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Table of Contents
REVIEW ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 2  |  Page : 37-40

Mucormycosis: An insight into its early diagnosis and prosthodontic rehabilitation


Department of Prosthodontics, Regional Dental College, Guwahati, Assam, India

Date of Submission26-May-2022
Date of Acceptance03-Jun-2022
Date of Web Publication29-Jun-2022

Correspondence Address:
Dr. Debjani Chakraborty
Department of Prosthodontics, Regional Dental College, P.O. Indrapur, Guwahati, Kamrup (M), Assam
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INJO.INJO_14_22

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  Abstract 

During COVID-19 pandemic, mucormycosis has gained limelight with inadvertent increase in number of cases, despite being an uncommon, opportunistic, invasive mycotic infection otherwise. Suspected mucormycosis cases require rapid therapeutic and diagnostic intervention; delayed initiation of treatment is associated with increased mortality. It is of particular interest to prosthodontist because of the presenting symptoms and the oral and facial defects that result from the extensive surgical resection done in order to treat such aggressive disease.

Keywords: COVID-19, mucormycosis, prosthodontic rehabilitation


How to cite this article:
Barman J, Chakraborty D, Nath S. Mucormycosis: An insight into its early diagnosis and prosthodontic rehabilitation. Int J Oral Care Res 2022;10:37-40

How to cite this URL:
Barman J, Chakraborty D, Nath S. Mucormycosis: An insight into its early diagnosis and prosthodontic rehabilitation. Int J Oral Care Res [serial online] 2022 [cited 2022 Aug 16];10:37-40. Available from: https://www.ijocr.org/text.asp?2022/10/2/37/348773




  Introduction Top


In the recent times of COVID-19 pandemic, mucormycosis has gained limelight with inadvertent increase in number of cases, despite being an uncommon, opportunistic, invasive mycotic infection otherwise.[1],[2],[3],[4],[5] The terms ‘mucormycosis’ and ‘zygomycosis’ are often used interchangeably in literature, however, after phylogenetic reanalysis of the Fungi kingdom the former is considered correct.[1] The present review aims to highlight important attributes of mucormycosis from a dentists’ perspective which would capacitate and further augment the ability of dental practitioners to restore and recreate the deformity caused by the already developed havoc and hence, reduce the burden of the associated disfigurement.


  Epidemiology Top


Globally, the reported prevalence of mucormycosis ranges from 0.005 to 1.7 per million population; however, the prevalence is nearly 80 times higher in India than in developed countries, in a recent estimate of year 2019–2020.[3] An alarming increase in the number of COVID-19-associated mucormycosis has been observed in India.[6] All-cause mortality rates for mucormycosis range from 40% to 80% with varying rates depending on underlying conditions and sites of infection.


  Etiology and Pathogenesis Top


In earlier times, the infection was termed as “Zygomycosis” with fungi belonging to the phylum Zygomycetes as causative agents. However, the phylum Zygomycetes involves different orders of fungi which cause distinct types of infections, and thus, the terminology was considered to be very broad. The order Mucorales comprises 261 species in 55 genera, 38 of which have been associated with human infections.[5] Over the years, the etiological fungi associated with mucormycosis have been methodically narrowed down to certain species belonging to the family Mucoraceae.[6] The most common species all over the world is Rhizopus arrhizus (formerly Rhizopus oryzae). Other isolated fungi belong to the genera Lichtheimia, Mucor, Rhizomucor, Cunninghamella, Saksenaea, Apophysomyces, Cokeromyces, Actinomucor and Syncephalastrum.[4] Mucorales can gain entry to a susceptible host through inhalation, ingestion of contaminated food, and through an abraded skin.[7],[8],[9] The most important conditions that predispose to mucormycosis include diabetes mellitus (DM), with or without ketoacidosis, hematological malignancies (HM), other malignancies, transplantation, prolonged neutropenia, corticosteroids, trauma, iron overload, illicit intravenous drug use, neonatal prematurity and malnourishment.


