Odontogenic-onset mucormycosis: A case series from a tertiary care institute in North India

Abstract

Mucormycosis is an angio-invasive, opportunistic fungal infection, which usually affects individuals with poorly controlled diabetes mellitus. While rhino-orbital-cerebral mucormycosis (ROCM) has been described in the English language literature, odontogenic-onset mucormycosis (OOM) is an emerging clinical entity, which is characterized by a unique port of entry, a distinct mode of onset and clinic-radiological features. We report a series of five cases of OOM managed in a tertiary care centre in North India. This series underscores the critical need for heightened awareness among dental practitioners about this entity, and highlights the importance of adhering to strict aseptic precautions.

1. Introduction

Mucormycosis is an aggressive angio-invasive fungal infection caused by fungi belonging to the Mucorales family, including Rhizopus, Mucor and Lichtheimia. The disease occurs in immunocompromised individuals, especially those with uncontrolled diabetes, hematological malignancies, solid organ transplant patients, COVID-19 patients, and patients who are on steroids or immunosuppressive drugs. Uncontrolled diabetes is the most common underlying disease associated with mucormycosis. India has an annual incidence of approximately 14 cases per 100,000 population, which is approximately 80 times higher than the global average of 0.06–0.3 cases per 100,000 [[1], [2], [3]]. Rhino-orbital-cerebral mucormycosis (ROCM) is the most common clinical form of mucormycosis in India, followed by lung and skin involvement. Recently, odontogenic-onset mucormycosis (OOM) has been increasingly recognized and reported. OOM is associated with initial dental symptoms with predominant involvement of the alveolar bone and comparatively limited sinus disease [4]. It has been recently described in the scientific literature, and inoculation during dental procedures is thought to be the cause of this form of mucormycosis. We present a series of five cases of OOM that developed within 4–6 weeks following dental procedures. We discuss clinico-radiological features, histopathological diagnosis, differential diagnostic entities, and diagnostic and therapeutic challenges encountered during the management of these cases.

2. Methods

We retrospectively reviewed cases of mucormycosis diagnosed at our tertiary care centre between March 2023 and April 2024. Patients who presented with predominant dental symptoms at onset, alveolar bone involvement, and limited paranasal sinus disease were classified as having OOM. Clinical and demographic data, including underlying comorbidities, details of proceeding dental procedures, radiological findings, microbiological confirmation, treatment, and outcomes, were analysed. Uncontrolled/poorly controlled diabetes was defined as patients not meeting the glycemic goals defined as per the practise recommendations by American Diabetes Association [5]. There was no recent history of COVID-19 infection in any of our cases. A detailed case description of all five cases is given in Table 1. Day 0 has been assigned to the day of dental procedure in each of the five patients.

Table 1.

Showing detailed case description of five cases of Mucormycosis.

S No	Age & Sex	Comorbid condition	Pre-procedure symptoms	Dental procedure	Interval	Post-procedure symptoms	Radiological features (NCCT-PNS features)	Surgical management	Medical management
1	66 F	Uncontrolled diabetes∗ (HbA1c: 8.2 %, TDI = 12 years), hypertension, coronary artery disease	Pain in the left upper premolar (day −30)	Teeth extraction: left upper premolars (day 0)	6 weeks	Swelling and pain in the left upper molar and premolar; Pus discharge, numbness (day +46)	Osteolytic lesion involving the alveolar-basal region, extending into the hard palate with minimal sinus involvement (day +47)	Maxillary sequestrectomy	LAmB for 11 days f/b Posaconazole for 9 months
2	55 M	Uncontrolled diabetes (HbA1c: N/A)# and hypertension	Pain in left upper molar and premolar	Root canal therapy [RCT] (day 0)	3 weeks	Pus discharge at the site of RCT, persistent pain, facial swelling and numbness (day +21)	Sclerosis of the posterior aspect of the left upper maxillary alveolus, soft tissue density in the left nasal cavity and formation of a sinus tract opening in left upper lip paramedian location (day +25)	Maxillary sequestrectomy	LAmB for 21 days f/b Posaconazole for 6 months
3	44 M	Uncontrolled diabetes (HbA1c: 12 %, TDI: 4 years, in DKA at presentation)	Pain in left upper premolar	Tooth extraction: Left upper premolar (day 0)	3 weeks	Left facial pain and non-healing wound (day +22)	Sclerosis of left maxillary alveolus, suggestive of osteomyelitis with mild left maxillary sinusitis (day +23)	Left infrastructural maxillectomy (day +27)	LAmB for 25 days f/b Posaconazole for 3 months
4	46 M	Diabetes: controlled (HbA1c: 5.7 %, TDI: 4 years)	Tooth pain, numbness, teeth loosening left upper side	Tooth extraction (day 0)	2 weeks	Nasal pus discharge (day +15)	Extensive erosion and bony destruction of left half of maxilla, with oro-antral fistula	Debridement, lateral rhinotomy	LAmB for 42 days f/b Posaconazole for 6 months
5	46 M	Uncontrolled diabetes (HbA1c: 9.75 %, TDI: 5 years)	Loosening of teeth right upper premolars and molar	Teeth extraction: Right upper premolar and molar (day 0)	4 weeks	Facial numbness, nasal pus discharge (day +28)	Hypodense osteolytic aggressive lesion involving left maxillary arch and alveolar crest	Medial maxillectomy, Uncinectomy, Antrostomy (day +64)	LAmB for 42 days f/b Posaconazole for 6 months

