Flesh-Eating Dual-Oral Fungal Infection 1Jobin Mathew, 2Siji Chiramel, 3E Anuradha Sunil, 4TR Ramna, 5Sadiya RV, 6Archana Nair

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Jobin Mathew et al 10.5005/jp-journals-10037-1078 Case Report

Flesh-eating Dual-oral Fungal Infection 1Jobin Mathew, 2Siji Chiramel, 3E Anuradha Sunil, 4TR Ramna, 5Sadiya RV, 6Archana Nair

ABSTRACT mucorales. These fungi are seen in soil containing decay- Context: Mucormycosis is a rare acute opportunistic fungal ing organic matter. Rhizopus oryzae (Rhizopus arrhizus), infection with a high mortality rate. It is commonly seen in a member of the family, is the chief offender although immunocompromised individuals. other members of the family like Rhizopus microspores, Aims: Oral manifestation of mucormycosis is rare. When it Rhizomucor pusillus, Mycocladus corymbifer, Apophysomyces does occur, it commonly affects the palate followed by alveolus. elegans can cause similar infections.3,4 Settings and design: The representative tissue received was Route of exposure may be by inhalation of fungal × 10% formalin fixed, 3 3 cm in diameter, and floated on the spores or by direct contact through skin.5 surface of the fixative. Materials and methods: Sections of 5 microns thick were CASE REPORT obtained from paraffin-embedded tissues that were processed and stained with hematoxylin and eosin, periodic acid-Schiff, A 55-year-old male patient presented with a complaint and Gomori methenamine stains. of inability to eat food normally for the past 3 months Conclusion: Examination of paraffin-embedded sections together with pain and numbness over the right eye since showed broad aseptate fungal hyphae branching at 90° 2 months. Extraoral examination revealed a 0.8 × 0.7 cm together with Candida pseudohyphae and yeast forms along with necrotic bone. skin nodule along the lateral canthus and periorbital edema of the right eye (Fig. 1). Intraoral examination Keywords: Aseptate fungal hyphae, Gomori methenamine stain, Mucormycosis, Periodic-acid schiff. showed a grayish necrotic mass extending along the posterior left maxillary facial alveolar ridge with an oro- How to cite this article: Mathew J, Chiramel S, Sunil EA, Ramna TR, Sadiya RV, Nair A. Flesh-eating Dual-oral Fungal antral communication in relation to 17, 18 (Fig. 2). Pus Infection. Oral Maxillofac Pathol J 2016;7(2):730-733. discharge and pain secondary to infection was noted. Source of support: Nil Medical history revealed uncontrolled type 2 diabetes Conflict of interest: None mellitus for which he was being treated, chronic alcoholic liver disease, cirrhosis of liver with mild chronic kidney INTRODUCTION disease, ischemic heart disease, hypertension, and a past history of pulmonary tuberculosis. Routine blood exami- Mucormycosis is an acute life-threatening opportunistic nation showed an elevated erythrocyte sedimentation fungal infection with a high mortality rate, occurring rate (ESR), increased fasting blood sugar levels, a reduced 1 predominantly in dehydrated and acidotic patients. hemoglobin count, a decreased neutrophil count, and an Mucormycosis, zygomycosis, or phycomycosis was first elevated serum albumin level, thereby confirming the 2 described by the German pathologist Paulltauf in 1885. compromised state of the liver and the kidney. Culture of Along with Candidiasis, it is the most common fungal necrotic bone was done. Strict aseptic precautions were infection of the oral cavity seen in debilitated patients with diabetic mellitus, neutropenia, immunosuppres- sive therapy, deferoxamine use associated dialysis, leukemia, lymphoma, renal failure, liver cirrhosis, etc. Mucormycosis is caused by fungi under the order

1,4,5Postgraduate Student, 2,3Professor, 6Senior Lecturer 1,3-6Department of Oral and Maxillofacial Pathology, Royal Dental College, Chalissery, Kerala, India 2Department of Dentistry, Amala Institute of Medical Sciences Thrissur, Kerala, India Corresponding Author: Jobin Mathew, Postgraduate Student Department of Oral and Maxillofacial Pathology, Royal Dental College, Chalissery, Kerala, India, e-mail: mathew. [email protected] Fig. 1: Extraoral view 730 OMPJ

Flesh-eating Dual-oral Fungal Infection maintained during the incision biopsy of the specimen. lymphocytes with isolated colonies of fungal hyphae Hematoxylin and eosin (H&E) staining of the specimen (Figs 3 to 5). These hyphae were broad, with nonparallel showed necrotic stroma with an intense inflammatory sides and irregular branching at 90°. Yeast forms were also infiltrate comprising neutrophils, plasma cells, and noted together with some necrotic bone (Figs 6 and 7).

