postgraduate Institute of Medical Education & Research, Chandigarh, India *Corresponding Author’s e-mail: drlevente.deak@gmail.com حالة عدوي بفطر كونيديوبولوس كوروناتوس يف األنف والوجه ظهرت كورم يف داخل األنف ليفنتي ديك، �شافيثا مودالقريييابا، انيلي�س بالن، ديفيد �شاكتون، اآرونالوك �شاكارباتي abstract: Conidiobolomycosis is a rare fungal infection that affects adults in tropical regions. We report a 42-year-old male patient who was referred to the Sulaiman Al Habib Hospital, Dubai, United Arab Emirates (UAE), in 2013 with excessive nasal bleeding and a suspected nasal tumour. He reported having briefly visited central India nine months previously. Computed tomography and magnetic resonance imaging showed a highly vascularised mass in the nasal cavity. However, after surgical excision, initial treatment with amphotericin B deoxycholate was unsuccessful and the disease progressed, leading to external and internal nasal deformation and necessitating further excision and facial reconstruction. Histopathological analysis of the second biopsy revealed Splendore- Hoeppli changes consistent with a fungal infection. Microbiological findings subsequently confirmed Conidiobolus coronatus. Subsequently, the patient was successfully treated with a combination of itraconazole and fluconazole. To the best of the authors’ knowledge, this is the first report of a case of rhinofacial conidiobolomycosis from the UAE. Keywords: Nasal Obstruction; Conidiobolus; Zygomycosis; Antifungal Agents; Case Report; United Arab Emirates. بحالة تقريرا هنا ونقدم املدارية. املناطق يف البالغني وي�شيب احلدوث، نادر داء لالأنف املجاورة واجليوب الأنف ُفَطار داء امللخ�ص: رجل يف 42 من العمر مت حتويله اإىل م�شت�شفى �شليمان حبيب يف دبي بالأمارات العربية املتحدة يف عام 2013م لإ�شابته بنزف اأنفي ويٌر املْقَطِعيٌّ امُلَحو�َشب مفرط، ولل�شك يف اإ�شابته بورم يف الأنف. ذكر املري�س اأنه زار و�شط الهند ملدة ق�شرية قبل ت�شعة اأ�شهر. واأظهر الَت�شْ والرنني املغنطي�شي كتلة غنية بالأوعية الدموية يف التجويف الأنفي. ومتت اإزالة تلك الكتلة جراحيا واأعطى املري�س دواء امفوتري�شني ب ديوك�شي كوليت؛ غري اأن ذلك العالج مل ينجح، وازداد تطور املر�س و�شبب ت�شوها خارجيا وداخليا يف الأنف، مما ا�شتدعى اإجراء عملية ا�شبيلندور- )تغريات َماِنّية جَنْ اأج�شام وجود ثانية خلزعة الهي�شتوباثلوجي الفح�س واأثبت للوجه. ا�ْشِتْبناء وعمل الورم لإزالة جراحية هوبلي( دالة على وجود عدوى فطرية. واأثبتت الختبارات امِلْكروبيولوجية لحقا وجود فطر كونيديوبولوس كوروناتوس. وعقب ذلك عولج املري�س بدوائي اتراكونازول وفلوكونازول. ونح�شب-مبلغ علمنا-اأن هذا التقرير هو اأول تقرير حلالة مري�س م�شاب ب داء ُفَطار الأنف والوجه يف الإمارات العربية املتحدة. الكلمات املفتاحية: ان�شداد اأنفي؛ كونيديوبولو�س؛ فطار عفني؛ دواء م�شاد للفطريات؛ تقرير حالة؛ الإمارات العربية املتحدة. A Rhinofacial Conidiobolus coronatus Fungal Infection Presenting as an Intranasal Tumour *Levente Deak,1 Savitha Mudalagiriyappa,2 Annelyse Ballin,3 David Saxton,1 Arunaloke Chakrabarti4 case report Sultan Qaboos University Med J, November 2018, Vol. 18, Iss. 4, pp. e549–552, Epub. 28 Mar 19 Submitted 30 May 18 Revision Req. 17 Jul 18; Revision Recd. 9 Sep 18 Accepted 27 Sep 18 doi: 10.18295/squmj.2018.18.04.022 First identified in mammals such as horses, dolphins and chimpanzees, Conidiobolus coron- atus is an opportunistic pathogen which causes rhinofacial conidiobolomycosis in humans.1,2 Initially, cases were restricted to areas with tropical and subtr- opical climates; however, due to climate change and modern advances in global travel, the disease can now be found on almost every continent.1 The main symptoms of C. coronatus infections are facial deformation with extensive nasal blockage and bleeding due to the presence of subcutaneous granulomatous lesions.1,3,4 The fungus usually infects healthy male farm workers between 20–60 years old.1,2 In humans, C. coronatus infections likely occur due to inhalation of the fungal spores which imbed into the nasal mucosa; subsequently, as a result of enzymatic activity, they can penetrate into the subcutaneous