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Review Article

P Roshan Kumar1 , N Kalavathy2 , Mitha M Shetty3 , Archana K Sanketh4 , Anuradha Venkataramani5 , Ramyashree SV6

1 Reader, 2 Professor and Head, 3 Reader, 4 Reader, 5 Lecturer, 6 Postgraduate student, Department of Prosthodontics, D. A. Pandu Memorial R.V. Dental College, Bangalore.

*Corresponding author:

Dr. P Roshan Kumar, Reader, Department of Prosthodontics, D. A. Pandu Memorial R.V. Dental College, Bangalore, Karnataka 560078, India. E-mail: dr_roshankumar_28@yahoo.co.in

Received date: August 17, 2021; Accepted date: September 17, 2021; Published date: October 31, 2021

Year: 2021, Volume: 13, Issue: 4, Page no. 293-302, DOI: 10.26715/rjds.13_4_4
Views: 3171, Downloads: 288
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CC BY NC 4.0 ICON
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0.
Abstract

Rhino-cerebral mucormycosis, a fateful fungal infection which was commonly known to affect the immunocompromised patients, is now thriving in conjunction with Corona virus disease 2019 (COVID-19). Early diagnosis and aggressive medical and surgical intervention are the key factors to extricate the patients. However, this leads to abundant hard and soft tissue loss, leaving behind a huge orofacial defect, along with certain morbidities and psychological trauma, necessitating surgical and prosthodontic rehabilitation. The present paper reviews on role of prosthodontist in various stages of treatment for mucormycosis patients. It also summarizes several treatment modalities including recent trends to rehabilitate the defect and restore the patients’ quality of life.

<p>Rhino-cerebral mucormycosis, a fateful fungal infection which was commonly known to affect the immunocompromised patients, is now thriving in conjunction with Corona virus disease 2019 (COVID-19). Early diagnosis and aggressive medical and surgical intervention are the key factors to extricate the patients. However, this leads to abundant hard and soft tissue loss, leaving behind a huge orofacial defect, along with certain morbidities and psychological trauma, necessitating surgical and prosthodontic rehabilitation. The present paper reviews on role of prosthodontist in various stages of treatment for mucormycosis patients. It also summarizes several treatment modalities including recent trends to rehabilitate the defect and restore the patients&rsquo; quality of life.</p>
Keywords
Mucormycosis, Rehabilitation, Reconstruction, Maxillofacial prosthesis
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Introduction

Mucormycosis is an uncommon opportunistic infection, often associated with immunocompromised states. It is one of the most common incursive fungal infection after aspergillosis and candidiasis. Mucormycosis, an angioinvasive infection is caused by certain Mucorales of class zycomycetes such as Rhizomucor, Rhizopus, Cunninghamella etc.1 However, this rare fulminant infection has seen a rising trend in Coronavirus disease 2019 (COVID-19) global pandemic, which is yet an unresolved challenge in the field of medicine.

Certain opportunistic bacterial and fungal infections have accompanied Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).2 Candida and Aspergillosis have also been reported as principal pathogens of fungal origin for co-infection in patients infected with COVID-19.3

Severe COVID-19 infection causes activation of the immune system which raises ferritin levels in the blood picture and it is noted that COVID-19 is usually aligned with lymphopenia.4 Therefore, there is an increase in the virulence of the fungi and enhancement of their adherence to the endothelium, leading patients who are uncontrollably diabetic and with iron overload susceptible to mucormycosis.5

Several other conditions that predispose patients to this fulminating infection are corticosteroid therapy, organ transplantation, uncontrolled diabetes mellitus, chemotherapy and certain hematologic malignancies.6 These organisms proliferate rapidly, as they gain access to the mucous membranes and invade the nearby blood vessels causing vascular thrombosis and subsequent necrosis, thereby leading to tissue destruction and non-healing necrotic ulcers with underlying bony destruction.7

Therefore, it necessitates utmost attention in previously infected COVID-19 patients, for early diagnosis and surgical intervention in order to cease the propagation of infection to the vital organs of the body.

Generally, the surgical resection is aggressive that creates oral, orbital or facial defects causing certain morbidities that are inevitable. This necessitates prosthodontic rehabilitation of the site to re-establish the patient’s quality of life.

