|Year : 2022 | Volume
| Issue : 1 | Page : 66-71
Mucormycosis and dentistry in the current pandemic scenario: A review of literature
Anup Gopi1, Satish R Iyer2, Amolika Choube3
1 Prosthodontics and Crown and Bridge, Meghalaya, India
2 Prosthodontics and Crown and Bridge, Dental Centre, Kolkata, West Bengal, India
3 Oral and Maxillofacial Pathology, Microbiology, Dental Centre, Happy Valley, Meghalaya, India
|Date of Submission||22-Jun-2021|
|Date of Acceptance||20-Dec-2021|
|Date of Web Publication||05-Apr-2022|
Oral and Maxillofacial Pathologist, Shillong - 793 007, Meghalaya
Source of Support: None, Conflict of Interest: None
The treatment protocol for COVID-19 along with the presence of important confounders like diabetes and immunocompromised states may predispose individuals to COVID-19-associated mucormycosis. Since mucormycosis is a rapidly progressive and invasive infection with intracranial complications, early diagnosis followed by aggressive medical and surgical interventions is imperative to reduce the morbidity and mortality associated with the disease. The role of dental practitioners in early recognition and referral of the patient is thus paramount. A systematic investigation on the PubMed Database was undertaken and available data were compiled. This paper presents a review of mucormycosis in the current COVID-19 scenario, to act as a ready reference for dental practitioners.
Keywords: COVID-19-associated mucormycosis, dentistry, fungal osteomyelitis, fungal sinusitis, Mucorales, mucormycosis
|How to cite this article:|
Gopi A, Iyer SR, Choube A. Mucormycosis and dentistry in the current pandemic scenario: A review of literature. J Dent Def Sect. 2022;16:66-71
|How to cite this URL:|
Gopi A, Iyer SR, Choube A. Mucormycosis and dentistry in the current pandemic scenario: A review of literature. J Dent Def Sect. [serial online] 2022 [cited 2022 Nov 29];16:66-71. Available from: http://www.journaldds.org/text.asp?2022/16/1/66/342639
| Introduction|| |
COVID-19 caused by severe acute respiratory syndrome (SARS) coronavirus-2 has caused significant mortality worldwide since its first presentation in Wuhan, China. Researchers have extensively studied this infectious disease, and knowledge in terms of its pathophysiology, diagnosis, management, sequelae, and complications is continuously evolving. The spectrum of COVID-19 has expanded since its first presentation, and the recent addition of invasive fungal sinusitis and osteomyelitis, resulting from mucormycosis, has raised concerns among treatment providers.
Mucormycosis or zygomycosis or phycomycosis is caused by Mucorales fungi and it is an opportunistic infection. Mucormycosis mainly affects immunocompromised patients. It has a sudden onset and it rapidly progresses involving the surrounding tissues. Before COVID-19, data regarding mucormycosis were limited as only a few case reports were published. Today, mucormycosis is increasingly being reported in patients treated or recovering from COVID-19. According to Garg and associates, the current treatment protocol for COVID-19 and administration of glucocorticoids can be the primary reason for COVID-19-associated mucormycosis.
Successful management includes early clinical recognition and microbiological confirmation of the disease followed by aggressive medical and surgical interventions. Early diagnosis is critical for the successful management of mucormycosis. For any clinically suspicious lesion, a confirmatory biopsy followed by early initiation of antifungal treatment is a must. With the rhinocerebral presentation being most common, dental practitioners should be well aware of rhinocerebral mucormycosis. Extra care should be maintained specifically while treating diabetics, immunocompromised, and COVID-19-positive or recovering individuals. Atypical symptoms of rhinocerebral mucormycosis such as pain over the maxillofacial region, sinus region, or pain associated with teeth that are otherwise healthy should not be neglected. This paper presents a review of mucormycosis in the current COVID-19 scenario to act as a ready reference for dental practitioners.
| Methods for Data Collection|| |
A systematic investigation on the PubMed Database till June 2021 was undertaken, using the following entities: (“coronavirus”) OR (“SARSCoV”) OR (COVID-19) AND (mucormycosis) OR (zygomycosis) OR (phycomycosis). We identified 24 case reports and four case series, which described mucormycosis in association with COVID-19. Twelve reviews described COVID-19 association with mucormycosis. Apart from these, epidemiological (one), prospective observational (two), retrospective observational (two), retrospective interventional (two), and cross-sectional descriptive (one) studies investigating COVID-19-associated mucormycosis were identified.
| Microbiology|| |
Mucormycosis a fungal infection is caused by the order Mucorales. Mucorales, along with the order Entomophthorales, belong to the class of fungi called Zygomycetes. These fungi are categorized further into six families, i.e., Mucoraceae, Cunninghamellaceae, Mortierellaceae, Saksenaea, Syncephalastraceae, and Thamnidaceae. The family Mucoraceae and the species Rhizopus arrhizus are frequently associated with mucormycosis.