area of the face as well as the nasal cavity and sinuses.1 Swelling inside the nasal cavity is usually localised to the lower turbinate and nasal mucosa.1,2 More fulminant progression has been reported in immunocompromised hosts, with invasion into the blood vessels; however, in otherwise healthy patients, the infection is non-fatal and localised to the subcutaneous and mucocutaneous tissues.2,5 Case Report A 42-year-old male patient was referred to the Sulaiman Al Habib Hospital, Dubai, United Arab Emirates (UAE), in 2013 with excessive nasal bleeding and a suspected nasal tumour. Nine months previously, the patient had A Rhinofacial Conidiobolus coronatus Fungal Infection Presenting as an Intranasal Tumour e550 | SQU Medical Journal, November 2018, Volume 18, Issue 4 Under general anaesthesia, resectioning of the lower turbinate was performed and a biopsy of the mass and the involved mucosa was taken. Significant bleeding was encountered and controlled by laser vaporisation of the mucosa edges. A fresh frozen section examination of the biopsy suggested a fungal infection; however, a fungal culture did not yield any growth. The patient was there- fore suspected of having aspergillosis. Following extensive nasal debridement, the patient was treated with 2.5 mg/kg/day of intravenous ampho- tericin B deoxycholate and was monitored for all necessary blood parameters. However, after 10 days of treatment, the mass regrew rapidly. A further tissue biopsy and culture were performed, followed by a radical turbinectomy and excision of the mucosa from the floor of the nose together with the mid-portion of the cartilaginous nasal septum. The vestibular skin was also found to be affected and was removed [Figure 2]. The second biopsy was sent for histopathological and microbiological analysis. A haematoxylin and eosin stain of the biopsy specimen showed eosinophilic deposits surrounded by hyphae (i.e. Splendore-Hoeppli phenomenon), while Gram staining showed broad sparsely septate hyphae. The biopsy specimen was cultured using both Sabouraud dextrose Agar (SDA) with chloramphenicol and cyclo- heximide and plain SDA and incubated at 30 °C and 37 °C. After five days of incubation at 30 °C, the plates with the plain SDA medium showed multiple flat, white, glabrous, slightly powdery-to-granular and radially furrowed colonies of mould with several peripheral satellite col- onies [Figure 3]. As these features were highly indicative of a Conidiobolus species, the lid of the plate was secured with a thermoplastic self-sealing film to prevent cont- agion (Parafilm®, Bemis Co. Inc., Neenah, Wisconsin, USA). In addition, a lactophenol cotton blue stain prep- aration showed broad hyaline sparsely septate hyphae with a few spherical conidia with hair-like appendages (i.e. villae), also characteristic of a Zygomycetes species. The cultured fungus was sent for molecular ident- ification and antifungal susceptibility testing at a reputable visited central India for a few days; subsequently, three months after returning to the UAE, he had noticed swelling and tenderness above his nasal dorsum, with progressive nasal blockage. Six months later, he developed recurrent epistaxis, resulting in admission to another healthcare facility. However, following failed convent- ional management, he was referred to the Sulaiman Al Habib Hospital. Upon physical examination, there was thickening of the right nasal vestibule as well as occlusion of the nasal cavity due to highly vascularised granulomatous tissue growth involving the right inferior turbinate, the floor of the nasal cavity and the right side of the nasal septum. No airway could be established, despite the administration of xylometazoline as a decongestant. In addition, the left nasal cavity was narrowed due to a deviated septum. The nasal mucosa was intact and the nasal dorsum was slightly tender and widened. The patient was otherwise in good health with no evidence of underlying disease. Computed tomography