This paper aims to review on various prosthodontic rehabilitative approaches following surgical treatment in mucormycosis cases.

Materials and Methods

The primary database was gathered through searching certain related keywords in several electronic databases that includes Medline, PubMed, Google Scholar, Wiley online library and Web of Science. A hand search of the reference lists of the included articles and textbooks was also carried out.

Clinical manifestations

Although, in general dental practice, patients infected with mucormycosis are not encountered frequently, they may consult dentists during the initial stage of the disease when the symptoms overlap with that of dental origin such as dental pain, periorbital cellulitis or mucosal sloughing.8 Sometimes, palatal ulceration alone may be the pathognomonic sign, that leads to the diagnosis of mucormycosis.9

Therefore, it necessitates consideration of mucormycosis as a differential diagnosis, when a patient presents with unilateral proptosis, swelling of the periorbital and perinasal tissues, dilation and fixation of the pupil, paranasal sinusitis, and cranial nerve involvement.10

Among the various clinical forms of mucormycosis, rhinocerebral is the predominant one, accounting for one third to half of the reported cases. It is further divided as rhinoorbitalcerebral (Type 1) (more fatal) and rhinomaxillary form (Type 2) (less fatal), involving ophthalmic with internal carotid arteries and sphenopalatine with greater palatine arteries respectively.11

In 1950, Smith and Krichner have developed certain criteria for the clinical diagnosis of mucormycosis that are yet observed to be the gold standard and are as follows: 12

1. Dark colored, blood-tinged, nasal discharge on the side where facial pain is elicited.

2. Soft periorbital or perinasal swelling that becomes indurated and discolored (with progressive vascular occlusion)

3. Proptosis of the globe and ptosis of the eyelid, dilatation and fixation of the pupil, limitation of global mobility

4. Progressive lethargy, despite good response to diabetic therapy

5. Black necrotic turbinates mimic dried blood

6. Loss of corneal reflex and onset of facial weakness that is evident, late in the course of invasion Nithyanandam et al., in 2003 came up with three distinct clinical stages based on the signs and symptoms and degree of disease progression, which are as follows (Table 1):13

Clinical stage 1: Signs and symptoms are referable only to Sino-Nasal disease.

Clinical stage 2: Signs and symptoms of Rhino-Orbital disease,

Clinical stage 3: Signs and symptoms of Rhino-OrbitoCerebral disease

Clinical classifications aid in appropriate surgical as well as prosthetic rehabilitative treatment planning to render comprehensive medical care to the patient.

Surgical considerations

Therapy for rhinocerebral mucormycosis necessitates an integrated approach that includes,

1. Antifungal agents mainly intravenous amphotericin B,

2. Surgical debridement, and

3. Control of the underlying disease that leads to infection.14,15

Early extensive surgical debridement of the infected tissues is of utmost importance for success of the treatment in rhinocerebral mucormycosis. This includes resection of involved facial tissues, along with the skin, muscle, and mucosa of nasal and oral cavity, maxillary and palatal bones along with ethmoid and maxillary sinuses and tissues that are necrotic in the temporal and infratemporal region. For an actively infected orbit with immobile and blind eye, orbital exenteration must be considered. It would be a life-saving decision if active fungal infection is present in the orbit.16

The swift progression of the mucormycosis infection creates a high necessity of early aggressive surgical intervention. Also, the fact that a clear-cut extent of excision cannot be decided prior to surgery based on radiological imaging unlike in tumor cases of benign and malignant origin. Presurgical prosthodontic planning may not be possible in all the cases.

After the surgical debridement, the patient is left with large bony and soft tissue defects. This entails reconstruction to protect the remaining vital structures, restore as much function and provide a socially acceptable appearance.

In the literature review conducted by Palacios et al., in 2019 to evaluate the feasibility of immediate reconstruction after surgical debridement,16 cases were collected since 1999, from 14 different publications, of which 15 were diagnosed as rhinocerebral and one as cutaneous mucormycosis. After surgical debridement, delayed reconstruction was performed in most cases (13/16) and only two described about immediate reconstruction with either a free flap (12/16) or pedicled flaps (4/16). The mean time of delayed reconstruction was 16.7 weeks, ranging from 2–36 weeks post-surgical debridement.