(NCCT-PNS: Non-contrast computed tomography of paranasal sinuses; LAmB: Liposomal Amphotericin B; f/b: followed by; N/A: Not available; TDI: Total duration of illness; DKA: Diabetic ketoacidosis) ∗Uncontrolled diabetes was defined as patients not meeting the glycaemic goals defined as per the practise recommendations by American Diabetes Association. [5]; ^# HbA1c values were not available, but patient was diagnosed at presentation with raised random blood sugar, with subsequent values not meeting glycaemic goals with 3 oral hypoglycaemic agents.

2.1. Case descriptions

Case 1: A 66-year-old female, a known hypertensive with coronary artery disease and long-standing uncontrolled type 2 diabetes mellitus underwent a maxillary tooth extraction of left upper premolars at a local clinic [day 0]. Details regarding the indication for the extraction were unavailable, but the patient had a history of pain in the left upper premolars for a duration of one month prior to the extraction [day −30]. She developed progressive swelling in the left upper molar and premolar associated with pain over the extraction site six weeks later [day +42]. This was also accompanied by continuous pus discharge and numbness over the site. She presented to our centre on day +46. Non-contrast computed tomography of paranasal sinuses (NCCT PNS) revealed an osteolytic lesion involving the alveolar-basal region, extending into the hard palate with minimal sinus involvement (Fig. 1a–c). She underwent a tissue biopsy on day +47, which revealed broad, aseptate hyphae on potassium hydroxide (KOH) calcofluor white staining (Fig. 1d). Decalcified sections showed irregular-shaped bony trabeculae with empty osteoid lacunae and intervening necrotic stroma and mixed inflammatory infiltrate with evidence of angioinvasion. (Fig. 1e). The patient underwent surgical debridement and was treated with liposomal amphotericin B from day +47 to day +58 There was significant clinical improvement and she was discharged on oral Posaconazole [day +60]. On follow up at day 335, she was asymptomatic.

Fig. 1.

A panel of images: 1a to 1c: NCCT PNS showing osteolytic lesions in the alveolar-basal region, extending into the hard palate with minimal sinus involvement; 1d: KOH- Calcofluor white staining under a fluorescent microscope showing broad aseptate hyphae; 1e: Histopathology showing angioinvasion by mucormycosis [arrows] (H&E x200).

Case 2: A 55-year-old male with a history of uncontrolled diabetes mellitus along with hypertension underwent a root canal therapy [RCT] (day 0) which was done in view of non-resolving pulpitis. She presented to our centre on day +21 with history of pus discharge at the site of RCT and gradually progressive facial numbness. The NCCT- PNS scan revealed sclerosis of the posterior aspect of the left upper maxillary alveolus, soft tissue density in the left nasal cavity, and formation of a sinus tract opening in the left upper lip paramedian location Biopsy and histopathological examination demonstrated angioinvasion by broad aseptate fungal hyphae with right-angle branching, which were consistent with the morphology of mucormycosis in the background of necrosis (Fig. 2c and d) He underwent maxillary sequestrectomy on day +25 and received intravenous liposomal amphotericin B therapy till day +46, followed by 6 months of oral posaconazole. He improved significantly and was asymptomatic on further follow-up visits after treatment was discontinued [day +260].

Fig. 2.

A panel of images; 2a and 2b: CECT scan of paranasal sinuses showing sclerosis of the posterior aspect of left upper maxillary alveolus with soft tissue density in left nasal cavity; 2c: Histopathology showing mucormycosis in the background of acellular necrotic material (H&E x200); 2d: broad aseptate hyphae with right angle branching, which were faintly positive with PAS stain [arrows] (Periodic acid- Schiff's stain x200).

