Analog and Digital Protocols for Functional Prosthetic Rehabilitation of Post-COVID-19 Rhino-Orbito Cerebral Mucormycosis Maxillofacial Defects: A Case Series

ABSTRACT

The current study aims to present our clinical observations and experience gathered during the diagnosis, clinical presentation, medical/surgical treatment, and functional prosthetic rehabilitation of cases of rhino-orbital/cerebral Mucormycosis patients. Mucormycosis is an aggressive, life-threatening invasive fungal infection that occurs in people who are immune-compromised. The rise of ROCM during the second wave of the COVID-19 pandemic in India suggests a more effective association between Mucormycosis and the SARS-CoV-2 delta variant. The treatment strategy for Mucormycosis is an early diagnosis which is critical for a successful outcome. The initial step is to reduce or remove underlying risk factors followed by surgical excision and debridement of the afflicted tissues supplemented with antifungal medication. The first-line antifungal treatment is Liposomal Amphotericin B. Postsurgical resection defects are rehabilitated by either removable partial prosthesis (obturators) or by fixed zygomatic implant/patient-specific implant supported prosthesis. Management of ROCM requires a multidisciplinary approach. This case series highlights detailed medical, surgical, and functional prosthetic management modalities adopted by our team in managing such a dreaded disease which may be used as a tool for the formulation of standardized prevention and management/treatment/rehabilitation protocols in the future so that disease morbidity and mortality be reduced and an endemic outbreak could be averted.

BACKGROUND

Immune compromised people can get mucormycosis, a deadly invasive fungus illness. In underdeveloped nations, uncontrolled hyperglycemia causes this fungus, while in wealthy countries, it is typically found in hematologic malignancies.[1] Symptoms include rhino-cerebral/rhino-orbital, pulmonary, gastrointestinal, cutaneous, and systemic mucormycosis.[2]

Infection spread from Nasopharynx mucosa to adjacent soft tissues. Fungus can spread inferiorly to the palate, posteriorly to the sphenoid sinus, laterally to the cavernous sinus and orbits, or cranially through orbital apex to the cribriform plate and brain.[2] Larger hyphae block larger arteries, producing thrombosis, infarction, and tissue necrosis.[3] During the second COVID-19 pandemic wave, Indian Mucormycosis cases increased, suggesting a relationship to the SARS-CoV-2 delta variant. Most likely because it is more contagious, resistant to vaccines, increases susceptibility to rhino-cerebral form risk, and affects the pancreas, causing hyperglycemia.[4,5]

Epidemiological studies show that mucormycosis is more common in men with diabetes, hypertension, or who use glucocorticoids. Most patients have rhino-orbital/cerebral mucormycosis. Rhizopus spp. causes most cases.[6,7]

In 2019-2020, India has 80 times more mucormycosis (0.14 per 1000 individuals) than wealthy nations.[8]

Mucormycosis treatment requires early diagnosis. First, eliminate diabetes, acidosis, and corticosteroid use.[9-11] Then, surgical excision and debridement of the affected tissues is recommended.[10,11] At least six weeks of amphotericin B (preferably liposomal) must follow.[11]

CASES DESCRIPTION

Patients got four therapy phases. Surgery and debridement followed diagnosis. Next, additional antifungal medication began gradually and continuously. Third, illness aetiology was rectified simultaneously. Fourth, acquired faulty prosthetic rehabilitation.

Case 1

A 52-year-old male with post-COVID-19 diabetes with left-side facial oedema and discomfort was admitted. COVID-19 was not vaccinated. The patient displayed left-sided oedema, proptosis, left eye ptosis, and a 2-1/2-finger mouth opening on extraoral inspection. Intraoral examination revealed left maxillary vestibule inflammation, necrotic soft tissue, and left hard palate bone exposure. MRI Paranasal Sinus and Orbit with contrast showed hyperintensity with heterogenous enhancement in soft tissue of left infraorbital regions bilateral premaxillary regions bilateral sphenopalatine fossa, infratemporal fossa, and masticator space, suggesting sinusitis. CT PNS showed left upper molar and hard palate bone density. A wide margin left infrastructure maxillectomy and left palatectomy removed the left hard, soft palate, antero-lateral maxillary wall, and maxillary teeth. Left orbital exenteration. Zygoma and left infraorbital margins survived. A removable partial denture with an obturator and silicone orbital prosthesis corrected the abnormality [Figure 1].