The study inferred that, as secondary reconstruction leads to tissue atrophy and retraction resulting in higher patient disfigurement, immediate reconstruction may be enforced, on the basis of clinical criteria, after an intraoperative study of wound edges and recipient’s vessels and by histologic confirmation of absence of hyphae invasion.

However, delayed reconstruction is recommended when there is hemodynamic instability, evidence of cellulitis or aggregated infections, when a complete resection cannot be accomplished, or intra-operatory biopsy of wound margins are unavailable.17

Though the existing literature discloses contradictory outlook regarding patient management, it is better that the reconstruction be delayed to be sure that the patient survives after surgical intervention, considering the high mortality rate of 85%.18,19

Prosthodontic considerations

The post-surgical defects of mucormycosis are remarkably different from the defects that result from tumor resection due to the unpredictable, indefinable advancement of the fungus and the probable requirement of additional debridement procedure. The surgical modifications that are done in favor of prosthetic rehabilitation in tumor cases cannot be accomplished in case of mucormycosis.

Therefore, provision of prosthodontic rehabilitation is compounded in mucormycosis patients especially when they are also edentulous, as the resultant defect often cannot be used effectively to retain, support, or stabilize the obturator prosthesis and the fact that these defects are let to epithelialize, result in a non-keratinized membrane formation, aiding in poor stress-bearing surface.

Definitive prosthodontic treatment should only be considered once the healing is complete since the presentation of the permanent defect is decided based on the healing process and scar contraction.15

The reconstructive and rehabilitative approach of the resultant defects differ widely. Therefore, classifications of maxillofacial defects that consider the functional and esthetic outcome, and also indicate the most appropriate form of management, are to be contemplated. Several classifications have been proposed such as Armany’s, Spiro’s, Liverpool classification by Brown et al, Cordeiro’s, Okay’s, Durrani’s and many more.

The classification of maxillary defects by Durrani et al., in 2013 seems to be appropriate to correlate with the clinical stages of mucormycosis. The classification is as follows:

Durrani et al., (2013), Classification of maxillary defects:20

1. Alveolectomy: - These defects involve the alveolar bone alone.

2. Sub-total Maxillectomy: - These defects cause oro-nasal or oro-antral fistula but do not disturb the orbital wall of maxilla.

3. Total Maxillectomy: - These defects are characterized by absence of complete maxilla including orbital floor but the orbital contents remain intact.

4. Radical Maxillectomy: - These defects are characterized by absence of orbital contents along with the maxilla.

5. Composite Maxillectomy: - These defects involve resection of facial skin, soft palate, and any other part of the oral cavity.

All these defects can be further classified into Unilateral and Bilateral defects.

Phases of Prosthodontic Treatment for Mucormycosis (Acquired Defects)

Prosthodontic therapy for patients with acquired surgical defect after maxillary resection are rehabilitated in three phases by an obturator prosthesis that supports the patients through different stages of healing. The phases of treatment are arbitrarily divided as follows:

1. Surgical obturation

2. Interim obturation

3. Definitive obturation

1. Surgical obturation

Immediate surgical obturation grants the placement of prosthesis at surgery. It is defined as the temporary prosthesis used to restore the continuity of the hard palate immediately after surgery. It is retained for about six days post-surgery. The obturator acts as an arrangement on which surgical dressing may be placed. It also decreases contamination of the raw wound, aids in deglutition, thereby permitting early removal of nasogastric tube. Altogether, it lessens the psychologic impact of surgery to some extent.

Prior to surgery, impressions are made, and the casts are mounted on the articulator. Later, the outline of surgical margins is discussed by the operating surgeon and prosthodontist on the cast and accordingly, the maxillary cast is altered and the prosthesis is fabricated.21

Explicit planning prior to surgery regarding the surgical margins may not be always possible especially in mucormycosis cases since it is rapidly progressive in nature.22 Nevertheless, a delayed surgical obturator can be planned in situations where it necessitates emergency surgical debridement which would be a lifesaving action, and also in cases where a prosthodontist could not be consulted beforehand. It could also be considered in cases where there is requirement of additional debridement procedure due to indefinable advancement of the fungus.