Case 3: A 44-year-old male with poorly controlled diabetes presented with a non-healing post-extraction wound and facial pain 3 weeks (day +22) after extraction of the left upper premolar at a peripheral centre (day 0). Examination revealed a palatal ulcer with a posterior bulge in the left upper jaw. Imaging showed sclerosis of the left maxillary alveolus, suggestive of osteomyelitis (Fig. 2a and b)(day +23). Primary debridement of bony tissue from the maxilla showed infarcted necrosis along with broad, pauci-septate fungal hyphae consistent with the morphology of mucormycosis [day +27]. He underwent a left-sided maxillectomy and received intravenous liposomal amphotericin B till day +52, followed by 3 months of oral posaconazole. He remained clinically well on follow-up visit after 6 months of discontinuing therapy [day + 327].

Case 4: A 46-year-old male with well-controlled diabetes mellitus underwent a molar extraction at a peripheral centre [day 0]. He presented to us at day +15 with toothache, numbness, and teeth loosening in the left upper side of his face. An NCCT scan showed extensive erosion and bony destruction of the left half of the maxilla, with an oro-antral fistula. Mucorales were identified on tissue KOH-calcofluor white staining, while histopathology confirmed the presence of mucormycosis. The patient had a prolonged in-hospital course requiring repeat debridement for source control. He received liposomal amphotericin B for 42 days and was discharged on day +61. He received oral posaconazole after discharge till day +244 and is clinically well 8 months after discontinuation of therapy [day +487].

Case 5: A 46-year-old diabetic male presented to our centre [day + 1095] with facial numbness, occasional pus discharge, and pain since 8 weeks. For a period of 3 years, the patient was being managed as a case of mucormycosis at a peripheral centre with history of uncinectomy [day +64], bilateral sino-nasal debridement [day + 321], medial maxillectomy and transposition flap repair [day + 667]. He had been inconsistent with the anti-fungal treatment advised and was not compliant with his diabetes medications. Detailed analysis revealed history of extraction of the right upper premolar and molar at a peripheral centre [day 0], followed by pus discharge which appeared at day +28. CT done at our centre showed a hypodense osteolytic aggressive lesion involving the maxillary arch [day +1098]. Repeat debridement was done,and tissue biopsy confirmed the presence of mucormycosis [day +1099]. He then underwent debridement and bilateral maxillary sequestrectomy [day +1105]. He received 6 weeks of liposomal amphotericin B and 6 months of oral posaconazole therapy with significant improvement on follow-up after 7 months [day +1318].

3. Discussion

Mucormycosis is a fulminant angio-invasive fungal infection caused by fungi of the order of Mucorales. The incidence of mucormycosis varies globally, with India's reporting rates being approximately 70–80 times higher than the global average [3]. The most common predisposing factor for mucormycosis is uncontrolled diabetes mellitus, accounting for 60–80 % of cases [6]. Other risk groups include immunocompromised patients, such as those with solid organ transplants, hematological malignancies, chronic renal disease, or patients on immunosuppressive drugs. India witnessed a significant surge in the cases of ROCM during the COVID-19 pandemic, especially following widespread usage of corticosteroids in order to manage the cytokine storm of COVID-19, leading to significant morbidity and mortality [7].

While the most common clinical form of mucormycosis described so far is ROCM, followed by pulmonary and cutaneous forms, a retrospective study from 2023 by Manesh et al. described odontogenic-onset mucormycosis (OOM) as a distinct clinical form of mucormycosis [4]. OOM is characterized by dental symptoms with predominant alveolar bony involvement with little or no paranasal sinus involvement [4].

The key features of OOM, distinguishing it from ROCM include a different port of entry-the dental alveolus, usually the maxilla, rather than through nasal inhalation; bony destruction of the alveolar ridge and maxilla; comparatively slower clinical progression, typically developing about a month after a dental procedure; as well as lower morbidity and mortality as compared to ROCM [4].

While OOM has only been recently recognized, more than 35 cases of post-extraction mucormycosis have been reported since 1974, with 18/35 cases reported from India [[8], [9], [10], [11], [12], [13]].

The potential risk factor associated with OOM appears to be dental extraction or other dental procedures such as root canal therapy, which cause traumatic or surgical breaches of tissue [14]. The mechanism by which the oral cavity, particularly the dental alveolus, acts as a portal of fungal entry is analogous to percutaneous inoculation, a recognized route of transmission in cutaneous mucormycosis.

OOM mainly results in osteolytic lesions in the alveolar or basal maxillary region and hard palate. In our cases, radiology revealed bony destruction of the maxilla centered in tooth sockets, with palatal involvement and only limited involvement of the paranasal sinus at presentation. Unlike OOM, the disease often originates in the sinuses and spreads to the palate in ROCM. While environmental exposure cannot be conclusively ruled out, the mode of presentation, symptom progression, and radiological features in our series of patients indicate dental inoculation as the likely point of entry.