Figure 1.

Clinical presentation of case 1: (a) Pre-operative Intraoral Facial View (b) Pre-operative Intraoral Palatal View, (c) Pre-operative MRI PNS with Contrast (d) Intra-operative Intraoral View (e) Excised Specimen (f) Intraoral View after 3 Months of Post-operative Follow-up (g) Removable Partial Denture with Obturator Intaglio Surface (h) Removable Partial Denture with Obturator Occlusal Surface (i) Removable Partial Denture with Obturator In-situ (j) Profile view of the Patient Before and After Eye Prosthesis

Case 2

A 48-year-old male had right facial oedema and right posterior maxillary tooth extraction for a month. Hospitalisation and Covid-19 infection occurred. Clinically, the right maxillary posterior 17,18 region had an unhealed tooth socket, soft, painful bone, and intact mucosal cover from the canine region to the contralateral edentulous alveolar ridge. The right hard palate had soft bone. Broad aseptate hyaline hyphae in the soft tissue KOH mount revealed zygomycetes. Right Infrastructure Maxillectomy and Right Palatectomy followed diagnosis. Obturator-cast partial denture following wound healing.

Case 3

A 38-year-old guy had upper front tooth movement and pus. Right maxillary lateral incisor sinus tract was found intraorally. The anterior hard palate rugae had uncomfortable bone. Palpation showed pre-maxilla, anterior vestibular, and maxillary anterior pain and movement.Oxygen therapy, steroids, Covid19 infection, and prolonged hospitalisation were present. Pathology indicated 157.70 mg/dl random blood glucose and 28.51 mg/l C-reactive protein. Histopathology showed reactive chronic inflammation with interspaced broad, non-septate fungal hyphae branching at wide angles, suggesting fungal infection. CT PNS indicated bilateral maxillary, ethmoidal, and sphenoidal sinusitis. Right-sided sphenopalatine, infratemporal, and masticator space soft tissue irritation. 12-23 segmental pre-maxilla excision and anterior palatectomy. Rehabilitated fixed partial dentures.

Case 4

A post-covid-19 70-year-old male had left maxillary vestibule pain, oedema, and difficulty chewing for 2-3 weeks. Left maxillary vestibule and tooth-bearing irritation was visible intraorally. The left canine fossa, maxillary sinus, and hard palate had soft bone. The left maxilla moved segmentally at le fort 1. Histopathology indicated fungal hyphae, and MRI showed diffuse mild concentric T1 hypointense and T2 hyperintense mucosal thickening involving bilateral maxillary sinuses s/o sinusitis. Left premaxillary, preantral, infraorbital, sphenopalatine, infratemporal, masticator, retromolar, soft palate, and superior alveolar process soft tissue inflammatory changes were identified on CT scan. Left Infrastructure Maxillectomy + Left Palatectomy and more were done. A removable partial denture takes 4 months to rehab. Speech was unaffected.

Case 5

A 55-year-old male was admitted with two days of left cheek and eye pain. Patient had CVA, Covid-19, and type II diabetes. The left maxillary premolar-molar vestibular sulcus had a necrotic soft tissue defect with bone exposure on intraoral inspection. Palpable left hard palate edoema was mild and painful. CT PNS and Orbit showed sinusitis and inflammatory alterations in left pre-maxillary, sphenopalatine, infratemporal, and masticator spaces. Histopathology revealed a white Zygomycetes colony. Left Infrastructure Maxillectomy + Palatectomy. Incomplete healing caused 2 oro-nasal communications/fistulas with inadequate soft tissue cover over the left maxillary buccal vestibular area. Speech impairment and nasal regurgitation occurred. A functional removable palatal obturator repaired the problem after 3 months.