Delayed surgical obturator is fabricated within few days of surgical resection. Since the impression procedure is carried out after the surgery, it is required to handle the fresh surgical site, and the patient, with utmost care as they tend to be apprehensive.

It is advised to reduce the time duration between impression making and obturator delivery, as the time lag would result in tissue contraction and edema, making it uncomfortable to the patient during obturator insertion. An additional advantage of delayed surgical obturator is that it can be readily converted to an interim obturator wherein the margins of the obturator are not compromised till the final prosthesis is fabricated.22

2. Interim obturation

Fabrication of definitive prosthesis cannot be considered till the surgical site is healed, dimensionally stable and most importantly, until the patient’s systemic condition becomes stable, specifically in rhinocerebral mucormycosis, which has a high chance of recurrence and high mortality rate even after treatment.15

Interim obturator is advised in cases with large defects, where appropriate function and comfort cannot be maintained until fabrication of a new prosthesis. The surgical and definitive obturators are intervened by the interim obturator.21

3. Definitive obturation

A definitive obturator is usually indicated on an average, three months after the surgery. The factors such as the state of healing, dimension of the defect, effectiveness of previous obturator and the remaining teeth present must be considered to construct a definitive obturator. In addition, the prognosis of the fungal infection along with the systemic condition of the patient must be determined. The dimensional changes occurring due to structuring of the wound and scar contracture is extended for at least one year and are fundamentally related to the lining soft tissues rather than the underlying bony area, thereby demanding periodic follow up.23

In edentulous patients, the obturator prosthesis may exhibit varying degrees of movement depending on the outline and amount of the residual hard palate, the contour, size and mucosal lining of the defect, the accessibility of undercuts, and the support areas that can be engaged within and peripheral to the defect. Engaging the defect extensively maximizes stability support and retention of the obturator. In edentulous patients, the defect margin in the posterior region plays a crucial role in treatment planning since it demands implant placement if the margin extends beyond the junction of soft and hard palate.

In dentulous patients, the status of remaining natural teeth should be carefully addressed as they play a decisive role in designing the obturator prosthesis. The diagnostic casts should be surveyed carefully for location of undercuts, location and contour of potential guide planes. A compound path of insertion must be employed to use the undercuts available in the defect adequately. Also, inclusion of multiple rests is suggested to improve support and stability for the prosthesis. In defects extending to or beyond the midline, additional bracing may be necessary to distribute lateral forces more widely among remaining dentitions.

Implants

Osseointegrated endosseous and maxillofacial implants such as zygomatic and pterygoid implants have dramatically raised the potential for reconstruction of the patients with varied soft and hard tissue maxillofacial defects. Implants contribute to the retention, support and enhance the stability of the prosthesis. Moreover, placement of implants along with staged surgical reconstruction of the extensive hard tissue defects facilitates prosthodontic rehabilitation with fixed prosthesis.

The decision whether to place implants or not should always be critically evaluated specifically in mucormycosis patients as they are systemically immunocompromised and may not be willing for another psychological burden due to surgical intervention. Patients suffering from chronic liver disease or in liver transplanted cases, it is estimated that approximately 30% patients suffer from osteoporosis which is a subject of concern. 24

Therefore, the decision making should involve a team comprising of a general surgeon, a physician, a maxillofacial surgeon, a prosthodontist along with the patient attendees.

Following is the table confining case reports of rehabilitation of various defects resulted due to rhino-orbital mucormycosis (Table 2)

Recent advances

The introduction of 3-D computer aided designing (CAD) and computer aided manufacturing (CAM) also known as rapid prototyping (RP) has transformed the field of maxillofacial prosthodontics. Ever since the digital technology has arrived, it has made it possible to record oral morphology devoid of traditional impression materials and methods. Digital scans can be combined with traditional laboratory procedures with the aid of three-dimensional modeling to fabricate complex prostheses.