Fig. 2: Intraoral view Fig. 3: Necrotic Stroma with an intense inflammatory infiltrate comprising of neutrophils, plasma cells and lymphocytes (H&E 100×)

Fig. 4: Isolated colonies of fungal hyphae (H&E 100×) Fig. 5: Asptate Fungi branching at 90º of mucor species (H&E 100×)

Fig. 6: Broad asptate fungi branching at 90° of mucor species Fig. 7: Broad asptate fungal hyphae with fungal spore along and yeast form of candida (H&E 100×) with necrotic bone (H&E 100×) Oral and Maxillofacial Pathology Journal, July-December 2016;7(2):730-733 731 Jobin Mathew et al

Fig. 8: Gomori methylamine silver staining for mucor species Fig. 9: PAS staining for candida species (100×) (100×)

Special stains, such as Gomori methenamine silver into the human body is through the respiratory tract. staining confirmed the presence of a Mucor species The most common symptom of mucormycosis infection whereas the periodic acid-Schiff (PAS) staining confirmed is fever, occurring in 51% of patients. Based on clinical Candida species (Figs 8 and 9). Ziehl–Neelsen staining presentation, this infectious disease can be randomly was negative, thus ruling out tuberculosis. Culture result divided into separate entities: Rhinocerebral, pulmo- of Sabouraud-Chloramphenicol-Gentamicin agar for nary, cutaneous, gastrointestinal, central nervous system 2 days at 30° was suggestive of fungal infection. A final related, and miscellaneous, in addition to a disseminated diagnosis of mixed fungal infection with mucormycosis disease resulting from progression of localized infection. and Candidiasis was made. Rhinocerebral mucormycosis is the most common form of 7,8 Computed tomography scan of facioaxial and coronal mucormycosis in patients with diabetes mellitus. The view showed osteolysis of the bilateral zygomaticomaxil- various clinical entities of mucormycosis are tabulated lary complexes to the orbital floor, thereby indicating its in Table 1. destruction. Patient was put on liposomal amphotericin B The predisposing conditions for being infected by this fungus include neutropenia or neutrophil dysfunc- 30 mg/kg. Deteriorating liver and renal functions pre- tion, malignancy, and desferrioxamine mesilate therapy.9 vented surgery. Local debridement of involved maxilla Roden et al showed that diabetic patients represented 36% under local anesthesia was done. Fifteen days of hospital of 929 reported cases. Early studies by Chinn et al and stay helped recovery of the patient who is currently under Artis et al have proven that diabetic ketoacidosis impairs follow-up. chemotactic and phagocytic activity of neutrophils and 10 DISCUSSION increases the availability of serum iron. Hyperglycemia and acidosis are known to impair the The incidence of mucormycosis in diabetic patients is ability of phagocytes to move toward the organisms and increasing.6 Mucor belongs to the class Zygomycetes, kill them by oxidative and nonoxidative mechanisms. a ubiquitous fungus whose commonest route of entry This patient had a serious localized rhinomaxillary

Table 1: Various clinical entities of mucormycosis Clinical type and Rhinocerebral Pulmonary Cutaneous Disseminated Gastrointestinal Miscellaneous prevalence 44–49% 10–11% 10–16% 6–11% 6–7% 5% CNS type Predisposing factor Uncontrolled Leukemia, Cases of burns Pulmonary Malnourished Intravenous drug diabetic patients receiving mucormycosis children abusers chemotherapy Clinical feature Periorbital Dyspnea, Cutaneous and Focal Nausea and Virtually any body cellulitis and cough, and subcutaneous neurological vomiting are the site facial numbness, chest pain necrotizing deficits or coma most common conjunctival fasciitis symptoms. Fever suffusion, blurry and hematochezia of vision intraabdominal abscess