Case 6

A 35-year-old male visited OPD to restore his upper jaw after post-covid mucormycosis. Patient was on nasogastric tube feed for about 6 months after bilateral maxillectomy. Facial disfigurement caused confidence issues and social stigma. A patient - specific implant was planned for the patient in 2 pieces for ease of placement.

Surgical and 3D Printing Digital Protocol Adopted for Placement and Fabrication of Patient Specific Zygomatic Implants (PSZI).

DISCUSSION

The 48 patients in this clinical case study had Post-COVID-19 Rhino-orbito-cerebral Mucormycosis. Thirty-nine male and nine female patients. In their ten-year investigation, Niranjan et al. found that fungal osteomyelitis is more common in men than women and in those over 40.[12] Deepak Garg et al. conducted a systematic study of PubMed and Embase databases through January 9, 2021, and found seven cases of Mucormycosis associated with COVID-19 and eight cases with diabetes mellitus as the common predisposing factor.[13] In our case study, 10 patients underwent orbital exenteration to debride devitalized orbital tissue, 5 of whom received ocular prostheses. Surgical debridement has no ideal timing in literature. Due to various organ involvements and underlying co-morbidities, some patients underwent surgery 24-48 hours after diagnosis, while others waited 1 to 30 days. Once Mucormycosis was suspected, Amphotericin B was administered until clinical improvement was seen.

Out of 48 mucormycosis patients 4 lost during treatment. All 4 patients had neurological involvement. CT/MRI was the gold standard for disease assessment and surgical debridement planning. Contrast-enhanced CT/MRI of Paranasal Sinuses, Orbits, and Brain revealed the diseased bone and soft tissue extent in this case series. Wide-ranging surgical excision affects facial appearance, produces psychosocial impairment, and hinders speech, swallowing, and mastication. A well-designed obturator prosthesis improves mastication, speech clarity, and psychological comfort. After infection recovery, start rehabilitation with a detachable prosthesis or zygomatic hybrid implant prosthesis.

Palatal obturators and microvascular free flaps treat maxillectomy deficits.[14] Rehabilitating maxillectomy faults using a palatal obturator has become the norm. This approach reduces operational time and allows full visualisation of the maxillectomy cavity to detect disease recurrence. Obturators cause nasal regurgitation and discomfort. Maxillofacial prosthodontics has also switched to digital impressions. 3D imaging and printing have simplified obturator fabrication. An obturator maintained by the zygomatic implants is another good choice for rehabilitating such significant abnormalities and patient - specific implants. With use of titanium alloy has improved reconstructive procedures and their outcomes Titanium alloy improves reconstructive surgery.[14]

Limitation of the study

This case series lost numerous individuals who underwent various resections. Future studies must assess the causes and quality of life. This would improve future therapy and recovery.

CONCLUSION AND CLINICAL SIGNIFICANCE

ROCM management is multifunctional. This case series illustrates significant etiological causes, clinical warning symptoms, thorough radiological presentation, and detailed medicinal, surgical, and functional prosthetic care methods employed by our team to manage such aggressive disease. The study also gives a substantial amount of clinical data that can be utilised to develop standardised preventive and management/treatment/rehabilitation methods to reduce disease morbidity and mortality and prevent endemic outbreaks.

Ethics approval

Not required as per Institutional Guidelines. However, Case Report (CARE) guidelines were followed.

Informed consents

Written informed consent was obtained from the patients for publication of this case series.

Data and material availability

Data and material used in this study are available on request to the corresponding author.

Authors contribution statements

Each author contributed equally in conceptualizing, collecting data, editing, and proofreading.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.