Mucormycosis of Maxilla Following Tooth Extraction in Immunocompetent Patients: Reports and Review

J Clin Exp Dent. 2018;10(3):e300-5. Nilesh; Mucormycosis of maxilla

Journal section: Oral Surgery doi:10.4317/jced.53655 Publication Types: Case Report http://dx.doi.org/10.4317/jced.53655

Mucormycosis of maxilla following tooth extraction in immunocompetent patients: Reports and review

Kumar Nilesh 1, Aaditee V. Vande 2

1 MDS. (Oral & Maxillofacial Surgery), Professor, Department of Oral & Maxillofacial Surgery, School of Dental Sciences, KIMSDU, Karad, India 2 Post-graduate student, Department of Prosthodontics, School of Dental Sciences, KIMSDU, Karad, Maharashtra, India

Correspondence: Dept. of Oral & Maxillofacial Surgery School of Dental Sciences, Krishna Hospital Nilesh K, Vande AV. Mucormycosis of maxilla following tooth extrac- Karad, Satara 415110, Maharashtra, India tion in immunocompetent patients: Reports and review. J Clin Exp Dent. [email protected] 2018;10(3):e300-5. http://www.medicinaoral.com/odo/volumenes/v10i3/jcedv10i3p300.pdf

Received: 13/12/2016 Accepted: 17/02/2018 Article Number: 53655 http://www.medicinaoral.com/odo/indice.htm © Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488 eMail: [email protected] Indexed in: Pubmed Pubmed Central® (PMC) Scopus DOI® System

Abstract Mucormycosis is a rare, fulminant, rapidly spreading fungal infection, which usually affects patient with underlying immune deficiency. If not managed promptly, the disease is characterized by progressive necrosis and is often fatal. A review of English literature shows that only fourteen cases of mucormycosis have been reported after tooth extraction. This paper highlights two cases of mucormycosis subsequent to tooth extraction in healthy adult patients. This first patient presented with an oroantral fistula and extensive maxillary necrosis. Whereas the second case was localized and presented as non-healing extraction socket with alveolar necrosis. This adds two more cases of this rare and serious complication of tooth extraction, to the present literature.

Key words: Fungal, infection, zygomycosis, exodontia, complication, jaw, necrosis.

Introduction and disseminated (2). Oral mucormycosis is usually cau- Mucormycosis is a rare opportunistic infection invariably sed by inhalation of spores or direct contamination of affecting immunocompromised patients. The organism open oral wound. Oral mucormycosis affecting immu- implicated to cause mucormycosis is a saprophytic fungus, nocompromised patients, mainly diabetes mellitus has mainly rhizopus or mucor. It is the most deadly and rapidly been reported in literature (3). However those occurring progressive form of fungal infection affecting humans (1). subsequent to tooth extraction are rare (4). In view of Clinical presentation of mucormycosis depends upon the serious and potentially fatal complication of tooth the site of entry of micro-organism and the organ sys- extraction, this paper reports two such cases of mucor- tems involved. The most common form includes rhi- mycosis presenting as oroantral fistula and non-healing nocerebral, which involve the nose, paranasal sinuses, extraction socket respectively, in healthy adult patients. orbits and central nervous system. Other forms of mu- The findings of the present cases are correlated with pre- cormycosis are cutaneous, gastrointestinal, pulmonary viously reported cases in English literature.

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Case Report antifungal therapy (amphotericin B; 0.8mg/kg/day for Case Report 1: 4 weeks) was immediately started after serum urea and A 52 years old male patient, farm labourer by occupation creatinine levels were found to be within normal range. presented with complaint of escape of fluid from nose Routine blood investigations, including serum glucose after taking liquids and foul smell from mouth since past and complete haemogram showed no deranged values. one week. Patient gave history of multiple teeth extrac- Laboratory examination revealed no underlying immune tion one month earlier at a local private clinic. No con- deficiency. tributory medical and family history was reported. In- The patient was subjected to computed tomography traoral examination revealed an area of dehiscence over (CT) scan in order to study the extent and location of left maxillary alveolus with an oroantral fistula (Fig. 1a). disease. Sectional views of CT scan showed thickening of left maxillary antrum lining, with destruction of anterior maxillary wall (Fig. 2a). Three dimensional forma-