and magnetic resonance imaging scans of the nose and paranasal sinuses revealed a highly vascularised mass occupying the entire nasal cavity. The sinuses were intact without bony erosion or extension to the adjacent anatomical areas [Figure 1]. Figure 2: Endoscopic photograph of the nasal cavity of a 42-year-old male patient showing the spread of a highly vascularised mass to both the nasal mucosa and vestibular skin, indicating subcutaneous fat involvement. NS = nasal mucosa; VS = vestibular skin. Figure 1: Imaging of a 42-year-old male patient with excessive nasal bleeding and a suspected nasal tumour. A & B: Computed tomography scans confirming the intact nasal bony wall (arrows). C: Magnetic resonance imaging showing increased T2 signals in the nasal cavity alone (arrow), without intracranial spread or extension to the sinuses. Levente Deak, Savitha Mudalagiriyappa, Annelyse Ballin, David Saxton and Arunaloke Chakrabarti Case Report | e551 Discussion As in the current case, most published reports of rhino- facial C. coronatus infections have occurred in males with normal immune status who have recently travelled to a tropical region.5,9–11 Overall, very few cases of rhinofacial C. coronatus infections have been reported in the liter- ature; as such, early identification of the organism remains challenging.1,3,4 To the best of the authors’ knowledge, the current case is the first report of a patient with rhinofacial conidiobolomycosis from the UAE. The diagnosis of a C. coronatus infection is based on a tissue biopsy in which eosinophilic deposits surr- ounding the hyphae can be seen (i.e. Splendore-Hoeppli phenomenon).1,2 However, physicians often face diffic- ulties in obtaining a positive culture in order to dem- onstrate antimicrobial susceptibility; as such, the disease has a high morbidity and mortality rate.1,2,9,12 Currently, there is no standard recommended therapy for conidiobolomycosis cases. Generally, treatment ranges from conservative options to the radical resect- ioning of infected tissues, with approaches varying according to individual cases and local drug resistance patterns.1,4,13,14 In the current case, the initial culture was negative and histopathologically misdiagnosed as aspergillosis. Following disease progression and unsucc- essful treatment with amphotericin B deoxycholate, the patient required extensive surgical debridement. At this point, a repeated culture confirmed a diagnosis of a C. coronatus infection and a detailed antifungal susceptib- ility profile was established. The patient was then success- fully treated with prolonged combination therapy involving itraconazole and fluconazole. Other researchers have reported similar success using potassium iodide, trimethoprim/sulfamethoxazole, amphotericin B, ketoconazole and itraconazole, either individually or in combination.1,3,15,16 Blumentrath et al. proposed a treatment strategy according to stages of disease progression; based on these classifications, the current case would be considered intermediate due to the incubation period and vestibular skin involvement and a surgical approach would not be recommended.17 However, the current patient had non-responsive bleeding and a blocked airway; as such, his quality of life immed- iately improved following surgical debridement. Conclusion Due to climate change and increasing global travel, rhino- facial C. coronatus infections are no longer restricted to tropical regions. However, successful management of such cases remains challenging due to the low laboratory affiliated with the Postgraduate Institute of Medical Education & Research, Chandigarh, India. Mol- ecular typing and an antifungal susceptibility profile was performed as per standard methods and the recomm- endations of the Clinical & Laboratory Standards Inst- itute (CLSI).6–8 Briefly, the macrobroth was diluted according to M61 CLSI standards and a final concentr- ation of 3.5 × 102 colony forming units/mL was used as the