Mucorales grow rapidly following incubation at 25°C to 30°C on both nonselective and selective culture media such as Sabouraud agar and potato dextrose agar. Identification of Mucorales is based on their macroscopic and microscopic growth characteristics. Macroscopically, growth is typically hyaline in appearance with light coloration on the reverse side of the culture plate. Sporulating surface of the colonies is variably colored, ranging from pure white to tan, brown, gray, or black.
Microscopically, hematoxylin and eosin and lactophenol cotton blue staining reveals fungal elements such as rhizoids, stolons, and columella. Periodic acid–Schiff or Grocott–Gomori's methenamine silver stains are used to visualize fungal hyphae in more detail. Characteristically, non-septate and perpendicularly branched hyphae are observed, which measure about 10–20 um in diameter.
| General Etiopathogenesis of Mucormycosis|| |
Spores of Mucorales fungi invade deep tissues after being inhaled or ingested. Risk factors for Mucorales infection include uncontrolled diabetes mellitus and immunocompromised states as seen following steroid and broad-spectrum antibiotic therapy. Immunocompromise associated with hematological malignancies, AIDS, organ or stem cell transplantation, and malnutrition are also contributory.
The ample availability of micronutrients and suboptimal defenses in diabetic patients enable development of mucormycosis, which can pursue a destructive and rapidly progressive course. Waldrof et al. in 1984 hypothesized that diabetics have low serum defense against Rhizopus species. Low pH due to acidosis in uncontrolled diabetes improves serum iron availability by reducing its binding with the iron-binding protein transferrin. Raised serum glucose levels cause glycosylation of transferrin and ferritin, which further raises serum free iron. In addition, pulmonary macrophages in diabetics with reduced phagocytic capabilities fail to inhibit Rhizopus germination. Neutrophils, which play a vital role in innate immunity, have diminished function in diabetes mellitus. High glucose and free iron availability, low pH due to acidosis, and reduced host defense capabilities are ideal conditions for the growth of Mucorales in diabetics. Together, these factors highly predispose diabetics to mucormycosis.,
| COVID-19-Associated Mucormycosis|| |
Fungal osteomyelitis of the craniomaxillofacial region in patients who were COVID-19 positive has increased drastically. White et al. in 2020 studied 135 COVID-19-infected adults and reported the occurrence of invasive fungal infections in 26.7% individuals. Song et al. studied the association between COVID-19 infection and invasive fungal sinusitis and concluded that individuals who have been infected by or have recovered from COVID-19 are more prone to invasive fungal infections. Rawson et al. in their review indicated that 8% of COVID-19-positive or recovered individuals, with a history of broad-spectrum antibiotic and steroid administration, had developed “secondary bacterial or fungal infections.” Furthermore, it is important to note that diabetes and other immunocompromised states were also associated with COVID-19-associated mucormycosis. Verma and Bali in 2021 in their study suggested that diabetes mellitus was the most common risk factor associated with COVID-19-associated mucormycosis.
The widespread pulmonary disease followed by alveolo-interstitial involvement caused by COVID-19 permits secondary fungal infections that may become invasive. The causative virus itself impairs the host's cell-mediated immunity, with decreased CD4 + T and CD8 + T cell counts. According to Yang et al., critically ill patients requiring prolonged hospital admission and mechanical ventilation were more likely to develop secondary fungal infections. Furthermore, current guidelines recommend administration of steroids to admitted patients requiring oxygen support. Hospitalized COVID-19 patients are thus at high risk to develop invasive fungal infections like mucormycosis.