  Clinical Presentation Top


Tissue necrosis due to invasion of blood vessels and subsequent thrombosis are the hallmarks of invasive mucormycosis.[10],[11],[12] Accordingly, invasive mucormycosis is classified as one of the following 6 major clinical forms: (1) Rhinocerebral, (2) Pulmonary, (3) Cutaneous, (4) Gastrointestinal, (5) Disseminated, and (6) Miscellaneous, such as endocarditis, osteomyelitis, peritonitis, and renal infection [Table 1].[5] Any of the species of the Mucorales may cause infection at these sites.
Table 1: Brief summary of clinical forms of mucormycosis

Click here to view



  Diagnosis Top


Diagnosis consists of recognition of risk factors, assessment of clinical manifestations, early use of imaging modalities and prompt initiation of diagnostic methods based on histopathology, cultures and advanced molecular techniques. The application of immunohistochemistry with commercially available monoclonal antibodies or PCR techniques. The in-house tests that have been developed so far use different probes and primers. Three Mucorales species- Rhizopus arrhizus var. arrhizus, R. arrhizus var. delemar and R. microsporus, had distinct breath profiles of the volatile metabolite sesquiterpene, which could be used to identify these infections in vivo by thermal desorption gas chromatography/tandem mass spectrometry (GC–MS).[8],[9],[10],[11],[12],[13],[14]


  Management Top


Mucormycosis treatment recommendations were published by the European Conference on Infections in Leukemia (ECIL) in 2017 and updated by the European Confederation of Medical Mycology (ECMM) in 2019. Liposomal Amphotericin B (L-AmB) remains the first-line drug in mucormycosis therapy. Isavuconazole (ISZ) and new Posaconazole (PSZ) formulations have been added to the guidelines but in second-line treatment following L-AmB. Few anti-Mucorales drugs such as Rezafungin, SCY-078, Orolofim, and encochleated amphotericin B etc. are currently under development.[5],[6],[7]

Prosthodontic management

Defects resulting from surgical debridement or disease extension from mucormycosis differ significantly from the defects that result from tumor resection because of the unpredictable, indefinable advancement of the fungus clinically and because of the probability that additional debridement procedures will be required. In addition, the marginal tissues may be ischemic, precluding the use of skin grafts to cover the raw tissue surfaces, at least during the treatment phase. These defects are allowed to epithelialize spontaneously, generally resulting in a nonkeratinized mucous membrane that provides a poor stress-bearing surface.[6] 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. The size and extension of the defects differ widely depending on the invasion of the fungus and may extend inferiorly from the paranasal sinuses to the palate and intraoral regions, and may also extend posteriorly and laterally to involve orbital compartments and midfacial regions, thus giving rise to extraoral defects as well. Accordingly, the prosthodontic treatment options for rehabilitation needs to be customized for each case and hence, it varies from patient to patient. 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.

Rehabilitation of intraoral defects

An obturator prosthesis is most frequently the choice of treatment due to the complexity of maxillary surgical reconstruction and the uncertainty of the functional outcome. It can be surgical, interim or definitive obturator prosthesis, which recreates a partition between the oral and nasal cavities, restores facial contour, improves mastication, articulation, and speech intelligibility, provides lip support, supports orbital content to prevent exophthalmos and diplopia, and reduces drooling. Weight reduction is critically important when the prosthesis is suspended without much remnant bone and tooth support. A lighter obturator improves suspension cantilever mechanics, prevents overstressing of the remaining supporting structures, and increases retention.[7] Since the margin of the defect resulting from surgery cannot be predicted beforehand, it is difficult to determine the exact extension of the immediate surgical obturator and often necessitates modification at surgery and after subsequent debridement procedures.. In order to cover the inadequate extension of the surgical resected site, soft liner is being used in immediate surgical obturator. The soft liner acts as a carrier of fungal and bacterial growth due to rough surface created by the leaching of the plasticizer and the poor maintenance of the prosthesis hygiene. Whereas, the delayed surgical obturator extends into the defect site without any additional reinforcement and benefits the patient during the swallowing providing comfort and reducing hypernasality. The impression for delayed surgical obturator is being made within few days of the surgical procedure; hence, the complete extension of the surgical site is obtained. It is highly recommended to reduce the time duration between an impression and obturator fabrication, as the time lag would result in tissue contraction and edema, making it extremely difficult to insert the obturator. An added advantage with delayed surgical obturator is that it could be easily converted into an interim obturator wherein the extension of the obturator is not compromised until a final prosthesis is fabricated. Definitive prosthodontic treatment should be considered only when healing is complete because the configuration of the permanent defect will be determined by the healing process and scar contraction will be a prominent feature. Definitive obturator prosthesis is fabricated when tissue changes or recurrence of the disease are unlikely. It incorporates a metal framework in its design which replicates the palate and supports the bulb portion of the obturator. The bulb portion of the obturator can be solid, open- hollow or closed- hollow in design.[1] The open-hollow bulb design is preferred over the closed-bulb design because it is lighter in weight, easier to fabricate, and produces noticeably better articulation. However, it should be used when the weight of the prosthesis is a major concern, and only when regular follow-up is feasible because the open design tends to accumulate mucous secretions, which can be a source of infection.