CAD/CAM technologies are capable of palliating most of the limitations of conventional techniques such as risk of impression material dislodgement into the surgical site, loss of impression accuracy due to nasal mucosal secretion on impression material, difficulty caused by severe trismus and the inconvenience caused to the patient.40

Cone beam computed tomography (CBCT) grants volumetric data which is convertable to standard tessellation language (STL) files that further can be used for rapid prototyping procedures such as stereolithography (SLA) 3D printing to fabricate accurate anatomic casts. By utilizing this model, maxillofacial prosthesis can be fabricated by conventional method.

Recently, intra oral scanning devices have also been developed and employed along with CAD/ CAM technology in dentistry, with numerous advantages. Intraoral optical impression systems provide three dimensional datasets, that are developed to obtain digital impressions of teeth, implants and surrounding soft tissues. Today, the intraoral scanner data and 3D volumetric data of craniofacial tissues from the CBCT images can be fused using certain software to obtain a resin master model with clearly defined soft tissue details to fabricate the prosthesis.41

The literature has also reported the use of combination of facial scanner and intraoral scanner to acquire the digital data for fabrication of extraoral prosthesis to obtain detailed skin textures.42

However, the unavailability of equipment in the clinic and that it is high-priced, limits their practical application. To overcome these constraints, the technology is stepped higher by introducing an in-house and also economical smartphone-integrated stereophotogrammetry (SPINS) 3D scanner. The palatal defects can be scanned using SPINS and the prosthesis can be designed and fabricated by utilizing the 3D models obtained with SPINS. 43

Advances in tissue engineering has also privileged maxillofacial reconstruction at a preliminary level as it has been considered as a possible solution to replace complex reconstructive methods. It is based on accumulating stem cells that possess capability to form an organ. These harvested cells are then laid on laboratory manufactured scaffolds, in order to resemble the desired tissue to be replaced. Simple tissue regeneration has been successfully achieved so far to restore tissue defects, but complex tissue structures along with its functional restoration are yet to be carried out.44

Adopting customized tissue-engineered biodegradable scaffolds, such as polycaprolactone (PCL), fabricated using the patient’s computed tomography data and an extrusion-based 3D printing system have been documented and confirmed to promote regeneration of the deficient tissue for maxillofacial bone reconstruction in patients with complex maxillary defects.45 Thus, future developments in the field of tissue engineering will have a significant influence on managing postsurgical defects.

Discussion

Mucormycosis has captured the attention of health care providers, as there is a surge in graph of these debilitating fungal diseases, during this COVID-19 pandemic situation due to its deleterious pathogenesis. It is not only life threatening but also leads to loss of critical maxillofacial structures post-surgery, thereby causing huge psychological trauma to the patients. Hence, the role of a prosthodontist has to be emphasized, especially the rhinocerebral mucormycosis in which there exists a great demand of maxillofacial rehabilitation postsurgery. Therefore, complete understanding with respect to the course of the disease, its pathogenesis and treatment protocols is necessary before rehabilitating the maxillofacial defect itself.

This article has summarized the clinical manifestations, classification of clinical stages and surgical considerations of mucormycosis. Durrani’s classification was selected and detailed in the article as it seemed suitable for defects caused after mucormycosis. However, various documented classifications of maxillary defects may be used. Prosthodontic considerations along with a summarized table of certain documented case reports consisting of various types of maxillary defects along with other maxillofacial defects were classified and their prosthetic treatment was listed.

The application of recent technologies such as 3D computer aided designing and manufacturing, use of combination of intraoral scanner and CBCT data, use of smartphone-integrated stereophotogrammetry (SPINS) 3D scanner and future perspectives of tissue engineering in maxillofacial reconstruction has also been briefed.

Conclusion

As mucormycosis is a fulminant fungal infection, it constrains early diagnosis and treatment intervention through a collaborative approach, in which the maxillofacial prosthodontist plays an important role in every step of management to improve the patients’ comprehensive quality of life. The defects that result after surgical debridement, in mucormycosis, are different from those that occur otherwise. Therefore, it demands thorough knowledge of course and nature of the disease, to critically analyze the available anatomic structures and prostheses designs to attain maximum retention, stability, and esthetics. Maxillofacial prosthesis not only rehabilitates the defect but also rejuvenates selfconfidence to lead life to the fullest.

Conflict of Interest

None. 

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References
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