Fig. 1: [Case 1] (Clinical presentation of the disease as oroantral fistula (a); Water’s view radiograph showing involvement of left maxillary sinus (b). Photomicrograph (H & E stained section; 40X magnification) showing broad and aseptate fungal hyphae with area Fig. 2: [Case 1] CT scan (axial section) showing thickening of antral of necrosed bone (c). lining and destruction of anterior wall of maxilla (a); Three dimensional formatted CT image showing involvement of left maxilla (b). Intraoperative pictures showing surgical debridement and removal of the sequestrum with the buccal fat pad mobilized into the defect Escape of water from left nostril after oral intake was (arrow) (c); closure of the oroantral communication (d). demonstrated clinically. The left maxillary premolars and 1st molar were missing, confirming the history of previous extraction. Water’s view radiograph was advi- tted CT image showed destruction of anterior maxillary sed to study the maxilla and the maxillary antrum. The wall extending antero-posteriorly from the lateral nasal radiograph showed destruction of left maxillary bone wall to the zygomatic bone and supero-inferiorly from extending superiorly to the infraorbital rim and latera- the maxillary alveolus to just below the infraorbital rim. lly to the zygomatic bone. Areas of radiopacity were Area of loose bone was seen within the lesion suggestive evident within the left maxillary antrum, suggestive of of bony sequestrum (Fig. 2b). sequestrum (Fig. 1b). Based on the clinical and radiolo- Patient was prepared for surgical debridement and se- gical findings the diagnosis of maxillary osteomyelitis questrectomy along with closure of oroantral fistula, causing oroantral fistula was given. Gingival and bone under general anesthesia. A written informed consent incision biopsies were taken for histopathological study. was taken for the same. Buccal mucoperiosteal flap was The microscopic evaluation revealed broad and aseptate raised after excision of the fistula lining. The maxillary fungal hyphae within the area of necrosed bone (Fig. 1c). bone was exposed and the sequestrum removed. Debri- Based on the findings, a final diagnosis of maxillary os- dement of maxillary antrum was done to remove the in- teonecrosis secondary to mucormycosis was established. flamed sinus lining, followed by copious irrigation with Patient was recalled for hospitalization and intravenous antiseptic solution. Pedicled buccal fat pad was mobi-