Rehabilitation of extraoral defects

Facial defects also heal by secondary intention, with considerable scarring, contracture, and distortion of adjacent facial tissues. The defects that result is very difficult to restore prosthetically since the mucormycosis is not confined within convenient boundaries and has varied presentation among different patients. Facial defects may result from surgical debridement of isolated lesions involving only orbit or nose with or without involvement of intra- oral regions and may also extend to ala of nose or malar regions in the perisinusal areas on the affected side. A team approach involving the ophthalmologist, oto-rhinolaryngologist, clinical microbiologist, plastic surgeon and maxillofacial prosthodontist is needed to help patient survive the disease with good result.[8] For the purpose of prosthetic rehabilitation of facial defects, biomaterials such as PMMA, PVC, polyurethane, and silicone have been used. Silicones gained more popularity through the years due to its good physical properties, excellent biocompatibility and good thermal stability. They can be extrinsically or intrinsically stained and is sanitary. Acceptable esthetic results usually can be obtained by a facial prosthesis. However, retention of a large prosthesis can be challenging. Various methods of auxiliary retention for facial prosthesis have been described in the literature; they include eyeglasses, denture extensions that engage tissue undercuts, magnets, facial prosthetic adhesives, or combination of the above, and craniofacial implants. All of these types of prosthesis retention can be broadly grouped under two headings: “osseointegrated systems” and “non- osseointegrated systems.” Osseointegrated implant retention systems include bar-clip, O-ring, or magnet. Furthermore, the “non- osseointegrated systems” retain prosthesis anatomically, mechanically, chemically, and surgically.[1] For rehabilitation of facial defects caused by mucormycosis, a direct contact of adhesive-retained silicone prosthesis is not recommended because of the risk of accelerated deterioration of the prosthesis and to minimize the risk of recurrence of infection. Although the placement of implants has been documented, there is an increased risk of failure due to soft tissue infections, decreased vascular perfusion, poor remodeling capacity of the bone-implant surface, and lack of stabilizing bone volume in proximity to the frontal sinus.

Rehabilitation of combined extra- and intraoral defects

Extensive maxillary resection along with debridement of necrotic facial tissues leads to complex maxillofacial defect that needs rehabilitation with obturator along with facial or orbital prosthesis. For such combined prosthesis, the extra-oral and intra-oral components of the prostheses can be attached to each other with magnetic attachments and buttons, or other innovative tools such as a brass cylinder and housing, a pin and socket of an electricity plug, etc.[9] For complex defects with compromised bony and dental support, where an increased movement of the obturator is expected, providing a non rigid attachment with a movable joint between both components helps to reduce the movement of the extraoral prosthesis when the obturator functions.