inoculum, before being incubated at 35 °C for 48 hours.8 Based on these findings, the fungus was identified to be C. coronatus. As per the antifungal susceptibility profile, oral anti- fungal treatment was initiated with 200 mg/day of itra- conazole combined with 100 mg/day of fluconazole [Table 1]. After six months of treatment, only a small granulomatous lesion remained which was subseq- uently removed under local anaesthesia. The nasal def- ormation resulting from the nostril retraction was corrected with a skin flap rotation procedure. The prev- iously noted enlargement of the nasal dorsum reduced without the need for surgical intervention. Antifungal therapy was continued for a total of 18 months. There was no sign of disease recurrence at a three-year follow-up. Table 1: Antifungal susceptibility profile of a cultured fungus identified as Conidiobolus coronatus Antifungal agent MIC in µg/mL Amphotericin B deoxycholate 2 Voriconazole >16 Itraconazole >16 Posaconazole >16* Caspofungin >64 Anidulafungin 8 Micafungin >8 MIC = minimal inhibitory concentration. *80% inhibition at 4 µg/mL. Figure 3: Photograph of a nasal mass culture showing multiple, flat, white, glabrous, slightly powdery-to-granular and radially furrowed colonies of fungus with several peri- pheral satellite colonies. A Rhinofacial Conidiobolus coronatus Fungal Infection Presenting as an Intranasal Tumour e552 | SQU Medical Journal, November 2018, Volume 18, Issue 4 7. Gil-Lamaignere C, Roilides E, Hacker J, Müller FM. Molecular typing for fungi: A critical review of the possibilities and lim- itations of currently and future methods. Clin Microbiol Infect 2003; 9:172–85. https://doi.org/10.1046/j.1469-0691.2003.00649.x. 8. Clinical and Laboratory Standards Institute. M61: Performance standards for antifungal susceptibility testing of filamentous fungi, 1st edition. From: https://clsi.org/standards/products/mi crobiology/documents/m61/ Accessed: Sep 2018. 9. Gonzalez CE, Rinaldi MG, Sugar AM. Zygomycosis. Infect Dis Clin North Am 2002; 16:895–914. https://doi.org/10.1016/S0 891-5520(02)00037-5. 10. Yang X, Li Y, Zhou X, Wang Y, Geng S, Liu H, et al. Rhinofacial conidiobolomycosis caused by Conidiobolus coronatus in a Chinese rice farmer. Mycoses 2010; 53:369–73. https://doi.org/ 10.1111/j.1439-0507.2009.01716.x. 11. Moncada DC, Montes M, Molina V, Velásquez JB, Gómez CI. Orofacial infection by Conidiobolus coronatus. Biomedica 2016; 36:15–22. https://doi.org/10.7705/biomedica.v36i2.2806. 12. Gilbert EF, Khoury GH, Pore RS. Histopathological ident- ification of Entomophthora phycomycosis: Deep mycotic inf- ection in an infant. Arch Pathol 1970; 90:583–7. 13. Kimura M, Yaguchi T, Sutton DA, Fothergill AW, Thompson EH, Wickes BL. Disseminated human conidiobolomycosis due to Conidiobolus lamprauges. J Clin Microbiol 2011; 49:752–6. https://doi.org/10.1128/JCM.01484-10. 14. Fischer N, Ruef Ch, Ebnöther C, Bächli EB. Rhinofacial Conidiobolus coronatus infection presenting with nasal enlar- gement. Infection 2008; 36:594–6. https://doi.org/10.1007/s15 010-008-8056-5. 15. Cherian LM, Varghese L, Panchatcharam BS, Parmar HV, Varghese GM. Nasal conidiobolomycosis: A successful treat- ment option for localized disease. J Postgrad Med 2015; 61:143–4. https://doi.org/10.4103/0022-3859.153112. 16. Mukhopadhyay D, Ghosh LM, Thammayya A, Sanyal M. Entomophthoromycosis caused by Conidobolus coronatus: Clinicomycological study of a case. Auris Nasus Larynx 1995; 22:139–42. https://doi.org/10.1016/S0385-8146(12)80113-1. 17. Blumentrath CG, Grobusch MP, Matsiégui PB, Pahlke F, Zoleko-Manego R, Nzenze-Aféne S, et al. Classification of rhinoentomophthoromycosis into atypical, early, intermediate, and late disease: A proposal. PLoS Negl Trop Dis 2015; 9:e0003984. https://doi.org/10.1371/journal.pntd.0003984. incidence of the disease, difficulties in confirming the diagnosis and the lack of established treatment strategies. 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