e301 J Clin Exp Dent. 2018;10(3):e300-5. Nilesh; Mucormycosis of maxilla lized by blunt dissection and used to close the defect for the same. The excised specimen was submitted for posteriorly. The buccal mucoperiosteal flap was then histopathological evaluation. Microscopic study of the advanced palatally over the buccal fat pad to attain two necrotic alveolar bone showed presence of broad asep- layered closure of oroantral communication (Fig. 2c,d). tate, thin walled fungal hyphae (Fig. 3d). Based on the The patient showed uneventful recovery and was kept presentation and histological findings, diagnosis of oral on regular recall visits. At 6 months follow-up patient mucormycosis subsequent to tooth extraction was given. did not show any further progression of the disease. Patient was admitted and put on intravenous antifungal Case Report 2: therapy (amphotericin B; 0.8mg/kg/day for 3 weeks). A 37 years old male patient reported to our clinic with Periodic monitoring of serum urea, creatinine and re- complaint of pain over upper right posterior region of nal function test were done, during antifungal therapy. jaw since past 2 weeks. Patient gave history of extrac- There was no further progression of the disease and on tion of right upper right molars about six weeks back at four month follow-up visit patient showed satisfactory a private dental clinic. The extraction was non-traumatic healing. and the immediate post-extraction period was uneventful. No contributory medical and family history was re- Discussion ported. Intraoral examination showed dehiscence of mu- Mucormycosis is a rare opportunistic fungal infection cosa over right maxillary alveolus. The crestal alveolar caused by mucorales. It was first reported in humans by bone was exposed and appeared yellowish-white with no Paultaufin in 1885 (2). It is also known as zygomyco- bleeding on probing (Fig. 3a). Orthopantomogram was sis or phycomycosis. Three common genera of mucora- advised, which showed missing mandibular right poste- le which cause this disease in human include rhizopus, rhizomucor and absidia. Rhizopus accounts for 90% of cases involving head and neck region. These fungi exist in natural environment including soil, air, food, compo- site piles, and animal excreta and play role in decompo- sition. These fungal spores may be inhaled, ingested or may enter human body through open wound. Mucorales have been cultured from the oral cavity, nasal passage and pharynx of healthy individuals without any clinical signs of infection. Invariably this disease manifests, when the organisms affect an immunocompromised patients. Angioinvasion of mucorales and its spores into the blood vessels lead to the formation of thrombus, which causes progressive necrosis of associated hard and soft tissues. The most common form of this disease in maxillofacial region is rhinocerebral mucormycosis, with widespread involvement of oral cavity, maxilla, palate, nose, para- Fig. 3: Case 2] Clinical presentation as necrosed alveolar bone at site of extraction (a); Orthopantamogram showing of the involved region nasal sinuses, orbits and central nervous system. Early (b). Intra-operative photograph showing closure of the surgical site symptoms of this disease include facial cellulitis, perior- after removal of the necrosed alveolar bone (inset image) (c). Photo- bital edema and nasal inflammation, followed by- wi micrograph (H & E stained section; 100X magnification) showing despread tissue necrosis. Failure of prompt medical and aseptate, thin walled fungal hyphae with irregular contour (d). surgical intervention may lead to cerebral spread, caver- nous sinus thrombosis, septicemia and multiple organ rior teeth, with empty extraction sockets, indicative of failure lending to high morbidity and mortality (3). The recent extraction. The floor of the right maxillary sinus, cases reported in this paper presented with a localized in-relation to the apical aspect of the extraction sockets form of oral mucormycosis affecting immunocompetent could not appreciated (Fig. 3b). Routine blood investiga- patients, after tooth extraction. tions were within normal limit. No underlying immune Search of English literature from PubMed database, deficiency was evident on laboratory examination. Pa- using combination of terms; mucormycosis, zygomyco- tient was prescribed oral antibiotics (Tablet Amocicillin sis, extraction, exodontia, and maxillary necrosis revea- 500mg + Potassium Clavulanate 125 two times a day) led 34 titles, of which only eight cases were reported to and nasal decongestant. Excision of the necrosed alveo- be associated with tooth extraction. References of these lar bone with closure of the defect with buccal advance- papers were further scrutinized and additional five titles ment flap was planned and executed under local anes- were identified. In total 13 papers (total of 14 cases) thesia (Fig. 3c). A written informed consent was taken on mucormycosis secondary to tooth extraction were

e302 J Clin Exp Dent. 2018;10(3):e300-5. Nilesh; Mucormycosis of maxilla reviewed for demographic details, clinical presentation, across the globe involving both developed and develo- extent of involvement, treatment provided and outcome ping countries can be explained by relative lack of me- (Table 1, 1 continue) (4-16). These cases were reported dical health care facility and more number of immuno- from all over the world, with 7 cases (50%) from India compromised patients in developing countries like India. and 2 cases (14%) from USA. This unique distribution Whereas reports from developed country like USA can

Table 1: Review of previously reported cases of mucormycosis after tooth extraction.