  Recommendations for Prosthodontic Rehabilitation of Mucormycosis Top


Early recognition, diagnosis and prompt extensive surgical debridement of infected tissues must be emphasized which increases survival and limits the extent of disfigurement and suffering. Particular attention should be given towards recognition and correction of underlying predisposing factors. Explicit planning prior to surgery regarding the surgical margins may not be possible in mucormycosis cases which precludes the use of immediate surgical obturator. However, fabrication of delayed surgical obturator can be planned in such cases with careful consideration. Careful evaluation of surgical margins and tissue bed of the resected site facilitates planning for future prosthodontic rehabilitation, since prosthodontic planning prior to surgery is often not possible while treating such life threatening disease. Definitive rehabilitation should begin only after complete healing and after bypassing any chances of recurrence. Daily care of the prosthesis should be advised with suitable cleansing agents such as 1% chlorhexidine solution and oral hygiene procedures should be insisted at each visit. A frequent follow- up schedule must be devised for each patient to rule out recurrence and to evaluate functioning of the existing prosthesis.


  Conclusion Top


As India is a developing country with limited health infrastructure, spreading mass awareness is crucial, since prevention of such life threatening disease would result in lesser economic burden than therapeutic control of the same, if outbreak occurs. It is important to understand various reconstructive and rehabilitative procedures and encourage prosthodontists to share their experiences which would ultimately help to cater services to these large group of population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SCA, Dannaoui E, Hochhegger B, et al; Mucormycosis ECMM MSG Global Guideline Writing Group. Global guideline for the diagnosis and management of mucormycosis: An initiative of the european confederation of medical mycology in cooperation with the mycoses study group education and research consortium. Lancet Infect Dis 2019;19:e405-21.  Back to cited text no. 1
    
2.
Chamilos G, Lewis RE, Kontoyiannis DP Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis 2008;47:503-9.  Back to cited text no. 2
    
3.
Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Kong DCM, et al. The epidemiology and clinical manifestations of mucormycosis: A systematic review and meta-analysis of case reports. Clin Microbiol Infect 2019;25:26-34.  Back to cited text no. 3
    
4.
Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54(suppl 1):S23-34.  Back to cited text no. 4
    
5.
Patel A, Agarwal R, Rudramurthy SM, Shevkani M, Xess I, Sharma R, et al; MucoCovi Network3. Multicenter epidemiologic study of coronavirus disease-associated mucormycosis, India. Emerg Infect Dis 2021;27:2349-59.  Back to cited text no. 5
    
6.
Kumar M, Sarma DK, Shubham S, Kumawat M, Verma V, Singh B, et al. Mucormycosis in COVID-19 pandemic: Risk factors and linkages. Curr Res Microb Sci 2021;2:100057.  Back to cited text no. 6
    
7.
Prakash H, Chakrabarti A Epidemiology of mucormycosis in India. Microorganisms 2021;9:523.  Back to cited text no. 7
    
8.
Walther G, Wagner L, Kurzai O Updates on the taxonomy of mucorales with an emphasis on clinically important taxa. J Fungi 2019;5:106.  Back to cited text no. 8
    
9.
Ribes JA, Vanover-Sams CL, Baker DJ Zygomycetes in human disease. Clin Microbiol Rev 2000;13:236-301.  Back to cited text no. 9
    
10.
Spellberg B, Edwards J Jr, Ibrahim A Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.  Back to cited text no. 10
    
11.
Gomes MZ, Lewis RE, Kontoyiannis DP Mucormycosis caused by unusual mucormycetes, non-rhizopus, -mucor, and -lichtheimia species. Clin Microbiol Rev 2011;24:411-45.  Back to cited text no. 11
    
12.
Ibrahim AS, Edwards JEJ, Filler SG Zygomycosis. In: Dismukes WE, Pappas PG, Sobel JD, editors. Clinical Mycology. New York: Oxford University Press; 2003. p. 241-51.  Back to cited text no. 12
    
13.
Skiada A, Pavleas I, Drogari-Apiranthitou M Epidemiology and diagnosis of mucormycosis: An update. J Fungi 2020;6:265.  Back to cited text no. 13
    
14.
Kennedy KJ, Daveson K, Slavin MA, van Hal SJ, Sorrell TC, Lee A, et al; Australia and New Zealand Mycoses Interest Group of the Australasian Society for Infectious Diseases. Mucormycosis in Australia: Contemporary epidemiology and outcomes. Clin Microbiol Infect 2016;22:775-81.  Back to cited text no. 14
    



 
 
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