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Flesh-eating Dual-oral Fungal Infection form of mucormycosis. Early diagnosis and treatment REFERENCES are of extreme importance for successful eradication of 1. Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on infection and for patient survival. The Grocott-Gomori mucormycosis: pathophysiology, presentation, and manage- methenamine silver stain is the most effective for iden- ment. Clin Microbiol Rev 2005 Jul;18(3):556-569. tifying fungi.11-13 However, hematoxylin and eosin, 2. Paulltauf A. Mycosis mucorina. Virchows Arch Pathol Anat periodic-acid Schiff, or calcofluor white stains may also 1885;102:543-564. 3. Lunge SB, Sajjan V, Pandith AM, Patil VB. Rhinocerebro- be used. The fungi observed are nonseptate hyphae cutaneous mucormycosis caused by mucor species: a rare cau- with a right-angled branching. Because initial cultures sation. Indian Dermatol Online J 2015 May-Jun;6(3):189-192. of diseased tissue may be negative, histopathological 4. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, examination is essential for early diagnosis. The initial Kontoyiannis DP. Epidemiology and clinical manifestations of medical treatment of mucormycosis comprises aggres- mucormycosis. Clin Infect Dis 2012 Feb;54 (Suppl 1):S23-S34. 5. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, sively treating any underlying predisposing factors Sarkisova TA, Schaufele RL, Sein M, Sein T, Chiou CC, Chu JH, like diabetes followed by surgical management. In et al. Epidemiology and outcome of zygomycosis: a review of some cases, radical resection may be required includ- 929 reported cases. Clin Infect Dis 2005 Sep 1;41(5):634-653. ing partial or total maxillectomy, mandibulectomy, and 6. Chinn RY, Diamond RD. Generation of chemotactic factors by orbital exoneration. Debridement of all infected tissues Rhizopus oryzae in the presence and absence of serum: rela- tionship to hyphal damage mediated by human neutrophils should also be done.14 and effects of hyperglycemia and ketoacidosis. Infect Immun Hyperbaric oxygen therapy (HBO) has been consid- 1982 Dec;38(3):1123-1129. ered as a mode of treatment but retrospective study has 7. Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, Lagrou K, shown no significant difference between the effectiveness Lass-Florl C, Bouza E, Klimko N, Gaustad P, et al. Zygomycosis of therapy with and without HBO.15,16 in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin CONCLUSION Microbiol Infect 2011 Dec;17(12):1859-1867. Probability of fungal infection should always be consid- 8. Pagano L, Ricci P, Tonso A, Nosari A, Cudillo L, Montillo M, Cenacchi A, Pacilli L, Fabbiano F, Del Favero A. Mucormycosis ered in cases of diabetes mellitus. Diagnosis should be in patients with hematological malignancies: a retrospective based mainly on clinical manifestation and morphologi- clinical study of 37 cases. Br J Haematol 1997 Nov:99(2): cal findings of Mucor hyphae in the tissue specimen. As 331-336. mortality rate is 50 to 70%, early detection of the organism 9. Tugsel Z, Sezer B, Akalin T. Facial swelling and palatal ulcer- is imperative to institute timely surgical and antifungal ation in a diabetic patient. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004 Dec;98(6):630-636. treatment. 10. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000 Apr;13(2):236-301. PATIENT CONSENT 11. Sujatha RS, Rakesh N, Deepa J, Ashish L, Shridevi B. Rhino cerebral mucormycosis. A report of two cases and review of Verbal informed consent was obtained from the patient literature. J Clin Exp Dent 2011;33(3):e256-e260. for publication of this case report and accompanying 12. Dhiwakar M, Thakar A, Bahadur S. Improving outcomes in images. rhinocerebral mucormycosis – early diagnostic pointers and prognostic factors. J Laryngol Otol 2003 Nov;117(11):861-865. AUTHORS’ CONTRIBUTIONS 13. Khor BS, Lee MH, Leu HS, Liu JW. Rhinocerebral mucormycosis in Taiwan. J Microbiol Immunol Infect 2003 Dec;36(4): The oral surgeon performed the surgical debridement of 266-269. the lesion. The two authors have contributed in analyzing, 14. Lador N, Polacheck I, Gural A, Sanatski E, Garfunkel A. A trifungal infection of the mandible: case report and literature reading, writing, and researching this article. review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006 Apr;101(4):451-456. ACKNOWLEDGMENTS 15. Ferguson BJ, Mitchell TG, Moon R, Camporesi EM, Farmer J. Adjunctive hyperbaric oxygen for treatment of rhinocerebral Authors would like to thank the Principal and staff of mucormycosis. Rev Infect Dis 1998 May-Jun;10(3):551-559. Department of Oral Pathology of the institution for kindly 16. Kajs-Wyllie M. Hyperbaric oxygen therapy for rhinocerebral guiding us in writing this article. fungal infection. J Neurosci Nurs 1995 Jun;27(3):174-181.

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