Author & year Country Age Underling History of Clinical Extent of Management Outcome /sex disease extraction presentation involvement on imaging Kim J.; 20014 USA 57/M DM Maxillary right Cellulitis, Left maxilla, Surgical debridement, Fa 1st molar, left periorbital odema maxillary, bilateral endoscopic 2nd & 3rd molars (left face); ethmoidal & ethmoidectomy, bilateral chemosis, ptosis, frontal sinus, maxillary and left frontal proptosis, orbit, parotid, sinusotomy; IVAB ecchymosis, zygoma, ophthalmoplegia, supraorbital and and loss of vision frontal region (left eye). Fogarty C.; USA 74/M COPD Multiple Non healing Left maxilla, Low level maxillectomy; Fa 20065 (treated maxillary teeth extraction site, inferior zygoma, IVAB with Alveolar necrosis, nasal septum, steroid) purulent discharge pterygoid plate from nose Bakathir A; Oman Case Leukemia Maxillary right Pain at extraction Right maxillary Surgical debridement with Sh 20066 1: (chemothe premolar site, nasal sinus, nose and partial maxillectomy and 14 /M rapy) Mandibular blockage ethmoid FESS; IVAB right 1st molar Surgical debridement; Sh Non healing Mandible alveolar IVAB extraction socket bone Case DM & Mandibular Pain and necrosis Mandible Surgical debridement; Sh 2: Leukemia right 2nd molar at extraction site IVAB 49/M with lower lip paresthesia Auluck A.; India 58/M DM Maxillary right Painful non- Maxillary Excision of necrotic bone; Sh 20077 1st, 2nd & 3rd healing extraction alveolus and right IVAB molars site, nasal maxillary sinus congestion and headache Papadogeorgaki Greece 22/F DM Maxillary right Facial edema, Paranasal sinus on Subtotal maxillectomy Sh s N.; 20108 3rd molar pain and double right side followed by obturator; vision IVAB and posaconazole Kumar JA.; India 65/M DM Multiple Pain and difficulty Maxillary NA NA 20139 maxillary teeth on taking food, alveolus, palate necrosis of and right alveolar bone and maxillary sinus palate Choudhary P.; India 48/F NIC Maxillary left Pain in upper left Maxillary NA NA 201410 3rd molar jaw, ear & nose alveolus, palate, blockage left maxillary sinus and nose Nilesh K.; India 72/M NIC Left maxillary Escape of fluid Left maxillary Surgical debridement, Sh 201511 molars through nose alveolus and closure of OAC; Oral (OAC) maxillary sinus antifungal therapy (posaconazole) Motaleb H.; Egypt 57/F DM Maxillary right Diffuse painful Right maxilla, Surgical debridement; Fa 201512 posterior teeth swelling of right nasal cavity, IVAB face, chemosis, frontal and palatal necrosis ethmoidal sinus Kumar N.; India 63/F DM Maxillary Pain in upper jaw, Left maxillary Surgical debridement; Sh 201513 anterior teeth nasal congestion, sinus and maxilla IVAB headache, necrosis of anterior maxilla Arya A.; 201514 India 54/M DM, Maxillary right Fluid discharge Bilateral Surgical debridement NA

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Table 1 continue: Review of previously reported cases of mucormycosis after tooth extraction. Psoriasia posterior teeth through nose, maxillary & With maxillary obturator; on topical non-healing sphenoid sinuses, IVAB & oral antifungal steroid extraction socket, right maxilla, therapy (voriconazole) palatal necrosis, bilateral nasal epiphora of eyes cavity, ethmoidal air cells and pterygoid. Laihad F.; Indonesia 46/F NIC Maxillary left Painful swelling NA HBO therapy Sh 201515 2nd premolar of left face, difficulty in swallowing, facial paresthesia, trismus Selvamani M.; India 52/M DM Maxillary right Painful swelling Right maxillary Surgical debridement with NA 201516 3rd molar of right face, sinus and anterior anterior maxillectomy; water discharge palate IVAB through nose Present report India Case NIC Maxillary left Escape of fluid Left maxilla and Surgical debridement, Sh 1: premolars & 1st through nose maxillary sinus closure of OAC 52/M molar (OAC) Case NIC Maxillary right Pain at extraction Maxillary alveolar Surgical debridement & Sh 2: 2nd premolar, site bone primary closure 37/M 1st, 2nd & 3rd molars DM – Diabetes Mellitus, Fa - Fatal, F - Female, FESS - functional endoscopic sinus surgery, HBO - Hyperbaric Oxygen , IVAB - Intravenous amphotericin B , M - Male, NA - Data not available , NIC- Non immuno-compromised , Sh - Satisfactory healing.