| Sdiagnosis of COVID-19-Associated Mucormycosis|| |
Mucorales infection most commonly presents with rhinocerebral, pulmonary, soft tissue, and disseminated manifestations. Widespread tissue necrosis is characteristic of mucormycosis. Characteristic “red-flag” signs and symptoms that are associated with rhinocerebral mucormycosis include ulcers of the palate, sinus pain, periorbital swelling, diplopia, proptosis, orbital apex syndrome, and cranial nerve palsy. Smith and Krichner criteria of 1950 are considered the gold standard for clinical diagnosis of mucormycosis:
- Black, necrotic appearance of turbinates that is easily misinterpreted as dried, crusted blood
- Blood-tinged nasal discharge and facial pain on the affected side
- Discolored and indurated periorbital or perinasal swelling
- Complete ophthalmoplegia along with proptosis of the eyeball and ptosis of the eyelid and
- Multiple cranial nerve palsies unrelated to documented lesions.
Immediate diagnosis of mucormycosis microscopically on KOH-mounted slides is achieved by visualization of broad, ribbon-shaped, perpendicularly branched, nonseptate hyphae. Definitive diagnosis is made following culture and histological evaluation of tissue invasion. Nasal endoscopy is also a useful tool for diagnosis and debridement of the fungus. Nasal endoscopy may show black or brown crust and erosion of turbinates. Suppuration and septal perforation in the nasal cavity may be readily visualized by nasal endoscopy.
Endobronchial ultrasound-guided fine-needle aspiration is another diagnostic tool to harvest samples from cavitary lung lesions. The potential of endobronchial ultrasound-guided fine-needle aspiration is increasing being explored for real-time histological diagnosis of pulmonary mucormycosis. Sputum and bronchoalveolar lavage are usually nondiagnostic, while core lung biopsies are high-risk procedures for critically ill patients. Thus, being rapid, safe, and noninvasive, endobronchial ultrasound-guided fine-needle aspiration has gained popularity among clinicians.
Radiographically, rhinocerebral mucormycosis shows thickening of sinus lining and osseous distraction from sinus walls. Radiodensities without fluid level are observed in paranasal sinuses. Noncontrast computed tomography (CT) of paranasal sinuses is recommended. Gadolinium-enhanced magnetic resonance imaging (MRI) is recommended for intraorbital and intracranial lesions. Focal bony erosions and extrasinus involvement may suggest the diagnosis of mucormycosis. MRI of the head and neck may show multiple areas of infarction and ischemia, indicative of the invasive nature of the disease. Apart from CT and MRI, positron-emission tomography-computed tomography with 18F-fluorodeoxyglucose is also an upcoming valuable diagnostic tool for mucormycosis.
Tissue histopathology is shown neutrophilic or granulomatous inflammation, which may be absent in immunosuppressed individuals. Prominent infarcts and angioinvasion are histopathological indicators of invasiveness. Molecular diagnostics comprise conventional polymerase chain reaction (PCR) analysis, DNA sequencing of defined gene regions, and melt curve analysis of PCR products.
| Role of Dental Practitioner|| |
Early diagnosis is the most important criterion for the successful management of mucormycosis and mortality reduction. Rhinocerebral mucormycosis progresses rapidly to invade the hard palate, paranasal sinuses, orbit, and brain. Black eschar, though not characteristic, is usually seen in the nasal cavity and on hard palate. Few case reports have also described rhinocerebral mucormycosis in the mandible., Patients with rhinocerebral mucormycosis usually present with malaise, low-grade fever, headache, facial pain, and swelling. Orbital apex syndrome may ensue following the involvement of orbital region, causing proptosis, ptosis, pupillary dilatation, orbital cellulitis, and, finally, loss of vision owing to cranial nerve palsy. Local tissue invasion, direct penetration, and hematogenous spread may result in cavernous sinus thrombosis and widespread tissue necrosis.,
Patients usually report to the dental office with the chief complaint of pain in the maxillary premolar-molar region, radiating to the maxillary sinus. Common orofacial symptoms reported by patients include the following:
- Pain or loss of sensation over the maxillofacial region
- Facial puffiness
- Localized discoloration of the skin of maxillofacial region
- Loosening of teeth, especially in the maxillary arch, without evidence of significant bone loss radiologically
- Ulceration of the palate
- Trismus and/or pain in the temporomandibular joint.
Ulceration and extraction sockets can introduce the fungi into the maxillofacial region, which can develop into mucormycosis, particularly in immunocompromised hosts. Cases of development of postextraction fungal osteomyelitis in immunocompromised and diabetic patients have been reported in the past., Thus, nonhealing ulcers, areas of necrosis, and maxillary sinusitis following dental treatment and extractions should be carefully reviewed by dental practitioners.