Mucormycosis occurring after dental procedures also raises questions regarding healthcare-associated mucormycosis. Contaminated medical items, including wooden tongue depressors, adhesive bandages, and hospital linen, have been implicated in previous hospital outbreaks. Mucorales, although ubiquitous in the environment, are not part of the normal oral commensal flora [15]. Although no formal outbreak investigations were conducted, our patients presented from different peripheral centres, making it unlikely that the cases were related to a common outbreak. As the patients presented to our centre after undergoing procedures at multiple primary care facilities, inadequate sterilization practices and elevated environmental fungal burden are likely contributing factors. As previous outbreaks have implicated percutaneous inoculation through contaminated linen and bandages, a plausible source in our cases could be the use of contaminated gauze applied post-dental extraction [3,16].

Information on zinc supplementation and antibiotic use, both of which have been previously implicated in the pathogenesis of COVID-19- associated mucormycosis was unavailable, as the procedures had been performed in peripheral centres without adequate documentation [17]. Current consensus, supported by large systematic reviews, indicates that prophylactic antibiotics are not warranted for dental extractions except in two groups: patients at high risk for infective endocarditis and those with severe neutropenia, solid organ transplantation, or primary immunodeficiency [[18], [19], [20]].

OOM patients present initially with oral symptoms such as severe and persistent toothache, facial mainly gingival swelling, sudden tooth loosening, and pus discharge. Manesh et al. reported that dental pain with loosening of teeth is the most common symptom in OOM cases [4].

OOM often spares extensive orbital or cerebral involvement at presentation. Manesh et al. highlighted that only 28.6 % of all cases of OOM had an orbital extension and 9.5 % of all cases of OOM had cerebral involvement, with an overall mortality of 9.5 % [4]. Similarly, none of the patients in our series had orbital or neurological/cerebral complications. This indicates that OOM has a favourable prognosis as compared to ROCM, which is associated with higher rates of cerebral involvement and a reported mortality exceeding 50 %.

A prompt tissue diagnosis of mucormycosis is of utmost importance to initiate timely treatment. KOH smear and calcofluor staining can help in a presumptive diagnosis within a few hours; however, confirmation needs tissue diagnosis [17]. Fungal culture and PCR can further confirm the diagnosis.

Treatment of OOM includes early initiation of antifungal therapy with liposomal amphotericin B and surgical debridement [21]. One of the most important roles in disease progression as well as response to therapy is played by glycaemic control. In our series, all patients showed clinical improvement with a combination of antifungal treatment and surgical intervention and were doing well on follow-up (Table 1).

Glycaemic control is also an important consideration prior to elective procedures. The American Diabetes Association suggests targeting preoperative HbA1c <8 % and blood glucose 100–180 mg/dL for elective surgical procedures [22]. Our series highlights the importance of dental professionals adhering to this recommendation, as underlying hyperglycaemia likely contributed to the pathogenesis of mucormycosis in these patients.

In conclusion, this case series of five patients underscores the emerging recognition of odontogenic-onset mucormycosis (OOM) as a distinct clinical entity. The findings emphasize the critical importance of maintaining a high index of suspicion to enable early diagnosis and timely intervention. Our series highlights the need to recognize this distinct form of mucormycosis among patients currently being classified broadly as rhino-orbito-cerebral mucormycosis. Further studies are warranted to clarify the path of spread, delineate specific risk factors, and develop targeted preventive strategies. As dental practitioners are often the first point of contact in these cases, clear differentiation between OOM and ROCM is essential to aid in prompt recognition and to reinforce the need for strict aseptic precautions during dental procedures.

CRediT authorship contribution statement

Sandeep Rao Kordcal: Writing – review & editing, Writing – original draft, Resources, Methodology, Formal analysis, Data curation, Conceptualization. Ishan Gupta: Writing – review & editing, Writing – original draft, Resources, Methodology, Formal analysis, Conceptualization. Kanika Chaudhary: Writing – review & editing, Writing – original draft, Resources, Formal analysis. Md Tariq Maula: Writing – review & editing, Supervision, Methodology, Investigation, Data curation, Conceptualization. Rahul Yadav: Writing – review & editing, Visualization, Supervision, Methodology, Investigation, Formal analysis. Gagandeep Singh: Writing – review & editing, Validation, Software, Methodology, Formal analysis. Manish Soneja: Writing – review & editing, Supervision, Methodology, Investigation, Formal analysis. Immaculata Xess: Writing – review & editing, Validation, Supervision, Formal analysis.

Consent to publish

Available.

Data availability statement

Data pertaining to the study is available from the corresponding author on request.

Patients consent

We declare that we (the authors) have obtained written and signed consent to publish this case series from the patients.

Funding

None.

Conflicts of interest

Nil.

Abbreviations

KOH

Potassium hydroxide

NCCT-PNS

Non-contrast computed tomography of paranasal sinuses

OOM

Odontogenic-onset mucormycosis

ROCM

Rhino-orbital-cerebral mucormycosis