possibly be attributed to presence of multiethnic popu- of maxillary posterior teeth can possibly be due to their lation (17). In this review, males were more commonly proximity to the maxillary sinus, which often get invol- affected than females (in ratio of 13:5). While age of pa- ved when fungal spores are inhaled through nasal route. tient ranged from 14 to 74 years (mean of 52.21 years). Clinical features of the reviewed case included, The underlying condition predisposing this fungal infec- non-healing extraction site (5,6,7,8,14,15,16), edema tion included diabetes mellitus (8 cases), leukemia on of face (4,12), alveolar bone necrosis with palatal ulcer chemotherapy (1 case), chronic obstructive pulmonary (5,9,12,13), nasal discharge/blockage (5,6,7,10,13), pa- disease treated with steroid therapy (1 case) and diabe- resthesia of lower lip (6), facial paresthesia (15), trismus tes mellitus along with leukemia (1 case). This finding (15) and headache (7). Further spread of infection result was consistent with the fact that mucormycosis affect in orbital involvement, causing chemosis (edema of con- patients with compromised immunity. According to lite- junctiva), epiphora (excessive watering of eye), diplopia rature, 40-50% of patients suffering from mucormycosis (double/blur vision), ptosis (drooping of upper eyelid), have diabetes mellitus as a predisposing factor (3). Aci- proptosis (protrusion of eye ball), ophthalmoplegia (pa- dosis in diabetes mellitus compromises the phagocytic ralysis of eye muscles), and vision loss (4,8,12,14). As ability of white blood cells thereby affecting the host the disease is rapidly progressive, imaging modalities immunity. Interestingly among the cases reviewed in like computed tomography and magnetic resonance ima- this paper, three were reported in patients with no immu- ging are useful tools to study the extent of necrosis, pa- nocompromised condition (10,11,15). This finding was ranasal sinuses involvement, orbital and cerebral spread. consistent with our cases. According to Mignogna M.D. In the present review, majority of the cases showed ex- et al. (17), mucormycosis affecting healthy individuals tensive involvement of maxillofacial skeleton (71% of can be due to the role of local factors in pathogenesis of cases). However, the cases presented, along with three this disease. Local factors like surgical trauma from too- of the reviewed cases manifested as localized disease in- th extraction may compromise the local vascularity, as volving only the maxillary alveolar bone and maxillary well as provide a portal of entry to the microorganisms. sinus (7,11,13), whereas one case was localized only to Tooth decay with periapical infection or periodontitis, mandibular alveolus (6). which invariably are the most common cause of tooth Mucormycosis require prompt management to prevent removal, may further lower the local host defense me- further spread and avoid fatal complications. Treatment chanism. In the present review, extraction of maxillary includes immediate hospitalization and systemic anti- posterior teeth was most commonly associated with this fungal therapy. Amphotericin B is the drug of choice in disease, accounting for 85% of all cases. While extrac- mucormycosis. Supportive therapy includes; fluid -ba tion of maxillary anterior teeth contributed for one case lance, nutritional supplements and correction of under- and mandibular molar for two cases (6,13). High pro- lying immune deficiency. Surgical intervention is often pensity of association of mucormycosis with extraction required to remove the necrosed tissue. In the present

e304 J Clin Exp Dent. 2018;10(3):e300-5. Nilesh; Mucormycosis of maxilla review, surgical management included combination of 14. Arya S, Sharanamma B, Patil N, Anitha B, Bhateja S, Basavaraj. one or more procedures like tissue debridement, maxi- Rhino-maxillary form of mucormycosis causing sinusitis: a rare case report with review of literature. Journal of Oral Medicine Oral Surgery llectomy, sinus exploration and curettage. Functional Oral Pathology and Oral Radiology. 2015;1:39-44 endoscopic sinus surgery and hyperbaric oxygen thera- 15. Fanny M. Laihad, I Ketut Sudiana & M. Guritno Suryokusumo py has also been reported for treatment of mucormyco- “Case Report: The Diagnosis, Treatment and Outcome of a Rare Case sis (6,15). The cases presented were managed by local Suspected as Mucormycosis” Pinnacle Medicine & Medical Sciences. 2015;2:502-5. debridement and sequestrectomy. Oroantral fistula in 16. Selvamani M, Donoghue M, Bharani S, Madhushankari GS. the first case was closed using double layered pedicled Mucormycosis causing maxillary osteomyelitis. J Nat Sc Biol Med buccal fat pad and buccal advancement flap. The outco- 2015;6:456-9. me of management of mucormycosis often depends on 17. Mignogna MD, Fortuna G, Leuci S, Adamo D, Ruoppo E, Sia- no M, Mariani U.Mucormycosis in immunocompetent patients: a ca- immune status of individual, extent of spread, cerebral se-series of patients with maxillary sinus involvement and a critical involvement and systemic dissemination. The review of review of the literature. International Journal of Infectious Diseases. cases showed satisfactory result in 11 cases (79%), whe- 2011;15:e533-40. reas three patients (21%) showed fatal outcome. Early Conflict of interest diagnosis and intervention reduces the extent of spread The authors have declared that no conflict of interest exist. and limits the risk of serious complications.

Conclusions Mucormycosis is a rare fungal infection which can cause widespread necrosis of orofacial tissues in susceptible host. Though incidence of mucormycosis secondary to tooth extraction is extremely low, however when it occurs, may cause significant morbidity and mortality. Hence dental professionals must be aware of the possibi- lity of this serious and fatal complication, so as to avoid unfavorable outcome in clinical practice.

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