Early recognition is necessary to limit the high morbidity and mortality associated with the infection. Therefore, dental surgeons and medical practitioners should be familiar with signs and symptoms of the infection and should maintain high levels of caution while treating immunocompromised and diabetic patients. A similar high index of suspicion should also be maintained for COVID-19 patients reporting with history of prolonged hospital stay for oxygen support.
| Current Treatment Strategies Against COVID-19-Associated Mucormycosis|| |
Systemic antifungal treatment with liposomal amphotericin B, oral posaconazole, or IV/oral isavuconazonium is the treatment of choice. Early surgical debridement of all infected and necrotic tissues is crucial. Radical resection with partial or total maxillectomy, mandibulectomy, and orbital exenteration may be needed in some cases.
Dental treatment procedures are associated with acute inflammatory response and release of acute inflammatory mediators. These inflammatory mediators can alter the severity of pre-existing COVID-19. Thus, post-COVID patients should be screened with a detailed history and psychological counseling is a must for all post-COVID-19 patients. All treatment procedures must be explained in detail along with the probable complications.
Certain general precautions to be followed include:
- Keep the toothbrush of COVID-19 patient/COVID-19-recovered individual separately
- Clean the toothbrush and tongue cleaner regularly using an antiseptic mouthwash
- Change the toothbrush once individuals test positive and immediately after they test negative for COVID-19
- Brush twice or thrice daily followed by a mouthrinse both during and postrecovery from COVID-19.
| Prosthodontic Rehabilitation|| |
The widespread and undefined involvement of mucormycysis in the oromaxillofacial region result in surgical defects that are different from the defects resulting after tumor resection. Additional surgical debridement may be needed in the course of treatment. In addition, the nonkeratinized mucosa left post debridement has poor stress-bearing capabilities. Thus, most techniques for prosthetic rehabilitation used after tumor resection cannot be applied to rehabilitate a patient with mucormycosis. Challenges involved in prosthetic rehabilitation of a patient with mucormycosis include the following:,,,,
- Difficulty in predetermining the borders/extension of the lesion due to the invasive nature of the disease
- Recording of the impression can only be done after progression of infection is controlled or when no further debridement is required
- Large size of the defect presents a challenge for retention of the prosthesis, especially in bimaxillary resection that involves the entire dentition, palate, paranasal sinuses, and orbital floor
- Denture liners or soft tissue liners cannot be used as they are susceptible to fungal growth
Following points should be considered for prosthetic rehabilitation:
- Immediate surgical obturator should be provided considering the psychological impact the prosthesis can give after the surgical procedure since the speech, mastication, deglutition, and even breathing of the patient is compromised. The surgical obturator must be made such that it allows constant monitoring of the wounds and application of medicaments
- Retention, stability, and support of the prosthesis must be derived from all available tissue/bony undercuts. Split-thickness skin grafts may be considered depending upon the presenting condition of the patient in order to utilize keratinized tissue for denture/prosthesis support. It is hence important that the treating surgeon and the prosthodontist are part of the rehabilitation team and all modalities of postsurgical rehabilitation are discussed well in advance before surgery
- The patient must be trained to utilize his neuromuscular control and the dorsum of the tongue to effectively support the prosthesis
- Definitive prosthesis must be planned only after complete healing. Two-piece, hollow prostheses that are retained using magnets would be the modality of choice
- Zygomatic implants and secondary reconstruction with delayed implant placement may be considered as long-term rehabilitation options
- Thorough and repetitive recall to examine both tissue and prosthesis surface for any recurrence of the infection is a must.
| Conclusion|| |
Coronavirus disease association with invasive mucormycosis is progresses rapidly and is associated with significant morbidity. Uncontrolled diabetes and immunocompromised states are high-risk factors for development of mucormycosis among COVID-19-infected and recovered individuals. Corticosteroids and broad-spectrum antibiotics must be cautiously administered in such cases. Early recognition of rhinocerebral COVID-19-associated mucormycosis by dental practitioners is crucial to reduce mortality. A thorough knowledge of pathogenesis, clinical presentation, sequelae, and treatment of COVID-19-associated mucormycosis in dental practice is thus essential.
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Conflicts of interest
There are no conflicts of interest.
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